Patent application title: BIOMARKERS FOR THE PREDICTION OF RENAL INJURY
Inventors:
IPC8 Class: AC12Q168FI
USPC Class:
506 9
Class name: Combinatorial chemistry technology: method, library, apparatus method of screening a library by measuring the ability to specifically bind a target molecule (e.g., antibody-antigen binding, receptor-ligand binding, etc.)
Publication date: 2016-06-23
Patent application number: 20160177395
Abstract:
The present invention relates to means and methods for predicting the
onset of renal injury based on measuring the expression of
polynucleotides and proteins, particularly on measuring the expression of
sets of novel as well as known polynucelotides and proteins, and to kits
utilizing same.Claims:
1-32. (canceled)
33. A kit for assaying a sample for gene sets predictive of onset of renal injury, comprising: a set of probes and/or pairs of primers that hybridize to at least two polynucleotide markers, wherein said at least two polynucleotide markers are selected from the group consisting of: SEQ ID NO:1, 3, 48, 6, 12, 52 or a fragment thereof and sequences homologous thereto; reagents for detecting the at least two polynucleotide markers and for measuring the expression level of said at least two polynucleotide markers; and instructional material directing the correlation of said expression level of said at least two polynucleotide markers with onset of renal injury using a classifier capable of classifying renal injury using said expression level of said at least two polynucleotide markers.
34. The kit of claim 33, said kit comprises a plurality of probes and/or pairs of primers for detecting a set of four polynucleotide markers, wherein the set of four polynucleotide markers comprises: a first polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:1, or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:2, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:254; a second polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:3, or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOs:4 and 5, or having an amplicon consisting of the nucleic acid sequence set forth in any one of SEQ ID NO:266 and 329; a third polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:6, or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:7 and 8, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:287; and a fourth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:12, or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:13 and 14, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:296, and sequences homologous thereto.
35. The kit of claim 33, said kit comprises a plurality of probes and/or pairs of primers for detecting a set of four polynucleotide markers, wherein the set of four polynucleotide markers comprises: a first polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:1, or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:2, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:254; a second polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:3, or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:4 and 5, or having an amplicon consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:266 and 329; a third polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:48, or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:49, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:263; and a fourth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:52 or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:53 or having an amplicon consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:290 and 332, and sequences homologous thereto.
36. The kit of claim 33, said kit comprises a plurality of probes and/or pairs of primers for detecting a set of six polynucleotide markers, wherein the set of six polynucleotide markers comprises: a first polynucleotide the nucleic acid sequence set forth in SEQ ID NO:1, or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:2, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:254; a second polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:3, or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:4 and 5, or having an amplicon consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:266 and 329; a third polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:48, or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:49, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:263; a fourth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:6, or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:7 and 8, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:287; a fifth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:12, or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:13 and 14, or having an amplicon consisting of the nucleic acid sequence set forth in SEQ ID NO:296; and a sixth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:52, or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:53, or having an amplicon consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:290 and 332, and sequences homologous thereto.
37. The kit of claim 33, wherein the plurality of pairs of primers is selected from the group consisting of: SEQ ID NOS:252 and 253, SEQ ID NOS:261 and 262, SEQ ID NOS:264 and 265, SEQ ID NOS:327 and 328, SEQ ID NOS:285 and 286, SEQ ID NOS:288 and 289, SEQ ID NOS:294 and 295, and SEQ ID NOS:330 and 331.
38. The kit of claim 33, wherein the reagent for detecting the plurality of polynucleotide markers and for measuring their expression level are reagent for employing at least one NAT-based technology selected from the group consisting of: a PCR; Real-Time PCR; LCR; Self-Sustained Synthetic Reaction; Q-Beta Replicase; Cycling Probe Reaction; Branched DNA; RFLP analysis; DGGE/TGGE; Single-Strand Conformation Polymorphism; Dideoxy Fingerprinting; Microarrays; Fluorescence In Situ Hybridization; and Comparative Genomic Hybridization.
39. The kit of claim 33, wherein the classifier is selected from the group consisting of: linear classifier and non-linear classifier.
40. The kit of claim 33, wherein the classifier has a training accuracy of at least 83%.
41. A method for predicting onset of renal injury caused by treatment with a compound, comprising: (i) administering a dose of the compound to at least one test subject; (ii) obtaining a biological sample from the at least one test subject; and (iii) determining whether the biological sample is in the positive class for onset of renal injury using the kit of claim 33.
42. The method of claim 41, wherein the biological sample is obtained from the at least one test subject after a time period selected from the group consisting of: 1 day after administering the dose of the compound; 5 days after administering the dose of the compound; 7 days after administering the dose of the compound; 14 days after administering the dose of the compound; 21 days after administering the dose of the compound; and 28 days after administering the compound.
43. A method for predicting onset of renal injury caused by treatment with a compound, comprising: (i) administering a dose of the compound to at least one test subject; (ii) obtaining a biological sample from the at least one test subject; (iii) measuring the expression level of at least two polynucleotide markers selected from the group consisting of: SEQ ID NO:1, 3, 48, 6, 12, 52 and sequences homologous thereto; and (iv) determining whether the biological sample is in the positive class for onset of renal injury.
44. The method of claim 43, wherein the polynucleotide markers comprises a set of four polynucleotide markers comprising: a first polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:1 or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:2; a second polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:3 or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:4 and 5; a third polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:6 or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:7 and 8; and a fourth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:12 or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:13 and 14, and sequences homologous thereto.
45. The method of claim 44, wherein the expression of the four polynucleotide markers is measured using a set of probes that hybridize to: a nucleic acid sequence set form in SEQ ID NO:254; a nucleic acid sequence set forth in any one of SEQ ID NO:266 and 329; a nucleic acid sequence set forth in SEQ ID NO:287; and a nucleic acid sequence set forth in SEQ ID NO:296, and sequences homologous thereto.
46. The method of claim 43, wherein the set of probes hybridizes a set of four polynucleotide markers, wherein the set of four polynucleotide markers comprises: a first polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:1 or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:2; a second polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:3 or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:4 and 5; a third polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:48 or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:49; and a fourth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:52 or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:53, and sequences homologous thereto.
47. The method of claim 46, wherein the expression of the four polynucleotide markers is measured using a set of probes that hybridize to: a nucleic acid sequence set form in SEQ ID NO:254; a nucleic acid sequence set forth in any one of SEQ ID NO:266 and 329; a nucleic acid sequence set forth in SEQ ID NO:263; and a nucleic acid sequence set forth in in any one of SEQ ID NOS:290 and 332, and sequences homologous thereto.
48. The method of claim 43, wherein the set of probes hybridizes to a set of six polynucleotide markers, wherein the set of six polynucleotide markers comprises: a first polynucleotide the nucleic acid sequence set forth in SEQ ID NO:1 or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:2; a second polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:3 or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:4 and 5; a third polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:48 or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:49; a fourth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:6 or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:7 and 8; a fifth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:12 or having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:13 and 14; and a sixth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:52 or having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:53, and sequences homologous thereto.
49. The method of claim 48, wherein the expression of the six polynucleotide markers is measured using a set of probes that hybridize to: a nucleic acid sequence set form in SEQ ID NO:254; a nucleic acid sequence set forth in any one of SEQ ID NO:266 and 329; a nucleic acid sequence set forth in SEQ ID NO:263; a nucleic acid sequence set forth in SEQ ID NO:287; a nucleic acid sequence set forth in SEQ ID NO:296; and a nucleic acid sequence set forth in in any one of SEQ ID NOS:290 and 332, and sequences homologous thereto.
50. The method of claim 43, wherein the expression of the plurality of polynucleotide markers is measured using a set of probes selected from the group consisting of: SEQ ID NO:252 and/or SEQ ID NO:253, SEQ ID NO:261 and/or SEQ ID NO:262, SEQ ID NO:264 and/or SEQ ID NO:265, SEQ ID NO:327 and/or SEQ ID NO:328, SEQ ID NO:285 and/or SEQ ID NO:286, SEQ ID NO:288 and/or SEQ ID NO:289, SEQ ID NO:294 and/or SEQ ID NO:295, and SEQ ID NO:330 and/or SEQ ID NO:331.
51. The kit of claim 33, wherein the set of probes is selected from the group consisting of: SEQ ID NO:252 and/or SEQ ID NO:253, SEQ ID NO:261 and/or SEQ ID NO:262, SEQ ID NO:264 and/or SEQ ID NO:265, SEQ ID NO:327 and/or SEQ ID NO:328, SEQ ID NO:285 and/or SEQ ID NO:286, SEQ ID NO:288 and/or SEQ ID NO:289, SEQ ID NO:294 and/or SEQ ID NO:295, and SEQ ID NO:330 and/or SEQ ID NO:331, and sequences homologous thereto.
52. The kit of claim 33, wherein the set of probes hybridizes to a set of four polynucleotide markers, wherein the set of four polynucleotide markers comprises: a first polynucleotide having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:2 or the nucleic acid sequence set forth in SEQ ID NO:254; a second polynucleotide having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:4 and 5 or the nucleic acid sequence set forth in any one of SEQ ID NO:266 and 329; a third polynucleotide having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:7 and 8 or having the nucleic acid sequence set forth in SEQ ID NO:287; and a fourth polynucleotide having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:13 and 14 or having the nucleic acid sequence set forth in SEQ ID NO:296, and sequences homologous thereto.
53. The kit of claim 33, wherein the set of probes hybridizes to a set of four polynucleotide markers, wherein the set of four polynucleotide markers comprises: a first polynucleotide having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:2 or having the nucleic acid sequence set forth in SEQ ID NO:254; a second polynucleotide having a node consisting of the nucleic acid sequence set forth in any one of SEQ ID NOS:4 and 5 or having the nucleic acid sequence set forth in any one of SEQ ID NOS:266 and 329; a third polynucleotide having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:49 or having the nucleic acid sequence set forth in SEQ ID NO:263; and a fourth polynucleotide having a node consisting of the nucleic acid sequence set forth in SEQ ID NO:53 or having the nucleic acid sequence set forth in any one of SEQ ID NOS:290 and 332, and sequences homologous thereto.
54. The kit of claim 33, wherein the set of probes hybridizes to a set of six polynucleotide markers, wherein the set of six polynucleotide markers comprises: a first polynucleotide the nucleic acid sequence set forth in SEQ ID NO:1; a second polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:3; a third polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:48; a fourth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:6; a fifth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:12; and a sixth polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:52, and sequences homologous thereto.
Description:
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation-in-part of International Application No. PCT/IL2008/001561 filed Dec. 1, 2008, which claims priority to U.S. Provisional Application No. 61/016,837, filed Dec. 27, 2007, and is also a continuation-in-part of PCT/IL2009/000235 filed Mar. 1, 2009, the contents of each of which are incorporated herein by reference thereto.
INCORPORATION-BY-REFERENCE OF MATERIAL ELECTRONICALLY FILED
[0002] Incorporated by reference in its entirety herein is a computer-readable nucleotide/amino acid sequence listing submitted concurrently herewith and identified as follows: One 555,789 byte ASCII (text) file named "Seq_List" created on Jun. 25, 2010.
FIELD OF THE INVENTION
[0003] The present invention relates to means and methods for predicting the onset of renal injury based on measuring the expression of polynucleotides and proteins, particularly measuring the expression of sets of novel polynucelotides and proteins as well as known genes.
BACKGROUND OF THE INVENTION
[0004] Renal injury is a general term used to describe any damage to the kidney caused by various conditions including primary renal dysfunction, response to external substances or secondary renal pathology.
[0005] Renal injury commonly occurs after administration of pharmaceutical or toxic agents of various types. The process is typically initiated by a toxic injury to tubular epithelial cells in various nephron segments or by injury to specific cell types in the glomerulus. The initial injury is often followed by cellular proliferation and repair processes that attempts to restore normal renal function.
[0006] Early recognition of renal injury is hampered by the lack of accurate markers and the shortcoming of and over-reliance on serum markers of impaired glomerular filtration rate (i.e., serum creatinine and blood urea nitrogen, see e.g., Schrier et al, J Clin Invest, 114(1):5-14 (2004)). Drugs associated with the development of tubular nephrosis include aminoglycoside antibiotics, antifungals, antineoplastics, immunosuppresants and radiocontrast dyes, among others.
[0007] Similarly to the human clinical setting, long-term treatment of rats during preclinical drug development with relatively low doses of, for example, aminoglycoside antibiotics, heavy metal toxicants or antineoplastic drugs, leads to the development of degenerative lesions of the renal tubules. However, histopathological or clinical indications of kidney injury are not readily apparent in the early course of treatment, thus necessitating expensive and lengthy studies.
[0008] Changes in the expression of mRNA specifically expressed in the injured kidney cells are some of the earliest events that accompany renal injury. This is further accompanied by changes in the expression of other genes that contribute either to cellular repair or recovery of renal function or in those that mediate fibrosis and further pathology of the kidney (Matejka G L. et al., Exp Nephrol, 1998 6:253-264; Norman J T. et al. Proc Natl Acad Sci USA, 1988 85:6768-6772; Safirstein R. et al. Kidney Int, 1990 37:1515-1521). For example, elevation in the expression of heme oxygenase I (HO-1), kidney injury molecule-1 (KIM-1), clusterin, thymosin beta-4, osteopontin, and several growth factors have been reported in various models of renal injury (Hammerman et al, 1998 Curr Oppin Nephrol Hypertens 7:419-424; Yoshida et al, 2002 Kidney International 61: 1646-1654; Amin R P et al. 2004 Environ Health Perspect. 112(4):465-479; Thomas R. S et. al. 2001 Mol Pharmacol. 60(6): 1189-1194).
[0009] International Patent Application Publication No. WO 2006/033701 provides gene signatures as well as methods, apparatuses and reagents useful for predicting future renal tubule injury, based on the expression levels of genes in the signatures. In one particular embodiment that invention provides a method for predicting whether a compound will induce renal tubule injury using gene expression data from sub-acute treatments. However, the WO 2006/033701 application discloses that the necessary set useful for generating meaningful signatures of 186 genes. Such vast number of genes in a single signature requires cumbersome analyses, rendering the method unefficient.
[0010] International Patent Application Publication No. WO 02/095000 provides toxicity markers identified in tissues or cells exposed to a known renal toxin, based on the elucidation of the global changes in gene expression. The genes may be used as toxicity markers in drug screening and toxicity assays. That application includes a database of genes characterized by toxin-induced differential expression designed for use with microarrays and other solid-phase probes. The WO 02/095000 Application does not provide specific combination(s) of markers that can be used for toxicity prediction, and thus the methods disclosed require measuring expression of a vast number of genes.
[0011] The development of methods to predict the future onset of renal injury and gain a greater understanding of its underlying mechanism would facilitate the development of more reliable clinical diagnostics and safer therapeutic drugs. Moreover, improved preclinical markers for renal injury, particularly of well-defined gene signatures including small number of genes would dramatically reduce the time, cost, and amount of compound required for prioritizing and selecting lead candidates for progression through drug development.
[0012] International Patent Application No. PCT/IL2008/001561 to the inventors of the present invention discloses markers and marker sets for predicting the onset of renal injury. The markers are capable of detecting the expression of novel polynucleotide variants, known genes and combinations thereof, and expression of only small number of genes and/or variant suffice to obtain the required prediction.
[0013] It will be advantageous to have additional markers and marker sets useful for predicting the onset of renal injury.
SUMMARY OF THE INVENTION
[0014] The present invention provides marker sets including novel variants, known genes and combinations thereof, the expression of which is useful in predicting the onset of renal injury, particularly an injury resulting from exposure to a toxin or pharmaceutical agent. The present invention further provides novel isolated polynucleotide and protein variants. The present invention further provides novel isolated polynucleotide and protein variants.
[0015] The present invention is based in part on the elucidation of the global changes in gene expression in tissues or cells exposed to known toxins, in particular renal toxins, as compared to unexposed, or exposed to control compounds, tissues or cells, as well as on the identification of individual genes that are differentially expressed upon exposure of the cells to a toxin. The present invention is advantageous over hitherto known methods using gene sets for predicting renal injury, because it provides small sets of only few genes necessary for accurate prediction. Moreover, the present invention provides sets based on the expression of unique polynucleotides and proteins associated with renal injury.
[0016] Thus, according to one aspect, the present invention provides an isolated polynucleotide encoding a protein having an amino acid sequence as set forth in any one of SEQ ID NOs: 62-71, 141, 143, 144, 146-153, 155, 156, 158-160, 162, 167-169, 172, 174-176, 210-214, 218, 221-223, 225, 227-228, 233, 235, 236.
[0017] According to certain embodiments, the polynucleotide has a nucleic acid sequence as set forth in any one of the SEQ. ID NOs: 1, 3, 6, 9, 12, 15, 20, 24, 27, 30, 32, 34, 36, 38, 40, 82, 84-90, 92, 94, 95-99, 101-104, 106-108, 110, 111, 113, 114, 116-119, 133, 135-137, 178, 180-184, 189, 192-194, 196, 198, 199, 203, 206, 207, or a sequence homologous thereto. According to one embodiment, the isolated polynucleotide is at least 85% homologous to any one of SEQ. ID NOs: 1, 3, 6, 9, 12, 15, 20, 24, 27, 30, 32, 34, 36, 38, 40, 82, 84-90, 92, 94, 95-99, 101-104, 106-108, 110, 111, 113, 114, 116-119, 133, 135-137, 178, 180-184, 189, 192-194, 196, 198, 199, 203, 206, 207. According to another embodiment, the isolated polynucleotide is at least 95% homologous to any one of SEQ. ID NOs: 1, 3, 6, 9, 12, 15, 20, 24, 27, 30, 32, 34, 36, 38, 40, 82, 84-90, 92, 94, 95-99, 101-104, 106-108, 110, 111, 113, 114, 116-119, 133, 135-137, 178, 180-184, 189, 192-194, 196, 198, 199, 203, 206, 207.
[0018] According to certain embodiments, the polynucleotide has a nucleic acid sequence as set forth in any one of the SEQ. ID NOs: 2, 4, 5, 7, 8, 10, 11, 13, 14, 16-19, 21-23, 25, 26, 28, 29, 31, 33, 35, 37, 39, 41.
[0019] According to other embodiments, the present invention provides an isolated protein or polypeptide having an amino acid sequence as set forth in any one of SEQ. ID NOs: 62-71, 141, 143, 144, 146-153, 155, 156, 158-160, 162, 167-169, 172, 174-176, 210-214, 218, 221-223, 225, 227-228, 233, 235, 236, or a sequence homologous thereto. According to one embodiment, the isolated protein or polypeptide is at least 85% homologous to any one of SEQ. ID NOs: 62-71, 141, 143, 144, 146-153, 155, 156, 158-160, 162, 167-169, 172, 174-176, 210-214, 218, 221-223, 225, 227-228, 233, 235, 236. According to another embodiment, the isolated polypeptide is at least 95% homologous to any one of SEQ. ID NOs: 62-71, 141, 143, 144, 146-153, 155, 156, 158-160, 162, 167-169, 172, 174-176, 210-214, 218, 221-223, 225, 227-228, 233, 235, 236.
[0020] According to certain embodiments, the isolated protein or polypeptide is encoded by an isolated polynucleotide comprising a nucleic acid sequence as set forth in any one of SEQ. ID NOs: 1, 3, 6, 9, 12, 15, 20, 24, 27, 30, 32, 34, 36, 38, 40, 82, 84-90, 92, 94, 95-99, 101-104, 106-108, 110, 111, 113, 114, 116-119, 133, 135-137, 178, 180-184, 189, 192-194, 196, 198, 199, 203, 206, 207, or a sequence homologous thereto.
[0021] According to certain embodiments of the present invention, the novel polynucleotides and proteins described herein are non-limiting examples of markers for diagnosing renal injury. The markers of the invention can be employed for various uses, including but not limited to, prognosis, prediction, screening, early diagnosis, determination of progression, staging, therapy selection and treatment monitoring of renal injury.
[0022] According to certain embodiments, the presence of at least one novel nucleic acid sequence in a biological sample predicts the onset of renal injury in the subject. According to certain embodiments, the nucleic acid sequence is as set forth in any one of SEQ ID NO: 1, 3, 6, 9, 12, 15, 20, 24, 27, 30, 32, 34, 36, 38, 40, 82, 84-90, 92, 94, 95-99, 101-104, 106-108, 110, 111, 113, 114, 116-119, 133, 135-137, 178, 180-184, 189, 192-194, 196, 198, 199, 203, 206, 207.
[0023] The present invention further provides sets of the novel polynucleotides and proteins of the present invention, sets of polynucleotides corresponding to known genes proteins encoded therefrom; and sets comprising combinations thereof, wherein expression of these nucleic acid sets is indicative of the onset of renal injury. The novel polynucleotides and proteins and sets of the invention are therefore referred to as markers of renal injury.
[0024] According to another aspect, the present invention provides a set of markers of renal injury comprising at least two markers having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 6, 9, 12, 15, 20, 24, 27, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, listed in Table 19, and the corresponding human and mouse homologues thereto as set forth in any one of SEQ ID NOs: 81-137 and 177-207, respectively, listed in Table 21.
[0025] According to certain embodiments, the at least two markers have a nucleic acid sequence selected form the group consisting of SEQ ID NOs: 1, 3, 6, 9, 12, 20, 24, 27, 30, 32, 34, 36, 38, 46, 50, 54, 56, 60 corresponding to genes listed in any one of Table 14 or 15.
[0026] According to certain embodiments, the at least two markers have a nucleic acid sequence selected form the group consisting of SEQ ID NOs: 1, 3, 6, 12, 48, 52 corresponding to genes listed in any one of Table 26 or 27, and the corresponding human and mouse homologues thereto as set forth in any one of SEQ ID NOs: 81-137 and 177-207, respectively, listed in Table 21.
[0027] According to further embodiments, the at least two markers are selected from a combination of novel polynucleotides and known genes having nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 6, 12 corresponding to genes listed in Table 13.
[0028] According to particular embodiments, the set comprises all four markers having a nucleic acid sequence set forth in SEQ ID NOs: 1, 3, 6, 12 corresponding to genes listed in Table 13, wherein expression of the four markers is indicative of the onset of renal injury.
[0029] According to additional particular embodiments, the set comprises all four markers having a nucleic acid sequence set forth in SEQ ID NOs: 1, 3, 48, 52 corresponding to genes listed in Table 26, wherein expression of the four markers is indicative of the onset of renal injury.
[0030] According to further particular embodiments, the set comprises all six markers having a nucleic acid sequence set forth in SEQ ID NOs: 1, 3, 6, 12, 48, 52 corresponding to genes listed in Table 27, wherein expression of the six markers is indicative of the onset of renal injury.
[0031] According to yet further embodiments, the at least two markers are novel polynucleotides selected from the group consisting of a nucleic acid sequence consisting of SEQ ID NOs: 1, 9, 12, 15, 24, 32, 36, 40, 44, 46, 48, 52, 54, 56, 58, 60 corresponding to genes listed in any one of Table 17 and Table 18.
[0032] According to yet additional embodiments, the at least two markers are selected from a combination of novel polynucleotides and known genes having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1, 12, 46, 48, 56, 58, 60 corresponding to genes listed in Table 16.
[0033] According to particular embodiments, the set comprises all seven markers having a nucleic acid sequence set forth in SEQ ID NOs: 1, 12, 46, 48, 56, 58, 60 corresponding to genes listed in Table 16, wherein expression of the seven markers is indicative of the onset of renal injury.
[0034] According to another aspect, the present invention provides a set of markers of renal injury comprising at least two markers having an amino acid sequence encoded by the nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1, 3, 6, 9, 12, 15, 20, 24, 27, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, listed in Table 12 or 19, or the corresponding human and mouse homologues, SEQ ID NOs: 81-137 and 177-207, respectively, listed in Table 21. According to one embodiment, the set of markers of renal injury comprises at least two markers having an amino acid sequence selected from the group consisting of SEQ ID NOs: 62-80, listed in Table 19, and the corresponding human and mouse homologues as set forth in SEQ ID NOs: 138-176 and 208-236, respectively, listed in Table 21.
[0035] According to certain embodiments, the at least two markers are novel polypeptides having an amino acid sequence selected form the group consisting of SEQ ID NO: 62-66, 68-70 corresponding to genes listed in Table 14.
[0036] According to other embodiments, the at least two markers are known proteins having an amino acid sequence selected from the group consisting of SEQ ID NO: 75, 77, 78, 80 corresponding to markers listed in Table 15.
[0037] According to other embodiments, the at least two markers are known proteins having an amino acid sequence selected from the group consisting of SEQ ID NO: 62, 63, 74, 76 corresponding to genes listed in Table 26.
[0038] According to other embodiments, the at least two markers are known proteins having an amino acid sequence selected from the group consisting of SEQ ID NO: 62-64, 66, 74, 76 corresponding to genes listed in Table 27.
[0039] According to further embodiments, the at least two markers are selected from a combination of novel and known proteins having an amino acid sequence selected from the group consisting of SEQ ID NO: 62-64, 66 corresponding to genes listed in Table 13.
[0040] According to particular embodiments, the set comprises all four markers having an amino acid sequence set forth in SEQ ID NO: 62-64, 66 corresponding to genes listed in Table 13, wherein expression of the four markers is indicative of the onset of renal injury.
[0041] According to particular embodiments, the set comprises all four markers having an amino acid sequence set forth in SEQ ID NO: 62, 63, 74, 76 corresponding to genes listed in Table 26, wherein expression of the four markers is indicative of the onset of renal injury.
[0042] According to particular embodiments, the set comprises all six markers having an amino acid sequence set forth in SEQ ID NO: 62-64, 66, 74, 76 corresponding to genes listed in Table 27, wherein expression of the four markers is indicative of the onset of renal injury.
[0043] According to yet further embodiments, the at least two markers are novel polypeptides having an amino acid sequence selected form the group consisting of SEQ ID NO: 62, 65-67, 69, 71 corresponding to genes listed in Table 17.
[0044] According to additional embodiments, the at least two markers are known proteins having an amino acid sequence selected from the group consisting of SEQ ID NO: 73, 74, 76-80 corresponding to genes listed in Table 18.
[0045] According to yet additional embodiments, the at least two markers are selected from a combination of novel and known proteins having an amino acid sequence selected from the group consisting of SEQ ID NO: 62, 66, 74, 78-80 corresponding to genes listed in Table 16.
[0046] According to particular embodiments, the set comprises six markers having an amino acid sequence set forth in SEQ ID NO: 62, 66, 74, 78-80 corresponding to genes listed in Table 16, wherein expression of the six markers is indicative of the onset of renal injury.
[0047] The markers of the invention described herein are information-rich with respect to classifying biological samples for onset of renal injury, even before histopathological or clinical indications are apparent. Thus, the marker sets of the present invention are highly efficient for the early detection of renal injury that may be caused by various conditions and/or treatments.
[0048] The present invention further provides a method for testing whether a compound will induce renal injury. According to yet another aspect, the present invention provides a method for predicting renal injury in a subject receiving a treatment with a compound, comprising (a) administering a dose of the compound to at least one test subject; (b) after a selected time period, obtaining a biological sample from the at least one test subject; (c) measuring in the biological sample the expression level of at least two markers selected from those listed in Table 12; and (d) determining whether the sample is in the positive class for onset of renal injury using a classifier comprising at least the two markers for which the expression level is measured.
[0049] According to certain embodiments, the subject is a mammal selected from the group consisting of a human, cat, dog, monkey, mouse, pig, rabbit, and rat. According to other embodiments, the subject is a test subject. According to typical embodiments the test subject is a rat. According to other embodiments, the test compound is administered to the subject in a form selected from the group consisting of intravenously (IV), orally (PO, per os), intraperitoneally (IP), intranasal, inhalation, eye drops and ointments. According to yet other embodiments, the biological sample is selected from the group consisting of kidney tissue, body fluid and body secretion.
[0050] The compound may be administered once or the administration may be repeated at any desired regime. It is to be understood that the selected period of time after which the sample is obtained refers to the time after the last compound administration.
[0051] According to other embodiments, the test compound is nephrotoxic agent. According to one embodiment, the nephrotoxic agent is selected from the group consisting of aminoglycosides; platinum based chemotherapy agents; heavy metals; DNA interacting drugs; antifungal agents; proximal tubule damaging agents; and vasoconstriction compounds.
[0052] According to one embodiment, the renal injury is associated with at least one kidney disease or pathology, selected from the group consisting of nephrotoxicity, renal toxicity, nephritis, kidney necrosis, kidney damage, glomerular and tubular injury, focal segmental glomerulosclerosis, kidney dysfunction, nephritic syndrome, acute renal failure, chronic renal failure, proximal tubal dysfunction, acute kidney transplant rejection and chronic kidney transplant refection.
[0053] According to other embodiments, the method is used for predicting at least one toxic effect of the compound; predicting the progression of a toxic effect of the compound; predicting the renal toxicity of the compound; or identifying an agent that modulates the onset or progression of a toxic response.
[0054] According to certain embodiments, the selected time period after which the sample is obtained from the test subject is prior to the appearance of histopathological or clinical indications of renal injury. According to one embodiment, the selected time period is any one of about 1 day, about 5 days, about 7 days, about 14 days, about 21 or about 28 days after administering the compound to the at least one test subject. According to typical embodiments, the selected time period is 1 day or less after administration. According to typical embodiments, the selected time period is 5 days after administration. According to other typical embodiments, the selected time period is 7 days after administration.
[0055] The at least two markers can be selected as to produce any one of the marker sets disclosed in the present invention. According to certain embodiments, the method is performed with a marker set comprising SEQ ID NO: 1, 3, 6, 12 corresponding to sequences within the genes listed in Table 13 or polypeptide or proteins encoded therefrom. According to other typical embodiments, the method is performed with a marker set comprising SEQ ID NO: 1, 12, 46, 48, 56, 58, 60 corresponding to sequences within the genes listed in Table 16 or polypeptide or proteins encoded therefrom. According to other typical embodiments, the method is performed with a marker set comprising SEQ ID NO: 1, 3, 6, 9, 12, 20, 24, 27, 30, 32, 34, 36, 38 corresponding to sequences within the genes listed in Table 14 or polypeptide or proteins encoded therefrom. According to other typical embodiments, the method is performed with a marker set comprising SEQ ID NO: 46, 50, 54, 56, 60 corresponding to sequences within the genes listed in Table 15 or polypeptide or proteins encoded therefrom. According to other typical embodiments, the method is performed with a marker set comprising SEQ ID NO: 1, 9, 12, 15, 24, 32, 36, 40 corresponding to sequences within the genes listed in Table 17 or polypeptide or proteins encoded therefrom. According to other typical embodiments, the method is performed with a marker set comprising SEQ ID NO: 44, 46, 48, 52, 54, 56, 58, 60 corresponding to sequences within the genes listed in Table 18 or polypeptide or proteins encoded therefrom. According to other typical embodiments, the method is performed with a marker set comprising SEQ ID NO: 1, 3, 48, 52 corresponding to sequences within the genes listed in Table 26 or polypeptide or proteins encoded therefrom. According to other typical embodiments, the method is performed with a marker set comprising SEQ ID NO: 1, 3, 6, 12, 48, 52 corresponding to sequences within the genes listed in Table 18 or polypeptide or proteins encoded therefrom.
[0056] According to certain typical embodiments, the method is performed with a marker set comprising markers listed in any one of Tables 13, 14, 15, 26 or 27, and the selected time period is 5 days after compound administration. According to other typical embodiments, the method is performed with a marker set comprising markers listed in any one of Tables 16, 17 or 18, and the selected time period is 1 day after compound administration.
[0057] According to other embodiments, the classifier is a random forest classifier. In alternative embodiments, the classifier may be another linear or non-linear classifier. According to currently typical embodiments the classifier for renal injury is capable of performing with a training log odds ratio of greater than or equal to 3.75.
[0058] Any method for detecting the marker expression as is known to a person skilled in the art may be used according to the teachings of the present invention. According to certain embodiments, the expression level of the at least two markers is detected at the polynucleotide level by an amplification or hybridization assay. According to typical embodiments, the amplification assay is selected from the group consisting of quantitative or semi-quantitative PCR, Northern blot, dot or slot blot, nuclease protection and microarray assays. According to other embodiments, the expression level of the at least two markers is detected at the polypeptide level by an immunoassay. According to typical embodiments the immunoassay is selected from the group consisting of an ELISA, an RIA, a slot blot, immunohistochemical assay, FACS, a radio-imaging assay or a Western blot.
[0059] The present invention also provides means and methods for detecting the expression of the markers disclosed herein in a sample. According to certain embodiments, the present invention provides probes and primers for detecting the polynucleotide expression of the markers disclosed herein. According to one embodiment, the probe or the primer comprises a nucleic acid sequence that specifically hybridizes to sequences within a gene selected from Table 12 or Table 21.
[0060] According to other embodiments, the present invention provides a set of at least two probes or primers, wherein each of the probes or primers comprises a sequence that specifically hybridizes to a marker selected from Table 19 or Table 21.
[0061] According to additional embodiments, the present invention provides a set of at least two probes or primers, wherein each of the probes or primers comprises a sequence that specifically hybridizes to an amplicon comprising any one of SEQ ID NOs: 251, 254, 257, 260, 263, 266, 269, 272, 275, 278, 281, 284, 287, 290, 293, 296, 299, 302, 305, 308, 311, 314, 317, 320, 323, 326.
[0062] According to further embodiments, the set comprises primers comprising a nucleic acid sequence set forth in any one of SEQ ID NO: 249-250, 252-253, 255-256, 258-259, 261-262, 264-265, 267-268, 270-271, 273-274, 276-277, 279-280, 282-283, 285-286, 288-289, 291-292, 294-295, 297-298, 300-301, 303-304, 306-307, 309-310, 312-313, 315-316, 318-319, 321-322, 324-325.
[0063] According to yet further embodiments, the set comprises probes or primers that hybridize to at least a plurality of markers selected from any one of Tables 13, Table 14, Table 15, Table 26 and Table 27. According to certain currently preferred embodiments, the plurality of markers comprises all the markers of Table 13. According to other certain currently preferred embodiments, the plurality of markers comprises all the markers of Table 26. According to other certain currently preferred embodiments, the plurality of markers comprises all the markers of Table 27.
[0064] According to yet additional embodiments, the set comprises probes or primers that hybridize to at least a plurality of markers selected from any one of Tables 16, Table 17 and Table 18. According to certain currently preferred embodiments, the plurality of markers comprises all the markers of Table 16.
[0065] The hybridization probes for detecting the polynucleotides of the present invention can be used as free polynucleotides in a solution or can be attached to a solid support as is known to a person skilled in the art. According to certain embodiments, the solid support is selected from the group consisting of a membrane, a glass support and a silicon support.
[0066] According to one embodiment, detecting the presence of the polypeptide or polynucleotide is indicative of renal injury. According to another embodiment, a change in the expression level of the polynucleotide or polypeptide compared to its expression and/or level in a sample obtained from a healthy subject is indicative of the renal injury. According to a further embodiment, a change in the expression and/or level of the polynucleotide or polypeptide compared to its level and/or expression in a sample obtained from the said subject at earlier stage is indicative of the renal injury. According to still further embodiment, detecting the presence and/or relative change in the expression and/or level of the polynucleotide or polypeptide is useful for selecting a treatment and/or monitoring a treatment of renal injury.
[0067] According to additional aspect, the present invention provides a method for selecting a treatment or monitoring a treatment for renal injury comprising (a) obtaining a first sample from a subject suffering from renal injury; (b) administering the treatment to the subject; (c) obtaining a second sample from said subject; (d) measuring in the first and second samples the expression level of at least two markers selected from those listed in Table 12 or Table 21; and (d) determining a change in the expression and/or level of the polynucleotides or polypeptides in said second sample compared to the level and/or expression in said first sample, wherein relative change in said expression and/or level of the polynucleotide or polypeptide is useful for selecting a treatment and/or monitoring a treatment of the renal injury.
[0068] The present invention also provides a kit for predicting whether renal injury will occur in a test subject comprising at least one means for detecting the expression of at least two markers as described hereinabove, further comprising reagents for performing the detection. According to certain embodiments, the kit comprises at least two primers or probes and reagents for detecting at least two genes listed in Table 12. According to other embodiments, the kit comprises at least two polypeptides and reagents for detecting at least two polypeptides encoded by the genes listed in Table 12.
[0069] In one embodiment, the kit comprises at least a plurality of polynucleotides or polypeptides corresponding to a plurality of genes selected from those listed in Table 12 as described hereinabove. In one embodiment the kit comprising a plurality of markers includes markers corresponding to at least 2 genes selected from those listed in Table 12. In another preferred embodiment the plurality of genes are variables in a classifier capable of classifying renal injury with a training log odds ratio of greater than or equal to 3.75. In one typical embodiment, the kit comprises polynucleotides or polypeptides capable of detecting a subset of genes listed in any one of tables 13, 26, 27 and 16, as described hereinabove. In one preferred embodiment, the kit comprises polynucleotide probes capable of hybridizing to a plurality of transcripts of genes selected from those listed in Table 12 as described hereinabove. In one preferred embodiment, the kit comprises polynucleotide probes capable of hybridizing to a plurality of amplicons selected from those listed in Table 20. In one preferred embodiment, the kit comprises polynucleotide probes selected from those listed in Table 20. According to further embodiments, the kit further comprises at least one solid surface, wherein a plurality of polynucleotide probes are bound the at least one solid surface. In one embodiment, the plurality of probes is bound to a single solid surface in an array. Alternatively, the plurality of probes is bound to the solid surface on a plurality of beads.
[0070] According to one embodiment, the kit comprises reagents for detecting the marker expression by employing a NAT-based technology. In one embodiment, the NAT-based assay is selected from the group consisting of a PCR, Real-Time PCR, LCR, Self-Sustained Synthetic Reaction, Q-Beta Replicase, Cycling Probe Reaction, Branched DNA, RFLP analysis, DGGE/TGGE, Single-Strand Conformation Polymorphism, Dideoxy Fingerprinting, Microarrays, Fluorescence, In Situ Hybridization or Comparative Genomic Hybridization.
[0071] According to other preferred embodiments, the kit comprises a plurality of antibodies capable of recognizing or interacting with a plurality of polypeptides encoded by genes selected from those listed in Table 12. In certain embodiments, the polypeptides are secreted proteins encoded by genes listed in Table 12. According to other embodiments, the kit further comprises at least one reagent for performing an ELISA, an RIA, a slot blot, an immunohistochemical assay, FACS, in vivo imaging, a radio-imaging assay, or a Western blot.
[0072] Other objects, features and advantages of the present invention will become clear from the following description and drawings.
BRIEF DESCRIPTION OF THE FIGURES
[0073] FIG. 1 presents chemical structure of T1 drug
[0074] FIG. 2 presents chemical structure of T2 drug
[0075] FIGS. 3A-3B present histological section of the kidney, magnified .times.200. FIG. 3A presents a control animal. The arrows represent normal aspects of cortical tubules (eosinophilic cytoplasm). FIG. 3B presents 50 mg/kg T2-treated animal. The arrows represent basophilic tubules in the cortex, indicating post-necrotic regeneration.
[0076] FIGS. 4A-4B present histological section of the kidney, magnified .times.400. FIG. 4A presents a control animal. The arrows represent normal aspects of cortical tubules (eosinophilic cytoplasm). FIG. 4B presents 50 mg/kg T2-treated animal. The arrows represent basophilic tubules in the cortex, indicating post-necrotic regeneration.
[0077] FIGS. 5A-5B present histological section of the kidney, magnified .times.600. FIG. 5A presents a control animal. The arrows represent normal aspects of cortical tubules (eosinophilic cytoplasm). FIG. 5B presents 50 mg/kg T2-treated animal. The arrows represent basophilic tubules in the cortex, indicating post-necrotic regeneration.
[0078] FIG. 6 presents the ROC curve of the Random-Forest classifier based on the Real Time PCR measurements from the validation stage of the labeled samples. The ROC curve is based on the out-of-the-bag method for estimating the performance of a Random-Forest classifier.
DETAILED DESCRIPTION OF THE INVENTION
[0079] The present invention provides novel polynucleotides and polypeptides, as well as sets of these novel compounds and sets of known genes which are useful as diagnostic markers, particularly for predicting the onset of renal injury.
[0080] The present invention further provides methods for predicting whether a treatment with a compound would induce renal injury, following sub-chronic or long-term treatment. The present invention is based in part on gene expression data obtained from sub-acute or short-term treatments with a certain compound. The present invention now discloses necessary and sufficient sets of genes and specific signatures comprising these genes that allow gene expression data to be used to identify the ability of a compound treatment to induce late onset of renal injury before actual histological or clinical indication are apparent. Further, the invention provides kits comprising means for detecting the expression of the disclosed gene sets and signatures. The means and methods provided by the present invention enable the detection of a compound toxicity using short term studies, avoiding lengthy and costly long term studies.
DEFINITIONS
[0081] "Marker": in some embodiments, the phrase "marker" in the context of the present invention refers to a nucleic acid fragment, a peptide, or a polypeptide, which is differentially expressed in a sample taken from subjects exposed to a toxin, as compared to a comparable sample taken from subjects
[0082] As used herein, the term "expression" refers to the presence and/or level of a nucleic acid molecule, peptide or polypeptide in a sample at a certain time point, which amount may be the result of any process taking place in a cell within the sample, including, but not limited to, gene transcription and translation (gene expression) and degradation or stabilization of the gene product.
[0083] "Renal injury" refers to any damage to the kidney that can be caused by primary renal dysfunction (i.e Alport's syndrome, response to external substances (nephrotoxicants), infections, altered blood supply, malignancies, etc.) or secondary renal pathology (i.e. complications of diabetes mellitus, multiple myeloma, etc.).
[0084] Renal injury includes but is not limited to: nephritis, kidney necrosis, kidney damage, nephrotoxicity, renal toxicity, glomerular and tubular injury, focal segmental glomerulosclerosis, kidney dysfunction, nephritic syndrome, acute renal failure, chronic renal failure, proximal tubal dysfunction, acute kidney transplant rejection, chronic kidney transplant refection.
[0085] "Nephrotoxicant": in the context of the present invention is used interchangeably with the phrase "nephrotoxic agent" and/or "renal toxin", and refers to every substance (chemical compound and/or protein, recombinant or endogenous, including toxins or medications) that accumulates or that its clearance is via the renal system and causes renal injury. Examples of substance families that can cause such renal injury include but are not limited to: Aminoglycosides (i.e. Gentamicin Tobramycin, Amikacin, Kanamycin, Neomycin, Netilmicin, Paromomycin, Streptomycin, Tobramycin and Apramycin); Platinum based chemotherapy (i.e. Cisplatic, carboplatin); Heavy metals (i.e. Cadmium Chloride, Chromium, Arsenic, Lead, Mercury, Mangane); DNA interacting drugs (i.e. Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Mitoxantrone); Antifungal (i.e. Amphotericin B); Proximal tubule damaging agents (i.e. Acyclovir, Foscarnet, Pentamidine, Ifosfamide); and Vasoconstriction compounds (i.e. Radiocontrast agents, Cyclosporine, Tacrolimus).
[0086] As used herein, the term "test subject" refers to a subject receiving a compound or a treatment in order to evaluate the effect of the compound or treatment on the subject, including its efficacy, side effects, adverse effects and the like. According to typical embodiments, the test subject is a mammal.
[0087] "Multivariate dataset" as used herein, refers to any dataset comprising a plurality of different variables including but not limited to chemogenomic datasets comprising intensity measurements from gene expression experiments, such as those carried out on polynucleotide microarrays, or multiple protein binding affinities measured using a protein chip. Other examples of multivariate data include assemblies of data from a plurality of standard toxicological or pharmacological assays (e.g., blood analytes measured using enzymatic assays, antibody based ELISA or other detection techniques).
[0088] "Variable" as used herein, refers to any value that may vary. For example, variables may include relative or absolute amounts of biological molecules, such as mRNA or proteins, or other biological metabolites. Variables may also include dosing amounts of test compounds.
[0089] "Classifier" as used herein, refers to a function of a set of variables that is capable of answering a classification question. A "classification question" may be of any type susceptible to yielding a yes or no answer (e.g., "Is the unknown a member of the class or does it belong with everything else outside the class?"). A valid classifier is defined as a classifier capable of achieving a performance for its classification task at or above a selected threshold value. For example, a log odds ratio >3.75 represents a preferred threshold of the present invention. Higher or lower threshold values may be selected depending of the specific classification task.
[0090] "Random Forest" as used herein, refers to a type of non-linear classifier based on the majority decision of a collection of decision trees, each stating the outcome label (e.g. --the answer to the classification question), according to the values of the input variables. (Breiman, Leo "Random Forests". Machine Learning 45 (1), 5-32, 2001). We use the random forest algorithm supplied by the R programming language.
[0091] "Signature" as used herein, refers to a combination of variables. As well as, possibly, a classification algorithm that provides a unique value or function capable of answering a classification question. A signature may include as few as one variable. Signatures include but are not limited to Random Forest classifiers.
[0092] "Log odds ratio" or "LOR" is used herein to summarize the performance of classifiers or signatures. LOR is defined generally as the natural log of the ratio of predicting a subject to be positive when it is positive, versus the odds of predicting a subject to be positive when it is negative. LOR is estimated herein using a set of training or test cross-validation partitions according to the following equation,
LOR = ln ( i = 1 c TP i + 0.5 ) * ( i = 1 c TN i + 0.5 ) ( i = 1 c FP i + 0.5 ) * ( i = 1 c FN i + 0.5 ) ##EQU00001##
[0093] Where c (typically c=100 as described herein) equals the number of partitions, and TP.sub.i, TN.sub.i, FP.sub.i and FN.sub.i represent the number of true positive, true negative, false positive, and false negative occurrences in the test set of the i.sup.th partition, respectively.
[0094] "Accuracy" as used herein, refers to an alternative mean of summarizing the performance of classifiers of signatures. Accuracy is the percentage of correctly labeled samples. It is estimated herein using a set of training or test cross-validation partitions according to the following equation,
ACC = 100 * i = 1 c ( TP i + TN i ) i = 1 c N i ##EQU00002##
[0095] Where c (typically c=100 as described herein) equals the number of partitions, TP.sub.i, TN.sub.i, and N.sub.i represent the number of true positive, true negative, and all samples in the test set of the i.sup.th partition, respectively.
[0096] "Array" as used herein, refers to a set of different biological molecules (e.g., polynucleotides, peptides, carbohydrates, etc.). An array may be immobilized in or on one or more solid substrates (e.g., glass slides, beads, or gels) or may be a collection of different molecules in solution (e.g., a set of PCR primers). An array may include a plurality of biological polymers of a single class (e.g., polynucleotides) or a mixture of different classes of biopolymers (e.g., an array including both proteins and nucleic acids immobilized on a single substrate).
[0097] "Array data" as used herein refers to any set of constants and/or variables that may be observed, measured or otherwise derived from an experiment using an array, including but not limited to: fluorescence (or other signaling moiety) intensity ratios, binding affinities, hybridization stringency, temperature, buffer concentrations.
[0098] "Proteomic data" as used herein refers to any set of constants and/or variables that may be observed, measured or otherwise derived from an experiment involving a plurality of mPvNA translation products (e.g., proteins, peptides, etc) and/or small molecular weight metabolites or exhaled gases associated with these translation products.
General Methods of the Invention
[0099] The present invention provides novel polynucleotide and protein and gene signatures useful for detecting renal injury. The invention discloses lists of genes that may be used to create a signature that performs above a certain minimal threshold level for a specific prediction of renal injury. This set of genes also may be used to derive additional signatures with varying numbers of genes and levels of performance for particular applications (e.g., diagnostic assays and devices).
Using Signatures for Predicting Renal Injury
[0100] A diagnostic usually consists in performing one or more assays and in assigning a sample to one or more categories based on the results of the assay(s). Desirable attributes of diagnostic assays include high sensitivity and specificity measured in terms of low false negative and false positive rates and overall accuracy. Because diagnostic assays are often used to assign large number of samples to given categories, the issues of cost per assay and throughput (number of assays per unit time or per worker hour) are of paramount importance. Typically the development of a diagnostic assay involves the following steps: (1) define the end point to diagnose, e.g., renal injury; (2) identify one or more markers whose alteration correlates with the end point, e.g., elevation of expression of a gene set; and (3) develop a specific, accurate, high-throughput and cost-effective assay for that marker. In order to increase throughput and decrease costs several diagnostics are often combined in a panel of assays, especially when the detection methodologies are compatible. For example several ELISA-based assays, each using different antibodies to ascertain different end points may be combined in a single panel and commercialized as a single kit. Even in this case, however, each of the ELISA-based assays had to be developed individually often requiring the generation of specific reagents.
[0101] The present invention provides signatures comprising as few as 2 genes, preferably as few as 4 genes, preferably as few as 5 genes, that are useful for determining a therapeutic or toxicological end-point for renal injury. These signatures (and the genes from which they are composed) may also be used in the design of improved diagnostic kits that answer the same questions as a large microarray but using a much smaller fraction of data. Generally, the reduction of information in a large chemogenomic dataset to a simple signature enables much simpler devices compatible with low cost high throughput multi-analyte measurement.
[0102] Consequently, the signatures of the present invention provide the ability to produce cheaper, higher throughput, diagnostic measurement methods or strategies. In particular, the invention provides diagnostic marker sets useful in diagnostic assays and the associated diagnostic kits. As used herein, diagnostic assays include assays that may be used for test subjects, patient prognosis and therapeutic monitoring.
[0103] Diagnostic marker sets may include markers representing a subset of genes disclosed in Table 12-18, and tables 26-27, and the genes homologous thereto, disclosed in table 21. In one preferred embodiment, the diagnostic marker set is a plurality of polynucleotides or polypeptides representing specific genes in the list contained in these tables. Such biopolymer marker sets are immediately applicable in any of the diagnostic assay methods (and the associate kits) well known for polynucleotides and polypeptides (e.g., DNA arrays, RT-PCR, immunoassays or other receptor based assays for polypeptides or proteins). Thus, a very simple diagnostic array may be designed that answers 3 or 4 specific classification questions and includes only 10-20 polynucleotides representing the approximately 5-10 genes in each of the signatures. Of course, depending on the level of accuracy required the LOR threshold for selecting a sufficient gene signature may be varied.
[0104] The diagnostic marker sets of the invention may be provided in kits, wherein the kits may or may not comprise additional reagents or components necessary for the particular diagnostic application in which the marker set is to be employed. Thus, for a polynucleotide array applications, the diagnostic marker sets may be provided in a kit which further comprises one or more of the additional requisite reagents for amplifying and/or labeling a microarray probe or target (e.g., polymerases, labeled nucleotides, and the a variety of array formats (for either polynucleotides and/or polypeptides) are well-known in the art and may be used with the methods and subsets produced by the present invention. In one embodiment, photolithographic or micromirror methods may be used to spatially direct light-induced chemical modifications of spacer units or functional groups resulting in attachment at specific localized regions on the surface of the substrate. Light-directed methods of controlling reactivity and immobilizing chemical compounds on solid substrates are well-known in the art and described in U.S. Pat. Nos. 4,562,157, 5,143,854, 5,556,961, 5,968,740, and 6,153,744, and PCT publication WO 99/42813, each of which is hereby incorporated by reference herein.
[0105] Alternatively, a plurality of molecules may be attached to a single substrate by precise deposition of chemical reagents. For example, methods for achieving high spatial resolution in depositing small volumes of a liquid reagent on a solid substrate are disclosed in U.S. Pat. Nos. 5,474,796 and 5,807,522, both of which are hereby incorporated by reference herein.
[0106] It should also be noted that in many cases a single diagnostic device may not satisfy all needs. However, even for an initial exploratory investigation {e.g., classifying drug-treated rats) DNA arrays with sufficient gene sets of varying size (number of genes), each adapted to a specific follow-up technology, can be created. In addition, in the case of drug-treated rats, different arrays may be defined for each tissue.
[0107] Alternatively, a single substrate may be produced with several different small arrays of genes in different areas on the surface of the substrate. Each of these different arrays may represent a sufficient set of genes for the same classification question but with a different optimal gene signature for each different tissue. Thus, a single array could be used for particular diagnostic question regardless of the tissue source of the sample (or even if the sample was from a mixture of tissue sources, e.g., in a forensic sample).
[0108] According to the present invention, the genes identified in Table 12 may be used as markers or drug targets to evaluate the effects of a candidate drug, chemical compound or other agent on a cell or tissue sample. The genes may also be used as drug targets to screen for agents that modulate their expression and/or activity. In various formats, a candidate drug or agent can be screened for the ability to stimulate the transcription or expression of a given marker or markers or to down-regulate or counteract the transcription or expression of a marker or markers. According to the present invention, one can also compare the specificity of a drug's effects by looking at the number of markers which the drug induces and comparing them. More specific drugs will have less transcriptional targets. Similar sets of markers identified for two drugs may indicate a similarity of effects.
[0109] Assays to monitor the expression of a marker or markers as defined in Table 12 may utilize any available means of monitoring for changes in the expression level of the nucleic acids of the invention. As used herein, an agent is said to modulate the expression of a nucleic acid of the invention if it is capable of up- or down-regulating expression of the nucleic acid in a cell.
Nucleic Acid Assay Formats
[0110] The genes identified as being differentially expressed upon exposure to a known renal toxin (Tables 12-18 and 26-27, and Table 21) may be used in a variety of nucleic acid detection assays to detect or quantify the expression level of a gene or multiple genes in a given sample.
[0111] Any assay format to detect gene expression may be used. For example, traditional Northern blotting, dot or slot blot, nuclease protection, primer directed amplification, RT-PCR, semi- or quantitative PCR, branched-chain DNA and differential display methods may be used for detecting gene expression levels. Those methods are useful for some embodiments of the invention. In cases where smaller numbers of genes are detected, amplification based assays may be most efficient.
[0112] Methods and assays of the invention, however, may be most efficiently designed with hybridization-based methods for detecting the expression of a large number of genes.
[0113] Any hybridization assay format may be used, including solution-based and solid support-based assay formats. Solid supports containing oligonucleotide probes for differentially expressed genes of the invention can be filters, polyvinyl chloride dishes, particles, beads, microparticles or silicon or glass based chips, etc. Such chips, wafers and hybridization methods are widely available, for example, those disclosed by Beattie (WO 95/11755).
[0114] Any solid surface, to which oligonucleotides can be bound, either directly or indirectly, either covalently or non-covalently, can be used. A preferred solid support is a high density array or DNA chip. These contain a particular oligonucleotide probe in a predetermined location on the array. Each predetermined location may contain more than one molecule of the probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features. There may be, for example, from 2, 10, 100, 1000 to 10,000, 100,000 or 400,000 or more of such features on a single solid support. The solid support or the area within which the probes are attached may be on the order of about a square centimeter. Probes corresponding to the genes of Tables 12-18 and 26-27, or Table 21 may be attached to single or multiple solid support structures, e.g., the probes may be attached to a single chip or to multiple chips to comprise a chip set.
[0115] Oligonucleotide probe arrays for expression monitoring can be made and used according to any techniques known in the art (see for example, Lockhart et al. (1996), NatBiotechnol 14: 1675-1680; McGall et al. (1996), Proc Nat Acad Sci USA 93: 13555-13460). Such probe arrays may contain at least two or more oligonucleotides that are complementary to or hybridize to two or more of the genes described in Tables 12-18 and 26-27 or Table 21. In one embodiment, such arrays contain oligonucleotides that are complementary to or hybridize to any subset of the genes in any one or all of Tables 14, 15, 17, 18, 26 and 27. In a preferred embodiment, such arrays contain oligonucleotides that are complementary to or hybridize to all or nearly all of the genes in any one of Tables 13, 16, 26 and 27. Preferred arrays contain all or nearly all of the genes listed in Tables 12-18 and 26-27 or Table 21. In a preferred embodiment, arrays are constructed that contain oligonucleotides to detect all or nearly all of the genes in any one or all of Tables 12-18, 26-27 and Table 21, in particular Tables 13, 14, 16, 27, 26 and 27 on a single solid support substrate, such as a chip.
NAT Assays
[0116] Detection of a nucleic acid of interest in a biological sample may also optionally be effected by NAT-based assays, which involve nucleic acid amplification technology, such as PCR for example (or variations thereof such as real-time PCR for example).
[0117] As used herein, a "primer" defines an oligonucleotide which is capable of annealing to (hybridizing with) a target sequence, thereby creating a double stranded region which can serve as an initiation point for DNA synthesis under suitable conditions.
[0118] Amplification of a selected, or target, nucleic acid sequence may be carried out by a number of suitable methods. See generally Kwoh et al., 1990, Am. Biotechnol. Lab. 8:14 Numerous amplification techniques have been described and can be readily adapted to suit particular needs of a person of ordinary skill. Non-limiting examples of amplification techniques include polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), transcription-based amplification, the q3 replicase system and NASBA (Kwoh et al., 1989, Proc. NatI. Acad. Sci. USA 86, 1173-1177; Lizardi et al., 1988, BioTechnology 6:1197-1202; Malek et al., 1994, Methods Mol. Biol., 28:253-260; and Sambrook et al., 1989, supra).
[0119] The terminology "amplification pair" (or "primer pair") refers herein to a pair of oligonucleotides (oligos) of the present invention, which are selected to be used together in amplifying a selected nucleic acid sequence by one of a number of types of amplification processes, preferably a polymerase chain reaction. Other types of amplification processes include ligase chain reaction, strand displacement amplification, or nucleic acid sequence-based amplification, as explained in greater detail below. As commonly known in the art, the oligos are designed to bind to a complementary sequence under selected conditions.
[0120] In one particular embodiment, amplification of a nucleic acid sample from a patient is amplified under conditions which favor the amplification of the most abundant differentially expressed nucleic acid. In one preferred embodiment, RT-PCR is carried out on an mRNA sample from a patient under conditions which favor the amplification of the most abundant mRNA. In another preferred embodiment, the amplification of the differentially expressed nucleic acids is carried out simultaneously. It will be realized by a person skilled in the art that such methods could be adapted for the detection of differentially expressed proteins instead of differentially expressed nucleic acid sequences.
[0121] The nucleic acid (i.e. DNA or RNA) for practicing the present invention may be obtained according to well known methods.
[0122] Oligonucleotide primers of the present invention may be of any suitable length, depending on the particular assay format and the particular needs and targeted genomes employed. Optionally, the oligonucleotide primers are at least 12 nucleotides in length, preferably between 15 and 24 molecules, and they may be adapted to be especially suited to a chosen nucleic acid amplification system. As commonly known in the art, the oligonucleotide primers can be designed by taking into consideration the melting point of hybridization thereof with its targeted sequence (Sambrook et al., 1989, Molecular Cloning--A Laboratory Manual, 2nd Edition, CSH Laboratories; Ausubel et al., 1989, in Current Protocols in Molecular Biology, John Wiley & Sons Inc., N.Y.).
[0123] It will be appreciated that antisense oligonucleotides may be employed to quantify expression of a splice isoform of interest. Such detection is effected at the pre-mRNA level. Essentially the ability to quantitate transcription from a splice site of interest can be effected based on splice site accessibility. Oligonucleotides may compete with splicing factors for the splice site sequences. Thus, low activity of the antisense oligonucleotide is indicative of splicing activity.
[0124] The polymerase chain reaction and other nucleic acid amplification reactions are well known in the art (various non-limiting examples of these reactions are described in greater detail below). The pair of oligonucleotides according to this aspect of the present invention are preferably selected to have compatible melting temperatures (Tm), e.g., melting temperatures which differ by less than that 7.degree. C., preferably less than 5.degree. C., more preferably less than 4.degree. C., most preferably less than 3.degree. C., ideally between 3.degree. C. and 0.degree. C.
[0125] Polymerase Chain Reaction (PCR): The polymerase chain reaction (PCR), as described in U.S. Pat. Nos. 4,683,195 and 4,683,202 to Mullis and Mullis et al., is a method of increasing the concentration of a segment of target sequence in a mixture of genomic DNA without cloning or purification. This technology provides one approach to the problems of low target sequence concentration. PCR can be used to directly increase the concentration of the target to an easily detectable level. This process for amplifying the target sequence involves the introduction of a molar excess of two oligonucleotide primers which are complementary to their respective strands of the double-stranded target sequence to the DNA mixture containing the desired target sequence. The mixture is denatured and then allowed to hybridize. Following hybridization, the primers are extended with polymerase so as to form complementary strands. The steps of denaturation, hybridization (annealing), and polymerase extension (elongation) can be repeated as often as needed, in order to obtain relatively high concentrations of a segment of the desired target sequence.
[0126] The length of the segment of the desired target sequence is determined by the relative positions of the primers with respect to each other, and, therefore, this length is a controllable parameter. Because the desired segments of the target sequence become the dominant sequences (in terms of concentration) in the mixture, they are said to be "PCR-amplified."
[0127] Ligase Chain Reaction (LCR or LAR): The ligase chain reaction [LCR; sometimes referred to as "Ligase Amplification Reaction" (LAR)] has developed into a well-recognized alternative method of amplifying nucleic acids. In LCR, four oligonucleotides, two adjacent oligonucleotides which uniquely hybridize to one strand of target DNA, and a complementary set of adjacent oligonucleotides, which hybridize to the opposite strand are mixed and DNA ligase is added to the mixture. Provided that there is complete complementarity at the junction, ligase will covalently link each set of hybridized molecules. Importantly, in LCR, two probes are ligated together only when they base-pair with sequences in the target sample, without gaps or mismatches. Repeated cycles of denaturation, and ligation amplify a short segment of DNA. LCR has also been used in combination with PCR to achieve enhanced detection of single-base changes: see for example Segev, PCT Publication No. WO9001069 A1 (1990). However, because the four oligonucleotides used in this assay can pair to form two short ligatable fragments, there is the potential for the generation of target-independent background signal. The use of LCR for mutant screening is limited to the examination of specific nucleic acid positions.
[0128] Self-Sustained Synthetic Reaction (3SR/NASBA): The self-sustained sequence replication reaction (3SR) is a transcription-based in vitro amplification system that can exponentially amplify RNA sequences at a uniform temperature. The amplified RNA can then be utilized for mutation detection. In this method, an oligonucleotide primer is used to add a phage RNA polymerase promoter to the 5' end of the sequence of interest. In a cocktail of enzymes and substrates that includes a second primer, reverse transcriptase, RNase H, RNA polymerase and ribo- and deoxyribonucleoside triphosphates, the target sequence undergoes repeated rounds of transcription, cDNA synthesis and second-strand synthesis to amplify the area of interest. The use of 3SR to detect mutations is kinetically limited to screening small segments of DNA (e.g., 200-300 base pairs).
[0129] Q-Beta (Q.beta.) Replicase: In this method, a probe which recognizes the sequence of interest is attached to the replicatable RNA template for Q.beta. replicase. A previously identified major problem with false positives resulting from the replication of unhybridized probes has been addressed through use of a sequence-specific ligation step. However, available thermostable DNA ligases are not effective on this RNA substrate, so the ligation must be performed by T4 DNA ligase at low temperatures (37 degrees C.). This prevents the use of high temperature as a means of achieving specificity as in the LCR, the ligation event can be used to detect a mutation at the junction site, but not elsewhere.
[0130] A successful diagnostic method must be very specific. A straight-forward method of controlling the specificity of nucleic acid hybridization is by controlling the temperature of the reaction. While the 3SR/NASBA, and Q.beta. systems are all able to generate a large quantity of signal, one or more of the enzymes involved in each cannot be used at high temperature (i.e., >55.degree. C.). Therefore the reaction temperatures cannot be raised to prevent non-specific hybridization of the probes. If probes are shortened in order to make them melt more easily at low temperatures, the likelihood of having more than one perfect match in a complex genome increases. For these reasons, PCR and LCR currently dominate the research field in detection technologies.
[0131] The basis of the amplification procedure in the PCR and LCR is the fact that the products of one cycle become usable templates in all subsequent cycles, consequently doubling the population with each cycle. The final yield of any such doubling system can be expressed as: (1+X).sup.n=y, where "X" is the mean efficiency (percent copied in each cycle), "n" is the number of cycles, and "y" is the overall efficiency, or yield of the reaction. If every copy of a target DNA is utilized as a template in every cycle of a polymerase chain reaction, then the mean efficiency is 100%. If 20 cycles of PCR are performed, then the yield will be 2.sup.20, or 1,048,576 copies of the starting material. If the reaction conditions reduce the mean efficiency to 85%, then the yield in those 20 cycles will be only 1.85.sup.20, or 220,513 copies of the starting material. In other words, a PCR running at 85% efficiency will yield only 21% as much final product, compared to a reaction running at 100% efficiency. A reaction that is reduced to 50% mean efficiency will yield less than 1% of the possible product.
[0132] In practice, routine polymerase chain reactions rarely achieve the theoretical maximum yield, and PCRs are usually run for more than 20 cycles to compensate for the lower yield. At 50% mean efficiency, it would take 34 cycles to achieve the million-fold amplification theoretically possible in 20, and at lower efficiencies, the number of cycles required becomes prohibitive. In addition, any background products that amplify with a better mean efficiency than the intended target will become the dominant products.
[0133] Also, many variables can influence the mean efficiency of PCR, including target DNA length and secondary structure, primer length and design, primer and dNTP concentrations, and buffer composition, to name but a few. Contamination of the reaction with exogenous DNA (e.g., DNA spilled onto lab surfaces) or cross-contamination is also a major consideration. Reaction conditions must be carefully optimized for each different primer pair and target sequence, and the process can take days, even for an experienced investigator. The laboriousness of this process, including numerous technical considerations and other factors, presents a significant drawback to using PCR in the clinical setting. Indeed, PCR has yet to penetrate the clinical market in a significant way. The same concerns arise with LCR, as LCR must also be optimized to use different oligonucleotide sequences for each target sequence. In addition, both methods require expensive equipment, capable of precise temperature cycling.
[0134] Many applications of nucleic acid detection technologies, such as in studies of allelic variation, involve not only detection of a specific sequence in a complex background, but also the discrimination between sequences with few, or single, nucleotide differences. One method of the detection of allele-specific variants by PCR is based upon the fact that it is difficult for Taq polymerase to synthesize a DNA strand when there is a mismatch between the template strand and the 3' end of the primer. An allele-specific variant may be detected by the use of a primer that is perfectly matched with only one of the possible alleles; the mismatch to the other allele acts to prevent the extension of the primer, thereby preventing the amplification of that sequence. This method has a substantial limitation in that the base composition of the mismatch influences the ability to prevent extension across the mismatch, and certain mismatches do not prevent extension or have only a minimal effect.
[0135] A similar 3'-mismatch strategy is used with greater effect to prevent ligation in the LCR. Any mismatch effectively blocks the action of the thermostable ligase, but LCR still has the drawback of target-independent background ligation products initiating the amplification. Moreover, the combination of PCR with subsequent LCR to identify the nucleotides at individual positions is also a clearly cumbersome proposition for the clinical laboratory.
[0136] The direct detection method according to various preferred embodiments of the present invention may be, for example a cycling probe reaction (CPR) or a branched DNA analysis.
[0137] When a sufficient amount of a nucleic acid to be detected is available, there are advantages to detecting that sequence directly, instead of making more copies of that target, (e.g., as in PCR and LCR). Most notably, a method that does not amplify the signal exponentially is more amenable to quantitative analysis. Even if the signal is enhanced by attaching multiple dyes to a single oligonucleotide, the correlation between the final signal intensity and amount of target is direct. Such a system has an additional advantage that the products of the reaction will not themselves promote further reaction, so contamination of lab surfaces by the products is not as much of a concern. Recently devised techniques have sought to eliminate the use of radioactivity and/or improve the sensitivity in automatable formats. Two examples are the "Cycling Probe Reaction" (CPR), and "Branched DNA" (bDNA).
[0138] Cycling probe reaction (CPR): The cycling probe reaction (CPR), uses a long chimeric oligonucleotide in which a central portion is made of RNA while the two termini are made of DNA. Hybridization of the probe to a target DNA and exposure to a thermostable RNase H causes the RNA portion to be digested. This destabilizes the remaining DNA portions of the duplex, releasing the remainder of the probe from the target DNA and allowing another probe molecule to repeat the process. The signal, in the form of cleaved probe molecules, accumulates at a linear rate. While the repeating process increases the signal, the RNA portion of the oligonucleotide is vulnerable to RNases that may carried through sample preparation.
[0139] Branched DNA: Branched DNA (bDNA), involves oligonucleotides with branched structures that allow each individual oligonucleotide to carry 35 to 40 labels (e.g., alkaline phosphatase enzymes). While this enhances the signal from a hybridization event, signal from non-specific binding is similarly increased.
[0140] The detection of at least one sequence change according to various preferred embodiments of the present invention may be accomplished by, for example restriction fragment length polymorphism (RFLP analysis), allele specific oligonucleotide (ASO) analysis, Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE), Single-Strand Conformation Polymorphism (SSCP) analysis or Dideoxy fingerprinting (ddF).
[0141] The demand for tests which allow the detection of specific nucleic acid sequences and sequence changes is growing rapidly in clinical diagnostics. As nucleic acid sequence data for genes from humans and pathogenic organisms accumulates, the demand for fast, cost-effective, and easy-to-use tests for as yet mutations within specific sequences is rapidly increasing.
[0142] A handful of methods have been devised to scan nucleic acid segments for mutations. One option is to determine the entire gene sequence of each test sample (e.g., a bacterial isolate). For sequences under approximately 600 nucleotides, this may be accomplished using amplified material (e.g., PCR reaction products). This avoids the time and expense associated with cloning the segment of interest. However, specialized equipment and highly trained personnel are required, and the method is too labor-intense and expensive to be practical and effective in the clinical setting.
[0143] In view of the difficulties associated with sequencing, a given segment of nucleic acid may be characterized on several other levels. At the lowest resolution, the size of the molecule can be determined by electrophoresis by comparison to a known standard run on the same gel. A more detailed picture of the molecule may be achieved by cleavage with combinations of restriction enzymes prior to electrophoresis, to allow construction of an ordered map. The presence of specific sequences within the fragment can be detected by hybridization of a labeled probe, or the precise nucleotide sequence can be determined by partial chemical degradation or by primer extension in the presence of chain-terminating nucleotide analogs.
[0144] Restriction fragment length polymorphism (RFLP): For detection of single-base differences between like sequences, the requirements of the analysis are often at the highest level of resolution. For cases in which the position of the nucleotide in question is known in advance, several methods have been developed for examining single base changes without direct sequencing. For example, if a mutation of interest happens to fall within a restriction recognition sequence, a change in the pattern of digestion can be used as a diagnostic tool (e.g., restriction fragment length polymorphism [RFLP] analysis).
[0145] Single point mutations have been also detected by the creation or destruction of RFLPs. Mutations are detected and localized by the presence and size of the RNA fragments generated by cleavage at the mismatches. Single nucleotide mismatches in DNA heteroduplexes are also recognized and cleaved by some chemicals, providing an alternative strategy to detect single base substitutions, generically named the "Mismatch Chemical Cleavage" (MCC). However, this method requires the use of osmium tetroxide and piperidine, two highly noxious chemicals which are not suited for use in a clinical laboratory.
[0146] RFLP analysis suffers from low sensitivity and requires a large amount of sample. When RFLP analysis is used for the detection of point mutations, it is, by its nature, limited to the detection of only those single base changes which fall within a restriction sequence of a known restriction endonuclease. Moreover, the majority of the available enzymes has 4 to 6 base-pair recognition sequences, and cleave too frequently for many large-scale DNA manipulations. Thus, it is applicable only in a small fraction of cases, as most mutations do not fall within such sites.
[0147] A handful of rare-cutting restriction enzymes with 8 base-pair specificities have been isolated and these are widely used in genetic mapping, but these enzymes are few in number, are limited to the recognition of G+C-rich sequences, and cleave at sites that tend to be highly clustered. Recently, endonucleases encoded by group I introns have been discovered that might have greater than 12 base-pair specificity, but again, these are few in number.
[0148] Allele specific oligonucleotide (ASO): If the change is not in a recognition sequence, then allele-specific oligonucleotides (ASOs), can be designed to hybridize in proximity to the mutated nucleotide, such that a primer extension or ligation event can bused as the indicator of a match or a mis-match. Hybridization with radioactively labeled allelic specific oligonucleotides (ASO) also has been applied to the detection of specific point mutations. The method is based on the differences in the melting temperature of short DNA fragments differing by a single nucleotide. Stringent hybridization and washing conditions can differentiate between mutant and wild-type alleles. The ASO approach applied to PCR products also has been extensively utilized by various researchers to detect and characterize point mutations in ras genes and gsp/gip oncogenes. Because of the presence of various nucleotide changes in multiple positions, the ASO method requires the use of many oligonucleotides to cover all possible oncogenic mutations.
[0149] With either of the techniques described above (i.e., RFLP and ASO), the precise location of the suspected mutation must be known in advance of the test. That is to say, they are inapplicable when one needs to detect the presence of a mutation within a gene or sequence of interest.
[0150] Denaturing/Temperature Gradient Gel Electrophoresis (DGGE/TGGE): Two other methods rely on detecting changes in electrophoretic mobility in response to minor sequence changes. One of these methods, termed "Denaturing Gradient Gel Electrophoresis" (DGGE) is based on the observation that slightly different sequences will display different patterns of local melting when electrophoretically resolved on a gradient gel. In this manner, variants can be distinguished, as differences in melting properties of homoduplexes versus heteroduplexes differing in a single nucleotide can detect the presence of mutations in the target sequences because of the corresponding changes in their electrophoretic mobilities. The fragments to be analyzed, usually PCR products, are "clamped" at one end by a long stretch of G-C base pairs (30-80) to allow complete denaturation of the sequence of interest without complete dissociation of the strands. The attachment of a GC "clamp" to the DNA fragments increases the fraction of mutations that can be recognized by DGGE. Attaching a GC clamp to one primer is critical to ensure that the amplified sequence has a low dissociation temperature. Modifications of the technique have been developed, using temperature gradients, and the method can be also applied to RNA:RNA duplexes.
[0151] Limitations on the utility of DGGE include the requirement that the denaturing conditions must be optimized for each type of DNA to be tested. Furthermore, the method requires specialized equipment to prepare the gels and maintain the needed high temperatures during electrophoresis. The expense associated with the synthesis of the clamping tail on one oligonucleotide for each sequence to be tested is also a major consideration. In addition, long running times are required for DGGE. The long running time of DGGE was shortened in a modification of DGGE called constant denaturant gel electrophoresis (CDGE). CDGE requires that gels be performed under different denaturant conditions in order to reach high efficiency for the detection of mutations.
[0152] A technique analogous to DGGE, termed temperature gradient gel electrophoresis (TGGE), uses a thermal gradient rather than a chemical denaturant gradient. TGGE requires the use of specialized equipment which can generate a temperature gradient perpendicularly oriented relative to the electrical field. TGGE can detect mutations in relatively small fragments of DNA therefore scanning of large gene segments requires the use of multiple PCR products prior to running the gel.
[0153] Single-Strand Conformation Polymorphism (SSCP): Another common method, called "Single-Strand Conformation Polymorphism" (SSCP) was developed by Hayashi, Sekya and colleagues and is based on the observation that single strands of nucleic acid can take on characteristic conformations in non-denaturing conditions, and these conformations influence electrophoretic mobility. The complementary strands assume sufficiently different structures that one strand may be resolved from the other. Changes in sequences within the fragment will also change the conformation, consequently altering the mobility and allowing this to be used as an assay for sequence variations.
[0154] The SSCP process involves denaturing a DNA segment (e.g., a PCR product) that is labeled on both strands, followed by slow electrophoretic separation on a non-denaturing polyacrylamide gel, so that intra-molecular interactions can form and not be disturbed during the run. This technique is extremely sensitive to variations in gel composition and temperature. A serious limitation of this method is the relative difficulty encountered in comparing data generated in different laboratories, under apparently similar conditions.
[0155] Dideoxy fingerprinting (ddF): The dideoxy fingerprinting (ddF) is another technique developed to scan genes for the presence of mutations. The ddF technique combines components of Sanger dideoxy sequencing with SSCP. A dideoxy sequencing reaction is performed using one dideoxy terminator and then the reaction products are electrophoresed on nondenaturing polyacrylamide gels to detect alterations in mobility of the termination segments as in SSCP analysis. While ddF is an improvement over SSCP in terms of increased sensitivity, ddF requires the use of expensive dideoxynucleotides and this technique is still limited to the analysis of fragments of the size suitable for SSCP (i.e., fragments of 200-300 bases for optimal detection of mutations).
[0156] In addition to the above limitations, all of these methods are limited as to the size of the nucleic acid fragment that can be analyzed. For the direct sequencing approach, sequences of greater than 600 base pairs require cloning, with the consequent delays and expense of either deletion sub-cloning or primer walking, in order to cover the entire fragment. SSCP and DGGE have even more severe size limitations. Because of reduced sensitivity to sequence changes, these methods are not considered suitable for larger fragments. Although SSCP is reportedly able to detect 90% of single-base substitutions within a 200 base-pair fragment, the detection drops to less than 50% for 400 base pair fragments. Similarly, the sensitivity of DGGE decreases as the length of the fragment reaches 500 base-pairs. The ddF technique, as a combination of direct sequencing and SSCP, is also limited by the relatively small size of the DNA that can be screened.
[0157] According to a presently preferred embodiment of the present invention the step of searching for any of the nucleic acid sequences described here, in cells derived from a cancer patient is effected by any suitable technique, including, but not limited to, nucleic acid sequencing, polymerase chain reaction, ligase chain reaction, self-sustained synthetic reaction, Q.beta.-Replicase, cycling probe reaction, branched DNA, restriction fragment length polymorphism analysis, mismatch chemical cleavage, heteroduplex analysis, allele-specific oligonucleotides, denaturing gradient gel electrophoresis, constant denaturant gel electrophoresis, temperature gradient gel electrophoresis and dideoxy fingerprinting.
[0158] Detection may also optionally be performed with a chip or other such device. The nucleic acid sample which includes the candidate region to be analyzed is preferably isolated, amplified and labeled with a reporter group. This reporter group can be a fluorescent group such as phycoerythrin. The labeled nucleic acid is then incubated with the probes immobilized on the chip using a fluidics station.
[0159] Once the reaction is completed, the chip is inserted into a scanner and patterns of hybridization are detected. The hybridization data is collected, as a signal emitted from the reporter groups already incorporated into the nucleic acid, which is now bound to the probes attached to the chip. Since the sequence and position of each probe immobilized on the chip is known, the identity of the nucleic acid hybridized to a given probe can be determined.
[0160] It will be appreciated that when utilized along with automated equipment, the above described detection methods can be used to screen multiple samples for a disease and/or pathological condition both rapidly and easily.
Immunoassays
[0161] Assays to monitor the expression of a marker or markers as defined in Table 12 may utilize any available means of monitoring for changes in the expression level of the polypeptides and/or proteins of the present invention. As used herein, an agent is said to modulate the expression of an amino acid of the invention if it is capable of up- or down-regulating expression of the amino acid in a cell.
[0162] The genes identified as being differentially expressed upon exposure to a known renal toxin (Tables 12-18, 26-27 and Table 21) may be used in a variety of amino acid detection assays to detect or quantify the level of a polypeptide and/or protein or multiple polypeptides and/or proteins in a given sample.
[0163] Any assay format to detect polypeptide and/or protein levels may be used. For example, immunoassay, such as ELISA, an RIA, a slot blot, immunohistochemical assay, FACS, a radio-imaging assay or a Western blot, or other receptor based assays for polypeptides or proteins.
[0164] "Immunoassay" is an assay that uses an antibody to specifically bind an antigen. The immunoassay is characterized by the use of specific binding properties of a particular antibody to isolate, target, and/or quantify the antigen.
[0165] The phrase "specifically (or selectively) binds" to an antibody or "specifically (or selectively) immunoreactive with," or "specifically interacts or binds" when referring to a protein or peptide (or other epitope), refers, in some embodiments, to a binding reaction that is determinative of the presence of the protein in a heterogeneous population of proteins and other biologics. Thus, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times greater than the background (non-specific signal) and do not substantially bind in a significant amount to other proteins present in the sample. Specific binding to an antibody under such conditions may require an antibody that is selected for its specificity for a particular protein. For example, polyclonal antibodies raised to seminal basic protein from specific species such as rat, mouse, or human can be selected to obtain only those polyclonal antibodies that are specifically immunoreactive with seminal basic protein and not with other proteins, except for polymorphic variants and alleles of seminal basic protein. This selection may be achieved by subtracting out antibodies that cross-react with seminal basic protein molecules from other species. A variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A Laboratory Manual (1988), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity). Typically a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 to 100 times background.
[0166] Exemplary detectable labels, optionally and preferably for use with immunoassays, include but are not limited to magnetic beads, fluorescent dyes, radiolabels, enzymes (e.g., horse radish peroxide, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic beads. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and/or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture.
Kits
[0167] The invention further includes kits combining, in different combinations, high density oligonucleotide arrays, reagents for use with the arrays, protein encoded by the genes of Table 12 and homologous genes thereto, signal detection and array-processing instruments, gene expression databases and analysis and database management software described above.
[0168] The kits may be used, for example, to predict or model the toxic response of a test compound, to monitor the progression of renal disease states, to identify genes that show promise as new drug targets and to screen known and newly designed drugs as discussed above. The kits may be used in the pharmaceutical industry, where the need for receiving toxicity and other indications relating to a drug as early as possible is strong due to the high costs associated with drug development, but where bioinformatics, in particular gene expression informatics, is still lacking. These kits will reduce the costs, time and risks associated with traditional new drug screening using cell cultures and laboratory animals. The results of large-scale drug screening of pre-grouped patient populations, pharmacogenomics testing, can also be applied to select drugs with greater efficacy and fewer side-effects. The kits may also be used by smaller biotechnology companies and research institutes who do not have the facilities for performing such large-scale testing themselves.
[0169] Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the compounds of the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting.
[0170] The general means and methods of the invention as described above are exemplified below. The following examples are offered as illustrations of specific embodiments and are not intended to limit the inventions disclosed throughout the whole of the specification.
EXAMPLES
Example 1
Identification of Toxicity Markers
Experimental Design
[0171] The renal toxins Gentamycin (antibiotic), Cisplatin (chemotherapeutic agent), Tobramycin (antibiotic), Cadmium chloride (heavy metal in the following industries: plastic, electroplating, batteries, paints, smelter), Doxorubicin (chemotherapeutic antibiotic) and Valprioc acid (antiepileptic agent that was used as a negative control), were administered to male and female Sprague-Dawley rats at various time points and routes of administration as describes below. The Sprague-Dawley Crl:CD(SD) rats were selected for the current investigation, since this strain is frequently used in preclinical investigations including investigations of microarray expression profiling during preclinical drug development.
[0172] The test items (positive and negative controls) were administered to animals in accordance with the usual route of administration in humans (i.e. IP for gentamycin, cisplatin, tobramycin and cadmium; IV for doxorubicin; and oral for valproic acid). Control animals were treated intraperitoneal with saline.
[0173] Each substance was administered to the animals once or daily for 5 days or 28 days at the appropriate dose level. The test substances and dose levels were selected according to the predicted pathological effects of each compound: the selected dose of each compound was expected to cause no histological changes after single dose administration, but to induce significant kidney toxicity after 28 days of daily treatment.
Dose Formulation:
[0174] Gentamycin: intraperitoneal (IP) injection (80 mg/mL)
[0175] Cisplatin: injection (10 mg/20 mL)
[0176] Tobramycin (Brulamycin): injection (40 mg/1 mL and 80 mg/2 mL)
[0177] Cadmium chloride: a stock solution was prepared according to the valid SOP of IDRI (VIG/010 "Preparation of injection").
[0178] Doxorubicin: intravenous (IV) injection (20 mg/10 mL),
[0179] Valproic acid--negative control: a suspension in concentration of 100 mg/mL for oral use (PO).
[0180] Randomization and group allocation: prior to treatment, the animals were assigned to the experimental groups based on their body weight. Mean body weight of each group at randomization was not deviate.+-.20% of the mean population weight. Males and females were randomized separately. For the randomization, a computer program was used.
[0181] The original study groups and doses are shown in Table 1 below. Allocation to the dose group, 3 animals in each group, is shown in Table 2.
TABLE-US-00001 TABLE 1 Original study groups and doses Conc. Dose of Dose Volume stock Route of No. of animals Groups Test items (mg/kg) (ml/kg) (mg/ml) administration Males Females 1MF Control/Saline -- 5 -- IP 9 9 2MF Gentamycin 40 2 20 IP 9 9 3MF Cisplatin 0.5 2 0.25 IP 9 9 4MF Tobramycin 40 2 20 IP 9 9 5MF Cadmium 2 2 1 IP 9 9 chloride 6MF Doxorubicin 4 2 2 IV 9 9 7MF Valproic acid 500 5 100 PO 9 9
TABLE-US-00002 TABLE 2 Allocation to the dose group, 3 animals in each group Duration of treatment Groups (days) 1MF 1, 5, 28 2MF 1, 5, 28 3MF 1, 5, 28 4MF 1, 5, 28 5MF 1, 5, 28 6MF 1, 5, 28 7MF 1, 5, 28
Results
[0182] The animals were treated with 6 different test items each for 3 duration of treatment (1, 5 and 28 days). The actual study design is shown in Table 3.
TABLE-US-00003 TABLE 3 Study design Conc. Dose of Dose Volume stock Route of No. of animals Groups Test items (mg/kg) (ml/kg) (mg/ml) administration Males Females 1MF Control/Saline -- 2 -- IP 9 9 2MF Gentamycin 40 2 20 IP 9 9 3MF Cisplatin 0.5 2 0.25 IP 9 9 4MF Tobramycin 40 2 20 IP 9 9 5MF Cadmium cl.* 20.75* 2 10.375 IP 9 9 6MF Doxorubicin** 41** 2 20.5 IV 9 9 7MF Valproic acid 500 5 100 PO 9 9 8MF*** -- -- -- -- -- 3 3 IV--intravenous, IP--intraperitoneal, PO--oral (per os) Modifications to the original study design: *Animals treated with Cadmium chloride did not tolerate the treatment well, for that reason the dose was modified from 2 mg/kg to 0.75 mg/kg. Since males were in poor condition and excluded from the study, control (naive) animals were introduced to the 5M dose group and treated with the lower dose for 24 days. **From day 7 onwards, a sudden decay was observed in the condition of males and females treated with 4 mg/kg Doxorubicin (6MF group). This decay affected the 28-days study group of 6MF. These animals died or became moribund; therefore, naive animals were introduced into this group. The dose of the Doxorubicin treated group was lowered .from 4 mg/kg to 1 mg/kg. However, males from Day 19-20 and females from Day 22 received 0.5 mg/kg dose of Doxorubicin, due to their decrease in body weight. ***8MF control groups were introduced in the study, including 3 males and 3 females. Animals from these groups did not receive any treatment; however samples (tissue, blood, urine) were taken from them.
[0183] During the treatment period the animals were observed daily for clinical symptoms, their body weight was measured weekly and the water consumption was measured daily.
[0184] The day before autopsy, urinalysis was performed and blood samples were taken for hematology and clinical chemistry examinations.
[0185] On the day of autopsy the animals were anaesthetized with isoflurane, blood was collected for PBMC isolation then subjected to autopsy. Tissues and organs (adrenals, brain, kidneys, liver, spleen and thymus) were weighed and subjected to gross pathological and histopathological examinations.
[0186] Sterile kidney and liver samples were taken from the animals, frozen in liquid nitrogen and stored at -80.degree. C. PBMC (Peripheral Blood Mononuclear Cell) and urine samples were stored at 80.degree. C. as well. RNA was extracted from Kidney samples for toxicogenomic analysis for prediction of nephrotoxicity.
Finding Summary:
1. Toxicants Effects
[0187] 28-Day
[0188] Gentamycin: Signs of nephrotoxicity occurred in all animals of both sexes. During autopsy enlarged and discolored kidneys were observed in males. Kidney weight increased in both sexes. These changes were accompanied by clinical pathological findings: higher creatinine values in males and granular cylinders in the urine of females. The test item affected body weight gain of animals in both sexes. The nephrotoxic effect of the test item was confirmed by histopathology.
[0189] Cisplatin: The most severe nephrotoxic changes were found in Cisplatin treated groups of both sexes. Enlarged and discolored kidneys, increased kidneys and decreased thymus weight were found in both sexes. The nephrotoxic effect was detected during clinical pathology: Higher values of creatinine and urea nitrogen in both sexes & mild changes in the urine sediment. The test item affected body weight gain and water consumption in both sexes.
[0190] Tobramycin: Enlarged, discolored kidneys, with increased weights were observed in males. Clinical pathology revealed a nephrotoxic effect and higher values of creatinine and urea nitrogen in the blood as well as granular cylinders in the urine sediment of both sexes. Histopathological examinations confirmed nephrotoxic changes in both sexes.
[0191] Cadmium chloride: Mild clinical symptoms (hollow psoas, colic) were recorded in both sexes immediately after the administration. The test item affected body weight gain in both sexes. Slightly lower water consumption was recorded in males. Round bordered spleen and liver and thickening of peritoneum were recorded in both sexes, which correspond with higher liver and spleen weight. In addition increased weight of kidneys and decreased thymus were recorded in females. AST (Aspartate Aminotransferase) values were elevated in both sexes. A few transitional epithelial cells were observed in the urine of females. During histopathological examination significant nephrotoxicity was found only in a single female.
[0192] Doxorubicin: The test item caused severe clinical symptoms and lethality when administered in a 4 mg/kg dose. Two out of 3 males and 1 out of 3 females died. The lowered dose of 1 mg/kg of the test item was not lethal, but affected body weight gain in both sexes and water consumption in males. An increased weight of kidneys was found in males. The liver weight increased, while the weight of the thymus and spleen decreased significantly in both sexes. Elevated values of AST, ALT and Gamma GT were recorded in the male and decreased values of total protein, Albumin and Globulin were found in both sexes. Mild to moderate lymphoid depletion of the thymus was observed in both sexes.
[0193] Valproic acid: No histopathological signs of nephrotoxicity were found. The only toxic effect was a decreased total protein and Globulin value found in males.
[0194] Control/Saline: No histopathological signs of nephrotoxicity were found
[0195] 5-Day
[0196] No lethality was recorded in any groups of both sexes.
[0197] Gentamycin: No nephrotoxicity was observed, except elevated urea nitrogen levels found in females. Body weight gain was decreased in females. No renal damage was found at histopathological examination.
[0198] Cisplatin: Mild, focal tubular epithelial cell necrosis in the medulla of kidneys was noted in a single male. No remarkable observations were found at autopsy. Decreased body weight gain and water consumption were recorded in both sexes.
[0199] Tobramycin: No renal damage was found during histopathology. Elevated urea nitrogen levels were found in females. Cadmium chloride: No renal damage was found. The test item caused mild clinical symptoms (hollow psoas, colic) immediately after the administration. Body weight gain decreased in both sexes. Slightly increased Gamma GT values were recorded in females.
[0200] Doxorubicin: No renal damage was found. Decreased body weight gain and water consumption was recorded in both sexes. Minimal to mild thymus atrophy and minimal lymphoid depletion of the spleen were found in males which was in accordance with gross pathological findings. RBC, HBG, HCT, reticulocyte and WBC counts were lower in both sexes.
[0201] Valproic acid: No renal damage was found. Slightly lower total protein and Albumin values were found in males.
[0202] Control/Saline: No histopathological signs of nephrotoxicity were found
[0203] SINGLE DAY: No renal damage was found.
[0204] Cisplatin: Decreased body weight gain was recorded in both sexes. Slightly lower lymphocytes and increased neutrophils counts were recorded in males.
[0205] Cadmium chloride: Mild clinical symptoms (hollow psoas, colic) were observed in both sexes immediately after the administration. Decreased body weight gain was recorded in both sexes. Lower lymphocytes and increased neutrophils counts were found in males.
[0206] Doxorubicin: Decreased body weight gain was recorded in both sexes. Lower relative weights of spleen were recorded in females. Higher WBC and neutrophil counts, decreasing tendency of total protein, Albumin and Globulin were found in males.: Control/Saline
[0207] No histopathological signs of nephrotoxicity were found
2. Histopathology
[0208] At histopathological examination after 28-day treatment, nephrotoxicity occurred in the following decreasing order: Cisplatin, Gentamycin, Tobramycin and Doxorubicin in males; Cisplatin, Cadmium chloride, Gentamycin, Doxorubicin and Tobramycin in females. Males were more sensitive to most of the substances.
[0209] Valproic acid proved to be non-nephrotoxic.
[0210] No renal damage was found after 5-day treatment in all dosed groups of both sexes, compared to the controls, except a single male treated with Cisplatin, where mild, focal tubular epithelial cell necrosis in the medulla was found.
[0211] No test item related renal damage was found after single treatment in all dosed groups of both sexes, compared to the controls.
[0212] Table 4 presents the summarized findings recorded after the 28-day treatment period in the different dosed groups of both sexes.
TABLE-US-00004 TABLE 4 Findings after the 28-day treatment period Findings Dose Organ Clinical Compound (mg/kg) Autopsy weight pathology Histopathology Gentamycin 40 : .uparw..uparw., pale : : .uparw.CREA Kidneys : lymphocytic kidneys .uparw..uparw. : granular inflammation, tubular kidneys cylinders in basophilia in the cortex. urine : tubular dilatation in the medulla Cisplatin 0.5 : .uparw..uparw., pale : : .uparw..uparw.BUN, Kidneys : lymphocytic kidneys .uparw..uparw. CREA inflammation, tubular kidneys : trans. epith. basophilia in the cortex. cells in urine Tubular dilatation, bizarre (1/3): oval forms in the medulla. lipid cell in urine Tobramycin 40 : .uparw..uparw., pale : : .uparw..uparw.BUN, Kidneys: kidneys .uparw..uparw. CREA : lymphocytic kidneys : granular inflammation, tubular cylinders in basophilia in the cortex. urine : tubular dilatation and : trans. epith. basophilia in the medulla. cells in urine Cadmium 0.75 : : : .uparw..uparw. AST Spleen: chloride .uparw..uparw. liver, spleen, .uparw..uparw. liver, : trans. epith. : lymphoid depletion thickening of spleen cells in urine peritoneum Doxorubicin 1 : : : .uparw..uparw.AST, Kidneys: .uparw..uparw. thymus .uparw..uparw. ALT, .gamma.GT : tubular dilatation and thymus : .dwnarw..dwnarw.TP, basophilia in the cortex. Alb., Glob. Tubular dilatation in the medulla. Thymus: : lymphoid depletion CREA--creatinine, BUN--Blood urea nitrogen, AST--aspartate aminotransferase, ALT--alanine aminotransferase, Alb--Albumin
[0213] Table 5 presents the summarized findings recorded after the 5-day treatment period in the different dosed groups.
TABLE-US-00005 TABLE 5 Findings after the 5-day treatment period Dose Findings Compound (mg/kg) Autopsy Organ weight Clinical pathology Histopathology Gentamycin 40 No effect No effect : .uparw..uparw.BUN No renal damage Cisplatin 0.5 No effect No effect (No. 24): .uparw..uparw.PLT, (No. 24): tubular .dwnarw..dwnarw.reticulocytes, .uparw.BUN necrosis in the medulla and CREA Tobramycin 40 No effect No effect : .uparw..uparw.BUN No renal damage Cadmium 2. No effect : .dwnarw.thymus : .uparw. .gamma.GT No renal damage chloride Doxorubicin 4 : : : .dwnarw..dwnarw.RBC, HGB, No renal damage. .dwnarw..dwnarw.thymus .dwnarw..dwnarw.thymus HCT, reticulocytes, : and spleen and spleen WBC Thymus: atrophy Spleen: lymphoid depletion
[0214] No test item related renal damage was found after single treatment in all dosed groups of both sexes, compared to the controls.
3. Lethality
28-Days Treatment
[0215] Death occurred only in Doxorubicin treated groups with the originally planned dose. No lethality was recorded after lowering the dose from 4 mg/kg to 1 mg/kg.
TABLE-US-00006 TABLE 6 Lethality in Doxorubicin treated groups Died Moribund Males 2/3 (Day 8) 1/3 (Day 8) Females 1/3 (Day 9) 2/3 (Day 9)
[0216] Single and 5-Days Treatment
[0217] No lethality was recorded in any groups of both sexes.
4. Clinical Symptoms
28-Days Treatment
[0218] Clinical symptoms were observed only in Cadmium chloride groups and in the 4 mg/kg (originally planned dose) Doxorubicin treated groups of both sexes.
[0219] Single and 5-Day Treatment
[0220] Clinical symptoms were observed only in Cadmium chloride groups of both sexes. No clinical symptoms were observed in any other groups of both sexes.
5. Body Weight and Body Gain
[0221] 28-Day Treatment
[0222] Effect on body weight and body weight gain was seen in groups of both sexes treated with Doxorubicin, Cadmium chloride, Cisplatin and Gentamycin.
[0223] 5-Days Treatment
[0224] Decreased body weight gain was recorded in males treated with Cisplatin, Cadmium chloride, Doxorubicin, Valproic acid and in all dosed groups of females.
6. Water Consumption
[0225] Compared with controls the following observations were made concerning water consumption:
[0226] 28-Day Treatment
[0227] Males
[0228] Sight decrease during the last week in groups dosed with Cisplatin, Cadmium chloride and Valproic acid; Significant decrease from Week 2 in the Doxorubicin treated group.
[0229] Females
[0230] Decreased during Week 4 in Cisplatin treated group.
[0231] 5-Day Treatment
[0232] Decrease in Cisplatin and Doxorubicin treated groups of both sexes.
[0233] Decrease in Tobramycin and Cadmium chloride treated females
[0234] Increase in Valproic acid treated females
7. Autopsy
[0235] 28-Day Treatment
[0236] At necropsy of animals treated with 4 mg/kg Doxorubicin who died (male No.: 52, 54 and female No.: 154) dehydration and anaemic organs were observed.
[0237] Scheduled Autopsy
[0238] Alterations were found in the kidneys in both sexes treated with Cisplatin and in males treated with Gentamycin and Tobramycin. Pale and enlarged kidneys were found in a single female (No. 145) treated with Cadmium chloride. Smaller thymuses were found in Doxorubicin treated groups of both sexes. Round bordered liver, enlarged spleen and thickening of the peritoneum were found in both sexes treated with Cadmium chloride.
[0239] 5-Day Treatment
[0240] No alterations were found in the kidneys in the dosed groups of both sexes. No remarkable observations were found at autopsy in females. Smaller thymus and spleen were recorded in the Doxorubicin treated group of males.
[0241] Single Treatment
[0242] No alterations were found in the kidneys in the dosed groups of both sexes. No remarkable observations were found in females. Hemorrhagic thymus were found with different incidence in the dosed groups in males, including controls.
8. Organ Weights
[0243] 28-Day Treatment
[0244] Compared with controls the following observations were made concerning the relative organ weights, taking into consideration the small number of groups (3/sex/group):
[0245] Increased liver weights in groups of both sexes treated with Cadmium chloride and Doxorubicin; Increased weights of kidneys in males treated with Gentamycin, Cisplatin, Tobramycin and Doxorubicin; Higher weights of kidneys in females treated with Gentamycin, Cisplatin and Cadmium chloride; Weights of spleen were higher in Gentamycin treated males and Cadmium chloride treated groups of both sexes. Lower weights were recorded in Doxorubicin treated groups of both sexes; Decreased thymus weights were found in Gentamycin and Tobramycin treated males, in Cisplatin and Doxorubicin treated groups of both sexes and in females treated with Cadmium chloride.
[0246] 5-Day Treatment
[0247] No effect was observed in kidneys of the dosed groups of both sexes.
[0248] Compared with controls the following observations were made concerning the relative organ weights, taking into consideration the small number of groups (3/sex/group): Lower weights of spleen in Doxorubicin treated groups of both sexes; Lower thymus weights in Doxorubicin, Cadmium chloride and Valproic acid treated groups of both sexes.
[0249] Single Treatment
[0250] No effect was observed in kidneys of the dosed groups of both sexes. No significant alterations were recorded in males.
[0251] Compared with controls the following tendencies were observed in females concerning the relative organ weights, taking into consideration the small number of groups (3/sex/group): Lower weights of liver in Cisplatin treated group; Lower weights of thymus in Gentamycin, Cisplatin and Valproic acid treated groups; Lower weights of spleen in Cisplatin and Doxorubicin treated groups.
Expression Analysis
[0252] RNA Isolation from Kidney Tissues
[0253] RNA was isolated from the kidney tissues using the following procedure:
[0254] Step 1: Homogenization of Tissue: Add 200 mg of tissue sample to 7 ml of cold TRI Reagent (MRC) on ice. Homogenize tissue using several short pulses (5 sec.) of the homogenizer.
[0255] Step 2: Phase separation: Add 0.2 ml of BCP (1-BROMO-3-CHLORO-PROPANE, SIGMA, Cat. No. B-9673) per 1 ml TRI Reagent. Cover the sample tightly and mix vigorously for 15 sec. Incubate the sample at RT 2-3 min. Spin the sample at 12000 g for 20 min at 4.degree. C.
[0256] Step 3: RNA precipitation: Following centrifugation, the mixture separates into a lower red, phenol-chloroform phase, an interphase, and a colorless upper aqueous phase. Remove the top aqueous layer to a fresh tube. Add 0.5 ml Isopropanol per 1 ml TRI Reagent used in the original homogenization step. Mix the tube by vortex and incubate the sample at RT for 7-8 min. Spin the sample at 12000 g for 15 min at 4.degree. C.
[0257] Step 4: RNA wash: Remove the sup and add a volume of 80% ethanol (made with DEPC-treated water, stored at -20.degree. C.) equal to the original volume of TRI Reagent to rinse the pellet. Centrifuge the sample at 12000 g for 5 min at 4.degree. C. Remove the ethanol and resuspend the RNA pellet in 400 ul DEPC water.
[0258] Step 5: RNA purification using phenol-chlorophorm extraction and MaXtract low Density tubes: Equilibrate the phenol:chlorophorm:isoamyl alcohol mix (25:24:1) (Ambion, Cat. No. 9732) to room temperature. Pellet the MaXtract tubes (QIAGEN, Cat. No. 129016) prior to use by centrifugation 1 minute at maximum speed. To the RNA dissolved add an equal volume (400 ul) of phenol:chlorophorm:isoamyl (25:24:1) alcohol mix and vortex. Transfer the entire Total RNA-phenol/chlorophorm mix to MaXtract tube. Centrifuge at 13000 rpm for 2 min. Transfer the aqueous upper phase to a fresh non-stick 1.5 ml tube (Ambion, Cat. No. AM12450). Pay attention not to touch the gel with the pipet tip as it reduces the grade of RNA purity. Repeat steps 5.3-5.5.
[0259] Step 6: RNA precipitation II: Precipitate the RNA by adding 0.1 vol 3M sodium acetate (RNAse free, Sigma Cat. No. S-7899) and 0.8 volume isopropanol (RNA vol.+sodium acetate vol.) For 400 .mu.l RNA: 40 .mu.l Sodium acetate and 352 .mu.l isopropanol. Vortex 5 sec. Store at -20.degree. C. over night. Fast cool the centrifuge. Spin the samples at full speed (14000 RPM) for 20 min at 4.degree. C. pellet would be at the bottom.
[0260] Step 7: RNA wash II and resuspending: Pipette off the supernatant. Rinse twice the pellet with 0.5 ml 80% ethanol (made with DEPC-treated water, stored at -20.degree. C.), centrifuge for 5 min at 9500 RPM, 4.degree. C. Pipette out the ethanol, then short spin the samples in Eppendorf centrifuge at full speed for 10 sec., and pipette out the remainder of ethanol. Air dry the pellet. Simultaneously, preheat the DEPC treated water to 55-70.degree. C. Check the RNA for dryness. When dry, it is almost completely transparent. Add appropriate volume of DEPC treated water to the pellet (20-150 .mu.l) depending on the size of the pellet--do not mix! Heat the samples 10 min. at 55-70.degree. C. Mix well by pipetation.
[0261] Final RNA product was quantified by spectrophotometric quantification. The quality of the RNA was evaluated by measuring the 260/280 and 260/230 ratios and confirmed by agarose gel. RNA was deemed of a suitable quality for microarray analysis if the 260/280 ratio was between 1.8 and 2.1, 260/230 ratio was higher than 1.5 and the gel showed no visible degradation products lower than the 18S ribosomal band.
Microarray Hybridization
[0262] RNA samples extracted from the 1-Day and 5-Days treated animals and were sent to hybridization on Affymetrix array GeneChip.RTM. Rat Genome 230 2.0. The hybridization was performed according to the Affymetrix' following protocol:
[0263] Step 1: Target Preparation: Using protocols in Affymetrix' manual Section 2, double-stranded cDNA is synthesized from total RNA (or purified poly-A messenger RNA) isolated from tissue or cells. An in vitro transcription (NT) reaction is then done to produce biotin-labeled cRNA from the cDNA. The cRNA is fragmented before hybridization.
[0264] Step 2: Target Hybridization: A hybridization cocktail is prepared, including the fragmented target, probe array controls, BSA, and herring sperm DNA. It is then hybridized to the probe array during a 16-hour incubation. The hybridization process is describes in Affymetrix' manuals.
[0265] Step 3: Fluidics Station Setup: Specific experimental information is defined using Affymetrix.RTM. Microarray Suite or GeneChip Operating Software (GCOS) on a PC-compatible workstation. The probe array type, sample description, and comments are entered and saved with a unique experiment name. The fluidics station is then prepared for use by priming with the appropriate buffers.
[0266] Step 4: Probe Array Washing and Staining: Immediately following hybridization, the probe array undergoes an automated washing and staining protocol on the fluidics station.
[0267] Step 5: Probe Array Scan: Once the probe array has been hybridized, washed, and stained, it is scanned. Each workstation running Affymetrix Microarray Suite or GCOS can control one scanner. The software defines the probe cells and computes intensity for each cell. Each complete probe array image is stored in a separate data file identified by the experiment name and is saved with a data image file (.dat) extension.
[0268] Step 6: Data Analysis: The .dat image is analyzed for probe intensities; results are reported in tabular and graphical formats.
[0269] The expression levels were extracted using Affymetrix' MASS algorithm. Further multiplicative normalization on the data--setting the 95th percentile of the expression vector of each sample to an arbitrary constant value (1200)--was then performed.
Classifier on Microarray Data
[0270] Finding signatures using machine learning algorithms requires two steps--selecting a limited set of features to be used for the signature, and building a classifier using these features. The feature selection stage is especially significant here for several reasons. Large number of features means a low signal to noise ratio, tampering the classifier performance, large number of features, compared to the relatively small number of samples, means that spurious features might exists. These are features that give good classification on the experiment data by chance, causing the classifier to be over-fitted to the learning set and have low prediction ability, and finally--a small number of features is important for practical application of the signature.
[0271] The initial features selection process is done by performing Mann-Whitney (Wilcoxon) rank-sum test on the data, considering only probesets whose overall normalized expression mean is over 25, to avoid working at noise-level.
[0272] Further features selection is done iteratively by building a Random Forest classifier, using the initial list of features, and estimating the importance of features as given by the algorithm's "Out of the Bag" approach. Less important features (those that have low impact on the performance of the classifier) are removed from the features list and the process is repeated.
[0273] The performance of the classifier built as just described, is estimated by calculating the LOR and Accuracy after performing a cross validation process--some of the samples are removed from the data. The whole process of features-selection and classifier building is performed on the data, and the prediction is tested on the left-out samples.
[0274] The following example illustrates the results of the process--working on the Day-5 samples of animals treated with toxic compounds, not including animals treated with Cadmium-Chloride (see pathological data, above) ("Toxic"), as compared to all controls samples (Saline and Valproic-acid treated animals at Day-1 and Day-5, as well as naive rats) ("Control"). A list of 20 features (probesets) was initially selected, and then iteratively reduced to 6 features. The random forest classifier was used with the iterative list of features, as well as the gender of the rat used as an extra two-value feature. The random forest classifier was used with 2500 decision trees in each run. The cross validation was performed by leaving-out randomly selected samples--3 control samples and 3 toxic samples. This was repeated 350 times. The bound for deciding whether a sample is predicted as toxic or control, was chosen as to maximize the Accuracy. The "Confusion matrix" for this optimal bound is given in Table 7.
TABLE-US-00007 TABLE 7 "Confusion matrix" Control Toxic Predicted as Control 965 85 Predicted as Toxic 151 899
[0275] The Accuracy of the signatures as evaluated by this process is 89%, and the LOR is 4.2
Selecting Genes for Validation
[0276] Following the analysis performed on the Day-5 data, 20 top-scoring probesets were selected for further validation using qRT-PCR. The probesets were mapped to the trasnscriptome produced by the LEADS clustering and assembly system (described in Sorek, R., Ast, G. & Graur, D. Alu-containing exons are alternatively spliced. Genome Res 12, 1060-7 (2002); U.S. Pat. No. 6,625,545; and U.S. patent application Ser. No. 10/426,002, published as US20040101876 on May 27 2004; all of which are hereby incorporated by reference as if fully set forth herein. Briefly, the software cleans the expressed sequences from repeats, vectors and immunoglobulins. It then aligns the expressed sequences to the genome taking alternatively splicing into account and clusters overlapping expressed sequences into "clusters" that represent genes or partial genes) and the relevant contig and gene (whenever existing) were identified. As evident in table 8 bellow, the mapping of the probeset 1375422_at was not unique so we selected all relevant contigs.
[0277] Novel variants for the relevant genes were also identified. This was done based on the available rat ESTs and mRNAs and, when a human and mouse homologues was identified--the mouse ESTs and mRNAs and human transcripts were added the relevant rat ESTs and mRNAs to construct a combined informative contigs.
TABLE-US-00008 TABLE 8 Probe sets selected for qRT-PCR validation, with their LEADS gene name and internal candidate name Probe set Internal Name Gene Name 1375422_at BE097535_DB71_T0 BE097535 1390507_at AI045075_DB71_T0 ISG20 1367764_at H31883_DB71_T0 CCNG1 1369268_at RATERFI_DB71_T0 ATF3 1380692_at BE104394_DB71_T0 BE104394 1388674_at RNU24174_DB71_T0 CDKN1A 1371785_at AA686189_DB71_T0 TNFRSF12A 1393728_at AA964541_DB71_T0 AA964541 1369814_at RNU90447_DB71_T0 CCL20 1397637_at AI502869_DB71_T0 AI502869 1388560_at H33998_DB71_T0 WDR77 1392102_at AI454051_DB71_T0 AI454051 1370153_at BI293562_DB71_T0 GDF15 1388140_at RATRAB13X_DB71_T0 RAB13 1390833_at AW919147_DB71_T0 AW919147 1384934_at BQ200887_DB71_T0 BQ200887 1375895_at AI549068_DB71_T0 AI549068 1388642_at H31799_DB71_T0 EI24 1383162_at AA799594_DB71_T0 AA799594 1384070_at H31045_DB71_T0 H31045
RT Preparation and Real-Time qRT-PCR Analysis
[0278] Before RT preparation the RNA was treated with DNA-free (Ambion, cat. No. AM1906) DNase treatment and removal--according to manufacturer protocol. DNase procedure was repeated until no DNA is detected in a PCR reaction using the RNA samples.
[0279] RT preparation--Purified RNA (4 .mu.g) is mixed with 600 ng Random Hexamer primers (Invitrogen, Cat. No. 48190-011) and 500 .mu.M dNTP (Takara, Cat. No. 4030) in a total volume of 62.4 .mu.l. The mixture is then incubated for 5 min at 65.degree. C. and then quickly chilled on ice. Thereafter, 20 .mu.l of 5.times. SuperscriptII first strand buffer (Invitrogen, Cat. No. Y00146), 9.6 .mu.l 0.1M DTT (Invitrogen, Cat. No. Y00147) and 160 units RNasin (Promega, Cat. No. N251A) are added, and the mixture is incubated for 10 min at 25.degree. C., followed by further incubation at 42.degree. C. for 2 min. Then, 4 .mu.l (800 units) of SuperscriptII (Invitrogen, Cat. No. 18064-022) is added and the reaction (final volume of 100 .mu.l) is incubated for 50 min at 42.degree. C. and then inactivated at 70.degree. C. for 15 min. The resulting cDNA is diluted 1:20 in TE buffer (10 mM Tris pH=8, 1 mM EDTA pH=8).
[0280] cDNA (5 .mu.l), prepared as described above, is used as a template in Real-Time PCR reactions using the SYBR Green I assay (PE Applied Biosystem) with specific primers in 100 nM concentration if not indicated otherwise and UNG Enzyme (Eurogentech or equal) Amplification is effected as follows: 50.degree. C. for 2 min, 95.degree. C. for 10 min, and then 40 cycles of 95.degree. C. for 15 sec, followed by 60.degree. C. for 1 min (if not indicated otherwise). Amplification step is followed by dissociation step. Detection is performed by using the PE Applied Biosystem SDS 7000. The cycle in which the reactions achieved a threshold level (Ct) of fluorescence is registered and is used to calculate the relative transcript quantity in the RT reactions. Non-detected samples are assigned Ct value of 41 and are calculated accordingly. The relative quantity is calculated using the equation Q=efficiency -Ct. The efficiency of the PCR reaction is calculated from a standard curve, created by using serial dilutions of several reverse transcription (RT) reactions. To minimize inherent differences in the RT reaction, the resulting relative quantities are normalized to normalization factor calculated as follows:
[0281] The expression of four housekeeping (HSKP) genes from different pathways, ACTB (Entrez Gene ID: 81822), ACTG2 (Entrez Gene ID: 25365), HPRT (Entrez Gene ID: 24465) and YWHAZ (Entrez Gene ID: 25578), is found by SYBR green detection. The relative quantity (Q) of each housekeeping gene in each sample is calculated as described above. In order to calculate the "relative Q relative to MED" each Q for each HSKP gene is divided by the median quantity of this gene in all panel samples. To finally achieve the normalization factor of each sample the geometric mean of all four "relative Q relative to MED" was calculated. The normalization factor was then used for further calculations.
[0282] The sequences of the amplicons derived from the housekeeping genes measured in all the examples were as follows:
[0283] ACTB (Entrez Gene ID: 81822),
[0284] Forward Primer (SEQ ID NO: 237):
TABLE-US-00009 GGGAAATCGTGCGTGACATT
[0285] Reverse Primer: (SEQ ID NO: 238):
TABLE-US-00010 GCGGCAGTGGCCATCTC
[0286] Amplicon (SEQ ID NO: 239):
TABLE-US-00011 GGGAAATCGTGCGTGACATTAAAGAGAAGCTGTGCTATGTTGCCCTAGAC TTCGAGCAAGAGATGGCCACTGCCGC
[0287] ACTG2 (Entrez Gene ID: 25365),
[0288] Forward Primer (SEQ ID NO: 240):
TABLE-US-00012 TACCCTATTGAGCACGGCAT
[0289] Reverse Primer (SEQ ID NO: 241):
TABLE-US-00013 CGCAGCTCGTTGTAGAAGGT
[0290] Amplicon (SEQ ID NO: 242):
TABLE-US-00014 TACCCCATTGAACACGGCATCATCACGAACTGGGATGACATGGAGAAGAT CTGGCACCACTCCTTCTACAACGAGCTGCG
[0291] HPRT (Entrez Gene ID: 24465)
[0292] Forward Primer (SEQ ID NO: 243):
TABLE-US-00015 GCGAAAGTGGAAAAGCCAAGT
[0293] Reverse Primer (SEQ ID NO: 244):
TABLE-US-00016 GCCACATCAACAGGACTCTTGTAG
[0294] Amplicon (SEQ ID NO: 245):
TABLE-US-00017 GCGAAAGTGGAAAAGCCAAGTACAAAGCCTAAAAGACAGCGGCAAGTTGA ATCTACAAGAGTCCTGTTGATGTGGC
[0295] YWHAZ (Entrez Gene ID: 25578)
[0296] Forward Primer (SEQ ID NO: 246):
TABLE-US-00018 CAAGCATACCAAGAAGCATTTGA
[0297] Reverse Primer (SEQ ID NO: 247):
TABLE-US-00019 GGGCCAGACCCAGTCTGA
[0298] Amplicon (SEQ ID NO: 248):
TABLE-US-00020 CAAGCATACCAAGAAGCATTTGAAATCAGCAAAAAGGAGATGCAGCCGAC ACACCCCATCAGACTGGGTCTGGCCC
[0299] The markers of the present invention were tested with regard to their expression in a panel of kidney tissues samples from treated and control rats. Unless otherwise noted, all experimental data relates to the novel polynucleotides and proteins of the present invention, named according to the segment being tested (as expression was tested through RT-PCR as described). A description of the tissue samples used in the kidney testing panel is provided in Table 9 below. Tests were then performed as described in the "Materials and Experimental Procedures" section above.
[0300] The name comprises of the rat's group, as was described in table 2, the rats ID number, day of treatment and the nephrotoxicant it was exposed to:
[0301] Gent--Gentamycin, Cis--Cisplatin, Tob--Tobramycin, CadCl--Cadmium chloride, Dox--Doxorubicin, ValpA--Valproic Acid.
TABLE-US-00021 TABLE 9 Definitions of the tissue samples included in the panel based on their origin and treatment # Toxin used Day Name 1 Gentamycin 1 day 1 toxicants M 1_2M10_day1_Gent 2 Gentamycin 1 2_2M11_day1_Gent 3 Gentamycin 1 3_2M12_day1_Gent 4 Cisplatin 1 4_3M19_day1_Cis 5 Cisplatin 1 5_3M20_day1_Cis 6 Cisplatin 1 6_3M21_day1_Cis 7 Tobramycin 1 7_4M28_day1_Tob 8 Tobramycin 1 8_4M29_day1_Tob 9 Tobramycin 1 9_4M30_day1_Tob 10 Cadmium chloride 1 10_5M37_day1_CadCl 11 Cadmium chloride 1 11_5M38_day1_CadCl 12 Cadmium chloride 1 12_5M39_day1_CadCl 13 Doxorubicin 1 13_6M46_day1_Dox 14 Doxorubicin 1 14_6M47_day1_Dox 15 Doxorubicin 1 15_6M48_day1_Dox 16 Gentamycin 1 day 1 toxicants F 16_2F110_day1_Gent 17 Gentamycin 1 17_2F111_day1_Gent 18 Gentamycin 1 18_2F112_day1_Gent 19 Cisplatin 1 19_3F119_day1_Cis 20 Cisplatin 1 20_3F120_day1_Cis 21 Cisplatin 1 21_3F121_day1_Cis 22 Tobramycin 1 22_4F128_day1_Tob 23 Tobramycin 1 23_4F129_day1_Tob 24 Tobramycin 1 24_4F130_day1_Tob 25 Cadmium chloride 1 25_5F137_day1_CadCl 26 Cadmium chloride 1 26_5F138_day1_CadCl 27 Cadmium chloride 1 27_5F139_day1_CadCl 28 Doxorubicin 1 28_6F146_day1_Dox 29 Doxorubicin 1 29_6F147_day1_Dox 30 Doxorubicin 1 30_6F148_day1_Dox 31 Gentamycin 5 day 5 toxicants M 31_2M13_day5_Gent 32 Gentamycin 5 32_2M14_day5_Gent 33 Gentamycin 5 33_2M15_day5_Gent 34 Cisplatin 5 34_3M22_day5_Cis 35 Cisplatin 5 35_3M23_day5_Cis 36 Cisplatin 5 36_3M24_day5_Cis 37 Tobramycin 5 37_4M31_day5_Tob 38 Tobramycin 5 38_4M32_day5_Tob 39 Tobramycin 5 39_4M33_day5_Tob 40 Cadmium chloride 5 40_5M40_day5_CadCl 41 Cadmium chloride 5 41_5M41_day5_CadCl 42 Cadmium chloride 5 42_5M42_day5_CadCl 43 Doxorubicin 5 43_6M49_day5_Dox 44 Doxorubicin 5 44_6M50_day5_Dox 45 Gentamycin 5 day 5 toxicants F 45_2F113_day5_Gent 46 Gentamycin 5 46_2F114_day5_Gent 47 Gentamycin 5 47_2F115_day5_Gent 48 Cisplatin 5 48_3F122_day5_Cis 49 Cisplatin 5 49_3F123_day5_Cis 50 Cisplatin 5 50_3F124_day5_Cis 51 Tobramycin 5 51_4F131_day5_Tob 52 Tobramycin 5 52_4F132_day5_Tob 53 Tobramycin 5 53_4F133_day5_Tob 54 Cadmium chloride 5 54_5F141_day5_CadCl 55 Cadmium chloride 5 55_5F142_day5_CadCl 56 Doxorubicin 5 56_6F149_day5_Dox 57 Doxorubicin 5 57_6F150_day5_Dox 58 Doxorubicin 5 58_6F151_day5_Dox 59 Naive 28 Controls All days 59_8M81_day28_Naive 60 Naive 28 60_8M82_day28_Naive 61 Naive 28 61_8M83_day28_Naive 62 Naive 28 62_8F181_day28_Naive 63 Naive 28 63_8F182_day28_Naive 64 Naive 28 64_8F183_day28_Naive 65 Control/Saline 1 65_1M1_day1_Saline 66 Control/Saline 1 66_1M2_day1_Saline 67 Control/Saline 1 67_1M3_day1_Saline 68 Control/Saline 1 68_1F101_day1_Saline 69 Control/Saline 1 69_1F102_day1_Saline 70 Control/Saline 1 70_1F103_day1_Saline 71 Control/Saline 5 71_1M4_day5_Saline 72 Control/Saline 5 72_1M5_day5_Saline 73 Control/Saline 5 73_1M6_day5_Saline 74 Control/Saline 5 74_1F104_day5_Saline 75 Control/Saline 5 75_1F105_day5_Saline 76 Gentamycin 28 day 28 toxicants M 76_2M16_day28_Gent 77 Gentamycin 28 77_2M17_day28_Gent 78 Gentamycin 28 78_2M18_day28_Gent 79 Cisplatin 28 79_3M25_day28_Cis 80 Cisplatin 28 80_3M26_day28_Cis 81 Cisplatin 28 81_3M27_day28_Cis 82 Tobramycin 28 82_4M34_day28_Tob 83 Tobramycin 28 83_4M35_day28_Tob 84 Tobramycin 28 84_4M36_day28_Tob 85 Cadmium chloride 28 85_5M43_day28_CadCl 86 Cadmium chloride 28 86_5M44_day28_CadCl 87 Cadmium chloride 28 87_5M45_day28_CadCl 88 Doxorubicin 28 88_6M71_day28_Dox 89 Doxorubicin 28 89_6M72_day28_Dox 90 Doxorubicin 28 90_6M73_day28_Dox 91 Gentamycin 28 day 28 toxicants F 91_2F116_day28_Gent 92 Gentamycin 28 92_2F117_day28_Gent 93 Gentamycin 28 93_2F118_day28_Gent 94 Cisplatin 28 94_3F125_day28_Cis 95 Cisplatin 28 95_3F126_day28_Cis 96 Cisplatin 28 96_3F127_day28_Cis 97 Tobramycin 28 97_4F134_day28_Tob 98 Tobramycin 28 98_4F135_day28_Tob 99 Tobramycin 28 99_4F136_day28_Tob 100 Cadmium chloride 28 100_5F143_day28_CadCl 101 Cadmium chloride 28 101_5F144_day28_CadCl 102 Cadmium chloride 28 102_5F145_day28_CadCl 103 Doxorubicin 28 103_6F171_day28_Dox 104 Doxorubicin 28 104_6F172_day28_Dox 105 Doxorubicin 28 105_6F173_day28_Dox 106 Control/Saline 28 Day 28 control 106_1M7_day28_Saline 107 Control/Saline 28 107_1M8_day28_Saline 108 Control/Saline 28 108_1M9_day28_Saline 109 Control/Saline 28 109_1F107_day28_Saline 110 Control/Saline 28 110_1F108_day28_Saline 111 Control/Saline 28 111_1F109_day28_Saline 112 Valproic acid 1 Valproic acid - all days 112_7M55_day1_ValpA 113 Valproic acid 1 113_7M56_day1_ValpA 114 Valproic acid 1 114_7M57_day1_ValpA 115 Valproic acid 1 115_7F155_day1_ValpA 116 Valproic acid 1 116_7F156_day1_ValpA 117 Valproic acid 1 117_7F157_day1_ValpA 118 Valproic acid 5 118_7M58_day5_ValpA 119 Valproic acid 5 119_7M59_day5_ValpA 120 Valproic acid 5 120_7M60_day5_ValpA 121 Valproic acid 5 121_7F158_day5_ValpA 122 Valproic acid 5 122_7F159_day5_ValpA 123 Valproic acid 5 123_7F160_day5_ValpA 124 Valproic acid 28 124_7M61_day28_ValpA 125 Valproic acid 28 125_7M62_day28_ValpA 126 Valproic acid 28 126_7M63_day28_ValpA 127 Valproic acid 28 127_7F161_day28_ValpA 128 Valproic acid 28 128_7F162_day28_ValpA 129 Valproic acid 28 129_7F163_day28_ValpA
Classifier on qRT-PCR Data
[0302] The following tables summarize the microarray and qRT-PCR data for the markers of the present invention. The mean normalized expression level as measured by the microarray, as well as the mean normalized qRT-PCR expression levels, and the relevant Mann-Whitney scores p-values are given for each candidate.
TABLE-US-00022 TABLE 10 Mean expression levels and Mann-Whitney rank sum score p-values for microarray data of Day-1, Day-5 and control samples Microarray Data Candidate Normal Tox Day-1 Tox Day-5 Day-1 Day-5 Probeset Gene name mean mean mean p-value p-value 1371785_at TNFRSF12A 212 312 392 0.002 3.00E.sup.-05 1383162_at AA799594 4055 3521 3385 0.002 6.00E.sup.-03 1393728_at AA964541 35 46 56 0.01 6.00E.sup.-05 1390507_at ISG20 32 47 48 0.0006 6.00E.sup.-06 1392102_at AI454051 85 87 98 0.95 6.00E.sup.-04 1397637_at AI502869 65 59 56 0.03 3.00E.sup.-04 1390833_at AW919147 32 28 25 0.04 2.00E.sup.-04 1370153_at GDF15 38 48 73 0.01 1.00E.sup.-04 1384070_at H31045 88 99 108 0.02 3.50E.sup.-05 1388642_at EI24 867 860 917 0.38 8.00E.sup.-04 1367764_at CCNG1 757 864 1229 0.03 4.50E.sup.-05 1388560_at WDR77 532 529 572 0.82 4.00E.sup.-04 1369268_at ATF3 30 69 86 0.007 4.00E.sup.-06 1388140_at RAB13 171 180 193 0.004 8.00E.sup.-04 1388674_at CDKN1A 97 123 192 0.003 5.00E.sup.-06
TABLE-US-00023 TABLE 11 Mean expression levels and Mann-Whitney rank sum score p-values for qRT-PCR data of Day-1, Day-5 and control samples qRT-PCR Data Tox Tox Candidate Normal Day-1 Day-5 Day-1 Day 5 Internal name Gene name mean mean mean p-value p-value W41270_DB81_seg11 TNFRSF12A 1.08 1.42 2.27 4.00E.sup.-04 7.50E.sup.-10 AA686189_DB71_seg6 TNFRSF12A 0.99 1.27 1.44 8.00E.sup.-04 7.50E.sup.-06 AA799594_DB71_seg0 AA799594 1.66 1.45 1.48 8.00E.sup.-03 0.01 AA964541_DB71_seg0 AA964541 0.87 1.24 1.43 2.00E.sup.-06 3.00E.sup.-08 W64472_DB81_seg2 ISG20 1.06 1.14 2.32 0.35 2.00E.sup.-10 AI045075_DB71_seg6 ISG20 1.14 1.58 1.46 2.50E.sup.-04 6.50E.sup.-04 AI454051_DB71_seg0 AI454051 1.53 1.46 1.48 0.4 0.7 AI502869_DB71_seg0 AI502869 1.62 1.34 1.21 7.00E.sup.-03 2.50E.sup.-05 AW919147_DB71_seg0 AW919147 1.60 1.52 1.43 0.4 0.01 BI293562_DB71_seg2 GDF15 0.97 1.11 1.64 0.03 7.50E.sup.-07 H31045_DB71_seg5 H31045 1.51 0.99 1.51 0.015 0.5 W83813_DB81_seg27 EI24 1.30 1.42 2.18 0.55 1.50E.sup.-08 H31799_DB71_seg23 EI24 1.48 1.56 1.43 0.25 0.01 MUSCYCG1R_DB81_seg15-17 CCNG1 1.20 1.17 2.18 0.25 1.00E.sup.-07 MUSCYCG1R_DB81_seg19-20 CCNG1 1.16 1.35 2.2 6.00E.sup.-03 3.00E.sup.-09 H31883_DB71_seg13 CCNG1 1.25 1.41 1.51 5.00E.sup.-03 0.04 W33294_DB81_seg23 WDR77 1.44 1.27 1.9 0.05 7.00E.sup.-04 W33294_DB81_seg44 WDR77 1.37 1.42 2.02 0.6 8.00E.sup.-06 H33998_DB71_seg19 WDR77 1.31 1.58 2.13 0.04 2.00E.sup.-07 RATLRFI_DB71_seg9 ATF3 0.84 1.47 1.39 0.025 5.00E.sup.-04 RATRAB13X_DB81_seg15-17 RAB13 1.32 1.37 1.89 0.05 3.00E.sup.-07 RATRAB13X_DB81_seg22 RAB13 1.36 1.37 2.12 0.04 3.00E.sup.-07 RATRAB13X_s DB71_eg11-13 RAB13 1.40 1.59 1.42 1.00E.sup.-03 0.6 MMU09507_DB81_seg15 CDKN1A 0.88 0.94 1.74 0.08 2.00E.sup.-06 RNU24174_DB71_seg8 CDKN1A 0.76 0.91 1.21 2.00E.sup.-05 3.00E.sup.-05
[0303] The qRT-PCR data was used to construct the optimal Random-Forest classifier for Day-5 (Table 13) and Day-1 (Table 16). The optimal performance of the Day-5 signatures, as measured by cross validation is--Accuracy of 94% and LOR of 5.6. We further tested the performance of the optimal classifier on the Day-5 animals treated with Cadmium Chloride and found that 5 out of 6 samples were classified correctly as toxic. The optimal performance of the Day-1 signature is--Accuracy of 89% and LOR of 4.2
[0304] Table 14 and Table 15 further list genes that contribute to signatures for classification of Day-5 data. Table 17 and Table 18 further list genes that contribute to signatures of classification of Day-1. These genes can be used to replace the genes in Table 13 and Table 16 to yield classifiers with LOR of at least 3.75.
TABLE-US-00024 TABLE 12 All genes Candidate NV*/ ID Contig Internal name Gene name Genbank ID Reference 1 AA686189 W41270_DB81_seg11 TNFRSF12A NV of NM181086 2 AA686189 AA686189_DB71_seg6 TNFRSF12A NM181086 Peter et al., Physiol. Genomics 25: 375-386, 2006. 3 AA799594 AA799594_DB71_seg0 AA799594 AI008646; DY471185 (ESTS, no RNA) 4 AA964541 AA964541_DB71_seg0 AA964541 AA964541 (one WO02095000 sequence - EST) 5 AI045075 W64472_DB81_seg2 ISG20 NV of NM001008510 6 AI045075 AI045075_DB71_seg6 ISG20 NM001008510 WO02095000 7 AI454051 AI454051_DB71_seg0 AI454051 BE118959 (EST, no RNA) 8 AI502869 AI502869_DB71_seg0 AI502869 AI502869; DV713733; AI145914; CB796640 (ESTs, no RNA) 9 AW919147 AW919147_DB71_seg0 AW919147 AW91914; BF392593 (ESTS, no RNA) 10 BI293562 BI293562_DB71_seg2 GDF15 NM01921; BI293562 Peter et al., (BI293562 is an EST Physiol. that extends the Genomics 25: transcript) 375-386, 2006. 11 H31045 H31045_DB71_seg5 H31045 CO569017; DY312216; CF115262; BM392249; AI556451 (ESTS, no RNA.) 12 H31799 W83813_DB81_seg27 EI24 NV of NM001025660 13 H31799 H31799_DB71_seg23 EI24 NM001025660 14 H31883 MUSCYCG1R_DB81_seg15-17 CCNG1 NV of NM012923 15 H31883 MUSCYCG1R_DB81_seg19-20 CCNG1 NV of NM012923 16 H31883 H31883_DB71_seg13 CCNG1 NM012923 Thompson et al., Environ Health Perspect. 2004 Mar; 112(4): 488-94; WO02095000 17 H33998 W33294_DB81_seg23 WDR77 NV of NM001008771 18 H33998 W33294_DB81_seg44 WDR77 NV of NM001008771 19 H33998 H33998_DB71_seg19 WDR77 NM001008771 20 RATLRFI RATLRFI_DB71_seg9 ATF3 NM012912 Peter et al., Physiol. Genomics 25: 375-386, 2006. WO2004048598; WO200295000 21 RATRAB13X RATRAB13X_DB81_seg15-17 RAB13 NV of NM031092 22 RATRAB13X RATRAB13X_DB81_seg22 RAB13 NV of NM031092 23 RATRAB13X RATRAB13X_DB71_seg11-13 RAB13 NM031092 WO02095000 24 RNU24174 MMU09507_DB81_seg15 CDKN1A NV of NM080782 25 RNU24174 RNU24174_DB71_seg8 CDKN1A NM080782 Peter et al., Physiol. Genomics 25: 375-386, 2006. WO2004048598; WO0295000 *NV identifies novel polynucleotides and proteins, which may or may be not variants of known proteins.
TABLE-US-00025 TABLE 13 Optimal signature for Day-5 data Candi- date ID Contig Internal name Gene name 1 AA686189 W41270_DB81_seg11 TNFRSF12A 5 AI045075 W64472_DB81_seg2 ISG20 12 H31799 W83813_DB81_seg27 EI24 15 H31883 MUSCYCG1R_DB81_seg19-20 CCNG1
TABLE-US-00026 TABLE 14 Novel-Variants for Day-5 signatures Can- di- date ID Contig Internal name Gene name 1 AA686189 W41270_DB81_seg11 TNFRSF12A 3 AA799594 AA799594_DB71_seg0 AA799594 5 AI045075 W64472_DB81_seg2 ISG20 7 AI454051 AI454051_DB71_seg0 AI454051 8 AI502869 AI502869_DB71_seg0 AI502869 9 AW919147 AW919147_DB71_seg0 AW919147 12 H31799 W83813_DB81_seg27 EI24 14 H31883 MUSCYCG1R_DB81_seg15-17 CCNG1 15 H31883 MUSCYCG1R_DB81_seg19-20 CCNG1 18 H33998 W33294_DB81_seg44 WDR77 21 RATRAB13X RATRAB13X_DB81_seg15-17 RAB13 22 RATRAB13X RATRAB13X_DB81_seg22 RAB13 24 RNU24174 MMU09507_DB81_seg15 CDKN1A
TABLE-US-00027 TABLE 15 Wild-Types for Day-5 signatures Candidate ID Contig Internal name Gene name 4 AA964541 AA964541_DB71_seg0 AA964541 10 BI293562 BI293562_DB71_seg2 GDF15 19 H33998 H33998_DB71_seg19 WDR77 20 RATLRFI RATLRFI_DB71_seg9 ATF3 25 RNU24174 RNU24174_DB71_seg8 CDKN1A
TABLE-US-00028 TABLE 16 Optimal signature for Day-1 data Can- di- date ID Contig Internal name Gene name 1 AA686189 W41270_DB81_seg11 TNFRSF12A 4 AA964541 AA964541_DB71_seg0 AA964541 6 AI045075 AI045075_DB71_seg6 ISG20 15 H31883 MUSCYCG1R_DB81_seg19-20 CCNG1 20 RATLRFI RATLRFI_DB71_seg9 ATF3 23 RATRAB13X RATRAB13X_DB71_seg11-13 RAB13 25 RNU24174 RNU24174_DB71_seg8 CDKN1A
TABLE-US-00029 TABLE 17 Novel-Variants for Day-1 signatures Can- di- date ID Contig Internal name Gene name 1 AA686189 W41270_DB81_seg11 TNFRSF12A 3 AA799594 AA799594_DB71_seg0 AA799594 8 AI502869 AI502869_DB71_seg0 AI502869 11 H31045 H31045_DB71_seg5 H31045 14 H31883 MUSCYCG1R_DB81_seg15-17 CCNG1 15 H31883 MUSCYCG1R_DB81_seg19-20 CCNG1 17 H33998 W33294_DB81_seg23 WDR77 21 RATRAB13X RATRAB13X_DB81_seg15-17 RAB13
TABLE-US-00030 TABLE 18 Wild-Types for Day-1 signatures Candi- date ID Contig Internal name Gene name 2 AA686189 AA686189_DB71_seg6 TNFRSF12A 4 AA964541 AA964541_DB71_seg0 AA964541 6 AI045075 AI045075_DB71_seg6 ISG20 16 H31883 H31883_DB71_seg13 CCNG1 19 H33998 H33998_DB71_seg19 WDR77 20 RATLRFI RATLRFI_DB71_seg9 ATF3 23 RATRAB13X RATRAB13X_DB71_seg11-13 RAB13 25 RNU24174 RNU24174_DB71_seg8 CDKN1A
[0305] Table 19 below summarizes the SEQ ID NOs for nodes, detector nodes, other unique nodes, transcripts and proteins for each marker of the invention. Nodes are segments within a transcript that might, according to the predictions made by the LEADS platform, represent a single exon or an alternative extension of an exon. Unique nodes are the ones that appear only in a novel variant or polynucleotide and not in the wild-type. The nodes listed for new variants and polynucleotides are unique nodes. When other unique nodes exist for new-variants and polynucleotides of the same genes, they are also given. The detector nodes are the set of nodes within which the primers were designed. When possible it is the same as the unique node (and not given separately), but when the unique node is too short the detector node might include other neighboring nodes as well.
TABLE-US-00031 TABLE 19 Candidate SEQ IDs Other Detector unique Node nodes nodes Transcript Protein SEQ. SEQ. SEQ. SEQ. SEQ. Candidate ID ID ID ID ID Contig Internal name ID No. No. No. No. No. AA686189 W41270_DB81_seg11 1 2 1 62 AA686189 AA686189_DB71_seg6 2 45 44 73 AA799594 AA799594_DB71_seg0 3 33 32 AA964541 AA964541_DB71_seg0 4 47 46 AI045075 W64472_DB81_seg2 5 4 5 3 63 AI045075 AI045075_DB71_seg6 6 49 48 74 AI454051 AI454051_DB71_seg0 7 35 34 AI502869 AI502869_DB71_seg0 8 37 36 AW919147 AW919147_DB71_seg0 9 39 38 BI293562 BI293562_DB71_seg2 10 51 50 75 H31045 H31045_DB71_seg5 11 41 40 71 H31799 W83813_DB81_seg27 12 7 8 6 64 H31799 H31799_DB71_seg23 13 43 42 72 H31883 MUSCYCG1R_DB81_seg15-17 14 10 11 9 65 H31883 MUSCYCG1R_DB81_seg19-20 15 13 14 12 66 H31883 H31883_DB71_seg13 16 53 52 76 H33998 W33294_DB81_seg23 17 16 17 18 19 15 67 H33998 W33294_DB81_seg44 18 21 22 23 20 68 H33998 H33998_DB71_seg19 19 55 54 77 RATLRFI RATLRFI_DB71_seg9 20 57 56 78 RATRAB13X RATRAB13X_DB81_seg15-17 21 25 26 24 69 RATRAB13X RATRAB13X_DB81_seg22 22 28 29 27 70 RATRAB13X RATRAB13X_DB71_seg11-13 23 59 58 79 RNU24174 MMU09507_DB81_seg15 24 31 30 RNU24174 RNU24174_DB71_seg8 25 61 60 80
[0306] Table 20 below summarizes the SEQ ID NOs for primers used to amplify specific amplicons for each marker of the invention.
TABLE-US-00032 TABLE 20 Candidate Primers and Amplicons Forward Reverse primer primer Amplicon Candidate SEQ. ID SEQ. ID SEQ. ID Contig Internal name ID No. No. No. AA686189 W41270_DB81_seg11 1 252 253 254 AA686189 AA686189_DB71_seg6 2 249 250 251 AA799594 AA799594_DB71_seg0 3 255 256 257 AA964541 AA964541_DB71_seg0 4 258 259 260 AI045075 W64472_DB81_seg2 5 264 265 266 AI045075 W64472_DB81_seg2_F6R1 5 327 328 329 AI045075 AI045075_DB71_seg6 6 261 262 263 AI454051 AI454051_DB71_seg0 7 267 268 269 AI502869 AI502869_DB71_seg0 8 270 271 272 AW919147 AW919147_DB71_seg0 9 273 274 275 BI293562 BI293562_DB71_seg2 10 276 277 278 H31045 H31045_DB71_seg5 11 279 280 281 H31799 W83813_DB81_seg27 12 285 286 287 H31799 H31799_DB71_seg23 13 282 283 284 H31883 MUSCYCG1R_DB81_seg15-17 14 291 292 293 H31883 MUSCYCG1R_DB81_seg19-20 15 294 295 296 H31883 H31883_DB71_seg13 16 288 289 290 H31883 H31883_DB71_seg13_F5R5 16 330 331 332 H33998 W33294_DB81_seg23 17 297 298 299 H33998 W33294_DB81_seg44 18 300 301 302 H33998 H33998_DB71_seg19 19 303 304 305 RATLRFI RATLRFI_DB71_seg9 20 306 307 308 RATRAB13X RATRAB13X_DB81_seg15-17 21 309 310 311 RATRAB13X RATRAB13X_DB81_seg22 22 312 313 314 RATRAB13X RATRAB13X_DB71_seg11-13 23 315 316 317 RNU24174 MMU09507_DB81_seg15 24 321 322 323 RNU24174 RNU24174_DB71_seg8 25 324 325 326
[0307] Table 21 below provides human and mouse orthologous sequences for each rat marker of the invention.
TABLE-US-00033 TABLE 21 Candidates Homologues Human Human Mouse Mouse homologue homologue homologue homologue Candidate transcripts protein SEQ. transcripts proteins Contig Internal name ID SEQ. ID No. ID No. SEQ. ID No. SEQ. ID No. AA686189 W41270_DB81_ 1 105 106 107 157 158 159 197 198 199 226 227 228 seg11 108 160 200 229 AA686189 AA686189_DB71_ 2 105 106 107 157 158 159 197 198 199 226 227 228 seg6 108 160 200 229 AA799594 AA799594_DB71_ 3 seg0 AA964541 AA964541_DB71_ 4 190 219 seg0 AI045075 W64472_DB81_ 5 112 113 114 163 164 202 203 204 231 232 233 seg2 AI045075 AI045075_DB71_ 6 112 113 114 163 164 202 203 204 231 232 233 seg6 AI454051 AI454051_DB71_ 7 185 seg0 AI502869 AI502869_DB71_ 8 seg0 AW919147 AW919147_DB71_ 9 195 196 224 225 seg0 BI293562 BI293562_DB71_ 10 100 101 102 154 155 156 186 215 seg2 103 104 H31045 H31045_DB71_ 11 134 135 136 173 174 175 179 180 181 209 210 211 seg5 137 176 182 183 184 212 213 214 H31799 W83813_DB81_ 12 83 84 85 86 87 140 141 142 205 206 207 234 235 236 seg27 88 89 143 144 H31799 H31799_DB71_ 13 83 84 85 86 87 140 141 142 205 206 207 234 235 236 seg23 88 89 143 144 H31883 MUSCYCG1R_ 14 109 110 111 161 162 188 189 217 218 DB81_seg15-17 H31883 MUSCYCG1R_ 15 109 110 111 161 162 188 189 217 218 DB81_seg19-20 H31883 H31883_DB71_ 16 109 110 111 161 162 188 189 217 218 seg13 H33998 W33294_DB81_ 17 90 91 92 93 94 145 146 147 191 192 193 220 221 222 seg23 95 96 97 98 99 148 149 150 194 223 151 152 153 H33998 W33294_DB81_ 18 90 91 92 93 94 145 146 147 191 192 193 220 221 222 seg44 95 96 97 98 99 148 149 150 194 223 151 152 153 H33998 H33998_DB71_ 19 90 91 92 93 94 145 146 147 191 192 193 220 221 seg19 95 96 97 98 99 148 149 150 194 222 223 151 152 153 RATLRFI RATLRFI_DB71_ 20 81 82 138 139 177 178 208 seg9 RATRAB13X RATRAB13X_ 21 115 116 117 165 166 167 201 230 DB81_seg15-17 118 119 168 169 RATRAB13X RATRAB13X_ 22 115 116 117 165 166 167 201 230 DB81_seg22 118 119 168 169 RATRAB13X RATRAB13X_ 23 115 116 117 165 166 167 201 230 DB71_seg11-13 118 119 168 169 RNU24174 MMU09507_ 24 120 121 122 170 171 172 187 216 DB81_seg15 123 124 125 126 127 128 129 130 131 132 133 RNU24174 RNU24174_DB71_ 25 120 121 122 170 171 172 187 216 seg8 123 124 125 126 127 128 129 130 131 132 133
Example 2
Real Time qPCR Analysis of the Selected Markers
Example 2.1
[0308] Expression of tumor necrosis factor receptor superfamily, member 12a, AA686189, transcripts which are detectable by amplicon as depicted in sequence name AA686189_DB71_seg6 in kidney tissues of treated or untreated rats
[0309] Expression of tumor necrosis factor receptor superfamily, member 12a transcripts detectable by or according to seg6--AA686189_DB71_seg6_F1R1 (SEQ ID NO: 251) amplicon and primers AA686189_DB71_seg6_F1 (SEQ ID NO: 249) and AA686189_DB71_seg6_R1 (SEQ ID NO: 250) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0310] The column entitled AA686189_DB71_seg6 in Table 22 contains the normalized expression values of the above-indicated tumor necrosis factor receptor superfamily, member 12a transcript in treated or untreated kidney samples.
[0311] As is evident from the column entitled AA686189_DB71_seg6 in Table 22, the level of expression of the tumor necrosis factor receptor superfamily, member 12a transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 8.00E.sup.-04 and P-value for day 5: 7.5E.sup.-06.
[0312] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair AA686189_DB71_seg6_F1 (SEQ ID NO: 249) forward primer; and AA686189_DB71_seg6_R1 (SEQ ID NO: 250) reverse primer.
[0313] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: AA686189_DB71_seg6_F1R1 (SEQ ID NO: 251).
[0314] Forward primer (AA686189_DB71_seg6_F1 (SEQ ID NO: 249)):
TABLE-US-00034 CCAAGGACTGGGCTTAGGGT
[0315] Reverse primer (AA686189_DB71_seg6_R1 (SEQ ID NO: 250)):
TABLE-US-00035 AGAGATTCCCTTGTGCAAATGC
[0316] Amplicon (AA686189_DB71_seg6_F1R1 (SEQ ID NO: 251))
TABLE-US-00036 CCAAGGACTGGGCTTAGGGTTCAGGGGAGCCTTCCAGGGTGTCTAATTGC CCTGTCTCTGGTTCTGGGGCAGACAGAGAGCCTCAAGCTAGGTCACAAAG CGACTCATACTAAGGATCTGCAGCATTTGCACAAGGGAATCTCT
Example 2.2
[0317] Expression of tumor necrosis factor receptor superfamily, member 12a, AA686189, transcripts which are detectable by amplicon as depicted in sequence name W41270_DB81_seg11 in kidney tissues of treated or untreated rats
[0318] Expression of tumor necrosis factor receptor superfamily, member 12a transcripts detectable by or according to seg11--W41270_DB81_seg11_F2R2 (SEQ ID NO: 254) amplicon and primers W41270_DB81_seg11_F2 (SEQ ID NO: 252) and W41270_DB81_seg11R2 (SEQ ID NO: 253) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0319] The column entitled W41270_DB81_seg11 in Table 22 contains the normalized expression values of the above-indicated tumor necrosis factor receptor superfamily, member 12a transcript in treated or untreated kidney samples.
[0320] As is evident from the column entitled W41270_DB81_seg11 in Table 22, the level of expression of the tumor necrosis factor receptor superfamily, member 12a transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 4.00E.sup.-04, and P-value fro day 5: 7.50E.sup.-10.
[0321] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: W41270_DB81_seg11_F2 (SEQ ID NO: 252) forward primer; and W41270_DB81_seg11_R2 (SEQ ID NO: 253) reverse primer.
[0322] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: W41270_DB81_seg11_F2R2 (SEQ ID NO: 254).
[0323] Forward primer (W41270_DB81_seg11_F2 (SEQ ID NO: 252)):
TABLE-US-00037 GATCTGGGTAGGTGGTTGTTGG
[0324] Reverse primer (W41270_DB81_seg11_R2 (SEQ ID NO: 253)):
TABLE-US-00038 CGCACACCCTTATAAAAGTCCC
[0325] Amplicon (W41270_DB81_seg11_F2R2 (SEQ ID NO: 254)):
TABLE-US-00039 GATCTGGGTAGGTGGTTGTTGGGGCAGAAAGGAGGTCGTAGACTTAGGAT ATAGGAAACCAGGAAAAACTGACTGAGGAAGGGACTTTTATAAGGGTGTGC G
Example 2.3
[0326] Expression of AA799594, transcripts which are detectable by amplicon as depicted in sequence name AA799594_DB71_seg0 in kidney tissues of treated or untreated rats
[0327] Expression of AA799594 detectable by or according to seg0--AA799594_DB71_seg0_F1R1 (SEQ ID NO: 257) amplicon and primers AA799594_DB71_seg0_F1 (SEQ ID NO: 255) and AA799594_DB71_seg0_R1 (SEQ ID NO: 256) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0328] The column entitled AA799594_DB71_seg0 in Table 22 contains the normalized expression values of the above-indicated AA799594 transcript in treated or untreated kidney samples.
[0329] As is evident from the column entitled AA799594_DB71_seg0 in Table 22, the level of expression of AA799594 transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 8.00E.sup.-03 and P-value for day 5: 0.01.
[0330] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair:
[0331] AA799594_DB71_seg0_F1 (SEQ ID NO: 255) forward primer; and AA799594_DB71_seg0_R1 (SEQ ID NO: 256) reverse primer.
[0332] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: AA799594_DB71_seg0_F1R1 (SEQ ID NO: 257).
[0333] Forward primer (AA799594_DB71_seg0_F1 (SEQ ID NO: 255)):
TABLE-US-00040 ATCTCGATGGTAACGGGTCTAATC
[0334] Reverse primer (AA799594_DB71_seg0_R1 (SEQ ID NO: 256)):
TABLE-US-00041 TTTGTGCTGACCTTCATGCC
[0335] Amplicon (AA799594_DB71_seg0_F1R1 (SEQ ID NO: 257)):
TABLE-US-00042 ATCTCGATGGTAACGGGTCTAATCAGCCCATGATCAACATAACTGTGGTG ATATACATTTGGTATTTTTTAATTTTCGGATGCCTTCCTCAACATAGCCG TCAAGGCATGAAGGTCAGCACAAA
Example 2.4
[0336] Expression of AA964541, transcripts which are detectable by amplicon as depicted in sequence name AA964541_DB71_seg0 in kidney tissues of treated or untreated rats
[0337] Expression of AA964541 transcripts detectable by or according to seg0--AA964541_DB71_seg0_F2R2 (SEQ ID NO: 260) amplicon and primers AA964541_DB71_seg0_F2 (SEQ ID NO: 258) and AA964541_DB71_seg0_R2 (SEQ ID NO: 259) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0338] The column entitled AA964541_DB71_seg0 in Table 22 contains the normalized expression values of the above-indicated AA964541 transcript in treated or untreated kidney samples.
[0339] As is evident from the column entitled AA964541_DB71_seg0 in Table 22, the level of expression of
[0340] AA964541 transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 2.00E.sup.-06, and P-Value for day 5: 3.00E.sup.-08.
[0341] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AA964541_DB71_seg0_F2 (SEQ ID NO: 258) forward primer; and AA964541_DB71_seg0_R2 (SEQ ID NO: 259) reverse primer.
[0342] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon:
[0343] AA964541_DB71_seg0_F2R2 (SEQ ID NO: 260).
[0344] Forward primer (AA964541_DB71_seg0_F2 (SEQ ID NO: 258)):
TABLE-US-00043 CCAGCCTAGCCTCTCTTTTGC
[0345] Reverse primer (AA964541_DB71_seg0_R2 (SEQ ID NO: 259)):
TABLE-US-00044 AACATTCCCACAGGGTACATTCA
[0346] Amplicon (AA964541_DB71_seg0_F2R2 (SEQ ID NO: 260)):
TABLE-US-00045 CCAGCCTAGCCTCTCTTTTGCACTGCTGGTTCAGCCCACTGGGCCTCCGT CCTTTCCTCTGGAAGGGACTTGGCCTTGGGTGACAAATTCCTCTTTGATG AATGTACCCTGTGGGAATGTT
Example 2.5
[0347] Expression of Interferon stimulated exonuclease 20 (ISG20), AI045075, transcripts which are detectable by amplicon as depicted in sequence name AI045075_DB71_seg6 in kidney tissues of treated or untreated rats
[0348] Expression of Interferon stimulated exonuclease 20 (ISG20) transcripts detectable by or according to seg6--AI045075_DB71_seg6_F2R2 (SEQ ID NO: 263) amplicon and primers AI045075_DB71_seg6_F2 (SEQ ID NO: 261) and AI045075_DB71_seg6_R2 (SEQ ID NO: 262) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0349] The column entitled AI045075_DB71_seg6 in Table 22 contains the normalized expression values of the above-indicated Interferon stimulated exonuclease 20 (ISG20) transcript in treated or untreated kidney samples.
[0350] As is evident from the column entitled AI045075_DB71_seg6 in Table 22, the level of expression of the Interferon stimulated exonuclease 20 (ISG20) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-Value for day 1: 2.50E.sup.-04, and P-Value for day 5: 6.50E.sup.-04.
[0351] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AI045075_DB71_seg6_F2 (SEQ ID NO: 261) forward primer; and AI045075_DB71_seg6_R2 (SEQ ID NO: 262) reverse primer.
[0352] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: AI045075_DB71_seg6_F2R2 (SEQ ID NO: 263).
[0353] Forward primer (AI045075_DB71_seg6_F2 (SEQ ID NO: 261)):
TABLE-US-00046 GGGCCACAATGGAGCTCTAC
[0354] Reverse primer (AI045075_DB71_seg6_R2 (SEQ ID NO: 262)):
TABLE-US-00047 ACAGGTCTCATTCATGGAAAACTATG
[0355] Amplicon (AI045075_DB71_seg6_F2R2 (SEQ ID NO: 263)):
TABLE-US-00048 GGGCCACAATGGAGCTCTACAAAATCTCTCAGCGACTCAGAGCCCAGCGA GGGCTGCCCTGCCTGGGAACATCAGCCTGAACTTCATCCTCATCCAGGAT CAGAAGCAGCTACTCCTTGAAGGACCATAGTTTTCCATGAATGAGACCTG T
Example 2.6
[0356] Expression of Interferon stimulated exonuclease 20 (ISG20), AI045075, transcripts which are detectable by amplicon as depicted in sequence name W64472_DB81_seg2.sub.-- in kidney tissues of treated or untreated rats
[0357] Expression of Interferon stimulated exonuclease 20 (ISG20), AI045075, transcripts detectable by or according to seg2--W64472_DB81_seg2_F1R1 (SEQ ID NO: 266) amplicon and primers W64472_DB81_seg2_F1 (SEQ ID NO: 264) and W64472_DB81_seg2_R1 (SEQ ID NO: 265) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0358] The column entitled W64472_DB81_seg2 in Table 22 contains the normalized expression values of the above-indicated Interferon stimulated exonuclease 20 (ISG20), AI045075, transcript in treated or untreated kidney samples.
[0359] As is evident from the column entitled W64472_DB81_seg2 in Table 22, the level of expression of the Interferon stimulated exonuclease 20 (ISG20), AI045075, transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 2.00E.sup.-10.
[0360] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: W64472_DB81_seg2_F1 (SEQ ID NO: 264) forward primer; and W64472_DB81_seg2_R1 (SEQ ID NO: 265) reverse primer.
[0361] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon:
[0362] W64472_DB81_seg2_F1R1 (SEQ ID NO: 266).
[0363] Forward primer (W64472_DB81_seg2_F1 (SEQ ID NO: 264)):
TABLE-US-00049 GGAGGAGGGCAGAGCCA
[0364] Reverse primer (W64472_DB81_seg2_R1 (SEQ ID NO: 265)):
TABLE-US-00050 TCTGGTTCATTATCAAGGGAAGTTG
[0365] Amplicon (W64472_DB81_seg2_F1R1 (SEQ ID NO: 266)):
TABLE-US-00051 GGAGGAGGGCAGAGCCAGAGGAGGGACAGCCTGATGCAGACAGCCCTGAC TCAACCTGCCAGCCCCCTTACCTGTCAGCCTTGAGGAGATGGAACAGCCC AGCCTACTAGGCCTGCCCCCACTCCCCAACTTCCCTTGATAATGAACCAG A
Example 2.7
[0366] Expression of AI454051 transcripts which are detectable by amplicon as depicted in sequence name AI454051_DB71_seg0 in kidney tissues of treated or untreated rats
[0367] Expression of AI454051 transcripts detectable by or according to seg0--AI454051_DB71_seg0_F1R1 (SEQ ID NO: 269) amplicon and primers AI454051_DB71_seg0_F1 (SEQ ID NO: 267) and AI454051_DB71_seg0_R1 (SEQ ID NO: 268) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0368] The column entitled AI454051_DB71_seg0 in Table 22 contains the normalized expression values of the above-indicated AI454051 transcript in treated or untreated kidney samples.
[0369] As is evident from the column entitled AI454051_DB71_seg0 in Table 22, the level of expression of the AI454051 transcript detectable by the above amplicon was lower in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove).
[0370] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AI454051_DB71_seg0_F1 (SEQ ID NO: 267) forward primer; and AI454051_DB71_seg0_R1 (SEQ ID NO: 268) reverse primer.
[0371] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: AI454051_DB71_seg0_F1R1 (SEQ ID NO: 269).
[0372] Forward primer (AI454051_DB71_seg0_F1 (SEQ ID NO: 267)):
TABLE-US-00052 ATCCTGTTGGGTCTGCTTCTCA
[0373] Reverse primer (AI454051_DB71_seg0_R1 (SEQ ID NO: 268)):
TABLE-US-00053 CACAAGTAAATACATAGACTGGAATCAATG
[0374] Amplicon (AI454051_DB71_seg0_F1R1 (SEQ ID NO: 269)):
TABLE-US-00054 ATCCTGTTGGGTCTGCTTCTCACAGCGTATGGGGCTGTGTGCTTTTACTC ATGGTGGCAGCAGCAGTTGTTGTCACTTCTTTGGCCAGGCACAGTGGGTG ATCCTTACAGAGCAGCACAGATTCCCATTGATTCCAGTCTATGTATTTAC TTGTG
Example 2.8
Expression of AI502869 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name AI502869_DB71_Seg0 in Kidney Tissues of Treated or Untreated Rats
[0375] Expression of AI502869 transcripts detectable by or according to seg0--AI502869_DB71_seg0_F1R1 (SEQ ID NO: 272) amplicon and primers AI502869_DB71_seg0_F1 (SEQ ID NO: 270) and AI502869_DB71_seg0_R1 (SEQ ID NO: 271) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0376] The column entitled AI502869_DB71_seg0 in Table 22 contains the normalized expression values of the above-indicated AI502869 transcript in treated or untreated kidney samples.
[0377] As is evident from the column entitled AI502869_DB71_seg0_F1R1 (SEQ ID NO: 272) in Table 22, the level of expression of the AI502869 transcript detectable by the above amplicon was significantly lower in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 7.00E.sup.-03 and P-value for day 5: 2.50E.sup.-05.
[0378] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AI502869_DB71_seg0_F1 (SEQ ID NO: 270) forward primer; and AI502869_DB71_seg0_R1 (SEQ ID NO: 271) reverse primer.
[0379] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon:
[0380] Forward primer (AI502869_DB71_seg0_F1 (SEQ ID NO: 270)):
TABLE-US-00055 TGTTTAAAATCTGGGCTCTTGATTC
[0381] Reverse primer (AI502869_DB71_seg0_R1 (SEQ ID NO: 271)):
TABLE-US-00056 GTATTTCCAATAGTCAATGCAGTAACTCTAC
[0382] Amplicon (AI502869_DB71_seg0_F1R1 (SEQ ID NO: 272)):
TABLE-US-00057 TGTTTAAAATCTGGGCTCTTGATTCAGACCGAGTTTTAATACTGGATCTC ATTCAATCTTTGTGTTTTTTCTTTTTCTTTTCTTTTTTTTCCAATAGTAC GGCAGTGCTAATAGCAGTCCTTTAGTAGAGTTACTGCATTGACTATTGGA AATAC
Example 2.9
Expression of AW919147 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name AW919147_DB71_Seg0 in Kidney Tissues of Treated or Untreated Rats
[0383] Expression of AW919147 transcripts detectable by or according to seg0--AW919147_DB71_seg0_F2R2 (SEQ ID NO: 275) amplicon and primers AW919147_DB71_seg0_F2 (SEQ ID NO: 273) and AW919147_DB71_seg0_R2 (SEQ ID NO: 274) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0384] The column entitled AW919147_DB71_seg0 in Table 22 contains the normalized expression values of the above-indicated AW919147 transcript in treated or untreated kidney samples.
[0385] As is evident from the column entitled AW919147_DB71_seg0 in Table 22, the level of expression of the AW919147 transcript detectable by the above amplicon was lower in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 0.01.
[0386] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AW919147_DB71_seg0_F2 (SEQ ID NO: 273) forward primer; and AW919147_DB71_seg0_R2 (SEQ ID NO: 274) reverse primer.
[0387] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon AW919147_DB71_seg0_F2R2 (SEQ ID NO: 275):
[0388] Forward primer (AW919147_DB71_seg0_F2 (SEQ ID NO: 273)):
TABLE-US-00058 GCCACAGTAGAGGCTGCACTT
[0389] Reverse primer (AW919147_DB71_seg0_R2 (SEQ ID NO: 274)):
TABLE-US-00059 GAATCAACTGGAAATGTTCTAGGG
[0390] Amplicon (AW919147_DB71_seg0_F2R2 (SEQ ID NO: 275)):
TABLE-US-00060 GCCACAGTAGAGGCTGCACTTGCCACTGCTGTGTAGCGGCACTCTCCTGA CTCACTTAAAAATTCTCTGGAGGTTTAAGTGAGGACCCAGTTCCATCTCT AGATATCCAGGCTCCCTAGAACATTTCCAGTTGATTC
Example 2.10
Expression of Growth Differentiation Factor 15 (GDF15), BI293562, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name BI293562_DB71_Seg2 in Kidney Tissues of Treated or Untreated Rats
[0391] Expression of growth differentiation factor 15 (GDF15) transcripts detectable by or according to seg2--BI293562_DB71_seg2_F2R2 (SEQ ID NO: 278) amplicon and primers BI293562_DB71_seg2_F2 (SEQ ID NO: 276) and BI293562_DB71_seg2_R2 (SEQ ID NO: 277) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0392] The column entitled BI293562_DB71_seg2 in Table 22 contains the normalized expression values of the above-indicated growth differentiation factor 15 (GDF15) transcript in treated or untreated kidney samples.
[0393] As is evident from the column entitled BI293562_DB71_seg2 in Table 22, the level of expression of the growth differentiation factor 15 (GDF15) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 0.03 and P-value for day 5: 7.50E.sup.-07.
[0394] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: BI293562_DB71_seg2_F2 (SEQ ID NO: 276) forward primer; and BI293562_DB71_seg2_R2 (SEQ ID NO: 277) reverse primer.
[0395] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon BI293562_DB71_seg2_F2R2 (SEQ ID NO: 278):
[0396] Forward primer (BI293562_DB71_seg2_F2 (SEQ ID NO: 276)):
TABLE-US-00061 CTGCAACTGAGCATGTGCGT
[0397] Reverse primer (BI293562_DB71_seg2_R2 (SEQ ID NO: 277)):
TABLE-US-00062 TGCATAAGAACCACCGGGG
[0398] Amplicon (BI293562_DB71_seg2_F2R2 (SEQ ID NO: 278)):
TABLE-US-00063 CTGCAACTGAGCATGTGCGTGGGCGAGTGCCCCCACCTCTACCGGTCGGC CAACACGCATGCGCAGATCAAAGCACGCCTGCATGGCCTGCAGCCCGACA GAGTGCCGGCCCCGTGCTGTGTCCCCTCCAGCTACACCCCGGTGGTTCTT ATGCA
Example 2.11
Expression H31045 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name
[0399] H31045_DB71_Seg5 in Kidney Tissues of Treated or Untreated Rats
[0400] Expression of H31045 transcripts detectable by or according to seg5--H31045_DB71_seg5_F3R3 (SEQ ID NO: 281) amplicon and primers H31045_DB71_seg5_F3 (SEQ ID NO: 279) and H31045_DB71_seg5_R3 (SEQ ID NO: 280) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0401] The column entitled H31045_DB71_seg5 in Table 22 contains the normalized expression values of the above-indicated H31045 transcript in treated or untreated kidney samples.
[0402] As is evident from the column entitled H31045_DB71_seg5 in Table 22, the level of expression of the H31045 transcript detectable by the above amplicon was significantly lower in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 0.015.
[0403] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: H31045_DB71_seg5_F3 (SEQ ID NO: 279) forward primer; and H31045_DB71_seg5_R3 (SEQ ID NO: 280) reverse primer.
[0404] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon H31045_DB71_seg5_F3R3 (SEQ ID NO: 281):
[0405] Forward primer (H31045_DB71_seg5_F3 (SEQ ID NO: 279)):
TABLE-US-00064 GGACGGCCGAGCACAA
[0406] Reverse primer (H31045_DB71_seg5_R3 (SEQ ID NO: 280)):
TABLE-US-00065 GTGTGCATGTGCATAGGTCAGA
[0407] Amplicon (H31045_DB71_seg5_F3R3 (SEQ ID NO: 281)):
TABLE-US-00066 GGACGGCCGAGCACAATGGTGCTTGCTGTACAGCCTCATAGACCTTCCTT GGATCTCCCAGACACACTTAGTGGAAGGAGAGAATCCATTCTTGCAAATT GTCTGACCTATGCACATGCACAC
Example 2.12
Expression Etoposide Induced 2.4 mRNA (EI24) H31799 Transcripts which are Detectable by Amplicon as Depicted in Sequence Name H31799_DB71_Seg23 in Kidney Tissues of Treated or Untreated Rats
[0408] Expression of Etoposide induced 2.4 mRNA (EI24) transcripts detectable by or according to seg23--H31799_DB71_seg23_F1R1 (SEQ ID NO: 284) amplicon and primers H31799_DB71_seg23_F1 (SEQ ID NO: 282) and H31799_DB71_seg23_R1 (SEQ ID NO: 283) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0409] The column entitled H31799_DB71_seg23 in Table 22 contains the normalized expression values of the above-indicated Etoposide induced 2.4 mRNA (EI24) transcript in treated or untreated kidney samples.
[0410] As is evident from the column entitled H31799_DB71_seg23 in Table 22, the level of expression of the Etoposide induced 2.4 mRNA (EI24) transcript detectable by the above amplicon was higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 0.01.
[0411] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: H31799_DB71_seg23_F1 (SEQ ID NO: 282) forward primer; and H31799_DB71_seg23_R1 (SEQ ID NO: 283) reverse primer.
[0412] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon H31799_DB71_seg23_F1R1 (SEQ ID NO: 284):
[0413] Forward primer (H31799_DB71_seg23_F1 (SEQ ID NO: 282)):
TABLE-US-00067 TACTGTTTCCTGTGAAGCACATACCT
[0414] Reverse primer (H31799_DB71_seg23_R1 (SEQ ID NO: 283)):
TABLE-US-00068 GCAGAGCAGTAAAGACCAAAACC
[0415] Amplicon (H31799_DB71_seg23_F1R1 (SEQ ID NO: 284)):
TABLE-US-00069 TACTGTTTCCTGTGAAGCACATACCTTGTATGTGGGAGGTAAAGGAGCAC GCCAGCTGCTCCATGTCACTCCCTCTATAGCCATCACTGTCTTGTTTTTT TGTAACTCAGGTTAGGTTTTGGTCTTTACTGCTCTGC
Example 2.13
Expression Etoposide Induced 2.4 (EI24) mRNA, H31799, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name W83813_DB81_Seg27 in Kidney Tissues of Treated or Untreated Rats
[0416] Expression of Etoposide induced 2.4 mRNA (EI24) transcripts detectable by or according to seg27--W83813_DB81_seg27_F1R1 (SEQ ID NO: 287) amplicon and primers W83813_DB81_seg27_F1 (SEQ ID NO: 285) and W83813_DB81_seg27_R1 (SEQ ID NO: 286) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0417] The column entitled W83813_DB81_seg27 in Table 22 contains the normalized expression values of the above-indicated Etoposide induced 2.4 mRNA (EI24) transcript in treated or untreated kidney samples.
[0418] As is evident from the column entitled W83813_DB81_seg27 in Table 22, the level of expression of the Etoposide induced 2.4 mRNA (EI24) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 1.50E.sup.-08.
[0419] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: W83813_DB81_seg27_F1 (SEQ ID NO: 285) forward primer; and W83813_DB81_seg27_R1 (SEQ ID NO: 286) reverse primer.
[0420] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon W83813_DB81_seg27_F1R1 (SEQ ID NO: 287):
[0421] Forward primer (W83813_DB81_seg27_F1 (SEQ ID NO: 285)):
TABLE-US-00070 AATCTAGGCTGCCTCCTGGAG
[0422] Reverse primer (W83813_DB81_seg27_R1 (SEQ ID NO: 286)):
TABLE-US-00071 AGGTCAATTATACAAGGCATGACTTTAG
[0423] Amplicon (W83813_DB81_seg27_F1R1 (SEQ ID NO: 287)):
TABLE-US-00072 AATCTAGGCTGCCTCCTGGAGGAAGATACTTAGGAGTTCAGAAGTGAAGA GATGAGGCTTATAATACTTTTTCCTAAAGTCATGCCTTGTATAATTGACC T
Example 2.14
Expression of Cyclin-G1 (CCNG1), H31883, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name H31883_DB71_Seg13 in Kidney Tissues of Treated or Untreated Rats
[0424] Expression of Cyclin-G1 (CCNG1) transcripts detectable by or according to seg13--H31883_DB71_seg13_F1R1 (SEQ ID NO: 290) amplicon and primers H31883_DB71_seg13_F1 (SEQ ID NO: 288) and H31883_DB71_seg13_R1 (SEQ ID NO: 289) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0425] The column entitled H31883_DB71_seg13 in Table 22 contains the normalized expression values of the above-indicated Cyclin-G1 (CCNG1) transcript in treated or untreated kidney samples.
[0426] As is evident from the column entitled H31883_DB71_seg13 in Table 22, the level of expression of the Cyclin-G1 (CCNG1) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 5.00E.sup.-03 and P-value for day 5: 0.04.
[0427] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: H31883_DB71_seg13_F1 (SEQ ID NO: 288) forward primer; and H31883_DB71_seg13_R1 (SEQ ID NO: 289) reverse primer.
[0428] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: H31883_DB71_seg13_F1R1 (SEQ ID NO: 290).
[0429] Forward primer (H31883_DB71_seg13_F1 (SEQ ID NO: 288)):
TABLE-US-00073 TCGTCAGAATTGCTGCCTCA
[0430] Reverse primer (H31883_DB71_seg13_R1 (SEQ ID NO: 289)):
TABLE-US-00074 TCTGTGGTAAAAACCTCCTGGAGT
[0431] Amplicon (H31883_DB71_seg13_F1R1 (SEQ ID NO: 290)):
TABLE-US-00075 TCGTCAGAATTGCTGCCTCAATCTAGTCCCATTTGAGAAAATTTGTTTCT ACTGTCTCAATAACTGGATGAAATATCACTCTGAAAACTTGCCTATTGCA CTAAAGCTAGTTTAGGCTTGATAAAACACTCCAGGAGGTTTTTACCACAG A
Example 2.15
Expression of Cyclin-G1 (CCNG1), 1131883, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name MUSCYCG1R_DB81_Seg15-17 in Kidney Tissues of Treated or Untreated Rats
[0432] Expression of Cyclin-G1 (CCNG1) detectable by or according to seg15-17--MUSCYCG1R_DB81_seg15-17_F1R1 (SEQ ID NO: 293) amplicon and primers MUSCYCG1R_DB81_seg15-17_F1 (SEQ ID NO: 291) and MUSCYCG1R_DB81_seg15-17_R1 (SEQ ID NO: 292) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0433] The column entitled MUSCYCG1R_DB81_seg15-17 in Table 22 contains the normalized expression values of the above-indicated Cyclin-G1 (CCNG1) transcript in treated or untreated kidney samples.
[0434] As is evident from the column entitled MUSCYCG1R_DB81_seg15-17 in Table 22, the level of expression of the Cyclin-G1 (CCNG1) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 1.00E.sup.-07.
[0435] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: MUSCYCG1R_DB81_seg15-17_F1 (SEQ ID NO: 291) forward primer; and MUSCYCG1R_DB81_seg15-17_R1 (SEQ ID NO: 292) reverse primer.
[0436] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: MUSCYCG1R_DB81_seg15-17_F1R1 (SEQ ID NO: 293).
[0437] Forward primer (MUSCYCG1R_DB81_seg15-17_F1 (SEQ ID NO: 291)):
TABLE-US-00076 ATAAAATCAATCCCACTTTCTTGTTAAAAG
[0438] Reverse primer (MUSCYCG1R_DB81_seg15-17_R1 (SEQ ID NO: 292)):
TABLE-US-00077 CTTTGCCTTAGAAAATATGATCCTGC
[0439] Amplicon (MUSCYCG1R_DB81_seg15-17_F1R1 (SEQ ID NO: 293)):
TABLE-US-00078 ATAAAATCAATCCCACTTTCTTGTTAAAAGGAGAAACGATCTGAATTTTG AAAGACTAGAAGCCCAACTTAAGGCCTGCCACTGCAGGATCATATTTTCT AAGGCAAAG
Example 2.16
Expression of Cyclin-G1 (CCNG1), 1131883, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name MUSCYCG1R_DB81_Seg19-20 in Kidney Tissues of Treated or Untreated Rats
[0440] Expression of Cyclin-G1 (CCNG1) transcripts detectable by or according to seg19-20--MUSCYCG1R_DB81_seg19-20_F1R1 (SEQ ID NO: 296) amplicon and primers MUSCYCG1R_DB81_seg19-20_F1 (SEQ ID NO: 294) and MUSCYCG1R_DB81_seg19-20_R1 (SEQ ID NO: 295) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0441] The column entitled MUSCYCG1R_DB81_seg19-20 in Table 22 contains the normalized expression values of the above-indicated Cyclin-G1 (CCNG1) transcript in treated or untreated kidney samples.
[0442] As is evident from the column entitled MUSCYCG1R_DB81_seg19-20 in Table 22, the level of expression of the Cyclin-G1 (CCNG1) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 6.00E.sup.-03 and P-value for day 5: 3.00E.sup.-09.
[0443] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: MUSCYCG1R_DB81_seg19-20_F1 (SEQ ID NO: 294) forward primer; and MUSCYCG1R_DB81_seg19-20_R1 (SEQ ID NO: 295) reverse primer.
[0444] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: MUSCYCG1R_DB81_seg19-20_F1R1 (SEQ ID NO: 296).
[0445] Forward primer (MUSCYCG1R_DB81_seg19-20_F1 (SEQ ID NO: 294)):
TABLE-US-00079 GAGATCCAAGCACTGAAGTATGTAGAGT
[0446] Reverse primer (MUSCYCG1R_DB81_seg19-20_R1 (SEQ ID NO: 295)):
TABLE-US-00080 TCAGGAGTACAGTGGATACATTTCTCTT
[0447] Amplicon (MUSCYCG1R_DB81_seg19-20_F1R1 (SEQ ID NO: 296)):
TABLE-US-00081 GAGATCCAAGCACTGAAGTATGTAGAGTTAACAGAAGGAGTAGAATGTAT TCAGAAACATTCCAAGGTATGCCAAGGTGATAGCATTGATCCTATTAGCA AGCTACAAGAGAAATGTATCCACTGTACTCCTGA
Example 2.17
Expression of Repeat Domain 77 (WDR77), 1133998, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name W33294_DB81_Seg23 in Kidney Tissues of Treated or Untreated Rats
[0448] Expression of repeat domain 77 (WDR77) transcripts detectable by or according to seg23--W33294_DB81_seg23_F1R1 (SEQ ID NO: 299) amplicon and primers W33294_DB81_seg23_F1 (SEQ ID NO: 297) and W33294_DB81_seg23_R1 (SEQ ID NO: 298) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0449] The column entitled W33294_DB81_seg23 in Table 22 contains the normalized expression values of the above-indicated repeat domain 77 (WDR77) transcript in treated or untreated kidney samples.
[0450] As is evident from the column entitled W33294_DB81_seg23 in Table 22, the level of expression of the repeat domain 77 (WDR77) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 7.00E.sup.-04.
[0451] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: W33294_DB81_seg23_F1 (SEQ ID NO: 297) forward primer; and W33294_DB81_seg23_R1 (SEQ ID NO: 298) reverse primer.
[0452] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: W33294_DB81_seg23_F1R1 (SEQ ID NO: 299).
[0453] Forward primer (W33294_DB81_seg23_F1 (SEQ ID NO: 297)):
TABLE-US-00082 GGGCACTGCATGGATTATGTC
[0454] Reverse primer (W33294_DB81_seg23_R1 (SEQ ID NO: 298)):
TABLE-US-00083 CCATGCCCAGAATAAAGGAGC
[0455] Amplicon (W33294_DB81_seg23_F1R1 (SEQ ID NO: 299)):
TABLE-US-00084 GGGCACTGCATGGATTATGTCGGTTTTACCTAGCTTTGGAGACCATCATT TTTTCCTAATAGGTTTGCTTCATTGTTTCAGCTCCTTTATTCTGGGCA TGG
Example 2.18
Expression of Repeat Domain 77 (WDR77), 1133998, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name W33294_DB81_Seg44 in Kidney Tissues of Treated or Untreated Rats
[0456] Expression of repeat domain 77 (WDR77) transcripts detectable by or according to seg44--W33294_DB81_seg44_F1R1 (SEQ ID NO: 302) amplicon and primers W33294_DB81_seg44_F1 (SEQ ID NO: 300) and W33294_DB81_seg44_R1 (SEQ ID NO: 301) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0457] The column entitled W33294_DB81_seg44 in Table 22 contains the normalized expression values of the above-indicated repeat domain 77 (WDR77) transcript in treated or untreated kidney samples.
[0458] As is evident from the column entitled W33294_DB81_seg44 in Table 22, the level of expression of the repeat domain 77 (WDR77) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 8.00E.sup.-06.
[0459] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: W33294_DB81_seg44_F1 (SEQ ID NO: 300) forward primer; and W33294_DB81_seg44_R1 (SEQ ID NO: 301) reverse primer.
[0460] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: W33294_DB81_seg44_F1R1 (SEQ ID NO: 302).
[0461] Forward primer (W33294_DB81_seg44_F1 (SEQ ID NO: 300)):
TABLE-US-00085 CTCCGTTAGCAATTATGGGTCAGT
[0462] Reverse primer (W33294_DB81_seg44_R1 (SEQ ID NO: 301)):
TABLE-US-00086 GAAGCTCATGGTCCTTCAGGG
[0463] Amplicon (W33294_DB81_seg44_F1R1 (SEQ ID NO: 302)):
TABLE-US-00087 CTCCGTTAGCAATTATGGGTCAGTAACTGATCTTATTAGAGCTTTACAAC TTTGGTTTAGGAAAAGCACATAAAATGGGCGCCCTGAAGGACCATGAGCT TC
Example 2.19
Expression of Repeat Domain 77 (WDR77), 1133998, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name H33998_DB71_Seg19 in Kidney Tissues of Treated or Untreated Rats
[0464] Expression of repeat domain 77 (WDR77) transcripts detectable by or according to seg19--H33998_DB71_seg19_F3R3 (SEQ ID NO: 305) amplicon and primers H33998_DB71_seg19_F3 (SEQ ID NO: 303) and H33998_DB71_seg19_R3 (SEQ ID NO: 304) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0465] The column entitled H33998_DB71_seg19 in Table 22 contains the normalized expression values of the above-indicated repeat domain 77 (WDR77) transcript in treated or untreated kidney samples.
[0466] As is evident from the column entitled H33998_DB71_seg19 in Table 22, the level of expression of the repeat domain 77 (WDR77) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers-59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 0.04 and P-value fro day 5: 2.00E.sup.-07.
[0467] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: H33998_DB71_seg19_F3 (SEQ ID NO: 303) forward primer; and H33998_DB71_seg19_R3 (SEQ ID NO: 304) reverse primer.
[0468] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: H33998_DB71_seg19_F3R3 (SEQ ID NO: 305).
[0469] Forward primer (H33998_DB71_seg19_F3R3 (SEQ ID NO: 303)):
TABLE-US-00088 CTGTCATTGTCATTTTTCCCACC
[0470] Reverse primer (H33998_DB71_seg19_F3R3 (SEQ ID NO: 304)):
TABLE-US-00089 ATGCCGGATCTTCAATCTTAGG
[0471] Amplicon (H33998_DB71_seg19_F3R3 (SEQ ID NO: 305)):
TABLE-US-00090 CTGTCATTGTCATTTTTCCCACCTAAAAATTCCCTGAGGACTGATCTGGG TACTTTGCTCTGGAGAGCTGAAGTCTGAGCGCTGTATATTTGGACTCCTA AGATTGAAGATCCGGCAT
Example 2.20
Expression of Activating Transcription Factor 3 (ATF3), RATLRFI, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name RATLRFI_DB71_Seg9 in Kidney Tissues of Treated or Untreated Rats
[0472] Expression of Activating transcription factor 3 (ATF3) transcripts detectable by or according to seg9--RATLRFI_DB71_seg9_F1R1 (SEQ ID NO: 308) amplicon and primers RATLRFI_DB71_seg9_F1 (SEQ ID NO: 306) and RATLRFI_DB71_seg9_R1 (SEQ ID NO: 307) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0473] The column entitled RATLRFI_DB71_seg9 in Table 22 contains the normalized expression values of the above-indicated Activating transcription factor 3 (ATF3) transcript in treated or untreated kidney samples.
[0474] As is evident from the column entitled RATLRFI_DB71_seg9 in Table 22, the level of expression of the Activating transcription factor 3 (ATF3) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 0.025 and P-value fro day 5: 5.00E.sup.-04.
[0475] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: RATLRFI_DB71_seg9_F1 (SEQ ID NO: 306) forward primer; and RATLRFI_DB71_seg9_R1 (SEQ ID NO: 307) reverse primer.
[0476] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: RATLRFI_DB71_seg9_F1R1 (SEQ ID NO: 308).
[0477] Forward primer (RATLRFI_DB71_seg9_F1 (SEQ ID NO: 306)):
TABLE-US-00091 AACTGGCTGATGACCAGCTGT
[0478] Reverse primer (RATLRFI_DB71_seg9_R1 (SEQ ID NO: 307)):
TABLE-US-00092 TGCTGTGCCCGGGTTCT
[0479] Amplicon (RATLRFI_DB71_seg9_F1R1 (SEQ ID NO: 308)):
TABLE-US-00093 AACTGGCTGATGACCAGCTGTGCTACTCTGTGCTGACCGAGGACTGATGC CTCCTTCCCCTGTACCCACTGCTGAGGAAGAACCCGGGCACAGCA
Example 2.21
Expression of Ras-Related Protein Rab-13 (RAB13), RATRAB13X, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name RATRAB13X_DB81_Seg15-17 in Kidney Tissues of Treated or Untreated Rats
[0480] Expression of Ras-related protein Rab-13 (RAB13) transcripts detectable by or according to seg15-17--RATRAB13X_DB81_seg15-17_F1R1 (SEQ ID NO: 311) amplicon and primers RATRAB13X_DB81_seg15-17_F1 (SEQ ID NO: 309) and RATRAB13X_DB81_seg15-17_R1 (SEQ ID NO: 310) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0481] The column entitled RATRAB13X_DB81_seg15-17 in Table 22 contains the normalized expression values of the above-indicated Ras-related protein Rab-13 (RAB13) transcript in treated or untreated kidney samples.
[0482] As is evident from the column entitled RATRAB13X_DB81_seg15-17 in Table 22, the level of expression of the Ras-related protein Rab-13 (RAB13) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 0.05 and P-value for day 5: 3.00E.sup.-07.
[0483] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: RATRAB13X_DB81_seg15-17_F1 (SEQ ID NO: 309) forward primer; and RATRAB13X_DB81_seg15-17_R1 (SEQ ID NO: 310) reverse primer.
[0484] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: RATRAB13X_DB81_seg15-17_F1R1 (SEQ ID NO: 311).
[0485] Forward primer (RATRAB13X_DB81_seg15-17_F1 (SEQ ID NO: 309)):
TABLE-US-00094 GTGAGTCAGGCCGGGCT
[0486] Reverse primer (RATRAB13X_DB81_seg15-17_R1 (SEQ ID NO: 310)):
TABLE-US-00095 TCAAAAAATCGGATTCTGTGCTC
[0487] Amplicon (RATRAB13X_DB81_seg15-17_F1R1 (SEQ ID NO: 311)):
TABLE-US-00096 GTGAGTCAGGCCGGGCTGCTGTGGCCGAATGCCTTGCTTCTGCCCTTTAT CCAGCTCTCTCCTTCCTACCTCATCCCCTACAGTTGGCTCGAGAGCACAG AATCCGATTTTTTGA
Example 2.22
Expression of Ras-Related Protein Rab-13 (RAB13), RATRAB13X, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name RATRAB13X_DB81_Seg22 in Kidney Tissues of Treated or Untreated Rats
[0488] Expression of Ras-related protein Rab-13 (RAB13) transcripts detectable by or according to seg22--RATRAB13X_DB81_seg22_F2R2 (SEQ ID NO: 314) amplicon and primers RATRAB13X_DB81_seg22_F2 (SEQ ID NO: 312) and RATRAB13X_DB81_seg22_R2 (SEQ ID NO: 313) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0489] The column entitled RATRAB13X_DB81_seg22 in Table 22 contains the normalized expression values of the above-indicated Ras-related protein Rab-13 (RAB13) transcript in treated or untreated kidney samples.
[0490] As is evident from the column entitled RATRAB13X_DB81_seg22 in Table 22, the level of expression of the Ras-related protein Rab-13 (RAB13) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 0.04 and P-value for day 5: 3.00E.sup.-07.
[0491] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: RATRAB13X_DB81_seg22_F2 (SEQ ID NO: 312) forward primer; and RATRAB13X_DB81_seg22_R2 (SEQ ID NO: 313) reverse primer.
[0492] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: RATRAB13X_DB81_seg22_F2R2 (SEQ ID NO: 314).
[0493] Forward primer (RATRAB13X_DB81_seg22_F2 (SEQ ID NO: 312)):
TABLE-US-00097 TTCTCCTGAATCTGGCTGGGT
[0494] Reverse primer (RATRAB13X_DB81_seg22_R2 (SEQ ID NO: 313)):
TABLE-US-00098 TGGAAAAAGGATGTCCATTCTTC
[0495] Amplicon (RATRAB13X_DB81_seg22_F2R2 (SEQ ID NO: 314)):
TABLE-US-00099 TTCTCCTGAATCTGGCTGGGTCCCCCTTCCTTACCCCAACTCTTTAACTG GTGATGAAAACAGCAAGGAGAAAGGGCAGCCTGAAGAATGGACATCCTTT TTCCA
Example 2.23
Expression of Ras-Related Protein Rab-13 (RAB13), RATRAB13X, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name RATRAB13X_DB71_Seg11-13 in Kidney Tissues of Treated or Untreated Rats
[0496] Expression of Ras-related protein Rab-13 (RAB13) transcripts detectable by or according to seg11-13--RATRAB13X_DB71_seg11-13_F1R1 (SEQ ID NO: 317) amplicon and primers RATRAB13X_DB71_seg11-13_F1 (SEQ ID NO: 315) and RATRAB13X_DB71_seg11-13_R1 (SEQ ID NO: 316) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0497] The column entitled RATRAB13X_DB71_seg11-13 in Table 22 contains the normalized expression values of the above-indicated Ras-related protein Rab-13 (RAB13) transcript in treated or untreated kidney samples.
[0498] As is evident from the column entitled RATRAB13X_DB71_seg11-13 in Table 22, the level of expression of the Ras-related protein Rab-13 (RAB13) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 1.00E.sup.-03.
[0499] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: RATRAB13X_DB71_seg11-13_F1 (SEQ ID NO: 315) forward primer; and RATRAB13X_DB71_seg11-13_R1 (SEQ ID NO: 316) reverse primer.
[0500] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: RATRAB13X_DB71_seg11-13_F1R1 (SEQ ID NO: 317).
[0501] Forward primer (RATRAB13X_DB71_seg11-13_F1 (SEQ ID NO: 315)):
TABLE-US-00100 AGAATCCGATTTTTTGAGACAAGTG
[0502] Reverse primer (RATRAB13X_DB71_seg11-13_R1 (SEQ ID NO: 316)):
TABLE-US-00101 GATCTCCGGCCTCCTGTCTT
[0503] Amplicon (RATRAB13X_DB71_seg11-13_F1R1 (SEQ ID NO: 317)):
TABLE-US-00102 AGAATCCGATTTTTTGAGACAAGTGCCAAATCCAGTGTGAATGTGGATGA GGCTTTCAGTTCCCTGGCCCGTGACATCTTGCTCAAGACAGGAGGCCGGA GATC
Example 2.24
Expression of Cyclin-Dependent Kinase Inhibitor 1a (CDKN1A), RNU24174, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name MMU09507_DB81_Seg15 in Kidney Tissues of Treated or Untreated Rats
[0504] Expression of Cyclin-dependent kinase inhibitor 1A (CDKN1A) transcripts detectable by or according to seg15--MMU09507_DB81_seg15_F1R1 (SEQ ID NO: 323) amplicon and primers MMU09507_DB81_seg15_F1 (SEQ ID NO: 321) and MMU09507_DB81_seg15_R1 (SEQ ID NO: 322) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0505] The column entitled MMU09507_DB81_seg15 in Table 22 contains the normalized expression values of the above-indicated Cyclin-dependent kinase inhibitor 1A (CDKN1A) transcript in treated or untreated kidney samples.
[0506] As is evident from the column entitled MMU09507_DB81_seg15 in Table 22, the level of expression of the Cyclin-dependent kinase inhibitor 1A (CDKN1A) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 3.00E.sup.-03.
[0507] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: MMU09507_DB81_seg15_F1 (SEQ ID NO: 321) forward primer; and MMU09507_DB81_seg15_R1 (SEQ ID NO: 322) reverse primer.
[0508] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: MMU09507_DB81_seg15_F1R1 (SEQ ID NO: 323).
[0509] Forward primer (MMU09507_DB81_seg15_F1 (SEQ ID NO: 321)):
TABLE-US-00103 GGGTGGGGGAATCTAGCCT
[0510] Reverse primer (MMU09507_DB81_seg15_R1 (SEQ ID NO: 322)):
TABLE-US-00104 CCCCAGACAAAGGGACATGT
[0511] Amplicon (MMU09507_DB81_seg15_F1R1 (SEQ ID NO: 323)):
TABLE-US-00105 GGGTGGGGGAATCTAGCCTCTCTAGAGCCCTAGCCCTCTGACGAGGAGGA GGTGTAGTGCCCTGTAGCTTTTCCCCAGGACTCGCCACATGTCCCTTTGT CTGGGG
Example 2.25
Expression of Cyclin-Dependent Kinase Inhibitor 1a (CDKN1A), RNU24174, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name RNU24174_DB71_Seg8 in Kidney Tissues of Treated or Untreated Rats
[0512] Expression of Cyclin-dependent kinase inhibitor 1A (CDKN1A) transcripts detectable by or according to seg8--RNU24174_DB71_seg8_F1R1 (SEQ ID NO: 326) amplicon and primers RNU24174_DB71_seg8_F1 (SEQ ID NO: 324) and RNU24174_DB71_seg8_R1 (SEQ ID NO: 325) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT PREPARATION and Real-TIME RT-PCR ANALYSIS" hereinabove.
[0513] The column entitled RNU24174_DB71_seg8 in Table 22 contains the normalized expression values of the above-indicated Cyclin-dependent kinase inhibitor 1A (CDKN1A) transcript in treated or untreated kidney samples.
[0514] As is evident from the column entitled RNU24174_DB71_seg8 in Table 22, the level of expression of the Cyclin-dependent kinase inhibitor 1A (CDKN1A) transcript detectable by the above amplicon was significantly higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 1: 2.00E.sup.-05 and P-value for day 5: 3.00E.sup.-05.
[0515] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: RNU24174_DB71_seg8_F1 (SEQ ID NO: 324) forward primer; and RNU24174_DB71_seg8_R1 (SEQ ID NO: 325) reverse primer.
[0516] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: RNU24174_DB71_seg8_F1R1 (SEQ ID NO: 326).
[0517] Forward primer (RNU24174_DB71_seg8_F1 (SEQ ID NO: 324)):
TABLE-US-00106 CGCTGAAGTCCTCAGTGACTTG
[0518] Reverse primer (RNU24174_DB71_seg8_R1 (SEQ ID NO: 325)):
TABLE-US-00107 CACTAAGTGCTTCGACACCCAC
[0519] Amplicon (RNU24174_DB71_seg8_F1R1 (SEQ ID NO: 326)):
TABLE-US-00108 CGCTGAAGTCCTCAGTGACTTGTCCCATTTCTTAGTAGTTGTACAAGGAG TCAGGCCAAGATGGTGCCTCGGGGGCTGAGGGAGCTCACAGGAACTGAGC AGTGACTGGTCCTTTCCCAGTATTGAATACTGAGCCCCTGTGGGTGTCGA AGCACTTAGTG
[0520] Table 22 presents the normalized Real Time PCR results for all 25 amplicons detailed in examples 2.1-2.25 for all samples checked. The qRT-PCR measurements were normalized according to each samples normalization factor as described in "RT Preparation and Real-Time qRT-PCR Analysis" and further multiplied by a constant factor for ease of viewing.
TABLE-US-00109 TABLE 22 normalized Real Time PCR Sample AA686189_DB71_seg6 AA799594_DB71_seg0 AA964541_DB71_seg0 AI045075_DB71_seg6 68_1F101_day1_Saline 0.44 1.17 0.25 0.51 69_1F102_day1_Saline 0.38 1.16 0.28 0.44 70_1F103_day1_Saline 0.64 0.92 0.77 0.54 74_1F104_day5_Saline 0.63 1.69 0.41 0.42 75_1F105_day5_Saline 0.54 1.56 0.42 0.59 109_1F107_day28_Saline 0.78 1.6 0.49 0.79 110_1F108_day28_Saline 0.62 1.08 0.46 0.65 111_1F109_day28_Saline 0.68 0.9 0.45 0.9 65_1M1_day1_Saline 0.72 1.02 0.54 0.79 66_1M2_day1_Saline 0.65 0.87 0.65 0.36 67_1M3_day1_Saline 0.55 1.17 0.4 0.84 71_1M4_day5_Saline 0.45 1.28 0.49 0.6 72_1M5_day5_Saline 0.54 0.67 0.38 0.56 73_1M6_day5_Saline 0.41 0.86 0.41 0.45 106_1M7_day28_Saline 0.81 1.06 0.48 0.64 107_1M8_day28_Saline 0.36 1.24 0.25 0.42 108_1M9_day28_Saline 0.73 1.36 0.3 0.55 16_2F110_day1_Gent 1.19 1.25 1.35 1.5 17_2F111_day1_Gent 0.65 0.72 0.74 0.93 18_2F112_day1_Gent 1.07 0.93 1.29 0 45_2F113_day5_Gent 0.64 0.99 0.86 0.76 46_2F114_day5_Gent 0.72 0.89 0.58 1.04 47_2F115_day5_Gent 1.21 1.52 1.04 0.62 91_2F116_day28_Gent 2.7 0.84 3.19 2.09 92_2F117_day28_Gent 2.09 0.8 1.77 3.14 93_2F118_day28_Gent 2.48 0.89 2.16 1.74 1_2M10_day1_Gent 0.94 0.57 0.9 1.07 2_2M11_day1_Gent 1.04 0.95 1.19 1.03 3_2M12_day1_Gent 0.6 0.92 0.44 0.78 31_2M13_day5_Gent 0.81 0.89 0.91 1.1 32_2M14_day5_Gent 0.83 0.56 0.76 0 33_2M15_day5_Gent 0.75 1.04 0.87 1.04 76_2M16_day28_Gent 1.98 0.54 3.33 1.25 77_2M17_day28_Gent 1.23 0.5 1.45 1.99 78_2M18_day28_Gent 2.51 0.67 3.18 1.29 19_3F119_day1_Cis 0.7 1.17 0.88 1.01 20_3F120_day1_Cis 0.44 0.39 0.58 0.68 21_3F121_day1_Cis 0.66 0.98 0.41 0.79 48_3F122_day5_Cis 1.08 1.16 0.99 0.86 49_3F123_day5_Cis 0.93 1.34 0.74 0.53 50_3F124_day5_Cis 0.76 1.11 0.76 0.76 94_3F125_day28_Cis 0 0.74 2.63 2.17 95_3F126_day28_Cis 3.57 0.64 5.28 3.09 96_3F127_day28_Cis 6.06 0.52 6.85 3.37 4_3M19_day1_Cis 0.48 0.59 0.4 0.64 5_3M20_day1_Cis 0.42 0.99 0.29 0.62 6_3M21_day1_Cis 0.68 0.87 0.56 1.09 34_3M22_day5_Cis 1.5 0.93 1.94 1.93 35_3M23_day5_Cis 0.69 0.71 0.67 0.81 36_3M24_day5_Cis 4.48 0.75 4.8 1.33 79_3M25_day28_Cis 3.15 0.36 3.72 3.18 80_3M26_day28_Cis 4.29 0.97 4.71 2.72 81_3M27_day28_Cis 3.86 0.62 3.97 1.57 22_4F128_day1_Tob 1.19 0.87 0.56 1.66 23_4F129_day1_Tob 0.77 0.83 0.82 0.88 24_4F130_day1_Tob 2.14 1.07 2.02 3.16 51_4F131_day5_Tob 0.85 1.38 0.82 0.92 52_4F132_day5_Tob 1.04 0.88 0.77 1.61 53_4F133_day5_Tob 0.78 0.88 0.65 1.56 97_4F134_day28_Tob 2.1 0.71 1.68 0.94 98_4F135_day28_Tob 1.65 0.75 1.37 0.79 99_4F136_day28_Tob 2.23 0.84 1.59 1.19 7_4M28_day1_Tob 0.65 0.94 0.47 0.56 8_4M29_day1_Tob 0.85 1 0.75 1.03 9_4M30_day1_Tob 1.11 0.61 1.28 1.07 37_4M31_day5_Tob 0.53 0.81 0.53 0.74 38_4M32_day5_Tob 0.6 0.74 0.59 0.63 39_4M33_day5_Tob 0.44 1.03 0.34 0.69 82_4M34_day28_Tob 2.37 0.63 2.42 1.04 83_4M35_day28_Tob 3.35 0.66 3.33 1.76 84_4M36_day28_Tob 2.4 0.62 2.07 0.99 25_5F137_day1_CadCl 0.38 1.25 0.41 0.6 26_5F138_day1_CadCl 0.52 1.43 0.55 0.54 27_5F139_day1_CadCl 0.36 1.27 0.3 0.5 54_5F141_day5_CadCl 0.47 1.12 0.29 0.98 55_5F142_day5_CadCl 0.29 0.9 0.27 0.49 100_5F143_day28_CadCl 0.64 1.14 0.32 1.72 101_5F144_day28_CadCl 0.58 0.88 0.42 1.15 102_5F145_day28_CadCl 1.94 0.37 1.72 0.86 10_5M37_day1_CadCl 0.38 1.09 0.28 0.66 11_5M38_day1_CadCl 0.59 1.15 0.6 0.87 12_5M39_day1_CadCl 0.64 1.05 0.56 0.84 40_5M40_day5_CadCl 0.39 1.23 0.42 0.85 41_5M41_day5_CadCl 0.5 0.98 0.41 0.81 42_5M42_day5_CadCl 0.38 1.01 0.42 0.83 85_5M43_day28_CadCl 0.4 0.66 0.32 0.75 86_5M44_day28_CadCl 0.51 0.77 0.55 0.63 87_5M45_day28_CadCl 0.82 0.83 0.72 0.71 28_6F146_day1_Dox 0.78 1.1 0.62 0.61 29_6F147_day1_Dox 0.4 1.52 0.46 0.64 30_6F148_day1_Dox 0.26 1.52 0.33 3.12 56_6F149_day5_Dox 0.51 0.91 0.5 0.76 57_6F150_day5_Dox 0.48 0.84 0.46 0.93 58_6F151_day5_Dox 0.38 1.24 0.4 0.57 103_6F171_day28_Dox 1.5 1.24 1.04 0.66 104_6F172_day28_Dox 0.62 1.39 0.55 0.82 105_6F173_day28_Dox 0.04 1.29 1.3 1.6 13_6M46_day1_Dox 0.59 1.26 0.54 1.12 14_6M47_day1_Dox 0.49 0.92 0.55 1.21 15_6M48_day1_Dox 0.39 0.99 0.38 0.78 43_6M49_day5_Dox 1.2 0.84 1.14 0.93 44_6M50_day5_Dox 0.6 1.22 0.48 2.05 88_6M71_day28_Dox 6.37 0.45 5.73 1.49 89_6M72_day28_Dox 0.92 1.06 0.96 0.9 90_6M73_day28_Dox 1.28 0.92 1.43 0.87 115_7F155_day1_ValpA 0.45 1.42 0.4 1.22 116_7F156_day1_ValpA 0.42 1.1 0.31 0.01 117_7F157_day1_ValpA 0.37 1.1 0.32 0.57 121_7F158_day5_ValpA 0.36 1.33 0.38 0.79 122_7F159_day5_ValpA 0.02 1.21 0.36 0.66 123_7F160_day5_ValpA 0.53 1.37 0.28 0.66 127_7F161_day28_ValpA 0.45 1.17 0.28 0.68 128_7F162_day28_ValpA 0.58 1.55 0.32 1.12 129_7F163_day28_ValpA 0.42 1.32 0.28 1.23 112_7M55_day1_ValpA 0.4 0.92 0.39 0.88 113_7M56_day1_ValpA 0.5 1.28 0.33 0.83 114_7M57_day1_ValpA 0.48 0.84 0.42 0.72 118_7M58_day5_ValpA 0.37 0.99 0.15 0.92 119_7M59_day5_ValpA 0.36 0.86 0.25 0.47 120_7M60_day5_ValpA 0.29 0.91 0.18 0.42 124_7M61_day28_ValpA 0.21 1.05 0.15 0.62 125_7M62_day28_ValpA 0.45 0.81 0.36 0.86 126_7M63_day28_ValpA 0.4 1.23 0.25 0.59 62_8F181_day28_Naive 0.47 1.59 0.39 0.55 63_8F182_day28_Naive 0.6 1.23 0.37 0.51 64_8F183_day28_Naive 0.42 0.84 0.38 0.52 59_8M81_day28_Naive 0.74 1.46 0.68 0.7 60_8M82_day28_Naive 0.46 1.26 0.3 0.33 61_8M83_day28_Naive 0.45 1.18 0.34 0.53 Sample AI454051_DB71_seg0 AW919147_DB71_seg0 BI293562_DB71_seg2 68_1F101_day1_Saline 0.96 0.9 0.61 69_1F102_day1_Saline 0.99 0.96 0.67 70_1F103_day1_Saline 0.88 1.03 0.68 74_1F104_day5_Saline 1.08 0.92 0.2 75_1F105_day5_Saline 0.93 0.9 0.41 109_1F107_day28_Saline 1.3 1.09 0.29 110_1F108_day28_Saline 1.33 1.12 0.37 111_1F109_day28_Saline 0.7 0.84 0.16 65_1M1_day1_Saline 0.91 0.9 1.45 66_1M2_day1_Saline 0.11 0.73 0.42 67_1M3_day1_Saline 1.13 1.05 0.7 71_1M4_day5_Saline 1.01 0.86 0.83 72_1M5_day5_Saline 0.73 1.17 0.4 73_1M6_day5_Saline 0.49 0.92 0.33 106_1M7_day28_Saline 0.86 1.3 0.63 107_1M8_day28_Saline 0.88 1.28 0.32 108_1M9_day28_Saline 1.16 1.7 0.87 16_2F110_day1_Gent 0.9 1.72 0.59 17_2F111_day1_Gent 0.75 0.72 0.94 18_2F112_day1_Gent 0.57 0.76 1.04 45_2F113_day5_Gent 0.63 0.86 0.95 46_2F114_day5_Gent 1.04 0.88 0.76 47_2F115_day5_Gent 1.19 0.95 2.8 91_2F116_day28_Gent 0.67 0.73 2.01 92_2F117_day28_Gent 1 1.12 1.19 93_2F118_day28_Gent 0.95 0.89 0.81 1_2M10_day1_Gent 0.4 0.72 0.93 2_2M11_day1_Gent 0.54 1.1 0.55 3_2M12_day1_Gent 0.79 0.99 0.41 31_2M13_day5_Gent 0.8 0.71 2.32 32_2M14_day5_Gent 0.63 0.79 1.61 33_2M15_day5_Gent 0.82 0.78 0.93 76_2M16_day28_Gent 1.14 0.75 0.63 77_2M17_day28_Gent 0.64 0.57 0.72 78_2M18_day28_Gent 0.71 0.93 1.16 19_3F119_day1_Cis 0.94 0.8 0.74 20_3F120_day1_Cis 1.22 1.09 0.5 21_3F121_day1_Cis 1 0.87 0.38 48_3F122_day5_Cis 1.05 1.39 0.74 49_3F123_day5_Cis 1.43 1.05 0.67 50_3F124_day5_Cis 1.39 0.83 0.7 94_3F125_day28_Cis 0.68 1.08 5.98 95_3F126_day28_Cis 0.8 0.54 12.27 96_3F127_day28_Cis 0.87 0.72 8.01 4_3M19_day1_Cis 0.65 0.87 0.7 5_3M20_day1_Cis 0.96 1.21 0.39 6_3M21_day1_Cis 1.45 0.88 0.71 34_3M22_day5_Cis 0.92 1.08 3.45 35_3M23_day5_Cis 1.16 0.8 0.81 36_3M24_day5_Cis 0.86 0.88 1.76 79_3M25_day28_Cis 0.73 0.66 6.24 80_3M26_day28_Cis 0.82 0.84 2.93 81_3M27_day28_Cis 0.78 0.54 3.33 22_4F128_day1_Tob 1.16 0.8 0.29 23_4F129_day1_Tob 1.36 1.06 0.42 24_4F130_day1_Tob 0.8 0.98 0.73 51_4F131_day5_Tob 1.26 0.88 0.71 52_4F132_day5_Tob 1.23 0.99 1.62 53_4F133_day5_Tob 1.32 1.05 0.84 97_4F134_day28_Tob 0.94 0.8 1.32 98_4F135_day28_Tob 1.29 0.86 1.02 99_4F136_day28_Tob 0.72 0.72 0.35 7_4M28_day1_Tob 0.86 0.82 0.58 8_4M29_day1_Tob 1.29 1.33 1.38 9_4M30_day1_Tob 1.17 1.22 1.04 37_4M31_day5_Tob 0.61 0.58 0.3 38_4M32_day5_Tob 0.57 0.63 0.44 39_4M33_day5_Tob 0.63 1.14 0.59 82_4M34_day28_Tob 1 0.76 0.84 83_4M35_day28_Tob 0.94 1.23 1.78 84_4M36_day28_Tob 1 0.63 1.07 25_5F137_day1_CadCl 1.47 1 0.36 26_5F138_day1_CadCl 1.46 1.21 0.4 27_5F139_day1_CadCl 1.08 0.76 0.61 54_5F141_day5_CadCl 1.54 1.06 0.43 55_5F142_day5_CadCl 1.35 1.86 0.63 100_5F143_day28_CadCl 0.79 0.77 0.4 101_5F144_day28_CadCl 1.05 0.91 0.81 102_5F145_day28_CadCl 0.54 0.42 2.59 10_5M37_day1_CadCl 1.48 1 0.5 11_5M38_day1_CadCl 2.13 1.1 0.51 12_5M39_day1_CadCl 0.77 1.02 0.39 40_5M40_day5_CadCl 0.84 1.3 0.48 41_5M41_day5_CadCl 0.68 0.94 0.88 42_5M42_day5_CadCl 0.92 1 0.78 85_5M43_day28_CadCl 1.29 1.31 0.72 86_5M44_day28_CadCl 1.31 1.18 1.35 87_5M45_day28_CadCl 0.75 0.68 0.31 28_6F146_day1_Dox 1.2 1.35 0.38 29_6F147_day1_Dox 1.05 1.2 0.39 30_6F148_day1_Dox 1.54 1.09 0.42 56_6F149_day5_Dox 1.17 0.99 0.68 57_6F150_day5_Dox 1.35 0.89 0.51 58_6F151_day5_Dox 1.44 1.1 0.7 103_6F171_day28_Dox 0.85 0.88 0.99 104_6F172_day28_Dox 0.92 1.05 0.58 105_6F173_day28_Dox 0.87 0.82 0 13_6M46_day1_Dox 0.8 1.1 0.53 14_6M47_day1_Dox 0.8 1.11 0.42 15_6M48_day1_Dox 1.03 0.91 0.32 43_6M49_day5_Dox 0.3 1.01 1.39 44_6M50_day5_Dox 0.95 1.16 1.04 88_6M71_day28_Dox 0.96 0.48 1.81 89_6M72_day28_Dox 1.11 1.42 0.55 90_6M73_day28_Dox 0.72 1.2 0.71 115_7F155_day1_ValpA 1.56 1.43 0.45 116_7F156_day1_ValpA 1.08 0.84 0.38 117_7F157_day1_ValpA 1.17 1.84 0.4 121_7F158_day5_ValpA 1.49 1.69 0.36 122_7F159_day5_ValpA 1.52 1.83 0.39
123_7F160_day5_ValpA 1.72 0.94 0.12 127_7F161_day28_ValpA 1.16 0.92 0.18 128_7F162_day28_ValpA 1.31 1.31 0.59 129_7F163_day28_ValpA 1.32 1.06 0.5 112_7M55_day1_ValpA 1.08 0.83 0.46 113_7M56_day1_ValpA 0.97 0.96 0.52 114_7M57_day1_ValpA 0.86 1.02 0.5 118_7M58_day5_ValpA 1 0.97 0.59 119_7M59_day5_ValpA 0.99 1.27 0.45 120_7M60_day5_ValpA 0.81 0.79 0.62 124_7M61_day28_ValpA 0.91 1.12 0.21 125_7M62_day28_ValpA 1.16 1.16 0.31 126_7M63_day28_ValpA 0.95 1.11 0.35 62_8F181_day28_Naive 0.92 1.02 0.41 63_8F182_day28_Naive 1.07 1.08 0.49 64_8F183_day28_Naive 0.81 1.23 0.38 59_8M81_day28_Naive 1.75 1.27 0.72 60_8M82_day28_Naive 0.75 0.8 0.3 61_8M83_day28_Naive 0.66 0.94 0.39 Sample H31045_DB71_seg5 H31799_DB71_seg23 H31883_DB71_seg13 AI502869_DB71_seg0 68_1F101_day1_Saline 0.16 1.05 0.88 0.98 69_1F102_day1_Saline 1.03 0.96 0.36 0.68 70_1F103_day1_Saline 0.24 1.06 0.75 0.73 74_1F104_day5_Saline 0.15 1.16 0.71 0.99 75_1F105_day5_Saline 0.67 0.7 0.59 0.67 109_1F107_day28_Saline 0.81 1.21 0.83 1.25 110_1F108_day28_Saline 1 1.13 0.89 2.1 111_1F109_day28_Saline 2.96 1.06 0.83 1.32 65_1M1_day1_Saline 0.93 1.12 0.68 0.62 66_1M2_day1_Saline 0.69 0.87 0.69 0.6 67_1M3_day1_Saline 0.19 1.06 0.78 0.62 71_1M4_day5_Saline 0.28 0.98 0.63 0.82 72_1M5_day5_Saline 0.18 1.11 0.56 0.86 73_1M6_day5_Saline 0.25 0.88 0.68 0.52 106_1M7_day28_Saline 0.42 0.82 0.88 1.24 107_1M8_day28_Saline 2.19 1.13 0.73 1.14 108_1M9_day28_Saline 0.36 1.06 0.84 1.31 16_2F110_day1_Gent 0.27 1.19 0.99 0.83 17_2F111_day1_Gent 0.22 0.88 0.92 0.61 18_2F112_day1_Gent 0.73 0.93 0.82 0.53 45_2F113_day5_Gent 0.52 0.92 0.73 0.73 46_2F114_day5_Gent 1.01 0.91 0.55 0.62 47_2F115_day5_Gent 0.4 1.36 0.91 0.96 91_2F116_day28_Gent 0.79 0.88 0.88 0.66 92_2F117_day28_Gent 0.84 1.05 0.98 0.74 93_2F118_day28_Gent 0.67 1.17 0.96 0.73 1_2M10_day1_Gent 0.16 1 0.82 1.53 2_2M11_day1_Gent 0.19 1.04 0.61 0.99 3_2M12_day1_Gent 0.15 1.2 0.73 0.76 31_2M13_day5_Gent 1.57 1.08 1.01 0.51 32_2M14_day5_Gent 1.47 0.76 0.7 0.43 33_2M15_day5_Gent 0.33 0.88 0.65 0.53 76_2M16_day28_Gent 1.11 1.17 1.05 1.36 77_2M17_day28_Gent 4.65 0.37 0.64 0.92 78_2M18_day28_Gent 0.45 1.06 0.8 0.77 19_3F119_day1_Cis 0.24 1.03 2.03 0.67 20_3F120_day1_Cis 0.28 1.09 1.06 0.78 21_3F121_day1_Cis 0.22 1.04 1.07 0.74 48_3F122_day5_Cis 1.8 1.1 1.17 0.8 49_3F123_day5_Cis 0.34 0.74 1.44 0.93 50_3F124_day5_Cis 0.51 1.23 1.2 0.74 94_3F125_day28_Cis 0.73 1.05 2.72 1.03 95_3F126_day28_Cis 0.73 1.15 4.07 1.03 96_3F127_day28_Cis 0.81 0.98 3.83 1.25 4_3M19_day1_Cis 0.82 1.22 0.74 0.87 5_3M20_day1_Cis 0.21 1.27 0.71 0.87 6_3M21_day1_Cis 1.22 1.12 1.52 0.84 34_3M22_day5_Cis 3.25 0.92 1.73 0.52 35_3M23_day5_Cis 0.23 1.05 1.3 1.13 36_3M24_day5_Cis 1.66 1.06 2.43 0.61 79_3M25_day28_Cis 0.88 0.88 2.41 0.74 80_3M26_day28_Cis 2.92 1.21 3.37 1.35 81_3M27_day28_Cis 2.96 0.9 2.23 0.95 22_4F128_day1_Tob 0.2 0.91 0.87 0.52 23_4F129_day1_Tob 0.18 0.87 0.68 1.32 24_4F130_day1_Tob 0.74 1.2 0.87 0.79 51_4F131_day5_Tob 1.19 1.1 0.82 0.81 52_4F132_day5_Tob 0.42 0.92 0.69 0.74 53_4F133_day5_Tob 0.38 0.83 0.52 0.74 97_4F134_day28_Tob 0.76 1.03 0.84 1.08 98_4F135_day28_Tob 1 0.71 0.63 2.38 99_4F136_day28_Tob 0.63 1.15 0.84 1.04 7_4M28_day1_Tob 0.2 1.09 0.83 0.87 8_4M29_day1_Tob 1.03 1.14 0.69 1.02 9_4M30_day1_Tob 0.22 1.17 0.61 1.28 37_4M31_day5_Tob 0.9 0.71 0.48 0.42 38_4M32_day5_Tob 0.29 0.72 0.47 0.5 39_4M33_day5_Tob 1.65 0.96 0.82 0.72 82_4M34_day28_Tob 2.08 0.94 0.6 1.22 83_4M35_day28_Tob 2.68 0.88 0.73 0.99 84_4M36_day28_Tob 2.92 1.12 0.73 1.22 25_5F137_day1_CadCl 1.97 1 0.73 0.54 26_5F138_day1_CadCl 0.39 1.24 0.63 1.37 27_5F139_day1_CadCl 0.39 1 0.87 0.56 54_5F141_day5_CadCl 0.56 0.83 0.87 0.94 55_5F142_day5_CadCl 0.32 0.99 0.86 0.73 100_5F143_day28_CadCl 2.88 1.59 0.97 0.73 101_5F144_day28_CadCl 0.83 0.94 1.02 1.22 102_5F145_day28_CadCl 0.57 0.67 0.86 0.44 10_5M37_day1_CadCl 0.19 0.91 0.65 1.14 11_5M38_day1_CadCl 0.19 0.9 0.71 2.59 12_5M39_day1_CadCl 0.18 1.15 0.78 0.86 40_5M40_day5_CadCl 0.42 1.17 0.83 0.69 41_5M41_day5_CadCl 0.4 0.98 0.78 0.68 42_5M42_day5_CadCl 0.46 0.94 0.64 0.85 85_5M43_day28_CadCl 2.23 1.05 0.95 2.47 86_5M44_day28_CadCl 2.41 1.02 0.8 2.93 87_5M45_day28_CadCl 2 0.76 0.86 1.18 28_6F146_day1_Dox 1.15 1.04 0.93 0.71 29_6F147_day1_Dox 0.3 0.99 0.89 0.81 30_6F148_day1_Dox 1.95 0.87 0.67 0.67 56_6F149_day5_Dox 1.86 0.95 1.16 0.51 57_6F150_day5_Dox 1.19 1.08 1.03 1 58_6F151_day5_Dox 0.52 0.66 0.9 1.07 103_6F171_day28_Dox 2.16 1.16 1.48 1.33 104_6F172_day28_Dox 2.58 1.25 1.77 1.48 105_6F173_day28_Dox 0.51 1.57 2.29 0.98 13_6M46_day1_Dox 0.23 1.07 1.02 0.77 14_6M47_day1_Dox 0.32 1.26 1.07 0.68 15_6M48_day1_Dox 0.75 0.92 0.9 0.78 43_6M49_day5_Dox 0.35 0.56 1.21 0.73 44_6M50_day5_Dox 1.41 0.9 1.38 0.71 88_6M71_day28_Dox 1.57 0.64 1.45 0.42 89_6M72_day28_Dox 2.33 1.11 1.59 1.49 90_6M73_day28_Dox 2.12 1.06 1.93 1.28 115_7F155_day1_ValpA 0.68 1.29 1.02 0.86 116_7F156_day1_ValpA 1.71 0.9 0.01 1.09 117_7F157_day1_ValpA 0.53 0 0.66 1.13 121_7F158_day5_ValpA 0.56 0.94 1.54 1.81 122_7F159_day5_ValpA 1 1.19 1.1 2.53 123_7F160_day5_ValpA 0.57 1.15 1.05 1.94 127_7F161_day28_ValpA 4.35 0.98 0.92 1.24 128_7F162_day28_ValpA 0.58 0.67 0.9 1.19 129_7F163_day28_ValpA 1.41 0.99 0.81 1.18 112_7M55_day1_ValpA 3.33 1.11 0.75 1.33 113_7M56_day1_ValpA 2.68 1.23 0.9 1 114_7M57_day1_ValpA 0.73 1.16 0.95 1.43 118_7M58_day5_ValpA 2.42 0.51 1 1.37 119_7M59_day5_ValpA 0.83 1.06 0.48 1.06 120_7M60_day5_ValpA 2.53 1.02 0.63 1.29 124_7M61_day28_ValpA 1.58 0.98 0.71 0.97 125_7M62_day28_ValpA 0.2 1.03 1.11 1.46 126_7M63_day28_ValpA 0.47 0.75 0.72 1.43 62_8F181_day28_Naive 1.21 1.05 0.79 1.24 63_8F182_day28_Naive 0.25 0.94 0.73 0.78 64_8F183_day28_Naive 0.25 1 0.66 0.77 59_8M81_day28_Naive 0.54 1.26 0 1 60_8M82_day28_Naive 0.26 1.05 0.58 0.79 61_8M83_day28_Naive 0.29 0.82 0.68 0.64 Sample H33998_DB71_seg19 RATLRFI_DB71_seg9 RATRAB13X_DB71_seg11-13 68_1F101_day1_Saline 0.73 0.37 0.97 69_1F102_day1_Saline 1.01 0.28 0.78 70_1F103_day1_Saline 0.88 0.09 0.98 74_1F104_day5_Saline 0.93 0.36 0.97 75_1F105_day5_Saline 1.1 0.49 0.94 109_1F107_day28_Saline 0.41 0.44 1 110_1F108_day28_Saline 0.59 0.37 1.11 111_1F109_day28_Saline 0.57 0.58 0.92 65_1M1_day1_Saline 0.51 0.01 0.83 66_1M2_day1_Saline 0.98 0.32 1.06 67_1M3_day1_Saline 0.51 0.36 0.87 71_1M4_day5_Saline 1.26 0.21 0.76 72_1M5_day5_Saline 1.13 0.25 0.76 73_1M6_day5_Saline 0.98 0.22 0.64 106_1M7_day28_Saline 0.6 0.32 0.82 107_1M8_day28_Saline 0.36 0.12 0.77 108_1M9_day28_Saline 0.73 0.43 0.91 16_2F110_day1_Gent 1.31 0.98 1.16 17_2F111_day1_Gent 0.83 1.54 0.7 18_2F112_day1_Gent 0.56 1.09 0.77 45_2F113_day5_Gent 1.9 0.48 0.9 46_2F114_day5_Gent 1.5 0.43 0.82 47_2F115_day5_Gent 2.19 4.15 1.12 91_2F116_day28_Gent 0.4 5.63 0.83 92_2F117_day28_Gent 0.7 4.17 1.12 93_2F118_day28_Gent 0.56 2.43 0.88 1_2M10_day1_Gent 1.51 2.74 2.79 2_2M11_day1_Gent 1.35 1.72 1.14 3_2M12_day1_Gent 0.99 0.27 1.03 31_2M13_day5_Gent 1.91 1.35 0.9 32_2M14_day5_Gent 0.83 1.13 0.61 33_2M15_day5_Gent 1.16 0.59 0.8 76_2M16_day28_Gent 0.4 2.56 1.17 77_2M17_day28_Gent 0.49 1.59 0.76 78_2M18_day28_Gent 0.42 2.51 1.22 19_3F119_day1_Cis 0.85 1.49 0.91 20_3F120_day1_Cis 1 0.3 1.12 21_3F121_day1_Cis 0.87 0.57 1.09 48_3F122_day5_Cis 1.79 0.79 1.06 49_3F123_day5_Cis 1.84 0.44 1.01 50_3F124_day5_Cis 1.95 0.32 1.02 94_3F125_day28_Cis 0.55 2.33 1.29 95_3F126_day28_Cis 0.69 3.05 1.62 96_3F127_day28_Cis 0.85 3.8 1.78 4_3M19_day1_Cis 0.65 0.24 0.87 5_3M20_day1_Cis 0.75 0.2 1.15 6_3M21_day1_Cis 1.14 0.37 1.16 34_3M22_day5_Cis 1.49 0.65 1.13 35_3M23_day5_Cis 0.46 0.34 0.74 36_3M24_day5_Cis 2.14 1.97 1.27 79_3M25_day28_Cis 0.61 3.03 1.57 80_3M26_day28_Cis 0.62 2.4 1.24 81_3M27_day28_Cis 0.41 2.26 1.31 22_4F128_day1_Tob 0.75 1.03 1.11 23_4F129_day1_Tob 0.76 0.68 1.06 24_4F130_day1_Tob 0.77 3.08 1.22 51_4F131_day5_Tob 1.65 0.75 1.21 52_4F132_day5_Tob 1.88 3.08 0.98 53_4F133_day5_Tob 1.61 0.79 0.87 97_4F134_day28_Tob 0.99 1.94 1.25 98_4F135_day28_Tob 0.44 2.39 0.9 99_4F136_day28_Tob 0.74 1.98 1.29 7_4M28_day1_Tob 0.7 0.22 1.12 8_4M29_day1_Tob 0.98 1.63 1.01 9_4M30_day1_Tob 0.71 3.36 1.08 37_4M31_day5_Tob 1.1 0.88 0.59 38_4M32_day5_Tob 0.88 0.72 0.71 39_4M33_day5_Tob 1.3 0.17 0.81 82_4M34_day28_Tob 0.61 2.01 1.12 83_4M35_day28_Tob 0.54 3.78 1.34 84_4M36_day28_Tob 0.69 2.37 1.31 25_5F137_day1_CadCl 2.29 0.27 0.95 26_5F138_day1_CadCl 2.51 0.33 1.2 27_5F139_day1_CadCl 0.01 0.32 0.95 54_5F141_day5_CadCl 2 0.35 0.95 55_5F142_day5_CadCl 0.82 0.31 0.9 100_5F143_day28_CadCl 1.26 0.66 1.37 101_5F144_day28_CadCl 0.59 0.85 0.92 102_5F145_day28_CadCl 0.43 1.78 0.96 10_5M37_day1_CadCl 0.76 0.27 1.05 11_5M38_day1_CadCl 0.66 0.36 1.22 12_5M39_day1_CadCl 0.69 0.23 1.14 40_5M40_day5_CadCl 1.39 0.17 0.75 41_5M41_day5_CadCl 1.36 0.18 0.75 42_5M42_day5_CadCl 1.64 0.29 0.62 85_5M43_day28_CadCl 0.45 0.28 1.11 86_5M44_day28_CadCl 0.26 0.67 1.08 87_5M45_day28_CadCl 0.41 0.56 0.88 28_6F146_day1_Dox 1.25 0.25 1.1 29_6F147_day1_Dox 1.34 0.21 0.9 30_6F148_day1_Dox 2.14 0.31 1 56_6F149_day5_Dox 2.39 0.46 1.17 57_6F150_day5_Dox 1.29 0.29 1.16 58_6F151_day5_Dox 3.68 0.18 0.94 103_6F171_day28_Dox 0.48 0.72 0.74 104_6F172_day28_Dox 0.58 0.4 0.95
105_6F173_day28_Dox 0.96 1.47 1.05 13_6M46_day1_Dox 0.97 0.46 0.88 14_6M47_day1_Dox 1.07 0.48 1.09 15_6M48_day1_Dox 2.75 0.24 0.86 43_6M49_day5_Dox 1.19 0.47 0.7 44_6M50_day5_Dox 1.37 0.25 0.83 88_6M71_day28_Dox 0.64 8.34 0.91 89_6M72_day28_Dox 0.44 0.53 0.77 90_6M73_day28_Dox 0.54 1.08 0.84 115_7F155_day1_ValpA 1.48 0.55 1.32 116_7F156_day1_ValpA 0.82 0.32 0.96 117_7F157_day1_ValpA 1.15 0.45 1.01 121_7F158_day5_ValpA 0.76 0.39 0.79 122_7F159_day5_ValpA 0.88 0.41 1.26 123_7F160_day5_ValpA 1.19 0.39 1.41 127_7F161_day28_ValpA 0.71 0.36 0.91 128_7F162_day28_ValpA 0.56 0.54 0.91 129_7F163_day28_ValpA 0.58 0.53 0.96 112_7M55_day1_ValpA 0.37 0.39 0.79 113_7M56_day1_ValpA 0.77 0.36 0.93 114_7M57_day1_ValpA 0.53 0.44 0.83 118_7M58_day5_ValpA 1.36 0.22 0.67 119_7M59_day5_ValpA 1.11 0.21 0.8 120_7M60_day5_ValpA 1.03 0.3 0.65 124_7M61_day28_ValpA 0.69 0.23 0.88 125_7M62_day28_ValpA 0.78 0.48 0.99 126_7M63_day28_ValpA 0.52 0.33 0.69 62_8F181_day28_Naive 0.69 0.39 1.07 63_8F182_day28_Naive 1.23 0.45 1.07 64_8F183_day28_Naive 0.85 0.34 0.79 59_8M81_day28_Naive 1.25 0.42 1.08 60_8M82_day28_Naive 0.99 0.25 0.66 61_8M83_day28_Naive 0 0.26 0.77 Sample RNU24174_DB71_seg8 W41270_DB81_seg11 68_1F101_day1_Saline 0.57 0.6 69_1F102_day1_Saline 0.41 0.86 70_1F103_day1_Saline 0.32 1.31 74_1F104_day5_Saline 0.26 0.59 75_1F105_day5_Saline 0.28 0.83 109_1F107_day28_Saline 0.33 0.36 110_1F108_day28_Saline 0.24 0.41 111_1F109_day28_Saline 0.33 0.39 65_1M1_day1_Saline 0.24 0.57 66_1M2_day1_Saline 0.15 0.99 67_1M3_day1_Saline 0.29 0.54 71_1M4_day5_Saline 0.15 0.68 72_1M5_day5_Saline 0.33 1 73_1M6_day5_Saline 0.12 0.46 106_1M7_day28_Saline 0.24 0.33 107_1M8_day28_Saline 0.15 0.26 108_1M9_day28_Saline 0.27 0.33 16_2F110_day1_Gent 0.47 1.24 17_2F111_day1_Gent 0.5 0.67 18_2F112_day1_Gent 0.47 1.19 45_2F113_day5_Gent 0.31 2.04 46_2F114_day5_Gent 0.22 1.34 47_2F115_day5_Gent 0.81 2.42 91_2F116_day28_Gent 1.53 0.94 92_2F117_day28_Gent 1.2 0.81 93_2F118_day28_Gent 0.59 0.81 1_2M10_day1_Gent 0.74 0.46 2_2M11_day1_Gent 0.37 0.68 3_2M12_day1_Gent 0.26 0.57 31_2M13_day5_Gent 0.65 2.03 32_2M14_day5_Gent 0.36 1.08 33_2M15_day5_Gent 0.4 1.2 76_2M16_day28_Gent 1.91 1.42 77_2M17_day28_Gent 0.69 0.75 78_2M18_day28_Gent 0.65 0.84 19_3F119_day1_Cis 0.57 1.11 20_3F120_day1_Cis 0.32 0.86 21_3F121_day1_Cis 0.36 0.76 48_3F122_day5_Cis 0.97 1.97 49_3F123_day5_Cis 0.7 1.9 50_3F124_day5_Cis 0.6 1.79 94_3F125_day28_Cis 8.38 1.45 95_3F126_day28_Cis 12.63 1.8 96_3F127_day28_Cis 12.14 1.48 4_3M19_day1_Cis 0.2 0.33 5_3M20_day1_Cis 0.27 0.63 6_3M21_day1_Cis 0.69 0.71 34_3M22_day5_Cis 1.3 1.51 35_3M23_day5_Cis 0.31 1.07 36_3M24_day5_Cis 3.6 3.12 79_3M25_day28_Cis 10.21 1.94 80_3M26_day28_Cis 7.3 1.11 81_3M27_day28_Cis 8.08 1.45 22_4F128_day1_Tob 0.29 1.01 23_4F129_day1_Tob 0.32 0.44 24_4F130_day1_Tob 0.53 0.83 51_4F131_day5_Tob 0.46 2.6 52_4F132_day5_Tob 0.76 3.25 53_4F133_day5_Tob 0.47 2.67 97_4F134_day28_Tob 0.55 1.01 98_4F135_day28_Tob 0.65 0.73 99_4F136_day28_Tob 0.69 0.9 7_4M28_day1_Tob 0.29 0.57 8_4M29_day1_Tob 0.49 0.79 9_4M30_day1_Tob 0.51 0.76 37_4M31_day5_Tob 0.09 0.62 38_4M32_day5_Tob 0.2 0.81 39_4M33_day5_Tob 0.14 1.21 82_4M34_day28_Tob 0.54 0.92 83_4M35_day28_Tob 0.93 1.03 84_4M36_day28_Tob 0.62 0.79 25_5F137_day1_CadCl 0.3 1.44 26_5F138_day1_CadCl 0.29 1.78 27_5F139_day1_CadCl 0.49 1.48 54_5F141_day5_CadCl 0.33 2.49 55_5F142_day5_CadCl 0.27 1.17 100_5F143_day28_CadCl 0.21 0.86 101_5F144_day28_CadCl 0.45 0.55 102_5F145_day28_CadCl 1.21 0.83 10_5M37_day1_CadCl 0.2 0.5 11_5M38_day1_CadCl 0.4 0.62 12_5M39_day1_CadCl 0.22 0.43 40_5M40_day5_CadCl 0.12 1.02 41_5M41_day5_CadCl 0.13 1.43 42_5M42_day5_CadCl 0.12 1.52 85_5M43_day28_CadCl 0.25 0.33 86_5M44_day28_CadCl 0.39 0.27 87_5M45_day28_CadCl 0.25 0.39 28_6F146_day1_Dox 0.29 2.24 29_6F147_day1_Dox 0.35 1.2 30_6F148_day1_Dox 0.31 1.56 56_6F149_day5_Dox 0.83 1.71 57_6F150_day5_Dox 0.59 1.37 58_6F151_day5_Dox 0.63 2.13 103_6F171_day28_Dox 1.99 0.84 104_6F172_day28_Dox 2.06 0.44 105_6F173_day28_Dox 4.39 0.77 13_6M46_day1_Dox 0.48 1.74 14_6M47_day1_Dox 0.49 0.95 15_6M48_day1_Dox 0.36 0.91 43_6M49_day5_Dox 1.08 1.64 44_6M50_day5_Dox 0.87 1.35 88_6M71_day28_Dox 3.5 1.64 89_6M72_day28_Dox 2.2 0.54 90_6M73_day28_Dox 2.91 0.5 115_7F155_day1_ValpA 0.45 0.87 116_7F156_day1_ValpA 0.28 0.42 117_7F157_day1_ValpA 0.28 0.64 121_7F158_day5_ValpA 0.35 0.54 122_7F159_day5_ValpA 0.51 0.55 123_7F160_day5_ValpA 0.36 0.37 127_7F161_day28_ValpA 0.23 0.65 128_7F162_day28_ValpA 0.28 0.3 129_7F163_day28_ValpA 0.29 0.4 112_7M55_day1_ValpA 0.16 0.57 113_7M56_day1_ValpA 0.19 0.49 114_7M57_day1_ValpA 0.25 0.57 118_7M58_day5_ValpA 0.2 0.7 119_7M59_day5_ValpA 0.14 0.86 120_7M60_day5_ValpA 0.17 0.62 124_7M61_day28_ValpA 0.09 0.39 125_7M62_day28_ValpA 0.19 0.42 126_7M63_day28_ValpA 0.09 0.36 62_8F181_day28_Naive 0.26 0.62 63_8F182_day28_Naive 0.36 0.01 64_8F183_day28_Naive 0.37 0.83 59_8M81_day28_Naive 0.2 1.24 60_8M82_day28_Naive 0.15 0.59 61_8M83_day28_Naive 0.24 0.37 Sample W64472_DB81_seg2 W83813_DB81_seg27 MUSCYCG1R_DB81_seg15-17 68_1F101_day1_Saline 0.45 0.94 0.67 69_1F102_day1_Saline 0.35 0.77 0.94 70_1F103_day1_Saline 0.43 1.03 0.6 74_1F104_day5_Saline 0.35 1.03 0.76 75_1F105_day5_Saline 0.56 0.99 0.75 109_1F107_day28_Saline 0.24 0.48 0.57 110_1F108_day28_Saline 0.38 0.66 0.76 111_1F109_day28_Saline 0.61 0.67 0.7 65_1M1_day1_Saline 0.65 0.68 0.47 66_1M2_day1_Saline 0.56 0.87 0.41 67_1M3_day1_Saline 1.02 0.94 0.4 71_1M4_day5_Saline 1.02 1.29 0.86 72_1M5_day5_Saline 0.75 1.2 0.92 73_1M6_day5_Saline 0.62 1.07 0.54 106_1M7_day28_Saline 0.4 0.5 0.41 107_1M8_day28_Saline 0.23 0.38 0.45 108_1M9_day28_Saline 0.53 0.43 0.43 16_2F110_day1_Gent 0.63 0.84 0.63 17_2F111_day1_Gent 0.45 0.79 0.53 18_2F112_day1_Gent 0.61 0.78 0.66 45_2F113_day5_Gent 1.5 2.07 1.51 46_2F114_day5_Gent 1.2 1.82 1.61 47_2F115_day5_Gent 0.94 1.7 1.51 91_2F116_day28_Gent 0.92 0.45 0.69 92_2F117_day28_Gent 0.66 0.34 0.62 93_2F118_day28_Gent 0.54 0.62 0.57 1_2M10_day1_Gent 0.4 0.53 0.5 2_2M11_day1_Gent 0.54 0.58 0.49 3_2M12_day1_Gent 0.54 0.71 0.41 31_2M13_day5_Gent 1.95 1.35 0.95 32_2M14_day5_Gent 1.62 0.88 0.79 33_2M15_day5_Gent 1.61 1.4 1.02 76_2M16_day28_Gent 1.49 0.78 0.65 77_2M17_day28_Gent 0.84 0.54 0.56 78_2M18_day28_Gent 0.81 0.38 0.54 19_3F119_day1_Cis 0.8 1.1 0.77 20_3F120_day1_Cis 0.54 0.97 0.85 21_3F121_day1_Cis 0.55 0.99 0.72 48_3F122_day5_Cis 2.23 2.12 3.12 49_3F123_day5_Cis 2.1 2.25 3.59 50_3F124_day5_Cis 1.99 2.12 2.07 94_3F125_day28_Cis 1.81 0.71 1.96 95_3F126_day28_Cis 3.16 0.7 2.57 96_3F127_day28_Cis 2.87 0.78 2.7 4_3M19_day1_Cis 0.3 0.5 0.54 5_3M20_day1_Cis 0.51 0.66 0.35 6_3M21_day1_Cis 0.92 0.94 0.67 34_3M22_day5_Cis 2.64 1.39 2.31 35_3M23_day5_Cis 0.95 0.94 0.92 36_3M24_day5_Cis 4.55 1.41 2.34 79_3M25_day28_Cis 2.8 0.51 2.09 80_3M26_day28_Cis 3.04 0.51 2.31 81_3M27_day28_Cis 1.65 0.57 1.93 22_4F128_day1_Tob 0.35 0.86 0.72 23_4F129_day1_Tob 0.26 0.61 0.46 24_4F130_day1_Tob 0.49 1 0.61 51_4F131_day5_Tob 1.4 2.61 1.95 52_4F132_day5_Tob 1.55 1.93 1.44 53_4F133_day5_Tob 1.27 1.76 1.15 97_4F134_day28_Tob 0.48 0.75 0.77 98_4F135_day28_Tob 0.43 0.49 0.59 99_4F136_day28_Tob 0.62 0.63 0.73 7_4M28_day1_Tob 0.45 0.65 0.43 8_4M29_day1_Tob 0.66 0.73 0.49 9_4M30_day1_Tob 0.44 0.48 0.47 37_4M31_day5_Tob 0.93 0.7 0.4 38_4M32_day5_Tob 0.96 1.13 0.69 39_4M33_day5_Tob 1.3 1.4 1.07 82_4M34_day28_Tob 0.44 0.48 0.72 83_4M35_day28_Tob 0.85 0.56 0.59 84_4M36_day28_Tob 0.79 0.55 0.71 25_5F137_day1_CadCl 1.07 2.07 1.91 26_5F138_day1_CadCl 1.07 2.19 1.36 27_5F139_day1_CadCl 1.1 1.66 1.68 54_5F141_day5_CadCl 1.65 3.79 1.72 55_5F142_day5_CadCl 0.78 1.59 1.13 100_5F143_day28_CadCl 0.89 0.95 0.88 101_5F144_day28_CadCl 0.55 0.64 0.71 102_5F145_day28_CadCl 0.43 0.46 0.65 10_5M37_day1_CadCl 0.55 0.47 0.61 11_5M38_day1_CadCl 1.45 0.51 0.73 12_5M39_day1_CadCl 0.41 0.65 0.36 40_5M40_day5_CadCl 2.23 1.48 1.2
41_5M41_day5_CadCl 1.89 1.67 0.97 42_5M42_day5_CadCl 1.63 1.76 1.15 85_5M43_day28_CadCl 0.67 0.46 0.72 86_5M44_day28_CadCl 0.47 0.34 0.44 87_5M45_day28_CadCl 0.57 0.53 0.58 28_6F146_day1_Dox 1.58 2.9 1.66 29_6F147_day1_Dox 1.09 1.56 1.12 30_6F148_day1_Dox 1.15 2 1.36 56_6F149_day5_Dox 1.97 2.28 1.51 57_6F150_day5_Dox 1.36 1.99 1.97 58_6F151_day5_Dox 2.36 2.9 3.17 103_6F171_day28_Dox 0.8 0.58 1.07 104_6F172_day28_Dox 0.69 0.61 1.52 105_6F173_day28_Dox 1.73 0.63 1.26 13_6M46_day1_Dox 0.86 0.68 0.56 14_6M47_day1_Dox 0.77 0.78 0.64 15_6M48_day1_Dox 0.56 0.64 0.66 43_6M49_day5_Dox 3 1.3 1.65 44_6M50_day5_Dox 2.54 1.41 2 88_6M71_day28_Dox 1.71 0.51 0.99 89_6M72_day28_Dox 0.83 0.55 0.98 90_6M73_day28_Dox 1.15 0.51 1.28 115_7F155_day1_ValpA 0.77 0.98 0.86 116_7F156_day1_ValpA 0.36 0.52 0.61 117_7F157_day1_ValpA 0.47 0.74 0.8 121_7F158_day5_ValpA 0.49 0.59 0.94 122_7F159_day5_ValpA 0.57 0.55 0.77 123_7F160_day5_ValpA 0.33 0.74 1.07 127_7F161_day28_ValpA 0.47 0.69 0.89 128_7F162_day28_ValpA 0.2 0.41 0.61 129_7F163_day28_ValpA 0.24 0.58 0.68 112_7M55_day1_ValpA 0.85 0.82 0.67 113_7M56_day1_ValpA 0.73 0.64 0.42 114_7M57_day1_ValpA 0.44 0.53 0.51 118_7M58_day5_ValpA 0.99 0.68 0.8 119_7M59_day5_ValpA 0.83 1.11 1.1 120_7M60_day5_ValpA 0.93 0.93 1.03 124_7M61_day28_ValpA 0.66 0.52 0.77 125_7M62_day28_ValpA 0.55 0.65 0.71 126_7M63_day28_ValpA 0.24 0.39 0.39 62_8F181_day28_Naive 0.47 1.03 0.68 63_8F182_day28_Naive 0.57 1.24 0.65 64_8F183_day28_Naive 0.46 1.03 0.58 59_8M81_day28_Naive 1.26 2 1.31 60_8M82_day28_Naive 0.69 0.94 0.83 61_8M83_day28_Naive 0.39 0.58 0.45 Sample MUSCYCG1R_DB81_seg19-20 W33294_DB81_seg23 W33294_DB81_seg44 68_1F101_day1_Saline 0.74 0.78 0.8 69_1F102_day1_Saline 0.84 0.65 0.96 70_1F103_day1_Saline 0.64 0.8 0.72 74_1F104_day5_Saline 1.28 0.86 0.65 75_1F105_day5_Saline 0.75 0.97 0.88 109_1F107_day28_Saline 0.57 1 0.88 110_1F108_day28_Saline 0.5 0.79 0.59 111_1F109_day28_Saline 0.79 1.24 1 65_1M1_day1_Saline 0.44 0.69 0.64 66_1M2_day1_Saline 0.43 0.3 0.69 67_1M3_day1_Saline 0.36 0.46 0.53 71_1M4_day5_Saline 0.87 0.78 1.69 72_1M5_day5_Saline 0.85 1.18 1 73_1M6_day5_Saline 0.78 0.9 0.86 106_1M7_day28_Saline 0.44 0.61 0.63 107_1M8_day28_Saline 0.34 0.62 0.48 108_1M9_day28_Saline 0.51 0.84 0.55 16_2F110_day1_Gent 0.67 1 1.02 17_2F111_day1_Gent 0.55 0.51 0.8 18_2F112_day1_Gent 0.44 0.94 0.77 45_2F113_day5_Gent 1.23 1.64 1.64 46_2F114_day5_Gent 1.41 1.96 1.72 47_2F115_day5_Gent 1.42 1.51 2.13 91_2F116_day28_Gent 0.56 0.64 0.66 92_2F117_day28_Gent 0.74 1.3 0.71 93_2F118_day28_Gent 0.42 0.85 1.04 1_2M10_day1_Gent 1.7 0.57 0.77 2_2M11_day1_Gent 0.48 0.74 0.5 3_2M12_day1_Gent 0.92 0.61 0.64 31_2M13_day5_Gent 1.43 1.25 1.12 32_2M14_day5_Gent 1.04 0.82 0.93 33_2M15_day5_Gent 1 0.95 0.94 76_2M16_day28_Gent 0.79 0.57 0.42 77_2M17_day28_Gent 0.4 0.8 0.85 78_2M18_day28_Gent 0.55 0.67 0.69 19_3F119_day1_Cis 0.86 0.36 1 20_3F120_day1_Cis 0.81 0.28 0.95 21_3F121_day1_Cis 0.81 1.11 1.04 48_3F122_day5_Cis 2.77 2.03 2.31 49_3F123_day5_Cis 3.44 1.99 2.19 50_3F124_day5_Cis 2.45 1.58 2.15 94_3F125_day28_Cis 1.64 0.95 0.35 95_3F126_day28_Cis 2.47 0.97 0.67 96_3F127_day28_Cis 1.67 0.82 0.73 4_3M19_day1_Cis 0.85 0.59 0.6 5_3M20_day1_Cis 0.71 0.49 0.84 6_3M21_day1_Cis 1.18 0.64 0.96 34_3M22_day5_Cis 1.83 0.84 1.47 35_3M23_day5_Cis 1.47 0.59 1.16 36_3M24_day5_Cis 2.33 1.34 1.51 79_3M25_day28_Cis 2.13 0.95 0.83 80_3M26_day28_Cis 1.97 0.82 0.89 81_3M27_day28_Cis 2.21 0.88 0.83 22_4F128_day1_Tob 0.73 0.85 0.98 23_4F129_day1_Tob 0.63 0.56 0.57 24_4F130_day1_Tob 0.58 0.59 0.62 51_4F131_day5_Tob 1.42 2.16 2.01 52_4F132_day5_Tob 1.31 2.37 2.06 53_4F133_day5_Tob 1.2 1.2 1.72 97_4F134_day28_Tob 0.45 0.91 0.95 98_4F135_day28_Tob 0.62 1.16 0.75 99_4F136_day28_Tob 0.58 0.91 0.7 7_4M28_day1_Tob 0.72 0.52 0.78 8_4M29_day1_Tob 0.84 0.91 0.88 9_4M30_day1_Tob 0.63 0.35 0.46 37_4M31_day5_Tob 0.72 0.61 0.48 38_4M32_day5_Tob 0.72 0.81 0.69 39_4M33_day5_Tob 1.53 1.25 1.27 82_4M34_day28_Tob 0.49 1.02 0.75 83_4M35_day28_Tob 0.51 0.78 0.86 84_4M36_day28_Tob 0.6 0.73 0.86 25_5F137_day1_CadCl 2.22 1.9 1.79 26_5F138_day1_CadCl 1 1.74 1.39 27_5F139_day1_CadCl 1.68 1.36 1.57 54_5F141_day5_CadCl 1.21 1.76 2.05 55_5F142_day5_CadCl 1.01 1.7 1.37 100_5F143_day28_CadCl 0.54 0.94 0.88 101_5F144_day28_CadCl 0.62 0.97 0.69 102_5F145_day28_CadCl 0.56 0.85 0.7 10_5M37_day1_CadCl 0.58 0.62 0.63 11_5M38_day1_CadCl 1.03 0.31 0.26 12_5M39_day1_CadCl 0.78 0.37 0.63 40_5M40_day5_CadCl 1.22 1.41 1.32 41_5M41_day5_CadCl 1.12 1.45 1.43 42_5M42_day5_CadCl 1.04 1.03 1.42 85_5M43_day28_CadCl 0.31 0.7 0.73 86_5M44_day28_CadCl 0.75 0.65 0.53 87_5M45_day28_CadCl 0.44 0.65 0.53 28_6F146_day1_Dox 1.17 2.47 2.1 29_6F147_day1_Dox 1.12 1.04 1.3 30_6F148_day1_Dox 1.16 1.36 2.02 56_6F149_day5_Dox 1.94 1.06 1.19 57_6F150_day5_Dox 1.79 2.06 1.76 58_6F151_day5_Dox 3.43 2.03 2.76 103_6F171_day28_Dox 1.24 0.82 0.87 104_6F172_day28_Dox 1.29 0.97 1.09 105_6F173_day28_Dox 0.93 0.62 0.65 13_6M46_day1_Dox 0.98 0.74 0.74 14_6M47_day1_Dox 1.04 0.61 1.01 15_6M48_day1_Dox 0.95 0.82 0.83 43_6M49_day5_Dox 1.7 1.25 1 44_6M50_day5_Dox 1.66 1.06 0.95 88_6M71_day28_Dox 0.88 0.96 0.45 89_6M72_day28_Dox 1.33 1 0.77 90_6M73_day28_Dox 1.26 0.82 0.66 115_7F155_day1_ValpA 0.68 1.67 0.86 116_7F156_day1_ValpA 0.43 0.84 0.72 117_7F157_day1_ValpA 0.77 1.21 1.19 121_7F158_day5_ValpA 0.6 1.14 1.06 122_7F159_day5_ValpA 0.45 1.13 0.85 123_7F160_day5_ValpA 1.11 1.24 0.79 127_7F161_day28_ValpA 0.55 0.98 0.61 128_7F162_day28_ValpA 0.62 0.89 0.74 129_7F163_day28_ValpA 0.5 1.16 0.95 112_7M55_day1_ValpA 0.63 1.32 1.01 113_7M56_day1_ValpA 0.53 0.94 0.7 114_7M57_day1_ValpA 0.44 0.92 0.69 118_7M58_day5_ValpA 0.88 1.09 1.66 119_7M59_day5_ValpA 1.1 1.32 1.33 120_7M60_day5_ValpA 1.08 1.01 1.31 124_7M61_day28_ValpA 0.56 0.52 0.75 125_7M62_day28_ValpA 0.44 0.85 0.85 126_7M63_day28_ValpA 0.33 0.88 0.34 62_8F181_day28_Naive 0.55 0.94 0.73 63_8F182_day28_Naive 0.7 1.02 0.76 64_8F183_day28_Naive 0.79 0.82 0.77 59_8M81_day28_Naive 1.24 1.65 2.01 60_8M82_day28_Naive 0.86 0.85 1.12 61_8M83_day28_Naive 0.44 0.79 0.39 Sample RATRAB13X_DB81_seg15-17 RATRAB13X_DB81_seg22 MMU09507_DB81_seg15 68_1F101_day1_Saline 0.7 1.29 1.03 69_1F102_day1_Saline 0.59 0.81 1.13 70_1F103_day1_Saline 0.68 0.66 0.51 74_1F104_day5_Saline 0.64 0.82 0.42 75_1F105_day5_Saline 0.77 1.04 0.01 109_1F107_day28_Saline 1.08 0.69 0.67 110_1F108_day28_Saline 0.95 0.61 0.2 111_1F109_day28_Saline 1.03 0.97 0.33 65_1M1_day1_Saline 0.48 1 0.14 66_1M2_day1_Saline 0.55 0.65 0.24 67_1M3_day1_Saline 0.48 0.44 0.24 71_1M4_day5_Saline 1.11 0.86 1 72_1M5_day5_Saline 1.02 1.06 0.37 73_1M6_day5_Saline 0.78 0.75 0.25 106_1M7_day28_Saline 0.58 0.68 0.23 107_1M8_day28_Saline 0.5 0.51 0.17 108_1M9_day28_Saline 0.7 0.8 0.19 16_2F110_day1_Gent 0.9 0.98 0.41 17_2F111_day1_Gent 0.63 0.71 0.43 18_2F112_day1_Gent 0.55 0.51 0.23 45_2F113_day5_Gent 1.68 2.16 0.78 46_2F114_day5_Gent 1.5 2.11 0.62 47_2F115_day5_Gent 1.59 1.91 1.13 91_2F116_day28_Gent 0.84 0.68 1.38 92_2F117_day28_Gent 0.9 0.56 0.96 93_2F118_day28_Gent 0.88 0.57 0.7 1_2M10_day1_Gent 0 0.8 0.56 2_2M11_day1_Gent 1.16 0.99 0.32 3_2M12_day1_Gent 0.82 0.6 0.37 31_2M13_day5_Gent 1.25 1.25 0.71 32_2M14_day5_Gent 0.76 0.77 0.41 33_2M15_day5_Gent 1.35 1.16 0.68 76_2M16_day28_Gent 0.77 0.91 0.82 77_2M17_day28_Gent 0.76 0.88 0.59 78_2M18_day28_Gent 1.22 0.58 0.84 19_3F119_day1_Cis 0.82 0.88 0 20_3F120_day1_Cis 1.11 0.87 0.44 21_3F121_day1_Cis 1.1 1.02 0.52 48_3F122_day5_Cis 1.37 1.71 1.96 49_3F123_day5_Cis 1.53 1.92 2.32 50_3F124_day5_Cis 1.53 1.99 1.14 94_3F125_day28_Cis 1.33 0.61 8.1 95_3F126_day28_Cis 1.27 0.65 6.58 96_3F127_day28_Cis 1.21 0.89 5.53 4_3M19_day1_Cis 0.73 0.65 0.35 5_3M20_day1_Cis 0.84 0.66 0.19 6_3M21_day1_Cis 0.98 1.11 0.5 34_3M22_day5_Cis 1.8 1.53 2.07 35_3M23_day5_Cis 1.03 1.2 0.57 36_3M24_day5_Cis 1.77 1.28 3.87 79_3M25_day28_Cis 1.08 0.66 8.05 80_3M26_day28_Cis 0.95 0.76 2.96 81_3M27_day28_Cis 1.28 0.65 5.45 22_4F128_day1_Tob 1.02 0.41 0.35 23_4F129_day1_Tob 0.77 0.71 0.3 24_4F130_day1_Tob 0.87 0.78 0.22 51_4F131_day5_Tob 1.71 2.49 1.04 52_4F132_day5_Tob 1.44 2.11 0.99 53_4F133_day5_Tob 1.23 1.57 0.92 97_4F134_day28_Tob 1.28 0.88 0.84 98_4F135_day28_Tob 1.01 0.63 0.52 99_4F136_day28_Tob 0.73 0.88 0.85 7_4M28_day1_Tob 0.78 0.82 0.34 8_4M29_day1_Tob 0.98 0.95 0.7 9_4M30_day1_Tob 0.91 0.82 0.56 37_4M31_day5_Tob 0.75 0.68 0.17 38_4M32_day5_Tob 1.04 0.81 0.28 39_4M33_day5_Tob 1.32 1.26 0.27 82_4M34_day28_Tob 0.93 0.67 0.66 83_4M35_day28_Tob 1.05 0.8 0.97
84_4M36_day28_Tob 0.94 0.62 0.68 25_5F137_day1_CadCl 1.63 1.73 0.81 26_5F138_day1_CadCl 1.8 1.83 0.42 27_5F139_day1_CadCl 1.55 1.16 1.1 54_5F141_day5_CadCl 1.81 1.56 0.87 55_5F142_day5_CadCl 0.97 1.1 0.56 100_5F143_day28_CadCl 0.83 0.7 0.33 101_5F144_day28_CadCl 0.89 0.9 0.66 102_5F145_day28_CadCl 0.82 0.46 1.58 10_5M37_day1_CadCl 0.73 0.92 0.15 11_5M38_day1_CadCl 0.92 1.29 0.32 12_5M39_day1_CadCl 1.01 0.67 0.33 40_5M40_day5_CadCl 1.18 1.65 0.33 41_5M41_day5_CadCl 0.88 1.58 0.49 42_5M42_day5_CadCl 1.07 1.21 0.38 85_5M43_day28_CadCl 1.43 0.63 0.42 86_5M44_day28_CadCl 0.8 0.87 0.45 87_5M45_day28_CadCl 0.64 0.49 0.42 28_6F146_day1_Dox 0.99 2.07 0.48 29_6F147_day1_Dox 1.04 0.89 0.52 30_6F148_day1_Dox 1.32 1.66 0.93 56_6F149_day5_Dox 1.85 1.95 2.07 57_6F150_day5_Dox 1.51 1.89 1.46 58_6F151_day5_Dox 1.9 3.3 1.82 103_6F171_day28_Dox 0.66 0.54 4.47 104_6F172_day28_Dox 0.69 1.05 2.99 105_6F173_day28_Dox 0.91 0.63 2.89 13_6M46_day1_Dox 0.88 0.69 0.74 14_6M47_day1_Dox 1.15 0.58 0.71 15_6M48_day1_Dox 0.75 0.77 0.59 43_6M49_day5_Dox 0.96 1.06 1.74 44_6M50_day5_Dox 1.2 1.32 1.67 88_6M71_day28_Dox 0.54 0.37 3.04 89_6M72_day28_Dox 0.78 0.64 2.93 90_6M73_day28_Dox 1.02 0.45 2.13 115_7F155_day1_ValpA 1.28 1.05 0.48 116_7F156_day1_ValpA 0.7 0.56 0.34 117_7F157_day1_ValpA 0.82 0.87 0.27 121_7F158_day5_ValpA 0.7 1.07 0.62 122_7F159_day5_ValpA 0.91 0.78 0.31 123_7F160_day5_ValpA 1.47 1.13 0.42 127_7F161_day28_ValpA 0.73 0.71 0.23 128_7F162_day28_ValpA 0.82 0.85 0.45 129_7F163_day28_ValpA 0.44 0.74 0.24 112_7M55_day1_ValpA 0.79 1.45 0.2 113_7M56_day1_ValpA 0.7 0.86 0.2 114_7M57_day1_ValpA 0.75 0.63 0.29 118_7M58_day5_ValpA 1.38 0.95 0.26 119_7M59_day5_ValpA 1.14 1.14 0.3 120_7M60_day5_ValpA 1.45 1.1 0.24 124_7M61_day28_ValpA 0.59 0.96 0.12 125_7M62_day28_ValpA 0.77 0.75 0.11 126_7M63_day28_ValpA 0.49 0.62 0.21 62_8F181_day28_Naive 0.68 0.9 0.5 63_8F182_day28_Naive 0.77 0.84 0.6 64_8F183_day28_Naive 0.68 0.88 0.73 59_8M81_day28_Naive 1.77 1.46 0.47 60_8M82_day28_Naive 0.83 0.8 0.8 61_8M83_day28_Naive 0.54 0.53 0.43
Example 3
Validation Analysis of the Selected Markers
[0521] To validate the optimal signature for classification of renal toxicity of a compound after five days of application a test of the signatory polynucleotide/gene expression in rat kidney samples consisting of tissues from rats exposed to three drug compounds and a single control group was carried out (Teva Pharmaceutical Industries, IL). The purpose of this analysis was to test the ability of the optimized signature to correctly predict the level of toxicity of the three drug compounds prior to the ability to demonstrate renal damage using histopathological examination of the rat kidney samples.
[0522] In this Example, the samples with known renal toxic effect (detailed in plates 1-3 described in Table 25 and in Table 9) are referred to as the "labeled samples", and the samples of the blind test (detailed in plates 4-7 described in Table 25), where no information on the renal toxic effect was available, are referred to as the "un-labeled samples". The experimental details and the analysis performed initially on the labeled samples, as described in Example 2, are referred to as the "discovery stage" of the study, while the details and analysis performed at the second stage of the study are referred to as the "validation stage".
[0523] The signature disclosed in Table 13 herein was further revised and refined, and then validated by testing the un-labeled rat kidney samples, consisting of tissues from rats exposed to three drug compounds (T1 and T2 presented in FIGS. 1-2 and compound T3, Riluzole (6-(trifluoromethoxy)benzothiazol-2-amine) and from a single control group.
[0524] qRT-PCR was performed on the labeled and un-labeled samples as described in section "RT Preparation and Real-Time qRT-PCR Analysis" hereinabove, using primers for 8 amplicons of 4 genes (a wild-type and a splice-variant amplicon for each gene disclosed in Table 13), as detailed in Example 2 hereinabove. New primers were designed for part of the transcripts, and new conditions for several qRT-PCR reactions were used, as described below.
[0525] Two equivalent modified signatures were constructed based on new qRT-PCR results obtained from the test conducted with the labeled samples, which are listed in Tables 26 and 27 below. The modified signatures were then applied to the un-labeled samples and successfully predicted the level of toxicity of the three test compounds as well as of the control.
[0526] Table 23 provides the normalized qRT-PCR results for the amplicons used for both classifiers (shown in Tables 26 and 27) on the labeled and un-labeled samples. The measurements were normalized in two steps. First--according to the house-keeping-genes normalization factor, and second--each plate was normalized according to ratio of the intensity measurements from samples appearing in it and in the shuffled (normalization) plate (Table 25 provides the plates details and the section "Inter-Plate Normalization" provides details of the normalization process). The normalized values were further scaled by a factor, for ease of viewing. This data, as well as the additional gender column was used by the classifiers to reach the toxicity calls. Table 23 also provides the true label (Normal/Toxic) for the labeled samples.
TABLE-US-00110 TABLE 23 Normalized qRT-PCR results for amplicons used with labeled and un-labeled samples Sample W41270_DB81_seg11 H31883_DB71_seg13 MUSCYCG1R_DB81_seg19-20 56_6F149_day5_Dox 0.851 1.377 1.438 48_3F122_day5_Cis 0.705 2.695 1.643 47_2F115_day5_Gent 2.64 1.515 1.644 110_1F108_day28_Saline 0.775 0.741 0.431 34_3M22_day5_Cis 1.262 3.816 2.034 44_6M50_day5_Dox 1.017 2.129 1.321 106_1M7_day28_Saline 0.489 0.728 0.804 116_7F156_day1_ValpA 1.134 1.026 2.289 59_8M81_day28_Naive 1.117 0.965 1.232 124_7M61_day28_ValpA 0.543 0.732 0.588 65_1M1_day1_Saline 1.029 0.933 1.176 74_1F104_day5_Saline 0.801 0.911 1.516 57_6F150_day5_Dox 1.053 0.905 1.723 43_6M49_day5_Dox 1.551 2.586 1.536 128_7F162_day28_ValpA 0.95 0.774 1.731 120_7M60_day5_ValpA 0.631 0.846 1.019 114_7M57_day1_ValpA 0.939 1.488 1.581 37_4M31_day5_Tob 0.559 0.863 0.99 126_7M63_day28_ValpA 0.459 0.713 0.589 112_7M55_day1_ValpA 1.405 1.506 1.842 73_1M6_day5_Saline 0.413 0.966 0.768 62_8F181_day28_Naive 0.931 1.262 0.933 123_7F160_day5_ValpA 1.428 0.85 1.509 109_1F107_day28_Saline 0.743 0.775 0.942 118_7M58_day5_ValpA 1.002 0.975 1.372 68_1F101_day1_Saline 1.725 1.074 1.424 117_7F157_day1_ValpA 1.225 0.999 1.929 36_3M24_day5_Cis 3.597 5.526 4.156 33_2M15_day5_Gent 0.983 0.948 1.085 127_7F161_day28_ValpA 1.044 0.872 1.171 75_1F105_day5_Saline 0.044 0.838 1.262 52_4F132_day5_Tob 2.483 0.855 1.589 50_3F124_day5_Cis 1.404 3.771 4.947 63_8F182_day28_Naive 0.809 0.95 0.772 38_4M32_day5_Tob 0.802 1.237 0.968 72_1M5_day5_Saline 0.654 0.963 1.245 67_1M3_day1_Saline 0.805 1.2 0.903 35_3M23_day5_Cis 0.843 1.509 0.981 51_4F131_day5_Tob 1.529 0.988 1.6 32_2M14_day5_Gent 0.954 1.09 0.993 122_7F159_day5_ValpA 0.617 0.791 0.94 121_7F158_day5_ValpA 1.258 0.694 1.425 119_7M59_day5_ValpA 0.997 1.082 1.585 71_1M4_day5_Saline 0.605 0.731 0.975 111_1F109_day28_Saline 0.996 0.904 1.014 60_8M82_day28_Naive 0.631 1.255 1.006 129_7F163_day28_ValpA 0.587 0.57 1.037 69_1F102_day1_Saline 0.573 0.793 1.449 108_1M9_day28_Saline 0.831 0.812 0.634 46_2F114_day5_Gent 1.104 0.78 0.955 125_7M62_day28_ValpA 1.011 0.979 0.52 113_7M56_day1_ValpA 0.547 0.721 0.637 45_2F113_day5_Gent 1.699 1.142 1.442 61_8M83_day28_Naive 0.411 0.637 1.209 53_4F133_day5_Tob 2.317 0.858 1.424 107_1M8_day28_Saline 0.562 0.719 0.642 115_7F155_day1_ValpA 1.544 1.041 0.9 58_6F151_day5_Dox 1.791 1.227 2.913 31_2M13_day5_Gent 0.82 1.402 1.842 49_3F123_day5_Cis 2.113 1.642 3.172 39_4M33_day5_Tob 0.946 1.646 2.062 70_1F103_day1_Saline 1.021 1.173 1.629 66_1M2_day1_Saline 0.753 0.883 0.705 64_8F183_day28_Naive 0.843 0.943 1.282 54_UK5F126_T1_Ds2_Day1 1.265 1.153 0.609 123_UK4F119_T1_Ds1_Day5 0.657 1.01 0.816 60_UK7F139_T2_Ds1_Day1 3.38 0.7 0.126 17_UK5M29_T1_Ds2_Day1 0.653 1.19 0.835 117_UK2F107_control_Day5 1.229 2.274 0.68 109_UK12M69_T3_Ds1_Day5 0.482 1.3 0.62 18_UK5M30_T1_Ds2_Day1 0.383 0.623 0.696 57_UK5F129_T1_Ds2_Day1 0.472 0.798 0.804 151_UK14F180_T3_Ds2_Day5 0.363 0.705 1.004 7_UK3M13_T1_Ds1_Day1 0.734 0.923 0.299 113_UK14M80_T3_Ds2_Day5 0.605 0.846 0.658 72_UK11F164_T3_Ds1_Day1 0.282 0.582 0.114 104_UK10M56_T2_Ds2_Day5 0.668 1.256 0.655 91_UK6M31_T1_Ds2_Day5 1.164 1.663 1.018 124_UK4F120_T1_Ds1_Day5 0.703 1.013 1.499 114_UK14M81_T3_Ds2_Day5 0.43 0.949 1.003 69_UK9F154_T2_Ds2_Day1 0.92 0.762 0.111 46_UK1F105_control_Day1 0.349 0.692 0.164 34_UK11M64_T3_Ds1_Day1 0.649 1.074 0.726 130_UK6F132_T1_Ds2_Day5 1 1.554 0.919 3_UK1M3_control_Day1 0.398 0.756 0.171 75_UK13F173_T3_Ds2_Day1 0.897 0.662 0.798 101_UK8M47_T2_Ds1_Day5 0.397 1.149 0.172 102_UK8M48_T2_Ds1_Day5 0.337 2.147 0.179 96_UK6M36_T1_Ds2_Day5 0.71 0.996 0.756 39_UK13M76_T3_Ds2_Day1 0.359 0.643 0.158 19_UK7M37_T2_Ds1_Day1 0.623 0.7 0.51 144_UK12F167_T3_Ds1_Day5 1.957 1.301 0.638 2_UK1M2_control_Day1 0.342 0.812 0.222 52_UK3F118_T1_Ds1_Day1 0.566 0.706 2.31 31_UK11M61_T3_Ds1_Day1 0.64 0.919 0.96 129_UK6F131_T1_Ds2_Day5 0.009 1.36 0.359 23_UK7M41_T2_Ds1_Day1 0.481 0.88 0.938 43_UK1F102_control_Day1 0.406 2.051 0.328 81_UK2M8_control_Day5 0.686 1.318 0.252 80_UK2M7_control_Day5 0.788 1.981 0.273 70_UK11F161_T3_Ds1_Day1 0.457 0.764 0.232 16_UK5M28_T1_Ds2_Day1 0.78 0.517 0.385 79_UK13F178_T3_Ds2_Day1 0.49 0.802 0.92 50_UK3F116_T1_Ds1_Day1 0.66 0.913 1.49 112_UK12M72_T3_Ds1_Day5 0.722 1.65 0.649 146_UK12F169_T3_Ds1_Day5 1.807 1.003 0.716 140_UK10F156_T2_Ds2_Day5 1.186 1.386 0.345 143_UK10F160_T2_Ds2_Day5 0.308 0.676 0.169 10_UK3M16_T1_Ds1_Day1 0.181 0.757 0.291 94_UK6M34_T1_Ds2_Day5 0.391 1.037 0.871 147_UK12F170_T3_Ds1_Day5 0.483 1.338 1.035 71_UK11F163_T3_Ds1_Day1 0.575 0.611 0.183 122_UK2F112_control_Day5 0.592 1.127 0.159 47_UK1F106_control_Day1 0.405 0.823 0.196 15_UK5M27_T1_Ds2_Day1 0.755 0.906 0.76 97_UK8M43_T2_Ds1_Day5 0.233 1.884 0.107 106_UK10M59_T2_Ds2_Day5 0.497 1.01 0.513 118_UK2F108_control_Day5 0.911 2.171 0.279 148_UK12F171_T3_Ds1_Day5 0.899 0.576 1.226 35_UK11M65_T3_Ds1_Day1 0.374 0.663 1.044 21_UK7M39_T2_Ds1_Day1 0.662 0.67 0.555 38_UK13M75_T3_Ds2_Day1 0.347 0.969 0.203 55_UK5F127_T1_Ds2_Day1 0.885 0.849 0.739 100_UK8M46_T2_Ds1_Day5 0.493 1.539 0.113 67_UK9F152_T2_Ds2_Day1 1.747 0.832 0.211 131_UK6F133_T1_Ds2_Day5 0.964 1.84 0.852 142_UK10F159_T2_Ds2_Day5 0.711 1.128 0.148 128_UK4F124_T1_Ds1_Day5 1.527 1.373 1.598 95_UK6M35_T1_Ds2_Day5 0.713 1.348 0.761 8_UK3M14_T1_Ds1_Day1 0.396 0.615 0.271 138_UK8F147_T2_Ds1_Day5 0.626 1.163 1.399 41_UK13M78_T3_Ds2_Day1 0.174 0.632 0.275 76_UK13F175_T3_Ds2_Day1 0.912 1.119 2.153 152_UK14F181_T3_Ds2_Day5 0.762 0.942 1.567 86_UK4M20_T1_Ds1_Day5 0.473 1.353 0.183 59_UK7F137_T2_Ds1_Day1 0.473 0.613 0.115 111_UK12M71_T3_Ds1_Day5 0.832 1.082 0.857 145_UK12F168_T3_Ds1_Day5 1.015 1.358 0.625 28_UK9M52_T2_Ds2_Day1 1.016 0.773 0.531 108_UK12M67_T3_Ds1_Day5 0.699 1.585 0.525 11_UK3M17_T1_Ds1_Day1 0.198 0.73 0.376 24_UK7M42_T2_Ds1_Day1 0.76 0.695 0.859 42_UK1F101_control_Day1 0.415 0.976 0.276 29_UK9M53_T2_Ds2_Day1 0.424 0.635 0.505 61_UK7F140_T2_Ds1_Day1 0.474 0.464 0.124 20_UK7M38_T2_Ds1_Day1 0.876 0.951 0.888 141_UK10F158_T2_Ds2_Day5 1.237 1.161 0.185 87_UK4M21_T1_Ds1_Day5 0.702 1.266 0.149 150_UK14F179_T3_Ds2_Day5 1.066 0.718 0.875 136_UK8F144_T2_Ds1_Day5 1.149 1.329 1.006 93_UK6M33_T1_Ds2_Day5 1.825 2.423 1.197 85_UK4M19_T1_Ds1_Day5 0.356 1.783 0.214 4_UK1M4_control_Day1 0.617 0.668 0.192 126_UK4F122_T1_Ds1_Day5 1.325 1.477 3.532 36_UK11M66_T3_Ds1_Day1 0.468 0.569 1.137 74_UK11F166_T3_Ds1_Day1 0.465 1.366 0.132 14_UK5M26_T1_Ds2_Day1 0.462 0.696 0.478 119_UK2F109_control_Day5 0.994 1.083 0.162 25_UK9M49_T2_Ds2_Day1 0.589 0.722 0.585 103_UK10M55_T2_Ds2_Day5 0.857 1.146 0.997 27_UK9M51_T2_Ds2_Day1 0.545 0.618 0.475 26_UK9M50_T2_Ds2_Day1 0.528 0.999 0.661 44_UK1F103_control_Day1 0.563 0.692 0.161 62_UK7F141_T2_Ds1_Day1 0.959 0.536 0.267 92_UK6M32_T1_Ds2_Day5 0.453 1.13 0.631 12_UK3M18_T1_Ds1_Day1 0.231 0.524 0.135 5_UK1M5_control_Day1 0.3 1.146 0.184 153_UK14F182_T3_Ds2_Day5 1.119 1.058 1.708 56_UK5F128_T1_Ds2_Day1 0.413 0.611 0.738 58_UK5F130_T1_Ds2_Day1 0.762 0.707 0.652 132_UK6F134_T1_Ds2_Day5 1.254 2.468 1.238 49_UK3F114_T1_Ds1_Day1 0.758 0.783 1.436 90_UK4M24_T1_Ds1_Day5 0.657 1.097 0.296 64_UK9F149_T2_Ds2_Day1 0.384 0.602 0.197 110_UK12M70_T3_Ds1_Day5 0.495 0.946 0.398 127_UK4F123_T1_Ds1_Day5 1.014 2.104 3.397 121_UK2F111_control_Day5 0.394 0.882 0.222 83_UK2M10_control_Day5 0.719 1.033 0.103 98_UK8M44_T2_Ds1_Day5 0.321 1.66 0.148 99_UK8M45_T2_Ds1_Day5 0.477 1.079 0.127 107_UK10M60_T2_Ds2_Day5 0.788 1.057 0.746 73_UK11F165_T3_Ds1_Day1 0.344 0.637 0.134 40_UK13M77_T3_Ds2_Day1 0.418 0.923 0.29 89_UK4M23_T1_Ds1_Day5 1.11 1.249 0.186 134_UK6F136_T1_Ds2_Day5 1.111 1.684 0.528 133_UK6F135_T1_Ds2_Day5 1.126 1.672 1.583 1_UK1M1_control_Day1 0.578 0.554 0.148 30_UK9M54_T2_Ds2_Day1 0.577 0.522 0.458 82_UK2M9_control_Day5 0.269 1.398 0.157 37_UK13M73_T3_Ds2_Day1 0.359 0.767 0.152 45_UK1F104_control_Day1 0.754 0.709 0.197 105_UK10M57_T2_Ds2_Day5 0.457 0.942 0.686 135_UK8F143_T2_Ds1_Day5 0.83 0.936 0.736 33_UK11M63_T3_Ds1_Day1 0.568 0.949 0.767 77_UK13F176_T3_Ds2_Day1 0.667 1.13 1.45 63_UK7F142_T2_Ds1_Day1 0.518 0.646 0.157 48_UK3F113_T1_Ds1_Day1 0.646 0.912 1.195 65_UK9F150_T2_Ds2_Day1 1.729 1.006 0.167 84_UK2M11_control_Day5 0.152 0.819 0.093 125_UK4F121_T1_Ds1_Day5 1.337 1.458 1.317 139_UK8F148_T2_Ds1_Day5 1.524 0.978 1.386 9_UK3M15_T1_Ds1_Day1 0.47 0.87 0.249 115_UK14M82_T3_Ds2_Day5 0.472 1.087 1.024 137_UK8F145_T2_Ds1_Day5 1.111 1.439 1.293 13_UK5M25_T1_Ds2_Day1 0.644 0.517 0.654 66_UK9F151_T2_Ds2_Day1 1.125 1.079 0.192 88_UK4M22_T1_Ds1_Day5 0.638 1.23 0.189 149_UK12F172_T3_Ds1_Day5 1.093 1.094 1.413 32_UK11M62_T3_Ds1_Day1 0.551 0.7 0.441 68_UK9F153_T2_Ds2_Day1 0.594 0.84 0.14 22_UK7M40_T2_Ds1_Day1 0.823 0.629 0.47 6_UK1M6_control_Day1 0.245 0.66 0.402 120_UK2F110_control_Day5 0.456 1.399 0.233 78_UK13F177_T3_Ds2_Day1 0.956 1.47 2.313 53_UK5F125_T1_Ds2_Day1 1.034 0.867 1.261 116_UK14M83_T3_Ds2_Day5 0.766 2.34 1.119 51_UK3F117_T1_Ds1_Day1 1.082 0.957 1.891 154_UK14F183_T3_Ds2_Day5 0.944 1.259 1.475 16_2F110_day1_Gent 1.361 0.772 0.842 42_5M42_day5_CadCl 1.067 1.057 1.036 102_5F145_day28_CadCl 1.138 0.785 0.769 9_4M30_day1_Tob 1.601 1.137 1.582 97_4F134_day28_Tob 1.189 0.624 0.713 105_6F173_day28_Dox 1.263 1.328 0.985 79_3M25_day28_Cis 4.741 4.41 3.509 78_2M18_day28_Gent 1.614 0.853 0.863 54_5F141_day5_CadCl 2.101 1.154 2.018 5_3M20_day1_Cis 0.679 0.668 0.806 77_2M17_day28_Gent 1.342 0.861 1.072 82_4M34_day28_Tob 1.217 0.324 0.76 12_5M39_day1_CadCl 0.727 0.919 1.224 26_5F138_day1_CadCl 1.183 1.005 1.097 94_3F125_day28_Cis 4.104 2.839 3.443 93_2F118_day28_Gent 1.315 0.553 0.617 17_2F111_day1_Gent 1.037 1.118 1.155 92_2F117_day28_Gent 1.194 0.817 0.865 89_6M72_day28_Dox 0.73 1.54 2.342 55_5F142_day5_CadCl 1.109 0.786 1.292 15_6M48_day1_Dox 0.824 0.993 1.387 3_2M12_day1_Gent 0.904 0.987 1.361 84_4M36_day28_Tob 1.099 0.69 1.087 87_5M45_day28_CadCl 0.529 0.652 1.356
25_5F137_day1_CadCl 1.265 1.446 2.129 98_4F135_day28_Tob 1.267 0.528 0.889 41_5M41_day5_CadCl 0.769 1.132 3.613 83_4M35_day28_Tob 1.373 0.551 1.268 2_2M11_day1_Gent 1.08 1.115 2.011 13_6M46_day1_Dox 1.286 1.283 1.761 24_4F130_day1_Tob 1.084 1.104 0.967 101_5F144_day28_CadCl 0.772 0.712 1.068 21_3F121_day1_Cis 0.759 0.853 1.514 88_6M71_day28_Dox 2.381 1.434 1.437 100_5F143_day28_CadCl 0.578 0.681 0.68 10_5M37_day1_CadCl 0.993 1.239 2.276 7_4M28_day1_Tob 0.577 1.132 1.506 18_2F112_day1_Gent 2.078 0.84 1.387 28_6F146_day1_Dox 1.43 1.41 2.256 8_4M29_day1_Tob 0.949 0.912 1.173 91_2F116_day28_Gent 1.188 0.554 0.729 22_4F128_day1_Tob 0.809 0.563 1.025 86_5M44_day28_CadCl 0.654 0.849 2.128 14_6M47_day1_Dox 1.148 1.042 1.516 40_5M40_day5_CadCl 1.211 1.051 2.866 96_3F127_day28_Cis 2.053 2.398 1.813 30_6F148_day1_Dox 1.501 1.46 1.627 103_6F171_day28_Dox 1.44 1.642 1.991 19_3F119_day1_Cis 1.331 1.416 1.492 85_5M43_day28_CadCl 0.522 0.578 0.932 80_3M26_day28_Cis 1.904 2.653 3.094 27_5F139_day1_CadCl 0.983 1.632 1.856 76_2M16_day28_Gent 1.941 0.842 1.661 90_6M73_day28_Dox 0.652 1.611 2.105 29_6F147_day1_Dox 0.935 1.116 1.551 23_4F129_day1_Tob 0.983 0.661 0.987 1_2M10_day1_Gent 0.85 1.053 2.861 20_3F120_day1_Cis 1.029 2.092 3.259 104_6F172_day28_Dox 0.787 1.408 1.779 6_3M21_day1_Cis 1.224 2.559 2.003 95_3F126_day28_Cis 4.516 5.592 7.02 81_3M27_day28_Cis 3.866 3.563 3.473 99_4F136_day28_Tob 1.798 0.807 0.903 4_3M19_day1_Cis 0.496 1.134 1.277 11_5M38_day1_CadCl 1 1.143 3.981 Sample W64472_DB81_seg2 W83813_DB81_seg27 AI045075_DB71_seg6 Gender Label 56_6F149_day5_Dox 2.03 1.442 1.248 F Toxic 48_3F122_day5_Cis 1.795 1.716 1.804 F Toxic 47_2F115_day5_Gent 1.733 1.688 1.337 F Toxic 110_1F108_day28_Saline 0.865 1.019 0.724 F Normal 34_3M22_day5_Cis 3.64 0.857 1.683 M Toxic 44_6M50_day5_Dox 2.924 0.986 1.348 M Toxic 106_1M7_day28_Saline 0.775 0.535 0.544 M Normal 116_7F156_day1_ValpA 1.082 1.179 1.006 F Normal 59_8M81_day28_Naive 2.184 1.679 1.27 M Normal 124_7M61_day28_ValpA 1.085 0.493 0.696 M Normal 65_1M1_day1_Saline 1.57 1.166 1.202 M Normal 74_1F104_day5_Saline 1.013 0.889 0.535 F Normal 57_6F150_day5_Dox 1.441 1.177 1.319 F Toxic 43_6M49_day5_Dox 3.4 1.095 1.844 M Toxic 128_7F162_day28_ValpA 0.788 1.254 0.906 F Normal 120_7M60_day5_ValpA 0.92 0.778 1.017 M Normal 114_7M57_day1_ValpA 1.123 0.912 1.436 M Normal 37_4M31_day5_Tob 1.193 0.589 1.327 M Toxic 126_7M63_day28_ValpA 0.965 0.46 0.669 M Normal 112_7M55_day1_ValpA 1.887 1.495 2.189 M Normal 73_1M6_day5_Saline 0.801 0.629 0.518 M Normal 62_8F181_day28_Naive 1.493 1.594 1.044 F Normal 123_7F160_day5_ValpA 1.226 1.17 1.145 F Normal 109_1F107_day28_Saline 0.718 0.642 0.982 F Normal 118_7M58_day5_ValpA 1.169 0.876 0.997 M Normal 68_1F101_day1_Saline 1.041 1.508 0.905 F Normal 117_7F157_day1_ValpA 0.995 1.13 0.983 F Normal 36_3M24_day5_Cis 6.414 1.461 4.298 M Toxic 33_2M15_day5_Gent 2.048 1.042 1.374 M Toxic 127_7F161_day28_ValpA 1.51 0.875 0.822 F Normal 75_1F105_day5_Saline 1.154 1.395 0.845 F Normal 52_4F132_day5_Tob 1.871 1.262 1.644 F Toxic 50_3F124_day5_Cis 1.976 1.366 1.503 F Toxic 63_8F182_day28_Naive 0.899 1.367 0.915 F Normal 38_4M32_day5_Tob 1.449 0.892 1.614 M Toxic 72_1M5_day5_Saline 0.943 1.059 0.763 M Normal 67_1M3_day1_Saline 3.263 1.107 1.751 M Normal 35_3M23_day5_Cis 1.448 0.758 0.93 M Toxic 51_4F131_day5_Tob 1.063 1.058 1.367 F Toxic 32_2M14_day5_Gent 1.962 0.702 1.402 M Toxic 122_7F159_day5_ValpA 0.702 0.926 0.883 F Normal 121_7F158_day5_ValpA 0.812 1.146 1.052 F Normal 119_7M59_day5_ValpA 0.894 0.992 0.877 M Normal 71_1M4_day5_Saline 1.141 0.796 0.887 M Normal 111_1F109_day28_Saline 0.864 1.01 1.061 F Normal 60_8M82_day28_Naive 2.082 1.127 1.021 M Normal 129_7F163_day28_ValpA 0.478 0.761 0.77 F Normal 69_1F102_day1_Saline 0.5 0.819 0.476 F Normal 108_1M9_day28_Saline 1.037 0.889 0.829 M Normal 46_2F114_day5_Gent 1.427 1.441 1.778 F Toxic 125_7M62_day28_ValpA 0.991 1.208 0.719 M Normal 113_7M56_day1_ValpA 1.092 0.818 1.098 M Normal 45_2F113_day5_Gent 1.403 1.395 1.636 F Toxic 61_8M83_day28_Naive 0.965 0.736 0.548 M Normal 53_4F133_day5_Tob 1.785 0.942 2.402 F Toxic 107_1M8_day28_Saline 0.596 0.284 0.393 M Normal 115_7F155_day1_ValpA 1.596 1.366 1.522 F Normal 58_6F151_day5_Dox 2.561 1.399 1.18 F Toxic 31_2M13_day5_Gent 1.53 0.76 1.256 M Toxic 49_3F123_day5_Cis 1.265 1.265 1.09 F Toxic 39_4M33_day5_Tob 1.447 1.117 1.224 M Toxic 70_1F103_day1_Saline 0.876 1.169 0.753 F Normal 66_1M2_day1_Saline 0.897 0.674 0.582 M Normal 64_8F183_day28_Naive 0.683 1.224 0.868 F Normal 54_UK5F126_T1_Ds2_Day1 0.944 1.186 0.483 F 123_UK4F119_T1_Ds1_Day5 0.571 0.795 0.692 F 60_UK7F139_T2_Ds1_Day1 1.863 0.305 1.308 F 17_UK5M29_T1_Ds2_Day1 1.213 0.984 0.759 M 117_UK2F107_control_Day5 4.213 0.933 3.974 F 109_UK12M69_T3_Ds1_Day5 0.852 0.754 0.615 M 18_UK5M30_T1_Ds2_Day1 0.661 0.34 0.448 M 57_UK5F129_T1_Ds2_Day1 0.559 0.689 0.547 F 151_UK14F180_T3_Ds2_Day5 0.368 0.729 0.37 F 7_UK3M13_T1_Ds1_Day1 1.118 0.216 0.843 M 113_UK14M80_T3_Ds2_Day5 0.779 0.728 1.451 M 72_UK11F164_T3_Ds1_Day1 0.483 0.322 0.354 F 104_UK10M56_T2_Ds2_Day5 0.731 0.601 0.609 M 91_UK6M31_T1_Ds2_Day5 0.803 1.092 0.797 M 124_UK4F120_T1_Ds1_Day5 0.528 0.885 0.627 F 114_UK14M81_T3_Ds2_Day5 0.656 0.933 0.53 M 69_UK9F154_T2_Ds2_Day1 0.804 0.201 1.43 F 46_UK1F105_control_Day1 0.734 0.542 0.825 F 34_UK11M64_T3_Ds1_Day1 1.31 0.663 1.103 M 130_UK6F132_T1_Ds2_Day5 0.863 1.125 0.766 F 3_UK1M3_control_Day1 0.883 0.267 1.049 M 75_UK13F173_T3_Ds2_Day1 0.659 0.67 0.444 F 101_UK8M47_T2_Ds1_Day5 0.929 0.248 1.016 M 102_UK8M48_T2_Ds1_Day5 0.996 0.203 1.11 M 96_UK6M36_T1_Ds2_Day5 0.982 0.885 1.01 M 39_UK13M76_T3_Ds2_Day1 1.566 0.137 1.146 M 19_UK7M37_T2_Ds1_Day1 0.632 0.666 0.744 M 144_UK12F167_T3_Ds1_Day5 1.176 1.146 1.082 F 2_UK1M2_control_Day1 0.91 0.216 0.885 M 52_UK3F118_T1_Ds1_Day1 0.683 0.843 0.636 F 31_UK11M61_T3_Ds1_Day1 1.296 0.497 0.678 M 129_UK6F131_T1_Ds2_Day5 0.554 0.55 0.629 F 23_UK7M41_T2_Ds1_Day1 1.305 0.84 1.159 M 43_UK1F102_control_Day1 1.43 0.612 0.851 F 81_UK2M8_control_Day5 1.317 0.25 2.054 M 80_UK2M7_control_Day5 2.363 0.112 1.078 M 70_UK11F161_T3_Ds1_Day1 0.52 0.402 0.596 F 16_UK5M28_T1_Ds2_Day1 0.462 0.56 0.396 M 79_UK13F178_T3_Ds2_Day1 0.602 0.761 0.527 F 50_UK3F116_T1_Ds1_Day1 0.49 0.926 0.572 F 112_UK12M72_T3_Ds1_Day5 1.034 1.388 1.102 M 146_UK12F169_T3_Ds1_Day5 0.822 0.659 1.032 F 140_UK10F156_T2_Ds2_Day5 1.178 0.555 1.842 F 143_UK10F160_T2_Ds2_Day5 0.485 0.354 0.637 F 10_UK3M16_T1_Ds1_Day1 0.778 0.155 0.574 M 94_UK6M34_T1_Ds2_Day5 0.527 0.654 0.539 M 147_UK12F170_T3_Ds1_Day5 0.479 0.701 0.501 F 71_UK11F163_T3_Ds1_Day1 0.859 0.394 0.85 F 122_UK2F112_control_Day5 1.05 0.522 1.214 F 47_UK1F106_control_Day1 0.495 0.276 0.605 F 15_UK5M27_T1_Ds2_Day1 1.326 0.889 0.932 M 97_UK8M43_T2_Ds1_Day5 1.445 0.11 1.566 M 106_UK10M59_T2_Ds2_Day5 0.899 0.615 1.338 M 118_UK2F108_control_Day5 1.325 0.362 1.597 F 148_UK12F171_T3_Ds1_Day5 0.546 1.155 0.727 F 35_UK11M65_T3_Ds1_Day1 0.567 0.898 0.918 M 21_UK7M39_T2_Ds1_Day1 0.801 0.955 0.98 M 38_UK13M75_T3_Ds2_Day1 2.291 0.276 1.479 M 55_UK5F127_T1_Ds2_Day1 0.898 0.861 1.067 F 100_UK8M46_T2_Ds1_Day5 1.42 0.209 1.449 M 67_UK9F152_T2_Ds2_Day1 1.104 0.289 2.008 F 131_UK6F133_T1_Ds2_Day5 0.989 1.025 0.935 F 142_UK10F159_T2_Ds2_Day5 0.554 0.269 0.799 F 128_UK4F124_T1_Ds1_Day5 0.745 1.511 1.162 F 95_UK6M35_T1_Ds2_Day5 1.181 1.077 1.161 M 8_UK3M14_T1_Ds1_Day1 1.501 0.178 1.13 M 138_UK8F147_T2_Ds1_Day5 0.464 0.865 0.771 F 41_UK13M78_T3_Ds2_Day1 1.042 0.164 0.566 M 76_UK13F175_T3_Ds2_Day1 0.847 0.874 1.132 F 152_UK14F181_T3_Ds2_Day5 0.587 0.81 0.666 F 86_UK4M20_T1_Ds1_Day5 1.835 0.125 2.031 M 59_UK7F137_T2_Ds1_Day1 0.492 0.183 0.54 F 111_UK12M71_T3_Ds1_Day5 0.88 1.054 1.285 M 145_UK12F168_T3_Ds1_Day5 0.601 0.791 0.928 F 28_UK9M52_T2_Ds2_Day1 1.462 0.773 1.006 M 108_UK12M67_T3_Ds1_Day5 0.8 0.818 1.133 M 11_UK3M17_T1_Ds1_Day1 0.981 0.143 0.805 M 24_UK7M42_T2_Ds1_Day1 0.791 0.798 0.709 M 42_UK1F101_control_Day1 0.569 0.323 0.674 F 29_UK9M53_T2_Ds2_Day1 0.692 0.595 0.729 M 61_UK7F140_T2_Ds1_Day1 0.468 0.213 0.419 F 20_UK7M38_T2_Ds1_Day1 1.076 0.931 1.059 M 141_UK10F158_T2_Ds2_Day5 1.029 0.354 3.003 F 87_UK4M21_T1_Ds1_Day5 0.991 0.208 0.904 M 150_UK14F179_T3_Ds2_Day5 0.623 0.711 0.977 F 136_UK8F144_T2_Ds1_Day5 0.532 0.922 1.02 F 93_UK6M33_T1_Ds2_Day5 2.203 1.236 1.793 M 85_UK4M19_T1_Ds1_Day5 0.687 0.165 0.937 M 4_UK1M4_control_Day1 1.352 0.235 1.318 M 126_UK4F122_T1_Ds1_Day5 0.945 1.328 1.367 F 36_UK11M66_T3_Ds1_Day1 1.106 0.512 0.845 M 74_UK11F166_T3_Ds1_Day1 1.064 0.356 1.252 F 14_UK5M26_T1_Ds2_Day1 0.785 0.656 0.544 M 119_UK2F109_control_Day5 0.907 0.515 1.067 F 25_UK9M49_T2_Ds2_Day1 0.656 0.741 0.541 M 103_UK10M55_T2_Ds2_Day5 1.446 1.022 0.831 M 27_UK9M51_T2_Ds2_Day1 1.23 0.777 1.015 M 26_UK9M50_T2_Ds2_Day1 0.866 0.725 0.588 M 44_UK1F103_control_Day1 0.524 0.2 0.503 F 62_UK7F141_T2_Ds1_Day1 1.072 0.29 0.836 F 92_UK6M32_T1_Ds2_Day5 0.784 0.596 0.73 M 12_UK3M18_T1_Ds1_Day1 0.439 0.169 0.4 M 5_UK1M5_control_Day1 1.411 0.299 1.289 M 153_UK14F182_T3_Ds2_Day5 1.24 1.599 1.436 F 56_UK5F128_T1_Ds2_Day1 0.415 0.549 0.514 F 58_UK5F130_T1_Ds2_Day1 0.502 0.725 0.639 F 132_UK6F134_T1_Ds2_Day5 1.223 0.454 1.478 F 49_UK3F114_T1_Ds1_Day1 0.752 0.825 0.49 F 90_UK4M24_T1_Ds1_Day5 0.902 0.207 0.783 M 64_UK9F149_T2_Ds2_Day1 0.741 0.365 0.857 F 110_UK12M70_T3_Ds1_Day5 0.499 0.72 1.175 M 127_UK4F123_T1_Ds1_Day5 0.938 1.593 1.089 F 121_UK2F111_control_Day5 0.609 0.276 0.702 F 83_UK2M10_control_Day5 1.034 0.412 1.069 M 98_UK8M44_T2_Ds1_Day5 1.258 0.27 1.516 M 99_UK8M45_T2_Ds1_Day5 1.447 0.299 1.237 M 107_UK10M60_T2_Ds2_Day5 0.623 0.962 0.83 M 73_UK11F165_T3_Ds1_Day1 0.507 0.205 0.37 F 40_UK13M77_T3_Ds2_Day1 1.597 0.218 1.063 M 89_UK4M23_T1_Ds1_Day5 1.35 0.2 1.364 M 134_UK6F136_T1_Ds2_Day5 0.652 1.074 0.868 F 133_UK6F135_T1_Ds2_Day5 1.056 1.674 1.487 F 1_UK1M1_control_Day1 0.783 0.17 0.633 M 30_UK9M54_T2_Ds2_Day1 0.837 0.614 0.471 M 82_UK2M9_control_Day5 2.621 0.25 1.879 M 37_UK13M73_T3_Ds2_Day1 1.35 0.211 1.117 M 45_UK1F104_control_Day1 0.897 0.381 1.062 F 105_UK10M57_T2_Ds2_Day5 1.049 0.626 0.878 M 135_UK8F143_T2_Ds1_Day5 0.616 0.961 1.923 F 33_UK11M63_T3_Ds1_Day1 1.844 0.989 1.025 M 77_UK13F176_T3_Ds2_Day1 1.043 0.929 1.211 F 63_UK7F142_T2_Ds1_Day1 0.969 0.387 0.49 F 48_UK3F113_T1_Ds1_Day1 0.548 0.917 0.762 F 65_UK9F150_T2_Ds2_Day1 1.73 0.32 3.044 F 84_UK2M11_control_Day5 0.629 0.162 0.645 M 125_UK4F121_T1_Ds1_Day5 0.606 0.893 0.831 F 139_UK8F148_T2_Ds1_Day5 0.572 0.824 1.232 F 9_UK3M15_T1_Ds1_Day1 1.502 0.245 1.416 M 115_UK14M82_T3_Ds2_Day5 0.494 1.103 0.765 M 137_UK8F145_T2_Ds1_Day5 0.773 1.303 0.94 F 13_UK5M25_T1_Ds2_Day1 0.592 0.473 0.541 M 66_UK9F151_T2_Ds2_Day1 1.211 0.444 2.152 F 88_UK4M22_T1_Ds1_Day5 0.684 0.323 0.717 M
149_UK12F172_T3_Ds1_Day5 0.677 1.096 1.021 F 32_UK11M62_T3_Ds1_Day1 0.808 0.789 0.713 M 68_UK9F153_T2_Ds2_Day1 0.666 0.254 0.71 F 22_UK7M40_T2_Ds1_Day1 1.477 1.182 1.253 M 6_UK1M6_control_Day1 0.749 0.127 0.476 M 120_UK2F110_control_Day5 0.898 0.34 0.976 F 78_UK13F177_T3_Ds2_Day1 1.227 1.454 0.575 F 53_UK5F125_T1_Ds2_Day1 1.028 1.045 0.965 F 116_UK14M83_T3_Ds2_Day5 3.181 0.911 1.037 M 51_UK3F117_T1_Ds1_Day1 1.047 1.186 0.981 F 154_UK14F183_T3_Ds2_Day5 0.704 1.018 0.58 F 16_2F110_day1_Gent 0.763 0.963 1.251 F 42_5M42_day5_CadCl 1.337 1.104 1.083 M 102_5F145_day28_CadCl 0.414 0.259 0.728 F 9_4M30_day1_Tob 1.43 1.126 2.04 M 97_4F134_day28_Tob 1.073 0.876 0.959 F 105_6F173_day28_Dox 2.157 0.734 0.964 F 79_3M25_day28_Cis 5.917 1.587 4.504 M 78_2M18_day28_Gent 1.55 0.852 1.734 M 54_5F141_day5_CadCl 2.282 1.782 1.866 F 5_3M20_day1_Cis 0.815 0.799 0.495 M 77_2M17_day28_Gent 1.353 0.857 3.06 M 82_4M34_day28_Tob 0.61 0.39 0.679 M 12_5M39_day1_CadCl 1.499 1.034 0.951 M 26_5F138_day1_CadCl 1.059 1.194 1.133 F 94_3F125_day28_Cis 2.504 1.749 2.301 F 93_2F118_day28_Gent 0.806 0.421 0.967 F 17_2F111_day1_Gent 0.963 0.98 0.889 F 92_2F117_day28_Gent 1.079 0.441 2.632 F 89_6M72_day28_Dox 1.613 0.686 0.669 M 55_5F142_day5_CadCl 0.854 0.906 0.805 F 15_6M48_day1_Dox 1.26 0.956 1.257 M 3_2M12_day1_Gent 1.567 1.02 1.072 M 84_4M36_day28_Tob 1.379 0.832 1.273 M 87_5M45_day28_CadCl 0.781 0.531 0.672 M 25_5F137_day1_CadCl 1.155 1.772 1.64 F 98_4F135_day28_Tob 1.144 0.621 1.021 F 41_5M41_day5_CadCl 1.662 1.157 1.409 M 83_4M35_day28_Tob 1.281 0.803 1.397 M 2_2M11_day1_Gent 1.869 1.409 1.848 M 13_6M46_day1_Dox 2.478 0.936 1.622 M 24_4F130_day1_Tob 1.5 1.153 5.307 F 101_5F144_day28_CadCl 0.827 0.783 0.975 F 21_3F121_day1_Cis 0.81 0.844 0.631 F 88_6M71_day28_Dox 3.226 0.442 1.434 M 100_5F143_day28_CadCl 1.098 1.033 1.58 F 10_5M37_day1_CadCl 1.622 1.027 1.108 M 7_4M28_day1_Tob 1.083 0.999 0.825 M 18_2F112_day1_Gent 1.408 0.898 2.053 F 28_6F146_day1_Dox 1.548 2.054 1.631 F 8_4M29_day1_Tob 1.619 1.049 1.223 M 91_2F116_day28_Gent 1.164 0.434 1.78 F 22_4F128_day1_Tob 0.73 0.799 1.195 F 86_5M44_day28_CadCl 1.107 0.817 0.836 M 14_6M47_day1_Dox 1.45 0.964 1.454 M 40_5M40_day5_CadCl 1.675 1.671 2.393 M 96_3F127_day28_Cis 2.643 0.786 1.555 F 30_6F148_day1_Dox 1.367 1.752 1.268 F 103_6F171_day28_Dox 1.462 0.719 0.653 F 19_3F119_day1_Cis 1.261 1.209 0.788 F 85_5M43_day28_CadCl 0.807 0.633 0.333 M 80_3M26_day28_Cis 3.371 0.786 1.428 M 27_5F139_day1_CadCl 1.372 1.894 1.263 F 76_2M16_day28_Gent 1.245 0.756 1.469 M 90_6M73_day28_Dox 1.604 0.586 0.785 M 29_6F147_day1_Dox 0.977 1.003 0.741 F 23_4F129_day1_Tob 1.166 0.982 1.623 F 1_2M10_day1_Gent 1.48 1.161 1.221 M 20_3F120_day1_Cis 1.096 1.345 0.899 F 104_6F172_day28_Dox 1.023 0.955 0.54 F 6_3M21_day1_Cis 2.455 1.09 1.64 M 95_3F126_day28_Cis 5.783 1.864 3.336 F 81_3M27_day28_Cis 3.008 1.371 1.753 M 99_4F136_day28_Tob 1.118 0.987 1.478 F 4_3M19_day1_Cis 1.176 0.902 0.811 M 11_5M38_day1_CadCl 1.512 0.957 1.069 M
[0527] Experimental Design
[0528] Three compounds (T1, T2, T3) and a control were administered to male and female rats at various time points by oral gavage: 3 treatments (T1, T2, T3) were given in 2 doses (Ds1, Ds2) for two periods (one day and 5 days). Each group consisted of 6 male and 6 female rats. The additional groups consisted of 6 males and 6 female rats treated with control compound for a single day and for five days, as described in Table 24.
TABLE-US-00111 TABLE 24 Un-labeled samples groups and doses Animals Dose Route of Days of per Groups Test Items (mg/kg) administration treatment group 1 M, F Control - -- Oral gavage 1 6 2 M, F 1% methyl- -- Oral gavage 5 6 cellulose 3 M, F T1 10 Oral gavage 1 6 4 M, F 10 Oral gavage 5 6 5 M, F 40 Oral gavage 1 6 6 M, F 40 Oral gavage 5 6 7 M, F T2 25 Oral gavage 1 6 8 M, F 25 Oral gavage 5 6 9 M, F 50 Oral gavage 1 6 10 M, F 50 Oral gavage 5 6 11 M, F T3 5 Oral gavage 1 6 12 M, F 5 Oral gavage 5 6 13 M, F 10 Oral gavage 1 6 14 M, F 10 Oral gavage 5 6
[0529] T2 is a drug known to cause renal damage after 7 days of treatment at the 50 mg/kg dose. The chemical structure of T2 is shown in FIG. 2. T2 "no observed effect level" (NOEL, i.e., the maximal dose at which no toxic effect is visible) is 15 mg/kg. Kidneys obtained from rats receiving 50 mg/kg of T2, demonstrated direct cortical tubular toxicity. FIGS. 3-5 demonstrate the results of histopathological examination of the treated kidneys after 7 days (FIGS. 3B, 4B and 5B), or of the control animals (FIGS. 3A, 4A and 5A). As demonstrated in FIGS. 3B, 4B and 5B the changes were multifocal, consisting of tubular basophilia, indicating regeneration following necrosis.
[0530] FIG. 3 demonstrates histological section of the kidney, magnified .times.200. FIG. 3A represents a histological section of the kidney of a control animal. Normal aspects of cortical tubules (eosinophilic cytoplasm) are marked by arrows. FIG. 3B represents a histological section of the kidney of a 50 mg/kg treated animal. Basophilic tubules in the Cortex, indicating post-necrotic regeneration are marked by arrows.
[0531] FIG. 4 demonstrates histological section of the kidney, magnified .times.400. FIG. 4A represents a histological section of the kidney of a control animal. Normal aspects of cortical tubules (eosinophilic cytoplasm) are marked by arrows. FIG. 4B represents a histological section of the kidney of a 50 mg/kg treated animal. Basophilic tubules in the Cortex, indicating post-necrotic regeneration are marked by arrows.
[0532] FIG. 5 demonstrates histological section of the kidney, magnified .times.600. FIG. 5A represents a histological section of the kidney of a control animal. Normal aspects of cortical tubules (eosinophilic cytoplasm) are marked by arrows. FIG. 5B represents a histological section of the kidney of a 50 mg/kg treated animal. Basophilic tubules in the Cortex, indicating post-necrotic regeneration are marked by arrows.
[0533] T1 is another drug which shows renal damage, mainly in females, after 28 days of treatment at the 30 mg/kg dose. The chemical structure of T1 is shown in FIG. 1.
[0534] T3 is Riluzole (6-(trifluoromethoxy)benzothiazol-2-amine), which shows no renal damage after up to 35 days of treatment, and therefore was used as a negative control.
[0535] At autopsy, both kidneys of each animal were removed and each kidney was cross sectioned. Half of each kidney was sent to RNA extraction and analysis.
RNA Isolation from Kidney Tissues
[0536] RNA was isolated as described previously. RNA samples which did not meet the conventional RNA quality criteria including A260: A280 ratio, A260:A230 ratio; and RNA integrity as detected in agarose gel, were omitted from further processing.
RT Preparation and Real-Time qRT-PCR Analysis
[0537] RT was prepared and qRT-PCR performed and analyzed as described hereinabove. qRT-PCR was performed for the four genes comprising the signature of the discovery stage described in Table 13. Two amplicons were tested for each gene--one representing the wild-type transcript, and another representing an alternative splice variant. Each amplicon was measured using the labeled samples described in Table 9 herein, as well as the un-labeled samples. Samples from both groups (labeled and un-labeled) were tested in seven 96 well plates as described in Table 25. In order to correct possible run to run variations, the following controls were added: 1. several samples were repeated in all 96 wells plates; 2. control shuffled plate was designed which combined samples from all seven test plates.
[0538] Table 25 presents plates set up in a validation stage. The names of the un-labeled samples comprise of the rat's group, the rats ID number starts with UK (stand for unknown), the toxicant it was exposed to (T1, T2 or T3), the dose given Ds1 or Ds2 and day of treatment.
TABLE-US-00112 TABLE 25 Plates set up in the validation stage Plate 1 1 Gentamycin 1 day 1 toxicants M 1_2M10_day1_Gent 2 Gentamycin 1 2_2M11_day1_Gent 3 Gentamycin 1 3_2M12_day1_Gent 4 Cisplatin 1 4_3M19_day1_Cis 5 Cisplatin 1 5_3M20_day1_Cis 6 Cisplatin 1 6_3M21_day1_Cis 7 Tobramycin 1 7_4M28_day1_Tob 8 Tobramycin 1 8_4M29_day1_Tob 9 Tobramycin 1 9_4M30_day1_Tob 10 Cadmium 1 10_5M37_day1_CadCl chloride 11 Cadmium 1 11_5M38_day1_CadCl chloride 12 Cadmium 1 12_5M39_day1_CadCl chloride 13 Doxorubicin 1 13_6M46_day1_Dox 14 Doxorubicin 1 14_6M47_day1_Dox 15 Doxorubicin 1 15_6M48_day1_Dox 16 Valproic acid 1 112_7M55_day1_ValpA 17 Valproic acid 1 113_7M56_day1_ValpA 18 Valproic acid 1 114_7M57_day1_ValpA 19 Gentamycin 1 day 1 toxicants F 16_2F110_day1_Gent 20 Gentamycin 1 17_2F111_day1_Gent 21 Gentamycin 1 18_2F112_day1_Gent 22 Cisplatin 1 19_3F119_day1_Cis 23 Cisplatin 1 20_3F120_day1_Cis 24 Cisplatin 1 21_3F121_day1_Cis 25 Tobramycin 1 22_4F128_day1_Tob 26 Tobramycin 1 23_4F129_day1_Tob 27 Tobramycin 1 24_4F130_day1_Tob 28 Cadmium 1 25_5F137_day1_CadCl chloride 29 Cadmium 1 26_5F138_day1_CadCl chloride 30 Cadmium 1 27_5F139_day1_CadCl chloride 31 Doxorubicin 1 28_6F146_day1_Dox 32 Doxorubicin 1 29_6F147_day1_Dox 33 Doxorubicin 1 30_6F148_day1_Dox 34 Valproic acid 1 115_7F155_day1_ValpA 35 Valproic acid 1 116_7F156_day1_ValpA 36 Valproic acid 1 117_7F157_day1_ValpA 37 Naive 28 Controls All days 59_8M81_day28_Naive 38 Naive 28 60_8M82_day28_Naive 39 Naive 28 61_8M83_day28_Naive 40 Naive 28 62_8F181_day28_Naive 41 Naive 28 63_8F182_day28_Naive 42 Naive 28 64_8F183_day28_Naive 43 Control/Saline 1 65_1M1_day1_Saline 44 Control/Saline 1 66_1M2_day1_Saline 45 Control/Saline 1 67_1M3_day1_Saline 46 Control/Saline 1 68_1F101_day1_Saline 47 Control/Saline 1 69_1F102_day1_Saline 48 Control/Saline 1 70_1F103_day1_Saline Plate 2 1 Gentamycin 5 day 5 toxicants M 31_2M13_day5_Gent 2 Gentamycin 5 32_2M14_day5_Gent 3 Gentamycin 5 33_2M15_day5_Gent 4 Cisplatin 5 34_3M22_day5_Cis 5 Cisplatin 5 35_3M23_day5_Cis 6 Cisplatin 5 36_3M24_day5_Cis 7 Tobramycin 5 37_4M31_day5_Tob 8 Tobramycin 5 38_4M32_day5_Tob 9 Tobramycin 5 39_4M33_day5_Tob 10 Cadmium 5 40_5M40_day5_CadCl chloride 11 Cadmium 5 41_5M41_day5_CadCl chloride 12 Cadmium 5 42_5M42_day5_CadCl chloride 13 Doxorubicin 5 43_6M49_day5_Dox 14 Doxorubicin 5 44_6M50_day5_Dox 15 Valproic acid 5 118_7M58_day5_ValpA 16 Valproic acid 5 119_7M59_day5_ValpA 17 Valproic acid 5 120_7M60_day5_ValpA 18 Gentamycin 5 day 5 toxicants F 45_2F113_day5_Gent 19 Gentamycin 5 46_2F114_day5_Gent 20 Gentamycin 5 47_2F115_day5_Gent 21 Cisplatin 5 48_3F122_day5_Cis 22 Cisplatin 5 49_3F123_day5_Cis 23 Cisplatin 5 50_3F124_day5_Cis 24 Tobramycin 5 51_4F131_day5_Tob 25 Tobramycin 5 52_4F132_day5_Tob 26 Tobramycin 5 53_4F133_day5_Tob 27 Cadmium 5 54_5F141_day5_CadCl chloride 28 Cadmium 5 55_5F142_day5_CadCl chloride 29 Doxorubicin 5 56_6F149_day5_Dox 30 Doxorubicin 5 57_6F150_day5_Dox 31 Doxorubicin 5 58_6F151_day5_Dox 32 Valproic acid 5 121_7F158_day5_ValpA 33 Valproic acid 5 122_7F159_day5_ValpA 34 Valproic acid 5 123_7F160_day5_ValpA 35 Control/Saline 5 71_1M4_day5_Saline 36 Control/Saline 5 72_1M5_day5_Saline 37 Control/Saline 5 73_1M6_day5_Saline 38 Control/Saline 5 74_1F104_day5_Saline 39 Control/Saline 5 75_1F105_day5_Saline 40 Amph. Control 1 Control 130_1M6a_day1_Ctrl 41 Amph. Control 5 131_1M13a_day5_Ctrl 42 Amph. Control 28 132_1M20a_day28_Ctrl 43 Amph. Control 1 133_1F106a_day1_Ctrl 44 Amph. Control 5 134_1F113a_day5_Ctrl 45 Amph. Control 28 135_1F120a_day28_Ctrl 46 Amphotericin 1 Amphotericin 136_6M61a_day1_Amp 47 Amphotericin 1 137_6M62a_day1_Amp 48 Amphotericin 1 138_6M63a_day1_Amp 49 Amphotericin 5 139_6M67a_day5_Amp 50 Amphotericin 5 140_6M68a_day5_Amp 51 Amphotericin 5 141_6M69a_day5_Amp 52 Amphotericin 28 142_6M73a_day28_Amp 53 Amphotericin 28 143_6M74a_day28_Amp 54 Amphotericin 28 144_6M75a_day28_Amp 55 Amphotericin 1 145_6F161a_day1_Amp 56 Amphotericin 1 146_6F162a_day1_Amp 57 Amphotericin 1 147_6F163a_day1_Amp 58 Amphotericin 5 148_6F167a_day5_Amp 59 Amphotericin 5 149_6F168a_day5_Amp 60 Amphotericin 5 150_6F169a_day5_Amp 61 Amphotericin 28 151_6F173a_day28_Amp 62 Amphotericin 28 152_6F174a_day28_Amp 63 Amphotericin 28 153_6F175a_day28_Amp Plate 3 1 Gentamycin 28 day 28 toxicants M 76_2M16_day28_Gent 2 Gentamycin 28 77_2M17_day28_Gent 3 Gentamycin 28 78_2M18_day28_Gent 4 Cisplatin 28 79_3M25_day28_Cis 5 Cisplatin 28 80_3M26_day28_Cis 6 Cisplatin 28 81_3M27_day28_Cis 7 Tobramycin 28 82_4M34_day28_Tob 8 Tobramycin 28 83_4M35_day28_Tob 9 Tobramycin 28 84_4M36_day28_Tob 10 Cadmium 28 85_5M43_day28_CadCl chloride 11 Cadmium 28 86_5M44_day28_CadCl chloride 12 Cadmium 28 87_5M45_day28_CadCl chloride 13 Doxorubicin 28 88_6M71_day28_Dox 14 Doxorubicin 28 89_6M72_day28_Dox 15 Doxorubicin 28 90_6M73_day28_Dox 16 Valproic acid 28 124_7M61_day28_ValpA 17 Valproic acid 28 125_7M62_day28_ValpA 18 Valproic acid 28 126_7M63_day28_ValpA 19 Gentamycin 28 day 28 toxicants F 91_2F116_day28_Gent 20 Gentamycin 28 92_2F117_day28_Gent 21 Gentamycin 28 93_2F118_day28_Gent 22 Cisplatin 28 94_3F125_day28_Cis 23 Cisplatin 28 95_3F126_day28_Cis 24 Cisplatin 28 96_3F127_day28_Cis 25 Tobramycin 28 97_4F134_day28_Tob 26 Tobramycin 28 98_4F135_day28_Tob 27 Tobramycin 28 99_4F136_day28_Tob 28 Cadmium 28 100_5F143_day28_CadCl chloride 29 Cadmium 28 101_5F144_day28_CadCl chloride 30 Cadmium 28 102_5F145_day28_CadCl chloride 31 Doxorubicin 28 103_6F171_day28_Dox 32 Doxorubicin 28 104_6F172_day28_Dox 33 Doxorubicin 28 105_6F173_day28_Dox 34 Valproic acid 28 127_7F161_day28_ValpA 35 Valproic acid 28 128_7F162_day28_ValpA 36 Valproic acid 28 129_7F163_day28_ValpA 37 Control/Saline 28 Day 28 control 106_1M7_day28_Saline 38 Control/Saline 28 107_1M8_day28_Saline 39 Control/Saline 28 108_1M9_day28_Saline 40 Control/Saline 28 109_1F107_day28_Saline 41 Control/Saline 28 110_1F108_day28_Saline 42 Control/Saline 28 111_1F109_day28_Saline Plate 4 1 control 1 1_UK1M1_control_Day1 TT4: Male Day 1 2 control 1 2_UK1M2_control_Day1 3 control 1 3_UK1M3_control_Day1 4 control 1 4_UK1M4_control_Day1 5 control 1 5_UK1M5_control_Day1 6 control 1 6_UK1M6_control_Day1 7 T1 Ds1 1 7_UK3M13_T1 Ds1_Day1 8 T1 Ds1 1 8_UK3M14_T1 Ds1_Day1 9 T1 Ds1 1 9_UK3M15_T1 Ds1_Day1 10 T1 Ds1 1 10_UK3M16_T1 Ds1_Day1 11 T1 Ds1 1 11_UK3M17_T1 Ds1_Day1 12 T1 Ds1 1 12_UK3M18_T1 Ds1_Day1 13 T1 Ds2 1 13_UK5M25_T1 Ds2_Day1 14 T1 Ds2 1 14_UK5M26_T1 Ds2_Day1 15 T1 Ds2 1 15_UK5M27_T1 Ds2_Day1 16 T1 Ds2 1 16_UK5M28_T1 Ds2_Day1 17 T1 Ds2 1 17_UK5M29_T1 Ds2_Day1 18 T1 Ds2 1 18_UK5M30_T1 Ds2_Day1 19 T2 Ds1 1 19_UK7M37_T2 Ds1_Day1 20 T2 Ds1 1 20_UK7M38_T2 Ds1_Day1 21 T2 Ds1 1 21_UK7M39_T2 Ds1_Day1 22 T2 Ds1 1 22_UK7M40_T2 Ds1_Day1 23 T2 Ds1 1 23_UK7M41_T2 Ds1_Day1 24 T2 Ds1 1 24_UK7M42_T2 Ds1_Day1 25 T2 Ds2 1 25_UK9M49_T2 Ds2_Day1 26 T2 Ds2 1 26_UK9M50_T2 Ds2_Day1 27 T2 Ds2 1 27_UK9M51_T2 Ds2_Day1 28 T2 Ds2 1 28_UK9M52_T2 Ds2_Day1 29 T2 Ds2 1 29_UK9M53_T2 Ds2_Day1 30 T2 Ds2 1 30_UK9M54_T2 Ds2_Day1 31 T3 Ds1 1 31_UK11M61_T3 Ds1_Day1 32 T3 Ds1 1 32_UK11M62_T3 Ds1_Day1 33 T3 Ds1 1 33_UK11M63_T3 Ds1_Day1 34 T3 Ds1 1 34_UK11M64_T3 Ds1_Day1 35 T3 Ds1 1 35_UK11M65_T3 Ds1_Day1 36 T3 Ds1 1 36_UK11M66_T3 Ds1_Day1 37 T3 Ds2 1 37_UK13M73_T3 Ds2_Day1 38 T3 Ds2 1 38_UK13M75_T3 Ds2_Day1 39 T3 Ds2 1 39_UK13M76_T3 Ds2_Day1 40 T3 Ds2 1 40_UK13M77_T3 Ds2_Day1 41 T3 Ds2 1 41_UK13M78_T3 Ds2_Day1 Plate 5 42 control 1 42_UK1F101_control_Day1 TT5: 43 control 1 43_UK1F102_control_Day1 44 control 1 44_UK1F103_control_Day1 45 control 1 45_UK1F104_control_Day1 46 control 1 46_UK1F105_control_Day1 47 control 1 47_UK1F106_control_Day1 48 T1 Ds1 1 48_UK3F113_T1 Ds1_Day1 49 T1 Ds1 1 49_UK3F114_T1 Ds1_Day1 50 T1 Ds1 1 50_UK3F116_T1 Ds1_Day1 51 T1 Ds1 1 51_UK3F117_T1 Ds1_Day1 52 T1 Ds1 1 52_UK3F118_T1 Ds1_Day1 53 T1 Ds2 1 53_UK5F125_T1 Ds2_Day1 54 T1 Ds2 1 54_UK5F126_T1 Ds2_Day1 55 T1 Ds2 1 55_UK5F127_T1 Ds2_Day1 56 T1 Ds2 1 56_UK5F128_T1 Ds2_Day1 57 T1 Ds2 1 57_UK5F129_T1 Ds2_Day1 58 T1 Ds2 1 58_UK5F130_T1 Ds2_Day1 59 T2 Ds1 1 59_UK7F137_T2 Ds1_Day1 60 T2 Ds1 1 60_UK7F139_T2 Ds1_Day1 61 T2 Ds1 1 61_UK7F140_T2 Ds1_Day1 62 T2 Ds1 1 62_UK7F141_T2 Ds1_Day1 63 T2 Ds1 1 63_UK7F142_T2 Ds1_Day1 64 T2 Ds2 1 64_UK9F149_T2 Ds2_Day1 65 T2 Ds2 1 65_UK9F150_T2 Ds2_Day1 66 T2 Ds2 1 66_UK9F151_T2 Ds2_Day1 67 T2 Ds2 1 67_UK9F152_T2 Ds2_Day1 68 T2 Ds2 1 68_UK9F153_T2 Ds2_Day1 69 T2 Ds2 1 69_UK9F154_T2 Ds2_Day1 70 T3 Ds1 1 70_UK11F161_T3 Ds1_Day1 71 T3 Ds1 1 71_UK11F163_T3 Ds1_Day1
72 T3 Ds1 1 72_UK11F164_T3 Ds1_Day1 73 T3 Ds1 1 73_UK11F165_T3 Ds1_Day1 74 T3 Ds1 1 74_UK11F166_T3 Ds1_Day1 75 T3 Ds2 1 75_UK13F173_T3 Ds2_Day1 76 T3 Ds2 1 76_UK13F175_T3 Ds2_Day1 77 T3 Ds2 1 77_UK13F176_T3 Ds2_Day1 78 T3 Ds2 1 78_UK13F177_T3 Ds2_Day1 79 T3 Ds2 1 79_UK13F178_T3 Ds2_Day1 Plate 6 80 control 5 80_UK2M7_control_Day5 TT6 Male Day 5 81 control 5 81_UK2M8_control_Day5 82 control 5 82_UK2M9_control_Day5 83 control 5 83_UK2M10_control_Day5 84 control 5 84_UK2M11_control_Day5 85 T1 Ds1 5 85_UK4M19_T1 Ds1_Day5 86 T1 Ds1 5 86_UK4M20_T1 Ds1_Day5 87 T1 Ds1 5 87_UK4M21_T1 Ds1_Day5 88 T1 Ds1 5 88_UK4M22_T1 Ds1_Day5 89 T1 Ds1 5 89_UK4M23_T1 Ds1_Day5 90 T1 Ds1 5 90_UK4M24_T1 Ds1_Day5 91 T1 Ds2 5 91_UK6M31_T1 Ds2_Day5 92 T1 Ds2 5 92_UK6M32_T1 Ds2_Day5 93 T1 Ds2 5 93_UK6M33_T1 Ds2_Day5 94 T1 Ds2 5 94_UK6M34_T1 Ds2_Day5 95 T1 Ds2 5 95_UK6M35_T1 Ds2_Day5 96 T1 Ds2 5 96_UK6M36_T1 Ds2_Day5 97 T2 Ds1 5 97_UK8M43_T2 Ds1_Day5 98 T2 Ds1 5 98_UK8M44_T2 Ds1_Day5 99 T2 Ds1 5 99_UK8M45_T2 Ds1_Day5 100 T2 Ds1 5 100_UK8M46_T2 Ds1_Day5 101 T2 Ds1 5 101_UK8M47_T2 Ds1_Day5 102 T2 Ds1 5 102_UK8M48_T2 Ds1_Day5 103 T2 Ds2 5 103_UK10M55_T2 Ds2_Day5 104 T2 Ds2 5 104_UK10M56_T2 Ds2_Day5 105 T2 Ds2 5 105_UK10M57_T2 Ds2_Day5 106 T2 Ds2 5 106_UK10M59_T2 Ds2_Day5 107 T2 Ds2 5 107_UK10M60_T2 Ds2_Day5 108 T3 Ds1 5 108_UK12M67_T3 Ds1_Day5 109 T3 Ds1 5 109_UK12M69_T3 Ds1_Day5 110 T3 Ds1 5 110_UK12M70_T3 Ds1_Day5 111 T3 Ds1 5 111_UK12M71_T3 Ds1_Day5 112 T3 Ds1 5 112_UK12M72_T3 Ds1_Day5 113 T3 Ds2 5 113_UK14M80_T3 Ds2_Day5 114 T3 Ds2 5 114_UK14M81_T3 Ds2_Day5 115 T3 Ds2 5 115_UK14M82_T3 Ds2_Day5 116 T3 Ds2 5 116_UK14M83_T3 Ds2_Day5 Plate 7 117 control 5 117_UK2F107_control_Day5 TT7: Female Day 5 118 control 5 118_UK2F108_control_Day5 119 control 5 119_UK2F109_control_Day5 120 control 5 120_UK2F110_control_Day5 121 control 5 121_UK2F111_control_Day5 122 control 5 122_UK2F112_control_Day5 123 T1 Ds1 5 123_UK4F119_T1 Ds1_Day5 124 T1 Ds1 5 124_UK4F120_T1 Ds1_Day5 125 T1 Ds1 5 125_UK4F121_T1 Ds1_Day5 126 T1 Ds1 5 126_UK4F122_T1 Ds1_Day5 127 T1 Ds1 5 127_UK4F123_T1 Ds1_Day5 128 T1 Ds1 5 128_UK4F124_T1 Ds1_Day5 129 T1 Ds2 5 129_UK6F131_T1 Ds2_Day5 130 T1 Ds2 5 130_UK6F132_T1 Ds2_Day5 131 T1 Ds2 5 131_UK6F133_T1 Ds2_Day5 132 T1 Ds2 5 132_UK6F134_T1 Ds2_Day5 133 T1 Ds2 5 133_UK6F135_T1 Ds2_Day5 134 T1 Ds2 5 134_UK6F136_T1 Ds2_Day5 135 T2 Ds1 5 135_UK8F143_T2 Ds1_Day5 136 T2 Ds1 5 136_UK8F144_T2 Ds1_Day5 137 T2 Ds1 5 137_UK8F145_T2 Ds1_Day5 138 T2 Ds1 5 138_UK8F147_T2 Ds1_Day5 139 T2 Ds1 5 139_UK8F148_T2 Ds1_Day5 140 T2 Ds2 5 140_UK10F156_T2 Ds2_Day5 141 T2 Ds2 5 141_UK10F158_T2 Ds2_Day5 142 T2 Ds2 5 142_UK10F159_T2 Ds2_Day5 143 T2 Ds2 5 143_UK10F160_T2 Ds2_Day5 144 T3 Ds1 5 144_UK12F167_T3 Ds1_Day5 145 T3 Ds1 5 145_UK12F168_T3 Ds1_Day5 146 T3 Ds1 5 146_UK12F169_T3 Ds1_Day5 147 T3 Ds1 5 147_UK12F170_T3 Ds1_Day5 148 T3 Ds1 5 148_UK12F171_T3 Ds1_Day5 149 T3 Ds1 5 149_UK12F172_T3 Ds1_Day5 150 T3 Ds2 5 150_UK14F179_T3 Ds2_Day5 151 T3 Ds2 5 151_UK14F180_T3 Ds2_Day5 152 T3 Ds2 5 152_UK14F181_T3 Ds2_Day5 153 T3 Ds2 5 153_UK14F182_T3 Ds2_Day5 154 T3 Ds2 5 154_UK14F183_T3 Ds2_Day5 Shuffled plate Toxin used Day Final name Cadmium 1 26_5F138_day1_CadCl chloride Cisplatin 1 6_3M21_day1_Cis Cisplatin 1 5_3M20_day1_Cis Control/Saline 1 66_1M2_day1_Saline Doxorubicin 1 30_6F148_day1_Dox Doxorubicin 1 28_6F146_day1_Dox Naive 28 61_8M83_day28_Naive Naive 28 62_8F181_day28_Naive Tobramycin 1 8_4M29_day1_Tob Valproic acid 1 112_7M55_day1_ValpA Valproic acid 1 117_7F157_day1_ValpA Cadmium 5 54_5F141_day5_CadCl chloride Cadmium 5 41_5M41_day5_CadCl chloride Cisplatin 5 50_3F124_day5_Cis Cisplatin 5 36_3M24_day5_Cis Control/Saline 5 73_1M6_day5_Saline Control/Saline 5 71_1M4_day5_Saline Doxorubicin 5 43_6M49_day5_Dox Tobramycin 5 51_4F131_day5_Tob Valproic acid 5 123_7F160_day5_ValpA Valproic acid 5 122_7F159_day5_ValpA Cadmium 28 85_5M43_day28_CadCl chloride Cadmium 28 86_5M44_day28_CadCl chloride Cisplatin 28 79_3M25_day28_Cis Cisplatin 28 94_3F125_day28_Cis Cisplatin 28 81_3M27_day28_Cis Control/Saline 28 106_1M7_day28_Saline Control/Saline 28 107_1M8_day28_Saline Control/Saline 28 111_1F109_day28_Saline Doxorubicin 28 104_6F172_day28_Dox Tobramycin 28 84_4M36_day28_Tob Valproic acid 28 126_7M63_day28_ValpA control 1 2_UK1M2_control_Day1 T1 Ds1 1 7_UK3M13_T1 Ds1_Day1 T1 Ds1 1 12_UK3M18_T1 Ds1_Day1 T1 Ds2 1 16_UK5M28_T1 Ds2_Day1 T2 Ds1 1 24_UK7M42_T2 Ds1_Day1 T2 Ds1 1 20_UK7M38_T2 Ds1_Day1 T3 Ds1 1 31_UK11M61_T3 Ds1_Day1 T3 Ds2 1 38_UK13M75_T3 Ds2_Day1 T3 Ds2 1 41_UK13M78_T3 Ds2_Day1 control 1 43_UK1F102_control_Day1 control 1 46_UK1F105_control_Day1 T1 Ds1 1 51_UK3F117_T1 Ds1_Day1 T1 Ds1 1 52_UK3F118_T1 Ds1_Day1 T1 Ds2 1 56_UK5F128_T1 Ds2_Day1 T2 Ds1 1 63_UK7F142_T2 Ds1_Day1 T2 Ds1 1 61_UK7F140_T2 Ds1_Day1 T2 Ds2 1 68_UK9F153_T2 Ds2_Day1 T2 Ds2 1 66_UK9F151_T2 Ds2_Day1 T3 Ds1 1 72_UK11F164_T3 Ds1_Day1 T3 Ds2 1 78_UK13F177_T3 Ds2_Day1 control 5 80_UK2M7_control_Day5 control 5 83_UK2M10_control_Day5 control 5 84_UK2M11_control_Day5 control 5 82_UK2M9_control_Day5 T1 Ds1 5 86_UK4M20_T1 Ds1_Day5 T1 Ds1 5 88_UK4M22_T1 Ds1_Day5 T1 Ds2 5 93_UK6M33_T1 Ds2_Day5 T1 Ds2 5 94_UK6M34_T1 Ds2_Day5 T2 Ds1 5 97_UK8M43_T2 Ds1_Day5 T3 Ds1 5 108_UK12M67_T3 Ds1_Day5 T3 Ds1 5 110_UK12M70_T3 Ds1_Day5 control 5 118_UK2F108_control_Day5 T1 Ds1 5 125_UK4F121_T1 Ds1_Day5 T1 Ds2 5 129_UK6F131_T1 Ds2_Day5 T1 Ds2 5 131_UK6F133_T1 Ds2_Day5 T2 Ds1 5 139_UK8F148_T2 Ds1_Day5 T2 Ds2 5 140_UK10F156_T2 Ds2_Day5 T2 Ds2 5 143_UK10F160_T2 Ds2_Day5 T3 Ds1 5 147_UK12F170_T3 Ds1_Day5 T3 Ds1 5 146_UK12F169_T3 Ds1_Day5 T3 Ds2 5 151_UK14F180_T3 Ds2_Day5 T3 Ds2 5 153_UK14F182_T3 Ds2_Day5 indicates data missing or illegible when filed
Plate 6
Plate 7
Inter-Plate Normalization
[0539] To account for possible differences of qRT-PCR measurements between the different plates due to experimental artifacts, a normalization plate was planned. This plate, designated hereinabove `shuffled plate`, contained samples from all other plates. Real Time PCR was performed on this plate using the primers appropriate for all candidates in tables 26 and 27. For each other plate (plates 1-7 above) and each amplicon, the samples appearing also in the shuffled plate were examined--the ratio between the transcript abundance as measured in the plate to the abundance as measured in the shuffled plate was calculated, outliers were manually removed, and the geometric mean of the left ratios was taken as an additional multiplicative normalization factor for the plate and amplicon.
Real Time qPCR Analysis of the Selected Markers
Example 3.1
Expression of Tumor Necrosis Factor Receptor Superfamily, Member 12a, AA686189, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name W41270_DB81_Seg11 in Kidney Tissues of Treated or Untreated Rats
[0540] Expression of tumor necrosis factor receptor superfamily, member 12a transcripts detectable by or according to seg11--W41270_DB81_seg11_F2R2 (SEQ ID NO: 254) amplicon and primers W41270_DB81_seg11_F2 (SEQ ID NO: 252) and W41270_DB81_seg11_R2 (SEQ ID NO: 253) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT Preparation and Real-Time RT-PCR Analysis" hereinabove and by the shuffled plate values, as described in section "Inter-Plate Normalization". Following optimization, described in Example 3 herein, the experiments were done using primers concentration of 50 nM.
[0541] The column entitled W41270_DB81_seg11 in Table 23 contains the normalized expression values of the above-indicated tumor necrosis factor receptor superfamily, member 12a transcript in treated or untreated kidney samples.
[0542] As is evident from the column entitled W41270_DB81_seg11 in Table 23, the level of expression of the tumor necrosis factor receptor superfamily, member 12a transcript detectable by the above amplicon was higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers 59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, with a P-value for day 5 of 3.4E.sup.-05.
[0543] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: W41270_DB81_seg11_F2 (SEQ ID NO: 252) forward primer; and W41270_DB81_seg11_R2 (SEQ ID NO: 253) reverse primer.
[0544] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon:
[0545] W41270_DB81_seg11_F2R2 (SEQ ID NO: 254).
[0546] Forward primer (W41270_DB81_seg11_F2 (SEQ ID NO: 252)):
TABLE-US-00113 GATCTGGGTAGGTGGTTGTTGG
[0547] Reverse primer (W41270_DB81_seg11_R2 (SEQ ID NO: 253)):
TABLE-US-00114 CGCACACCCTTATAAAAGTCCC
[0548] Amplicon (W41270_DB81_seg11_F2R2 (SEQ ID NO: 254)):
TABLE-US-00115 GATCTGGGTAGGTGGTTGTTGGGGCAGAAAGGAGGTCGTAGACTTAGGAT ATAGGAAACCAGGAAAAACTGACTGAGGAAGGGACTTTTATAAGGGTGTG CG
Example 3.2
Expression of Interferon Stimulated Exonuclease 20 (ISG20), AI045075, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name AI045075_DB71_Seg6 in Kidney Tissues of Treated or Untreated Rats
[0549] Expression of Interferon stimulated exonuclease 20 (ISG20) transcripts detectable by or according to seg6--AI045075_DB71_seg6_F2R2 (SEQ ID NO: 263) amplicon and primers AI045075_DB71_seg6_F2 (SEQ ID NO: 261) and AI045075_DB71_seg6_R2 (SEQ ID NO: 262) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT Preparation and Real-Time RT-PCR Analysis" hereinabove and by the shuffled plate values, as described in section "Inter-Plate Normalization".
[0550] The column entitled AI045075_DB71_seg6 in Table 23 contains the normalized expression values of the above-indicated Interferon stimulated exonuclease 20 (ISG20) transcript in treated or untreated kidney samples.
[0551] As is evident from the column entitled AI045075_DB71_seg6 in Table 23, the level of expression of the Interferon stimulated exonuclease 20 (ISG20) transcript detectable by the above amplicon was higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 1.1E.sup.-06.
[0552] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: AI045075_DB71_seg6_F2 (SEQ ID NO: 261) forward primer; and AI045075_DB71_seg6_R2 (SEQ ID NO: 262) reverse primer.
[0553] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon:
[0554] AI045075_DB71_seg6_F2R2 (SEQ ID NO: 263).
[0555] Forward primer (AI045075_DB71_seg6_F2 (SEQ ID NO: 261)):
TABLE-US-00116 GGGCCACAATGGAGCTCTAC
[0556] Reverse primer (AI045075_DB71_seg6_R2 (SEQ ID NO: 262)):
TABLE-US-00117 ACAGGTCTCATTCATGGAAAACTATG
[0557] Amplicon (AI045075_DB71_seg6_F2R2 (SEQ ID NO: 263)):
TABLE-US-00118 GGGCCACAATGGAGCTCTACAAAATCTCTCAGCGACTCAGAGCCCAGCGA GGGCTGCCCTGCCTGGGAACATCAGCCTGAACTTCATCCTCATCCAGGAT CAGAAGCAGCTACTCCTTGAAGGACCATAGTTTTCCATGAATGAGACCT GT
Example 3.3
Expression of Interferon Stimulated Exonuclease 20 (ISG20), AI045075, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name W64472_DB81_Seg2 in Kidney Tissues of Treated or Untreated Rats
[0558] Expression of Interferon stimulated exonuclease 20 (ISG20), AI045075, transcripts detectable by or according to seg2--W64472_DB81_seg2_F6R1 (SEQ ID NO: 329) amplicon and primers W64472_DB81_seg2_F6 (SEQ ID NO: 327) and W64472_DB81_seg2_R1 (SEQ ID NO: 328) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT Preparation and Real-Time RT-PCR Analysis" hereinabove and by the shuffled plate values, as described in section "Inter-Plate Normalization".
[0559] The column entitled W64472_DB81_seg2 in Table 23 contains the normalized expression values of the above-indicated Interferon stimulated exonuclease 20 (ISG20), AI045075, transcript in treated or untreated kidney samples.
[0560] As is evident from the column entitled W64472_DB81_seg2 in Table 23, the level of expression of the Interferon stimulated exonuclease 20 (ISG20), AI045075, transcript detectable by the above amplicon was higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 1.0E.sup.-05.
[0561] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: W64472_DB81_seg2_F6 (SEQ ID NO: 327) forward primer; and W64472_DB81_seg2_R1 (SEQ ID NO:328) reverse primer.
[0562] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon:
[0563] W64472_DB81_seg2_F6R1 (SEQ ID NO: 329).
[0564] Following optimization described in Example 3 herein, the following primers were used to amplify W64472_DB81_seg2_F6R1 (SEQ ID NO: 329) amplicon:
[0565] Forward primer (W64472_DB81_seg2_F6 (SEQ ID NO: 327)):
TABLE-US-00119 ACAGCCTGATGCAGACAGC
[0566] Reverse primer (W64472_DB81_seg2_R1 (SEQ ID NO:328)):
TABLE-US-00120 TCTGGTTCATTATCAAGGGAAGTTG
[0567] Amplicon (W64472_DB81_seg2_F6R1 (SEQ ID NO: 329)):
TABLE-US-00121 ACAGCCTGATGCAGACAGCCCTGACTCAACCTGCCAGCCCCCTTACCTGG CCAGCCTTGAGGAGATGGAACAGCCCAGGCTACAAGGCCTGCCCCCACT CCTCAACTTCCCTTGATAATGAACCAGA
Example 3.4
Expression of Cyclin-G1 (CCNG1), 1131883, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name H31883_DB71_Seg13 in Kidney Tissues of Treated or Untreated Rats
[0568] Expression of Cyclin-G1 (CCNG1) transcripts detectable by or according to seg13--H31883_DB71_seg13_F5R5 (SEQ ID NO: 332) amplicon and primers H31883_DB71_seg13_F5 (SEQ ID NO: 330) and H31883_DB71_seg13_R5 (SEQ ID NO: 331) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT Preparation and Real-Time RT-PCR Analysis" hereinabove and by the shuffled plate values, as described in section "Inter-Plate Normalization".
[0569] The column entitled H31883_DB71_seg13 in Table 23 contains the normalized expression values of the above-indicated Cyclin-G1 (CCNG1) transcript in treated or untreated kidney samples.
[0570] As is evident from the column entitled H31883_DB71_seg13 in Table 23, the level of expression of the Cyclin-G1 (CCNG1) transcript detectable by the above amplicon was higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 2.1E.sup.-05.
[0571] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: H31883_DB71_seg13_F5 (SEQ ID NO: 330) forward primer; and H31883_DB71_seg13_R5 (SEQ ID NO: 331) reverse primer.
[0572] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon:
[0573] H31883_DB71_seg13_F5R5 (SEQ ID NO: 332).
[0574] Following optimization described in Example 3 herein, the following primers were used to amplify H31883_DB71_seg13_F5R5 (SEQ ID NO: 332) amplicon:
[0575] Forward primer (H31883_DB71_seg13_F5 (SEQ ID NO: 330)):
TABLE-US-00122 CAGAATTGCTGCCTCAATCTAGTCC
[0576] Reverse primer (H31883_DB71_seg13_R5 (SEQ ID NO: 331)):
TABLE-US-00123 GGTTTTGCAGATGTACTCGGTTCC
[0577] Amplicon (H31883_DB71_seg13_F5R5 (SEQ ID NO: 332)):
TABLE-US-00124 CAGAATTGCTGCCTCAATCTAGTCCCATTTGAGAAAATTTGTTTCTACTG TCTCAATAACTGGATGAAATATCACTCTGAAAACTTGCCTATTGCACTAA AGCTAGTTTAGGCTTGATAAAACACTCCAGGAGGTTTTTACCACAGACTG TTTCTATTAAAACTGCTGCTTCTCATGTACAATTTTGTTTTAAAAGGAAC CGAGTACATCTGCAAAACC
Example 3.5
Expression of Cyclin-G1 (CCNG1), H31883, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name MUSCYCG1R_DB81_Seg19-20 in Kidney Tissues of Treated or Untreated Rats
[0578] Expression of Cyclin-G1 (CCNG1) transcripts detectable by or according to seg19-20--MUSCYCG1R_DB81_seg19-20_F1R1 (SEQ ID NO: 296) amplicon and primers MUSCYCG1R_DB81_seg19-20_F1 (SEQ ID NO: 294) and MUSCYCG1R_DB81_seg19-20_R1 (SEQ ID NO: 295) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT Preparation and Real-Time RT-PCR Analysis" hereinabove and by the shuffled plate values, as described in section "Inter-Plate Normalization". Following optimization described in Example 3 herein, the annealing temperature of the PCR was 62.degree. C.
[0579] The column entitled MUSCYCG1R_DB81_seg19-20 in Table 23 contains the normalized expression values of the above-indicated Cyclin-G1 (CCNG1) transcript in treated or untreated kidney samples.
[0580] As is evident from the column entitled MUSCYCG1R_DB81_seg19-20 in Table 23, the level of expression of the Cyclin-G1 (CCNG1) transcript detectable by the above amplicon was higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 1.3E.sup.-04.
[0581] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: MUSCYCG1R_DB81_seg19-20_F1 (SEQ ID NO: 294) forward primer; and MUSCYCG1R_DB81_seg19-20_R1 (SEQ ID NO: 295) reverse primer.
[0582] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon: MUSCYCG1R_DB81_seg19-20_F1R1 (SEQ ID NO: 296).
[0583] Forward primer (MUSCYCG1R_DB81_seg19-20_F1 (SEQ ID NO: 294)):
TABLE-US-00125 GAGATCCAAGCACTGAAGTATGTAGAGT
[0584] Reverse primer (MUSCYCG1R_DB81_seg19-20_R1 (SEQ ID NO: 295)):
TABLE-US-00126 TCAGGAGTACAGTGGATACATTTCTCTT
[0585] Amplicon (MUSCYCG1R_DB81_seg19-20_F1R1 (SEQ ID NO: 296)):
TABLE-US-00127 GAGATCCAAGCACTGAAGTATGTAGAGTTAACAGAAGGAGTAGAATGT ATTCAGAAACATTCCAAGGTATGCCAAGGTGATAGCATTGATCCTATT AGCAAGCTACAAGAGAAATGTATCCACTGTACTCCTGA
Example 3.6
Expression Etoposide Induced 2.4 (EI24) mRNA, 1131799, Transcripts which are Detectable by Amplicon as Depicted in Sequence Name W83813_DB81_Seg27 in Kidney Tissues of Treated or Untreated Rats
[0586] Expression of Etoposide induced 2.4 mRNA (EI24) transcripts detectable by or according to seg27--W83813_DB81_seg27_F1R1 (SEQ ID NO: 287) amplicon and primers W83813_DB81_seg27_F1 (SEQ ID NO: 285) and W83813_DB81_seg27_R1 (SEQ ID NO: 286) was measured by real time PCR. The value of the expression was measured by Real-Time PCR and normalized relative to the expression of the house keeping genes, as described in section "RT Preparation and Real-Time RT-PCR Analysis" hereinabove and by the shuffled plate values, as described in section "Inter-Plate Normalization".
[0587] The column entitled W83813_DB81_seg27 in Table 23 contains the normalized expression values of the above-indicated Etoposide induced 2.4 mRNA (EI24) transcript in treated or untreated kidney samples.
[0588] As is evident from the column entitled W83813_DB81_seg27 in Table 23, the level of expression of the Etoposide induced 2.4 mRNA (EI24) transcript detectable by the above amplicon was higher in the samples treated with toxic compounds (samples 1-58 and 76-105, in kidney tissue panel described in Table 9 hereinabove) than in the control samples (naive, saline and valproic acid treated samples; samples numbers--59-75 and 106-129, in kidney tissue panel described in Table 9 hereinabove). Statistical analysis was applied to verify the significance of these results, P-value for day 5: 0.04.
[0589] Primer pairs are also optionally and preferably encompassed within the present invention; for example, for the above experiment, the following primer pair was used as a non-limiting illustrative example only of a suitable primer pair: W83813_DB81_seg27_F1 (SEQ ID NO: 285) forward primer; and W83813_DB81_seg27_R1 (SEQ ID NO: 286) reverse primer.
[0590] The present invention also preferably encompasses any amplicon obtained through the use of any suitable primer pair; for example, for the above experiment, the following amplicon was obtained as a non-limiting illustrative example only of a suitable amplicon W83813_DB81_seg27_F1R1 (SEQ ID NO: 287):
[0591] Forward primer (W83813_DB81_seg27_F1 (SEQ ID NO: 285)):
TABLE-US-00128 AATCTAGGCTGCCTCCTGGAG
[0592] Reverse primer (W83813_DB81_seg27_R1 (SEQ ID NO: 286)):
TABLE-US-00129 AGGTCAATTATACAAGGCATGACTTTAG
[0593] Amplicon (W83813_DB81_seg27_F1R1 (SEQ ID NO: 287)):
TABLE-US-00130 AATCTAGGCTGCCTCCTGGAGGAAGATACTTAGGAGTTCAGAAGTGAA GAGATGAGGCTTATAATACTTTTTCCTAAAGTCATGCCTTGTATAATTG ACCT
Classification Using qRT-PCR Data
[0594] Given the qRT-PCR panel for the selected genes detailed in Table 23, the optimal classifier was built based on the measured expression levels of the labeled samples, as described in Table 9. This was performed again to achieve a more accurate and controlled signature.
[0595] Two equivalent optimal signatures for prediction of renal damage at day-5, as derived in the validation stage analysis of the labeled samples, are given in Table 26 (four amplicons of three genes) and Table 27 (six amplicons of four genes). Table 28 summarizes the performance of the 4-genes signature on the various groups of the labeled samples.
TABLE-US-00131 TABLE 26 Optimal Signature Day 5 (Validation Stage Analysis) Splice Variant/ Contig Gene name Wild Type Internal name Probeset AA686189 TNFRSF12A SV W41270_DB81_seg11 1371785_at AI045075 ISG20 SV W64472_DB81_seg2 1390507_at AI045075 ISG20 WT AI045075_DB71_seg6 1390507_at H31883 CCNG1 WT H31883_DB71_seg13 1367764_at
TABLE-US-00132 TABLE 27 Optimal Signature Day 5 (Validation Stage Analysis) Splice Variant/ Contig Gene name Wild Type Internal name Probeset AA686189 TNFRSF12A SV W41270_DB81_seg11 1371785_at AI045075 ISG20 SV W64472_DB81_seg2 1390507_at AI045075 ISG20 WT AI045075_DB71_seg6 1390507_at H31883 CCNG1 WT H31883_DB71_seg13 1367764_at H31883 CCNG1 SV MUSCYCG1R_DB81_seg19-20 1367764_at H31799 EI24 SV W83813_DB81_seg27 1388642_at
TABLE-US-00133 TABLE 28 Performance of the 4-genes signature on the various groups of the labeled samples Standard Average Deviation Group (Compound, Period, No. of Toxicity of Toxicity Gender) samples Score Score Doxorubicin Day5 Male 2 0.77 0.07 Gentamycin Day5 Female 3 0.73 0.12 Cisplatin Day5 Female 3 0.69 0.14 Gentamycin Day5 Male 3 0.63 0.03 Cisplatin Day5 Male 3 0.63 0.27 Tobramycin Day5 Female 3 0.61 0.28 Doxorubicin Day5 Female 3 0.61 0.19 Tobramycin Day5 Male 3 0.59 0.18 Valproic-Acid Day1 Male 3 0.57 0.42 Saline Day1 Male 3 0.51 0.45 Naive Male 3 0.41 0.42 Valproic-Acid Day1 Female 3 0.33 0.51 Valproic-Acid Day5 Female 3 0.18 0.3 Naive Female 3 0.14 0.24 Saline Day1 Female 3 0.11 0.14 Valproic-Acid Day28 Female 3 0.07 0.12 Valproic-Acid Day5 Male 3 0.02 0.02 Valproic-Acid Day28 Male 3 0.01 0 Saline Day5 Female 2 0.01 0.01 Saline Day28 Female 3 0.01 0.01 Saline Day5 Male 3 0 0 Saline Day28 Male 3 0 0
[0596] The two optimal classifiers (signatures described in Tables 26 and 27) were applied to the qRT-PCR reads of the un-labeled samples and their calls was used to assign a level of toxicity to each group and, eventually, each compound.
Results
[0597] qRT-PCR Data Analysis of Labeled Samples Described in Table 9 and Plate 1-3 in Table 25.
[0598] Transcripts abundance was measured using qRT-PCR for 8 amplicons from the 4 genes disclosed in Table 13 hereinabove. As in Example 1, an optimal signature for day-5 was identified, distinguishing the day-5 "Toxic" samples from all control (and naive rats) samples. Iterative feature selection and Random-Forest classifier were used as in the discovery stage, described in Example 1 hereinabove. The input data was the new qRT-PCR measurements and the gender of the rat as an extra two-values features. The same parameters as in the discovery stage were used again, performing cross validation by leaving-out randomly selected samples--3 control samples and 3 toxic samples and repeating 500 times, choosing the bound on `toxicity` as to maximize the accuracy. Two equivalent (but not identical in results) signatures were found, presented in Tables 26 and 27, consisting of 4 and 6 amplicons, coming from 3 and 4 genes, respectively. The cross-validation performance evaluations of these signatures show 80% sensitivity at about 85% specificity. The Out-Of-Bag OOB performance evaluation gave the confusion matrix presented in Table 29 (overall accuracy of 83%) and ROC curve presented in FIG. 6.
TABLE-US-00134 TABLE 29 Confusion matrix Normal Toxic Predicted as Normal 34 4 Predicted as Toxic 7 19
[0599] It was possible to find a bound on the Random-Forest call--30% of the trees in the forests giving a "Toxic" call--such that all "Toxic" samples pass that bound while only one group of control samples (Naive males) has more than 50% (2 out of 3) of its members pass that bound. See Tables 26 and 27 for details on the signatures and Table 28 for their performance
[0600] qRT-PCR Data Analysis of the Un-Labeled Samples, Described in Plates 4-7 in Table 25
[0601] The classifiers described in Tables 26 and 27, were used for testing the un-labeled samples. Both classifiers were applied to the measurements of each sample, used the 30% bound from above, and the number of samples pass that bound in each group were summarized. The results are given in the following Table 30
TABLE-US-00135 TABLE 30 `Toxic` by `Toxic` by `Toxic` by `Toxic` by Group (Compound, 4-genes 6-genes 4-genes 6-genes Average Dose, Period, Animals Classifier Classifier Classifier Classifier `Toxic` Gender) (#) (#) (#) (%) (#) (%) T2 Ds1 Day5 Male 6 5 5 83 83 0.83 T1 Ds2 Day5 Female 6 5 3 83 50 0.665 control Day5 Male 5 3 3 60 60 0.6 T2 Ds2 Day1 Female 6 4 3 67 50 0.585 T3 Ds1 Day5 Male 5 3 2 60 40 0.5 T2 Ds2 Day5 Female 4 2 2 50 50 0.5 T1 Ds1 Day5 Male 6 3 3 50 50 0.5 T1 Ds1 Day5 Female 6 3 3 50 50 0.5 control Day5 Female 6 3 2 50 33 0.415 T3 Ds2 Day5 Male 4 2 1 50 25 0.375 control Day1 Male 6 2 2 33 33 0.33 T1 Ds2 Day5 Male 6 2 2 33 33 0.33 T3 Ds2 Day1 Male 5 2 1 40 20 0.3 T2 Ds2 Day5 Male 5 1 2 20 40 0.3 T2 Ds1 Day5 Female 5 2 1 40 20 0.3 T2 Ds1 Day1 Male 6 2 1 33 17 0.25 T3 Ds2 Day5 Female 5 1 1 20 20 0.2 T3 Ds2 Day1 Female 5 1 1 20 20 0.2 T3 Ds1 Day1 Female 5 1 1 20 20 0.2 T2 Ds1 Day1 Female 5 1 1 20 20 0.2 control Day1 Female 6 1 1 17 17 0.17 T1 Ds1 Day1 Male 6 1 1 17 17 0.17 T3 Ds1 Day5 Female 6 1 0 17 0 0.085 T3 Ds1 Day1 Male 6 0 0 0 0 0 T2 Ds2 Day1 Male 6 0 0 0 0 0 T1 Ds2 Day1 Male 6 0 0 0 0 0 T1 Ds2 Day1 Female 6 0 0 0 0 0 T1 Ds1 Day1 Female 5 0 0 0 0 0
[0602] The first two groups--"T2 Ds1 Day5 Male" and "T1 Ds2 Day5 Female" showed a clear nephrotoxic effect (more than 66% of samples were marked as "Toxic" when averaging the two classifiers), while the following six groups--"control Day5 Male", "T2 Ds2 Day1 Female", "T3 Ds1 Day5 Male", "T2 Ds2 Day5 Female", "T1 Ds1 Day5 Male", "T1 Ds1 Day5 Female" were also suspicious of showing the effect (at least 50% of samples predicted as `Toxic` on average). Therefore, consistently with the information available for the compounds T1 and T2, the results demonstrated that T1 and T2 are nephrotoxic agents. The T3 and control groups showing `possible` toxic effect are either real false-positive of the classifier, or a result of some technical problem.
[0603] Using the classifier the toxicity was established after the rats were treated for 5 days only, while the visible pathological damage was seen only after 28 days for T1 and after 7 days for T2, as shown in FIGS. 3-5.
[0604] Therefore, combinations of biomarkers according to the present invention can be used for early detection of drug-induced nephrotoxicity. These signatures predict the future occurrence of drug induced renal toxicity before it is detected using the traditional endpoint analysis such as histopathology or clinical chemistry.
[0605] According to the present invention, an optimized assay based on these signatures can be implemented in pre-clinical studies. The markers of the invention can be used alone or in combination with other known markers for renal damage identification.
[0606] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.
[0607] Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.
Sequence CWU
1
1
33211168DNARattus Norvegicus 1agccccgagt cttggctggc cggtggtggg agcagaccgt
tcttgcctct gaaccggcaa 60tcatggctcc gggttggccg cggcctctgc cgcagctcct
cgtgttggga ttcgggttgg 120tgttgataca cgccacggcc ggggagcaag caccaggcaa
cgccccatgc tcaagcggca 180gctcctggag cgcggacctc gacaagtgca tggactgcgc
ttcttgtcca gcgcgaccac 240acagcgactt ctgcctggga tgtgagtggg ggtggggacg
gggctggtgg caagcggatc 300ctagatctgg gtaggtggtt gttggggcag aaaggaggtc
gtagacttag gatataggaa 360accaggaaaa actgactgag gaagggactt ttataagggt
gtgcgttggg aggggggtaa 420gcttgagacc ctttgagggc aggctggatt ggcgtcccaa
gggcaagatc tgatttgaac 480ccgatcacta ggcgcagcag cacctcctgc ccacttcagg
atgctatggc ccattctggg 540aggcgctctt agtctggccc tggttttggc gctggtttct
ggttttcctg gtctggagac 600gatgccgccg gagagaaaag tttactaccc ccatagagga
gactggtgga gaaggctgcc 660caggtgtggc actgatccag tgaggagcac ccgcgctggt
gcccattcat cgtccattca 720ttcattctgg agccagcctg gctttccaga gacaagccgc
gccagactct tccaaccaca 780agggggtggg gcgaggtggt gattcacctc caaggactgg
gcttagggtt caggggagcc 840ttccagggtg tctaattgcc ctgtctctgg ttctggggca
gacagagagc ctcaagctag 900gtcacaaagc gactcatact aaggatctgc agcatttgca
caagggaatc tcttgctccc 960cacaagtcct ggaggcctgg ccgacttgag ggggcagaca
caacactggg ttccacccac 1020tcggatggac tgaaatgcca ctaccctgag ttttagccct
gggagtgggt tagattgagg 1080gacctgttca taacactaag ggggctggcc ctctgggagg
gctggtccca gtacacacaa 1140acacaaccca tcccccaagg gggtgata
11682230DNAArtificial SequenceSynthetic
polynucleotide 2gtgagtgggg gtggggacgg ggctggtggc aagcggatcc tagatctggg
taggtggttg 60ttggggcaga aaggaggtcg tagacttagg atataggaaa ccaggaaaaa
ctgactgagg 120aagggacttt tataagggtg tgcgttggga ggggggtaag cttgagaccc
tttgagggca 180ggctggattg gcgtcccaag ggcaagatct gatttgaacc cgatcactag
2303948DNARattus Norvegicus 3ggaggagggc agagccagag gagggacagc
ctgatgcaga cagccctgac tcaacctgcc 60agccccctta cctgtcagcc ttgaggagat
ggaacagccc agcctactag gcctgccccc 120actccccaac ttcccttgat aatgaaccag
aaactgaaac taaaacggct ccgcttgatg 180agtcacttcc caaagtgact aaagtagctg
agaagtagaa acagaggcag aagagaaccc 240agggcactgg gacaggactt cctgagggtc
tgaggagcat ggcagacagc ccagaggtgg 300tagccatgga ctgtgagatg gtggggctcg
ggcctcaaag ggtgagtggc ctcgcccgct 360gcagcattgt gaacgtccac agcgcagtcc
tctatgacaa gtacatccag cctgagggag 420agatcacgga ctacagaacc caagtcagcg
ggatcacgcc tcagcacatg gcgagggcca 480cgccatttgc tgaagccagg ctagagatcc
tgcagcttct gaaaggcaag ctggtggtgg 540gccatgacct gaagcatgac ttcagtgccc
tgaaggagga catgagaaaa tacaccatct 600acgacacgtc cacagacatg ctgctgtggc
acgaggccaa gctgcactgc tacagccgtg 660tgtccctgag gctgctgtgc aagcgcctgc
tgcacaagag catccaggtg aggagcttcc 720cggcccctgt gacccttctc tctcttctcc
ctcctctctc tctccctccc tcctcccact 780caggtaagga gtaacctgcc cttcctcttc
ctcctctcct cctccaagca aggagtcctc 840ctgctttctc ccttagtcct ccctctcctt
ccctgattct aaaagtgagg atcttcctct 900ccctcctccc cgtgctccca ctcctcccaa
gggcaggtca gtcccacc 9484255DNAArtificial
SequenceSynthetic polynucleotide 4ggaggagggc agagccagag gagggacagc
ctgatgcaga cagccctgac tcaacctgcc 60agccccctta cctgtcagcc ttgaggagat
ggaacagccc agcctactag gcctgccccc 120actccccaac ttcccttgat aatgaaccag
aaactgaaac taaaacggct ccgcttgatg 180agtcacttcc caaagtgact aaagtagctg
agaagtagaa acagaggcag aagagaaccc 240agggcactgg gacag
2555249DNAArtificial SequenceSynthetic
polynucleotide 5gtgaggagct tcccggcccc tgtgaccctt ctctctcttc tccctcctct
ctctctccct 60ccctcctccc actcaggtaa ggagtaacct gcccttcctc ttcctcctct
cctcctccaa 120gcaaggagtc ctcctgcttt ctcccttagt cctccctctc cttccctgat
tctaaaagtg 180aggatcttcc tctccctcct ccccgtgctc ccactcctcc caagggcagg
tcagtcccac 240ctggcctaa
24962438DNARattus Norvegicus 6agcgaccggc agggtgcccg
cccgacttcc cagctgcccc gtgcggcccg ggcatgccca 60gtgtgggcgc agccccggct
ctccgagcgc cggggcggag cgggcagccg ggcgcggagc 120aggcgaaccg aacctcggtg
ggcgagcgcc ggggctggag ccgcgggggg tcggtggcgg 180ggccttccat gatgagtgat
ttgggggcac ttccctctct ctgtaattga tagtctgggc 240agtgaagaga tggctgacag
tgtcaaaacc tttctgcagg accttggcag gggaatcaaa 300gactccatct ggggcatctg
taccatctca aagctagatg ctcggatcca gcagaagaga 360gaggagcagc gtcgaaggag
ggcaagtagc ctcttggccc agaggagagc ccagagtgta 420gagcggaagc aagagagtga
gccacgtatt gttagtagaa ttttccagtg ctgtgcttgg 480aatggtggag tattctggtt
cagtctcctc ttgttttacc gagtgtttat tcctgtgctt 540caatcagtaa cagcccgggt
tattggtgat ccgtcactac atggagatgt ttggtcatgg 600ctggaattct tcctcacatc
aattttcagt gctctttggg tgctgcccct gtttgtgctt 660agcaaagttg tgaatgccat
ttggttccaa gatatagctg acttggcatt tgaggtatca 720gggaggaaac ctcatccatt
ccccagtgtc agcaaaataa ttgctgacat gctcttcaac 780cttttgctac aggcactttt
ccttattcag gggatgtttg tgagtctctt ccccatccat 840cttgtgggtc agctggttag
tttgctgcat atgtctcttc tctactcact ctactgcttt 900gagtaccgtt ggttcaacaa
aggaattgaa atgcaccagc gattgtcaaa catagaaagg 960aactggcctt actactttgg
gtttggcttg cccttggctt tcctcacagc aatgcaatcc 1020tcctacatta tcaggtaatt
tgggtagaaa aagaattcgt aagcatcttt tgttcagcta 1080ctgtaccaac attttacatc
atttgaccat caggaagatt tgttgctgtt aatagtgaca 1140tttggtatca ttaaaatgaa
aatataaaaa gaaatctagg ctgcctcctg gaggaagata 1200cttaggagtt cagaagtgaa
gagatgaggc ttataatact ttttcctaaa gtcatgcctt 1260gtataattga cctttttttc
ccttaaacag tggctgcctc ttttctatcc tgtttccttt 1320attcatcatc agcgccaatg
aagcaaagac tcctggaaaa gcatatcttt tccagttgcg 1380cctcttctcc ttggtggtct
ttttaagcaa cagacttttc cacaagacgg tctacctaca 1440gtcggccctg agcagctcat
cctccgcaga gaaattccct tcgccacatc cttctcctgc 1500caaactgaaa gctgctgcag
gccactgagt cctgctgtca aaggggacgg gtgggactgg 1560gtggaggatg tggcagctct
tttcttggtt ttcctccccc tgctgtggaa ggcaggaccc 1620actgccaagg ggcctctgca
tattcccttt gtctttgaat tgggaatctt cctgactccg 1680gtatgtggat ttttaccacc
accctaggtc tggaaggacc agttttccag ctgtttttta 1740gcttttgcca gctcctgtgc
ctggactgat ttgagtactc ccccctccct tgtgtcattt 1800accttcccac ctcctcctgc
ctcccagcac ccctgggtga atgggctttg taattttaac 1860tgttgtattt tgtgaatttg
ttgttactgt ttcctgtgaa gcacatacct tgtatgtggg 1920aggtaaagga gcacgccagc
tgctccatgt cactccctct atagccatca ctgtcttgtt 1980tttttgtaac tcaggttagg
ttttggtctt tactgctctg ctgcagaaaa ggaaaggaat 2040gggggaaagg agcctaagag
atgggacaga tagacctcag ccaaactggt tgggttttga 2100ggagtcatgt tctttgttcc
ccttgaaggg gaaacaggtt ttttcactgg tacatttaaa 2160gttccccagc tatgggaagg
taccagttct ggacaagtgc cactgcatca tagcaactct 2220gaagatgaaa cttactgttg
gccactgcca ggtcagactc gtgttttaag gaatactggg 2280tgcttcatat aggaactgaa
ggggtaaact tactaaacca ttcaacctgt gattggtgat 2340gtttttctgt cattttaaga
gtcgacacat ggggtgggag ggcagatgta aaaaaacttg 2400tacaatttta aaatcacaat
taaacgtgag ctggtttc 24387256DNAArtificial
SequenceSynthetic polynucleotide 7gtaatttggg tagaaaaaga attcgtaagc
atcttttgtt cagctactgt accaacattt 60tacatcattt gaccatcagg aagatttgtt
gctgttaata gtgacatttg gtatcattaa 120aatgaaaata taaaaagaaa tctaggctgc
ctcctggagg aagatactta ggagttcaga 180agtgaagaga tgaggcttat aatacttttt
cctaaagtca tgccttgtat aattgacctt 240tttttccctt aaacag
2568137DNAArtificial SequenceSynthetic
polynucleotide 8agcgaccggc agggtgcccg cccgacttcc cagctgcccc gtgcggcccg
ggcatgccca 60gtgtgggcgc agccccggct ctccgagcgc cggggcggag cgggcagccg
ggcgcggagc 120aggcgaaccg aacctcg
13792422DNARattus Norvegicus 9ataaaatcaa tcccactttc
ttgttaaaag gagaaacgat ctgaattttg aaagactaga 60agcccaactg aaggcgtgcc
actgcaggat catattttct aaagcaaagg ccttctgtgc 120tggcgctggc aatcatcgct
ttggagatcc aagcactgaa gtatgtggag ttaacagaag 180gagtagaatg tattcagaaa
cattccaaga taagtggccg agatctgacc ttctggcaag 240agcttgtttc caagtgttta
actgaatatt catcaaacaa gtgttccaag ccgaacggtc 300agaagttaaa atggatcgtg
tctgggcgca ctgcacgaca actgaagcac agttattaca 360ggataaccca cctcccaaca
attcccgaaa ccatgggtta gttggcaaat ctggttgtta 420tcctctgtgt acagaacatt
tcccagtgag atcgtttttg tgctataact taaggattga 480aatactacct tcaatataaa
gaatacagga tgaaaacagt aaaggaaacg tgagtttgtt 540ggtctagaca gagaatactg
ggaggcattc actgtgtacc gcagtctgaa gagaaatgag 600tatcaaacct ctagacacat
gctcatactg ctgtcaaagg actagcgtag aaaagagagt 660cctccaaacc ggaagtttaa
atgtagttac taaaatagca cttctttaac ttacatatcc 720ccccactgtg gcttatttaa
agttacagaa gtccaagcag aacgacaaaa gatgtgaccc 780atatatgaac acattttaat
ctgttcattg attaggagag tgaatatgaa cttgcatgat 840gcccatgtta ggtttctgga
aactgccggg gtatcttaat tctctagtat tctccctctg 900tggcagttgg gctaatacaa
agtaactata cgcatgagaa tataaaatca gtctctgata 960catacacatt tttaccatca
aaatttctta atcatagcaa agacttacct ttttatgatt 1020aggaattttt tttttaatgt
atggcagcac atgcctttaa tcccaacact agggaggcag 1080aggcaggtgg atctctttga
gttcgaagcc aggctggtct ttacagtgag ttccaggaca 1140gctggagagc tacagaatgg
agagacgctg tctcaaaaac actgaaaaca aacaaacaaa 1200ccataccagt ttgtaggcag
acttctgttg ggttgggttt gtactgtttg cctatgcagt 1260gggattacag cagcagcaac
aaaaactgtc cctgaagtct ttctctgcca ctgtgacctg 1320agtttcctat ggtacgcgat
ttattctaag aaacctcagc ccctcaccac gttagctgtt 1380ggcaaatggc ctcacagttg
cggaaagtcc caattctagg cttgggaaag caatgcttag 1440atttgaattg gcccatgaag
cattcaaatc aaggctaaag acataaatgt gaaataaaac 1500tgtgaacctt cattttaaca
ttgatctcac ttcccagatt taatcaatat atacttaggt 1560ggtattaaaa atggtaaact
gcctaattta aatctcaaaa tttaaactat gaggtttaca 1620tcaaagccaa catttcacaa
atgtactttt aaggtattaa aagaggtatt taagcagtaa 1680atggtttctt ggcacccata
accaagtaat agttaagtta gaggtgggac ttttttattg 1740ctatgagaat tacatttaaa
cttttgggtg ttttataaaa agcagatttc acaagttttg 1800aaaattgtga cctttactga
aatttgttac ctttaatatt tcttctagag gataggtatt 1860tataaaagaa aaattcgtca
gaattgctgc ctcaatctag tcccatttga gaaaatttgt 1920ttctactgtc tcaataactg
gatgaaatat cactctgaaa acttgcctat tgcactaaag 1980ctagtttagg cttgataaaa
cactccagga ggtttttacc acagactgtt tctattaaaa 2040ctgctgcttc tcatgtacaa
ttttgtttta aaaggagaac cgagtacatc tgcaaaacct 2100aagtcttaag ggacgtcagg
aggtaccttc agaattatag gatcaccatg gtagtgggga 2160ttctccatgc tggccttgaa
tgtttgatct tcactgctga aatgtgggta gctcctcagc 2220gccctgtaga gcctgagtct
acctagaata gctgtaacca ttttgacaag taatggataa 2280gaaaattatc cattgagaag
ctaaaaacaa aacaaaacaa aaccaaagaa cgggtgtatt 2340ttattcttaa cctttgtaaa
ccatcactga gaacacttca gttcttccta acagctgtta 2400tgcttcgatt tgaaaaaaat
ac 24221030DNAArtificial
SequenceSynthetic polynucleotide 10ataaaatcaa tcccactttc ttgttaaaag
3011110DNAArtificial SequenceSynthetic
polynucleotide 11ataaaatcaa tcccactttc ttgttaaaag gagaaacgat ctgaattttg
aaagactaga 60agcccaactg aaggcgtgcc actgcaggat catattttct aaagcaaagg
110121111DNARattus Norvegicus 12agaggccatc catcaaaaga
atcacaccaa tcagaggcga agatgagtcc cagctagcaa 60tcctggtgcc cagcctatct
ccccgcggcc gggcgcagtc cttcaccgca cgctgaaccg 120gaggaaggct gcgcctagtc
ggggcgctga gggaccctcc accgggacgc cggcccctcc 180ccgggcctct gctcacttgc
ccccctctgc gagcccgtcc ccctagtcgg cctctcggat 240cggggacgtg gggcgagctg
agagcaggcc cggggtgggt ggtcactgtg gagaagacgt 300ggctgtcaag gatgatagaa
gtactgacaa ctgactctca gaaactgcta caccagctga 360acaccctgtt ggaacaggag
tccagatgtc agccaaaggg tctgtggcct gaaactgatt 420gagtctgcac atgataatgg
cctcaggatg actgcaagac tccgggactt tgaagtcaaa 480gatctactga gtctaactca
gttctttggc ttcgacacag aaacattttc ccttgctgtg 540aatttactgg acagattctt
gtctaaaatg aagggtacag gcgaagcatc tcggctgtgt 600cggactgagc tgcttttatt
tggctgtgaa atcgattgaa gaggaaagga acgtcccgct 660ggcaactgat ttgatccgga
taagtcagta taggttcaca gtttcagacc tgatgagaat 720ggaaaagatt gtgttggaga
aagtgtgctg gaaagtcaaa gctactactg ccttccaatt 780tctgcagctc tattactccc
tcattcggga gaccttgcca tttgaaagga gaaacgatct 840gaattttgaa agactagaag
cccaactgaa ggcgtgccac tgcaggatca tattttctaa 900agcaaaggcc ttctgtgctg
gcgctggcaa tcatcgcttt ggagatccaa gcactgaagt 960atgtggagtt aacagaagga
gtagaatgta ttcagaaaca ttccaaggta tgccaaggtg 1020atagcattga tcctattagc
aagctacaag agaaatgtat ccactgtact cctgaagtaa 1080aataaaatgc tgtgtattga
tttgaagctt a 111113104DNAArtificial
SequenceSynthetic polynucleotide 13gtatgccaag gtgatagcat tgatcctatt
agcaagctac aagagaaatg tatccactgt 60actcctgaag taaaataaaa tgctgtgtat
tgatctgaag ctta 10414203DNAArtificial
SequenceSynthetic polynucleotide 14ccttctgtgc tggcgctggc aatcatcgct
ttggagatcc aagcactgaa gtatgtggag 60ttaacagaag gagtagaatg tattcagaaa
cattccaagg tatgccaagg tgatagcatt 120gatcctatta gcaagctaca agagaaatgt
atccactgta ctcctgaagt aaaataaaat 180gctgtgtatt gatttgaagc tta
203151228DNARattus Norvegicus
15atcccgttgc gggtatagca gacggaaaag cgagctggaa gtgtagacac aactctcgcg
60agatgtagag cgaatccctg gagaggggcg gatgcgcaga ggtgcaccac gtgtggtgtt
120cctccagcgc agtcaggatc tcgtctagtt tgggtctagg ttagatttgg aatcgtggag
180atgcggaagg aaagcccacc ctccgctcgt gcccccggcg gcccgcgagt ggaacctgcc
240ccccaatgcg cccgcctgca tggaacggca gttggaagct gcacggtacc gctctgatgg
300ttcccttctg ctcggggctt ccagtctgag tggtcgctgc tgggcaggat ctctgtggtt
360tttcaaggat cctagtgcgg cccccaacga aggtttctgc tctgctggcg tccagacgga
420ggctggagta gctgacctca cttgggttgg ggacaaaggt atcttagtgg cttctgattc
480aggtgctgtt gaattgtggg agctagatga gaacgagaca cttattgtca gcaagttctg
540caagtatgag catgatgaca ttgtgtctac tgtcactgtc ctgagctccg gcacacaggc
600tgtcagtggt agcaaagact tctgcatcaa aatttgggac ctggctcagc agatgtcgct
660gaattcatac cgagctcatg cgggacaggt cacctgtgtt gctgcctctc cccacagaga
720aactgtgttt ctttcatgca gtgaggacag tagaattttg ctctgggata cccgctgtcc
780caagccggca tcacagatgg gctgcaatgc ctctggctac ctccctacct ccctggcttg
840gcatcctcag cagagtgaaa tctttgtctt tggtaaggca gcatgacgta tcgactctgg
900gaatggggcg gataccttgg agtacatgct cctgtcagca cacttgggca ctgcatggat
960tatgtcggtt ttacctagct ttggagacca tcattttttc ctaataggtt tgcttcattg
1020tttcagctcc tttattctgg gcatggttag aaatcagtga gctgcatagc aagtgcttgc
1080tgttagggaa ctatgttctg ctgtggtgtg actacacatg gcaagagttt gtagttaatt
1140aattcacagc cacatagtga ctgactgatt ctatatcaca aaggaaactg ttgtctacat
1200cttgagaaac taggattcat tcaaatct
122816224DNAArtificial SequenceSynthetic polynucleotide 16cttggagtac
atgctcctgt cagcacactt gggcactgca tggattatgt cggttttacc 60tagctttgga
gaccatcatt ttttcctaat aggtttgctt cattgtttca gctcctttat 120tctgggcatg
gttagaaatc agtgagctgc atagcaagtg cttgctgtta gggaactatg 180ttctgctgtg
gtgtgactac acatggcaag agtttgtagt taat
2241743DNAArtificial SequenceSynthetic polynucleotide 17gtaaggcagc
atgacgtatc gactctggga atggggcgga tac
431817DNAArtificial SequenceSynthetic polynucleotide 18gtaataactt tatccag
171988DNAArtificial
SequenceSynthetic polynucleotide 19taattcacag ccacatagtg actgactgat
tctatatcac aaaggaaact gttgtctaca 60tcttgagaaa ctaggattca ttcaaatc
88202510DNARattus Norvegicus
20atcccgttgc gggtatagca gacggaaaag cgagctggaa gtgtagacac aactctcgcg
60agatgtagag cgaatccctg gagaggggcg gatgcgcaga ggtgcaccac gtgtggtgtt
120cctccagcgc agtcaggatc tcgtctagtt tgggtctagg ttagatttgg aatcgtggag
180atgcggaagg aaagcccacc ctccgctcgt gcccccggcg gcccgcgagt ggaacctgcc
240ccccaatgcg cccgcctgca tggaacggca gttggaagct gcacggtacc gctctgatgg
300ttcccttctg ctcggggctt ccagtctgag tggtcgctgc tgggcaggat ctctgtggtt
360tttcaaggat cctagtgcgg cccccaacga aggtttctgc tctgctggcg tccagacgga
420ggctggagta gctgacctca cttgggttgg ggacaaaggt atcttagtgg cttctgattc
480aggtgctgtt gaattgtggg agctagatga gaacgagaca cttattgtca gcaagttctg
540caagtatgag catgatgaca ttgtgtctac tgtcactgtc ctgagctccg gcacacaggc
600tgtcagtggt agcaaagact tctgcatcaa aatttgggac ctggctcagc agatgtcgct
660gaattcatac cgagctcatg cgggacaggt cacctgtgtt gctgcctctc cccacagaga
720aactgtgttt ctttcatgca gtgaggacag tagaattttg ctctgggata cccgctgtcc
780caagccggca tcacagatgg gctgcaatgc ctctggctac ctccctacct ccctggcttg
840gcatcctcag cagagtgaaa tctttgtctt tggtgatgag aatggatctg tctcccttgt
900ggacaccaag aatgcaagct gcaccctcag ctcagctgtg cactcgcagt gtgtcactag
960actggtgttc tctccacaca ggtgttccct tcctggcctc tctcagtgaa gactgttcac
1020ttgctgtgct ggattcaagc ttttctgagg tggtttagaa gtcgagccca cagagacttt
1080gtgagagatg ctacatggtc tccactcaat cactcccttc ttaccacagt tggctgggac
1140catcaggtca tccaccatgt tgtgccgtta gagcctctcc cagcccctgg acctgacagt
1200gttgtggagt agaatggatt gcagaagaga aaagagcctt ctgtctgcaa gtgtcgactc
1260gcttgcccct gccttccatt tgtgagagag agagcacagg agccttgtag agcatgatta
1320ctccctagtc ccgtgcagta actagtcaga ttctcagcct gagggaggct gcatcccata
1380gtgacttgga ggaaaaagct tcctttataa atggatgtat gtgtgagtac acgtgtgagt
1440gcagtgtata gtttggagtg gagaaaatta tccttcagct ttcccaaagc aatgctcttt
1500acccccgaca aaatgaccag aggattttat gcttcccatg tctgggggct gactatgttg
1560ttagggatat ggagtgtggg tatccctgga tgcttgggaa tacttcacat tactcagagg
1620tgcgtaactt atttttatat agagtttaat tcactatatg ggaattactt cccatataca
1680aaagtctagc cagactacct tgagaagaca gaacagtttt gtacgaatgc ctgttaaatg
1740gaatcaaatc cactttctgg gtgaatcaat ttggcccttg gagttcgcgc tcgctcaccc
1800tgtgttcctt cttttgtgtt gtgtatgaga gatgagtgct ttcctgtcct agatttcaca
1860gttttaggga tgatggagta cttaaattaa aagtgtttca gtgaagcgag aagattgaca
1920tggattgtta cagagaaatc tgtcattgtc atttttccca cctaaaaatt ccctgaggac
1980tgatctgggt actttgctct ggagagctga agtctgagcg ctgtatattt ggactcctaa
2040gattgaagat ccggcatcag agaaactgtc aaaaatactg gaaggtgaaa taaagactta
2100tcctttcatc tttcctccaa agcttattta ttacctgctt tgcttaggtg agtcacctga
2160gtatcaatca gtcttaactg cccactgtct ttgtagtcta ctgttcggca ctccgttagc
2220aattatgggt cagtaactga tcttattaga gctttacaac tttggtttag gaaaagcaca
2280taaaatgggc gccctgaagg accatgagct tccattctac tcttgccagt caagagcctc
2340tcgtgatcac ccttgagtaa agcacttgaa tttgcagccg acttggaatt ttactaagtt
2400ccagggaagg cgtaagaggg aggtagaatc agtctctgct tctcaagaga taaagcttgt
2460attttgtgtt ccttagggaa ggacaaatta tccgtttaca cggcctgctt
251021171DNAArtificial SequenceSynthetic polynucleotide 21gcactccgtt
agcaattatg ggtcagtaac tgatcttatt agagctttac aactttggtt 60taggaaaagc
acataaaatg ggcgccctga aggaccatga gcttccattc tactcttgcc 120agtcaagagc
ctctcgtgat cacccttgag taaagcactt gaatttgcag c
1712213DNAArtificial SequenceSynthetic polynucleotide 22ctgtgtcagt cag
1323134DNAArtificial
SequenceSynthetic polynucleotide 23gacttggaat tttactaagt tccagggaag
gcgtaagagg gaggtagaat cagtctctgc 60ttctcaagag ataaagcttg tattttgtgt
tccttaggga aggacaaatt atccgtttac 120acggcctgct ttgg
134241168DNARattus Norvegicus
24tttcccgggg cctgggcgga gagggaggaa aacttcctgg ctgggactct ggcggtttct
60gcctgccaac cctccgatcc cgcctaccag cgttggctct tcccgacccc tcccccggcg
120cccccagtgt ccgccatggc caaagcctac gaccacctct tcaagttgct gctgatcggg
180gactcggggg tgggcaagac ttgtctcatc attcgctttg cagaggacaa cttcaacagc
240acttacatct ccaccatcgg aattgatttc aagatccgaa ctgtggaaat agaggggaag
300agaatcaaac tgcaagtctg ggacacagct ggccaagaac gattcaagac aataaccacc
360gcctattacc gtggagccat gggcattatc ctagtatatg acatcacaga tgagaaatcc
420ttcgagaata ttcagaactg gatgaaaagc atcaaagaga acgcgtctgc tggagtggag
480cgccttctgc tggggaacaa atgtgacatg gaagccaagc ggaaggtgca gagagagcag
540gctgagaggg tgagtcaggc cgggctgctg tggccgaatg ccttgcttct gccctttatc
600cagctctctc cttcctacct catcccctac agttggcccg agagcacaga atccgatttt
660ttgagacaag tgccaaatcc agtgtgaatg tggatgaggc tttcagttcc ctggcccgtg
720acatcttgct caagacagga ggccggagat cgggaaacag cagcaagccc tcaagcactg
780acctgaaagt atctgacaag aagaacagca acaagtgctc cttgggctga ggaacatttc
840ttgcctccta ttcaccctga acctggaggc tagacctgag ggaggtggac tgaggtagac
900tgatggaaaa cagaggggag gagctgtggt ggtgcctgga ggggtggatg acaggggagg
960aaggaaagat gaaatgggca gggaaaggag ggcgaggaac caaggacgtg aaaagtgaag
1020agaaggggtt tgagaagaga aaaagaagaa ggtctcaggt ctcggaccgt ccaacattaa
1080tgtcagtatg ctgatctctc cattcctggt tcagggttcg ggtcccgaga ggctggctcg
1140gccctactct gagggtctct cactccac
11682583DNAArtificial SequenceSynthetic polynucleotide 25gtgagtcagg
ccgggctgct gtggccgaat gccttgcttc tgccctttat ccagctctct 60ccttcctacc
tcatccccta cag
8326149DNAArtificial SequenceSynthetic polynucleotide 26gtgagtcagg
ccgggctgct gtggccgaat gccttgcttc tgccctttat ccagctctct 60ccttcctacc
tcatccccta cagttggctc gagagcacag aatccgattt tttgagacga 120gtgccaaatc
cagtgtgaat gtggatgag
149271356DNARattus Norvegicus 27gtgacgcgcc tgtgttgttt cgccattttg
ggaaggtcct acaggccgaa tgcaatccgg 60cgcccgttga ctgccatttt tagaaggtct
gtaaaggctc ctcgtgtcgc ggttgcgtag 120ccatggaatt gatttcaaga tccgaactgt
ggaaatagag gggaagagaa tcaaactgca 180agtctgggac acagctggcc aagaacgatt
caagacaata accaccgcct attaccgtgg 240agccatgggc attatcctag tatatgacat
cacagatgag aaatccttcg agaatattca 300gaactggatg aaaagcatca aagagaacgc
gtctgctgga gtggagcgcc ttctgctggg 360gaacaaatgt gacatggaag ccaagcggaa
ggtgcagaga gagcaggctg agaggttggc 420ccgagagcac agaatccgat tttttgagac
aagtgccaaa tccagtgtga atgtggatga 480ggctttcagt tccctggccc gtgacatctt
gctcaagaca ggaggccgga gatcgggaaa 540cagcagcaag ccctcaagca ctgacctgaa
agtatctgac aagaagaaca gcaacaagtg 600ctccttgggc tgaggaacat ttcttgcctc
ctattcaccc tgaacctgga ggctagacct 660gagggaggtg gactgaggta gactgatgga
aaacagaggg gaggagctgt ggtggtgcct 720ggaggggtgg atgacagggg aggaaggaaa
gatgaaatgg gcagggaaag gagggcgagg 780aaccaaggac gtgaaaagtg aagagaaggg
gtttgagaag agaaaaagaa gaaggtctca 840ggtctcggac cgtccaacat taatgtcagt
atgctgatct ctccattcct ggttcagggt 900tcgggtcccg agaggctggc tcggccctac
tctgagggtc tctcactcca cagatctttg 960ttagtattaa aggccactgt ttggcacgaa
tgttccattt gcattacttt cattattgtc 1020agaattgctc tttactcaaa tccaatttct
gtcatgccag gatattagtt ctcctgaatc 1080tggctgggtc ccccttcctt accccaactc
tttaactggt gatgaaaaca gcaaggagaa 1140agggcagcct gaagaatgga catccttttt
ccactatggg ttcctgagga caagagtggc 1200cggaaccatg cctttagcaa tagtaagcca
ggatgaagga tttgaaccaa gcttcaggaa 1260acagcagcac ttaatatggt ttacccaagg
agatgggaag catctttgat tctgctgtag 1320tcaaatggtg tttgatgggc actgttagct
gctttt 135628875DNAArtificial
SequenceSynthetic polynucleotide 28ggaaacagca gcaagccctc aagcactgac
ctgaaagtat ctgacaagaa gaacagcaac 60aagtgctcct tgggctgagg aacatttctt
gcctcctatt caccctgaac ctggaggcta 120gacctgaggg aggtggactg aggtagactg
atggaaaaca gaggggagga gctgtggtgg 180tgcctggagg ggtggatgac aggggaggaa
ggaaagatga aatgggcagg gaaaggaggg 240cgaggaacca aggacgtgaa aagtgaagag
aaggggtttg agaagagaaa aagaagaagg 300tctcaggtct cggacgtcca acattaatgt
cagtatgctg atctctccat tcctggttca 360gggttcgggt cccgagaggc tggctcggcc
ctactctgag ggtctctcac tccacagatc 420tttgttagta ttaaaggcca ctgtttggca
cgaatgttcc atttgcatta ctttcattat 480tgtcagaatt gctctttact caaatccaat
ttctgtcatg ccaggatatt agttctcctg 540aatctggctg ggtccccctt ccttacccca
actctttaac tggtgatgaa aacagcaagg 600agaaagggca gcctgaagaa tggacatcct
ttttccacta tgggttcctg aggacaagag 660tggccggaac catgccttta gcaatagtaa
gccaggatga aggatttgaa ccaagcttca 720ggaaacagca gcacttaata tggtttaccc
aaggagatgg gaagcatctt tgattctgct 780gtagtcaaat ggtgtttgat gggcactgtt
agctgctttt gttagaaaag aacattctca 840gtgttccacc aagaaacaca tgaacaaagt
aagag 87529125DNAArtificial
SequenceSynthetic polynucleotide 29gtgacgcgcc tgtgttgttt cgccattttg
ggaaggtcct acaggccgaa tgcaatccgg 60cgcccgttga ctgccatttt tagaaggtct
gtaaaggctc ctcgtgtcgc ggttgcgtag 120ccatg
12530407DNARattus Norvegicus
30tgggggtggg ggaatctagc ctctctagag ccctagccct ctgacgagga ggaggtgtag
60tgccctgtag cttttcccca ggactcgcca catgtccctt tgtctgggga atgatgccct
120caccctctgc atctggcctg acatctgttc tctctgcaga atttctatca ctccaagcgc
180cgattggtct tctgcaagag aaagccctga agtgcccacg ggaggctcgc cttcttctgc
240tgtgggtcag gaggcctctt ccccatcttc tgccttagcc ttcattcagt gtgtcttaat
300tattatttgt gttttaattt aaacttctcc tgtatatact ctgcctgccc cctcccagcc
360tccaaactta gttatttaaa aaacaaaaca aaacaatgaa attagta
40731159DNAArtificial SequenceSynthetic polynucleotide 31tgggggtggg
ggaatctagc ctctctagag ccctagccct ctgacgagga ggaggtgtag 60tgccctgtag
cttttcccca ggactcgcca catgtccctt tgtctgggga atgatgccct 120caccctctgc
atctggcctg acatctgttc tctctgcag
15932897DNARattus Norvegicus 32tcagtacata aaatgatata ggacattaaa
acatttatgt atatcgtaca ttaaattatt 60ttccccaagc atataagcat gtaatatata
tctaatgatt taggacatac atttaaactc 120aactataaat tcataacaac atgtctattc
tcaaatacat taagataatg cttgttagac 180atatctgtgt tattagacat gcaccattaa
gtcataaacc tttctcttcc atatgactat 240ccctgtcccc aattggtctc tatttctacc
atcctccgtg aaatcaacaa cccgcccact 300cgtccccctc ttctcgctcc gggcccattc
gtcctggggg tgactatact gaaactttac 360caggcatctg gttcttactt cagggccatc
aattggttca tcgtccatac gttcccctta 420aataagacat ctcgatggta acgggtctaa
tcagcccatg atcaacataa ctgtggtgat 480atacatttgg tattttttaa ttttcggatg
ccttcctcaa catagccgtc aaggcatgaa 540ggtcagcaca aagtcctgtg gaacctttta
gttaagggtc atttatcctc atagacaaag 600ctcgaaagac tattttattc atgtttgtaa
gacataaata tttataaata ctgaaaaatc 660tgtcaacaaa cccccccacc ccctacacct
gaaacttcaa tgccaaaccc caaaaacatt 720aaagcaagaa ttaaataaaa caaaaagcta
cttaattctt aaaaggcttc tccattctag 780tagaccacaa aattttaact taaatcttag
cattggtaaa atttcccgac acaaaatctt 840tccttctaac taaaccctct ttacttgcct
accctcagaa aattccacat acaccaa 89733897DNAArtificial
SequenceSynthetic polynucleotide 33tcagtacata aaatgatata ggacattaaa
acatttatgt atatcgtaca ttaaattatt 60ttccccaagc atataagcat gtaatatata
tctaatgatt taggacatac atttaaactc 120aactataaat tcataacaac atgtctattc
tcaaatacat taagataatg cttgttagac 180atatctgtgt tattagacat gcaccattaa
gtcataaacc tttctcttcc atatgactat 240ccctgtcccc aattggtctc tatttctacc
atcctccgtg aaatcaacaa cccgcccact 300cgtccccctc ttctcgctcc gggcccattc
gtcctggggg tgactatact gaaactttac 360caggcatctg gttcttactt cagggccatc
aattggttca tcgtccatac gttcccctta 420aataagacat ctcgatggta acgggtctaa
tcagcccatg atcaacataa ctgtggtgat 480atacatttgg tattttttaa ttttcggatg
ccttcctcaa catagccgtc aaggcatgaa 540ggtcagcaca aagtcctgtg gaacctttta
gttaagggtc atttatcctc atagacaaag 600ctcgaaagac tattttattc atgtttgtaa
gacataaata tttataaata ctgaaaaatc 660tgtcaacaaa cccccccacc ccctacacct
gaaacttcaa tgccaaaccc caaaaacatt 720aaagcaagaa ttaaataaaa caaaaagcta
cttaattctt aaaaggcttc tccattctag 780tagaccacaa aattttaact taaatcttag
cattggtaaa atttcccgac acaaaatctt 840tccttctaac taaaccctct ttacttgcct
accctcagaa aattccacat acaccaa 89734481DNARattus Norvegicus
34tcatctatct tatataagat aatgtctgat ctaaatatga gaccctgtga ggttggccat
60aagcacactg ttagctcctt ccgtcagacc tttttggggc tggctggtga aacagaatga
120atcctgttgg gtctgcttct cacagcgtat ggggctgtgt gcttttactc atggtggcag
180cagcagttgt tgtcacttct ttggccaggc acagtgggtg atccttacag agcagcacag
240attcccattg attccagtct atgtatttac ttgtggttgg tacagaattt aatgcagata
300gagtctttaa atatgtgaag atatgcagca ctgattttaa acttaaactg gcatgatact
360ttccatatgt ctagacacac tggtaaattt ttgttacata ttgttttcaa attttccgtt
420agtcttgttt ctatgagata cttttattgt gacttaaaat tcttagaaat taaagttctg
480a
48135481DNAArtificial SequenceSynthetic polynucleotide 35tcatctatct
tatataagat aatgtctgat ctaaatatga gaccctgtga ggttggccat 60aagcacactg
ttagctcctt ccgtcagacc tttttggggc tggctggtga aacagaatga 120atcctgttgg
gtctgcttct cacagcgtat ggggctgtgt gcttttactc atggtggcag 180cagcagttgt
tgtcacttct ttggccaggc acagtgggtg atccttacag agcagcacag 240attcccattg
attccagtct atgtatttac ttgtggttgg tacagaattt aatgcagata 300gagtctttaa
atatgtgaag atatgcagca ctgattttaa acttaaactg gcatgatact 360ttccatatgt
ctagacacac tggtaaattt ttgttacata ttgttttcaa attttccgtt 420agtcttgttt
ctatgagata cttttattgt gacttaaaat tcttagaaat taaagttctg 480a
481361233DNARattus Norvegicus 36aagttcagtg aaatcttgaa taccaaacat
ctgacatacc tcacaaattc aggaaagcaa 60ggatggacct tcacaagtga tgcaagttta
atcggataag ttccaaacga gttttaggtc 120tttagtattg taaataatca ttctgttttt
ctacttacct gtttttatca agatacattt 180ccatgtggag tgacttcaaa atgcttgatt
tcatagagcc actaggtggc atctttgtaa 240aagtggaagc acatgaaaag aaatagccta
ggagtaaatg caagatagca aggtagatga 300gtcgttttga acaagaccta agcaagtgca
cagatttagg atgaaaagtt aaattaaaag 360ctttaacact ttttattttg tgattaatac
tatttttcta ttgctatttt cattcagggg 420acattgacat ttatgtagcc aaacatgttt
atgtatttgt gagagagaaa gtgtgtgtgt 480gcgtgcgcgc gtgttcgtgc acttgctttt
gctatgttag taacctatgc agatagacca 540cctaagtaca ttctgtgtaa ggctttttaa
aattgagcat agaaagcaga gttcatagta 600cattatcaat aagttattaa gatatcacgc
tagacttaac agtggaaaga acatgaattt 660ttctgctgcc tctattccta accctggtgt
tttcattctg tccctaacag gaggctaatg 720aatgataaag ctttgaaggt gaaggggtgg
gaaagtgatg ttagtgaaga gatgagagtg 780gctttgtagc aacagggtat aaaaaagaca
acgacgatta taatgaggga gatggatttt 840acaacacgtt tttaatttca ctaaacttta
catgccaaag gatgttaaat atagcacgta 900ataagtgttt aaaatctggg ctcttgattc
agaccgagtt ttaatactgg atctcattca 960atctttgtgt tttttctttt tcttttcttt
tttttccaat agtacggcag tgctaatagc 1020agtcctttag tagagttact gcattgacta
ttggaaatac agataagttg ctgtgcttag 1080tgataaaact tactaaacat ttgctgtttt
ttgtgagata accacatgaa atttgttcag 1140ggaacatatt tgatctgttc tccaaaatgt
cttaagacta aagaatttga tgaaagaaaa 1200ataaaagctt tgcttctcct gacttagaaa
gca 1233371437DNAArtificial
SequenceSynthetic polynucleotide 37aagttcagtg aaatcttgaa taccaaacat
ctgacatacc tcacaaattc aggaaagcaa 60ggatggacct tcacaagtga tgcaagttta
atcggataag ttccaaacga gttttaggtc 120tttagtattg taaataatca ttctgttttt
ctacttacct gtttttatca agatacattt 180ccatgtggag tgacttcaaa atgcttgatt
tcatagagcc actaggtggc atctttgtaa 240aagtggaagc acatgaaaag aaatagccta
ggagtaaatg caagatagca aggtagatga 300gtcgttttga acaagaccta agcaagtgca
cagatttagg atgaaaagtt aaattaaaag 360ctttaacact ttttattttg tgattaatac
tatttttcta ttgctatttt cattcagggg 420acattgacat ttatgtagcc aaacatgttt
atgtatttgt gagagagaaa gtgtgtgtgt 480gcgtgcgcgc gtgttcgtgc acttgctttt
gctatgttag taacctatgc agatagacca 540cctaagtaca ttctgtgtaa ggctttttaa
aattgagcat agaaagcaga gttcatagta 600cattatcaat aagttattaa gatatcacgc
tagacttaac agtggaaaga acatgaattt 660ttctgctgcc tctattccta accctggtgt
tttcattctg tccctaacag gaggctaatg 720aatgataaag ctttgaaggt gaaggggtgg
gaaagtgatg ttagtgaaga gatgagagtg 780gctttgtagc aacagggtat aaaaaagaca
acgacgatta taatgaggga gatggatttt 840acaacacgtt tttaatttca ctaaacttta
catgccaaag gatgttaaat atagcacgta 900ataagtgttt aaaatctggg ctcttgattc
agaccgagtt ttaatactgg atctcattca 960atctttgtgt tttttctttt tcttttcttt
tttttccaat agtacggcag tgctaatagc 1020agtcctttag tagagttact gcattgacta
ttggaaatac agataagttg ctgtgcttag 1080tgataaaact tactaaacat ttgctgtttt
ttgtgagata accacatgaa atttgttcag 1140ggaacatatt tgatctgttc tccaaaatgt
cttaagacta aagaatttga tgaaagaaaa 1200ataaaagctt tgcttctcct gacttagaaa
gcagggtatt tgagagttct tcctgttctt 1260tctgggtgcc aggaagctaa agcacaaaag
caagtagata tacaacagtt gtaaacttgt 1320gttcttttat aatccctgtc tctcggtgtt
catatttgca tttttaaaga tgataacctg 1380tgagcttaga ctgcttacag gactgccttt
ccaaaagtgt gagagagctc ccagaga 143738627DNARattus Norvegicus
38gttataataa gtatcctggg tatctaatcc attagtgaca tttcataggc aaccgcatgg
60acccacatgg gagtgtgaat agaacaggat cccagaggaa cagttccagt aacagagccc
120acatctgttg ctagctcctt agtttagtat ggacggatgg taaagaccaa agtctatagc
180acggaaaaga ttaataaatg agtaataaat gggtgttaat aaatgataat ttttgtggta
240gttatgaagg atagttttag ctaatttaaa gagagtgtta gcttgtgttg gggagaggcc
300acagtagagg ctgcacttgc cactgctgtg tagcggcact ctcctgactc acttaaaaat
360tctctggagg tttaagtgag gacccagttc catctctaga tatccaggct ccctagaaca
420tttccagttg attccaacat gcatttggtg ttaaagacca ctgcagtgtc atttgcacat
480agacccaaga catggagtta ggttttgttt tttggggttt ttttttgcaa ttctaatgta
540taatatcaat caatattctt ttgtgtgata ccacatttgg actattgtcc cttcagctga
600taactgacat taaagaaata cagttga
62739627DNAArtificial SequenceSynthetic polynucleotide 39gttataataa
gtatcctggg tatctaatcc attagtgaca tttcataggc aaccgcatgg 60acccacatgg
gagtgtgaat agaacaggat cccagaggaa cagttccagt aacagagccc 120acatctgttg
ctagctcctt agtttagtat ggacggatgg taaagaccaa agtctatagc 180acggaaaaga
ttaataaatg agtaataaat gggtgttaat aaatgataat ttttgtggta 240gttatgaagg
atagttttag ctaatttaaa gagagtgtta gcttgtgttg gggagaggcc 300acagtagagg
ctgcacttgc cactgctgtg tagcggcact ctcctgactc acttaaaaat 360tctctggagg
tttaagtgag gacccagttc catctctaga tatccaggct ccctagaaca 420tttccagttg
attccaacat gcatttggtg ttaaagacca ctgcagtgtc atttgcacat 480agacccaaga
catggagtta ggttttgttt tttggggttt ttttttgcaa ttctaatgta 540taatatcaat
caatattctt ttgtgtgata ccacatttgg actattgtcc cttcagctga 600taactgacat
taaagaaata cagttga
627401654DNARattus Norvegicus 40gcctacattg ctgcggccac cagacggacc
aggggccacc agtgccagcc ctgtggcctg 60tctactggac tctggtcacc aggctcagct
tgttgagttc ctcattgtgc actatgagca 120gatcttcggg atggatgagc tccctctgac
ctctgagccc ctgactcaag accctgcctt 180ggctcctgca ctcctcgaat ccagtcccca
gcacccagcc ttactcgttg cccaagactc 240acagcccctg accatagcct cagattccag
cccagacccc aaacaacaca gtgccttgga 300gaagtgtccc aaggtcgcgc ctcctgagct
tacggctctg cagagtaacc gaaaggagga 360ggaggaggaa gacaccagag atggggcggg
ggatgggtcc agccactccc ccgaggactt 420gctcctggta gcacaatccc ggggccactt
cagccgccag ccagtgaagt attcccgggg 480aggtgtgcga ccagttactc atcagctctc
cagcctggct ctggtggcct ccaagctgtg 540tgaggagact cctatcactg tctcagcagt
gcaccgaggt agtttgaggg cacgaggcct 600gggccctgct gctgcctccc ctgaaggcgg
caccctgcgc cggaaccctc tgcccaagca 660ctttgagatc acccaggaga cagcccggct
actctccaag ctggacagtg aggctgtgtc 720cagaacctcc tgttgtgctg acccagagcc
ggaggagtct gaggagcacc tctgaccacc 780caccatcctg agggacctag gactgaattg
atggtcctat atgtctccct acctgaccca 840acctggtgac caaaccaatt ccatggggtg
tggggagaga tggggttacc gagagttcag 900gtaatgaaga ttacatgcct atgggagtcc
tgaaacactt ggttgaagtg tccctccctg 960ccagaggaga tttaaacaag caaggcaaca
caggcaattg gggtcaagac tcaatggtca 1020attcaggtca gtagatcctt caggtctacc
tcagtctctg acctcgagac aggcgtctga 1080ctgtttcagt cataatggct tctggtcctg
ctaccacttg cctccttggc agactccaat 1140tcagccctgt cacctttatt tactccttcc
ttttgtttgt ttgtttgttt gtttgttttg 1200agccaaggtc tttctgtagc tctggctggt
ctggagctcc ctttgcaaac cacaaatcct 1260ctgtctccca agtgctggcc aaatctgtgt
tcttacaacc tccaaataaa accctcttcc 1320tgcagccggc aggacggccg agcacaatgg
tgcttgctgt acagcctcat agaccttcct 1380tggatctccc agacacactt agtggaagga
gagaatccat tcttgcaaat tgtctgacct 1440atgcacatgc acacaaaaaa ataaattttt
aattaaaaaa atctgctggg tagtggtgcc 1500acacaccttt atttaaacct aacactcagg
aggtagaggc aggaggatct cttgagtttg 1560attccagaca ggtctacaga ttaagttcca
ggacagccag ggctacacag agacacccta 1620tcttgggaag caaaataaag taagataaat
cttg 1654411259DNAArtificial
SequenceSynthetic polynucleotide 41ggtccagcca ctcccccgag gacttgctcc
tggtagcaca atcccggggc cacttcagcc 60gccagccagt gaagtattcc cggggaggtg
tgcgaccagt tactcatcag ctctccagcc 120tggctctggt ggcctccaag ctgtgtgagg
agactcctat cactgtctca gcagtgcacc 180gaggtagttt gagggcacga ggcctgggcc
ctgctgctgc ctcccctgaa ggcggcaccc 240tgcgccggaa ccctctgccc aagcactttg
agatcaccca ggagacagcc cggctactct 300ccaagctgga cagtgaggct gtgtccagaa
cctcctgttg tgctgaccca gagccggagg 360agtctgagga gcacctctga ccacccacca
tcctgaggga cctaggactg aattgatggt 420cctatatgtc tccctacctg acccaacctg
gtgaccaaac caattccatg gggtgtgggg 480agagatgggg ttaccgagag ttcaggtaat
gaagattaca tgcctatggg agtcctgaaa 540cacttggttg aagtgtccct ccctgccaga
ggagatttaa acaagcaagg caacacaggc 600aattggggtc aagactcaat ggtcaattca
ggtcagtaga tccttcaggt ctacctcagt 660ctctgacctc gagacaggcg tctgactgtt
tcagtcataa tggcttctgg tcctgctacc 720acttgcctcc ttggcagact ccaattcagc
cctgtcacct ttatttactc cttccttttg 780tttgtttgtt tgtttgtttg ttttgagcca
aggtctttct gtagctctgg ctggtctgga 840gctccctttg caaaccacaa atcctctgtc
tcccaagtgc tggccaaatc tgtgttctta 900caacctccaa ataaaaccct cttcctgcag
ccggcaggac ggccgagcac aatggtgctt 960gctgtacagc ctcatagacc ttccttggat
ctcccagaca cacttagtgg aaggagagaa 1020tccattcttg caaattgtct gacctatgca
catgcacaca aaaaaataaa tttttaatta 1080aaaaaatctg ctgggtagtg gtgccacaca
cctttattta aacctaacac tcaggaggta 1140gaggcaggag gatctcttga gtttgattcc
agacaggtct acagattaag ttccaggaca 1200gccagggcta cacagagaca ccctatcttg
ggaagcaaaa taaagtaaga taaatcttg 1259422221DNARattus Norvegicus
42gcgaccggca gggtgcccgc ccgacttccc agctgccccg tgcggcccgg gcatgcccag
60tgtgggcgca gccccggctc tccgagcgcc ggggcggagc gggcagccgg gcgcggagca
120ggcgaaccga acctcggtgg gcgagcgccg gggctggagc cgcgggggtc ggtggcggga
180gctggggacc gaacccaggg ccttgcgctt cttaggcctt ccatgatgag tgatttgggg
240gcacttccct ctctctgtaa ttgatagtct gggcagtgaa gagatggctg acagtgtcaa
300aacctttctg caggaccttg gcaggggaat caaagactcc atctggggca tctgtaccat
360ctcaaagcta gatgctcgga tccagcagaa gagagaggag cagcgtcgaa ggagggcaag
420tagcctcttg gcccagagga gagcccagag tgtagagcgg aagcaagaga gtgagccacg
480tattgttagt agaattttcc agtgctgtgc ttggaatggt ggagtattct ggttcagtct
540cctcttgttt taccgagtgt ttattcctgt gcttcaatca gtaacagccc gggttattgg
600tgatccgtca ctacatggag atgtttggtc atggctggaa ttcttcctca catcaatttt
660cagtgctctt tgggtgctgc ccctgtttgt gcttagcaaa gttgtgaatg ccatttggtt
720ccaagatata gctgacttgg catttgaggt atcagggagg aaacctcatc cattccccag
780tgtcagcaaa ataattgctg acatgctctt caaccttttg ctacaggcac ttttccttat
840tcaggggatg tttgtgagtc tcttccccat ccatcttgtg ggtcagctgg ttagtttgct
900gcatatgtct cttctctact cactctactg ctttgagtac cgttggttca acaaaggaat
960tgaaatgcac cagcgattgt caaacataga aaggaactgg ccttactact ttgggtttgg
1020cttgcccttg gctttcctca cagcaatgca atcctcctac attatcagtg gctgcctctt
1080ttctatcctg tttcctttat tcatcatcag cgccaatgaa gcaaagactc ctggaaaagc
1140atatcttttc cagttgcgcc tcttctcctt ggtggtcttt ttaagcaaca gacttttcca
1200caagacggtc tacctacagt cggccctgag cagctcatcc tccgcagaga aattcccttc
1260gccacatcct tctcctgcca aactgaaagc tgctgcaggc cactgagtcc tgctgtcaaa
1320ggggacgggt gggactgggt ggaggatgtg gcagctcttt tcttggtttt cctcccctgc
1380tgtggaaggc aggacccact gccaaggggc ctctgcatat tcctttgtct ttgaattgga
1440atcttcctga ctccggtatg tggattttta ccaccaccct aggtctggaa ggaccagttt
1500tccagctgtt ttttagcttt tgccagctcc tgtgcctgga ctgatttgag tactcccccc
1560tcccttgtgt catttacctt cccacctcct cctgcctccc agcacccctg ggtgaatggg
1620ctttgtaatt ttaactgttg tattttgtga atttgttgtt actgtttcct gtgaagcaca
1680taccttgtat gtgggaggta aaggagcacg ccagctgctc catgtcactc cctctatagc
1740catcactgtc ttgttttttt gtaactcagg ttaggttttg gtctttactg ctctgctgca
1800gaaaaggaaa ggaatggggg aaaggagcct aagagatggg acagatagac ctcagccaaa
1860ctggttgggt tttgaggagt catgttcttt gttccccttg aaggggaaac aggttttttc
1920actggtacat ttaaagttcc ccagctatgg gaaggtacca gttctggaca agtgccactg
1980catcatagca actctgaaga tgaaacttac tgttggccac tgccaggtca gactcgtgtt
2040ttaaggaata ctgggtgctt catataggaa ctgaaggggt aaacttacta aaccattcaa
2100cctgtgattg gtgatgtttt tctgtcattt taagagtcga cacatggggt gggagggcag
2160atgtaaaaaa acttgtacaa ttttaaaatc acaattaaac gtgagctggt ttcccataaa
2220a
2221431078DNAArtificial SequenceSynthetic polynucleotide 43tcttttccag
ttgcgcctct tctccttggt ggtcttttta agcaacagac ttttccacaa 60gacggtctac
ctacagtcgg ccctgagcag ctcatcctcc gcagagaaat tcccttcgcc 120acatccttct
cctgccaaac tgaaagctgc tgcaggccac tgagtcctgc tgtcaaaggg 180gacgggtggg
actgggtgga ggatgtggca gctcttttct tggttttcct cccctgctgt 240ggaaggcagg
acccactgcc aaggggcctc tgcatattcc tttgtctttg aattggaatc 300ttcctgactc
cggtatgtgg atttttacca ccaccctagg tctggaagga ccagttttcc 360agctgttttt
tagcttttgc cagctcctgt gcctggactg atttgagtac tcccccctcc 420cttgtgtcat
ttaccttccc acctcctcct gcctcccagc acccctgggt gaatgggctt 480tgtaatttta
actgttgtat tttgtgaatt tgttgttact gtttcctgtg aagcacatac 540cttgtatgtg
ggaggtaaag gagcacgcca gctgctccat gtcactccct ctatagccat 600cactgtcttg
tttttttgta actcaggtta ggttttggtc tttactgctc tgctgcagaa 660aaggaaagga
atgggggaaa ggagcctaag agatgggaca gatagacctc agccaaactg 720gttgggtttt
gaggagtcat gttctttgtt ccccttgaag gggaaacagg ttttttcact 780ggtacattta
aagttcccca gctatgggaa ggtaccagtt ctggacaagt gccactgcat 840catagcaact
ctgaagatga aacttactgt tggccactgc caggtcagac tcgtgtttta 900aggaatactg
ggtgcttcat ataggaactg aaggggtaaa cttactaaac cattcaacct 960gtgattggtg
atgtttttct gtcattttaa gagtcgacac atggggtggg agggcagatg 1020taaaaaaact
tgtacaattt taaaatcaca attaaacgtg agctggtttc ccataaaa
107844966DNARattus Norvegicus 44agaccgttct tgcctctgaa ccggcaatca
tggctccggg ttggccgcgg cctctgccgc 60agctcctcgt gttgggattc gggttggtgt
tgatacgcgc cacggccggg gagcaagcac 120caggcaacgc cccatgctca agcggcagct
cctggagcgc ggacctcgac aagtgcatgg 180actgcgcttc ttgtccagcg cgaccacaca
gcgacttctg cctgggatgc gcagcagcac 240ctcctgccca cttcaggatg ctatggccca
ttctgggagg cgctcttagt ctggccctgg 300ttttggcgct ggtttctggt ttcctggtct
ggagacgatg ccgccggaga gaaaagttta 360ctacccccat agaggagact ggtggagaag
gctgcccagg tgtggcactg atccagtgag 420gagcacccgc gctggtgccc attcatcgtc
cattcattca ttctggagcc agcctggctt 480tccagagaca agccgcgcca gactcttcca
accacaaggg ggtggggcga ggtggtgatt 540cacctccaag gactgggctt agggttcagg
ggagccttcc agggtgtcta attgccctgt 600ctctggttct ggggcagaca gagagcctca
agctaggtca caaagcgact catactaagg 660atctgcagca tttgcacaag ggaatctctt
gctccccaca agtcctggag gcctggccga 720cttgaggggc agacacaaca ctgggttcca
cccactcgga tggactgaaa tgccactacc 780ctgagtttta gccctgggag tgggttagat
tgagggacct gttcataaca ctaagggggc 840tggccctctg ggagggctgg tcccagtaca
cacaaacaca acccatcccc caagggggtg 900atatttattt tggggataaa gtttggaggg
gagggagact tattaataaa agaatcttta 960acttta
96645603DNAArtificial SequenceSynthetic
polynucleotide 45cccccataga ggagactggt ggagaaggct gcccaggtgt ggcactgatc
cagtgaggag 60cacccgcgct ggtgcccatt catcgtccat tcattcattc tggagccagc
ctggctttcc 120agagacaagc cgcgccagac tcttccaacc acaagggggt ggggcgaggt
ggtgattcac 180ctccaaggac tgggcttagg gttcagggga gccttccagg gtgtctaatt
gccctgtctc 240tggttctggg gcagacagag agcctcaagc taggtcacaa agcgactcat
actaaggatc 300tgcagcattt gcacaaggga atctcttgct ccccacaagt cctggaggcc
tggccgactt 360gaggggcaga cacaacactg ggttccaccc actcggatgg actgaaatgc
cactaccctg 420agttttagcc ctgggagtgg gttagattga gggacctgtt cataacacta
agggggctgg 480ccctctggga gggctggtcc cagtacacac aaacacaacc catcccccaa
gggggtgata 540tttattttgg ggataaagtt tggaggggag ggagacttat taataaaaga
atctttaact 600tta
60346443DNARattus Norvegicus 46aagcactgtt agtttgctgg
tctgtctcct ctgtgctctt gtctgtgtct gtgtcctcga 60tcctgactca agcaatcccg
ctctgttttg ctgactcctg agcagacata gcttgtgggc 120caggaccttg ccagccttga
gtggcagtgg cttcagaagt gaaatgatct ggctgtctgc 180attcgaatga ctccccagtc
ccagcctagc ctctcttttg cactgctggt tcagcccact 240gggcctccgt cctttcctct
ggaagggact tggccttggg tgacaaattc ctctttgatg 300aatgtaccct gtgggaatgt
ttcatactga cagattattt ttatttattc aatgtcgtat 360ttaagatatt tattttttat
actgaaggag cacccttttt ttaagagaaa taaatgaaat 420aataaagaac ccattcttgt
cga 44347443DNAArtificial
SequenceSynthetic polynucleotide 47aagcactgtt agtttgctgg tctgtctcct
ctgtgctctt gtctgtgtct gtgtcctcga 60tcctgactca agcaatcccg ctctgttttg
ctgactcctg agcagacata gcttgtgggc 120caggaccttg ccagccttga gtggcagtgg
cttcagaagt gaaatgatct ggctgtctgc 180attcgaatga ctccccagtc ccagcctagc
ctctcttttg cactgctggt tcagcccact 240gggcctccgt cctttcctct ggaagggact
tggccttggg tgacaaattc ctctttgatg 300aatgtaccct gtgggaatgt ttcatactga
cagattattt ttatttattc aatgtcgtat 360ttaagatatt tattttttat actgaaggag
cacccttttt ttaagagaaa taaatgaaat 420aataaagaac ccattcttgt cga
44348808DNARattus Norvegicus
48cagaagagaa cccagggcac tgggacagga cttcctgagg gtctgaggag catggcagac
60agcccagagg tggtagccat ggactgtgag atggtggggc tcgggcctca aagggtgagt
120ggcctcgccc gctgcagcat tgtgaacgtc cacagcgcag tcctctatga caagtacatc
180cagcctgagg gagagatcac ggactacaga acccaagtca gcgggatcac gcctcagcac
240atggcgaggg ccacgccatt tgctgaagcc aggctagaga tcctgcagct tctgaaaggc
300aagctggtgg tgggccatga cctgaagcat gacttcagtg ccctgaagga ggacatgaga
360aaatacacca tctacgacac gtccacagac atgctgctgt ggcacgaggc caagctgcac
420tgctacagcc gtgtgtccct gaggctgctg tgcaagcgcc tgctgcacaa gagcatccag
480aacaactggc ggggccactg ctctgtagaa gatgccaggg ccacaatgga gctctacaaa
540atctctcagc gactcagagc ccagcgaggg ctgccctgcc tgggaacatc agcctgaact
600tcatcctcat ccaggatcag aagcagctac tccttgaagg accatagttt tccatgaatg
660agacctgttt ctagctacaa caacaacagc aacaaccaca aaatgcaaaa gcaagaacac
720tccgccatta cagcaattct cttgctttgg agcaaagaaa aaaaaaacca aactttagta
780ataaatgact ttgattttgt ctaatcaa
80849328DNAArtificial SequenceSynthetic polynucleotide 49aacaactggc
ggggccactg ctctgtagaa gatgccaggg ccacaatgga gctctacaaa 60atctctcagc
gactcagagc ccagcgaggg ctgccctgcc tgggaacatc agcctgaact 120tcatcctcat
ccaggatcag aagcagctac tccttgaagg accatagttt tccatgaatg 180agacctgttt
ctagctacaa caacaacagc aacaaccaca aaatgcaaaa gcaagaacac 240tccgccatta
cagcaattct cttgctttgg agcaaagaaa aaaaaaacca aactttagta 300ataaatgact
ttgattttgt ctaatcaa
328501491DNARattus Norvegicus 50gcaaagtcac actcaggaca caagcgacat
ggccctgcgc gcgctccatg cccagcctac 60aggcggtcct cagctgaggt tcctgctgtt
cctgctgctc ttgctgcttc tgctgtcatg 120gccatctcag ggggacgccc tggcattgcc
tgagcagcga cgctccctct ctgagtccca 180actcaacccg gacgagctac ggggtcgctt
ccaggacctg ctgagccgac tgcatgccaa 240ccagagccgg gaggactcga actcagaacc
aacccctgac ccagctgtcc ggatactcag 300tccagaggtg cgattggggt cccacggccg
gctgctgctc cgcgtcaacc gggcgtcgct 360gactcagggt ctccccgaag cctaccgcgt
gcaccgagcg ctgctcctgc tgacgccttc 420gtccaggccc tgggacatca ccaggcccct
gcaacgtgcg atcagcctcc agggacccca 480cgctcgcgca ctgcgcttgc gcctggcgcc
gcctcccgac ctagccgtgc tgccctctgg 540cggcgcgcgc ctggaactgc acttacgatc
ggccgccggc agggggcgcc gaagcgcgca 600tttgcaccca agagactcgt gcccgctggg
tcccgggcgc tgctgtcacc tggagactgt 660gcaggcaact ctcgaggacc taggttggag
cgactgggta ctgtccccgc gtcagctgca 720actgagcatg tgcgtgggcg agtgccccca
cctctaccgg tcggccaaca cgcatgcgca 780gatcaaagca cgcctgcatg gcctgcagcc
cgacagagtg ccggccccgt gctgtgtccc 840ctccagctac accccggtgg ttcttatgca
caggacagac agcggcgtgt cactgcagac 900ttatgatgat ctggtagccc agggctgcca
ctgcgcttga gcactgggcc ctgctcctta 960cctacactcc ccttccatga tgctatttat
atttttattt aataatatta ttaatttatt 1020ggggttgggc tgggtgggtg gattgtgtat
ttatttaaaa ctctgctaat aaaggtgagc 1080ttggtttcta tgcggcgtct cagtgatctc
ggcatgattc ccatcaccct agcctcagtt 1140tcccttgtca cctgagaagt ggagcagagg
acgggcctcc attaggctgg cctggggtga 1200ttttattgac tgacagctga tgtgagtgac
cagccagggc ctggtggtcc tgccatgttt 1260gagccgcaag gaggagcagg acagtcagca
gttcattgct gcagcctctg cttcagcgcc 1320cttctaggtt ccctctggac attcctccca
tccccatttc aagccaggcc taacatccca 1380gaatcagggg gcctctgcaa tccagatagt
ccgacaacgg ctggctggga atgaaaagtg 1440taagaagcca gtggctgctc agtcaacaag
actgggtgtc tcggctgctc t 1491511183DNAArtificial
SequenceSynthetic polynucleotide 51tgcgattggg gtcccacggc cggctgctgc
tccgcgtcaa ccgggcgtcg ctgactcagg 60gtctccccga agcctaccgc gtgcaccgag
cgctgctcct gctgacgcct tcgtccaggc 120cctgggacat caccaggccc ctgcaacgtg
cgatcagcct ccagggaccc cacgctcgcg 180cactgcgctt gcgcctggcg ccgcctcccg
acctagccgt gctgccctct ggcggcgcgc 240gcctggaact gcacttacga tcggccgccg
gcagggggcg ccgaagcgcg catttgcacc 300caagagactc gtgcccgctg ggtcccgggc
gctgctgtca cctggagact gtgcaggcaa 360ctctcgagga cctaggttgg agcgactggg
tactgtcccc gcgtcagctg caactgagca 420tgtgcgtggg cgagtgcccc cacctctacc
ggtcggccaa cacgcatgcg cagatcaaag 480cacgcctgca tggcctgcag cccgacagag
tgccggcccc gtgctgtgtc ccctccagct 540acaccccggt ggttcttatg cacaggacag
acagcggcgt gtcactgcag acttatgatg 600atctggtagc ccagggctgc cactgcgctt
gagcactggg ccctgctcct tacctacact 660ccccttccat gatgctattt atatttttat
ttaataatat tattaattta ttggggttgg 720gctgggtggg tggattgtgt atttatttaa
aactctgcta ataaaggtga gcttggtttc 780tatgcggcgt ctcagtgatc tcggcatgat
tcccatcacc ctagcctcag tttcccttgt 840cacctgagaa gtggagcaga ggacgggcct
ccattaggct ggcctggggt gattttattg 900actgacagct gatgtgagtg accagccagg
gcctggtggt cctgccatgt ttgagccgca 960aggaggagca ggacagtcag cagttcattg
ctgcagcctc tgcttcagcg cccttctagg 1020ttccctctgg acattcctcc catccccatt
tcaagccagg cctaacatcc cagaatcagg 1080gggcctctgc aatccagata gtccgacaac
ggctggctgg gaatgaaaag tgtaagaagc 1140cagtggctgc tcagtcaaca agactgggtg
tctcggctgc tct 1183523218DNARattus Norvegicus
52caatcctggt gcccagccta tctccccgcg gccgggcgca gtccttcacc gcacgctgaa
60ccggaggaag gctgcgccta gtcggggcgc tgagggaccc tccaccggga cgccggcccc
120tccccgggcc tctgctcact tgcccccctg cgagcccgtc cccctagtcg gcctctcgga
180tcggggacgt ggggcgagct gagagcaggc ccggggtggg tggtcactgt ggagaagacg
240tggctgtcaa gatgatagaa gtactgacaa ctgactctca gaaactgcta caccagctga
300acaccctgtt ggaacaggag tccagatgtc agccaaaggt ctgtggcctg aaactgattg
360agtctgcaca tgataatggc ctcaggatga ctgcaagact ccgggacttt gaagtcaaag
420atctactgag tctaactcag ttctttggct tcgacacaga aacattttcc cttgctgtga
480atttactgga cagattcttg tctaaaatga aggtacaggc gaagcatctc ggctgtgtcg
540gactgagctg cttttatttg gctgtgaaat cgattgaaga ggaaaggaac gtcccgctgg
600caactgattt gatccggata agtcagtata ggttcacagt ttcagacctg atgagaatgg
660aaaagattgt gttggagaaa gtgtgctgga aagtcaaagc tactactgcc ttccaatttc
720tgcagctcta ttactccctc attcgggaga ccttgccatt tgaaaggaga aacgatctga
780attttgaaag actagaagcc caactgaagg cgtgccactg caggatcata ttttctaagg
840caaagccttc tgtgctggcg ctggcaatca tcgctttgga gatccaagca ctgaagtatg
900tggagttaac agaaggagta gaatgtattc agaaacattc caagataagt ggccgagatc
960tgaccttctg gcaagagctt gtttccaagt gtttaactga atattcatca aacaagtgtt
1020ccaagccgaa cggtcagaag ttaaaatgga tcgtgtctgg gcgcactgca cgacaactga
1080agcacagtta ttacaggata acccacctcc caacaattcc cgaaaccatg ggttagttgg
1140caaatctggt tgttatcctc tgtgtacaga acatttccca gtgagatcgt ttttgtgcta
1200taacttaagg attgaaatac taccttcaat ataaagaata caggatgaaa acagtaaagg
1260aaacgtgagt ttgttggtct agacagagaa tactgggagg cattcactgt gtaccgcagt
1320ctgaagagaa atgagtatca aacctctaga cacatgctca tactgctgtc aaaggactag
1380cgtagaaaag agagtcctcc aaaccggaag tttaaatgta gttactaaaa tagcacttct
1440ttaacttaca tatcccccca ctgtggctta tttaaagtta cagaagtcca agcagaacga
1500caaaagatgt gacccatata tgaacacatt ttaatctgtt cattgattag gagagtgaat
1560atgaacttgc atgatgccca tgttaggttt ctggaaactg ccggggtatc ttaattctct
1620agtattctcc ctctgtggca gttgggctaa tacaaagtaa ctatacgcat gagaatataa
1680aatcagtctc tgatacatac acatttttac catcaaaatt tcttaatcat agcaaagact
1740taccttttta tgattaggaa tttttttttt aatgtatggc agcacatgcc tttaatccca
1800acactaggga ggcagaggca ggtggatctc tttgagttcg aagccaggct ggtctttaca
1860gtgagttcca ggacagctgg agagctacag aatggagaga cgctgtctca aaaacactca
1920aaacaaacaa acaaaccata ccagtttgta ggcagacttc tgttgggttg ggtttgtact
1980gtttgcctat gcagtgggat tacagcagca gcaacaaaaa ctgtccctga agtctttctc
2040tgccactgtg acctgagttt cctatggtac gcgatttact ctaagaaacc tcagcccctc
2100accacgttag ctgttggcaa atggcctcac agttgcggaa agtcccaatt ctaggcttgg
2160gaaagcaatg cttagatttg aattggccca tgaagcattc aaatcaaggc taaagacata
2220aatgtgaaat aaaactgtga accttcattt taacattgat ctcacttccc agatttaatc
2280aatatatact taggtggtat taaaaatggt aaactgccta atttaaatct caaaatttaa
2340actatgaggt ttacatcaaa gccaacattt cacaaatgta cttttaaggt attaaaagag
2400gtatttaagc agtaaatggt ttcttggcac ccataaccaa gtaatagtta agttagaggt
2460gggacttttt tattgctatg agaattacat ttaaactttt gggtgtttta taaaaagcag
2520atttcacaag ttttgaaaat tgtgaccttt actgaaattt gttaccttta atatttcttc
2580tagaggatag gtatttataa aagaaaaatt cgtcagaatt gctgcctcaa tctagtccca
2640tttgagaaaa tttgtttcta ctgtctcaat aactggatga aatatcactc tgaaaacttg
2700cctattgcac taaagctagt ttaggcttga taaaacactc caggaggttt ttaccacaga
2760ctgtttctat taaaactgct gcttctcatg tacaattttg ttttaaaagg aaccgagtac
2820atctgcaaaa cctaagtctt aagggacgtc aggaggtacc ttcagaatta taggatcacc
2880atggtagtgg ggattctcca tgctggcctt gaatgtttga tcttcactgc tgaaatgtgg
2940gtagctcctc agcgccctgt agagcctgag tctacctaga atagctgtaa ccattttgac
3000aagtaatgga taagaaaatt atccattgag aagctaaaaa caaaacaaaa caaaaccaaa
3060gaacgggtgt attttattct taacctttgt aaaccatcac tgagaacact tcagttcttc
3120ctaacagctg ttatgcttcg atttgaaaaa aatactgagt ggataaccaa ctaccatcat
3180gctttgggta cacctttcaa taaaattact gaaatgca
3218531558DNAArtificial SequenceSynthetic polynucleotide 53cagtaaagga
aacgtgagtt tgttggtcta gacagagaat actgggaggc attcactgtg 60taccgcagtc
tgaagagaaa tgagtatcaa acctctagac acatgctcat actgctgtca 120aaggactagc
gtagaaaaga gagtcctcca aaccggaagt ttaaatgtag ttactaaaat 180agcacttctt
taacttacat atccccccac tgtggcttat ttaaagttac agaagtccaa 240gcagaacgac
aaaagatgtg acccatatat gaacacattt taatctgttc attgattagg 300agagtgaata
tgaacttgca tgatgcccat gttaggtttc tggaaactgc cggggtatct 360taattctcta
gtattctccc tctgtggcag ttgggctaat acaaagtaac tatacgcatg 420agaatataaa
atcagtctct gatacataca catttttacc atcaaaattt cttaatcata 480gcaaagactt
acctttttat gattaggaat ttttttttta atgtatggca gcacatgcct 540ttaatcccaa
cactagggag gcagaggcag gtggatctct ttgagttcga agccaggctg 600gtctttacag
tgagttccag gacagctgga gagctacaga atggagagac gctgtctcaa 660aaacactcaa
aacaaacaaa caaaccatac cagtttgtag gcagacttct gttgggttgg 720gtttgtactg
tttgcctatg cagtgggatt acagcagcag caacaaaaac tgtccctgaa 780gtctttctct
gccactgtga cctgagtttc ctatggtacg cgatttactc taagaaacct 840cagcccctca
ccacgttagc tgttggcaaa tggcctcaca gttgcggaaa gtcccaattc 900taggcttggg
aaagcaatgc ttagatttga attggcccat gaagcattca aatcaaggct 960aaagacataa
atgtgaaata aaactgtgaa ccttcatttt aacattgatc tcacttccca 1020gatttaatca
atatatactt aggtggtatt aaaaatggta aactgcctaa tttaaatctc 1080aaaatttaaa
ctatgaggtt tacatcaaag ccaacatttc acaaatgtac ttttaaggta 1140ttaaaagagg
tatttaagca gtaaatggtt tcttggcacc cataaccaag taatagttaa 1200gttagaggtg
ggactttttt attgctatga gaattacatt taaacttttg ggtgttttat 1260aaaaagcaga
tttcacaagt tttgaaaatt gtgaccttta ctgaaatttg ttacctttaa 1320tatttcttct
agaggatagg tatttataaa agaaaaattc gtcagaattg ctgcctcaat 1380ctagtcccat
ttgagaaaat ttgtttctac tgtctcaata actggatgaa atatcactct 1440gaaaacttgc
ctattgcact aaagctagtt taggcttgat aaaacactcc aggaggtttt 1500taccacagac
tgtttctatt aaaactgctg cttctcatgt acaattttgt tttaaaag
1558542030DNARattus Norvegicus 54ggggcggatg cgcagaggtg caccacgtgt
ggtgttcctc cagcgcagtc aggatctcgt 60ctagtttggg tctaggttag atttggaatc
gtggagatgc ggaaggaaag cccacctccg 120ctcgtgcccc cggcggcccg cgagtggaac
ctgcccccca atgcgcccgc ctgcatggaa 180cggcagttgg aagctgcacg gtaccgctct
gatggttccc ttctgctcgg ggcttccagt 240ctgagtggtc gctgctgggc aggatctctg
tggtttttca aggatcctag tgcggccccc 300aacgaaggtt tctgctctgc tggcgtccag
acggaggctg gagtagctga cctcacttgg 360gttggggaca aaggtatctt agtggcttct
gattcaggtg ctgttgaatt gtgggagcta 420gatgagaacg agacacttat tgtcagcaag
ttctgcaagt atgagcatga tgacattgtg 480tctactgtca ctgtcctgag ctccggcaca
caggctgtca gtggtagcaa agacttctgc 540atcaaaattt gggacctggc tcagcagatg
tcgctgaatt cataccgagc tcatgcggga 600caggtcacct gtgttgctgc ctctccccac
agagaaactg tgtttctttc atgcagtgag 660gacagtagaa ttttgctctg ggatacccgc
tgtcccaagc cggcatcaca gatgggctgc 720aatgcctctg gctacctccc tacctccctg
gcttggcatc ctcagcagag tgaaatcttt 780gtctttggtg atgagaatgg atctgtctcc
cttgtggaca ccaagaatgc aagctgcacc 840ctcagctcag ctgtgcactc gcagtgtgtc
actagactgg tgttctctcc acacagtgtt 900cccttcctgg cctctctcag tgaagactgt
tcacttgctg tgctggattc aagcttttct 960gaggtgttta gaagtcgagc ccacagagac
tttgtgagag atgctacatg gtctccactc 1020aatcactccc ttcttaccac agttggctgg
gaccatcagg tcatccacca tgttgtgccg 1080ttagagcctc tcccagcccc tggacctgac
agtgttgtgg agtagaatgg attgcagaag 1140aaaagagcct tctgtctgca agtgtcgact
cgcttgcccc tgccttccat ttgtgagaga 1200gagagcacag gagccttgta gagcatgatt
actccctagt cccgtgcagt aactagtcag 1260attctcagcc tgagggaggc tgcatcccat
agtgacttgg aggaaaaagc ttcctttata 1320aatggatgta tgtgtgagta cacgtgtgag
tgcagtgtat agtttggagt ggagaaaatt 1380atccttcagc tttcccaaag caatgctctt
tacccccgac aaaatgacca gaggatttta 1440tgcttcccat gtctgggggc tgactatgtt
gttagggata tggagtgtgg gtatccctgg 1500atgcttggga atacttcaca ttactcagag
gtgcgtaact tatttttata tagagtttaa 1560ttcactatat gggaattact tcccatatac
aaaagtctag ccagactacc ttgagaagac 1620agaacagttt tgtacgaatg cctgttaaat
ggaatcaaat ccactttctg ggtgaatcaa 1680tttggccctt ggagttcgcg ctcgctcacc
ctgtgttcct tcttttgtgt tgtgtatgag 1740agatgagtgc tttcctgtcc tagatttcac
agttttaggg atgatggagt acttaaatta 1800aaagtgtttc agtgaagcga gaagattgac
atggattgtt acagagaaat ctgtcattgt 1860catttttccc acctaaaaat tccctgagga
ctgatctggg tactttgctc tggagagctg 1920aagtctgagc gctgtatatt tggactccta
agattgaaga tccggcatca gagaaactgt 1980caaaaatact ggaaggtgaa ataaagactt
atcctttcat ctttcctcca 2030551146DNAArtificial
SequenceSynthetic polynucleotide 55gtttagaagt cgagcccaca gagactttgt
gagagatgct acatggtctc cactcaatca 60ctcccttctt accacagttg gctgggacca
tcaggtcatc caccatgttg tgccgttaga 120gcctctccca gcccctggac ctgacagtgt
tgtggagtag aatggattgc agaagaaaag 180agccttctgt ctgcaagtgt cgactcgctt
gcccctgcct tccatttgtg agagagagag 240cacaggagcc ttgtagagca tgattactcc
ctagtcccgt gcagtaacta gtcagattct 300cagcctgagg gaggctgcat cccatagtga
cttggaggaa aaagcttcct ttataaatgg 360atgtatgtgt gagtacacgt gtgagtgcag
tgtatagttt ggagtggaga aaattatcct 420tcagctttcc caaagcaatg ctctttaccc
ccgacaaaat gaccagagga ttttatgctt 480cccatgtctg ggggctgact atgttgttag
ggatatggag tgtgggtatc cctggatgct 540tgggaatact tcacattact cagaggtgcg
taacttattt ttatatagag tttaattcac 600tatatgggaa ttacttccca tatacaaaag
tctagccaga ctaccttgag aagacagaac 660agttttgtac gaatgcctgt taaatggaat
caaatccact ttctgggtga atcaatttgg 720cccttggagt tcgcgctcgc tcaccctgtg
ttccttcttt tgtgttgtgt atgagagatg 780agtgctttcc tgtcctagat ttcacagttt
tagggatgat ggagtactta aattaaaagt 840gtttcagtga agcgagaaga ttgacatgga
ttgttacaga gaaatctgtc attgtcattt 900ttcccaccta aaaattccct gaggactgat
ctgggtactt tgctctggag agctgaagtc 960tgagcgctgt atatttggac tcctaagatt
gaagatccgg catcagagaa actgtcaaaa 1020atactggaag gtgaaataaa gacttatcct
ttcatctttc ctccaaagct tatttattac 1080ctgctttgct taggtgagtc acctgagtat
caatcagtct taactgccca ctgtctttgt 1140agtcta
1146561971DNARattus Norvegicus
56ggtaaccagg agttaagcgg gctccctgcc agcgcgaggg ctttaaaagg ggtgatgcaa
60cgcgctccca gtcacagtct cactcagcga gacgcgcggt gcacggtgct tccccggcgg
120agccgaccga ccaacccgcg ctccggcaga gtccttggcg ctcgcctgcc ggcgggacag
180acagcccgcc tctagccgct ctctggaccc tggccgcccc gagcgaagac tggagcaaaa
240tgatgcttca acatccaggc caggtctctg cctcagaagt cagcgcgacc gccatcgtcc
300cctgcctctc acctcctggg tcactggtgt ttgaggattt tgctaacctg acaccttttg
360tcaaggaaga gctgagattc gccatccaga acaagcacct ttgccatcgg atgtcctctg
420cgctggagtc agtcaccatc aacaacagac ctctggagat gtcagtcacc aagtctgagg
480tggcccctga agaagatgag agaaaaagga ggcggcggga aagaaacaaa attgctgctg
540ccaagtgtcg aaacaagaaa aaagagaaga cagagtgcct gcagaaggag tcagagaaac
600tggagagtgt gaatgccgaa ctgaaggccc agatcgagga gctgaagaat gagaagcagc
660atctgattta catgctcaac ctgcaccggc ccacgtgtat cgtccgggct cagaacgggc
720ggacgccgga agacgagagg aaccttttta tccaacagat aaaagaagga acattgcaga
780gctaagcaga ggtggcatgg gggcaattgg ggagtcctta ctgaatcctc cttttccacc
840ccaaaccctg aagccattgg aaaactggct tcctgtgcac ttctagaatc tcagcagcca
900cgagctgttg ggtcaggagg gcctgcggtg actactgcgt tgtcccactc tgtccccgag
960tgaaccgtgg agcaggcagg agcatccttt gtctcaccgg ctccaggatt taggccttac
1020catcccggcc attctcagat gacctagctg gccccaggct ggggtcccat gcaaagcagg
1080atcgcactaa tgggatgcag gcagaagtgt ctaccttgac aggtggggtg ggaccacgtc
1140ctccactgcg gctgacaaca tccctcctag ggaagatgga gtgagaacat tcatcattga
1200agttgtccaa tggccagggt atgctttcta gaaactatgc tgttctgtcc tagactgact
1260gtgcataggg cattcatttc tgagcctggt gttgtgctat ttagatgttt gtcttgcaca
1320acattggcgt gatttttttc cgggagtttc atcagacctg atttccgaga gtttgggggt
1380ctgccactgt ggacaatatc ccccaaaagt gtttgggtgg ccatgtaaac tggctgatga
1440ccagctgtgc tactctgtgc tgaccgagga ctgatgcctc cttcccctgt acccactgct
1500gaggaagaac ccgggcacag cagctgtcct tggctacaaa ctgttacaat gtcacagaac
1560gaaggcacaa agtcccgctt tcaaagggcg taggactcca cactcagtga cagggcagga
1620agagccaagg attctccgtt ttcccttcct tcccaccaaa aaccacagcc cgtggagact
1680ggtatttgaa gccaggagtg gggcaaggaa ggtgtctgca ctgtgggatg ttaactgcgc
1740ttttgtcttg aagctatttt gagatgcggt ccagagtatt tcagctggga ggtccctccc
1800actggccacc agggctctgg ctactgttaa aattctgatg tttctgtgaa atcctcagtg
1860ttcaatccag actcagtagt atattacagt tttctgtaag agagaacgtt acttatttat
1920cccagtattc ctagcctgtc aacgtaataa aatatcagaa tgagacctgg t
1971571384DNAArtificial SequenceSynthetic polynucleotide 57gagtcagaga
aactggagag tgtgaatgcc gaactgaagg cccagatcga ggagctgaag 60aatgagaagc
agcatctgat ttacatgctc aacctgcacc ggcccacgtg tatcgtccgg 120gctcagaacg
ggcggacgcc ggaagacgag aggaaccttt ttatccaaca gataaaagaa 180ggaacattgc
agagctaagc agaggtggca tgggggcaat tggggagtcc ttactgaatc 240ctccttttcc
accccaaacc ctgaagccat tggaaaactg gcttcctgtg cacttctaga 300atctcagcag
ccacgagctg ttgggtcagg agggcctgcg gtgactactg cgttgtccca 360ctctgtcccc
gagtgaaccg tggagcaggc aggagcatcc tttgtctcac cggctccagg 420atttaggcct
taccatcccg gccattctca gatgacctag ctggccccag gctggggtcc 480catgcaaagc
aggatcgcac taatgggatg caggcagaag tgtctacctt gacaggtggg 540gtgggaccac
gtcctccact gcggctgaca acatccctcc tagggaagat ggagtgagaa 600cattcatcat
tgaagttgtc caatggccag ggtatgcttt ctagaaacta tgctgttctg 660tcctagactg
actgtgcata gggcattcat ttctgagcct ggtgttgtgc tatttagatg 720tttgtcttgc
acaacattgg cgtgattttt ttccgggagt ttcatcagac ctgatttccg 780agagtttggg
ggtctgccac tgtggacaat atcccccaaa agtgtttggg tggccatgta 840aactggctga
tgaccagctg tgctactctg tgctgaccga ggactgatgc ctccttcccc 900tgtacccact
gctgaggaag aacccgggca cagcagctgt ccttggctac aaactgttac 960aatgtcacag
aacgaaggca caaagtcccg ctttcaaagg gcgtaggact ccacactcag 1020tgacagggca
ggaagagcca aggattctcc gttttccctt ccttcccacc aaaaaccaca 1080gcccgtggag
actggtattt gaagccagga gtggggcaag gaaggtgtct gcactgtggg 1140atgttaactg
cgcttttgtc ttgaagctat tttgagatgc ggtccagagt atttcagctg 1200ggaggtccct
cccactggcc accagggctc tggctactgt taaaattctg atgtttctgt 1260gaaatcctca
gtgttcaatc cagactcagt agtatattac agttttctgt aagagagaac 1320gttacttatt
tatcccagta ttcctagcct gtcaacgtaa taaaatatca gaatgagacc 1380tggt
1384581120DNARattus Norvegicus 58ggcctgggcg gagagggagg aaaacttcct
ggctgggact ctggcggttt ctgcctgcca 60accctccgat ccgcctacca gcgttggctc
ttcccgaccc ctcccccggc gcccccagtg 120tccgccatgg ccaaagccta cgaccacctc
ttcaagttgc tgctgatcgg ggactcgggg 180gtgggcaaga cttgtctcat cattcgcttt
gcagaggaca acttcaacag cacttacatc 240tccaccatcg gaattgattt caagatccga
actgtggaaa tagaggggaa gagaatcaaa 300ctgcaagtct gggacacagc tggccaagaa
cgattcaaga caataaccac cgcctattac 360cgtggagcca tgggcattat cctagtatat
gacatcacag atgagaaatc cttcgagaat 420attcagaact ggatgaaaag catcaaagag
aacgcgtctg ctggagtgga gcgccttctg 480ctggggaaca aatgtgacat ggaagccaag
cggaaggtgc agagagagca ggctgagagg 540ttggcccgag agcacagaat ccgatttttt
gagacaagtg ccaaatccag tgtgaatgtg 600gatgaggctt tcagttccct ggcccgtgac
atcttgctca agacaggagg ccggagatcg 660ggaaacagca gcaagccctc aagcactgac
ctgaaagtat ctgacaagaa gaacagcaac 720aagtgctcct tgggctgagg aacatttctt
gcctcctatt caccctgaac ctggaggcta 780gacctgaggg aggtggactg aggtagactg
atggaaaaca gaggggagga gctgtggtgg 840tgcctggagg ggtggatgac aggggaggaa
ggaaagatga aatgggcagg gaaaggaggg 900cgaggaacca aggacgtgaa aagtgaagag
aaggggtttg agaagagaaa aagaagaagg 960tctcaggtct cggaccgtcc aacattaatg
tcagtatgct gatctctcca ttcctggttc 1020agggttcggg tcccgagagg ctggctcggc
cctactctga gggtctctca ctccacagat 1080ctttgttagt attaaaggcc actgtttggc
acgaatgttc 112059120DNAArtificial
SequenceSynthetic polynucleotide 59ttggcccgag agcacagaat ccgatttttt
gagacaagtg ccaaatccag tgtgaatgtg 60gatgaggctt tcagttccct ggcccgtgac
atcttgctca agacaggagg ccggagatcg 120601877DNARattus Norvegicus
60gatgggatgc atctatcttg tgatatgtac cagccacagg caccatgtcc gatcctggtg
60atgtccgacc tgttccacac aggagcaaag tatgccgtcg tctgttcggt cccgtggaca
120gtgagcagtt gagccgcgat tgcgatgcgc tcatggcgag ctgtctccag gaggcccgag
180aacggtggaa ctttgacttc gccactgaga cgccactgga gggcaactac gtctgggagc
240gtgttcggag cccagggctg cccaagatct acctgagccc tgggtcccgc cgccgtgatg
300acctgggagg ggacaagagg cccagtacct cctcggccct gctgcagggg ccagggccag
360ctccggagga ccacgtggcc ttgtcgctgt cttgcactct ggtgtctcac gcccctgaga
420ggcctgaaga ctccccgggc gggaccggga catctcaggg ccgaaaacgg aggcagacca
480gcctaacaga tttctatcac tccaagcgcc gattggtctt ctgcaagaga aagccctgaa
540gtgcccacgg gaggctcgcc ttcttctgct gtgggtcagg aggcctcttc cccatcttct
600gccttagcct tcattcagtg tgtcttaatt attatttgtg ttttaattta aacttctcct
660gtatatactc tgcctgcccc ctcccagcct ccaaacttag ttatttaaaa aacaaaacaa
720aacaatgaaa ttagtaggac ggtaggctcc ttagtgctgt tttttttttt ttttatgtag
780accattattt aagtccttct caacccaagc tgtgtttctg atcctggcgg gatggtcctg
840gcgggatggt cctggcggga tggtcgcact ggcctcatgc catctgcatc tcgcatctcg
900cccaatcccc gcccctcccc cctagctcct cccccgcccc cactccctgc ctggttcctt
960gccacttctt acctgggggc gatcctcaga cctgaatagc actttggaca actgagtagg
1020acttcggggt ctccttgtca tctctaaggc ccgctaggat gacagtgaag cagtcacagc
1080ctagaacaaa gatgcccggt taggacctaa gcgtaccgtc cagagccttg acatttactc
1140agacctgtga agatcctttg ccactcctgg ggaccccgcc tcccctgtgg gtctctgcca
1200gctgcccctc tatttttgag ggttaatctg gtgatctgct gctctccctt cctcagaccc
1260ttcccctccc caggttggca ggaggcatcc tttccctcgc cacggctcag tggaccagaa
1320gggaacgggt acacagggta cactaagtgg ggtttcctgg tcctacctca ggcagctcca
1380gtggcaactg cccttcttat gggtctaggg taggtccttg gtgacgagac gggcttccca
1440gagcatccct gtgtgtgtgg tgtgtggtgg tggtgggggg tggacttatc tgggatgggg
1500accccagccg ctgaagtcct cagtgacttg tcccatttct tagtagttgt acaaggagtc
1560aggccaagat ggtgcctcgg gggctgaggg agctcacagg aactgagcag tgactggtcc
1620tttcccagta ttgaatactg agcccctgtg ggtgtcgaag cacttagtgg gtctggcccc
1680aaccccaaac acccctgttt ctgtaacacc ctgagctgga ctgtttatct ttagccggga
1740gaacatgtat tttggtcccc tccctgtctc cgctcggatt gtaaacctcc cacgtgtggg
1800gatcacaccc tgcactgtcc cgaatcttta caccctatcc caaagctggt gctcaataaa
1860tacttctaga tgatttg
1877611109DNAArtificial SequenceSynthetic polynucleotide 61ttttttatgt
agaccattat ttaagtcctt ctcaacccaa gctgtgtttc tgatcctggc 60gggatggtcc
tggcgggatg gtcctggcgg gatggtcgca ctggcctcat gccatctgca 120tctcgcatct
cgcccaatcc ccgcccctcc cccctagctc ctcccccgcc cccactccct 180gcctggttcc
ttgccacttc ttacctgggg gcgatcctca gacctgaata gcactttgga 240caactgagta
ggacttcggg gtctccttgt catctctaag gcccgctagg atgacagtga 300agcagtcaca
gcctagaaca aagatgcccg gttaggacct aagcgtaccg tccagagcct 360tgacatttac
tcagacctgt gaagatcctt tgccactcct ggggaccccg cctcccctgt 420gggtctctgc
cagctgcccc tctatttttg agggttaatc tggtgatctg ctgctctccc 480ttcctcagac
ccttcccctc cccaggttgg caggaggcat cctttccctc gccacggctc 540agtggaccag
aagggaacgg gtacacaggg tacactaagt ggggtttcct ggtcctacct 600caggcagctc
cagtggcaac tgcccttctt atgggtctag ggtaggtcct tggtgacgag 660acgggcttcc
cagagcatcc ctgtgtgtgt ggtgtgtggt ggtggtgggg ggtggactta 720tctgggatgg
ggaccccagc cgctgaagtc ctcagtgact tgtcccattt cttagtagtt 780gtacaaggag
tcaggccaag atggtgcctc gggggctgag ggagctcaca ggaactgagc 840agtgactggt
cctttcccag tattgaatac tgagcccctg tgggtgtcga agcacttagt 900gggtctggcc
ccaaccccaa acacccctgt ttctgtaaca ccctgagctg gactgtttat 960ctttagccgg
gagaacatgt attttggtcc cctccctgtc tccgctcgga ttgtaaacct 1020cccacgtgtg
gggatcacac cctgcactgt cccgaatctt tacaccctat cccaaagctg 1080gtgctcaata
aatacttcta gatgatttg
11096270PRTRattus Norvegicus 62Thr Gly Asn His Gly Ser Gly Leu Ala Ala
Ala Ser Ala Ala Ala Pro 1 5 10
15 Arg Val Gly Ile Arg Val Gly Val Asp Thr Arg His Gly Arg Gly
Ala 20 25 30 Ser
Thr Arg Gln Arg Pro Met Leu Lys Arg Gln Leu Leu Glu Arg Gly 35
40 45 Pro Arg Gln Val His Gly
Leu Arg Phe Leu Ser Ser Ala Thr Thr Gln 50 55
60 Arg Leu Leu Pro Gly Met 65
70 63171PRTRattus Norvegicus 63Met Ala Asp Ser Pro Glu Val Val Ala Met
Asp Cys Glu Met Val Gly 1 5 10
15 Leu Gly Pro Gln Arg Val Ser Gly Leu Ala Arg Cys Ser Ile Val
Asn 20 25 30 Val
His Ser Ala Val Leu Tyr Asp Lys Tyr Ile Gln Pro Glu Gly Glu 35
40 45 Ile Thr Asp Tyr Arg Thr
Gln Val Ser Gly Ile Thr Pro Gln His Met 50 55
60 Ala Arg Ala Thr Pro Phe Ala Glu Ala Arg Leu
Glu Ile Leu Gln Leu 65 70 75
80 Leu Lys Gly Lys Leu Val Val Gly His Asp Leu Lys His Asp Phe Ser
85 90 95 Ala Leu
Lys Glu Asp Met Arg Lys Tyr Thr Ile Tyr Asp Thr Ser Thr 100
105 110 Asp Met Leu Leu Trp His Glu
Ala Lys Leu His Cys Tyr Ser Arg Val 115 120
125 Ser Leu Arg Leu Leu Cys Lys Arg Leu Leu His Lys
Ser Ile Gln Val 130 135 140
Arg Ser Phe Pro Ala Pro Val Thr Leu Leu Ser Leu Leu Pro Pro Leu 145
150 155 160 Ser Leu Pro
Pro Ser Ser His Ser Gly Lys Glu 165 170
64262PRTRattus Norvegicus 64Met Ala Asp Ser Val Lys Thr Phe Leu Gln Asp
Leu Gly Arg Gly Ile 1 5 10
15 Lys Asp Ser Ile Trp Gly Ile Cys Thr Ile Ser Lys Leu Asp Ala Arg
20 25 30 Ile Gln
Gln Lys Arg Glu Glu Gln Arg Arg Arg Arg Ala Ser Ser Leu 35
40 45 Leu Ala Gln Arg Arg Ala Gln
Ser Val Glu Arg Lys Gln Glu Ser Glu 50 55
60 Pro Arg Ile Val Ser Arg Ile Phe Gln Cys Cys Ala
Trp Asn Gly Gly 65 70 75
80 Val Phe Trp Phe Ser Leu Leu Leu Phe Tyr Arg Val Phe Ile Pro Val
85 90 95 Leu Gln Ser
Val Thr Ala Arg Val Ile Gly Asp Pro Ser Leu His Gly 100
105 110 Asp Val Trp Ser Trp Leu Glu Phe
Phe Leu Thr Ser Ile Phe Ser Ala 115 120
125 Leu Trp Val Leu Pro Leu Phe Val Leu Ser Lys Val Val
Asn Ala Ile 130 135 140
Trp Phe Gln Asp Ile Ala Asp Leu Ala Phe Glu Val Ser Gly Arg Lys 145
150 155 160 Pro His Pro Phe
Pro Ser Val Ser Lys Ile Ile Ala Asp Met Leu Phe 165
170 175 Asn Leu Leu Leu Gln Ala Leu Phe Leu
Ile Gln Gly Met Phe Val Ser 180 185
190 Leu Phe Pro Ile His Leu Val Gly Gln Leu Val Ser Leu Leu
His Met 195 200 205
Ser Leu Leu Tyr Ser Leu Tyr Cys Phe Glu Tyr Arg Trp Phe Asn Lys 210
215 220 Gly Ile Glu Met His
Gln Arg Leu Ser Asn Ile Glu Arg Asn Trp Pro 225 230
235 240 Tyr Tyr Phe Gly Phe Gly Leu Pro Leu Ala
Phe Leu Thr Ala Met Gln 245 250
255 Ser Ser Tyr Ile Ile Arg 260
6556PRTRattus Norvegicus 65Met Ile Arg Asn Phe Phe Phe Asn Val Trp Gln
His Met Pro Leu Ile 1 5 10
15 Pro Thr Leu Gly Arg Gln Arg Gln Val Asp Leu Phe Glu Phe Glu Ala
20 25 30 Arg Leu
Val Phe Thr Val Ser Ser Arg Thr Ala Gly Glu Leu Gln Asn 35
40 45 Gly Glu Thr Leu Ser Gln Lys
His 50 55 6638PRTRattus Norvegicus 66Met Arg
Pro Ser Ile Lys Arg Ile Thr Pro Ile Arg Gly Glu Asp Glu 1 5
10 15 Ser Gln Leu Ala Ile Leu Val
Pro Ser Leu Ser Pro Arg Gly Arg Ala 20 25
30 Gln Ser Phe Thr Ala Arg 35
67208PRTRattus Norvegicus 67Met Glu Arg Gln Leu Glu Ala Ala Arg Tyr Arg
Ser Asp Gly Ser Leu 1 5 10
15 Leu Leu Gly Ala Ser Ser Leu Ser Gly Arg Cys Trp Ala Gly Ser Leu
20 25 30 Trp Phe
Phe Lys Asp Pro Ser Ala Ala Pro Asn Glu Gly Phe Cys Ser 35
40 45 Ala Gly Val Gln Thr Glu Ala
Gly Val Ala Asp Leu Thr Trp Val Gly 50 55
60 Asp Lys Gly Ile Leu Val Ala Ser Asp Ser Gly Ala
Val Glu Leu Trp 65 70 75
80 Glu Leu Asp Glu Asn Glu Thr Leu Ile Val Ser Lys Phe Cys Lys Tyr
85 90 95 Glu His Asp
Asp Ile Val Ser Thr Val Thr Val Leu Ser Ser Gly Thr 100
105 110 Gln Ala Val Ser Gly Ser Lys Asp
Phe Cys Ile Lys Ile Trp Asp Leu 115 120
125 Ala Gln Gln Met Ser Leu Asn Ser Tyr Arg Ala His Ala
Gly Gln Val 130 135 140
Thr Cys Val Ala Ala Ser Pro His Arg Glu Thr Val Phe Leu Ser Cys 145
150 155 160 Ser Glu Asp Ser
Arg Ile Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro 165
170 175 Ala Ser Gln Met Gly Cys Asn Ala Ser
Gly Tyr Leu Pro Thr Ser Leu 180 185
190 Ala Trp His Pro Gln Gln Ser Glu Ile Phe Val Phe Gly Lys
Ala Ala 195 200 205
68249PRTRattus Norvegicus 68Met Glu Arg Gln Leu Glu Ala Ala Arg Tyr Arg
Ser Asp Gly Ser Leu 1 5 10
15 Leu Leu Gly Ala Ser Ser Leu Ser Gly Arg Cys Trp Ala Gly Ser Leu
20 25 30 Trp Phe
Phe Lys Asp Pro Ser Ala Ala Pro Asn Glu Gly Phe Cys Ser 35
40 45 Ala Gly Val Gln Thr Glu Ala
Gly Val Ala Asp Leu Thr Trp Val Gly 50 55
60 Asp Lys Gly Ile Leu Val Ala Ser Asp Ser Gly Ala
Val Glu Leu Trp 65 70 75
80 Glu Leu Asp Glu Asn Glu Thr Leu Ile Val Ser Lys Phe Cys Lys Tyr
85 90 95 Glu His Asp
Asp Ile Val Ser Thr Val Thr Val Leu Ser Ser Gly Thr 100
105 110 Gln Ala Val Ser Gly Ser Lys Asp
Phe Cys Ile Lys Ile Trp Asp Leu 115 120
125 Ala Gln Gln Met Ser Leu Asn Ser Tyr Arg Ala His Ala
Gly Gln Val 130 135 140
Thr Cys Val Ala Ala Ser Pro His Arg Glu Thr Val Phe Leu Ser Cys 145
150 155 160 Ser Glu Asp Ser
Arg Ile Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro 165
170 175 Ala Ser Gln Met Gly Cys Asn Ala Ser
Gly Tyr Leu Pro Thr Ser Leu 180 185
190 Ala Trp His Pro Gln Gln Ser Glu Ile Phe Val Phe Gly Asp
Glu Asn 195 200 205
Gly Ser Val Ser Leu Val Asp Thr Lys Asn Ala Ser Cys Thr Leu Ser 210
215 220 Ser Ala Val His Ser
Gln Cys Val Thr Arg Leu Val Phe Ser Pro His 225 230
235 240 Arg Cys Ser Leu Pro Gly Leu Ser Gln
245 69183PRTRattus Norvegicus 69Met Ala Lys
Ala Tyr Asp His Leu Phe Lys Leu Leu Leu Ile Gly Asp 1 5
10 15 Ser Gly Val Gly Lys Thr Cys Leu
Ile Ile Arg Phe Ala Glu Asp Asn 20 25
30 Phe Asn Ser Thr Tyr Ile Ser Thr Ile Gly Ile Asp Phe
Lys Ile Arg 35 40 45
Thr Val Glu Ile Glu Gly Lys Arg Ile Lys Leu Gln Val Trp Asp Thr 50
55 60 Ala Gly Gln Glu
Arg Phe Lys Thr Ile Thr Thr Ala Tyr Tyr Arg Gly 65 70
75 80 Ala Met Gly Ile Ile Leu Val Tyr Asp
Ile Thr Asp Glu Lys Ser Phe 85 90
95 Glu Asn Ile Gln Asn Trp Met Lys Ser Ile Lys Glu Asn Ala
Ser Ala 100 105 110
Gly Val Glu Arg Leu Leu Leu Gly Asn Lys Cys Asp Met Glu Ala Lys
115 120 125 Arg Lys Val Gln
Arg Glu Gln Ala Glu Arg Val Ser Gln Ala Gly Leu 130
135 140 Leu Trp Pro Asn Ala Leu Leu Leu
Pro Phe Ile Gln Leu Ser Pro Ser 145 150
155 160 Tyr Leu Ile Pro Tyr Ser Trp Pro Glu Ser Thr Glu
Ser Asp Phe Leu 165 170
175 Arg Gln Val Pro Asn Pro Val 180
70122PRTRattus Norvegicus 70Met Gly Ile Ile Leu Val Tyr Asp Ile Thr Asp
Glu Lys Ser Phe Glu 1 5 10
15 Asn Ile Gln Asn Trp Met Lys Ser Ile Lys Glu Asn Ala Ser Ala Gly
20 25 30 Val Glu
Arg Leu Leu Leu Gly Asn Lys Cys Asp Met Glu Ala Lys Arg 35
40 45 Lys Val Gln Arg Glu Gln Ala
Glu Arg Leu Ala Arg Glu His Arg Ile 50 55
60 Arg Phe Phe Glu Thr Ser Ala Lys Ser Ser Val Asn
Val Asp Glu Ala 65 70 75
80 Phe Ser Ser Leu Ala Arg Asp Ile Leu Leu Lys Thr Gly Gly Arg Arg
85 90 95 Ser Gly Asn
Ser Ser Lys Pro Ser Ser Thr Asp Leu Lys Val Ser Asp 100
105 110 Lys Lys Asn Ser Asn Lys Cys Ser
Leu Gly 115 120 71257PRTRattus Norvegicus
71Pro Thr Leu Leu Arg Pro Pro Asp Gly Pro Gly Ala Thr Ser Ala Ser 1
5 10 15 Pro Val Ala Cys
Leu Leu Asp Ser Gly His Gln Ala Gln Leu Val Glu 20
25 30 Phe Leu Ile Val His Tyr Glu Gln Ile
Phe Gly Met Asp Glu Leu Pro 35 40
45 Leu Thr Ser Glu Pro Leu Thr Gln Asp Pro Ala Leu Ala Pro
Ala Leu 50 55 60
Leu Glu Ser Ser Pro Gln His Pro Ala Leu Leu Val Ala Gln Asp Ser 65
70 75 80 Gln Pro Leu Thr Ile
Ala Ser Asp Ser Ser Pro Asp Pro Lys Gln His 85
90 95 Ser Ala Leu Glu Lys Cys Pro Lys Val Ala
Pro Pro Glu Leu Thr Ala 100 105
110 Leu Gln Ser Asn Arg Lys Glu Glu Glu Glu Glu Asp Thr Arg Asp
Gly 115 120 125 Ala
Gly Asp Gly Ser Ser His Ser Pro Glu Asp Leu Leu Leu Val Ala 130
135 140 Gln Ser Arg Gly His Phe
Ser Arg Gln Pro Val Lys Tyr Ser Arg Gly 145 150
155 160 Gly Val Arg Pro Val Thr His Gln Leu Ser Ser
Leu Ala Leu Val Ala 165 170
175 Ser Lys Leu Cys Glu Glu Thr Pro Ile Thr Val Ser Ala Val His Arg
180 185 190 Gly Ser
Leu Arg Ala Arg Gly Leu Gly Pro Ala Ala Ala Ser Pro Glu 195
200 205 Gly Gly Thr Leu Arg Arg Asn
Pro Leu Pro Lys His Phe Glu Ile Thr 210 215
220 Gln Glu Thr Ala Arg Leu Leu Ser Lys Leu Asp Ser
Glu Ala Val Ser 225 230 235
240 Arg Thr Ser Cys Cys Ala Asp Pro Glu Pro Glu Glu Ser Glu Glu His
245 250 255 Leu
72340PRTRattus Norvegicus 72Met Ala Asp Ser Val Lys Thr Phe Leu Gln Asp
Leu Gly Arg Gly Ile 1 5 10
15 Lys Asp Ser Ile Trp Gly Ile Cys Thr Ile Ser Lys Leu Asp Ala Arg
20 25 30 Ile Gln
Gln Lys Arg Glu Glu Gln Arg Arg Arg Arg Ala Ser Ser Leu 35
40 45 Leu Ala Gln Arg Arg Ala Gln
Ser Val Glu Arg Lys Gln Glu Ser Glu 50 55
60 Pro Arg Ile Val Ser Arg Ile Phe Gln Cys Cys Ala
Trp Asn Gly Gly 65 70 75
80 Val Phe Trp Phe Ser Leu Leu Leu Phe Tyr Arg Val Phe Ile Pro Val
85 90 95 Leu Gln Ser
Val Thr Ala Arg Val Ile Gly Asp Pro Ser Leu His Gly 100
105 110 Asp Val Trp Ser Trp Leu Glu Phe
Phe Leu Thr Ser Ile Phe Ser Ala 115 120
125 Leu Trp Val Leu Pro Leu Phe Val Leu Ser Lys Val Val
Asn Ala Ile 130 135 140
Trp Phe Gln Asp Ile Ala Asp Leu Ala Phe Glu Val Ser Gly Arg Lys 145
150 155 160 Pro His Pro Phe
Pro Ser Val Ser Lys Ile Ile Ala Asp Met Leu Phe 165
170 175 Asn Leu Leu Leu Gln Ala Leu Phe Leu
Ile Gln Gly Met Phe Val Ser 180 185
190 Leu Phe Pro Ile His Leu Val Gly Gln Leu Val Ser Leu Leu
His Met 195 200 205
Ser Leu Leu Tyr Ser Leu Tyr Cys Phe Glu Tyr Arg Trp Phe Asn Lys 210
215 220 Gly Ile Glu Met His
Gln Arg Leu Ser Asn Ile Glu Arg Asn Trp Pro 225 230
235 240 Tyr Tyr Phe Gly Phe Gly Leu Pro Leu Ala
Phe Leu Thr Ala Met Gln 245 250
255 Ser Ser Tyr Ile Ile Ser Gly Cys Leu Phe Ser Ile Leu Phe Pro
Leu 260 265 270 Phe
Ile Ile Ser Ala Asn Glu Ala Lys Thr Pro Gly Lys Ala Tyr Leu 275
280 285 Phe Gln Leu Arg Leu Phe
Ser Leu Val Val Phe Leu Ser Asn Arg Leu 290 295
300 Phe His Lys Thr Val Tyr Leu Gln Ser Ala Leu
Ser Ser Ser Ser Ser 305 310 315
320 Ala Glu Lys Phe Pro Ser Pro His Pro Ser Pro Ala Lys Leu Lys Ala
325 330 335 Ala Ala
Gly His 340 73138PRTRattus Norvegicus 73Thr Val Leu Ala Ser
Glu Pro Ala Ile Met Ala Pro Gly Trp Pro Arg 1 5
10 15 Pro Leu Pro Gln Leu Leu Val Leu Gly Phe
Gly Leu Val Leu Ile Arg 20 25
30 Ala Thr Ala Gly Glu Gln Ala Pro Gly Asn Ala Pro Cys Ser Ser
Gly 35 40 45 Ser
Ser Trp Ser Ala Asp Leu Asp Lys Cys Met Asp Cys Ala Ser Cys 50
55 60 Pro Ala Arg Pro His Ser
Asp Phe Cys Leu Gly Cys Ala Ala Ala Pro 65 70
75 80 Pro Ala His Phe Arg Met Leu Trp Pro Ile Leu
Gly Gly Ala Leu Ser 85 90
95 Leu Ala Leu Val Leu Ala Leu Val Ser Gly Phe Leu Val Trp Arg Arg
100 105 110 Cys Arg
Arg Arg Glu Lys Phe Thr Thr Pro Ile Glu Glu Thr Gly Gly 115
120 125 Glu Gly Cys Pro Gly Val Ala
Leu Ile Gln 130 135 74198PRTRattus
Norvegicus 74Gln Lys Arg Thr Gln Gly Thr Gly Thr Gly Leu Pro Glu Gly Leu
Arg 1 5 10 15 Ser
Met Ala Asp Ser Pro Glu Val Val Ala Met Asp Cys Glu Met Val
20 25 30 Gly Leu Gly Pro Gln
Arg Val Ser Gly Leu Ala Arg Cys Ser Ile Val 35
40 45 Asn Val His Ser Ala Val Leu Tyr Asp
Lys Tyr Ile Gln Pro Glu Gly 50 55
60 Glu Ile Thr Asp Tyr Arg Thr Gln Val Ser Gly Ile Thr
Pro Gln His 65 70 75
80 Met Ala Arg Ala Thr Pro Phe Ala Glu Ala Arg Leu Glu Ile Leu Gln
85 90 95 Leu Leu Lys Gly
Lys Leu Val Val Gly His Asp Leu Lys His Asp Phe 100
105 110 Ser Ala Leu Lys Glu Asp Met Arg Lys
Tyr Thr Ile Tyr Asp Thr Ser 115 120
125 Thr Asp Met Leu Leu Trp His Glu Ala Lys Leu His Cys Tyr
Ser Arg 130 135 140
Val Ser Leu Arg Leu Leu Cys Lys Arg Leu Leu His Lys Ser Ile Gln 145
150 155 160 Asn Asn Trp Arg Gly
His Cys Ser Val Glu Asp Ala Arg Ala Thr Met 165
170 175 Glu Leu Tyr Lys Ile Ser Gln Arg Leu Arg
Ala Gln Arg Gly Leu Pro 180 185
190 Cys Leu Gly Thr Ser Ala 195
75312PRTRattus Norvegicus 75Gln Ser His Thr Gln Asp Thr Ser Asp Met Ala
Leu Arg Ala Leu His 1 5 10
15 Ala Gln Pro Thr Gly Gly Pro Gln Leu Arg Phe Leu Leu Phe Leu Leu
20 25 30 Leu Leu
Leu Leu Leu Leu Ser Trp Pro Ser Gln Gly Asp Ala Leu Ala 35
40 45 Leu Pro Glu Gln Arg Arg Ser
Leu Ser Glu Ser Gln Leu Asn Pro Asp 50 55
60 Glu Leu Arg Gly Arg Phe Gln Asp Leu Leu Ser Arg
Leu His Ala Asn 65 70 75
80 Gln Ser Arg Glu Asp Ser Asn Ser Glu Pro Thr Pro Asp Pro Ala Val
85 90 95 Arg Ile Leu
Ser Pro Glu Val Arg Leu Gly Ser His Gly Arg Leu Leu 100
105 110 Leu Arg Val Asn Arg Ala Ser Leu
Thr Gln Gly Leu Pro Glu Ala Tyr 115 120
125 Arg Val His Arg Ala Leu Leu Leu Leu Thr Pro Ser Ser
Arg Pro Trp 130 135 140
Asp Ile Thr Arg Pro Leu Gln Arg Ala Ile Ser Leu Gln Gly Pro His 145
150 155 160 Ala Arg Ala Leu
Arg Leu Arg Leu Ala Pro Pro Pro Asp Leu Ala Val 165
170 175 Leu Pro Ser Gly Gly Ala Arg Leu Glu
Leu His Leu Arg Ser Ala Ala 180 185
190 Gly Arg Gly Arg Arg Ser Ala His Leu His Pro Arg Asp Ser
Cys Pro 195 200 205
Leu Gly Pro Gly Arg Cys Cys His Leu Glu Thr Val Gln Ala Thr Leu 210
215 220 Glu Asp Leu Gly Trp
Ser Asp Trp Val Leu Ser Pro Arg Gln Leu Gln 225 230
235 240 Leu Ser Met Cys Val Gly Glu Cys Pro His
Leu Tyr Arg Ser Ala Asn 245 250
255 Thr His Ala Gln Ile Lys Ala Arg Leu His Gly Leu Gln Pro Asp
Arg 260 265 270 Val
Pro Ala Pro Cys Cys Val Pro Ser Ser Tyr Thr Pro Val Val Leu 275
280 285 Met His Arg Thr Asp Ser
Gly Val Ser Leu Gln Thr Tyr Asp Asp Leu 290 295
300 Val Ala Gln Gly Cys His Cys Ala 305
310 76294PRTRattus Norvegicus 76Met Ile Glu Val Leu Thr
Thr Asp Ser Gln Lys Leu Leu His Gln Leu 1 5
10 15 Asn Thr Leu Leu Glu Gln Glu Ser Arg Cys Gln
Pro Lys Val Cys Gly 20 25
30 Leu Lys Leu Ile Glu Ser Ala His Asp Asn Gly Leu Arg Met Thr
Ala 35 40 45 Arg
Leu Arg Asp Phe Glu Val Lys Asp Leu Leu Ser Leu Thr Gln Phe 50
55 60 Phe Gly Phe Asp Thr Glu
Thr Phe Ser Leu Ala Val Asn Leu Leu Asp 65 70
75 80 Arg Phe Leu Ser Lys Met Lys Val Gln Ala Lys
His Leu Gly Cys Val 85 90
95 Gly Leu Ser Cys Phe Tyr Leu Ala Val Lys Ser Ile Glu Glu Glu Arg
100 105 110 Asn Val
Pro Leu Ala Thr Asp Leu Ile Arg Ile Ser Gln Tyr Arg Phe 115
120 125 Thr Val Ser Asp Leu Met Arg
Met Glu Lys Ile Val Leu Glu Lys Val 130 135
140 Cys Trp Lys Val Lys Ala Thr Thr Ala Phe Gln Phe
Leu Gln Leu Tyr 145 150 155
160 Tyr Ser Leu Ile Arg Glu Thr Leu Pro Phe Glu Arg Arg Asn Asp Leu
165 170 175 Asn Phe Glu
Arg Leu Glu Ala Gln Leu Lys Ala Cys His Cys Arg Ile 180
185 190 Ile Phe Ser Lys Ala Lys Pro Ser
Val Leu Ala Leu Ala Ile Ile Ala 195 200
205 Leu Glu Ile Gln Ala Leu Lys Tyr Val Glu Leu Thr Glu
Gly Val Glu 210 215 220
Cys Ile Gln Lys His Ser Lys Ile Ser Gly Arg Asp Leu Thr Phe Trp 225
230 235 240 Gln Glu Leu Val
Ser Lys Cys Leu Thr Glu Tyr Ser Ser Asn Lys Cys 245
250 255 Ser Lys Pro Asn Gly Gln Lys Leu Lys
Trp Ile Val Ser Gly Arg Thr 260 265
270 Ala Arg Gln Leu Lys His Ser Tyr Tyr Arg Ile Thr His Leu
Pro Thr 275 280 285
Ile Pro Glu Thr Met Gly 290 77342PRTRattus Norvegicus
77Met Arg Lys Glu Ser Pro Pro Pro Leu Val Pro Pro Ala Ala Arg Glu 1
5 10 15 Trp Asn Leu Pro
Pro Asn Ala Pro Ala Cys Met Glu Arg Gln Leu Glu 20
25 30 Ala Ala Arg Tyr Arg Ser Asp Gly Ser
Leu Leu Leu Gly Ala Ser Ser 35 40
45 Leu Ser Gly Arg Cys Trp Ala Gly Ser Leu Trp Phe Phe Lys
Asp Pro 50 55 60
Ser Ala Ala Pro Asn Glu Gly Phe Cys Ser Ala Gly Val Gln Thr Glu 65
70 75 80 Ala Gly Val Ala Asp
Leu Thr Trp Val Gly Asp Lys Gly Ile Leu Val 85
90 95 Ala Ser Asp Ser Gly Ala Val Glu Leu Trp
Glu Leu Asp Glu Asn Glu 100 105
110 Thr Leu Ile Val Ser Lys Phe Cys Lys Tyr Glu His Asp Asp Ile
Val 115 120 125 Ser
Thr Val Thr Val Leu Ser Ser Gly Thr Gln Ala Val Ser Gly Ser 130
135 140 Lys Asp Phe Cys Ile Lys
Ile Trp Asp Leu Ala Gln Gln Met Ser Leu 145 150
155 160 Asn Ser Tyr Arg Ala His Ala Gly Gln Val Thr
Cys Val Ala Ala Ser 165 170
175 Pro His Arg Glu Thr Val Phe Leu Ser Cys Ser Glu Asp Ser Arg Ile
180 185 190 Leu Leu
Trp Asp Thr Arg Cys Pro Lys Pro Ala Ser Gln Met Gly Cys 195
200 205 Asn Ala Ser Gly Tyr Leu Pro
Thr Ser Leu Ala Trp His Pro Gln Gln 210 215
220 Ser Glu Ile Phe Val Phe Gly Asp Glu Asn Gly Ser
Val Ser Leu Val 225 230 235
240 Asp Thr Lys Asn Ala Ser Cys Thr Leu Ser Ser Ala Val His Ser Gln
245 250 255 Cys Val Thr
Arg Leu Val Phe Ser Pro His Ser Val Pro Phe Leu Ala 260
265 270 Ser Leu Ser Glu Asp Cys Ser Leu
Ala Val Leu Asp Ser Ser Phe Ser 275 280
285 Glu Val Phe Arg Ser Arg Ala His Arg Asp Phe Val Arg
Asp Ala Thr 290 295 300
Trp Ser Pro Leu Asn His Ser Leu Leu Thr Thr Val Gly Trp Asp His 305
310 315 320 Gln Val Ile His
His Val Val Pro Leu Glu Pro Leu Pro Ala Pro Gly 325
330 335 Pro Asp Ser Val Val Glu
340 78124PRTRattus Norvegicus 78Met Ser Ser Ala Leu Glu Ser Val
Thr Ile Asn Asn Arg Pro Leu Glu 1 5 10
15 Met Ser Val Thr Lys Ser Glu Val Ala Pro Glu Glu Asp
Glu Arg Lys 20 25 30
Arg Arg Arg Arg Glu Arg Asn Lys Ile Ala Ala Ala Lys Cys Arg Asn
35 40 45 Lys Lys Lys Glu
Lys Thr Glu Cys Leu Gln Lys Glu Ser Glu Lys Leu 50
55 60 Glu Ser Val Asn Ala Glu Leu Lys
Ala Gln Ile Glu Glu Leu Lys Asn 65 70
75 80 Glu Lys Gln His Leu Ile Tyr Met Leu Asn Leu His
Arg Pro Thr Cys 85 90
95 Ile Val Arg Ala Gln Asn Gly Arg Thr Pro Glu Asp Glu Arg Asn Leu
100 105 110 Phe Ile Gln
Gln Ile Lys Glu Gly Thr Leu Gln Ser 115 120
79203PRTRattus Norvegicus 79Met Ala Lys Ala Tyr Asp His Leu Phe
Lys Leu Leu Leu Ile Gly Asp 1 5 10
15 Ser Gly Val Gly Lys Thr Cys Leu Ile Ile Arg Phe Ala Glu
Asp Asn 20 25 30
Phe Asn Ser Thr Tyr Ile Ser Thr Ile Gly Ile Asp Phe Lys Ile Arg
35 40 45 Thr Val Glu Ile
Glu Gly Lys Arg Ile Lys Leu Gln Val Trp Asp Thr 50
55 60 Ala Gly Gln Glu Arg Phe Lys Thr
Ile Thr Thr Ala Tyr Tyr Arg Gly 65 70
75 80 Ala Met Gly Ile Ile Leu Val Tyr Asp Ile Thr Asp
Glu Lys Ser Phe 85 90
95 Glu Asn Ile Gln Asn Trp Met Lys Ser Ile Lys Glu Asn Ala Ser Ala
100 105 110 Gly Val Glu
Arg Leu Leu Leu Gly Asn Lys Cys Asp Met Glu Ala Lys 115
120 125 Arg Lys Val Gln Arg Glu Gln Ala
Glu Arg Leu Ala Arg Glu His Arg 130 135
140 Ile Arg Phe Phe Glu Thr Ser Ala Lys Ser Ser Val Asn
Val Asp Glu 145 150 155
160 Ala Phe Ser Ser Leu Ala Arg Asp Ile Leu Leu Lys Thr Gly Gly Arg
165 170 175 Arg Ser Gly Asn
Ser Ser Lys Pro Ser Ser Thr Asp Leu Lys Val Ser 180
185 190 Asp Lys Lys Asn Ser Asn Lys Cys Ser
Leu Gly 195 200 80164PRTRattus
Norvegicus 80Met Ser Asp Pro Gly Asp Val Arg Pro Val Pro His Arg Ser Lys
Val 1 5 10 15 Cys
Arg Arg Leu Phe Gly Pro Val Asp Ser Glu Gln Leu Ser Arg Asp
20 25 30 Cys Asp Ala Leu Met
Ala Ser Cys Leu Gln Glu Ala Arg Glu Arg Trp 35
40 45 Asn Phe Asp Phe Ala Thr Glu Thr Pro
Leu Glu Gly Asn Tyr Val Trp 50 55
60 Glu Arg Val Arg Ser Pro Gly Leu Pro Lys Ile Tyr Leu
Ser Pro Gly 65 70 75
80 Ser Arg Arg Arg Asp Asp Leu Gly Gly Asp Lys Arg Pro Ser Thr Ser
85 90 95 Ser Ala Leu Leu
Gln Gly Pro Gly Pro Ala Pro Glu Asp His Val Ala 100
105 110 Leu Ser Leu Ser Cys Thr Leu Val Ser
His Ala Pro Glu Arg Pro Glu 115 120
125 Asp Ser Pro Gly Gly Thr Gly Thr Ser Gln Gly Arg Lys Arg
Arg Gln 130 135 140
Thr Ser Leu Thr Asp Phe Tyr His Ser Lys Arg Arg Leu Val Phe Cys 145
150 155 160 Lys Arg Lys Pro
812077DNAHomo Sapiens 81tccgctccgt tcggccggtt ctcccgggaa gctattaata
gcattacgtc agcctgggac 60tggcaacacg gagtaaacga ccgcgccgcc agcctgaggg
ctataaaagg ggtgatgcaa 120cgctctccaa gccacagtcg cacgcagcca ggcgcgcact
gcacagctct cttctctcgc 180cgccgcccga gcgcaccctt cagcccgcgc gccggccgtg
agtcctcggt gctcgcccgc 240cggccagaca aacagcccgc ccgaccccgt cccgaccctg
gccgccccga gcggagcctg 300gagcaaaatg atgcttcaac acccaggcca ggtctctgcc
tcggaagtga gtgcttctgc 360catcgtcccc tgcctgtccc ctcctgggtc actggtgttt
gaggattttg ctaacctgac 420gccctttgtc aaggaagagc tgaggtttgc catccagaac
aagcacctct gccaccggat 480gtcctctgcg ctggaatcag tcactgtcag cgacagaccc
ctcggggtgt ccatcacaaa 540agccgaggta gcccctgaag aagatgaaag gaaaaagagg
cgacgagaaa gaaataagat 600tgcagctgca aagtgccgaa acaagaagaa ggagaagacg
gagtgcctgc agaaagagtc 660ggagaagctg gaaagtgtga atgctgaact gaaggctcag
attgaggagc tcaagaacga 720gaagcagcat ttgatataca tgctcaacct tcatcggccc
acgtgtattg tccgggctca 780gaatgggagg actccagaag atgagagaaa cctctttatc
caacagataa aagaaggaac 840attgcagagc taagcagtcg tggtatgggg gcgactgggg
agtcctcatt gaatcctcat 900tttataccca aaaccctgaa gccattggag agctgtcttc
ctgtgtacct ctagaatccc 960agcagcagag aaccatcaag gcgggagggc ctgcagtgat
tcagcaggcc cttcccattc 1020tgccccagag tgggtcttgg accagggcaa gtgcatcttt
gcctcaactc caggatttag 1080gccttaacac actggccatt cttatgttcc agatggcccc
cagctggtgt cctgcccgcc 1140tttcatctgg attctacaaa aaaccaggat gcccaccgtt
aggattcagg cagcagtgtc 1200tgtacctcgg gtgggaggga tggggccatc tccttcaccg
tggctaccat tgtcactcgt 1260aggggatgtg gagtgagaac agcatttagt gaagttgtgc
aacggccagg gttgtgcttt 1320ctagcaaata tgctgttatg tccagaaatt gtgtgtgcaa
gaaaactagg caatgtactc 1380ttccgatgtt tgtgtcacac aacactgatg tgacttttat
atgctttttc tcagatctgg 1440tttctaagag ttttgggggg cggggctgtc accacgtgca
gtatctcaag atattcaggt 1500ggccagaaga gcttgtcagc aagaggagga cagaattctc
ccagcgttaa cacaaaatcc 1560atgggcagca tgatggcagg tcctctgttg caaactcagt
tccaaagtca caggaagaaa 1620gcagaaagtt caacttccaa agggttagga ctctccactc
aatgtcttag gtcaggagtt 1680gtgtctaggc tggaagagcc aaagaatatt ccattttcct
ttccttgtgg ttgaaaacca 1740cagtcagtgg agagatgttt ggaaaccaca gtcagtggag
cctgggtggt acccaggctt 1800tagcattatt ggatgtcaat agcattgttt ttgtcatgta
gctgttttaa gaaatctggc 1860ccagggtgtt tgcagctgtg agaagtcact cacactggcc
acaaggacgc tggctactgt 1920ctattaaaat tctgatgttt ctgtgaaatt ctcagagtgt
ttaattgtac tcaatggtat 1980cattacaatt ttctgtaaga gaaaatatta cttatttatc
ctagtattcc taacctgtca 2040gaataataaa tattggaacc aagacatggt aaacatg
2077821925DNAHomo Sapiens 82gggcggaggt ggggttagct
tcagttgacc aaccatgcct tgaggataaa ttggatggga 60tcagatggga agatgtgaca
agaagagaaa tcctcctcta tataggatgc tctgctgttt 120cctaaggatt ttcagcacct
tgccccaaaa tcaaaatgat gcttcaacac ccaggccagg 180tctctgcctc ggaagtgagt
gcttctgcca tcgtcccctg cctgtcccct cctgggtcac 240tggtgtttga ggattttgct
aacctgacgc cctttgtcaa ggaagagctg aggtttgcca 300tccagaacaa gcacctctgc
caccggatgt cctctgcgct ggaatcagtc actgtcagcg 360acagacccct cggggtgtcc
atcacaaaag ccgaggtagc ccctgaagaa gatgaaagga 420aaaagaggcg acgagaaaga
aataagattg cagctgcaaa gtgccgaaac aagaagaagg 480agaagacgga gtgcctgcag
aaagagtcgg agaagctgga aagtgtgaat gctgaactga 540aggctcagat tgaggagctc
aagaacgaga agcagcattt gatatacatg ctcaaccttc 600atcggcccac gtgtattgtc
cgggctcaga atgggaggac tccagaagat gagagaaacc 660tctttatcca acagataaaa
gaaggaacat tgcagagcta agcagtcgtg gtatgggggc 720gactggggag tcctcattga
atcctcattt tatacccaaa accctgaagc cattggagag 780ctgtcttcct gtgtacctct
agaatcccag cagcagagaa ccatcaaggc gggagggcct 840gcagtgattc agcaggccct
tcccattctg ccccagagtg ggtcttggac cagggcaagt 900gcatctttgc ctcaactcca
ggatttaggc cttaacacac tggccattct tatgttccag 960atggccccca gctggtgtcc
tgcccgcctt tcatctggat tctacaaaaa accaggatgc 1020ccaccgttag gattcaggca
gcagtgtctg tacctcgggt gggagggatg gggccatctc 1080cttcaccgtg gctaccattg
tcactcgtag gggatgtgga gtgagaacag catttagtga 1140agttgtgcaa cggccagggt
tgtgctttct agcaaatatg ctgttatgtc cagaaattgt 1200gtgtgcaaga aaactaggca
atgtactctt ccgatgtttg tgtcacacaa cactgatgtg 1260acttttatat gctttttctc
agatctggtt tctaagagtt ttggggggcg gggctgtcac 1320cacgtgcagt atctcaagat
attcaggtgg ccagaagagc ttgtcagcaa gaggaggaca 1380gaattctccc agcgttaaca
caaaatccat gggcagcatg atggcaggtc ctctgttgca 1440aactcagttc caaagtcaca
ggaagaaagc agaaagttca acttccaaag ggttaggact 1500ctccactcaa tgtcttaggt
caggagttgt gtctaggctg gaagagccaa agaatattcc 1560attttccttt ccttgtggtt
gaaaaccaca gtcagtggag agatgtttgg aaaccacagt 1620cagtggagcc tgggtggtac
ccaggcttta gcattattgg atgtcaatag cattgttttt 1680gtcatgtagc tgttttaaga
aatctggccc agggtgtttg cagctgtgag aagtcactca 1740cactggccac aaggacgctg
gctactgtct attaaaattc tgatgtttct gtgaaattct 1800cagagtgttt aattgtactc
aatggtatca ttacaatttt ctgtaagaga aaatattact 1860tatttatcct agtattccta
acctgtcaga ataataaata ttggaaccaa gacatggtaa 1920acatg
1925832454DNAHomo Sapiens
83atctgtgaga acgggatcgg cgaggaggcg acggggagga ggcgacgcgg aggggtgagg
60ggtcctctcc gccgccaggc ggagttggga gccggacgat cccgcacgca gcgcgaggcg
120ggaccccgga ctgactacat ttcccagtct ccgtcgctcc gcgcggccca ccccttcggc
180tctgggcccc gcctcgtggt gccggctggt tcttcgcgct cgcccgactt cccagcggcc
240ccgtgcggcc cgggcatgcc cagtgcgggc gcagcggccc cggccctgga agcgccccgg
300cggagctggc ccgcggtggg ctaggggcag ggccggagcc gcggcggcgg agctgtggat
360ccttcatgat gagagatttg gggacacttc tctctcctgt gtgtagttga tagtttggtg
420gtgaagagat ggctgacagt gtcaaaacct ttctccagga ccttgccaga ggaatcaaag
480actccatctg gggtatttgt accatctcaa agctagatgc tcgaatccag caaaagagag
540aggagcagcg tcgaagaagg gcaagtagtg tcttggcaca gagaagagcc cagagtatag
600agcggaagca agagagtgag ccacgtattg ttagtagaat tttccagtgt tgtgcttgga
660atggtggagt gttctggttc agtctcctct tgttttatcg agtatttatt cctgtgcttc
720agtcggtaac agcccgaatt atcggtgacc catcactaca tggagatgtt tggtcgtggc
780tggaattctt cctcacgtca attttcagtg ctctttgggt gctccccttg tttgtgctta
840gcaaagtggt gaatgccatt tggtttcagg atatagctga cctggcattt gaggtatcag
900ggaggaagcc tcacccattc cctagtgtca gcaaaataat tgctgacatg ctcttcaacc
960ttttgctgca ggctcttttc ctcattcagg gaatgtttgt gagtctcttt cccatccatc
1020ttgtcggtca gctggttagt ctcctgcata tgtcccttct ctactcactg tactgctttg
1080aatatcgttg gttcaataaa ggaattgaaa tgcaccagcg gttgtctaac atagaaagga
1140attggcctta ctactttggg tttggtttgc ccttggcttt tctcacagca atgcagtcct
1200catatattat cagtggctgc cttttctcta tcctctttcc tttattcatt atcagcgcca
1260atgaagcaaa gaccctggca aagcatatct cttccagttg cgcctcttct ccttggtggt
1320cttcttaagc aacagactct tccacaagac agtctacctg cagtcggccc tgagcagctc
1380tacttctgca gagaagttcc cttcaccgca tccgtcgcct gccaaactga aggctactgc
1440aggtcactga gttgcctgcc atccaaaggg gatgggcggg attggaagaa gctgtggcag
1500ctcttttccc tgttcacctc ccgcctgcca gggaaggcag gacccgctct gccaagggcc
1560ctctgcgtat tcccttctct ctgaggaatt gaaatttttg tctctggtgc acgtaaggca
1620gaatgttccc tgacaccagt gtgtggattt ttaacatcac cgtgagtctg aaaggaccac
1680aggtttttct gcagctattt tctagcattt gccagtccct gtgcctggac tgattggaac
1740actttgtttt tctccctgtg ccatttaccc ttccaccttt ccatcctgcc ttctaccacc
1800cttggatgaa tggattttgt aattctagct gttgtatttt gtgaatttgt taattttgtt
1860gtttttctgt gaaacacata cattggatat gggaggtaaa ggagtgtccc agttgctcct
1920ggtcactccc tttatagcca ttactgtctt gtttcttgta actcaggtta ggttttggtc
1980tctcttgctc cactgcaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaag cctgaagaga
2040tgagatagga ggaaagacct cacagccaga tctgctgggt tttgaggagt gattttcttt
2100cttccccttg aaggggaaaa agctattttc attggtacat ttaaagtccc ccaactatgg
2160ggaggtacca attctggaca agtgccacta caacaacact aaacctgaac ttttcaactc
2220cgttggtggt gggaggcagc gggcagaaat ttactgttgg ccactgccag gtctatttca
2280tatttcaaag gaatattggg tgctgcatat aggaactgaa ggggtcaatg tattaaacct
2340gtgattggtt gttttcctgt cattttgaga gactaaatgt ggggggcaga tgtcaaaata
2400cctgtacaat tttaaaatgt cacaattaaa catgagctgg tttcccacaa agtg
2454843460DNAHomo Sapiens 84atctgtgaga acgggatcgg cgaggaggcg acggggagga
ggcgacgcgg aggggtgagg 60ggtcctctcc gccgccaggc ggagttggga gccggacgat
cccgcacgca gcgcgaggcg 120ggaccccgga ctgactacat ttcccagtct ccgtcgctcc
gcgcggccca ccccttcggc 180tctgggcccc gcctcgtggt gccggctggt tcttcgcgct
cgcccgactt cccagcggcc 240ccgtgcggcc cgggcatgcc cagtgcgggc gcagcggccc
cggccctgga agcgccccgg 300cggagctggc ccgcggtggg ctaggggcag ggccggagcc
gcggcggcgg agctgtggat 360ccttcatgat gagagatttg gggacacttc tctctcctgt
gtgtagttga tagtttggtg 420gtgaagagat ggctgacagt gtcaaaacct ttctccagga
ccttgccaga ggaatcaaag 480actccatctg gggtatttgt accatctcaa agctagatgc
tcgaatccag caaaagagag 540aggagcagcg tcgaagaagg gcaagtagtg tcttggcaca
gagaagagcc cagagtatag 600agcggaagca agagagtgag ccacgtattg ttagtagaat
tttccagtgt tgtgcttgga 660atggtggagt gttctggttc agtctcctct tgttttatcg
agtatttatt cctgtgcttc 720agtcggtaac agcccgaatt atcggtgacc catcactaca
tggagatgtt tggtcgtggc 780tggaattctt cctcacgtca attttcagtg ctctttgggt
gctccccttg tttgtgctta 840gcaaagtggt gaatgccatt tggtttcagg atatagctga
cctggcattt gaggtatcag 900ggaggaagcc tcacccattc cctagtgtca gcaaaataat
tgctgacatg ctcttcaacc 960ttttgctgca ggctcttttc ctcattcagg gaatgtttgt
gagtctcttt cccatccatc 1020ttgtcggtca gctggttagt ctcctgcata tgtcccttct
ctactcactg tactgctttg 1080aatatcgttg gttcaataaa ggtaagtcca tctaaagaaa
tccagaaaat ggaggcccag 1140tttggaaatg ctactgctaa gcagacttct taaactactc
atagtcaggc ttttggcaaa 1200caatcctttg agggaagcag cctcattggc aagagggagc
ttaccttcgg cttagtgggt 1260ttaactctca actttgaggc tgggggatgt ggtagtatgg
cattatcttt ttggtgctta 1320acatggtata tctctgactg ggttgtaaga tggcataaat
gagcatgagt tgctctaaat 1380tagagaagtc aaattgatgt cagcatctgg atccttttgg
gggtgtttta gaaagacctt 1440cagatattta ccagggtgtg cgtggttgaa agaggttaac
tgatacttac aggatggcat 1500ccttttgatt tgctatcttg cttagttcca gactaatcct
gacaaaggat gctggtgctg 1560aaattcttaa ttcacttagc ctgtcagctt tgaaattacg
attatagaat tctaagaaac 1620tttgcatgct ttatatcaga tttgtacact tctaatttat
atgctgtagc tctgttctaa 1680atctgtacct aggctgggtg tggtggctca cacctgtaat
cccaacactt tgggaggcca 1740aggtgggtgg atcgcctgag gtcaggagtt caagaccagc
ttggccaata tggtgaaacc 1800ctgtctctac taaaaataca aaaattagct gggcgaggtg
gcaggcgcct gtaatcccag 1860ctacttggga ggctgaggtg ggagaatcgc ttgaaaccag
gaggtggagg ttgcagtgag 1920ctgagattgc accaccgcac tcccgcctgg gcatcaaagc
aagactccat ctcaaataat 1980aataataata ataataataa taataataaa atctgtacct
aaaactcatg gtttgtctac 2040catagttact tagtcacttg actaaaagga aatataatat
ctaattgtat tggctttctt 2100gttttaggaa ttgaaatgca ccagcggttg tctaacatag
aaaggaattg gccttactac 2160tttgggtttg gtttgccctt ggcttttctc acagcaatgc
agtcctcata tattatcagt 2220ggctgccttt tctctatcct ctttccttta ttcattatca
gcgccaatga agcaaagacc 2280ctggcaaagc atatctcttc cagttgcgcc tcttctcctt
ggtggtcttc ttaagcaaca 2340gactcttcca caagacagtc tacctgcagt cggccctgag
cagctctact tctgcagaga 2400agttcccttc accgcatccg tcgcctgcca aactgaaggc
tactgcaggt cactgagttg 2460cctgccatcc aaaggggatg ggcgggattg gaagaagctg
tggcagctct tttccctgtt 2520cacctcccgc ctgccaggga aggcaggacc cgctctgcca
agggccctct gcgtattccc 2580ttctctctga ggaattgaaa tttttgtctc tggtgcacgt
aaggcagaat gttccctgac 2640accagtgtgt ggatttttaa catcaccgtg agtctgaaag
gaccacaggt ttttctgcag 2700ctattttcta gcatttgcca gtccctgtgc ctggactgat
tggaacactt tgtttttctc 2760cctgtgccat ttacccttcc acctttccat cctgccttct
accacccttg gatgaatgga 2820ttttgtaatt ctagctgttg tattttgtga atttgttaat
tttgttgttt ttctgtgaaa 2880cacatacatt ggatatggga ggtaaaggag tgtcccagtt
gctcctggtc actcccttta 2940tagccattac tgtcttgttt cttgtaactc aggttaggtt
ttggtctctc ttgctccact 3000gcaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaagcctg
aagagatgag ataggaggaa 3060agacctcaca gccagatctg ctgggttttg aggagtgatt
ttctttcttc cccttgaagg 3120ggaaaaagct attttcattg gtacatttaa agtcccccaa
ctatggggag gtaccaattc 3180tggacaagtg ccactacaac aacactaaac ctgaactttt
caactccgtt ggtggtggga 3240ggcagcgggc agaaatttac tgttggccac tgccaggtct
atttcatatt tcaaaggaat 3300attgggtgct gcatatagga actgaagggg tcaatgtatt
aaacctgtga ttggttgttt 3360tcctgtcatt ttgagagact aaatgtgggg ggcagatgtc
aaaatacctg tacaatttta 3420aaatgtcaca attaaacatg agctggtttc ccacaaagtg
3460852560DNAHomo Sapiens 85atctgtgaga acgggatcgg
cgaggaggcg acggggagga ggcgacgcgg aggggtgagg 60ggtcctctcc gccgccaggc
ggagttggga gccggacgat cccgcacgca gcgcgaggcg 120ggaccccgga ctgactacat
ttcccagtct ccgtcgctcc gcgcggccca ccccttcggc 180tctgggcccc gcctcgtggt
gccggctggt tcttcgcgct cgcccgactt cccagcggcc 240ccgtgcggcc cgggcatgcc
cagtgcgggc gcagcggccc cggccctgga agcgccccgg 300cggagctggc ccgcggtggg
ctaggggcag ggccggagcc gcggcggcgg agctgtggtt 360gtgcctaggg agaccagttt
tctgccgaat tgcctaggag ctgtggggag atgggcctga 420atggacccgt ggactcagag
gcagcccgtg gagccccgtg ggaaatcctt catgatgaga 480gatttgggga cacttctctc
tcctgtgtgt agttgatagt ttggtggtga agagatggct 540gacagtgtca aaacctttct
ccaggacctt gccagaggaa tcaaagactc catctggggt 600atttgtacca tctcaaagct
agatgctcga atccagcaaa agagagagga gcagcgtcga 660agaagggcaa gtagtgtctt
ggcacagaga agagcccaga gtatagagcg gaagcaagag 720agtgagccac gtattgttag
tagaattttc cagtgttgtg cttggaatgg tggagtgttc 780tggttcagtc tcctcttgtt
ttatcgagta tttattcctg tgcttcagtc ggtaacagcc 840cgaattatcg gtgacccatc
actacatgga gatgtttggt cgtggctgga attcttcctc 900acgtcaattt tcagtgctct
ttgggtgctc cccttgtttg tgcttagcaa agtggtgaat 960gccatttggt ttcaggatat
agctgacctg gcatttgagg tatcagggag gaagcctcac 1020ccattcccta gtgtcagcaa
aataattgct gacatgctct tcaacctttt gctgcaggct 1080cttttcctca ttcagggaat
gtttgtgagt ctctttccca tccatcttgt cggtcagctg 1140gttagtctcc tgcatatgtc
ccttctctac tcactgtact gctttgaata tcgttggttc 1200aataaaggaa ttgaaatgca
ccagcggttg tctaacatag aaaggaattg gccttactac 1260tttgggtttg gtttgccctt
ggcttttctc acagcaatgc agtcctcata tattatcagt 1320ggctgccttt tctctatcct
ctttccttta ttcattatca gcgccaatga agcaaagacc 1380ctggcaaagc atatctcttc
cagttgcgcc tcttctcctt ggtggtcttc ttaagcaaca 1440gactcttcca caagacagtc
tacctgcagt cggccctgag cagctctact tctgcagaga 1500agttcccttc accgcatccg
tcgcctgcca aactgaaggc tactgcaggt cactgagttg 1560cctgccatcc aaaggggatg
ggcgggattg gaagaagctg tggcagctct tttccctgtt 1620cacctcccgc ctgccaggga
aggcaggacc cgctctgcca agggccctct gcgtattccc 1680ttctctctga ggaattgaaa
tttttgtctc tggtgcacgt aaggcagaat gttccctgac 1740accagtgtgt ggatttttaa
catcaccgtg agtctgaaag gaccacaggt ttttctgcag 1800ctattttcta gcatttgcca
gtccctgtgc ctggactgat tggaacactt tgtttttctc 1860cctgtgccat ttacccttcc
acctttccat cctgccttct accacccttg gatgaatgga 1920ttttgtaatt ctagctgttg
tattttgtga atttgttaat tttgttgttt ttctgtgaaa 1980cacatacatt ggatatggga
ggtaaaggag tgtcccagtt gctcctggtc actcccttta 2040tagccattac tgtcttgttt
cttgtaactc aggttaggtt ttggtctctc ttgctccact 2100gcaaaaaaaa aaaaaaaaaa
aaaaaaaaaa aaaaagcctg aagagatgag ataggaggaa 2160agacctcaca gccagatctg
ctgggttttg aggagtgatt ttctttcttc cccttgaagg 2220ggaaaaagct attttcattg
gtacatttaa agtcccccaa ctatggggag gtaccaattc 2280tggacaagtg ccactacaac
aacactaaac ctgaactttt caactccgtt ggtggtggga 2340ggcagcgggc agaaatttac
tgttggccac tgccaggtct atttcatatt tcaaaggaat 2400attgggtgct gcatatagga
actgaagggg tcaatgtatt aaacctgtga ttggttgttt 2460tcctgtcatt ttgagagact
aaatgtgggg ggcagatgtc aaaatacctg tacaatttta 2520aaatgtcaca attaaacatg
agctggtttc ccacaaagtg 2560862179DNAHomo Sapiens
86ggctaccggc gaggacccct tatgggaagg ggccggaggg agcgggacgg ggccgggcac
60atccccgggc gaggctgccc cagatccttc atgatgagag atttggggac acttctctct
120cctgtgtgta gttgatagtt tggtggtgaa gagatggctg acagtgtcaa aacctttctc
180caggaccttg ccagaggaat caaagactcc atctggggta tttgtaccat ctcaaagcta
240gatgctcgaa tccagcaaaa gagagaggag cagcgtcgaa gaagggcaag tagtgtcttg
300gcacagagaa gagcccagag tatagagcgg aagcaagaga gtgagccacg tattgttagt
360agaattttcc agtgttgtgc ttggaatggt ggagtgttct ggttcagtct cctcttgttt
420tatcgagtat ttattcctgt gcttcagtcg gtaacagccc gaattatcgg tgacccatca
480ctacatggag atgtttggtc gtggctggaa ttcttcctca cgtcaatttt cagtgctctt
540tgggtgctcc ccttgtttgt gcttagcaaa gtggtgaatg ccatttggtt tcaggatata
600gctgacctgg catttgaggt atcagggagg aagcctcacc cattccctag tgtcagcaaa
660ataattgctg acatgctctt caaccttttg ctgcaggctc ttttcctcat tcagggaatg
720tttgtgagtc tctttcccat ccatcttgtc ggtcagctgg ttagtctcct gcatatgtcc
780cttctctact cactgtactg ctttgaatat cgttggttca ataaaggaat tgaaatgcac
840cagcggttgt ctaacataga aaggaattgg ccttactact ttgggtttgg tttgcccttg
900gcttttctca cagcaatgca gtcctcatat attatcagtg gctgcctttt ctctatcctc
960tttcctttat tcattatcag cgccaatgaa gcaaagaccc tggcaaagca tatctcttcc
1020agttgcgcct cttctccttg gtggtcttct taagcaacag actcttccac aagacagtct
1080acctgcagtc ggccctgagc agctctactt ctgcagagaa gttcccttca ccgcatccgt
1140cgcctgccaa actgaaggct actgcaggtc actgagttgc ctgccatcca aaggggatgg
1200gcgggattgg aagaagctgt ggcagctctt ttccctgttc acctcccgcc tgccagggaa
1260ggcaggaccc gctctgccaa gggccctctg cgtattccct tctctctgag gaattgaaat
1320ttttgtctct ggtgcacgta aggcagaatg ttccctgaca ccagtgtgtg gatttttaac
1380atcaccgtga gtctgaaagg accacaggtt tttctgcagc tattttctag catttgccag
1440tccctgtgcc tggactgatt ggaacacttt gtttttctcc ctgtgccatt tacccttcca
1500cctttccatc ctgccttcta ccacccttgg atgaatggat tttgtaattc tagctgttgt
1560attttgtgaa tttgttaatt ttgttgtttt tctgtgaaac acatacattg gatatgggag
1620gtaaaggagt gtcccagttg ctcctggtca ctccctttat agccattact gtcttgtttc
1680ttgtaactca ggttaggttt tggtctctct tgctccactg caaaaaaaaa aaaaaaaaaa
1740aaaaaaaaaa aaaagcctga agagatgaga taggaggaaa gacctcacag ccagatctgc
1800tgggttttga ggagtgattt tctttcttcc ccttgaaggg gaaaaagcta ttttcattgg
1860tacatttaaa gtcccccaac tatggggagg taccaattct ggacaagtgc cactacaaca
1920acactaaacc tgaacttttc aactccgttg gtggtgggag gcagcgggca gaaatttact
1980gttggccact gccaggtcta tttcatattt caaaggaata ttgggtgctg catataggaa
2040ctgaaggggt caatgtatta aacctgtgat tggttgtttt cctgtcattt tgagagacta
2100aatgtggggg gcagatgtca aaatacctgt acaattttaa aatgtcacaa ttaaacatga
2160gctggtttcc cacaaagtg
2179872583DNAHomo Sapiens 87atctgtgaga acgggatcgg cgaggaggcg acggggagga
ggcgacgcgg aggggtgagg 60ggtcctctcc gccgccaggc ggagttggga gccggacgat
cccgcacgca gcgcgaggcg 120ggaccccgga ctgactacat ttcccagtct ccgtcgctcc
gcgcggccca ccccttcggc 180tctgggcccc gcctcgtggt gccggctggt tcttcgcgct
cgcccgactt cccagcggcc 240ccgtgcggcc cgggcatgcc cagtgcgggc gcagcggccc
cggccctgga agcgccccgg 300cggagctggc ccgcggtggg ctaggggcag ggccggagcc
gcggcggcgg agctgtggat 360ccttcatgat gagagatttg gggacacttc tctctcctgt
gtgtagttga tagtttggtg 420gtgaagagat ggctgacagt gtcaaaacct ttctccagga
ccttgccaga ggaatcaaag 480actccatctg gggtatttgt accatctcaa agctagatgc
tcgaatccag caaaagagag 540aggagcagcg tcgaagaagg gcaagtagtg tcttggcaca
gagaagagcc cagagtatag 600agcggaagca agagagacgg attcttgccc tgtcaccaag
ctgtcacctg agattgccgt 660ggtgcaatct cagcttactg cagcctctgc ctcccaggtc
caagcaattc ttctgcctca 720gcgaaccggc tggctggaag tacagtgagc cacgtattgt
tagtagaatt ttccagtgtt 780gtgcttggaa tggtggagtg ttctggttca gtctcctctt
gttttatcga gtatttattc 840ctgtgcttca gtcggtaaca gcccgaatta tcggtgaccc
atcactacat ggagatgttt 900ggtcgtggct ggaattcttc ctcacgtcaa ttttcagtgc
tctttgggtg ctccccttgt 960ttgtgcttag caaagtggtg aatgccattt ggtttcagga
tatagctgac ctggcatttg 1020aggtatcagg gaggaagcct cacccattcc ctagtgtcag
caaaataatt gctgacatgc 1080tcttcaacct tttgctgcag gctcttttcc tcattcaggg
aatgtttgtg agtctctttc 1140ccatccatct tgtcggtcag ctggttagtc tcctgcatat
gtcccttctc tactcactgt 1200actgctttga atatcgttgg ttcaataaag gaattgaaat
gcaccagcgg ttgtctaaca 1260tagaaaggaa ttggccttac tactttgggt ttggtttgcc
cttggctttt ctcacagcaa 1320tgcagtcctc atatattatc agtggctgcc ttttctctat
cctctttcct ttattcatta 1380tcagcgccaa tgaagcaaag accctggcaa agcatatctc
ttccagttgc gcctcttctc 1440cttggtggtc ttcttaagca acagactctt ccacaagaca
gtctacctgc agtcggccct 1500gagcagctct acttctgcag agaagttccc ttcaccgcat
ccgtcgcctg ccaaactgaa 1560ggctactgca ggtcactgag ttgcctgcca tccaaagggg
atgggcggga ttggaagaag 1620ctgtggcagc tcttttccct gttcacctcc cgcctgccag
ggaaggcagg acccgctctg 1680ccaagggccc tctgcgtatt cccttctctc tgaggaattg
aaatttttgt ctctggtgca 1740cgtaaggcag aatgttccct gacaccagtg tgtggatttt
taacatcacc gtgagtctga 1800aaggaccaca ggtttttctg cagctatttt ctagcatttg
ccagtccctg tgcctggact 1860gattggaaca ctttgttttt ctccctgtgc catttaccct
tccacctttc catcctgcct 1920tctaccaccc ttggatgaat ggattttgta attctagctg
ttgtattttg tgaatttgtt 1980aattttgttg tttttctgtg aaacacatac attggatatg
ggaggtaaag gagtgtccca 2040gttgctcctg gtcactccct ttatagccat tactgtcttg
tttcttgtaa ctcaggttag 2100gttttggtct ctcttgctcc actgcaaaaa aaaaaaaaaa
aaaaaaaaaa aaaaaaaagc 2160ctgaagagat gagataggag gaaagacctc acagccagat
ctgctgggtt ttgaggagtg 2220attttctttc ttccccttga aggggaaaaa gctattttca
ttggtacatt taaagtcccc 2280caactatggg gaggtaccaa ttctggacaa gtgccactac
aacaacacta aacctgaact 2340tttcaactcc gttggtggtg ggaggcagcg ggcagaaatt
tactgttggc cactgccagg 2400tctatttcat atttcaaagg aatattgggt gctgcatata
ggaactgaag gggtcaatgt 2460attaaacctg tgattggttg ttttcctgtc attttgagag
actaaatgtg gggggcagat 2520gtcaaaatac ctgtacaatt ttaaaatgtc acaattaaac
atgagctggt ttcccacaaa 2580gtg
2583882906DNAHomo Sapiens 88atctgtgaga acgggatcgg
cgaggaggcg acggggagga ggcgacgcgg aggggtgagg 60ggtcctctcc gccgccaggc
ggagttggga gccggacgat cccgcacgca gcgcgaggcg 120ggaccccgga ctgactacat
ttcccagtct ccgtcgctcc gcgcggccca ccccttcggc 180tctgggcccc gcctcgtggt
gccggctggt tcttcgcgct cgcccgactt cccagcggcc 240ccgtgcggcc cgggcatgcc
cagtgcgggc gcagcggccc cggccctgga agcgccccgg 300cggagctggc ccgcggtggg
ctaggggcag ggccggagcc gcggcggcgg agctgtggat 360ccttcatgat gagagatttg
gggacacttc tctctcctgt gtgtagttga tagtttggtg 420gtgaagagat ggctgacagt
gtcaaaacct ttctccagga ccttgccaga ggaatcaaag 480actccatctg gggtatttgt
accatctcaa agctagatgc tcgaatccag caaaagagag 540aggagcagcg tcgaagaagg
gcaagtagtg tcttggcaca gagaagagcc cagagtatag 600agcggaagca agagagacgg
attcttgccc tgtcaccaag ctgtcacctg agattgccgt 660ggtgcaatct cagcttactg
cagcctctgc ctcccaggtc caagcaattc ttctgcctca 720gcgaaccggc tggctggaag
tacaggtgcg caccaccacg cctggctaat tttttatatt 780ctttagtgga gacagggttt
tgccatgttg gccaggctgg tctcgaactc ctgacctcag 840ttgatcgcct accacggcct
cccaaagtgt taggattaca gccgtgagcc actgcgcttg 900accatttttt tagtcttttc
tcattgactg acattagaac attgggagaa catgaggcac 960tgaaaaataa tacagtaccc
acaaaaggta agatataaaa tgaactactg aatgacaatt 1020aggaaataac ttatgcttta
taaactaaat acatgtgatc ttttccagtg agccacgtat 1080tgttagtaga attttccagt
gttgtgcttg gaatggtgga gtgttctggt tcagtctcct 1140cttgttttat cgagtattta
ttcctgtgct tcagtcggta acagcccgaa ttatcggtga 1200cccatcacta catggagatg
tttggtcgtg gctggaattc ttcctcacgt caattttcag 1260tgctctttgg gtgctcccct
tgtttgtgct tagcaaagtg gtgaatgcca tttggtttca 1320ggatatagct gacctggcat
ttgaggtatc agggaggaag cctcacccat tccctagtgt 1380cagcaaaata attgctgaca
tgctcttcaa ccttttgctg caggctcttt tcctcattca 1440gggaatgttt gtgagtctct
ttcccatcca tcttgtcggt cagctggtta gtctcctgca 1500tatgtccctt ctctactcac
tgtactgctt tgaatatcgt tggttcaata aaggaattga 1560aatgcaccag cggttgtcta
acatagaaag gaattggcct tactactttg ggtttggttt 1620gcccttggct tttctcacag
caatgcagtc ctcatatatt atcagtggct gccttttctc 1680tatcctcttt cctttattca
ttatcagcgc caatgaagca aagaccctgg caaagcatat 1740ctcttccagt tgcgcctctt
ctccttggtg gtcttcttaa gcaacagact cttccacaag 1800acagtctacc tgcagtcggc
cctgagcagc tctacttctg cagagaagtt cccttcaccg 1860catccgtcgc ctgccaaact
gaaggctact gcaggtcact gagttgcctg ccatccaaag 1920gggatgggcg ggattggaag
aagctgtggc agctcttttc cctgttcacc tcccgcctgc 1980cagggaaggc aggacccgct
ctgccaaggg ccctctgcgt attcccttct ctctgaggaa 2040ttgaaatttt tgtctctggt
gcacgtaagg cagaatgttc cctgacacca gtgtgtggat 2100ttttaacatc accgtgagtc
tgaaaggacc acaggttttt ctgcagctat tttctagcat 2160ttgccagtcc ctgtgcctgg
actgattgga acactttgtt tttctccctg tgccatttac 2220ccttccacct ttccatcctg
ccttctacca cccttggatg aatggatttt gtaattctag 2280ctgttgtatt ttgtgaattt
gttaattttg ttgtttttct gtgaaacaca tacattggat 2340atgggaggta aaggagtgtc
ccagttgctc ctggtcactc cctttatagc cattactgtc 2400ttgtttcttg taactcaggt
taggttttgg tctctcttgc tccactgcaa aaaaaaaaaa 2460aaaaaaaaaa aaaaaaaaaa
agcctgaaga gatgagatag gaggaaagac ctcacagcca 2520gatctgctgg gttttgagga
gtgattttct ttcttcccct tgaaggggaa aaagctattt 2580tcattggtac atttaaagtc
ccccaactat ggggaggtac caattctgga caagtgccac 2640tacaacaaca ctaaacctga
acttttcaac tccgttggtg gtgggaggca gcgggcagaa 2700atttactgtt ggccactgcc
aggtctattt catatttcaa aggaatattg ggtgctgcat 2760ataggaactg aaggggtcaa
tgtattaaac ctgtgattgg ttgttttcct gtcattttga 2820gagactaaat gtggggggca
gatgtcaaaa tacctgtaca attttaaaat gtcacaatta 2880aacatgagct ggtttcccac
aaagtg 2906893016DNAHomo Sapiens
89atctgtgaga acgggatcgg cgaggaggcg acggggagga ggcgacgcgg aggggtgagg
60ggtcctctcc gccgccaggc ggagttggga gccggacgat cccgcacgca gcgcgaggcg
120ggaccccgga ctgactacat ttcccagtct ccgtcgctcc gcgcggccca ccccttcggc
180tctgggcccc gcctcgtggt gccggctggt tcttcgcgct cgcccgactt cccagcggcc
240ccgtgcggcc cgggcatgcc cagtgcgggc gcagcggccc cggccctgga agcgccccgg
300cggagctggc ccgcggtggg ctaggggcag ggccggagcc gcggcggcgg agctgtggat
360ccttcatgat gagagatttg gggacacttc tctctcctgt gtgtagttga tagtttggtg
420gtgaagagat ggctgacagt gtcaaaacct ttctccagga ccttgccaga ggaatcaaag
480actccatctg gggtatttgt accatctcaa agctagatgc tcgaatccag caaaagagag
540aggagcagcg tcgaagaagg gcaagtagtg tcttggcaca gagaagagcc cagagtatag
600agcggaagca agagagtgag ccacgtattg ttagtagaat tttccagtgt tgtgcttgga
660atggtggagt gttctggttc agtctcctct tgttttatcg agtatttatt cctgtgcttc
720agtcggtaac agcccgaatt atcggtaagt gtataccctg ctccttgtct gttggggaca
780gagtgggaga tgatgtttca gtctccctca gtttactgaa catttcctgt gtaccaggag
840ctttcactgt ttattttctt ttttgttgtt ttattctttt taaaaattta tatttcgtta
900ttctcctaga ggccctttaa gaatgggtac tgttgttcta tccattttat gaatgaggaa
960atgcaagtta ccaaggttaa accattagta agaggcaaag ctgagattta aacccagatg
1020gtatcctgca gatagcgtac tggtaatcac tgtggcatct cgttaccatc atgtaagcag
1080gtttgtgtca agcagcacat atctatggtt tctttgaatt ggaattgtgg ccagaatgtg
1140gtgcgtctat tatgagttag actctttgag ataggtatag tgatgtgctg gcaagaacta
1200gaaagatcca ggaggagaca gagaatagtc acgagatggg ggttccgcat ttggtcttct
1260ggatttccat ttctccattt ctagtaactc gtttcctctt tcttaggtga cccatcacta
1320catggagatg tttggtcgtg gctggaattc ttcctcacgt caattttcag tgctctttgg
1380gtgctcccct tgtttgtgct tagcaaagtg gtgaatgcca tttggtttca ggatatagct
1440gacctggcat ttgaggtatc agggaggaag cctcacccat tccctagtgt cagcaaaata
1500attgctgaca tgctcttcaa ccttttgctg caggctcttt tcctcattca gggaatgttt
1560gtgagtctct ttcccatcca tcttgtcggt cagctggtta gtctcctgca tatgtccctt
1620ctctactcac tgtactgctt tgaatatcgt tggttcaata aaggaattga aatgcaccag
1680cggttgtcta acatagaaag gaattggcct tactactttg ggtttggttt gcccttggct
1740tttctcacag caatgcagtc ctcatatatt atcagtggct gccttttctc tatcctcttt
1800cctttattca ttatcagcgc caatgaagca aagaccctgg caaagcatat ctcttccagt
1860tgcgcctctt ctccttggtg gtcttcttaa gcaacagact cttccacaag acagtctacc
1920tgcagtcggc cctgagcagc tctacttctg cagagaagtt cccttcaccg catccgtcgc
1980ctgccaaact gaaggctact gcaggtcact gagttgcctg ccatccaaag gggatgggcg
2040ggattggaag aagctgtggc agctcttttc cctgttcacc tcccgcctgc cagggaaggc
2100aggacccgct ctgccaaggg ccctctgcgt attcccttct ctctgaggaa ttgaaatttt
2160tgtctctggt gcacgtaagg cagaatgttc cctgacacca gtgtgtggat ttttaacatc
2220accgtgagtc tgaaaggacc acaggttttt ctgcagctat tttctagcat ttgccagtcc
2280ctgtgcctgg actgattgga acactttgtt tttctccctg tgccatttac ccttccacct
2340ttccatcctg ccttctacca cccttggatg aatggatttt gtaattctag ctgttgtatt
2400ttgtgaattt gttaattttg ttgtttttct gtgaaacaca tacattggat atgggaggta
2460aaggagtgtc ccagttgctc ctggtcactc cctttatagc cattactgtc ttgtttcttg
2520taactcaggt taggttttgg tctctcttgc tccactgcaa aaaaaaaaaa aaaaaaaaaa
2580aaaaaaaaaa agcctgaaga gatgagatag gaggaaagac ctcacagcca gatctgctgg
2640gttttgagga gtgattttct ttcttcccct tgaaggggaa aaagctattt tcattggtac
2700atttaaagtc ccccaactat ggggaggtac caattctgga caagtgccac tacaacaaca
2760ctaaacctga acttttcaac tccgttggtg gtgggaggca gcgggcagaa atttactgtt
2820ggccactgcc aggtctattt catatttcaa aggaatattg ggtgctgcat ataggaactg
2880aaggggtcaa tgtattaaac ctgtgattgg ttgttttcct gtcattttga gagactaaat
2940gtggggggca gatgtcaaaa tacctgtaca attttaaaat gtcacaatta aacatgagct
3000ggtttcccac aaagtg
3016902665DNAHomo Sapiens 90aattctcgcg agaagtagag ttgcggttcc ctcgggagag
gggcggaggc tcagaggtgc 60accacgtggg gtttgctgcc ggagcggagt ctccggccgg
cgtccagttt gagtctaggt 120tggagttgga accgtggaga tgcggaagga aaccccaccc
cccctagtgc ccccggcggc 180ccgggagtgg aatcttcccc caaatgcgcc cgcctgcatg
gaacggcagt tggaggctgc 240gcggtaccgg tccgatgggg cgcttctcct cggggcctcc
agcctgagtg ggcgctgctg 300ggccggctcc ctctggcttt ttaaggaccc ctgtgccgcc
cccaacgaag gcttctgctc 360cgccggagtc caaacggagg ctggagtggc tgacctcact
tgggttgggg agagaggtat 420tctagtggcc tccgattcag gtgctgttga attgtgggaa
ctagatgaga atgagacact 480tattgtcagc aagttctgca agtatgagca tgatgacatt
gtgtctacag tcagtgtctt 540gagctctggc acacaagctg tcagtggtag caaagacatc
tgcatcaagg tttgggacct 600tgctcagcag gtggtactga gttcataccg agctcatgct
gctcaggtca cttgtgttgc 660tgcctctcct cacaaggact ctgtgtttct ttcatgcagc
gaggacaata gaattttact 720ctgggatacc cgctgtccca agccagcatc acagattggc
tgcagtgcgc ctggctacct 780tcctacctcg ctggcttggc atcctcagca aagtgaagtc
tttgtctttg gtgatgagaa 840tgggacagtc tcccttgtgg acaccaagag tacaagctgt
gtcctgagct cagctgtaca 900ctcccagtgt gtcactgggc tggtgttctc cccacacagt
gttcccttcc tggcctctct 960cagtgaagac tgctcacttg ctgtgctgga ctcaagcctt
tctgagttgt aagtgtgaag 1020tggaatcctt tgggaatcag ggaaggggag cagtgggtgg
gcgagtcatt ttcctcttca 1080gaaaactgtg ttgtgctttt ggagaacaga ttctccatct
gtatccgaag ggacttggta 1140atggaagcag gctggctgtt gaccctgtcc attcctgggg
cacattcaca accccaagga 1200caagccgtgt ccttggtaga ggggggtggt aggtgaaatt
tttaagtcta gccctccagc 1260gctctcccac aagggggcgg cagtctaccc tctcacataa
agaactgcgt atgaaatgca 1320gcctgctaca gggtaaaagg cagcacctgg aagacctgaa
ttgtacttcc ctccttgccg 1380tgatttgctg cctgttactg cccctcatca ctgtcttgtt
ctatccagca tttcttcatc 1440tatgaaaata gaagactgga ttggatgact gatgacatcc
actgtggata gctacactgc 1500tatcctggcg atgaggccat acagttggtg aaatgtttag
aagccaagcc cacagagact 1560ttgtgagaga tgcgacttgg tccccgctca atcactccct
gcttaccaca gtgggctggg 1620accatcaggt cgtccaccac gttgtgccca cagaacctct
cccagcccct ggacctgcaa 1680gtgttactga gtagattgga tttaagacaa aaagcaagtc
ccccatgagt gtccacttct 1740ttgccctgcc ctctcagctt gtgagacaac acaggagcct
tctatagtat gttgatatgc 1800tagatctgtg ccgttaatag gcatcgtctc tcagcctgag
ggaggctgga ttctgggttc 1860ctgtagtcac agggaggaaa agctttctta aaaatggaca
tgtatgtgcg tgtgagtgtg 1920tgtgtagatt tatagttttt ggtagtggca ggaataaaaa
aaatccatcc tacatcttcc 1980ctaagcactg cctctctctc accccccaaa acaagttgac
gaaagggttt tatgtagctg 2040tctatgagga attggccgtg tctgggtggg ttatgggatg
tgggcatccc tgggttcttg 2100gaagcagctc ttatgctact catagagatg ggattgactt
tattttttta tagtgcttaa 2160ttcaccatta tgagaaatgc ttccagtcac aaaaatgcag
cccagctcac tctgaggaag 2220aagcaggact tggtacggtt ttacacaact ccttaccatt
aaactgaatc agaaatccat 2280tttctggctg aataaaaagt ttggcttgcc tgtgtaatgc
ccactccctt ccccctggct 2340ccctagtgat gggacatata tgagagagaa gtgtttttct
atcatagaca ccatagggga 2400aagtttgggg atgaaggaga gcttaaaggt gtttcaatta
agttagaaaa ctgacacagg 2460ctgttgagaa ttctttgcca cttttcccac cccaaaacag
catggggcct gacatcttct 2520gccctggtcc cctttctctt gatgtggaaa gtctgaatgc
agtatttata gacttctaag 2580gttttaaaat ccagtatcaa gaagaaaatc agaaatactg
gttggtgaaa taaagagttt 2640aggcattgtt ggcctgtctt ttttg
2665912507DNAHomo Sapiens 91aattctcgcg agaagtagag
ttgcggttcc ctcgggagag gggcggaggc tcagaggtgc 60accacgtggg gtttgctgcc
ggagcggagt ctccggccgg cgtccagttt gagtctaggt 120tggagttgga accgtggaga
tgcggaagga aaccccaccc cccctagtgc ccccggcggc 180ccgggagtgg aatcttcccc
caaatgcgcc cgcctgcatg gaacggcagt tggaggctgc 240gcggtaccgg tccgatgggg
cgcttctcct cggggcctcc agcctgagtg ggcgctgctg 300ggccggctcc ctctggcttt
ttaaggaccc ctgtgccgcc cccaacgaag gcttctgctc 360cgccggagtc caaacggagg
ctggagtggc tgacctcact tgggttgggg agagaggtat 420tctagtggcc tccgattcag
gtgctgttga attgtgggaa ctagatgaga atgagacact 480tattgtcagc aagttctgca
agtatgagca tgatgacatt gtgtctacag tcagtgtctt 540gagctctggc acacaagctg
tcagtggtag caaagacatc tgcatcaagg tttgggacct 600tgctcagcag gtggtactga
gttcataccg agctcatgct gctcaggtca cttgtgttgc 660tgcctctcct cacaaggact
ctgtgtttct ttcatgcagc gaggacaata gaattttact 720ctgggatacc cgctgtccca
agccagcatc acagattggc tgcagtgcgc ctggctacct 780tcctacctcg ctggcttggc
atcctcagca aagtgaagtc tttgtctttg gtgatgagaa 840tgggacagtc tcccttgtgg
acaccaagag tacaagctgt gtcctgagct cagctgtaca 900ctcccagtgt gtcactgggc
tggtgttctc cccacacagt gttcccttcc tggcctctct 960cagtgaagac tgctcacttg
ctgtgctgga ctcaagcctt tctgagttgt ttagaagcca 1020agcccacaga gactttgtga
gagatgcgac ttggtccccg ctcaatcact ccctgcttac 1080cacagtgggc tgggaccatc
aggtcgtcca ccacgttgtg cccacagaac ctctcccagc 1140ccctggacct gcaagtgtta
ctgagtagat tggatttaag acaaaaagca agtcccccat 1200gagtgtccac ttctttgccc
tgccctctca gcttgtgaga caacacagga gccttctata 1260gtatgttgat atgctagatc
tgtgccgtta ataggcatcg tctctcagcc tgagggaggc 1320tggattctgg gttcctgtag
tcacagggag gaaaagcttt cttaaaaatg gacatgtatg 1380tgcgtgtgag tgtgtgtgta
gatttatagt ttttggtagt ggcaggaata aaaaaaatcc 1440atcctacatc ttccctaagc
actgcctctc tctcaccccc caaaacaagt tgacgaaagg 1500gttttatgta gctgtctatg
aggaattggc cgtgtctggg tgggttatgg gatgtgggca 1560tccctgggtt cttggaagca
gctcttatgc tactcataga gatgggattg actttatttt 1620tttatagtgc ttaattcacc
attatgagaa atgcttccag tcacaaaaat gcagcccagc 1680tcactctgag gaagaagcag
gacttggtac ggttttacac aactccttac cattaaactg 1740aatcagaaat ccattttctg
gctgaataaa aagtttggct tgcctgtgta atgcccactc 1800ccttccccct ggctccctag
tgatgggaca tatatgagag agaagtgttt ttctatcata 1860gacaccatag gggaaagttt
ggggatgaag gagagcttaa aggtgtttca attaagttag 1920aaaactgaca caggctgttg
agaattcttt gccacttttc ccaccccaaa acagcatggg 1980gcctgacatc ttctgccctg
gtcccctttc tcttgatgtg gaaagtctga atgcagtatt 2040tatagacttc taaggtttta
aaatccagta tcaagaagaa aatcagaaat actggttggt 2100gaaataaaga gtttaggcat
tgttggcctg tcttttttga agcatgtgtg ttatgtgtag 2160ttagatatat ttcacttatg
tgagtcatca tggtgttggt cttgtagccc attatttttc 2220ctgtgcttcc ccagcttccc
aaagtagcta gttagaactt aaggtaaata tttattcttg 2280ggttggtgga gtggatattg
ccagttagga gtcatggatc aattactgat tatattgaaa 2340gtaaatataa tcaattatgt
acttttgagc tttgcaggtt caatttaggt aaaaatcaca 2400ttatgaaact gggaaagtct
gaaggaatat gggcaaaata tttctcagta aagcttccat 2460gcttcaccct tgacatgatt
acccttgagt aaaacatggg aatttgt 2507922198DNAHomo Sapiens
92aattctcgcg agaagtagag ttgcggttcc ctcgggagag gggcggaggc tcagaggtgc
60accacgtggg gtttgctgcc ggagcggagt ctccggccgg cgtccagttt gagtctaggt
120tggagttgga accgtggaga tgcggaagga aaccccaccc cccctagtgc ccccggcggc
180ccgggagtgg aatcttcccc caaatgcgcc cgcctgcatg gaacggcagt tggaggctgc
240gcggtaccgg tccgatgggg cgcttctcct cggggcctcc agcctgagtg ggcgctgctg
300ggccggctcc ctctggcttt ttaaggaccc ctgtgccgcc cccaacgaag gcttctgctc
360cgccggagtc caaacggagg ctggagtggc tgacctcact tgggttgggg agagaggtat
420tctagtggcc tccgattcag gtgctgttga attgtgggaa ctagatgaga atgagacact
480tattgtcagc aagttctgca agtatgagca tgatgacatt gtgtctacag tcagtgtctt
540gagctctggc acacaagctg tcagtggtag caaagacatc tgcatcaagg tttgggacct
600tgctcagcag gtggtactga gttcataccg agctcatgct gctcaggtca cttgtgttgc
660tgcctctcct cacaaggact ctgtgtttct ttcatgcagc gaggacaata gaattttact
720ctgggatacc cgctgtccca agccagcatc acagattgtg aggctctgct aaccccattc
780tgtgcaatga ataccaagag gaagggccag ttcctgggct gcagtgcgcc tggctacctt
840cctacctcgc tggcttggca tcctcagcaa agtgaagtct ttgtctttgg tgatgagaat
900gggacagtct cccttgtgga caccaagagt acaagctgtg tcctgagctc agctgtacac
960tcccagtgtg tcactgggct ggtgttctcc ccacacagtg ttcccttcct ggcctctctc
1020agtgaagact gctcacttgc tgtgctggac tcaagccttt ctgagttgtt tagaagccaa
1080gcccacagag actttgtgag agatgcgact tggtccccgc tcaatcactc cctgcttacc
1140acagtgggct gggaccatca ggtcgtccac cacgttgtgc ccacagaacc tctcccagcc
1200cctggacctg caagtgttac tgagtagatt ggatttaaga caaaaagcaa gtcccccatg
1260agtgtccact tctttgccct gccctctcag cttgtgagac aacacaggag ccttctatag
1320tatgttgata tgctagatct gtgccgttaa taggcatcgt ctctcagcct gagggaggct
1380ggattctggg ttcctgtagt cacagggagg aaaagctttc ttaaaaatgg acatgtatgt
1440gcgtgtgagt gtgtgtgtag atttatagtt tttggtagtg gcaggaataa aaaaaatcca
1500tcctacatct tccctaagca ctgcctctct ctcacccccc aaaacaagtt gacgaaaggg
1560ttttatgtag ctgtctatga ggaattggcc gtgtctgggt gggttatggg atgtgggcat
1620ccctgggttc ttggaagcag ctcttatgct actcatagag atgggattga ctttattttt
1680ttatagtgct taattcacca ttatgagaaa tgcttccagt cacaaaaatg cagcccagct
1740cactctgagg aagaagcagg acttggtacg gttttacaca actccttacc attaaactga
1800atcagaaatc cattttctgg ctgaataaaa agtttggctt gcctgtgtaa tgcccactcc
1860cttccccctg gctccctagt gatgggacat atatgagaga gaagtgtttt tctatcatag
1920acaccatagg ggaaagtttg gggatgaagg agagcttaaa ggtgtttcaa ttaagttaga
1980aaactgacac aggctgttga gaattctttg ccacttttcc caccccaaaa cagcatgggg
2040cctgacatct tctgccctgg tcccctttct cttgatgtgg aaagtctgaa tgcagtattt
2100atagacttct aaggttttaa aatccagtat caagaagaaa atcagaaata ctggttggtg
2160aaataaagag tttaggcatt gttggcctgt cttttttg
2198933984DNAHomo Sapiens 93aattctcgcg agaagtagag ttgcggttcc ctcgggagag
gggcggaggc tcagaggtgc 60accacgtggg gtttgctgcc ggagcggagt ctccggccgg
cgtccagttt gagtctaggt 120tggagttgga accgtggaga tgcggaagga aaccccaccc
cccctagtgc ccccggcggc 180ccgggagtgg aatcttcccc caaatgcgcc cgcctgcatg
gaacggcagt tggaggctgc 240gcggtaccgg tccgatgggg cgcttctcct cggggcctcc
agcctgagtg ggcgctgctg 300ggccggctcc ctctggcttt ttaaggaccc ctgtgccgcc
cccaacgaag gcttctgctc 360cgccggagtc caaacggagg ctggagtggc tgacctcact
tgggttgggg agagaggtat 420tctagtggcc tccgattcag gtgctgttga attgtgggaa
ctagatgaga atgagacact 480tattgtcagc aagttctgca agtatgagca tgatgacatt
gtgtctacag tcagtgtctt 540gagctctggc acacaagctg tcagtggtag caaagacatc
tgcatcaagg tttgggacct 600tgctcagcag gtggtactga gttcataccg agctcatgct
gctcaggtca cttgtgttgc 660tgcctctcct cacaaggact ctgtgtttct ttcatgcagc
gaggacaata gaattttact 720ctgggatacc cgctgtccca agccagcatc acagattggc
tgcagtgcgc ctggctacct 780tcctacctcg ctggcttggc atcctcagca aagtgaagtc
tttgtctttg gtgatgagaa 840tgggacagtc tcccttgtgg acaccaagag tacaagctgt
gtcctgagct cagctgtaca 900ctcccagtgt gtcactgggc tggtgttctc cccacacagt
gttcccttcc tggcctctct 960cagtgaagac tgctcacttg ctgtgctgga ctcaagcctt
tctgagttgt ttagaagcca 1020agcccacaga gactttgtga gagatgcgac ttggtccccg
ctcaatcact ccctgcttac 1080cacagtgggc tgggaccatc aggtcgtcca ccacgttgtg
cccacagaac ctctcccagc 1140ccctggacct gcaagtgtta ctgagtagat tggatttaag
acaaaaagca agtcccccat 1200gagtgtccac ttctttgccc tgccctctca gcttgtgaga
caacacagga gccttctata 1260gtatgttgat atgctagatc tgtgccgtta ataggcatcg
tctctcagcc tgagggaggc 1320tggattctgg gttcctgtag tcacagggag gaaaagcttt
cttaaaaatg gacatgtatg 1380tgcgtgtgag tgtgtgtgta gatttatagt ttttggtagt
ggcaggaata aaaaaaatcc 1440atcctacatc ttccctaagc actgcctctc tctcaccccc
caaaacaagt tgacgaaagg 1500gttttatgta gctgtctatg aggaattggc cgtgtctggg
tgggttatgg gatgtgggca 1560tccctgggtt cttggaagca gctcttatgc tactcataga
gatgggattg actttatttt 1620tttatagtgc ttaattcacc attatgagaa atgcttccag
tcacaaaaat gcagcccagc 1680tcactctgag gaagaagcag gacttgctgt tctctggtcc
accaagggct atgaggctca 1740ccccttggat ggtgctcaga accacaagga atactgaaga
agccttgcct atgatttcag 1800gtggcatcag acattgggct aattttcaag gtgtctctcc
ttcccaacag gacagtcgga 1860gtctggttct ttaataaata gctatatgga tcttacttac
tggttcacaa tcatattaca 1920gcagcaaaaa cacccaagct ctaactgctc tgggcctcca
gccatgtttc ctccagatag 1980catgttagaa aggacaggag attttaaaaa tcagattgga
cttcagaggg ctccaaattt 2040tcttgccaca tctagacctg aaagtaaaga gctctgatta
ttaagaggca gattctcgtt 2100gcatttggac agcgtgagta atggtcacac tgaacacatt
agaatcagtt gtgaaattga 2160ttttgtttca aaaaaggata agcaagctgt agtctcaatt
ttgagttaat tgaaatttct 2220caagaacttc atcagcagct cacatgatac agttttggaa
gagtaaacaa ggtaagcaga 2280caaccctggg accccaaaca cattttcttt tttagttctc
catcaaaaat aggcatttct 2340ggagttttgg tctcactgag tgatcacagg actgctgcaa
tccagggaac tgagggagct 2400gtgagcatct gagaagaaag gttagctctt gttttaagtt
gtagagacaa cttaaaacaa 2460gttgtgacac aattagtgat cccataatct tttatcatct
ggtacaacat ttaatatagt 2520agcattctac ttactgtgga aactccttgt ttcacaaatg
atgttctgca gcttcaatat 2580gtaatggatg gaccatcaaa gttcaaaata taataaggaa
tttaattccc aaacaacatc 2640ctttaacatt ctggtgaaag cccagccagt gtcactggtt
gaaagtgcct tcagtggata 2700tagctatatt tcacctgtcc ctgtgatcat gaggtaccag
attccggtca agcatttcac 2760tttgggaggc accatgttgt aaacattagg aatttcaggt
gcaaactaat tttccattct 2820ggtagtaact cttacctgga gtgtcagcta agtcatgaaa
attgtttaga ttagaaaatg 2880cactttttat atatagccta aattagcttc atgttctgta
gtttctgcag cttgtctcag 2940aaatcctctg agtagaactg atgtatgaga ccctttaaga
ccattatcca actgcagttt 3000gcttggcaga gttagcatta atgcaccctt tgatctaggc
acctggaggc aggtaagaca 3060ggctctgcgt gcaccaccgt ccctggacct gttgtggcgg
actccttgaa gcaagatcaa 3120cttgggcttt gtttgagttt ttaaagtctt ttttttttaa
tgtaaaattt gtcattttaa 3180ctttttaagt atacagttca gtggcattaa gtttatttgc
atttttgtgc agctttcacc 3240acttccatct ccaaaacttt ttcatcatcc caaactgaaa
ctgtacttat taaacagtaa 3300ctccccttcc tcaagaccct ggcaatcacc attcatcttc
atttctataa atttgactat 3360tctagacata cgtgtaagtg ggagcataca atatttggtt
tttttagagg ggggttctgg 3420cttaatttta taaggtgtta acttgttcct caaaatgtgt
tctataaact ggcagcattt 3480gcatatcttg gaacttgctt gaaatacaga atgtccagat
ctactgagtc agaatttaca 3540ttttcaaaag cttcctacgt gactcatgca tattaaagtt
tgggaagcac tgacttagat 3600taccttttga gaattccaga tgggtcagaa accagacaga
aatactcagt agtgagaagc 3660tatggtgtat cagaagctgt taggcatttc atggtttggt
agtgagcaag acagatagtt 3720ttcctgtatt cagcgactta gtctagagag agacaggatg
gaattaagtg tttaggtgct 3780agccaaaagt aaagattcgt agaaaacaag ggttcatatc
ccagtcatca aagtgataaa 3840ttttccctgc ttaacattta gattaaaaag taataattag
gccgggtgtg agccctgcgt 3900ctggcccatg actatcattt ctttcttatg gggtttattg
tggtcactgc ctagcttgta 3960tctgattgat cagggaactg attc
3984942389DNAHomo Sapiens 94aattctcgcg agaagtagag
ttgcggttcc ctcgggagag gggcggaggc tcagaggtgc 60accacgtggg gtttgctgcc
ggagcggagt ctccggccgg cgtccagttt gagtctaggt 120tggagttgga accgtggaga
tgcggaagga aaccccaccc cccctagtgc ccccggcggc 180ccgggagtgg aatcttcccc
caaatgcgcc cgcctgcatg gaacggcagt tggaggctgc 240gcggtaccgg tccggtgagc
cgagatcccg ggcctgggag ctcccttacc ccggcccagg 300gcgcccctcc ccggagactg
accctcccag cccatccccg ccctgcatgt tatcctgacc 360ctgggtcgcg tcaccgagct
gtccccagcc ctgccccgcg ttcctgagct cagatccaga 420cccggccgga acgctgttct
gtgcggtctc catggaggcg aacccttcta cccttcacgc 480gctgacagct tgtacccccc
gtagatgggg cgcttctcct cggggcctcc agcctgagtg 540ggcgctgctg ggccggctcc
ctctggcttt ttaaggaccc ctgtgccgcc cccaacgaag 600gcttctgctc cgccggagtc
caaacggagg ctggagtggc tgacctcact tgggttgggg 660agagaggtat tctagtggcc
tccgattcag gtgctgttga attgtgggaa ctagatgaga 720atgagacact tattgtcagc
aagttctgca agtatgagca tgatgacatt gtgtctacag 780tcagtgtctt gagctctggc
acacaagctg tcagtggtag caaagacatc tgcatcaagg 840tttgggacct tgctcagcag
gtggtactga gttcataccg agctcatgct gctcaggtca 900cttgtgttgc tgcctctcct
cacaaggact ctgtgtttct ttcatgcagc gaggacaata 960gaattttact ctgggatacc
cgctgtccca agccagcatc acagattggc tgcagtgcgc 1020ctggctacct tcctacctcg
ctggcttggc atcctcagca aagtgaagtc tttgtctttg 1080gtgatgagaa tgggacagtc
tcccttgtgg acaccaagag tacaagctgt gtcctgagct 1140cagctgtaca ctcccagtgt
gtcactgggc tggtgttctc cccacacagt gttcccttcc 1200tggcctctct cagtgaagac
tgctcacttg ctgtgctgga ctcaagcctt tctgagttgt 1260ttagaagcca agcccacaga
gactttgtga gagatgcgac ttggtccccg ctcaatcact 1320ccctgcttac cacagtgggc
tgggaccatc aggtcgtcca ccacgttgtg cccacagaac 1380ctctcccagc ccctggacct
gcaagtgtta ctgagtagat tggatttaag acaaaaagca 1440agtcccccat gagtgtccac
ttctttgccc tgccctctca gcttgtgaga caacacagga 1500gccttctata gtatgttgat
atgctagatc tgtgccgtta ataggcatcg tctctcagcc 1560tgagggaggc tggattctgg
gttcctgtag tcacagggag gaaaagcttt cttaaaaatg 1620gacatgtatg tgcgtgtgag
tgtgtgtgta gatttatagt ttttggtagt ggcaggaata 1680aaaaaaatcc atcctacatc
ttccctaagc actgcctctc tctcaccccc caaaacaagt 1740tgacgaaagg gttttatgta
gctgtctatg aggaattggc cgtgtctggg tgggttatgg 1800gatgtgggca tccctgggtt
cttggaagca gctcttatgc tactcataga gatgggattg 1860actttatttt tttatagtgc
ttaattcacc attatgagaa atgcttccag tcacaaaaat 1920gcagcccagc tcactctgag
gaagaagcag gacttggtac ggttttacac aactccttac 1980cattaaactg aatcagaaat
ccattttctg gctgaataaa aagtttggct tgcctgtgta 2040atgcccactc ccttccccct
ggctccctag tgatgggaca tatatgagag agaagtgttt 2100ttctatcata gacaccatag
gggaaagttt ggggatgaag gagagcttaa aggtgtttca 2160attaagttag aaaactgaca
caggctgttg agaattcttt gccacttttc ccaccccaaa 2220acagcatggg gcctgacatc
ttctgccctg gtcccctttc tcttgatgtg gaaagtctga 2280atgcagtatt tatagacttc
taaggtttta aaatccagta tcaagaagaa aatcagaaat 2340actggttggt gaaataaaga
gtttaggcat tgttggcctg tcttttttg 2389952429DNAHomo Sapiens
95aattctcgcg agaagtagag ttgcggttcc ctcgggagag gggcggaggc tcagaggtgc
60accacgtggg gtttgctgcc ggagcggagt ctccggccgg cgtccagttt gagtctaggt
120tggagttgga accgtggaga tgcggaagga aaccccaccc cccctagtgc ccccggcggc
180ccgggagtgg aatcttcccc caaatgcgcc cgcctgcatg gaacggcagt tggaggctgc
240gcggtaccgg tccgatgggg cgcttctcct cggggcctcc agcctgagtg ggcgctgctg
300ggccggctcc ctctggcttt ttaaggaccc ctgtgccgcc cccaacgaag gcttctgctc
360cgccggagtc caaacggagg ctggagtggc tgacctcact tgggttgggg agagaggtat
420tctagtggcc tccgattcag gtgctgttga attgtgggaa ctagatgaga atgagacact
480tattgtcagc aagttctgca agtatgagca tgatgacatt gtgtctacag tcagtgtctt
540gagctctggc acacaagctg tcagtggtag caaagacatc tggtgggtcc ctgttctcat
600tgctcctgtc tctaagcctc ctgtgggtgc ctttcctatc ctgttaacct cattaggtaa
660cattttgggc ttattctaag aatccagtga cttattttag catgtctata aggtttcctt
720agggattttg cagtccatcg taagtagacc atagcagcag tccaagaggc aaagacttgg
780ggaatgttga ttacaggaag ttcttgtttg aacacgtttt tatgttgata gtgtaggtca
840agattaaatg tctgtttgct tttgcttctt agcatcaagg tttgggacct tgctcagcag
900gtggtactga gttcataccg agctcatgct gctcaggtca cttgtgttgc tgcctctcct
960cacaaggact ctgtgtttct ttcatgcagc gaggacaata gaattttact ctgggatacc
1020cgctgtccca agccagcatc acagattggc tgcagtgcgc ctggctacct tcctacctcg
1080ctggcttggc atcctcagca aagtgaagtc tttgtctttg gtgatgagaa tgggacagtc
1140tcccttgtgg acaccaagag tacaagctgt gtcctgagct cagctgtaca ctcccagtgt
1200gtcactgggc tggtgttctc cccacacagt gttcccttcc tggcctctct cagtgaagac
1260tgctcacttg ctgtgctgga ctcaagcctt tctgagttgt ttagaagcca agcccacaga
1320gactttgtga gagatgcgac ttggtccccg ctcaatcact ccctgcttac cacagtgggc
1380tgggaccatc aggtcgtcca ccacgttgtg cccacagaac ctctcccagc ccctggacct
1440gcaagtgtta ctgagtagat tggatttaag acaaaaagca agtcccccat gagtgtccac
1500ttctttgccc tgccctctca gcttgtgaga caacacagga gccttctata gtatgttgat
1560atgctagatc tgtgccgtta ataggcatcg tctctcagcc tgagggaggc tggattctgg
1620gttcctgtag tcacagggag gaaaagcttt cttaaaaatg gacatgtatg tgcgtgtgag
1680tgtgtgtgta gatttatagt ttttggtagt ggcaggaata aaaaaaatcc atcctacatc
1740ttccctaagc actgcctctc tctcaccccc caaaacaagt tgacgaaagg gttttatgta
1800gctgtctatg aggaattggc cgtgtctggg tgggttatgg gatgtgggca tccctgggtt
1860cttggaagca gctcttatgc tactcataga gatgggattg actttatttt tttatagtgc
1920ttaattcacc attatgagaa atgcttccag tcacaaaaat gcagcccagc tcactctgag
1980gaagaagcag gacttggtac ggttttacac aactccttac cattaaactg aatcagaaat
2040ccattttctg gctgaataaa aagtttggct tgcctgtgta atgcccactc ccttccccct
2100ggctccctag tgatgggaca tatatgagag agaagtgttt ttctatcata gacaccatag
2160gggaaagttt ggggatgaag gagagcttaa aggtgtttca attaagttag aaaactgaca
2220caggctgttg agaattcttt gccacttttc ccaccccaaa acagcatggg gcctgacatc
2280ttctgccctg gtcccctttc tcttgatgtg gaaagtctga atgcagtatt tatagacttc
2340taaggtttta aaatccagta tcaagaagaa aatcagaaat actggttggt gaaataaaga
2400gtttaggcat tgttggcctg tcttttttg
2429961563DNAHomo Sapiens 96aattctcgcg agaagtagag ttgcggttcc ctcgggagag
gggcggaggc tcagaggtgc 60accacgtggg gtttgctgcc ggagcggagt ctccggccgg
cgtccagttt gagtctaggt 120tggagttgga accgtggaga tgcggaagga aaccccaccc
cccctagtgc ccccggcggc 180ccgggagtgg aatcttcccc caaatgcgcc cgcctgcatg
gaacggcagt tggaggctgc 240gcggtaccgg tccgatgggg cgcttctcct cggggcctcc
agcctgagtg ggcgctgctg 300ggccggctcc ctctggcttt ttaaggaccc ctgtgccgcc
cccaacgaag gcttctgctc 360cgccggagtc caaacggagg ctggagtggc tgacctcact
tgggttgggg agagaggtat 420tctagtggcc tccgattcag gtgctgttga attgtgggaa
ctagatgaga atgagacact 480tattgtcagc aagttctgca agtatgagca tgatgacatt
gtgtctacag tcagtgtctt 540gagctctggc acacaagctg tcagtggtag caaagacatc
tgcatcaagg tttgggacct 600tgctcagcag gtggtactga gttcataccg agctcatgct
gctcaggtca cttgtgttgc 660tgcctctcct cacaaggact ctgtgtttct ttcatgcagc
gaggacaata gaattttact 720ctgggatacc cgctgtccca agccagcatc acagattggc
tgcagtgcgc ctggctacct 780tcctacctcg ctggcttggc atcctcagca aagtgaagtc
tttgtctttg gtgatgagaa 840tgggacagtc tcccttgtgg acaccaagag tacaagctgt
gtcctgagct cagctgtaca 900ctcccagtgt gtcactgggc tggtgttctc cccacacagt
gttcccttcc tggcctctct 960cagtgaagac tgctcacttg ctgtgctgga ctcaagcctt
tctgagttca tttcttcatc 1020tatgaaaata gaagactgga ttggatgact gatgacatcc
actgtggata gctacactgc 1080tatcctggcg atgaggccat acagttggtg aaatgtttag
aagccaagcc cacagagact 1140ttgtgagaga tgcgacttgg tccccgctca atcactccct
gcttaccaca gtgggctggg 1200accatcaggt cgtccaccac gttgtgccca cagaacctct
cccagcccct ggacctgcaa 1260gtgttactga gtagattgga tttaagacaa aaagcaagtc
ccccatgagt gtccacttct 1320ttgccctgcc ctctcagctt gtgagacaac acaggagcct
tctatagtat gttgatatgc 1380tagatctgtg ccgttaatag gcatcgtctc tcagcctgag
ggaggctgga ttctgggttc 1440ctgtagtcac agggaggaaa agctttctta aaaatggaca
tgtatgtgcg tgtgagtgtg 1500tgtgtagatt tatagttttt ggtagtggca ggaataaaaa
aaatccatcc tacatcttcc 1560cta
1563972289DNAHomo Sapiens 97aattctcgcg agaagtagag
ttgcggttcc ctcgggagag gggcggaggc tcagaggtgc 60accacgtggg gtttgctgcc
ggagcggagt ctccggccgg cgtccagttt gagtctaggt 120tggagttgga accgtggaga
tgcggaagga aaccccaccc cccctagtgc ccccggcggc 180ccgggagtgg aatcttcccc
caaatgcgcc cgcctgcatg gaacggcagt tggaggctgc 240gcggtaccgg tccgatgggg
cgcttctcct cggggcctcc agcctgagtg ggcgctgctg 300ggccggctcc ctctggcttt
ttaaggaccc ctgtgccgcc cccaacgaag gcttctgctc 360cgccggagtc caaacggagg
ctggagtggc tgacctcact tgggttgggg agagaggtat 420tctagtggcc tccgattcag
gtgagtcact atcccattat ccacccccac ccccgggtgg 480aacggtagaa tggagacttg
gggtaccgta gggttgagct caatatctaa cgtcctatac 540tcagtgcttg gaggagcctg
agagtgttgg ccccgaatgc aaactcttgt gtgctgttga 600attgtgggaa ctagatgaga
atgagacact tattgtcagc aagttctgca agtatgagca 660tgatgacatt gtgtctacag
tcagtgtctt gagctctggc acacaagctg tcagtggtag 720caaagacatc tgcatcaagg
tttgggacct tgctcagcag gtggtactga gttcataccg 780agctcatgct gctcaggtca
cttgtgttgc tgcctctcct cacaaggact ctgtgtttct 840ttcatgcagc gaggacaata
gaattttact ctgggatacc cgctgtccca agccagcatc 900acagattggc tgcagtgcgc
ctggctacct tcctacctcg ctggcttggc atcctcagca 960aagtgaagtc tttgtctttg
gtgatgagaa tgggacagtc tcccttgtgg acaccaagag 1020tacaagctgt gtcctgagct
cagctgtaca ctcccagtgt gtcactgggc tggtgttctc 1080cccacacagt gttcccttcc
tggcctctct cagtgaagac tgctcacttg ctgtgctgga 1140ctcaagcctt tctgagttgt
ttagaagcca agcccacaga gactttgtga gagatgcgac 1200ttggtccccg ctcaatcact
ccctgcttac cacagtgggc tgggaccatc aggtcgtcca 1260ccacgttgtg cccacagaac
ctctcccagc ccctggacct gcaagtgtta ctgagtagat 1320tggatttaag acaaaaagca
agtcccccat gagtgtccac ttctttgccc tgccctctca 1380gcttgtgaga caacacagga
gccttctata gtatgttgat atgctagatc tgtgccgtta 1440ataggcatcg tctctcagcc
tgagggaggc tggattctgg gttcctgtag tcacagggag 1500gaaaagcttt cttaaaaatg
gacatgtatg tgcgtgtgag tgtgtgtgta gatttatagt 1560ttttggtagt ggcaggaata
aaaaaaatcc atcctacatc ttccctaagc actgcctctc 1620tctcaccccc caaaacaagt
tgacgaaagg gttttatgta gctgtctatg aggaattggc 1680cgtgtctggg tgggttatgg
gatgtgggca tccctgggtt cttggaagca gctcttatgc 1740tactcataga gatgggattg
actttatttt tttatagtgc ttaattcacc attatgagaa 1800atgcttccag tcacaaaaat
gcagcccagc tcactctgag gaagaagcag gacttggtac 1860ggttttacac aactccttac
cattaaactg aatcagaaat ccattttctg gctgaataaa 1920aagtttggct tgcctgtgta
atgcccactc ccttccccct ggctccctag tgatgggaca 1980tatatgagag agaagtgttt
ttctatcata gacaccatag gggaaagttt ggggatgaag 2040gagagcttaa aggtgtttca
attaagttag aaaactgaca caggctgttg agaattcttt 2100gccacttttc ccaccccaaa
acagcatggg gcctgacatc ttctgccctg gtcccctttc 2160tcttgatgtg gaaagtctga
atgcagtatt tatagacttc taaggtttta aaatccagta 2220tcaagaagaa aatcagaaat
actggttggt gaaataaaga gtttaggcat tgttggcctg 2280tcttttttg
2289981118DNAHomo Sapiens
98aattctcgcg agaagtagag ttgcggttcc ctcgggagag gggcggaggc tcagaggtgc
60accacgtggg gtttgctgcc ggagcggagt ctccggccgg cgtccagttt gagtctaggt
120tggagttgga accgtggaga tgcggaagga aaccccaccc cccctagtgc ccccggcggc
180ccgggagtgg aatcttcccc caaatgcgcc cgcctgcatg gaacggcagt tggaggctgc
240gcggtaccgg tccgatgggg cgcttctcct cggggcctcc agcctgagtg ggcgctgctg
300ggccggctcc ctctggcttt ttaaggaccc ctgtgccgcc cccaacgaag gcttctgctc
360cgccggagtc caaacggagg ctggagtggc tgacctcact tgggttgggg agagaggtat
420tctagtggcc tccgattcag gtgctgttga attgtgggaa ctagatgaga atgagacact
480tattgtcagc aagttctgca agtatgagca tgatgacatt gtgtctacag tcagtgtctt
540gagctctggc acacaagctg tcagtggtag caaagacatc tgcatcaagg tttgggacct
600tgctcagcag gtggtactga gttcataccg agctcatgct gctcaggtca cttgtgttgc
660tgcctctcct cacaaggact ctgtgtttct ttcatgcagc gaggacaata gaattttact
720ctgggatacc cgctgtccca agccagcatc acagattggc tgcagtgcgc ctggctacct
780tcctacctcg ctggcttggc atcctcagca aagtgaagtc tttgtctttg gtgatgagaa
840tgggacagtc tcccttgtgg acaccaagag tacaagctgt gtcctgagct cagctgtaca
900ctcccagtgt gtcactgggc tggtgttctc cccacacagt gttcccttcc tggcctctct
960cagtgaagac tgctcacttg ctgtgctgga ctcaagcctt tctgagttgg ctggttcttg
1020tgctgaaaca ccacgatggt gctgcccata aactcgtgtg ttatttcacc aactgggcac
1080acagtcggcc aggccctgcc tcgatcttgc cccatgac
1118992105DNAHomo Sapiens 99aattctcgcg agaagtagag ttgcggttcc ctcgggagag
gggcggaggc tcagaggtgc 60accacgtggg gtttgctgcc ggagcggagt ctccggccgg
cgtccagttt gagtctaggt 120tggagttgga accgtggaga tgcggaagga aaccccaccc
cccctagtgc ccccggcggc 180ccgggagtgg aatcttcccc caaatgcgcc cgcctgcatg
gaacggcgct tctcctcggg 240gcctccagcc tgagtgggcg ctgctgggcc ggctccctct
ggctttttaa ggacccctgt 300gccgccccca acgaaggctt ctgctccgcc ggagtccaaa
cggaggctgg agtggctgac 360ctcacttggg ttggggagag aggtattcta gtggcctccg
attcaggtgc tgttgaattg 420tgggaactag atgagaatga gacacttatt gtcagcaagt
tctgcaagta tgagcatgat 480gacattgtgt ctacagtcag tgtcttgagc tctggcacac
aagctgtcag tggtagcaaa 540gacatctgca tcaaggtttg ggaccttgct cagcaggtgg
tactgagttc ataccgagct 600catgctgctc aggtcacttg tgttgctgcc tctcctcaca
aggactctgt gtttctttca 660tgcagcgagg acaatagaat tttactctgg gatacccgct
gtcccaagcc agcatcacag 720attggctgca gtgcgcctgg ctaccttcct acctcgctgg
cttggcatcc tcagcaaagt 780gaagtctttg tctttggtga tgagaatggg acagtctccc
ttgtggacac caagagtaca 840agctgtgtcc tgagctcagc tgtacactcc cagtgtgtca
ctgggctggt gttctcccca 900cacagtgttc ccttcctggc ctctctcagt gaagactgct
cacttgctgt gctggactca 960agcctttctg agttgtttag aagccaagcc cacagagact
ttgtgagaga tgcgacttgg 1020tccccgctca atcactccct gcttaccaca gtgggctggg
accatcaggt cgtccaccac 1080gttgtgccca cagaacctct cccagcccct ggacctgcaa
gtgttactga gtagattgga 1140tttaagacaa aaagcaagtc ccccatgagt gtccacttct
ttgccctgcc ctctcagctt 1200gtgagacaac acaggagcct tctatagtat gttgatatgc
tagatctgtg ccgttaatag 1260gcatcgtctc tcagcctgag ggaggctgga ttctgggttc
ctgtagtcac agggaggaaa 1320agctttctta aaaatggaca tgtatgtgcg tgtgagtgtg
tgtgtagatt tatagttttt 1380ggtagtggca ggaataaaaa aaatccatcc tacatcttcc
ctaagcactg cctctctctc 1440accccccaaa acaagttgac gaaagggttt tatgtagctg
tctatgagga attggccgtg 1500tctgggtggg ttatgggatg tgggcatccc tgggttcttg
gaagcagctc ttatgctact 1560catagagatg ggattgactt tattttttta tagtgcttaa
ttcaccatta tgagaaatgc 1620ttccagtcac aaaaatgcag cccagctcac tctgaggaag
aagcaggact tggtacggtt 1680ttacacaact ccttaccatt aaactgaatc agaaatccat
tttctggctg aataaaaagt 1740ttggcttgcc tgtgtaatgc ccactccctt ccccctggct
ccctagtgat gggacatata 1800tgagagagaa gtgtttttct atcatagaca ccatagggga
aagtttgggg atgaaggaga 1860gcttaaaggt gtttcaatta agttagaaaa ctgacacagg
ctgttgagaa ttctttgcca 1920cttttcccac cccaaaacag catggggcct gacatcttct
gccctggtcc cctttctctt 1980gatgtggaaa gtctgaatgc agtatttata gacttctaag
gttttaaaat ccagtatcaa 2040gaagaaaatc agaaatactg gttggtgaaa taaagagttt
aggcattgtt ggcctgtctt 2100ttttg
21051001720DNAHomo Sapiens 100agaaagcaac tagcacagcc
atgcccaggc caggacccgt gacacagcga tgctctcaga 60tgctgctgat gttacagatg
ttgttggggg caccctgagg gggcaccctg actctgcagg 120tgagaacctt ctggggttcc
taggaccctc ggacaagcac tctgatccgg atgactccag 180gtcccaggag ttgcagaaac
gccaccagga ccttcagagc accagttaga caaggagagc 240caggaggagc tgggccccaa
cctcatccaa aagcacagac tcccaggctg gaatggtgtc 300ctcatatcga ggaagaggat
actgaggccc agaaatgtgc cctagcttta ctaggagcgc 360ccccacctaa agatcctccc
cctaaataca cccccagacc ccgcccagct gtggtcattg 420gagtgtttac tctgcaggca
gggggaggag ggcgggactg agcaggcgga gacggacaaa 480gtccggggac tataaaggcc
ggtccggcag catctggtca gtcccagctc agagccgcaa 540cctgcacagc catgcccggg
caagaactca ggacggtgaa tggctctcag atgctcctgg 600tgttgctggt gctctcgtgg
ctgccgcatg ggggcgccct gtctctggcc gaggcgagcc 660gcgcaagttt cccgggaccc
tcagagttgc actccgaaga ctccagattc cgagagttgc 720ggaaacgcta cgaggacctg
ctaaccaggc tgcgggccaa ccagagctgg gaagattcga 780acaccgacct cgtcccggcc
cctgcagtcc ggatactcac gccagaagtg cggctgggat 840ccggcggcca cctgcacctg
cgtatctctc gggccgccct tcccgagggg ctccccgagg 900cctcccgcct tcaccgggct
ctgttccggc tgtccccgac ggcgtcaagg tcgtgggacg 960tgacacgacc gctgcggcgt
cagctcagcc ttgcaagacc ccaggcgccc gcgctgcacc 1020tgcgactgtc gccgccgccg
tcgcagtcgg accaactgct ggcagaatct tcgtccgcac 1080ggccccagct ggagttgcac
ttgcggccgc aagccgccag ggggcgccgc agagcgcgtg 1140cgcgcaacgg ggaccactgt
ccgctcgggc ccgggcgttg ctgccgtctg cacacggtcc 1200gcgcgtcgct ggaagacctg
ggctgggccg attgggtgct gtcgccacgg gaggtgcaag 1260tgaccatgtg catcggcgcg
tgcccgagcc agttccgggc ggcaaacatg cacgcgcaga 1320tcaagacgag cctgcaccgc
ctgaagcccg acacggtgcc agcgccctgc tgcgtgcccg 1380ccagctacaa tcccatggtg
ctcattcaaa agaccgacac cggggtgtcg ctccagacct 1440atgatgactt gttagccaaa
gactgccact gcatatgagc agtcctggtc cttccactgt 1500gcacctgcgc gggggacgcg
acctcagttg tcctgccctg tggaatgggc tcaaggttcc 1560tgagacaccc gattcctgcc
caaacagctg tatttatata agtctgttat ttattattaa 1620tttattgggg tgaccttctt
ggggactcgg gggctggtct gatggaactg tgtatttatt 1680taaaactctg gtgataaaaa
taaagctgtc tgaactgttc 17201011396DNAHomo Sapiens
101agaaagcaac tagcacagcc atgcccaggc caggacccgt gacacagcga tgctctcaga
60tgctgctgat gttacagatg ttgttggggg cacccctgac tctgcaggtg agaaccttct
120ggggttccta ggaccctcgg acaagcactc tgatccggat gactccaggt cccaggagtt
180gcagaaacgc caccaggacc ttcagagcac cagttagaca aggagagcca ggaggagctg
240ggccccaacc tcatccaaaa gcacagatgc tcctggtgtt gctggtgctc tcgtggctgc
300cgcatggggg cgccctgtct ctggccgagg cgagccgcgc aagtttcccg ggaccctcag
360agttgcactc cgaagactcc agattccgag agttgcggaa acgctacgag gacctgctaa
420ccaggctgcg ggccaaccag agctgggaag attcgaacac cgacctcgtc ccggcccctg
480cagtccggat actcacgcca gaagtgcggc tgggatccgg cggccacctg cacctgcgta
540tctctcgggc cgcccttccc gaggggctcc ccgaggcctc ccgccttcac cgggctctgt
600tccggctgtc cccgacggcg tcaaggtcgt gggacgtgac acgaccgctg cggcgtcagc
660tcagccttgc aagaccccag gcgcccgcgc tgcacctgcg actgtcgccg ccgccgtcgc
720agtcggacca actgctggca gaatcttcgt ccgcacggcc ccagctggag ttgcacttgc
780ggccgcaagc cgccaggggg cgccgcagag cgcgtgcgcg caacggggac cactgtccgc
840tcgggcccgg gcgttgctgc cgtctgcaca cggtccgcgc gtcgctggaa gacctgggct
900gggccgattg ggtgctgtcg ccacgggagg tgcaagtgac catgtgcatc ggcgcgtgcc
960cgagccagtt ccgggcggca aacatgcacg cgcagatcaa gacgagcctg caccgcctga
1020agcccgacac ggtgccagcg ccctgctgcg tgcccgccag ctacaatccc atggtgctca
1080ttcaaaagac cgacaccggg gtgtcgctcc agacctatga tgacttgtta gccaaagact
1140gccactgcat atgagcagtc ctggtccttc cactgtgcac ctgcgcgggg gacgcgacct
1200cagttgtcct gccctgtgga atgggctcaa ggttcctgag acacccgatt cctgcccaaa
1260cagctgtatt tatataagtc tgttatttat tattaattta ttggggtgac cttcttgggg
1320actcgggggc tggtctgatg gaactgtgta tttatttaaa actctggtga taaaaataaa
1380gctgtctgaa ctgttc
13961023148DNAHomo Sapiens 102agaaagcaac tagcacagcc atgcccaggc caggacccgt
gacacagcga tgctctcaga 60tgctgctgat gttacagatg ttgttggggg caccctgagg
gggcaccctg actctgcagg 120tgagaacctt ctggggttcc taggaccctc ggacaagcac
tctgatccgg atgactccag 180gtcccaggag ttgcagaaac gccaccagga ccttcagagc
accagttaga caaggagagc 240caggaggagc tgggccccaa cctcatccaa aagcacagac
tcccaggctg gaatggtgtc 300ctcatatcga ggaagaggat actgaggccc agaaatgtgc
cctagcttta ctaggagcgc 360ccccacctaa agatcctccc cctaaataca cccccagacc
ccgcccagct gtggtcattg 420gagtgtttac tctgcaggca gggggaggag ggcgggactg
agcaggcgga gacggacaaa 480gtccggggac tataaaggcc ggtccggcag catctggtca
gtcccagctc agagccgcaa 540cctgcacagc catgcccggg caagaactca ggacggtgaa
tggctctcag atgctcctgg 600tgttgctggt gctctcgtgg ctgccgcatg ggggcgccct
gtctctggcc gaggcgagcc 660gcgcaagttt cccgggaccc tcagagttgc actccgaaga
ctccagattc cgagagttgc 720ggaaacgcta cgaggacctg ctaaccaggc tgcgggccaa
ccagagctgg gaagattcga 780acaccgacct cgtcccggcc cctgcagtcc ggatactcac
gccagaaggt aagtgaaatc 840ttagagatcc cctcccaccc cccaagcagc ccccatatct
aatcagggat tcctcatctt 900gaaaagccca gacctacctt tgagcctcag ttgccccatc
tgtgccctgg gtaggaatat 960cctggatccc cttgggtctg atggggtagc cgatgcctga
tttgcaccca caacgtggga 1020ggttataacc tgtccccaag ttgcaaatgg ggaaactgag
gtacagggat gccagggacc 1080ctcctgaatg tgcacagcac ctgggaaacc cggggacggg
gtcgggcgtg cggtgtgggc 1140atggtccctg acctgggctg gggccaggat ccaagagaaa
caatgggggt gtggtgcatg 1200gatagaagtt tgtgatgggc agagccagct ggagctggtt
ctgaatctga tgaaatcgct 1260tgtcaaggca ctgctaaagt cacatgcaac gagcgacttg
ttaggggagg aggagagtat 1320tttccccatc tctgtgccct ccatggaggc tccaggggtg
cagggcactg gatgaggtct 1380gggctgtggt gggacccagg agggggcagg cagaggggca
cactcttagc ccgccctaaa 1440cccatctgtg ccgtgtgact ccggcaaacc tctcaccctt
gctaagccta gcaactaggt 1500taaggcaccc tcaaacccca gtctccccag tctccctaac
acttgtacca gcctgagggg 1560ctgtgattcc tagaggctca gtagtctgga atgtgatggg
tttggcactc ttcatttctc 1620gggattacac ctgtaatccc agcactttag gaggccaagg
tgggagcatc gctttaggcc 1680agaacattgc agcctgggca gtatagcgag aatccatctc
taccaaaaat gtttaaaaaa 1740aattagccag acatgatggt gtgtgcctgt agtctcagtt
attcaggagg ctgaggcggg 1800aggagcactt gaatccagga gattgaggct gcactgagcc
atgatgcagt ggcacgatct 1860tggctcactg caacctccac cgccccgatt caagccattc
ttctgcctca gcctcccgag 1920tagctgggat cacaggcgcc agccaccatg cccagctaat
ttttggtagt tttagtagaa 1980gcgggcgttt caccatattg gccacatatc ggccaggctg
gtcttgaact cctgacctca 2040agtgatccac ctgcatcggc ctcccaaagt gctgggatta
caggcgtgag ccaccgcgcc 2100cgcacggaga aatgctcttg gtaggggaaa taacttgtgc
aaaggcgccg ccgccgtggt 2160gagatccagc ttggcgtgtt aggggaaatg ggcaccctcg
ttcctggaaa acggtaggcc 2220tgtgggtgac cagcttccct atctgtcttc ccacagtgcg
gctgggatcc ggcggccacc 2280tgcacctgcg tatctctcgg gccgcccttc ccgaggggct
ccccgaggcc tcccgccttc 2340accgggctct gttccggctg tccccgacgg cgtcaaggtc
gtgggacgtg acacgaccgc 2400tgcggcgtca gctcagcctt gcaagacccc aggcgcccgc
gctgcacctg cgactgtcgc 2460cgccgccgtc gcagtcggac caactgctgg cagaatcttc
gtccgcacgg ccccagctgg 2520agttgcactt gcggccgcaa gccgccaggg ggcgccgcag
agcgcgtgcg cgcaacgggg 2580accactgtcc gctcgggccc gggcgttgct gccgtctgca
cacggtccgc gcgtcgctgg 2640aagacctggg ctgggccgat tgggtgctgt cgccacggga
ggtgcaagtg accatgtgca 2700tcggcgcgtg cccgagccag ttccgggcgg caaacatgca
cgcgcagatc aagacgagcc 2760tgcaccgcct gaagcccgac acggtgccag cgccctgctg
cgtgcccgcc agctacaatc 2820ccatggtgct cattcaaaag accgacaccg gggtgtcgct
ccagacctat gatgacttgt 2880tagccaaaga ctgccactgc atatgagcag tcctggtcct
tccactgtgc acctgcgcgg 2940gggacgcgac ctcagttgtc ctgccctgtg gaatgggctc
aaggttcctg agacacccga 3000ttcctgccca aacagctgta tttatataag tctgttattt
attattaatt tattggggtg 3060accttcttgg ggactcgggg gctggtctga tggaactgtg
tatttattta aaactctggt 3120gataaaaata aagctgtctg aactgttc
31481032268DNAHomo Sapiens 103agaaagcaac tagcacagcc
atgcccaggc caggacccgt gacacagcga tgctctcaga 60tgctgctgat gttacagatg
ttgttggggg caccctgagg gggcaccctg actctgcagg 120tgagaacctt ctggggttcc
taggaccctc ggacaagcac tctgatccgg atgactccag 180gtcccaggag ttgcagaaac
gccaccagga ccttcagagc accagttaga caaggagagc 240caggaggagc tgggccccaa
cctcatccaa aagcacagac tcccaggctg gaatggtgtc 300ctcatatcga ggaagaggat
actgaggccc agaaatgtgc cctagcttta ctaggagcgc 360ccccacctaa agatcctccc
cctaaataca cccccagacc ccgcccagct gtggtcattg 420gagtgtttac tctgcaggca
gggggaggag ggcgggactg agcaggcgga gacggacaaa 480gtccggggac tataaaggcc
ggtccggcag catctggtca gtcccagctc agagccgcaa 540cctgcacagc catgcccggg
caagaactca ggacggtgaa tggctctcag atgctcctgg 600tgttgctggt gctctcgtgg
ctgccgcatg ggggcgccct gtctctggcc gaggcgagcc 660gcgcaagttt cccgggaccc
tcagagttgc actccgaaga ctccagattc cgagagttgc 720ggaaacgcta cgaggacctg
ctaaccaggc tgcgggccaa ccagagctgg gaagattcga 780acaccgacct cgtcccggcc
cctgcagtcc ggatactcac gccagaaggt aagtgaaatc 840ttagagatcc cctcccaccc
cccaagcagc ccccatatct aatcagggat tcctcatctt 900gaaaagccca gacctacctt
tgagcctcag ttgccccatc tgtgccctgg gtaggaatat 960cctggatccc cttgggtctg
atggggtagc cgatgcctga tttgcaccca caacgtggga 1020ggttataacc tgtccccaag
ttgcaaatgg ggaaactgag gtacagggat gccagggacc 1080ctcctgaatg tgcacagcac
ctgggaaacc cggggacggg gtcgggcgtg cggtgtgggc 1140atggtccctg acctgggctg
gggccaggat ccaagagaaa caatgggggt gtggtgcatg 1200gatagaagtt tgtgatgggc
agagccagct ggagctggtt ctgaatctga tgaaatcgct 1260tgtcaaggca ctgctaaagt
cacatgcaac gagcgacttg ttaggggagg aggagagtat 1320tttccccatc tctgtgccct
ccatggaggc tccaggggtg cagggcactg gatgagtgcg 1380gctgggatcc ggcggccacc
tgcacctgcg tatctctcgg gccgcccttc ccgaggggct 1440ccccgaggcc tcccgccttc
accgggctct gttccggctg tccccgacgg cgtcaaggtc 1500gtgggacgtg acacgaccgc
tgcggcgtca gctcagcctt gcaagacccc aggcgcccgc 1560gctgcacctg cgactgtcgc
cgccgccgtc gcagtcggac caactgctgg cagaatcttc 1620gtccgcacgg ccccagctgg
agttgcactt gcggccgcaa gccgccaggg ggcgccgcag 1680agcgcgtgcg cgcaacgggg
accactgtcc gctcgggccc gggcgttgct gccgtctgca 1740cacggtccgc gcgtcgctgg
aagacctggg ctgggccgat tgggtgctgt cgccacggga 1800ggtgcaagtg accatgtgca
tcggcgcgtg cccgagccag ttccgggcgg caaacatgca 1860cgcgcagatc aagacgagcc
tgcaccgcct gaagcccgac acggtgccag cgccctgctg 1920cgtgcccgcc agctacaatc
ccatggtgct cattcaaaag accgacaccg gggtgtcgct 1980ccagacctat gatgacttgt
tagccaaaga ctgccactgc atatgagcag tcctggtcct 2040tccactgtgc acctgcgcgg
gggacgcgac ctcagttgtc ctgccctgtg gaatgggctc 2100aaggttcctg agacacccga
ttcctgccca aacagctgta tttatataag tctgttattt 2160attattaatt tattggggtg
accttcttgg ggactcgggg gctggtctga tggaactgtg 2220tatttattta aaactctggt
gataaaaata aagctgtctg aactgttc 22681041925DNAHomo Sapiens
104agaaagcaac tagcacagcc atgcccaggc caggacccgt gacacagcga tgctctcaga
60tgctgctgat gttacagatg ttgttggggg caccctgagg gggcaccctg actctgcagg
120tgagaacctt ctggggttcc taggaccctc ggacaagcac tctgatccgg atgactccag
180gtcccaggag ttgcagaaac gccaccagga ccttcagagc accagttaga caaggagagc
240caggaggagc tgggccccaa cctcatccaa aagcacagac tcccaggctg gaatggtgtc
300ctcatatcga ggaagaggat actgaggccc agaaatgtgc cctagcttta ctaggagcgc
360ccccacctaa agatcctccc cctaaataca cccccagacc ccgcccagct gtggtcattg
420gagtgtttac tctgcaggca gggggaggag ggcgggactg agcaggcgga gacggacaaa
480gtccggggac tataaaggcc ggtccggcag catctggtca gtcccagctc agagccgcaa
540cctgcacagc catgcccggg caagaactca ggacggtgaa tggctctcag atgctcctgg
600tgttgctggt gctctcgtgg ctgccgcatg ggggcgccct gtctctggcc gaggcgagcc
660gcgcaagttt cccgggaccc tcagagttgc actccgaaga ctccagattc cgagagttgc
720ggaaacgcta cgaggacctg ctaaccaggc tgcgggccaa ccagagctgg gaagattcga
780acaccgacct cgtcccggcc cctgcagtcc ggatactcac gccagaaggt aagtgaaatc
840ttagagatcc cctcccaccc cccaagcagc ccccatatct aatcagggat tcctcatctt
900gaaaagccca gacctacctt tgagcctcag ttgccccatc tgtgccctgg gtaggaatat
960cctggatccc cttgggtctg atggggtagc cgatgcctga tttgcaccca caacgtggga
1020ggttataacc tgtccccaag ttgcaaatgg ggaaactgag gtacagggat gccagggacc
1080ctcctgaatg tgcacagcac ctgggaaacc cggggacggg gtcgggcgtg cggtgtgggc
1140atggtccctg acctgggctg gggccaggat ccaagagaaa caatgggggt gtggtgcatg
1200gatagaagtt tgtgatgggc agagccagct ggagctggtt ctgaatctga tgaaatcgct
1260tgtcaaggca ctgctaaagt cacatgcaac gagcgacttg ttaggggagg aggagagtat
1320tttccccatc tctgtgccct ccatggaggc tccaggggtg cagggcactg gatgaggtct
1380gggctgtggt gggacccagg agggggcagg cagaggggca cactcttagc ccgccctaaa
1440cccatctgtg ccgtgtgact ccggcaaacc tctcaccctt gctaagccta gcaactaggt
1500taaggcaccc tcaaacccca gtctccccag tctccctaac acttgtacca gcctgagggg
1560ctgtgattcc tagaggctca gtagtctgga atgtgatggg tttggcactc ttcatttctc
1620gggattacac ctgtaatccc agcactttag gaggccaagg tgggagcatc gctttaggcc
1680agaacattgc agcctgggca gtatagcgag aatccatctc taccaaaaat gtttaaaaaa
1740aattagccag acatgatggt gtgtgcctgt agtctcagtt attcaggagg ctgaggcggg
1800aggagcactt gaatccagga gattgaggct gcactgagcc atgagtgccc cactgcactc
1860cagcctgggt aacagcaaga ccataataaa taaataaata agtgaagcaa gtaagttttt
1920gactg
19251051034DNAHomo Sapiens 105aaggcggggg cgggggcggg gcggcggccg tgggtccctg
ccggccggcg gcgggcgcag 60acagcggcgg gcgcaggacg tgcactatgg ctcggggctc
gctgcgccgg ttgctgcggc 120tcctcgtgct ggggctctgg ctggcgttgc tgcgctccgt
ggccggggag caagcgccag 180gcaccgcccc ctgctcccgc ggcagctcct ggagcgcgga
cctggacaag tgcatggact 240gcgcgtcttg cagggcgcga ccgcacagcg acttctgcct
gggctgcgct gcagcacctc 300ctgccccctt ccggctgctt tggcccatcc ttgggggcgc
tctgagcctg accttcgtgc 360tggggctgct ttctggcttt ttggtctgga gacgatgccg
caggagagag aagttcacca 420cccccataga ggagaccggc ggagagggct gcccagctgt
ggcgctgatc cagtgacaat 480gtgccccctg ccagccgggg ctcgcccact catcattcat
tcatccattc tagagccagt 540ctctgcctcc cagacgcggc gggagccaag ctcctccaac
cacaaggggg gtggggggcg 600gtgaatcacc tctgaggcct gggcccaggg ttcaggggaa
ccttccaagg tgtctggttg 660ccctgcctct ggctccagaa cagaaaggga gcctcacgct
ggctcacaca aaacagctga 720cactgactaa ggaactgcag catttgcaca ggggaggggg
gtgccctcct tcctagaggc 780cctgggggcc aggctgactt ggggggcaga cttgacacta
ggccccactc actcagatgt 840cctgaaattc caccacgggg gtcaccctgg ggggttaggg
acctattttt aacactaggg 900ggctggccca ctaggagggc tggccctaag atacagaccc
ccccaactcc ccaaagcggg 960gaggagatat ttattttggg gagagtttgg aggggaggga
gaatttatta ataaaagaat 1020ctttaacttt aaat
10341061757DNAHomo Sapiens 106aaggcggggg cgggggcggg
gcggcggccg tgggtccctg ccggccggcg gcgggcgcag 60acagcggcgg gcgcaggacg
tgcactatgg ctcggggctc gctgcgccgg ttgctgcggc 120tcctcgtgct ggggctctgg
ctggcgttgc tgcgctccgt ggccggggag caagcgccag 180gtacgcggga ctccggggtc
ggggaacccc gggccggggc tcgggagccg gactgggtgt 240ctggagaaca gcgccgaact
gggggaacag gcggatgtgg ggatctgggg tcaggtggcc 300ttcaaacagc tcgctcccgg
ctgtgggaag ttccatcact ctccaagctt cattcacaat 360ccgggcctca gtttctccca
ccgtccaatt ggggttgggg ggggtcttca gttccacaag 420tccgaagtac ttcgaatgga
gagagaaagt gagtgagggc gggatgttta gtctaggaag 480gggcacgccc ccagcctggt
ccgtacaggg tctaactagc cccagtgatc gacgagttgg 540ggaggccgtc gagaggcact
agggtctgtg ccctctatac catgtggggt gcccccttcc 600atccggtgac ttcagtgccc
agctatgcgg ggggagggac tggggtcggg cccggtgccc 660aggagtgagt cacccgccgg
cggcaggggg gttgtgggga cctgaccccc cccaccccca 720gcgtcccgcg ctacgccctc
cctcccggag ctgccgtgtc ccggtcgggc cgtgcggtca 780cctgtgagga atgcgcgggg
agggcgccgg tgactcacgt tattcgagcc ggccgaccct 840gacctcagac cccagaatag
ccgagtcccg cccccagcct ctgacccgag gccccctccc 900caggcaccgc cccctgctcc
cgcggcagct cctggagcgc ggacctggac aagtgcatgg 960actgcgcgtc ttgcagggcg
cgaccgcaca gcgacttctg cctgggctgc gctgcagcac 1020ctcctgcccc cttccggctg
ctttggccca tccttggggg cgctctgagc ctgaccttcg 1080tgctggggct gctttctggc
tttttggtct ggagacgatg ccgcaggaga gagaagttca 1140ccacccccat agaggagacc
ggcggagagg gctgcccagc tgtggcgctg atccagtgac 1200aatgtgcccc ctgccagccg
gggctcgccc actcatcatt cattcatcca ttctagagcc 1260agtctctgcc tcccagacgc
ggcgggagcc aagctcctcc aaccacaagg ggggtggggg 1320gcggtgaatc acctctgagg
cctgggccca gggttcaggg gaaccttcca aggtgtctgg 1380ttgccctgcc tctggctcca
gaacagaaag ggagcctcac gctggctcac acaaaacagc 1440tgacactgac taaggaactg
cagcatttgc acaggggagg ggggtgccct ccttcctaga 1500ggccctgggg gccaggctga
cttggggggc agacttgaca ctaggcccca ctcactcaga 1560tgtcctgaaa ttccaccacg
ggggtcaccc tggggggtta gggacctatt tttaacacta 1620gggggctggc ccactaggag
ggctggccct aagatacaga cccccccaac tccccaaagc 1680ggggaggaga tatttatttt
ggggagagtt tggaggggag ggagaattta ttaataaaag 1740aatctttaac tttaaat
17571071060DNAHomo Sapiens
107aaggcggggg cgggggcggg gcggcggccg tgggtccctg ccggccggcg gcgggcgcag
60acagcggcgg gcgcaggacg tgcactatgg ctcggggctc gctgcgccgg ttgctgcggc
120tcctcgtgct ggggctctgg ctggcgttgc tgcgctccgt ggccggggag caagcgccag
180cctctgaccc gaggccccct ccccaggcac cgccccctgc tcccgcggca gctcctggag
240cgcggacctg gacaagtgca tggactgcgc gtcttgcagg gcgcgaccgc acagcgactt
300ctgcctgggc tgcgctgcag cacctcctgc ccccttccgg ctgctttggc ccatccttgg
360gggcgctctg agcctgacct tcgtgctggg gctgctttct ggctttttgg tctggagacg
420atgccgcagg agagagaagt tcaccacccc catagaggag accggcggag agggctgccc
480agctgtggcg ctgatccagt gacaatgtgc cccctgccag ccggggctcg cccactcatc
540attcattcat ccattctaga gccagtctct gcctcccaga cgcggcggga gccaagctcc
600tccaaccaca aggggggtgg ggggcggtga atcacctctg aggcctgggc ccagggttca
660ggggaacctt ccaaggtgtc tggttgccct gcctctggct ccagaacaga aagggagcct
720cacgctggct cacacaaaac agctgacact gactaaggaa ctgcagcatt tgcacagggg
780aggggggtgc cctccttcct agaggccctg ggggccaggc tgacttgggg ggcagacttg
840acactaggcc ccactcactc agatgtcctg aaattccacc acgggggtca ccctgggggg
900ttagggacct atttttaaca ctagggggct ggcccactag gagggctggc cctaagatac
960agaccccccc aactccccaa agcggggagg agatatttat tttggggaga gtttggaggg
1020gagggagaat ttattaataa aagaatcttt aactttaaat
10601081269DNAHomo Sapiens 108aaggcggggg cgggggcggg gcggcggccg tgggtccctg
ccggccggcg gcgggcgcag 60acagcggcgg gcgcaggacg tgcactatgg ctcggggctc
gctgcgccgg ttgctgcggc 120tcctcgtgct ggggctctgg ctggcgttgc tgcgctccgt
ggccggggag caagcgccag 180gcaccgcccc ctgctcccgc ggcagctcct ggagcgcgga
cctggacaag tgcatggact 240gcgcgtcttg cagggcgcga ccgcacagcg acttctgcct
gggctgtgag tggggggcag 300ggccagtggc cagcggaccc cagactggga gggagggtgg
ctggtgcgca gagcggggcc 360gagagctttg catctgggaa atcattcggg aggaggtggg
agctgggagg gggctccggt 420cagggaggag gccacgtttg ggagaaggca gaaggctcag
tcttaggggg cggggctggc 480ctggagaggg gcgaggtctg actccgagtc ccgcccccag
gcgctgcagc acctcctgcc 540cccttccggc tgctttggcc catccttggg ggcgctctga
gcctgacctt cgtgctgggg 600ctgctttctg gctttttggt ctggagacga tgccgcagga
gagagaagtt caccaccccc 660atagaggaga ccggcggaga gggctgccca gctgtggcgc
tgatccagtg acaatgtgcc 720ccctgccagc cggggctcgc ccactcatca ttcattcatc
cattctagag ccagtctctg 780cctcccagac gcggcgggag ccaagctcct ccaaccacaa
ggggggtggg gggcggtgaa 840tcacctctga ggcctgggcc cagggttcag gggaaccttc
caaggtgtct ggttgccctg 900cctctggctc cagaacagaa agggagcctc acgctggctc
acacaaaaca gctgacactg 960actaaggaac tgcagcattt gcacagggga ggggggtgcc
ctccttccta gaggccctgg 1020gggccaggct gacttggggg gcagacttga cactaggccc
cactcactca gatgtcctga 1080aattccacca cgggggtcac cctggggggt tagggaccta
tttttaacac tagggggctg 1140gcccactagg agggctggcc ctaagataca gaccccccca
actccccaaa gcggggagga 1200gatatttatt ttggggagag tttggagggg agggagaatt
tattaataaa agaatcttta 1260actttaaat
12691092774DNAHomo Sapiens 109aatccggctg gcagccgatt
gacctgaccc aggcgagggt tgctgcaccg agtatttagt 60ttggccccct actgaatgaa
gacactttgt taaattctcc aatgagagac gcttagaggt 120aggggcgtgg aagggggccg
gggaatttga ggccagataa cgggaagtgt gagccgattg 180gccggacttc tcactccacg
gcccagccgt ttacggatcg cggaggccat ccatcaaaag 240aattacacca atcagcggcg
aaaatgcccc cttctcgcga gaaagccccg ccctccaata 300tattcctcgt tagggcaggc
gcggcccctt cggctccgag ctgaccctga tcagggccga 360gttgtctcgg cggcgctgcc
gaggcctcca cccaggacag tccccctccc cgggcctctc 420tcctcttgcc tacgagtccc
ctctcctcgt aggcctctcg gatctgatat cgtggggtga 480ggtgagcagg cccggggagg
gtggttaccg ctgaggagct gcagtctctg tcaagatgat 540agaggtactg acaacaactg
actctcagaa actgctacac cagctgaatg ccctgttgga 600acaggagtct agatgtcagc
caaaggtctg tggtttgaga ctaattgagt ctgcacacga 660taatggcctc agaatgactg
caagactaag ggactttgaa gtaaaagatc ttcttagtct 720aactcagttc tttggctttg
acacagagac attttctcta gctgtgaatt tactggacag 780attcctgtct aaaatgaagg
tacagcccaa gcaccttggg tgtgttggac tgagctgctt 840ttatttggct gtaaaatcaa
tagaagagga aaggaatgtc ccattggcaa ctgacttgat 900ccgaataagt caatataggt
ttacggtttc agacttgatg agaatggaaa agattgtatt 960ggagaaggtg tgttggaaag
tcaaagctac tactgccttt caatttctgc aactgtatta 1020ttcactcctt caagagaact
tgccacttga aaggagaaat agcattaatt ttgaaagact 1080agaagctcaa ctgaaggcat
gtcattgcag gatcatattt tctaaagcaa agccttctgt 1140gttggcattg tctatcattg
cattagagat ccaagcacag aagtgtgtag agttaacaga 1200aggaatagaa tgtcttcaga
aacattccaa gataaatggc agagatctga ccttctggca 1260agagcttgta tccaaatgtt
taactgaata ttcatcaaat aagtgttcca aaccaaatgt 1320tcagaagttg aaatggattg
tttctgggcg tactgcacgg caattgaagc atagctacta 1380cagaataact caccttccaa
caattcctga aatggtccct taactggatt attacagcac 1440caaaaaactt ctctgaagcc
tttctccaca accttgttct atggattcca taatgttaca 1500atggatttaa gctatgaagc
ctcaaaacat cacgagataa gcatgatggt ctcagacttg 1560ggaaaactgc ctaatattat
gctgtagtgg aattatgttt agatttgaat tcatctgtga 1620agcattcaaa tcaaagctaa
aagcctaaat gtgaaatgct aatgacaagc ctgagaaggt 1680aaactgtgaa tcttcatttc
tatcattgat ctaactttag atattggatc aatatattta 1740ggtggtattg aaaatgctat
tggaggagtc acactaatac tatcaactat cagtcttccc 1800acagcttcaa tcactgtcat
tattctaatc ctactcctac ttaaatttta agttatgagg 1860tttatgtcaa aagcaacatt
tcacaaatgt acttttaagg cataataagg gttaacattc 1920taggcagtat aaacacaccc
cataatgcaa gtaataggta atctagagat gtggacttta 1980ttgctatatg ggaattacat
ttaaatttga gggcatttta tataaagaaa aatacagacc 2040tataaagttt ggcatattca
ttaagttatc ttttaatatt tttttctaga aaacaggtga 2100catttgtatc tacgataaaa
atttttatac agaacctact gcctcaaact gaatcccatc 2160aagaaaacta gtttctattg
tattagtaac tcaaaataaa ttatcacttc gaaaacttgc 2220tttcccacac taaggtaagt
tcagactaga ttgaacactc cagaattttt tactacagac 2280tgtttttaag ttagaagtga
tggcaatttt ataaatagag aatatacttc cactgatgcc 2340cttactgtgc caaaacaaaa
atcttaagaa aagcaagtag acaccttcat aactatgaat 2400gaagctgctg aagtagtgtt
taggatcctc catggcagtt agtgaatgta agaagtacag 2460tgttaaagtg ttgtaaacag
ttactcagtg caatgtatag cctgagtcta tccatgatgg 2520ctatatccaa tttgacatca
cgttatggat cagtacacaa tgaaaaacca aagaaccaca 2580gtatatctta ttcttaactt
ttgtaaacca tgttttatgg gtaacttttt agttttccca 2640aaaggctgat aaatttcaat
attttgaata catcattgtt aattttgagt tggcagaggt 2700aaactaacca actaccatta
tgttttagta ctaagggata tacctttcaa taaagttaat 2760gaaattcaat cctt
2774110881DNAHomo Sapiens
110aatccggctg gcagccgatt gacctgaccc aggcgagggt tgctgcaccg agtatttagt
60ttggccccct actgaatgaa gacactttgt taaattctcc aatgagagac gcttagaggt
120aggggcgtgg aagggggccg gggaatttga ggccagataa cgggaagtgt gagccgattg
180gccggacttc tcactccacg gcccagccgt ttacggatcg cggaggccat ccatcaaaag
240aattacacca atcagcggcg aaaatgcccc cttctcgcga gaaagccccg ccctccaata
300tattcctcgt tagggcaggc gcggcccctt cggctccgag ctgaccctga tcagggccga
360gttgtctcgg cggcgctgcc gaggcctcca cccaggacag tccccctccc cgggcctctc
420tcctcttgcc tacgagtccc ctctcctcgt aggcctctcg gatctgatat cgtggggtga
480ggtgagcagg cccggggagg gtggttaccg ctgaggagct gcagtctctg tcaagatgat
540agaggtactg acaacaactg actctcagaa actgctacac cagctgaatg ccctgttgga
600acaggagtct agatgtcagc caaaggtctg tggtttgaga ctaattgagt ctgcacacga
660taatggcctc agaatgactg caagactaag ggactttgaa gtaaaagatc ttcttagtct
720aactcagttc tttggctttg acacagagac attttctcta gctgtgaatt tactggacag
780attcctgtct aaaatgaagg tatgtttgaa gctacatttt tgtaattttg ctcagtgtgt
840tttggagatg gaattgttac cttttggctg gtattcataa a
8811111951DNAHomo Sapiens 111ggcatagtac tattcatttt aattttttgg cccaaatcat
ctaaaactcc catatggtgc 60ctttagaagt tagtatctct gatggaaggg gaattccttt
caatagttca tttgctatgt 120taagtgtgca taagctttac tttaaaaatt gacttcaatg
tttttctaaa aacatctttt 180gactagatgt agtattacct aataaaagta ataccatttt
ctttttaaag gagaaatagc 240attaattttg aaagactaga agctcaactg aaggcatgtc
attgcaggat catattttct 300aaagcaaagc cttctgtgtt ggcattgtct atcattgcat
tagagatcca agcacagaag 360tgtgtagagt taacagaagg aatagaatgt cttcagaaac
attccaagat aaatggcaga 420gatctgacct tctggcaaga gcttgtatcc aaatgtttaa
ctgaatattc atcaaataag 480tgttccaaac caaatgttca gaagttgaaa tggattgttt
ctgggcgtac tgcacggcaa 540ttgaagcata gctactacag aataactcac cttccaacaa
ttcctgaaat ggtcccttaa 600ctggattatt acagcaccaa aaaacttctc tgaagccttt
ctccacaacc ttgttctatg 660gattccataa tgttacaatg gatttaagct atgaagcctc
aaaacatcac gagataagca 720tgatggtctc agacttggga aaactgccta atattatgct
gtagtggaat tatgtttaga 780tttgaattca tctgtgaagc attcaaatca aagctaaaag
cctaaatgtg aaatgctaat 840gacaagcctg agaaggtaaa ctgtgaatct tcatttctat
cattgatcta actttagata 900ttggatcaat atatttaggt ggtattgaaa atgctattgg
aggagtcaca ctaatactat 960caactatcag tcttcccaca gcttcaatca ctgtcattat
tctaatccta ctcctactta 1020aattttaagt tatgaggttt atgtcaaaag caacatttca
caaatgtact tttaaggcat 1080aataagggtt aacattctag gcagtataaa cacaccccat
aatgcaagta ataggtaatc 1140tagagatgtg gactttattg ctatatggga attacattta
aatttgaggg cattttatat 1200aaagaaaaat acagacctat aaagtttggc atattcatta
agttatcttt taatattttt 1260ttctagaaaa caggtgacat ttgtatctac gataaaaatt
tttatacaga acctactgcc 1320tcaaactgaa tcccatcaag aaaactagtt tctattgtat
tagtaactca aaataaatta 1380tcacttcgaa aacttgcttt cccacactaa ggtaagttca
gactagattg aacactccag 1440aattttttac tacagactgt ttttaagtta gaagtgatgg
caattttata aatagagaat 1500atacttccac tgatgccctt actgtgccaa aacaaaaatc
ttaagaaaag caagtagaca 1560ccttcataac tatgaatgaa gctgctgaag tagtgtttag
gatcctccat ggcagttagt 1620gaatgtaaga agtacagtgt taaagtgttg taaacagtta
ctcagtgcaa tgtatagcct 1680gagtctatcc atgatggcta tatccaattt gacatcacgt
tatggatcag tacacaatga 1740aaaaccaaag aaccacagta tatcttattc ttaacttttg
taaaccatgt tttatgggta 1800actttttagt tttcccaaaa ggctgataaa tttcaatatt
ttgaatacat cattgttaat 1860tttgagttgg cagaggtaaa ctaaccaact accattatgt
tttagtacta agggatatac 1920ctttcaataa agttaatgaa attcaatcct t
19511121023DNAHomo Sapiens 112atccactcca cgaacgtcaa
atgcgtcatc tgaggagggg gagggccggg gcaaaggagg 60ggcaccctga catggagcct
gccagctccg tcagccctga ctcggcccgg agctgagctc 120cccacctgcc ggtagcccag
gagatggagc agcccagccc acgtgcccgg ccttccgccc 180ctgacttcac ttgataacaa
actagaaact gaaacagggt cgggatgccg atgccggctt 240ggagttagag atgagtcacc
gctgagagca gctgcagtag ctgagcagtg gcagcagaga 300ggcagacgtg agctgagggc
gcagaggcag gcagcatctc tgagggtccc caaggaacat 360ggctgggagc cgtgaggtgg
tggccatgga ctgcgagatg gtggggctgg ggccccaccg 420ggagagtggc ctggctcgtt
gcagcctcgt gaacgtccac ggtgctgtgc tgtacgacaa 480gttcatccgg cctgagggag
agatcaccga ttacagaacc cgggtcagcg gggtcacccc 540tcagcacatg gtgggggcca
caccatttgc cgtggccagg ctagagatcc tgcagctcct 600gaaaggcaag ctggtggtgg
gtcatgacct gaagcacgac ttccaggcac tgaaagagga 660catgagcggc tacacaatct
acgacacgtc cactgacagg ctgttgtggc gtgaggccaa 720gctggaccac tgcaggcgtg
tctccctgcg ggtgctgagt gagcgcctcc tgcacaagag 780catccagaac agcctgcttg
gacacagctc ggtggaagat gcgagggcaa cgatggagct 840ctatcaaatc tcccagagaa
tccgagcccg ccgagggctg ccccgcctgg ctgtgtcaga 900ctgaagcccc atccagcccg
ttccgcaggg actagaggct ttcggctttt tgggacagca 960actaccttgc ttttggaaaa
tacattttta atagtaaagt ggctctatat tttctctacg 1020cca
10231131856DNAHomo Sapiens
113atccactcca cgaacgtcaa atgcgtcatc tgaggagggg gagggccggg gcaaaggagg
60ggcaccctga catggagcct gccagctccg tcagccctga ctcggcccgg agctgagctc
120cccacctgcc ggtagcccag gagatggagc agcccagccc acgtgcccgg ccttccgccc
180ctgacttcac ttgataacaa actagaaact gaaacagggt cgggatgccg atgccggctt
240ggagttagag atgagtcacc gctgagagca gctgcagtag ctgagcagtg gcagcagaga
300ggcagacgtg agctgagggc gcagaggcag gcagcatctc tgagggtccc caaggaacat
360ggctgggagc cgtgaggtgg tggccatgga ctgcgagatg gtggggctgg ggccccaccg
420ggagagtggc ctggctcgtt gcagcctcgt gaacgtccac ggtgctgtgc tgtacgacaa
480gttcatccgg cctgagggag agatcaccga ttacagaacc cgggtcagcg gggtcacccc
540tcagcacatg gtgggggcca caccatttgc cgtggccagg ctagagatcc tgcagctcct
600gaaaggcaag ctggtggtgg gtcatgacct gaagcacgac ttccaggcac tgaaagagga
660catgagcggc tacacaatct acgacacgtc cactgacagg ctgttgtggc gtgaggccaa
720gctggaccac tgcaggcgtg tctccctgcg ggtgctgagt gagcgcctcc tgcacaagag
780catccagaac agcctgcttg gacacagctc ggtggaagat gcgagggcaa cgatggagct
840ctatcaaatc tcccagagaa tccgagcccg ccgagggctg ccccgcctgg ctgtgtcaga
900ctgaagcccc atccagcccg ttccgcaggg actagaggct ttcggctttt tgggacagca
960actaccttgc ttttggaaaa tacattttta atagtaaagt ggctctatat tttctctacg
1020ccatcactgg gtcctcttct tattcttctc tccaagctgg gttaacagta gacaggaccc
1080atttctgtgt gatgttagga gggaatgaag tcttatgctg gggaggtggg caagtatcaa
1140tttccttaat atcttgaatc ctgtgggtcc aaaatgtggc ttggaaatct aagtagcatg
1200tggcttaatt actaatccca ccctttgctg ttgcatccca gccctattcc tggtgcattt
1260atgcccagag aggtggcatt atttcctggg gtggcattca gctcctcttg agttggtgcc
1320acagcatttg tgggctttga agcaaaggta caggaaatgt caagggtgcc accccggcaa
1380ccttgagcaa gtcacccctc ctatttgtaa aatgaggaag gaaaggtaac aaactgtgga
1440gtcagagaga agtaggttgg aatcctcttt gtcatttagt agctgtttga cctaaggtgg
1500tttactgaac ttctcagttt ctccatctgt aaaatgagaa ttctagcaac tcgtagggta
1560tttgtgagat gttgcatgca aagcccccag caccatgcct gtcctagctt aagcacccac
1620caggtgtcga taagtaattg ttcttccctg gactgcctgc acatctaggg caccccagga
1680agagtcaccg cactctgttt cggggctcgg ctctctgagg ggagggcatc ctgtatgggg
1740aggagggtct ggaccagagc tgtccctgat cgctagaatc aacggcagaa ttcttgttat
1800tttaataata attaataatt tagtgcttcc actaaataaa aatcattgga atggtg
18561142964DNAHomo Sapiens 114gcattgatgg taggtcctgc tgtgcctggt ccctggctgg
tagagtgagg atgagggcag 60ggaagggaaa acacccaaca aaggtttgct tttgttgttg
aaatcaagcc agttaccctg 120tgggaagtga agcttgctcc caccatagaa ctctgggcaa
tgatgtaaag cacacacctc 180acctcagata tgtctcacag caggggccgg ggaactggga
tatttgtaca ccagttccca 240tcagccacca gctgctgctg ctcctgcgca ctgattccgc
agcacttctg gctggtgggc 300aaagcaggca ggaaaaggca tacggatatg gggggttggg
agttcaccct gtgggaaggg 360cagagggaga ggcgccagac actaagagcc agggctgtac
acagggaccc ttcaggtcaa 420cagctcttta ttaaacacct gctgcctgct ctaggccaga
tcctagagac gcagggtgag 480caagacccrt ctctgtccct gagctcttgg ttggttggga
ggtggccctt aaccagatca 540tcagcacaca tggtaaggag tgtgtgacgg agggaagggc
agtgccctgg gagcaggatg 600aaggatgggg ctggcagggc aggagaccag atctgaacag
agcctggagg gtcttagtca 660aggagggcag aagaaggcat acagagtggg gccaggtgag
tcaaagcctg aggctcgggg 720aggggctggg gagcacggag cccgccccta gcctgctggc
aagagctgta ggaatcatgt 780ccggagtagg gaacagggct gagtctgggc ctgttagcct
caaagcacat aaggcacata 840agggccaggc tgggcttttc ctggagccct tgccgctctg
tggctctcag tctggggcct 900taagcctgac ccagggcctt ctcccaggct ctgtccctgg
gctcattaag cctggttgtt 960ccagaagctc agtaccccac caggcagctc ctgcctgcac
tgatgcccct agaaaccagc 1020cctcccgccc gcccccgctc acatggacag tggtgctact
gatcactgtg accagaactg 1080acccacagga cacraggagc taacatggta gagctgtcac
agttgggcag tggtgttact 1140gcccctcgag ggagtgaaat agcaggcctg tggctccctg
ccaagctgcg cgcatggtag 1200accgggctgc acaggaaagg aaagaccctg ccatttatga
agccctgtgg agggtgctgg 1260gcacagttct ctcattccat cctttaaggc aggtataatc
aggcccattt cacagaagag 1320gaaacagagg cccagaaagg aaaagtgact tgcccacggt
cacagagctc ataagcaggg 1380gagctgggaa ttgcagcctg gggtttgtct gattccaaat
ccggggctct ttacctcccc 1440acttggtaat aaagggtgct ggtgctgcat tctgcttctg
ttcttggctt ccttctccat 1500agagcagagt ggtagaacac ataacctccc tgtgcctcag
tttcctcatc tgtcaaggat 1560ggtgacaggg gcaggtatgc agaggcacag crcagacgac
gccaccatgc tacctgcttg 1620ctgattaatg atagggtgtc caagccaaaa aataaaacta
aacattaaaa aataaaacaa 1680tacagcgtaa taacggcaac aagaaaaagc ctttttgagc
tgggccgtct aaccaggtgt 1740ccccaacacc ctgtctggag tgcctggaaa aggagcccct
gtgagaacag gaagtcctct 1800ctcgacagag ggacaccaag aaaacgcagc caggtccaac
agcccgctgg ctcccatgct 1860gggtaccggc caggacacca gggctgagcg gggcatgcga
agggagatga aaggtgactg 1920cagtgaggat ttgccctgtg tactcgcctc tgcaagatcc
acatctcagc tgcacaactg 1980gctggcttgt gtgtgagcct cagttttatc atcagtaaaa
tgggggaata atcatatcca 2040gctcagaggt ttaacttcag cctagtgcac ggaagacatg
gtaaatggtc atcgcttctc 2100ccttgaatgg accgagggcc cccgactccc atagcactac
cccataaagt ctaggctccc 2160gacttcggca ttcaaggcct tcagtgataa atccaggccc
accatccgtc cccacaccac 2220ctttcacaca ccccctgccc ccaccctcgc aggcctctta
ttttagctgc acgtgctctc 2280cctgcctccg aaatgcttgc ggcctttcct ttccatttat
tgacgccctt gtgttctctg 2340tgagcagccc ttccctgtgt ccctagctgg agttcctcac
tccctcctca gtgtcctgaa 2400gcttcttgtt agagctgctg cagccactgc gtgtgtctga
cagcaagtct gcagcctctg 2460cctcccttgc gggactgcag gtgacttgaa ggcacagcct
ggttcccagg aggctggctt 2520tcgtgccact ggccccaggg ctgaaggcag gccagctcca
gccacctgct gagtctccta 2580agtccagagt gtcagagacc tcaagagact ctcacccact
gacccacctg gggactctgg 2640aaatcgggat gtgaccaggg aagaccctgt cacggggcct
ctgaattcag cctcatccca 2700agtccccact ctatacttgt gtctgcagaa cagcctgctt
ggacacagct cggtggaaga 2760tgcgagggca acgatggagc tctatcaaat ctcccagaga
atccgagccc gccgagggct 2820gccccgcctg gctgtgtcag actgaagccc catccagccc
gttccgcagg gactagaggc 2880tttcggcttt ttgggacagc aactaccttg cttttggaaa
atacattttt aatagtaaag 2940tggctctata ttttctctac gcca
29641151205DNAHomo Sapiens 115ctctttcccg gagcctgggc
ggagagggag gaaaacttct tcctggcctg ggctccgtgc 60cgctctgttt gccaaccgtc
cagtcccgcc taccagtgcc gggcgctccc cacccctccc 120ccggctcccc cggtgtccgc
catggccaaa gcctacgacc acctcttcaa gttgctgctg 180atcggggact cgggggtggg
caagacttgt ctgatcattc gctttgcaga ggacaacttc 240aacaacactt acatctccac
catcggaatt gatttcaaga tccgcactgt ggatatagag 300gggaagaaga tcaaactaca
agtctgggac acggctggcc aagagcggtt caagacaata 360actactgcct actaccgtgg
agccatgggc attatcctag tatacgacat cacggatgag 420aaatctttcg agaatattca
gaactggatg aaaagcatca aggagaatgc ctcggctggg 480gtggagcgcc tcttgctggg
gaacaaatgt gacatggagg ccaagaggaa ggtgcagaag 540gagcaggccg ataagttggc
tcgagagcat ggaatccgat ttttcgaaac tagtgctaaa 600tccagtatga atgtggatga
ggcttttagt tccctggccc gggacatctt gctcaagtca 660ggaggccgga gatcaggaaa
cggcaacaag cctcccagta ctgacctgaa aacttgtgac 720aagaagaaca ccaacaagtg
ctccctgggc tgaggaccct ttcttgcctc cccaccccgg 780aagctgaacc tgagggagac
aacggcagag ggagtgagca ggggagaaat agcagagggg 840cttggagggt cacataggta
gatggtaaag agaatgagga gaaaaaggag aaaagggaaa 900agcagaaagg aaaaaaagga
agagagagga agggagaagg gagaggaatg aattgaggaa 960gtgaaagaag gcaaggaggt
aggaagagag ggaggaggaa aggaaggaga gatgcctcag 1020gcttcagacc ttacctgggt
tttcagggca aacataaatg taaatacact gatttattct 1080gttactagat caggttttag
ggtcctgcaa aaggctagct cggcactaca ctagggaatt 1140tgctcctgtt ctgtcacttg
tcatggtctt tcttggtatt aaaggccacc atttgcacaa 1200atgtt
12051161323DNAHomo Sapiens
116ctctttcccg gagcctgggc ggagagggag gaaaacttct tcctggcctg ggctccgtgc
60cgctctgttt gccaaccgtc cagtcccgcc taccagtgcc gggcgctccc cacccctccc
120ccggctcccc cggtgtccgc catggccaaa gcctacgacc acctcttcaa gttgctgctg
180atcggggact cgggggtggg caagacttgt ctgatcattc gctttgcaga ggacaacttc
240aacaacactt acatctccac catcggaatt gatttcaaga tccgcactgt ggatatagag
300gggaagaaga tcaaactaca agtctgggac acggctggcc aagagcggtt caagacaata
360actactgcct actaccgtgg agccatgggc attatcctag tatacgacat cacggatgag
420aaatctttcg agaatattca gaactggatg aaaagcatca aggagaatgc ctcggctggg
480gtggagcgcc tcttgctggg gaacaaatgt gacatggagg ccaagaggaa ggtgcagaag
540gagcaggccg ataaggtgag ggccaggctg agcaatgttc tagaactggg ctgggagggc
600caagataggt tgcattgcag aggacttggc tgctgtcctt aattcaattc tcttcccact
660tcacccctta tagttggctc gagagcatgg aatccgattt ttcgaaacta gtgctaaatc
720cagtatgaat gtggatgagg cttttagttc cctggcccgg gacatcttgc tcaagtcagg
780aggccggaga tcaggaaacg gcaacaagcc tcccagtact gacctgaaaa cttgtgacaa
840gaagaacacc aacaagtgct ccctgggctg aggacccttt cttgcctccc caccccggaa
900gctgaacctg agggagacaa cggcagaggg agtgagcagg ggagaaatag cagaggggct
960tggagggtca cataggtaga tggtaaagag aatgaggaga aaaaggagaa aagggaaaag
1020cagaaaggaa aaaaaggaag agagaggaag ggagaaggga gaggaatgaa ttgaggaagt
1080gaaagaaggc aaggaggtag gaagagaggg aggaggaaag gaaggagaga tgcctcaggc
1140ttcagacctt acctgggttt tcagggcaaa cataaatgta aatacactga tttattctgt
1200tactagatca ggttttaggg tcctgcaaaa ggctagctcg gcactacact agggaatttg
1260ctcctgttct gtcacttgtc atggtctttc ttggtattaa aggccaccat ttgcacaaat
1320gtt
13231171301DNAHomo Sapiens 117ctctttcccg gagcctgggc ggagagggag gaaaacttct
tcctggcctg ggctccgtgc 60cgctctgttt gccaaccgtc cagtcccgcc taccagtgcc
gggcgctccc cacccctccc 120ccggctcccc cggtgtccgc catggccaaa gcctacgacc
acctcttcaa gttgctgctg 180atcggggact cgggggtggg caagacttgt ctgatcattc
gctttgcaga ggacaacttc 240aacaacactt acatctccac catcggtgag cccgctggcc
atgtcccaga ccccgactct 300cctgtgacct ccttctccgg ctcccggatt actagtgacc
ccacttttca gtccccttag 360agaattgatt tcaagatccg cactgtggat atagagggga
agaagatcaa actacaagtc 420tgggacacgg ctggccaaga gcggttcaag acaataacta
ctgcctacta ccgtggagcc 480atgggcatta tcctagtata cgacatcacg gatgagaaat
ctttcgagaa tattcagaac 540tggatgaaaa gcatcaagga gaatgcctcg gctggggtgg
agcgcctctt gctggggaac 600aaatgtgaca tggaggccaa gaggaaggtg cagaaggagc
aggccgataa gttggctcga 660gagcatggaa tccgattttt cgaaactagt gctaaatcca
gtatgaatgt ggatgaggct 720tttagttccc tggcccggga catcttgctc aagtcaggag
gccggagatc aggaaacggc 780aacaagcctc ccagtactga cctgaaaact tgtgacaaga
agaacaccaa caagtgctcc 840ctgggctgag gaccctttct tgcctcccca ccccggaagc
tgaacctgag ggagacaacg 900gcagagggag tgagcagggg agaaatagca gaggggcttg
gagggtcaca taggtagatg 960gtaaagagaa tgaggagaaa aaggagaaaa gggaaaagca
gaaaggaaaa aaaggaagag 1020agaggaaggg agaagggaga ggaatgaatt gaggaagtga
aagaaggcaa ggaggtagga 1080agagagggag gaggaaagga aggagagatg cctcaggctt
cagaccttac ctgggttttc 1140agggcaaaca taaatgtaaa tacactgatt tattctgtta
ctagatcagg ttttagggtc 1200ctgcaaaagg ctagctcggc actacactag ggaatttgct
cctgttctgt cacttgtcat 1260ggtctttctt ggtattaaag gccaccattt gcacaaatgt t
13011181197DNAHomo Sapiens 118ctctttcccg gagcctgggc
ggagagggag gaaaacttct tcctggcctg ggctccgtgc 60cgctctgttt gccaaccgtc
cagtcccgcc taccagtgcc gggcgctccc cacccctccc 120ccggctcccc cggtgtccgc
catggccaaa gcctacgacc acctcttcaa gttgctgctg 180atcggggact cgggggtggg
caagacttgt ctgatcattc gctttgcaga ggacaacttc 240aacaacactt acatctccac
catcggaatt gatttcaaga tccgcactgt ggatatagag 300gggaagaaga tcaaactaca
agtctgggac acggctggcc aagagcggtt caagacaata 360actactgcct actaccgtgg
agccatgggc attatcctag tatacgacat cacggatgag 420aaatctttcg agaatattca
gaactggatg aaaagcatca aggagaatgc ctcggctggg 480gtggagcgcc tcttgctggg
gaacaaatgt gacatggagg ccaagaggaa ggtgcagaag 540gagcaggccg ataagttggc
tcgagagcat ggaatccgat ttttcgaaac tagtgctaaa 600tccagtatga atgtggatga
gttccctggc ccgggacatc ttgctcaagt caggaggccg 660gagatcagga aacggcaaca
agcctcccag tactgacctg aaaacttgtg acaagaagaa 720caccaacaag tgctccctgg
gctgaggacc ctttcttgcc tccccacccc ggaagctgaa 780cctgagggag acaacggcag
agggagtgag caggggagaa atagcagagg ggcttggagg 840gtcacatagg tagatggtaa
agagaatgag gagaaaaagg agaaaaggga aaagcagaaa 900ggaaaaaaag gaagagagag
gaagggagaa gggagaggaa tgaattgagg aagtgaaaga 960aggcaaggag gtaggaagag
agggaggagg aaaggaagga gagatgcctc aggcttcaga 1020ccttacctgg gttttcaggg
caaacataaa tgtaaataca ctgatttatt ctgttactag 1080atcaggtttt agggtcctgc
aaaaggctag ctcggcacta cactagggaa tttgctcctg 1140ttctgtcact tgtcatggtc
tttcttggta ttaaaggcca ccatttgcac aaatgtt 11971191849DNAHomo Sapiens
119ctcctcattt tcttggtacc atcgccttag tctccccaaa tccacaagaa ctcttctcta
60tttttctctg ttcccctctt cccctacccc caccacctag aactctctcg atcctatctc
120catgtttcct gtatccctgt ccgccacatc tttttctccc gatccgatgc tagcctcttt
180ctgtcttgct gagcttcaaa ctctcccact gtgtccccac ctcaccatct acttcccagg
240ttccctgccc cagtctccct gcacctcagc tgaacaaggg tttgggaagg gtggaacaag
300gtggctgggt gtgctggagg gtggcccaag gactgtgatc atgaatatgc agccagcttg
360gtgaggaacg tggaaatgag gggacttttg gggtctctga gtcagcctgg tgactcatcc
420tcctcccagg ggcccccagc aggcttgggg gaggtgccca agtttctact aagaagaaca
480ttgtctcccc tcctcccttc tcttctttct tcatctcctc tggcttggga aatagacagg
540aagagtctca cgacaattct ggttacaaag gaaaaggaaa aatgcccctc tttcctaatt
600gtctcaaaag taatcctgtt tagcctcaga ctttcctagt gccaagtttg gcccactagt
660taattcacat agactggctt cagctacttt tttccttact ctctactagg agggtaggtg
720ggataccaag agtagagggc tctaagaaaa cagagaagag gaatgtgaaa gtaatatctg
780gggggagaca gagactgaat tcagagagtt gtcagctggt ataactgaat ggacccaaga
840ggcagcctaa ggattttaag cctccatgca gaattttcgt caccttttcc ctcccaaaat
900ccataaaatg aattgatttc aagatccgca ctgtggatat agaggggaag aagatcaaac
960tacaagtctg ggacacggct ggccaagagc ggttcaagac aataactact gcctactacc
1020gtggagccat gggcattatc ctagtatacg acatcacgga tgagaaatct ttcgagaata
1080ttcagaactg gatgaaaagc atcaaggaga atgcctcggc tggggtggag cgcctcttgc
1140tggggaacaa atgtgacatg gaggccaaga ggaaggtgca gaaggagcag gccgataagt
1200tggctcgaga gcatggaatc cgatttttcg aaactagtgc taaatccagt atgaatgtgg
1260atgaggcttt tagttccctg gcccgggaca tcttgctcaa gtcaggaggc cggagatcag
1320gaaacggcaa caagcctccc agtactgacc tgaaaacttg tgacaagaag aacaccaaca
1380agtgctccct gggctgagga ccctttcttg cctccccacc ccggaagctg aacctgaggg
1440agacaacggc agagggagtg agcaggggag aaatagcaga ggggcttgga gggtcacata
1500ggtagatggt aaagagaatg aggagaaaaa ggagaaaagg gaaaagcaga aaggaaaaaa
1560aggaagagag aggaagggag aagggagagg aatgaattga ggaagtgaaa gaaggcaagg
1620aggtaggaag agagggagga ggaaaggaag gagagatgcc tcaggcttca gaccttacct
1680gggttttcag ggcaaacata aatgtaaata cactgattta ttctgttact agatcaggtt
1740ttagggtcct gcaaaaggct agctcggcac tacactaggg aatttgctcc tgttctgtca
1800cttgtcatgg tctttcttgg tattaaaggc caccatttgc acaaatgtt
18491202184DNAHomo Sapiens 120gaggcgggcc cgggcggggc ggttgtatat cagggccgcg
ctgagctgcg ccagctgagg 60tgtgagcagc tgccgaagtc agttccttgt ggagccggag
ctgggcgcgg attcgccgag 120gcaccgaggc actcagagga ggcgccatgt cagaaccggc
tggggatgtc cgtcagaacc 180catgcggcag caaggcctgc cgccgcctct tcggcccagt
ggacagcgag cagctgagcc 240gcgactgtga tgcgctaatg gcgggctgca tccaggaggc
ccgtgagcga tggaacttcg 300actttgtcac cgagacacca ctggagggtg acttcgcctg
ggagcgtgtg cggggccttg 360gcctgcccaa gctctacctt cccacggggc cccggcgagg
ccgggatgag ttgggaggag 420gcaggcggcc tggcacctca cctgctctgc tgcaggggac
agcagaggaa gaccatgtgg 480acctgtcact gtcttgtacc cttgtgcctc gctcagggga
gcaggctgaa gggtccccag 540gtggacctgg agactctcag ggtcgaaaac ggcggcagac
cagcatgaca gatttctacc 600actccaaacg ccggctgatc ttctccaaga ggaagcccta
atccgcccac aggaagcctg 660cagtcctgga agcgcgaggg cctcaaaggc ccgctctaca
tcttctgcct tagtctcagt 720ttgtgtgtct taattattat ttgtgtttta atttaaacac
ctcctcatgt acataccctg 780gccgccccct gccccccagc ctctggcatt agaattattt
aaacaaaaac taggcggttg 840aatgagaggt tcctaagagt gctgggcatt tttattttat
gaaatactat ttaaagcctc 900ctcatcccgt gttctccttt tcctctctcc cggaggttgg
gtgggccggc ttcatgccag 960ctacttcctc ctccccactt gtccgctggg tggtaccctc
tggaggggtg tggctccttc 1020ccatcgctgt cacaggcggt tatgaaattc accccctttc
ctggacactc agacctgaat 1080tctttttcat ttgagaagta aacagatggc actttgaagg
ggcctcaccg agtgggggca 1140tcatcaaaaa ctttggagtc ccctcacctc ctctaaggtt
gggcagggtg accctgaagt 1200gagcacagcc tagggctgag ctggggacct ggtaccctcc
tggctcttga tacccccctc 1260tgtcttgtga aggcaggggg aaggtggggt cctggagcag
accaccccgc ctgccctcat 1320ggcccctctg acctgcactg gggagcccgt ctcagtgttg
agccttttcc ctctttggct 1380cccctgtacc ttttgaggag ccccagctac ccttcttctc
cagctgggct ctgcaattcc 1440cctctgctgc tgtccctccc ccttgtcctt tcccttcagt
accctctcag ctccaggtgg 1500ctctgaggtg cctgtcccac ccccaccccc agctcaatgg
actggaaggg gaagggacac 1560acaagaagaa gggcacccta gttctacctc aggcagctca
agcagcgacc gccccctcct 1620ctagctgtgg gggtgagggt cccatgtggt ggcacaggcc
cccttgagtg gggttatctc 1680tgtgttaggg gtatatgatg ggggagtaga tctttctagg
agggagacac tggcccctca 1740aatcgtccag cgaccttcct catccacccc atccctcccc
agttcattgc actttgatta 1800gcagcggaac aaggagtcag acattttaag atggtggcag
tagaggctat ggacagggca 1860tgccacgtgg gctcatatgg ggctgggagt agttgtcttt
cctggcacta acgttgagcc 1920cctggaggca ctgaagtgct tagtgtactt ggagtattgg
ggtctgaccc caaacacctt 1980ccagctcctg taacatactg gcctggactg ttttctctcg
gctccccatg tgtcctggtt 2040cccgtttctc cacctagact gtaaacctct cgagggcagg
gaccacaccc tgtactgttc 2100tgtgtctttc acagctcctc ccacaatgct gaatatacag
caggtgctca ataaatgatt 2160cttagtgact ttacttgtaa tatt
21841212088DNAHomo Sapiens 121gaggcgggcc cgggcggggc
ggttgtatat cagggccgcg ctgagctgcg ccagctgagg 60tgtgagcagc tgccgaagtc
agttccttgt ggagccggag ctgggcgcgg attcgccgag 120gcaccgaggc actcagagga
ggcgccatgt cagaaccggc tggggatgtc cgtcagaacc 180catgcggcag caaggcctgc
cgccgcctct tcggcccagt ggacagcgag cagctgagcc 240gcgactgtga tgcgctaatg
gcgggctgca tccaggaggc ccgtgagcga tggaacttcg 300actttgtcac cgagacacca
ctggagggtg acttcgcctg ggagcgtgtg cggggccttg 360gcctgcccaa gctctacctt
cccacggggc cccggcgagg ccgggatgag ttgggaggag 420gcaggcggcc tggcacctca
cctgctctgc tgcaggggac agcagaggaa gaccatgtgg 480acctgtcact gtcttgtacc
cttgtgcctc gctcagggga gcaggctgaa gggtccccag 540gtggacctgg agactctcag
ggtcgaaaac ggcggcagac cagcatgaca gatttctacc 600actccaaacg ccggctgatc
ttctccaaga ggaagcccta atccgcccac aggaagcctg 660cagtcctgga agcgcgaggg
cctcaaaggc ccgctctaca tcttctgcct tagtctcagt 720ttgtgtgtct taattattat
ttgtgtttta atttaaacac ctcctcatgt acataccctg 780gccgccccct gccccccagc
ctctggcatt agaattattt aaacaaaaac taggcggttg 840aatgagaggt tcctaagagt
gctgggcatt tttattttat gaaatactat ttaaagcctc 900ctcatcccgt gttctccttt
tcctctctcc cggaggttgg gtgggccggc ttcatgccag 960ctacttcctc ctccccactt
gtccgctggg tggtaccctc tggaggggtg tggctccttc 1020ccatcgctgt cacaggcggt
tatgaaattc accccctttc ctggacactc agacctgaat 1080tctttttcat ttgagaagta
aacagatggc actttgaagg ggcctcaccg agtgggggca 1140tcatcaaaaa ctttggagtc
ccctcacctc ctctaaggtt gggcagggtg accctgaagt 1200gagcacagcc tagggctgag
ctggggacct ggtaccctcc tggctcttga tacccccctc 1260tgtcttgtga aggcaggggg
aaggtggggt cctggagcag accaccccgc ctgccctcat 1320ggcccctctg acctgcactg
gggagcccgt ctcagtgttg agccttttcc ctctttggct 1380cccctgtacc ttttgaggag
ccccagctac ccttcttctc cagctgggct ctgcaattcc 1440cctctgctgc tgtccctccc
ccttgtcctt tcccttcagt accctctcag ctccaggcag 1500ctcaagcagc gaccgccccc
tcctctagct gtgggggtga gggtcccatg tggtggcaca 1560ggcccccttg agtggggtta
tctctgtgtt aggggtatat gatgggggag tagatctttc 1620taggagggag acactggccc
ctcaaatcgt ccagcgacct tcctcatcca ccccatccct 1680ccccagttca ttgcactttg
attagcagcg gaacaaggag tcagacattt taagatggtg 1740gcagtagagg ctatggacag
ggcatgccac gtgggctcat atggggctgg gagtagttgt 1800ctttcctggc actaacgttg
agcccctgga ggcactgaag tgcttagtgt acttggagta 1860ttggggtctg accccaaaca
ccttccagct cctgtaacat actggcctgg actgttttct 1920ctcggctccc catgtgtcct
ggttcccgtt tctccaccta gactgtaaac ctctcgaggg 1980cagggaccac accctgtact
gttctgtgtc tttcacagct cctcccacaa tgctgaatat 2040acagcaggtg ctcaataaat
gattcttagt gactttactt gtaatatt 20881222325DNAHomo Sapiens
122gaggcgggcc cgggcggggc ggttgtatat cagggccgcg ctgagctgcg ccagctgagg
60tgtgagcagc tgccgaagtc agttccttgt ggagccggag ctgggcgcgg attcgccgag
120gcaccgaggc actcagagga ggtgagagag cggcggcaga caacagggga ccccgggccg
180gcggcccaga gccgagccaa gcgtgcccgc gtgtgtccct gcgtgtccgc gaggatgcgt
240gttcgcgggt gtgtgctgcg ttcacaggtg tttctgcggc aggcgccatg tcagaaccgg
300ctggggatgt ccgtcagaac ccatgcggca gcaaggcctg ccgccgcctc ttcggcccag
360tggacagcga gcagctgagc cgcgactgtg atgcgctaat ggcgggctgc atccaggagg
420cccgtgagcg atggaacttc gactttgtca ccgagacacc actggagggt gacttcgcct
480gggagcgtgt gcggggcctt ggcctgccca agctctacct tcccacgggg ccccggcgag
540gccgggatga gttgggagga ggcaggcggc ctggcacctc acctgctctg ctgcagggga
600cagcagagga agaccatgtg gacctgtcac tgtcttgtac ccttgtgcct cgctcagggg
660agcaggctga agggtcccca ggtggacctg gagactctca gggtcgaaaa cggcggcaga
720ccagcatgac agatttctac cactccaaac gccggctgat cttctccaag aggaagccct
780aatccgccca caggaagcct gcagtcctgg aagcgcgagg gcctcaaagg cccgctctac
840atcttctgcc ttagtctcag tttgtgtgtc ttaattatta tttgtgtttt aatttaaaca
900cctcctcatg tacataccct ggccgccccc tgccccccag cctctggcat tagaattatt
960taaacaaaaa ctaggcggtt gaatgagagg ttcctaagag tgctgggcat ttttatttta
1020tgaaatacta tttaaagcct cctcatcccg tgttctcctt ttcctctctc ccggaggttg
1080ggtgggccgg cttcatgcca gctacttcct cctccccact tgtccgctgg gtggtaccct
1140ctggaggggt gtggctcctt cccatcgctg tcacaggcgg ttatgaaatt cacccccttt
1200cctggacact cagacctgaa ttctttttca tttgagaagt aaacagatgg cactttgaag
1260gggcctcacc gagtgggggc atcatcaaaa actttggagt cccctcacct cctctaaggt
1320tgggcagggt gaccctgaag tgagcacagc ctagggctga gctggggacc tggtaccctc
1380ctggctcttg atacccccct ctgtcttgtg aaggcagggg gaaggtgggg tcctggagca
1440gaccaccccg cctgccctca tggcccctct gacctgcact ggggagcccg tctcagtgtt
1500gagccttttc cctctttggc tcccctgtac cttttgagga gccccagcta cccttcttct
1560ccagctgggc tctgcaattc ccctctgctg ctgtccctcc cccttgtcct ttcccttcag
1620taccctctca gctccaggtg gctctgaggt gcctgtccca cccccacccc cagctcaatg
1680gactggaagg ggaagggaca cacaagaaga agggcaccct agttctacct caggcagctc
1740aagcagcgac cgccccctcc tctagctgtg ggggtgaggg tcccatgtgg tggcacaggc
1800ccccttgagt ggggttatct ctgtgttagg ggtatatgat gggggagtag atctttctag
1860gagggagaca ctggcccctc aaatcgtcca gcgaccttcc tcatccaccc catccctccc
1920cagttcattg cactttgatt agcagcggaa caaggagtca gacattttaa gatggtggca
1980gtagaggcta tggacagggc atgccacgtg ggctcatatg gggctgggag tagttgtctt
2040tcctggcact aacgttgagc ccctggaggc actgaagtgc ttagtgtact tggagtattg
2100gggtctgacc ccaaacacct tccagctcct gtaacatact ggcctggact gttttctctc
2160ggctccccat gtgtcctggt tcccgtttct ccacctagac tgtaaacctc tcgagggcag
2220ggaccacacc ctgtactgtt ctgtgtcttt cacagctcct cccacaatgc tgaatataca
2280gcaggtgctc aataaatgat tcttagtgac tttacttgta atatt
23251232634DNAHomo Sapiens 123gaggcgggcc cgggcggggc ggttgtatat cagggccgcg
ctgagctgcg ccagctgagg 60tgtgagcagc tgccgaagtc agttccttgt ggagccggag
ctgggcgcgg attcgccgag 120gcaccgaggc actcagagga ggtgagagag cggcggcaga
caacagggga ccccgggccg 180gcggcccaga gccgagccaa gcgtgcccgc gtgtgtccct
gcgtgtccgc gaggatgcgt 240gttcgcgggt gtgtgctgcg ttcacaggtg tttctgcggc
aggtgaatga cgggcgtggg 300tcggtgcgcg ctcggcttgc gcacacggtg tctctaagtg
cgcgggtgac gagagtcggg 360atgtgccgga gaccccgggg cggagagcgg gattacaagt
acaggaatcc ctggtcacgc 420tccccgcccc tggaaaccca gctggggcga gggagggcgt
ggacgggacc gttctgggag 480ctcgcctttg gctgcggttg gctccaggcc ccaggcgcag
tttgctcgcg gcgtggggat 540gaagtccgtg tccctggagg ggcccaggaa gggcgaggaa
agcggagtgg agcgccatgt 600cagaaccggc tggggatgtc cgtcagaacc catgcggcag
caaggcctgc cgccgcctct 660tcggcccagt ggacagcgag cagctgagcc gcgactgtga
tgcgctaatg gcgggctgca 720tccaggaggc ccgtgagcga tggaacttcg actttgtcac
cgagacacca ctggagggtg 780acttcgcctg ggagcgtgtg cggggccttg gcctgcccaa
gctctacctt cccacggggc 840cccggcgagg ccgggatgag ttgggaggag gcaggcggcc
tggcacctca cctgctctgc 900tgcaggggac agcagaggaa gaccatgtgg acctgtcact
gtcttgtacc cttgtgcctc 960gctcagggga gcaggctgaa gggtccccag gtggacctgg
agactctcag ggtcgaaaac 1020ggcggcagac cagcatgaca gatttctacc actccaaacg
ccggctgatc ttctccaaga 1080ggaagcccta atccgcccac aggaagcctg cagtcctgga
agcgcgaggg cctcaaaggc 1140ccgctctaca tcttctgcct tagtctcagt ttgtgtgtct
taattattat ttgtgtttta 1200atttaaacac ctcctcatgt acataccctg gccgccccct
gccccccagc ctctggcatt 1260agaattattt aaacaaaaac taggcggttg aatgagaggt
tcctaagagt gctgggcatt 1320tttattttat gaaatactat ttaaagcctc ctcatcccgt
gttctccttt tcctctctcc 1380cggaggttgg gtgggccggc ttcatgccag ctacttcctc
ctccccactt gtccgctggg 1440tggtaccctc tggaggggtg tggctccttc ccatcgctgt
cacaggcggt tatgaaattc 1500accccctttc ctggacactc agacctgaat tctttttcat
ttgagaagta aacagatggc 1560actttgaagg ggcctcaccg agtgggggca tcatcaaaaa
ctttggagtc ccctcacctc 1620ctctaaggtt gggcagggtg accctgaagt gagcacagcc
tagggctgag ctggggacct 1680ggtaccctcc tggctcttga tacccccctc tgtcttgtga
aggcaggggg aaggtggggt 1740cctggagcag accaccccgc ctgccctcat ggcccctctg
acctgcactg gggagcccgt 1800ctcagtgttg agccttttcc ctctttggct cccctgtacc
ttttgaggag ccccagctac 1860ccttcttctc cagctgggct ctgcaattcc cctctgctgc
tgtccctccc ccttgtcctt 1920tcccttcagt accctctcag ctccaggtgg ctctgaggtg
cctgtcccac ccccaccccc 1980agctcaatgg actggaaggg gaagggacac acaagaagaa
gggcacccta gttctacctc 2040aggcagctca agcagcgacc gccccctcct ctagctgtgg
gggtgagggt cccatgtggt 2100ggcacaggcc cccttgagtg gggttatctc tgtgttaggg
gtatatgatg ggggagtaga 2160tctttctagg agggagacac tggcccctca aatcgtccag
cgaccttcct catccacccc 2220atccctcccc agttcattgc actttgatta gcagcggaac
aaggagtcag acattttaag 2280atggtggcag tagaggctat ggacagggca tgccacgtgg
gctcatatgg ggctgggagt 2340agttgtcttt cctggcacta acgttgagcc cctggaggca
ctgaagtgct tagtgtactt 2400ggagtattgg ggtctgaccc caaacacctt ccagctcctg
taacatactg gcctggactg 2460ttttctctcg gctccccatg tgtcctggtt cccgtttctc
cacctagact gtaaacctct 2520cgagggcagg gaccacaccc tgtactgttc tgtgtctttc
acagctcctc ccacaatgct 2580gaatatacag caggtgctca ataaatgatt cttagtgact
ttacttgtaa tatt 26341242392DNAHomo Sapiens 124aacatgttga
gctctggcat agaagaggct ggtggctatt ttgtccttgg gctgcctgtt 60ttcaggtgag
gaaggggatg gtaggagaca ggagacctct aaagacccca gaaataaagg 120atgacaagca
gagagccccg ggcaggaggc aaaagtcctg tgttccaact atagtcattt 180ctttgctgca
tgatctgagt taggtcacca gacttctctg agccccagtt tccccagcag 240tgtatacggg
ctatgtgggg agtattcagg agacagacaa ctcactcgtc aaatcctccc 300cttcctggcc
aacaaagctg ctgcaaccac agggatttct tctgttcagg cgccatgtca 360gaaccggctg
gggatgtccg tcagaaccca tgcggcagca aggcctgccg ccgcctcttc 420ggcccagtgg
acagcgagca gctgagccgc gactgtgatg cgctaatggc gggctgcatc 480caggaggccc
gtgagcgatg gaacttcgac tttgtcaccg agacaccact ggagggtgac 540ttcgcctggg
agcgtgtgcg gggccttggc ctgcccaagc tctaccttcc cacggggccc 600cggcgaggcc
gggatgagtt gggaggaggc aggcggcctg gcacctcacc tgctctgctg 660caggggacag
cagaggaaga ccatgtggac ctgtcactgt cttgtaccct tgtgcctcgc 720tcaggggagc
aggctgaagg gtccccaggt ggacctggag actctcaggg tcgaaaacgg 780cggcagacca
gcatgacaga tttctaccac tccaaacgcc ggctgatctt ctccaagagg 840aagccctaat
ccgcccacag gaagcctgca gtcctggaag cgcgagggcc tcaaaggccc 900gctctacatc
ttctgcctta gtctcagttt gtgtgtctta attattattt gtgttttaat 960ttaaacacct
cctcatgtac ataccctggc cgccccctgc cccccagcct ctggcattag 1020aattatttaa
acaaaaacta ggcggttgaa tgagaggttc ctaagagtgc tgggcatttt 1080tattttatga
aatactattt aaagcctcct catcccgtgt tctccttttc ctctctcccg 1140gaggttgggt
gggccggctt catgccagct acttcctcct ccccacttgt ccgctgggtg 1200gtaccctctg
gaggggtgtg gctccttccc atcgctgtca caggcggtta tgaaattcac 1260cccctttcct
ggacactcag acctgaattc tttttcattt gagaagtaaa cagatggcac 1320tttgaagggg
cctcaccgag tgggggcatc atcaaaaact ttggagtccc ctcacctcct 1380ctaaggttgg
gcagggtgac cctgaagtga gcacagccta gggctgagct ggggacctgg 1440taccctcctg
gctcttgata cccccctctg tcttgtgaag gcagggggaa ggtggggtcc 1500tggagcagac
caccccgcct gccctcatgg cccctctgac ctgcactggg gagcccgtct 1560cagtgttgag
ccttttccct ctttggctcc cctgtacctt ttgaggagcc ccagctaccc 1620ttcttctcca
gctgggctct gcaattcccc tctgctgctg tccctccccc ttgtcctttc 1680ccttcagtac
cctctcagct ccaggtggct ctgaggtgcc tgtcccaccc ccacccccag 1740ctcaatggac
tggaagggga agggacacac aagaagaagg gcaccctagt tctacctcag 1800gcagctcaag
cagcgaccgc cccctcctct agctgtgggg gtgagggtcc catgtggtgg 1860cacaggcccc
cttgagtggg gttatctctg tgttaggggt atatgatggg ggagtagatc 1920tttctaggag
ggagacactg gcccctcaaa tcgtccagcg accttcctca tccaccccat 1980ccctccccag
ttcattgcac tttgattagc agcggaacaa ggagtcagac attttaagat 2040ggtggcagta
gaggctatgg acagggcatg ccacgtgggc tcatatgggg ctgggagtag 2100ttgtctttcc
tggcactaac gttgagcccc tggaggcact gaagtgctta gtgtacttgg 2160agtattgggg
tctgacccca aacaccttcc agctcctgta acatactggc ctggactgtt 2220ttctctcggc
tccccatgtg tcctggttcc cgtttctcca cctagactgt aaacctctcg 2280agggcaggga
ccacaccctg tactgttctg tgtctttcac agctcctccc acaatgctga 2340atatacagca
ggtgctcaat aaatgattct tagtgacttt acttgtaata tt
23921252300DNAHomo Sapiens 125aacatgttga gctctggcat agaagaggct ggtggctatt
ttgtccttgg gctgcctgtt 60ttcaggtgag gaaggggatg gtaggagaca ggagacctct
aaagacccca ggtcaccaga 120cttctctgag ccccagtttc cccagcagtg tatacgggct
atgtggggag tattcaggag 180acagacaact cactcgtcaa atcctcccct tcctggccaa
caaagctgct gcaaccacag 240ggatttcttc tgttcaggcg ccatgtcaga accggctggg
gatgtccgtc agaacccatg 300cggcagcaag gcctgccgcc gcctcttcgg cccagtggac
agcgagcagc tgagccgcga 360ctgtgatgcg ctaatggcgg gctgcatcca ggaggcccgt
gagcgatgga acttcgactt 420tgtcaccgag acaccactgg agggtgactt cgcctgggag
cgtgtgcggg gccttggcct 480gcccaagctc taccttccca cggggccccg gcgaggccgg
gatgagttgg gaggaggcag 540gcggcctggc acctcacctg ctctgctgca ggggacagca
gaggaagacc atgtggacct 600gtcactgtct tgtacccttg tgcctcgctc aggggagcag
gctgaagggt ccccaggtgg 660acctggagac tctcagggtc gaaaacggcg gcagaccagc
atgacagatt tctaccactc 720caaacgccgg ctgatcttct ccaagaggaa gccctaatcc
gcccacagga agcctgcagt 780cctggaagcg cgagggcctc aaaggcccgc tctacatctt
ctgccttagt ctcagtttgt 840gtgtcttaat tattatttgt gttttaattt aaacacctcc
tcatgtacat accctggccg 900ccccctgccc cccagcctct ggcattagaa ttatttaaac
aaaaactagg cggttgaatg 960agaggttcct aagagtgctg ggcattttta ttttatgaaa
tactatttaa agcctcctca 1020tcccgtgttc tccttttcct ctctcccgga ggttgggtgg
gccggcttca tgccagctac 1080ttcctcctcc ccacttgtcc gctgggtggt accctctgga
ggggtgtggc tccttcccat 1140cgctgtcaca ggcggttatg aaattcaccc cctttcctgg
acactcagac ctgaattctt 1200tttcatttga gaagtaaaca gatggcactt tgaaggggcc
tcaccgagtg ggggcatcat 1260caaaaacttt ggagtcccct cacctcctct aaggttgggc
agggtgaccc tgaagtgagc 1320acagcctagg gctgagctgg ggacctggta ccctcctggc
tcttgatacc cccctctgtc 1380ttgtgaaggc agggggaagg tggggtcctg gagcagacca
ccccgcctgc cctcatggcc 1440cctctgacct gcactgggga gcccgtctca gtgttgagcc
ttttccctct ttggctcccc 1500tgtacctttt gaggagcccc agctaccctt cttctccagc
tgggctctgc aattcccctc 1560tgctgctgtc cctccccctt gtcctttccc ttcagtaccc
tctcagctcc aggtggctct 1620gaggtgcctg tcccaccccc acccccagct caatggactg
gaaggggaag ggacacacaa 1680gaagaagggc accctagttc tacctcaggc agctcaagca
gcgaccgccc cctcctctag 1740ctgtgggggt gagggtccca tgtggtggca caggccccct
tgagtggggt tatctctgtg 1800ttaggggtat atgatggggg agtagatctt tctaggaggg
agacactggc ccctcaaatc 1860gtccagcgac cttcctcatc caccccatcc ctccccagtt
cattgcactt tgattagcag 1920cggaacaagg agtcagacat tttaagatgg tggcagtaga
ggctatggac agggcatgcc 1980acgtgggctc atatggggct gggagtagtt gtctttcctg
gcactaacgt tgagcccctg 2040gaggcactga agtgcttagt gtacttggag tattggggtc
tgaccccaaa caccttccag 2100ctcctgtaac atactggcct ggactgtttt ctctcggctc
cccatgtgtc ctggttcccg 2160tttctccacc tagactgtaa acctctcgag ggcagggacc
acaccctgta ctgttctgtg 2220tctttcacag ctcctcccac aatgctgaat atacagcagg
tgctcaataa atgattctta 2280gtgactttac ttgtaatatt
23001262186DNAHomo Sapiens 126aacatgttga gctctggcat
agaagaggct ggtggctatt ttgtccttgg gctgcctgtt 60ttcaggtgag gaaggggatg
gtaggagaca ggagacctct aaagacccca gctgctgcaa 120ccacagggat ttcttctgtt
caggcgccat gtcagaaccg gctggggatg tccgtcagaa 180cccatgcggc agcaaggcct
gccgccgcct cttcggccca gtggacagcg agcagctgag 240ccgcgactgt gatgcgctaa
tggcgggctg catccaggag gcccgtgagc gatggaactt 300cgactttgtc accgagacac
cactggaggg tgacttcgcc tgggagcgtg tgcggggcct 360tggcctgccc aagctctacc
ttcccacggg gccccggcga ggccgggatg agttgggagg 420aggcaggcgg cctggcacct
cacctgctct gctgcagggg acagcagagg aagaccatgt 480ggacctgtca ctgtcttgta
cccttgtgcc tcgctcaggg gagcaggctg aagggtcccc 540aggtggacct ggagactctc
agggtcgaaa acggcggcag accagcatga cagatttcta 600ccactccaaa cgccggctga
tcttctccaa gaggaagccc taatccgccc acaggaagcc 660tgcagtcctg gaagcgcgag
ggcctcaaag gcccgctcta catcttctgc cttagtctca 720gtttgtgtgt cttaattatt
atttgtgttt taatttaaac acctcctcat gtacataccc 780tggccgcccc ctgcccccca
gcctctggca ttagaattat ttaaacaaaa actaggcggt 840tgaatgagag gttcctaaga
gtgctgggca tttttatttt atgaaatact atttaaagcc 900tcctcatccc gtgttctcct
tttcctctct cccggaggtt gggtgggccg gcttcatgcc 960agctacttcc tcctccccac
ttgtccgctg ggtggtaccc tctggagggg tgtggctcct 1020tcccatcgct gtcacaggcg
gttatgaaat tcaccccctt tcctggacac tcagacctga 1080attctttttc atttgagaag
taaacagatg gcactttgaa ggggcctcac cgagtggggg 1140catcatcaaa aactttggag
tcccctcacc tcctctaagg ttgggcaggg tgaccctgaa 1200gtgagcacag cctagggctg
agctggggac ctggtaccct cctggctctt gatacccccc 1260tctgtcttgt gaaggcaggg
ggaaggtggg gtcctggagc agaccacccc gcctgccctc 1320atggcccctc tgacctgcac
tggggagccc gtctcagtgt tgagcctttt ccctctttgg 1380ctcccctgta ccttttgagg
agccccagct acccttcttc tccagctggg ctctgcaatt 1440cccctctgct gctgtccctc
ccccttgtcc tttcccttca gtaccctctc agctccaggt 1500ggctctgagg tgcctgtccc
acccccaccc ccagctcaat ggactggaag gggaagggac 1560acacaagaag aagggcaccc
tagttctacc tcaggcagct caagcagcga ccgccccctc 1620ctctagctgt gggggtgagg
gtcccatgtg gtggcacagg cccccttgag tggggttatc 1680tctgtgttag gggtatatga
tgggggagta gatctttcta ggagggagac actggcccct 1740caaatcgtcc agcgaccttc
ctcatccacc ccatccctcc ccagttcatt gcactttgat 1800tagcagcgga acaaggagtc
agacatttta agatggtggc agtagaggct atggacaggg 1860catgccacgt gggctcatat
ggggctggga gtagttgtct ttcctggcac taacgttgag 1920cccctggagg cactgaagtg
cttagtgtac ttggagtatt ggggtctgac cccaaacacc 1980ttccagctcc tgtaacatac
tggcctggac tgttttctct cggctcccca tgtgtcctgg 2040ttcccgtttc tccacctaga
ctgtaaacct ctcgagggca gggaccacac cctgtactgt 2100tctgtgtctt tcacagctcc
tcccacaatg ctgaatatac agcaggtgct caataaatga 2160ttcttagtga ctttacttgt
aatatt 21861272304DNAHomo Sapiens
127aacatgttga gctctggcat agaagaggct ggtggctatt ttgtccttgg gctgcctgtt
60ttcaggtgag gaaggggatg gtaggagaca ggagacctct aaagacccca gttaggtcac
120cagacttctc tgagccccag tttccccagc agtgtatacg ggctatgtgg ggagtattca
180ggagacagac aactcactcg tcaaatcctc cccttcctgg ccaacaaagc tgctgcaacc
240acagggattt cttctgttca ggcgccatgt cagaaccggc tggggatgtc cgtcagaacc
300catgcggcag caaggcctgc cgccgcctct tcggcccagt ggacagcgag cagctgagcc
360gcgactgtga tgcgctaatg gcgggctgca tccaggaggc ccgtgagcga tggaacttcg
420actttgtcac cgagacacca ctggagggtg acttcgcctg ggagcgtgtg cggggccttg
480gcctgcccaa gctctacctt cccacggggc cccggcgagg ccgggatgag ttgggaggag
540gcaggcggcc tggcacctca cctgctctgc tgcaggggac agcagaggaa gaccatgtgg
600acctgtcact gtcttgtacc cttgtgcctc gctcagggga gcaggctgaa gggtccccag
660gtggacctgg agactctcag ggtcgaaaac ggcggcagac cagcatgaca gatttctacc
720actccaaacg ccggctgatc ttctccaaga ggaagcccta atccgcccac aggaagcctg
780cagtcctgga agcgcgaggg cctcaaaggc ccgctctaca tcttctgcct tagtctcagt
840ttgtgtgtct taattattat ttgtgtttta atttaaacac ctcctcatgt acataccctg
900gccgccccct gccccccagc ctctggcatt agaattattt aaacaaaaac taggcggttg
960aatgagaggt tcctaagagt gctgggcatt tttattttat gaaatactat ttaaagcctc
1020ctcatcccgt gttctccttt tcctctctcc cggaggttgg gtgggccggc ttcatgccag
1080ctacttcctc ctccccactt gtccgctggg tggtaccctc tggaggggtg tggctccttc
1140ccatcgctgt cacaggcggt tatgaaattc accccctttc ctggacactc agacctgaat
1200tctttttcat ttgagaagta aacagatggc actttgaagg ggcctcaccg agtgggggca
1260tcatcaaaaa ctttggagtc ccctcacctc ctctaaggtt gggcagggtg accctgaagt
1320gagcacagcc tagggctgag ctggggacct ggtaccctcc tggctcttga tacccccctc
1380tgtcttgtga aggcaggggg aaggtggggt cctggagcag accaccccgc ctgccctcat
1440ggcccctctg acctgcactg gggagcccgt ctcagtgttg agccttttcc ctctttggct
1500cccctgtacc ttttgaggag ccccagctac ccttcttctc cagctgggct ctgcaattcc
1560cctctgctgc tgtccctccc ccttgtcctt tcccttcagt accctctcag ctccaggtgg
1620ctctgaggtg cctgtcccac ccccaccccc agctcaatgg actggaaggg gaagggacac
1680acaagaagaa gggcacccta gttctacctc aggcagctca agcagcgacc gccccctcct
1740ctagctgtgg gggtgagggt cccatgtggt ggcacaggcc cccttgagtg gggttatctc
1800tgtgttaggg gtatatgatg ggggagtaga tctttctagg agggagacac tggcccctca
1860aatcgtccag cgaccttcct catccacccc atccctcccc agttcattgc actttgatta
1920gcagcggaac aaggagtcag acattttaag atggtggcag tagaggctat ggacagggca
1980tgccacgtgg gctcatatgg ggctgggagt agttgtcttt cctggcacta acgttgagcc
2040cctggaggca ctgaagtgct tagtgtactt ggagtattgg ggtctgaccc caaacacctt
2100ccagctcctg taacatactg gcctggactg ttttctctcg gctccccatg tgtcctggtt
2160cccgtttctc cacctagact gtaaacctct cgagggcagg gaccacaccc tgtactgttc
2220tgtgtctttc acagctcctc ccacaatgct gaatatacag caggtgctca ataaatgatt
2280cttagtgact ttacttgtaa tatt
23041282140DNAHomo Sapiens 128aacatgttga gctctggcat agaagaggct ggtggctatt
ttgtccttgg gctgcctgtt 60ttcagctgct gcaaccacag ggatttcttc tgttcaggcg
ccatgtcaga accggctggg 120gatgtccgtc agaacccatg cggcagcaag gcctgccgcc
gcctcttcgg cccagtggac 180agcgagcagc tgagccgcga ctgtgatgcg ctaatggcgg
gctgcatcca ggaggcccgt 240gagcgatgga acttcgactt tgtcaccgag acaccactgg
agggtgactt cgcctgggag 300cgtgtgcggg gccttggcct gcccaagctc taccttccca
cggggccccg gcgaggccgg 360gatgagttgg gaggaggcag gcggcctggc acctcacctg
ctctgctgca ggggacagca 420gaggaagacc atgtggacct gtcactgtct tgtacccttg
tgcctcgctc aggggagcag 480gctgaagggt ccccaggtgg acctggagac tctcagggtc
gaaaacggcg gcagaccagc 540atgacagatt tctaccactc caaacgccgg ctgatcttct
ccaagaggaa gccctaatcc 600gcccacagga agcctgcagt cctggaagcg cgagggcctc
aaaggcccgc tctacatctt 660ctgccttagt ctcagtttgt gtgtcttaat tattatttgt
gttttaattt aaacacctcc 720tcatgtacat accctggccg ccccctgccc cccagcctct
ggcattagaa ttatttaaac 780aaaaactagg cggttgaatg agaggttcct aagagtgctg
ggcattttta ttttatgaaa 840tactatttaa agcctcctca tcccgtgttc tccttttcct
ctctcccgga ggttgggtgg 900gccggcttca tgccagctac ttcctcctcc ccacttgtcc
gctgggtggt accctctgga 960ggggtgtggc tccttcccat cgctgtcaca ggcggttatg
aaattcaccc cctttcctgg 1020acactcagac ctgaattctt tttcatttga gaagtaaaca
gatggcactt tgaaggggcc 1080tcaccgagtg ggggcatcat caaaaacttt ggagtcccct
cacctcctct aaggttgggc 1140agggtgaccc tgaagtgagc acagcctagg gctgagctgg
ggacctggta ccctcctggc 1200tcttgatacc cccctctgtc ttgtgaaggc agggggaagg
tggggtcctg gagcagacca 1260ccccgcctgc cctcatggcc cctctgacct gcactgggga
gcccgtctca gtgttgagcc 1320ttttccctct ttggctcccc tgtacctttt gaggagcccc
agctaccctt cttctccagc 1380tgggctctgc aattcccctc tgctgctgtc cctccccctt
gtcctttccc ttcagtaccc 1440tctcagctcc aggtggctct gaggtgcctg tcccaccccc
acccccagct caatggactg 1500gaaggggaag ggacacacaa gaagaagggc accctagttc
tacctcaggc agctcaagca 1560gcgaccgccc cctcctctag ctgtgggggt gagggtccca
tgtggtggca caggccccct 1620tgagtggggt tatctctgtg ttaggggtat atgatggggg
agtagatctt tctaggaggg 1680agacactggc ccctcaaatc gtccagcgac cttcctcatc
caccccatcc ctccccagtt 1740cattgcactt tgattagcag cggaacaagg agtcagacat
tttaagatgg tggcagtaga 1800ggctatggac agggcatgcc acgtgggctc atatggggct
gggagtagtt gtctttcctg 1860gcactaacgt tgagcccctg gaggcactga agtgcttagt
gtacttggag tattggggtc 1920tgaccccaaa caccttccag ctcctgtaac atactggcct
ggactgtttt ctctcggctc 1980cccatgtgtc ctggttcccg tttctccacc tagactgtaa
acctctcgag ggcagggacc 2040acaccctgta ctgttctgtg tctttcacag ctcctcccac
aatgctgaat atacagcagg 2100tgctcaataa atgattctta gtgactttac ttgtaatatt
21401292108DNAHomo Sapiens 129aacatgttga gctctggcat
agaagaggct ggtggctatt ttgtccttgg gctgcctgtt 60ttcaggcgcc atgtcagaac
cggctgggga tgtccgtcag aacccatgcg gcagcaaggc 120ctgccgccgc ctcttcggcc
cagtggacag cgagcagctg agccgcgact gtgatgcgct 180aatggcgggc tgcatccagg
aggcccgtga gcgatggaac ttcgactttg tcaccgagac 240accactggag ggtgacttcg
cctgggagcg tgtgcggggc cttggcctgc ccaagctcta 300ccttcccacg gggccccggc
gaggccggga tgagttggga ggaggcaggc ggcctggcac 360ctcacctgct ctgctgcagg
ggacagcaga ggaagaccat gtggacctgt cactgtcttg 420tacccttgtg cctcgctcag
gggagcaggc tgaagggtcc ccaggtggac ctggagactc 480tcagggtcga aaacggcggc
agaccagcat gacagatttc taccactcca aacgccggct 540gatcttctcc aagaggaagc
cctaatccgc ccacaggaag cctgcagtcc tggaagcgcg 600agggcctcaa aggcccgctc
tacatcttct gccttagtct cagtttgtgt gtcttaatta 660ttatttgtgt tttaatttaa
acacctcctc atgtacatac cctggccgcc ccctgccccc 720cagcctctgg cattagaatt
atttaaacaa aaactaggcg gttgaatgag aggttcctaa 780gagtgctggg catttttatt
ttatgaaata ctatttaaag cctcctcatc ccgtgttctc 840cttttcctct ctcccggagg
ttgggtgggc cggcttcatg ccagctactt cctcctcccc 900acttgtccgc tgggtggtac
cctctggagg ggtgtggctc cttcccatcg ctgtcacagg 960cggttatgaa attcaccccc
tttcctggac actcagacct gaattctttt tcatttgaga 1020agtaaacaga tggcactttg
aaggggcctc accgagtggg ggcatcatca aaaactttgg 1080agtcccctca cctcctctaa
ggttgggcag ggtgaccctg aagtgagcac agcctagggc 1140tgagctgggg acctggtacc
ctcctggctc ttgatacccc cctctgtctt gtgaaggcag 1200ggggaaggtg gggtcctgga
gcagaccacc ccgcctgccc tcatggcccc tctgacctgc 1260actggggagc ccgtctcagt
gttgagcctt ttccctcttt ggctcccctg taccttttga 1320ggagccccag ctacccttct
tctccagctg ggctctgcaa ttcccctctg ctgctgtccc 1380tcccccttgt cctttccctt
cagtaccctc tcagctccag gtggctctga ggtgcctgtc 1440ccacccccac ccccagctca
atggactgga aggggaaggg acacacaaga agaagggcac 1500cctagttcta cctcaggcag
ctcaagcagc gaccgccccc tcctctagct gtgggggtga 1560gggtcccatg tggtggcaca
ggcccccttg agtggggtta tctctgtgtt aggggtatat 1620gatgggggag tagatctttc
taggagggag acactggccc ctcaaatcgt ccagcgacct 1680tcctcatcca ccccatccct
ccccagttca ttgcactttg attagcagcg gaacaaggag 1740tcagacattt taagatggtg
gcagtagagg ctatggacag ggcatgccac gtgggctcat 1800atggggctgg gagtagttgt
ctttcctggc actaacgttg agcccctgga ggcactgaag 1860tgcttagtgt acttggagta
ttggggtctg accccaaaca ccttccagct cctgtaacat 1920actggcctgg actgttttct
ctcggctccc catgtgtcct ggttcccgtt tctccaccta 1980gactgtaaac ctctcgaggg
cagggaccac accctgtact gttctgtgtc tttcacagct 2040cctcccacaa tgctgaatat
acagcaggtg ctcaataaat gattcttagt gactttactt 2100gtaatatt
21081302275DNAHomo Sapiens
130gaggcgggcc cgggcggggc ggttgtatat cagggccgcg ctgagctgcg ccagctgagg
60tgtgagcagc tgccgaagtc agttccttgt ggagccggag ctgggcgcgg attcgccgag
120gcaccgaggc actcagagga gaaactgcaa gttgggactt gtccctagga aaatccagtt
180gctgccaagg tcgtgcagtc actcagccct ggagtcaagc cagagcaggc aggcgccatg
240tcagaaccgg ctggggatgt ccgtcagaac ccatgcggca gcaaggcctg ccgccgcctc
300ttcggcccag tggacagcga gcagctgagc cgcgactgtg atgcgctaat ggcgggctgc
360atccaggagg cccgtgagcg atggaacttc gactttgtca ccgagacacc actggagggt
420gacttcgcct gggagcgtgt gcggggcctt ggcctgccca agctctacct tcccacgggg
480ccccggcgag gccgggatga gttgggagga ggcaggcggc ctggcacctc acctgctctg
540ctgcagggga cagcagagga agaccatgtg gacctgtcac tgtcttgtac ccttgtgcct
600cgctcagggg agcaggctga agggtcccca ggtggacctg gagactctca gggtcgaaaa
660cggcggcaga ccagcatgac agatttctac cactccaaac gccggctgat cttctccaag
720aggaagccct aatccgccca caggaagcct gcagtcctgg aagcgcgagg gcctcaaagg
780cccgctctac atcttctgcc ttagtctcag tttgtgtgtc ttaattatta tttgtgtttt
840aatttaaaca cctcctcatg tacataccct ggccgccccc tgccccccag cctctggcat
900tagaattatt taaacaaaaa ctaggcggtt gaatgagagg ttcctaagag tgctgggcat
960ttttatttta tgaaatacta tttaaagcct cctcatcccg tgttctcctt ttcctctctc
1020ccggaggttg ggtgggccgg cttcatgcca gctacttcct cctccccact tgtccgctgg
1080gtggtaccct ctggaggggt gtggctcctt cccatcgctg tcacaggcgg ttatgaaatt
1140cacccccttt cctggacact cagacctgaa ttctttttca tttgagaagt aaacagatgg
1200cactttgaag gggcctcacc gagtgggggc atcatcaaaa actttggagt cccctcacct
1260cctctaaggt tgggcagggt gaccctgaag tgagcacagc ctagggctga gctggggacc
1320tggtaccctc ctggctcttg atacccccct ctgtcttgtg aaggcagggg gaaggtgggg
1380tcctggagca gaccaccccg cctgccctca tggcccctct gacctgcact ggggagcccg
1440tctcagtgtt gagccttttc cctctttggc tcccctgtac cttttgagga gccccagcta
1500cccttcttct ccagctgggc tctgcaattc ccctctgctg ctgtccctcc cccttgtcct
1560ttcccttcag taccctctca gctccaggtg gctctgaggt gcctgtccca cccccacccc
1620cagctcaatg gactggaagg ggaagggaca cacaagaaga agggcaccct agttctacct
1680caggcagctc aagcagcgac cgccccctcc tctagctgtg ggggtgaggg tcccatgtgg
1740tggcacaggc ccccttgagt ggggttatct ctgtgttagg ggtatatgat gggggagtag
1800atctttctag gagggagaca ctggcccctc aaatcgtcca gcgaccttcc tcatccaccc
1860catccctccc cagttcattg cactttgatt agcagcggaa caaggagtca gacattttaa
1920gatggtggca gtagaggcta tggacagggc atgccacgtg ggctcatatg gggctgggag
1980tagttgtctt tcctggcact aacgttgagc ccctggaggc actgaagtgc ttagtgtact
2040tggagtattg gggtctgacc ccaaacacct tccagctcct gtaacatact ggcctggact
2100gttttctctc ggctccccat gtgtcctggt tcccgtttct ccacctagac tgtaaacctc
2160tcgagggcag ggaccacacc ctgtactgtt ctgtgtcttt cacagctcct cccacaatgc
2220tgaatataca gcaggtgctc aataaatgat tcttagtgac tttacttgta atatt
22751312248DNAHomo Sapiens 131gaggcgggcc cgggcggggc ggttgtatat cagggccgcg
ctgagctgcg ccagctgagg 60tgtgagcagc tgccgaagtc agttccttgt ggagccggag
ctgggcgcgg attcgccgag 120gcaccgaggc actcagagga ggaaaatcca gttgctgcca
aggtcgtgca gtcactcagc 180cctggagtca agccagagca ggcaggcgcc atgtcagaac
cggctgggga tgtccgtcag 240aacccatgcg gcagcaaggc ctgccgccgc ctcttcggcc
cagtggacag cgagcagctg 300agccgcgact gtgatgcgct aatggcgggc tgcatccagg
aggcccgtga gcgatggaac 360ttcgactttg tcaccgagac accactggag ggtgacttcg
cctgggagcg tgtgcggggc 420cttggcctgc ccaagctcta ccttcccacg gggccccggc
gaggccggga tgagttggga 480ggaggcaggc ggcctggcac ctcacctgct ctgctgcagg
ggacagcaga ggaagaccat 540gtggacctgt cactgtcttg tacccttgtg cctcgctcag
gggagcaggc tgaagggtcc 600ccaggtggac ctggagactc tcagggtcga aaacggcggc
agaccagcat gacagatttc 660taccactcca aacgccggct gatcttctcc aagaggaagc
cctaatccgc ccacaggaag 720cctgcagtcc tggaagcgcg agggcctcaa aggcccgctc
tacatcttct gccttagtct 780cagtttgtgt gtcttaatta ttatttgtgt tttaatttaa
acacctcctc atgtacatac 840cctggccgcc ccctgccccc cagcctctgg cattagaatt
atttaaacaa aaactaggcg 900gttgaatgag aggttcctaa gagtgctggg catttttatt
ttatgaaata ctatttaaag 960cctcctcatc ccgtgttctc cttttcctct ctcccggagg
ttgggtgggc cggcttcatg 1020ccagctactt cctcctcccc acttgtccgc tgggtggtac
cctctggagg ggtgtggctc 1080cttcccatcg ctgtcacagg cggttatgaa attcaccccc
tttcctggac actcagacct 1140gaattctttt tcatttgaga agtaaacaga tggcactttg
aaggggcctc accgagtggg 1200ggcatcatca aaaactttgg agtcccctca cctcctctaa
ggttgggcag ggtgaccctg 1260aagtgagcac agcctagggc tgagctgggg acctggtacc
ctcctggctc ttgatacccc 1320cctctgtctt gtgaaggcag ggggaaggtg gggtcctgga
gcagaccacc ccgcctgccc 1380tcatggcccc tctgacctgc actggggagc ccgtctcagt
gttgagcctt ttccctcttt 1440ggctcccctg taccttttga ggagccccag ctacccttct
tctccagctg ggctctgcaa 1500ttcccctctg ctgctgtccc tcccccttgt cctttccctt
cagtaccctc tcagctccag 1560gtggctctga ggtgcctgtc ccacccccac ccccagctca
atggactgga aggggaaggg 1620acacacaaga agaagggcac cctagttcta cctcaggcag
ctcaagcagc gaccgccccc 1680tcctctagct gtgggggtga gggtcccatg tggtggcaca
ggcccccttg agtggggtta 1740tctctgtgtt aggggtatat gatgggggag tagatctttc
taggagggag acactggccc 1800ctcaaatcgt ccagcgacct tcctcatcca ccccatccct
ccccagttca ttgcactttg 1860attagcagcg gaacaaggag tcagacattt taagatggtg
gcagtagagg ctatggacag 1920ggcatgccac gtgggctcat atggggctgg gagtagttgt
ctttcctggc actaacgttg 1980agcccctgga ggcactgaag tgcttagtgt acttggagta
ttggggtctg accccaaaca 2040ccttccagct cctgtaacat actggcctgg actgttttct
ctcggctccc catgtgtcct 2100ggttcccgtt tctccaccta gactgtaaac ctctcgaggg
cagggaccac accctgtact 2160gttctgtgtc tttcacagct cctcccacaa tgctgaatat
acagcaggtg ctcaataaat 2220gattcttagt gactttactt gtaatatt
22481322154DNAHomo Sapiens 132aacatgttga gctctggcat
agaagaggct ggtggctatt ttgtccttgg gctgcctgtt 60ttcaggtgag gaaggggatg
gtaggagaca ggagacctct aaagacccca ggcgccatgt 120cagaaccggc tggggatgtc
cgtcagaacc catgcggcag caaggcctgc cgccgcctct 180tcggcccagt ggacagcgag
cagctgagcc gcgactgtga tgcgctaatg gcgggctgca 240tccaggaggc ccgtgagcga
tggaacttcg actttgtcac cgagacacca ctggagggtg 300acttcgcctg ggagcgtgtg
cggggccttg gcctgcccaa gctctacctt cccacggggc 360cccggcgagg ccgggatgag
ttgggaggag gcaggcggcc tggcacctca cctgctctgc 420tgcaggggac agcagaggaa
gaccatgtgg acctgtcact gtcttgtacc cttgtgcctc 480gctcagggga gcaggctgaa
gggtccccag gtggacctgg agactctcag ggtcgaaaac 540ggcggcagac cagcatgaca
gatttctacc actccaaacg ccggctgatc ttctccaaga 600ggaagcccta atccgcccac
aggaagcctg cagtcctgga agcgcgaggg cctcaaaggc 660ccgctctaca tcttctgcct
tagtctcagt ttgtgtgtct taattattat ttgtgtttta 720atttaaacac ctcctcatgt
acataccctg gccgccccct gccccccagc ctctggcatt 780agaattattt aaacaaaaac
taggcggttg aatgagaggt tcctaagagt gctgggcatt 840tttattttat gaaatactat
ttaaagcctc ctcatcccgt gttctccttt tcctctctcc 900cggaggttgg gtgggccggc
ttcatgccag ctacttcctc ctccccactt gtccgctggg 960tggtaccctc tggaggggtg
tggctccttc ccatcgctgt cacaggcggt tatgaaattc 1020accccctttc ctggacactc
agacctgaat tctttttcat ttgagaagta aacagatggc 1080actttgaagg ggcctcaccg
agtgggggca tcatcaaaaa ctttggagtc ccctcacctc 1140ctctaaggtt gggcagggtg
accctgaagt gagcacagcc tagggctgag ctggggacct 1200ggtaccctcc tggctcttga
tacccccctc tgtcttgtga aggcaggggg aaggtggggt 1260cctggagcag accaccccgc
ctgccctcat ggcccctctg acctgcactg gggagcccgt 1320ctcagtgttg agccttttcc
ctctttggct cccctgtacc ttttgaggag ccccagctac 1380ccttcttctc cagctgggct
ctgcaattcc cctctgctgc tgtccctccc ccttgtcctt 1440tcccttcagt accctctcag
ctccaggtgg ctctgaggtg cctgtcccac ccccaccccc 1500agctcaatgg actggaaggg
gaagggacac acaagaagaa gggcacccta gttctacctc 1560aggcagctca agcagcgacc
gccccctcct ctagctgtgg gggtgagggt cccatgtggt 1620ggcacaggcc cccttgagtg
gggttatctc tgtgttaggg gtatatgatg ggggagtaga 1680tctttctagg agggagacac
tggcccctca aatcgtccag cgaccttcct catccacccc 1740atccctcccc agttcattgc
actttgatta gcagcggaac aaggagtcag acattttaag 1800atggtggcag tagaggctat
ggacagggca tgccacgtgg gctcatatgg ggctgggagt 1860agttgtcttt cctggcacta
acgttgagcc cctggaggca ctgaagtgct tagtgtactt 1920ggagtattgg ggtctgaccc
caaacacctt ccagctcctg taacatactg gcctggactg 1980ttttctctcg gctccccatg
tgtcctggtt cccgtttctc cacctagact gtaaacctct 2040cgagggcagg gaccacaccc
tgtactgttc tgtgtctttc acagctcctc ccacaatgct 2100gaatatacag caggtgctca
ataaatgatt cttagtgact ttacttgtaa tatt 21541332413DNAHomo Sapiens
133gaggcgggcc cgggcggggc ggttgtatat cagggccgcg ctgagctgcg ccagctgagg
60tgtgagcagc tgccgaagtc agttccttgt ggagccggag ctgggcgcgg attcgccgag
120gcaccgaggc actcagagga ggcgccatgt cagaaccggc tggggatgtc cgtcagaacc
180catgcggcag caaggcctgc cgccgcctct tcggcccagt ggacagcgag cagctgagcc
240gcgactgtga tgcgctaatg gcgggctgca tccaggaggc ccgtgagcga tggaacttcg
300actttgtcac cgagacacca ctggagggtg acttcgcctg ggagcgtgtg cggggccttg
360gcctgcccaa gctctacctt cccacggggc cccggcgagg ccgggatgag ttgggaggag
420gcaggcggcc tggcacctca cctgctctgc tgcaggggac agcagaggaa gaccatgtgg
480acctgtcact gtcttgtacc cttgtgcctc gctcagggga gcaggctgaa gggtccccag
540gtggacctgg agactctcag ggtcgaaaac ggcggcagac cagcatgaca ggtgcggaca
600tgtgcacgga aggactttgt aagggaccag gattctcaga atccatggtc caagggctga
660cctgtctggt cctggtccag catgctccag gtagaaggaa acaggcccag agaggggaag
720caacctccct gaggtcacac agcaagtagg cagcaaagac caactagcta acatttattg
780ggaatgttca ttatgccagg ccctttgcca agcttctaag atttctacca ctccaaacgc
840cggctgatct tctccaagag gaagccctaa tccgcccaca ggaagcctgc agtcctggaa
900gcgcgagggc ctcaaaggcc cgctctacat cttctgcctt agtctcagtt tgtgtgtctt
960aattattatt tgtgttttaa tttaaacacc tcctcatgta cataccctgg ccgccccctg
1020ccccccagcc tctggcatta gaattattta aacaaaaact aggcggttga atgagaggtt
1080cctaagagtg ctgggcattt ttattttatg aaatactatt taaagcctcc tcatcccgtg
1140ttctcctttt cctctctccc ggaggttggg tgggccggct tcatgccagc tacttcctcc
1200tccccacttg tccgctgggt ggtaccctct ggaggggtgt ggctccttcc catcgctgtc
1260acaggcggtt atgaaattca ccccctttcc tggacactca gacctgaatt ctttttcatt
1320tgagaagtaa acagatggca ctttgaaggg gcctcaccga gtgggggcat catcaaaaac
1380tttggagtcc cctcacctcc tctaaggttg ggcagggtga ccctgaagtg agcacagcct
1440agggctgagc tggggacctg gtaccctcct ggctcttgat acccccctct gtcttgtgaa
1500ggcaggggga aggtggggtc ctggagcaga ccaccccgcc tgccctcatg gcccctctga
1560cctgcactgg ggagcccgtc tcagtgttga gccttttccc tctttggctc ccctgtacct
1620tttgaggagc cccagctacc cttcttctcc agctgggctc tgcaattccc ctctgctgct
1680gtccctcccc cttgtccttt cccttcagta ccctctcagc tccaggtggc tctgaggtgc
1740ctgtcccacc cccaccccca gctcaatgga ctggaagggg aagggacaca caagaagaag
1800ggcaccctag ttctacctca ggcagctcaa gcagcgaccg ccccctcctc tagctgtggg
1860ggtgagggtc ccatgtggtg gcacaggccc ccttgagtgg ggttatctct gtgttagggg
1920tatatgatgg gggagtagat ctttctagga gggagacact ggcccctcaa atcgtccagc
1980gaccttcctc atccacccca tccctcccca gttcattgca ctttgattag cagcggaaca
2040aggagtcaga cattttaaga tggtggcagt agaggctatg gacagggcat gccacgtggg
2100ctcatatggg gctgggagta gttgtctttc ctggcactaa cgttgagccc ctggaggcac
2160tgaagtgctt agtgtacttg gagtattggg gtctgacccc aaacaccttc cagctcctgt
2220aacatactgg cctggactgt tttctctcgg ctccccatgt gtcctggttc ccgtttctcc
2280acctagactg taaacctctc gagggcaggg accacaccct gtactgttct gtgtctttca
2340cagctcctcc cacaatgctg aatatacagc aggtgctcaa taaatgattc ttagtgactt
2400tacttgtaat att
24131343542DNAHomo Sapiens 134cgtggcctcc gctgggcagg gcgacgcgga accgaggcgg
cggcggcggc tgcggcggca 60ggaaatcggg gctcggcccc gccggcgcgc gaccccatcc
ccatcccggt ccctgcagag 120cgatccccgg gcccagatat ggacgcagca gagccgggac
tccccccagg tcctgagggc 180aggaagaggt acagtgacat cttccggagc ctggacaacc
tcgaaatctc actggggaac 240gtgacccttg agatgctggc tggagaccct ctactctcag
aagacccaga acctgacaag 300acccctacag ccactgttac caacgaagcc agctgttgga
gcggcccctc cccagagggt 360cctgtacccc tcacagggga ggaactggac ttgcggctca
ttcggacaaa ggggggtgtg 420gacgcagccc tggaatatgc caagacctgg agccgctatg
ccaaggaact gcttgcctgg 480actgaaaaga gagccagcta tgagctggag tttgctaaga
gcaccatgaa gatcgctgaa 540gctggcaagg tgtccattca acagcagagc cacatgcctc
tgcagtacat ctacaccctg 600tttctggagc acgatctcag cctgggaacc ctggccatgg
agacagtggc ccagcagaaa 660agagactact accagcccct cgccgccaaa cggactgaga
ttgagaagtg gcggaaggag 720ttcaaggagc agtggatgaa ggagcagaag cggatgaatg
aggcggtgca ggcactgcgg 780cgcgcccagc tgcagtatgt gcaacgcagc gaggacctgc
gggcacgctc ccaggggtcc 840cctgaggact cggcccccca ggcctcgccg ggacctagca
agcagcagga gcggcggcgg 900cgctcgcgag aggaggccca ggccaaggcg caggaggccg
aggcgctgta ccaggcctgt 960gtccgcgagg ccaacgcgcg gcagcaggac ctggagatcg
ccaagcagcg aatcgtgtcg 1020cacgtgcgca agctggtgtt tcagggggat gaagtgctga
ggcgggtgac gctgagtctc 1080ttcgggctgc ggggggcgca ggcagagcgt ggcccccgcg
ccttcgccgc cctggccgag 1140tgctgtgcgc cctttgagcc gggccagcgc taccaggagt
ttgtacgggc gctgcggccc 1200gaggccccgc cgcccccgcc gcccgccttc tccttccagg
agttccttcc ctccttgaac 1260agctcccctc tggacatcag aaagaagctc tctgggcctc
ttcctccaag gctggatgag 1320aattcagctg agccaggccc ttgggaggat ccgggcacag
gctggcgctg gcaagggact 1380ccaggcccca ctccgggcag cgatgtggac agcgtgggtg
gcggcagcga gtctcggtcc 1440ctggactcac ccacttccag cccaggcgct ggcacgaggc
agctggtgaa ggcttcgtcc 1500acaggcactg agtcctcaga tgactttgag gagcgagacc
ctgacctggg agacgggctg 1560gagaatgggc tgggcagccc cttcgggaag tggacactgt
ccagcgcggc tcagacccac 1620cagctgcggc gactgcgggg cccagccaag tgccgcgagt
gcgaagcctt catggtcagc 1680gggacggagt gtgaggagtg ctttctgacc tgccacaagc
gctgcctgga gactctcctg 1740atcctctgtg gacacaggcg gctcccagcc cggacacccc
tttttggggt tgacttcctg 1800cagctaccca gggacttccc ggaggaggta ccctttgtgg
tcacgaagtg cacggctgag 1860atagaacacc gtgccctgga tgtgcagggc atttaccggg
tcagcgggtc ccgggtccgt 1920gtggagcggc tgtgccaggc tttcgagaat ggccgagcgt
tggtggagct gtcggggaac 1980tcgcctcatg acgtctcgag tgtcctcaag cgatttcttc
aggagctcac cgagcccgtg 2040atccccttcc acctctacga cgccttcatc tctctggcta
agaccttgca tgcagaccct 2100ggggacgacc ctgggacccc cagccccagc cctgaggtta
tccgctcgct gaagaccctc 2160ttggtacagc tgcctgactc taactacaac accctgcggc
acctggtggc ccatctgttc 2220agggtggctg cacgatttat ggaaaacaag atgtctgcca
acaacctggg cattgtgttt 2280gggccgacac tgctgcggcc gccggacggc ccgcgggcag
ccagcgccat ccctgtcacc 2340tgcctgctgg actctgggca tcaggcccag cttgtggagt
tcctcatcgt gcactacgag 2400cagatctttg ggatggatga gctcccccag gccactgagc
ccccgcccca agactccagc 2460ccagcccctg ggcccctcac aaccagctcc caaccgccac
ccccgcacct tgacccagac 2520tcccagcccc cagtcctagc ctcagacccc ggcccagacc
cccagcacca cagtaccctg 2580gagcagcatc ccacggccac acctaccgag attccaactc
cacagagtga ccagagagag 2640gacgtggctg aagacaccaa agatggggga ggggaagtgt
ccagccaagg cccagaggac 2700tcactcctgg ggacacagtc tcgtggccac ttcagccgcc
agccagtgaa gtatccccgg 2760ggcggtgtga ggcctgtaac ccaccagctg tccagtctgg
ccctggtggc ttccaagctg 2820tgcgaggaga cccccatcac atcagtgccc agagggagtt
tgcgggggcg ggggcccagc 2880cctgcagctg cctcccctga gggcagcccc ctgcgccgca
ccccgctgcc caagcatttt 2940gagattaccc aggagacagc ccggctactc tcgaaattgg
acagcgaggc tgtgcccagg 3000gccacctgct gcccggacgt ccagcctgag gaagccgagg
accatctctg accaccctgg 3060caccttaaat aaggaagagg cccagattgt gaacacggac
ccatatatcc ctacctccca 3120ccacctagtg gccaaacacc ccgccaggag ttcaatgctg
ggagaggtcc agagggttcc 3180tataaggaaa aactatttaa tacatgacct aggggaggcc
taaaaccctt ttggggataa 3240tgtcccagag tccccccact agacacaggt cactgccaag
catcagggcc actcgggctc 3300agaggtcact cagggtcaat actcagggtc agtgcaggtt
atgagatcct tggggtccac 3360cctagtctct gacacctggg acaggggtgc ttttgctact
ttggttgtgg tcactccccc 3420acacctgcct gcctccttca cggactcgaa gtgaccttcc
tggaggaggt gggcagctca 3480gactccacat gctggtggtg cctgaggtct gatggcctct
aataaactgt gtcctatatg 3540cc
35421353616DNAHomo Sapiens 135cgtggcctcc gctgggcagg
gcgacgcgga accgaggcgg cggcggcggc tgcggcggca 60ggaaatcggg gctcggcccc
gccggcgcgc gaccccatcc ccatcccggt ccctgcagag 120cgatccccgg gcccagatat
ggacgcagca gagccgggac tccccccagg tcctgagggc 180aggaagaggt acagtgacat
cttccggagc ctggacaacc tcgaaatctc actggggaac 240gtgacccttg agatgctggc
tggagaccct ctactctcag aagacccaga acctgacaag 300acccctacag ccactgttac
caacgaagcc agctgttgga gcggcccctc cccagagggt 360cctgtacccc tcacagggga
ggaactggac ttgcggctca ttcggacaaa ggggggtgtg 420gacgcagccc tggaatatgc
caagacctgg agccgctatg ccaaggaact gcttgcctgg 480actgaaaaga gagccagcta
tgagctggag tttgctaaga gcaccatgaa gatcgctgaa 540gctggcaagg tgtccattca
acagcagagc cacatgcctc tgcagtacat ctacaccctg 600tttctggagc acgatctcag
cctgggaacc ctggccatgg agacagtggc ccagcagaaa 660agagactact accagcccct
cgccgccaaa cggactgaga ttgagaagtg gcggaaggag 720ttcaaggagc agtggatgaa
ggagcagaag cggatgaatg aggcggtgca ggcactgcgg 780cgcgcccagc tgcagtatgt
gcaacgcagc gaggacctgc gggcacgctc ccaggggtcc 840cctgaggact cggcccccca
ggcctcgccg ggacctagca agcagcagga gcggcggcgg 900cgctcgcgag aggaggccca
ggccaaggcg caggaggccg aggcgctgta ccaggcctgt 960gtccgcgagg ccaacgcgcg
gcagcaggac ctggagatcg ccaagcagcg aatcgtgtcg 1020cacgtgcgca agctggtgtt
tcagggggat gaagtgctga ggcgggtgac gctgagtctc 1080ttcgggctgc ggggggcgca
ggcagagcgt ggcccccgcg ccttcgccgc cctggccgag 1140tgctgtgcgc cctttgagcc
gggccagcgc taccaggagt ttgtacgggc gctgcggccc 1200gaggccccgc cgcccccgcc
gcccgccttc tccttccagg agttccttcc ctccttgaac 1260agctcccctc tggacatcag
aaagaagctc tctgggcctc ttcctccaag gctggatgag 1320aattcagctg agccaggccc
ttgggaggat ccgggcacag gctggcgctg gcaagggact 1380ccaggcccca ctccgggcag
cgatgtggac agcgtgggtg gcggcagcga gtctcggtcc 1440ctggactcac ccacttccag
cccaggcgct ggcacgaggc agctggtgaa ggcttcgtcc 1500acaggcactg agtcctcaga
tgactttgag gagcgagacc ctggtgaggc tgaagcaggg 1560taggtcagga tgggacaggg
cagggcacca ggcactcctg accctgtctc cctgcagacc 1620tgggagacgg gctggagaat
gggctgggca gccccttcgg gaagtggaca ctgtccagcg 1680cggctcagac ccaccagctg
cggcgactgc ggggcccagc caagtgccgc gagtgcgaag 1740ccttcatggt cagcgggacg
gagtgtgagg agtgctttct gacctgccac aagcgctgcc 1800tggagactct cctgatcctc
tgtggacaca ggcggctccc agcccggaca cccctttttg 1860gggttgactt cctgcagcta
cccagggact tcccggagga ggtacccttt gtggtcacga 1920agtgcacggc tgagatagaa
caccgtgccc tggatgtgca gggcatttac cgggtcagcg 1980ggtcccgggt ccgtgtggag
cggctgtgcc aggctttcga gaatggccga gcgttggtgg 2040agctgtcggg gaactcgcct
catgacgtct cgagtgtcct caagcgattt cttcaggagc 2100tcaccgagcc cgtgatcccc
ttccacctct acgacgcctt catctctctg gctaagacct 2160tgcatgcaga ccctggggac
gaccctggga cccccagccc cagccctgag gttatccgct 2220cgctgaagac cctcttggta
cagctgcctg actctaacta caacaccctg cggcacctgg 2280tggcccatct gttcagggtg
gctgcacgat ttatggaaaa caagatgtct gccaacaacc 2340tgggcattgt gtttgggccg
acactgctgc ggccgccgga cggcccgcgg gcagccagcg 2400ccatccctgt cacctgcctg
ctggactctg ggcatcaggc ccagcttgtg gagttcctca 2460tcgtgcacta cgagcagatc
tttgggatgg atgagctccc ccaggccact gagcccccgc 2520cccaagactc cagcccagcc
cctgggcccc tcacaaccag ctcccaaccg ccacccccgc 2580accttgaccc agactcccag
cccccagtcc tagcctcaga ccccggccca gacccccagc 2640accacagtac cctggagcag
catcccacgg ccacacctac cgagattcca actccacaga 2700gtgaccagag agaggacgtg
gctgaagaca ccaaagatgg gggaggggaa gtgtccagcc 2760aaggcccaga ggactcactc
ctggggacac agtctcgtgg ccacttcagc cgccagccag 2820tgaagtatcc ccggggcggt
gtgaggcctg taacccacca gctgtccagt ctggccctgg 2880tggcttccaa gctgtgcgag
gagaccccca tcacatcagt gcccagaggg agtttgcggg 2940ggcgggggcc cagccctgca
gctgcctccc ctgagggcag ccccctgcgc cgcaccccgc 3000tgcccaagca ttttgagatt
acccaggaga cagcccggct actctcgaaa ttggacagcg 3060aggctgtgcc cagggccacc
tgctgcccgg acgtccagcc tgaggaagcc gaggaccatc 3120tctgaccacc ctggcacctt
aaataaggaa gaggcccaga ttgtgaacac ggacccatat 3180atccctacct cccaccacct
agtggccaaa caccccgcca ggagttcaat gctgggagag 3240gtccagaggg ttcctataag
gaaaaactat ttaatacatg acctagggga ggcctaaaac 3300ccttttgggg ataatgtccc
agagtccccc cactagacac aggtcactgc caagcatcag 3360ggccactcgg gctcagaggt
cactcagggt caatactcag ggtcagtgca ggttatgaga 3420tccttggggt ccaccctagt
ctctgacacc tgggacaggg gtgcttttgc tactttggtt 3480gtggtcactc ccccacacct
gcctgcctcc ttcacggact cgaagtgacc ttcctggagg 3540aggtgggcag ctcagactcc
acatgctggt ggtgcctgag gtctgatggc ctctaataaa 3600ctgtgtccta tatgcc
36161363540DNAHomo Sapiens
136cgtggcctcc gctgggcagg gcgacgcgga accgaggcgg cggcggcggc tgcggcggca
60ggaaatcggg gctcggcccc gccggcgcgc gaccccatcc ccatcccggt ccctgcagag
120cgatccccgg gcccagatat ggacgcagca gagccgggac tccccccagg tcctgagggc
180aggaagaggt acagtgacat cttccggagc ctggacaacc tcgaaatctc actggggaac
240gacccttgag atgctggctg gagaccctct actctcagaa gacccagaac ctgacaagac
300ccctacagcc actgttacca acgaagccag ctgttggagc ggcccctccc cagagggtcc
360tgtacccctc acaggggagg aactggactt gcggctcatt cggacaaagg ggggtgtgga
420cgcagccctg gaatatgcca agacctggag ccgctatgcc aaggaactgc ttgcctggac
480tgaaaagaga gccagctatg agctggagtt tgctaagagc accatgaaga tcgctgaagc
540tggcaaggtg tccattcaac agcagagcca catgcctctg cagtacatct acaccctgtt
600tctggagcac gatctcagcc tgggaaccct ggccatggag acagtggccc agcagaaaag
660agactactac cagcccctcg ccgccaaacg gactgagatt gagaagtggc ggaaggagtt
720caaggagcag tggatgaagg agcagaagcg gatgaatgag gcggtgcagg cactgcggcg
780cgcccagctg cagtatgtgc aacgcagcga ggacctgcgg gcacgctccc aggggtcccc
840tgaggactcg gccccccagg cctcgccggg acctagcaag cagcaggagc ggcggcggcg
900ctcgcgagag gaggcccagg ccaaggcgca ggaggccgag gcgctgtacc aggcctgtgt
960ccgcgaggcc aacgcgcggc agcaggacct ggagatcgcc aagcagcgaa tcgtgtcgca
1020cgtgcgcaag ctggtgtttc agggggatga agtgctgagg cgggtgacgc tgagtctctt
1080cgggctgcgg ggggcgcagg cagagcgtgg cccccgcgcc ttcgccgccc tggccgagtg
1140ctgtgcgccc tttgagccgg gccagcgcta ccaggagttt gtacgggcgc tgcggcccga
1200ggccccgccg cccccgccgc ccgccttctc cttccaggag ttccttccct ccttgaacag
1260ctcccctctg gacatcagaa agaagctctc tgggcctctt cctccaaggc tggatgagaa
1320ttcagctgag ccaggccctt gggaggatcc gggcacaggc tggcgctggc aagggactcc
1380aggccccact ccgggcagcg atgtggacag cgtgggtggc ggcagcgagt ctcggtccct
1440ggactcaccc acttccagcc caggcgctgg cacgaggcag ctggtgaagg cttcgtccac
1500aggcactgag tcctcagatg actttgagga gcgagaccct gacctgggag acgggctgga
1560gaatgggctg ggcagcccct tcgggaagtg gacactgtcc agcgcggctc agacccacca
1620gctgcggcga ctgcggggcc cagccaagtg ccgcgagtgc gaagccttca tggtcagcgg
1680gacggagtgt gaggagtgct ttctgacctg ccacaagcgc tgcctggaga ctctcctgat
1740cctctgtgga cacaggcggc tcccagcccg gacacccctt tttggggttg acttcctgca
1800gctacccagg gacttcccgg aggaggtacc ctttgtggtc acgaagtgca cggctgagat
1860agaacaccgt gccctggatg tgcagggcat ttaccgggtc agcgggtccc gggtccgtgt
1920ggagcggctg tgccaggctt tcgagaatgg ccgagcgttg gtggagctgt cggggaactc
1980gcctcatgac gtctcgagtg tcctcaagcg atttcttcag gagctcaccg agcccgtgat
2040ccccttccac ctctacgacg ccttcatctc tctggctaag accttgcatg cagaccctgg
2100ggacgaccct gggaccccca gccccagccc tgaggttatc cgctcgctga agaccctctt
2160ggtacagctg cctgactcta actacaacac cctgcggcac ctggtggccc atctgttcag
2220ggtggctgca cgatttatgg aaaacaagat gtctgccaac aacctgggca ttgtgtttgg
2280gccgacactg ctgcggccgc cggacggccc gcgggcagcc agcgccatcc ctgtcacctg
2340cctgctggac tctgggcatc aggcccagct tgtggagttc ctcatcgtgc actacgagca
2400gatctttggg atggatgagc tcccccaggc cactgagccc ccgccccaag actccagccc
2460agcccctggg cccctcacaa ccagctccca accgccaccc ccgcaccttg acccagactc
2520ccagccccca gtcctagcct cagaccccgg cccagacccc cagcaccaca gtaccctgga
2580gcagcatccc acggccacac ctaccgagat tccaactcca cagagtgacc agagagagga
2640cgtggctgaa gacaccaaag atgggggagg ggaagtgtcc agccaaggcc cagaggactc
2700actcctgggg acacagtctc gtggccactt cagccgccag ccagtgaagt atccccgggg
2760cggtgtgagg cctgtaaccc accagctgtc cagtctggcc ctggtggctt ccaagctgtg
2820cgaggagacc cccatcacat cagtgcccag agggagtttg cgggggcggg ggcccagccc
2880tgcagctgcc tcccctgagg gcagccccct gcgccgcacc ccgctgccca agcattttga
2940gattacccag gagacagccc ggctactctc gaaattggac agcgaggctg tgcccagggc
3000cacctgctgc ccggacgtcc agcctgagga agccgaggac catctctgac caccctggca
3060ccttaaataa ggaagaggcc cagattgtga acacggaccc atatatccct acctcccacc
3120acctagtggc caaacacccc gccaggagtt caatgctggg agaggtccag agggttccta
3180taaggaaaaa ctatttaata catgacctag gggaggccta aaaccctttt ggggataatg
3240tcccagagtc cccccactag acacaggtca ctgccaagca tcagggccac tcgggctcag
3300aggtcactca gggtcaatac tcagggtcag tgcaggttat gagatccttg gggtccaccc
3360tagtctctga cacctgggac aggggtgctt ttgctacttt ggttgtggtc actcccccac
3420acctgcctgc ctccttcacg gactcgaagt gaccttcctg gaggaggtgg gcagctcaga
3480ctccacatgc tggtggtgcc tgaggtctga tggcctctaa taaactgtgt cctatatgcc
35401373345DNAHomo Sapiens 137cgtggcctcc gctgggcagg gcgacgcgga accgaggcgg
cggcggcggc tgcggcggca 60ggaaatcggg gctcggcccc gccggcgcgc gaccccatcc
ccatcccggt ccctgcagag 120cgatccccgg gcccagatat ggacgcagca gagccgggac
tccccccagg tcctgagggc 180aggaagaggt acagtgacat cttccggagc ctggacaacc
tcgaaatctc actggggaac 240gtgacccttg agatgctggc tggagaccct ctactctcag
aagacccaga acctgacaag 300acccctacag ccactgttac caacgaagcc agctgttgga
gcggcccctc cccagagggt 360cctgtacccc tcacagggga ggaactggac ttgcggctca
ttcggacaaa ggggggtgtg 420gacgcagccc tggaatatgc caagacctgg agccgctatg
ccaaggaact gcttgcctgg 480actgaaaaga gagccagcta tgagctggag tttgctaaga
gcaccatgaa gatcgctgaa 540gctggcaagg tgtccattca acagcagagc cacatgcctc
tgcagtacat ctacaccctg 600tttctggagc acgatctcag cctgggaacc ctggccatgg
agacagtggc ccagcagaaa 660agagactact accagcccct cgccgccaaa cggactgaga
ttgagaagtg gcggaaggag 720ttcaaggagc agtggatgaa ggagcagaag cggatgaatg
aggcggtgca ggcactgcgg 780cgcgcccagc tgcagtatgt gcaacgcagc gaggacctgc
gggcacgctc ccaggggtcc 840cctgaggact cggcccccca ggcctcgccg ggacctagca
agcagcagga gcggcggcgg 900cgctcgcgag aggaggccca ggccaaggcg caggaggccg
aggcgctgta ccaggcctgt 960gtccgcgagg ccaacgcgcg gcagcaggac ctggagatcg
ccaagcagcg aatcgtgtcg 1020cacgtgcgca agctggtgtt tcagggggat gaagtgctga
ggcgggtgac gctgagtctc 1080ttcgggctgc ggggggcgca ggcagagcgt ggcccccgcg
ccttcgccgc cctggccgag 1140tgctgtgcgc cctttgagcc gggccagcgc taccaggagt
ttgtacgggc gctgcggccc 1200gaggccccgc cgcccccgcc gcccgccttc tccttccagg
agttccttcc ctccttgaac 1260agctcccctc tggacatcag aaagaagctc tctgggcctc
ttcctccaag gctggatgag 1320aattcagctg agccaggccc ttgggaggat ccgggcacag
gctggcgctg gcaagggact 1380ccaggcccca ctccgggcag cgatgtggac agcgtgggtg
gcggcagcga gtctcggtcc 1440ctggactcac ccacttccag cccaggcgct ggcacgaggc
agctggtgaa ggcttcgtcc 1500acaggcactg agtcctcaga tgactttgag gagcgagacc
ctgacctggg agacgggctg 1560gagaatgggc tgggcagccc cttcgggaag tggacactgt
ccagcgcggc tcagacccac 1620cagctgcggc gactgcgggg cccagccaag tgccgcgagt
gcgaagcctt catggtcagc 1680gggacggagt gtgaggagtg ctttctgacc tgccacaagc
gctgcctgga gactctcctg 1740atcctctgtg gacacaggcg gctcccagcc cggacacccc
tttttggggt tgacttcctg 1800cagctaccca gggacttccc ggaggaggta ccctttgtgg
tcacgaagtg cacggctgag 1860atagaacacc gtgccctgga tgtgcagggc atttaccggg
tcagcgggtc ccgggtccgt 1920gtggagcggc tgtgccaggc tttcgagaat ggccgagcgt
tggtggagct gtcggggaac 1980tcgcctcatg acgtctcgag tgtcctcaag cgatttcttc
aggagggtgg ctgcacgatt 2040tatggaaaac aagatgtctg ccaacaacct gggcattgtg
tttgggccga cactgctgcg 2100gccgccggac ggcccgcggg cagccagcgc catccctgtc
acctgcctgc tggactctgg 2160gcatcaggcc cagcttgtgg agttcctcat cgtgcactac
gagcagatct ttgggatgga 2220tgagctcccc caggccactg agcccccgcc ccaagactcc
agcccagccc ctgggcccct 2280cacaaccagc tcccaaccgc cacccccgca ccttgaccca
gactcccagc ccccagtcct 2340agcctcagac cccggcccag acccccagca ccacagtacc
ctggagcagc atcccacggc 2400cacacctacc gagattccaa ctccacagag tgaccagaga
gaggacgtgg ctgaagacac 2460caaagatggg ggaggggaag tgtccagcca aggcccagag
gactcactcc tggggacaca 2520gtctcgtggc cacttcagcc gccagccagt gaagtatccc
cggggcggtg tgaggcctgt 2580aacccaccag ctgtccagtc tggccctggt ggcttccaag
ctgtgcgagg agacccccat 2640cacatcagtg cccagaggga gtttgcgggg gcgggggccc
agccctgcag ctgcctcccc 2700tgagggcagc cccctgcgcc gcaccccgct gcccaagcat
tttgagatta cccaggagac 2760agcccggcta ctctcgaaat tggacagcga ggctgtgccc
agggccacct gctgcccgga 2820cgtccagcct gaggaagccg aggaccatct ctgaccaccc
tggcacctta aataaggaag 2880aggcccagat tgtgaacacg gacccatata tccctacctc
ccaccaccta gtggccaaac 2940accccgccag gagttcaatg ctgggagagg tccagagggt
tcctataagg aaaaactatt 3000taatacatga cctaggggag gcctaaaacc cttttgggga
taatgtccca gagtcccccc 3060actagacaca ggtcactgcc aagcatcagg gccactcggg
ctcagaggtc actcagggtc 3120aatactcagg gtcagtgcag gttatgagat ccttggggtc
caccctagtc tctgacacct 3180gggacagggg tgcttttgct actttggttg tggtcactcc
cccacacctg cctgcctcct 3240tcacggactc gaagtgacct tcctggagga ggtgggcagc
tcagactcca catgctggtg 3300gtgcctgagg tctgatggcc tctaataaac tgtgtcctat
atgcc 3345138124PRTHomo Sapiens 138Met Ser Ser Ala Leu
Glu Ser Val Thr Val Ser Asp Arg Pro Leu Gly 1 5
10 15 Val Ser Ile Thr Lys Ala Glu Val Ala Pro
Glu Glu Asp Glu Arg Lys 20 25
30 Lys Arg Arg Arg Glu Arg Asn Lys Ile Ala Ala Ala Lys Cys Arg
Asn 35 40 45 Lys
Lys Lys Glu Lys Thr Glu Cys Leu Gln Lys Glu Ser Glu Lys Leu 50
55 60 Glu Ser Val Asn Ala Glu
Leu Lys Ala Gln Ile Glu Glu Leu Lys Asn 65 70
75 80 Glu Lys Gln His Leu Ile Tyr Met Leu Asn Leu
His Arg Pro Thr Cys 85 90
95 Ile Val Arg Ala Gln Asn Gly Arg Thr Pro Glu Asp Glu Arg Asn Leu
100 105 110 Phe Ile
Gln Gln Ile Lys Glu Gly Thr Leu Gln Ser 115 120
139181PRTHomo Sapiens 139Met Met Leu Gln His Pro Gly Gln
Val Ser Ala Ser Glu Val Ser Ala 1 5 10
15 Ser Ala Ile Val Pro Cys Leu Ser Pro Pro Gly Ser Leu
Val Phe Glu 20 25 30
Asp Phe Ala Asn Leu Thr Pro Phe Val Lys Glu Glu Leu Arg Phe Ala
35 40 45 Ile Gln Asn Lys
His Leu Cys His Arg Met Ser Ser Ala Leu Glu Ser 50
55 60 Val Thr Val Ser Asp Arg Pro Leu
Gly Val Ser Ile Thr Lys Ala Glu 65 70
75 80 Val Ala Pro Glu Glu Asp Glu Arg Lys Lys Arg Arg
Arg Glu Arg Asn 85 90
95 Lys Ile Ala Ala Ala Lys Cys Arg Asn Lys Lys Lys Glu Lys Thr Glu
100 105 110 Cys Leu Gln
Lys Glu Ser Glu Lys Leu Glu Ser Val Asn Ala Glu Leu 115
120 125 Lys Ala Gln Ile Glu Glu Leu Lys
Asn Glu Lys Gln His Leu Ile Tyr 130 135
140 Met Leu Asn Leu His Arg Pro Thr Cys Ile Val Arg Ala
Gln Asn Gly 145 150 155
160 Arg Thr Pro Glu Asp Glu Arg Asn Leu Phe Ile Gln Gln Ile Lys Glu
165 170 175 Gly Thr Leu Gln
Ser 180 140340PRTHomo Sapiens 140Met Ala Asp Ser Val Lys
Thr Phe Leu Gln Asp Leu Ala Arg Gly Ile 1 5
10 15 Lys Asp Ser Ile Trp Gly Ile Cys Thr Ile Ser
Lys Leu Asp Ala Arg 20 25
30 Ile Gln Gln Lys Arg Glu Glu Gln Arg Arg Arg Arg Ala Ser Ser
Val 35 40 45 Leu
Ala Gln Arg Arg Ala Gln Ser Ile Glu Arg Lys Gln Glu Ser Glu 50
55 60 Pro Arg Ile Val Ser Arg
Ile Phe Gln Cys Cys Ala Trp Asn Gly Gly 65 70
75 80 Val Phe Trp Phe Ser Leu Leu Leu Phe Tyr Arg
Val Phe Ile Pro Val 85 90
95 Leu Gln Ser Val Thr Ala Arg Ile Ile Gly Asp Pro Ser Leu His Gly
100 105 110 Asp Val
Trp Ser Trp Leu Glu Phe Phe Leu Thr Ser Ile Phe Ser Ala 115
120 125 Leu Trp Val Leu Pro Leu Phe
Val Leu Ser Lys Val Val Asn Ala Ile 130 135
140 Trp Phe Gln Asp Ile Ala Asp Leu Ala Phe Glu Val
Ser Gly Arg Lys 145 150 155
160 Pro His Pro Phe Pro Ser Val Ser Lys Ile Ile Ala Asp Met Leu Phe
165 170 175 Asn Leu Leu
Leu Gln Ala Leu Phe Leu Ile Gln Gly Met Phe Val Ser 180
185 190 Leu Phe Pro Ile His Leu Val Gly
Gln Leu Val Ser Leu Leu His Met 195 200
205 Ser Leu Leu Tyr Ser Leu Tyr Cys Phe Glu Tyr Arg Trp
Phe Asn Lys 210 215 220
Gly Ile Glu Met His Gln Arg Leu Ser Asn Ile Glu Arg Asn Trp Pro 225
230 235 240 Tyr Tyr Phe Gly
Phe Gly Leu Pro Leu Ala Phe Leu Thr Ala Met Gln 245
250 255 Ser Ser Tyr Ile Ile Ser Gly Cys Leu
Phe Ser Ile Leu Phe Pro Leu 260 265
270 Phe Ile Ile Ser Ala Asn Glu Ala Lys Thr Pro Gly Lys Ala
Tyr Leu 275 280 285
Phe Gln Leu Arg Leu Phe Ser Leu Val Val Phe Leu Ser Asn Arg Leu 290
295 300 Phe His Lys Thr Val
Tyr Leu Gln Ser Ala Leu Ser Ser Ser Thr Ser 305 310
315 320 Ala Glu Lys Phe Pro Ser Pro His Pro Ser
Pro Ala Lys Leu Lys Ala 325 330
335 Thr Ala Gly His 340 141228PRTHomo Sapiens
141Met Ala Asp Ser Val Lys Thr Phe Leu Gln Asp Leu Ala Arg Gly Ile 1
5 10 15 Lys Asp Ser Ile
Trp Gly Ile Cys Thr Ile Ser Lys Leu Asp Ala Arg 20
25 30 Ile Gln Gln Lys Arg Glu Glu Gln Arg
Arg Arg Arg Ala Ser Ser Val 35 40
45 Leu Ala Gln Arg Arg Ala Gln Ser Ile Glu Arg Lys Gln Glu
Ser Glu 50 55 60
Pro Arg Ile Val Ser Arg Ile Phe Gln Cys Cys Ala Trp Asn Gly Gly 65
70 75 80 Val Phe Trp Phe Ser
Leu Leu Leu Phe Tyr Arg Val Phe Ile Pro Val 85
90 95 Leu Gln Ser Val Thr Ala Arg Ile Ile Gly
Asp Pro Ser Leu His Gly 100 105
110 Asp Val Trp Ser Trp Leu Glu Phe Phe Leu Thr Ser Ile Phe Ser
Ala 115 120 125 Leu
Trp Val Leu Pro Leu Phe Val Leu Ser Lys Val Val Asn Ala Ile 130
135 140 Trp Phe Gln Asp Ile Ala
Asp Leu Ala Phe Glu Val Ser Gly Arg Lys 145 150
155 160 Pro His Pro Phe Pro Ser Val Ser Lys Ile Ile
Ala Asp Met Leu Phe 165 170
175 Asn Leu Leu Leu Gln Ala Leu Phe Leu Ile Gln Gly Met Phe Val Ser
180 185 190 Leu Phe
Pro Ile His Leu Val Gly Gln Leu Val Ser Leu Leu His Met 195
200 205 Ser Leu Leu Tyr Ser Leu Tyr
Cys Phe Glu Tyr Arg Trp Phe Asn Lys 210 215
220 Gly Lys Ser Ile 225 142342PRTHomo
Sapiens 142Met Ala Asp Ser Val Lys Thr Phe Leu Gln Asp Leu Ala Arg Gly
Ile 1 5 10 15 Lys
Asp Ser Ile Trp Gly Ile Cys Thr Ile Ser Lys Leu Asp Ala Arg
20 25 30 Ile Gln Gln Lys Arg
Glu Glu Gln Arg Arg Arg Arg Ala Ser Ser Val 35
40 45 Leu Ala Gln Arg Arg Ala Gln Ser Ile
Glu Arg Lys Gln Glu Arg Arg 50 55
60 Ile Leu Ala Leu Ser Pro Ser Cys His Leu Arg Leu Pro
Trp Cys Asn 65 70 75
80 Leu Ser Leu Leu Gln Pro Leu Pro Pro Arg Ser Lys Gln Phe Phe Cys
85 90 95 Leu Ser Glu Pro
Ala Gly Trp Lys Tyr Ser Glu Pro Arg Ile Val Ser 100
105 110 Arg Ile Phe Gln Cys Cys Ala Trp Asn
Gly Gly Val Phe Trp Phe Ser 115 120
125 Leu Leu Leu Phe Tyr Arg Val Phe Ile Pro Val Leu Gln Ser
Val Thr 130 135 140
Ala Arg Ile Ile Gly Asp Pro Ser Leu His Gly Asp Val Trp Ser Trp 145
150 155 160 Leu Glu Phe Phe Leu
Thr Ser Ile Phe Ser Ala Leu Trp Val Leu Pro 165
170 175 Leu Phe Val Leu Ser Lys Val Val Asn Ala
Ile Trp Phe Gln Asp Ile 180 185
190 Ala Asp Leu Ala Phe Glu Val Ser Gly Arg Lys Pro His Pro Phe
Pro 195 200 205 Ser
Val Ser Lys Ile Ile Ala Asp Met Leu Phe Asn Leu Leu Leu Gln 210
215 220 Ala Leu Phe Leu Ile Gln
Gly Met Phe Val Ser Leu Phe Pro Ile His 225 230
235 240 Leu Val Gly Gln Leu Val Ser Leu Leu His Met
Ser Leu Leu Tyr Ser 245 250
255 Leu Tyr Cys Phe Glu Tyr Arg Trp Phe Asn Lys Gly Ile Glu Met His
260 265 270 Gln Arg
Leu Ser Asn Ile Glu Arg Asn Trp Pro Tyr Tyr Phe Gly Phe 275
280 285 Gly Leu Pro Leu Ala Phe Leu
Thr Ala Met Gln Ser Ser Tyr Ile Ile 290 295
300 Ser Gly Cys Leu Phe Ser Ile Leu Phe Pro Leu Phe
Ile Ile Ser Ala 305 310 315
320 Asn Glu Ala Lys Thr Leu Ala Lys His Ile Ser Ser Ser Cys Ala Ser
325 330 335 Ser Pro Trp
Trp Ser Ser 340 143152PRTHomo Sapiens 143Met Ala Asp
Ser Val Lys Thr Phe Leu Gln Asp Leu Ala Arg Gly Ile 1 5
10 15 Lys Asp Ser Ile Trp Gly Ile Cys
Thr Ile Ser Lys Leu Asp Ala Arg 20 25
30 Ile Gln Gln Lys Arg Glu Glu Gln Arg Arg Arg Arg Ala
Ser Ser Val 35 40 45
Leu Ala Gln Arg Arg Ala Gln Ser Ile Glu Arg Lys Gln Glu Arg Arg 50
55 60 Ile Leu Ala Leu
Ser Pro Ser Cys His Leu Arg Leu Pro Trp Cys Asn 65 70
75 80 Leu Ser Leu Leu Gln Pro Leu Pro Pro
Arg Ser Lys Gln Phe Phe Cys 85 90
95 Leu Ser Glu Pro Ala Gly Trp Lys Tyr Arg Cys Ala Pro Pro
Arg Leu 100 105 110
Ala Asn Phe Leu Tyr Ser Leu Val Glu Thr Gly Phe Cys His Val Gly
115 120 125 Gln Ala Gly Leu
Glu Leu Leu Thr Ser Val Asp Arg Leu Pro Arg Pro 130
135 140 Pro Lys Val Leu Gly Leu Gln Pro
145 150 144163PRTHomo Sapiens 144Met Ala Asp Ser
Val Lys Thr Phe Leu Gln Asp Leu Ala Arg Gly Ile 1 5
10 15 Lys Asp Ser Ile Trp Gly Ile Cys Thr
Ile Ser Lys Leu Asp Ala Arg 20 25
30 Ile Gln Gln Lys Arg Glu Glu Gln Arg Arg Arg Arg Ala Ser
Ser Val 35 40 45
Leu Ala Gln Arg Arg Ala Gln Ser Ile Glu Arg Lys Gln Glu Ser Glu 50
55 60 Pro Arg Ile Val Ser
Arg Ile Phe Gln Cys Cys Ala Trp Asn Gly Gly 65 70
75 80 Val Phe Trp Phe Ser Leu Leu Leu Phe Tyr
Arg Val Phe Ile Pro Val 85 90
95 Leu Gln Ser Val Thr Ala Arg Ile Ile Gly Lys Cys Ile Pro Cys
Ser 100 105 110 Leu
Ser Val Gly Asp Arg Val Gly Asp Asp Val Ser Val Ser Leu Ser 115
120 125 Leu Leu Asn Ile Ser Cys
Val Pro Gly Ala Phe Thr Val Tyr Phe Leu 130 135
140 Phe Cys Cys Phe Ile Leu Phe Lys Asn Leu Tyr
Phe Val Ile Leu Leu 145 150 155
160 Glu Ala Leu 145342PRTHomo Sapiens 145Met Arg Lys Glu Thr Pro
Pro Pro Leu Val Pro Pro Ala Ala Arg Glu 1 5
10 15 Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys Met
Glu Arg Gln Leu Glu 20 25
30 Ala Ala Arg Tyr Arg Ser Asp Gly Ala Leu Leu Leu Gly Ala Ser
Ser 35 40 45 Leu
Ser Gly Arg Cys Trp Ala Gly Ser Leu Trp Leu Phe Lys Asp Pro 50
55 60 Cys Ala Ala Pro Asn Glu
Gly Phe Cys Ser Ala Gly Val Gln Thr Glu 65 70
75 80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Glu
Arg Gly Ile Leu Val 85 90
95 Ala Ser Asp Ser Gly Ala Val Glu Leu Trp Glu Leu Asp Glu Asn Glu
100 105 110 Thr Leu
Ile Val Ser Lys Phe Cys Lys Tyr Glu His Asp Asp Ile Val 115
120 125 Ser Thr Val Ser Val Leu Ser
Ser Gly Thr Gln Ala Val Ser Gly Ser 130 135
140 Lys Asp Ile Cys Ile Lys Val Trp Asp Leu Ala Gln
Gln Val Val Leu 145 150 155
160 Ser Ser Tyr Arg Ala His Ala Ala Gln Val Thr Cys Val Ala Ala Ser
165 170 175 Pro His Lys
Asp Ser Val Phe Leu Ser Cys Ser Glu Asp Asn Arg Ile 180
185 190 Leu Leu Trp Asp Thr Arg Cys Pro
Lys Pro Ala Ser Gln Ile Gly Cys 195 200
205 Ser Ala Pro Gly Tyr Leu Pro Thr Ser Leu Ala Trp His
Pro Gln Gln 210 215 220
Ser Glu Val Phe Val Phe Gly Asp Glu Asn Gly Thr Val Ser Leu Val 225
230 235 240 Asp Thr Lys Ser
Thr Ser Cys Val Leu Ser Ser Ala Val His Ser Gln 245
250 255 Cys Val Thr Gly Leu Val Phe Ser Pro
His Ser Val Pro Phe Leu Ala 260 265
270 Ser Leu Ser Glu Asp Cys Ser Leu Ala Val Leu Asp Ser Ser
Leu Ser 275 280 285
Glu Leu Phe Arg Ser Gln Ala His Arg Asp Phe Val Arg Asp Ala Thr 290
295 300 Trp Ser Pro Leu Asn
His Ser Leu Leu Thr Thr Val Gly Trp Asp His 305 310
315 320 Gln Val Val His His Val Val Pro Thr Glu
Pro Leu Pro Ala Pro Gly 325 330
335 Pro Ala Ser Val Thr Glu 340
146290PRTHomo Sapiens 146Met Arg Lys Glu Thr Pro Pro Pro Leu Val Pro Pro
Ala Ala Arg Glu 1 5 10
15 Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys Met Glu Arg Gln Leu Glu
20 25 30 Ala Ala Arg
Tyr Arg Ser Asp Gly Ala Leu Leu Leu Gly Ala Ser Ser 35
40 45 Leu Ser Gly Arg Cys Trp Ala Gly
Ser Leu Trp Leu Phe Lys Asp Pro 50 55
60 Cys Ala Ala Pro Asn Glu Gly Phe Cys Ser Ala Gly Val
Gln Thr Glu 65 70 75
80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Glu Arg Gly Ile Leu Val
85 90 95 Ala Ser Asp Ser
Gly Ala Val Glu Leu Trp Glu Leu Asp Glu Asn Glu 100
105 110 Thr Leu Ile Val Ser Lys Phe Cys Lys
Tyr Glu His Asp Asp Ile Val 115 120
125 Ser Thr Val Ser Val Leu Ser Ser Gly Thr Gln Ala Val Ser
Gly Ser 130 135 140
Lys Asp Ile Cys Ile Lys Val Trp Asp Leu Ala Gln Gln Val Val Leu 145
150 155 160 Ser Ser Tyr Arg Ala
His Ala Ala Gln Val Thr Cys Val Ala Ala Ser 165
170 175 Pro His Lys Asp Ser Val Phe Leu Ser Cys
Ser Glu Asp Asn Arg Ile 180 185
190 Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro Ala Ser Gln Ile Gly
Cys 195 200 205 Ser
Ala Pro Gly Tyr Leu Pro Thr Ser Leu Ala Trp His Pro Gln Gln 210
215 220 Ser Glu Val Phe Val Phe
Gly Asp Glu Asn Gly Thr Val Ser Leu Val 225 230
235 240 Asp Thr Lys Ser Thr Ser Cys Val Leu Ser Ser
Ala Val His Ser Gln 245 250
255 Cys Val Thr Gly Leu Val Phe Ser Pro His Ser Val Pro Phe Leu Ala
260 265 270 Ser Leu
Ser Glu Asp Cys Ser Leu Ala Val Leu Asp Ser Ser Leu Ser 275
280 285 Glu Leu 290
147302PRTHomo Sapiens 147Met Arg Lys Glu Thr Pro Pro Pro Leu Val Pro Pro
Ala Ala Arg Glu 1 5 10
15 Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys Met Glu Arg Gln Leu Glu
20 25 30 Ala Ala Arg
Tyr Arg Ser Asp Gly Ala Leu Leu Leu Gly Ala Ser Ser 35
40 45 Leu Ser Gly Arg Cys Trp Ala Gly
Ser Leu Trp Leu Phe Lys Asp Pro 50 55
60 Cys Ala Ala Pro Asn Glu Gly Phe Cys Ser Ala Gly Val
Gln Thr Glu 65 70 75
80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Glu Arg Gly Ile Leu Val
85 90 95 Ala Ser Asp Ser
Gly Ala Val Glu Leu Trp Glu Leu Asp Glu Asn Glu 100
105 110 Thr Leu Ile Val Ser Lys Phe Cys Lys
Tyr Glu His Asp Asp Ile Val 115 120
125 Ser Thr Val Ser Val Leu Ser Ser Gly Thr Gln Ala Val Ser
Gly Ser 130 135 140
Lys Asp Ile Cys Ile Lys Val Trp Asp Leu Ala Gln Gln Val Val Leu 145
150 155 160 Ser Ser Tyr Arg Ala
His Ala Ala Gln Val Thr Cys Val Ala Ala Ser 165
170 175 Pro His Lys Asp Ser Val Phe Leu Ser Cys
Ser Glu Asp Asn Arg Ile 180 185
190 Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro Ala Ser Gln Ile Gly
Cys 195 200 205 Ser
Ala Pro Gly Tyr Leu Pro Thr Ser Leu Ala Trp His Pro Gln Gln 210
215 220 Ser Glu Val Phe Val Phe
Gly Asp Glu Asn Gly Thr Val Ser Leu Val 225 230
235 240 Asp Thr Lys Ser Thr Ser Cys Val Leu Ser Ser
Ala Val His Ser Gln 245 250
255 Cys Val Thr Gly Leu Val Phe Ser Pro His Ser Val Pro Phe Leu Ala
260 265 270 Ser Leu
Ser Glu Asp Cys Ser Leu Ala Val Leu Asp Ser Ser Leu Ser 275
280 285 Glu Phe Ile Ser Ser Ser Met
Lys Ile Glu Asp Trp Ile Gly 290 295
300 148210PRTHomo Sapiens 148Met Arg Lys Glu Thr Pro Pro Pro Leu
Val Pro Pro Ala Ala Arg Glu 1 5 10
15 Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys Met Glu Arg Gln
Leu Glu 20 25 30
Ala Ala Arg Tyr Arg Ser Asp Gly Ala Leu Leu Leu Gly Ala Ser Ser
35 40 45 Leu Ser Gly Arg
Cys Trp Ala Gly Ser Leu Trp Leu Phe Lys Asp Pro 50
55 60 Cys Ala Ala Pro Asn Glu Gly Phe
Cys Ser Ala Gly Val Gln Thr Glu 65 70
75 80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Glu Arg
Gly Ile Leu Val 85 90
95 Ala Ser Asp Ser Gly Ala Val Glu Leu Trp Glu Leu Asp Glu Asn Glu
100 105 110 Thr Leu Ile
Val Ser Lys Phe Cys Lys Tyr Glu His Asp Asp Ile Val 115
120 125 Ser Thr Val Ser Val Leu Ser Ser
Gly Thr Gln Ala Val Ser Gly Ser 130 135
140 Lys Asp Ile Cys Ile Lys Val Trp Asp Leu Ala Gln Gln
Val Val Leu 145 150 155
160 Ser Ser Tyr Arg Ala His Ala Ala Gln Val Thr Cys Val Ala Ala Ser
165 170 175 Pro His Lys Asp
Ser Val Phe Leu Ser Cys Ser Glu Asp Asn Arg Ile 180
185 190 Leu Leu Trp Asp Thr Arg Cys Pro Lys
Pro Ala Ser Gln Ile Val Arg 195 200
205 Leu Cys 210 149179PRTHomo Sapiens 149Met Arg Lys
Glu Thr Pro Pro Pro Leu Val Pro Pro Ala Ala Arg Glu 1 5
10 15 Trp Asn Leu Pro Pro Asn Ala Pro
Ala Cys Met Glu Arg Gln Leu Glu 20 25
30 Ala Ala Arg Tyr Arg Ser Asp Gly Ala Leu Leu Leu Gly
Ala Ser Ser 35 40 45
Leu Ser Gly Arg Cys Trp Ala Gly Ser Leu Trp Leu Phe Lys Asp Pro 50
55 60 Cys Ala Ala Pro
Asn Glu Gly Phe Cys Ser Ala Gly Val Gln Thr Glu 65 70
75 80 Ala Gly Val Ala Asp Leu Thr Trp Val
Gly Glu Arg Gly Ile Leu Val 85 90
95 Ala Ser Asp Ser Gly Ala Val Glu Leu Trp Glu Leu Asp Glu
Asn Glu 100 105 110
Thr Leu Ile Val Ser Lys Phe Cys Lys Tyr Glu His Asp Asp Ile Val
115 120 125 Ser Thr Val Ser
Val Leu Ser Ser Gly Thr Gln Ala Val Ser Gly Ser 130
135 140 Lys Asp Ile Trp Trp Val Pro Val
Leu Ile Ala Pro Val Ser Lys Pro 145 150
155 160 Pro Val Gly Ala Phe Pro Ile Leu Leu Thr Ser Leu
Gly Asn Ile Leu 165 170
175 Gly Leu Phe 150123PRTHomo Sapiens 150Met Arg Lys Glu Thr Pro Pro
Pro Leu Val Pro Pro Ala Ala Arg Glu 1 5
10 15 Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys Met
Glu Arg Gln Leu Glu 20 25
30 Ala Ala Arg Tyr Arg Ser Asp Gly Ala Leu Leu Leu Gly Ala Ser
Ser 35 40 45 Leu
Ser Gly Arg Cys Trp Ala Gly Ser Leu Trp Leu Phe Lys Asp Pro 50
55 60 Cys Ala Ala Pro Asn Glu
Gly Phe Cys Ser Ala Gly Val Gln Thr Glu 65 70
75 80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Glu
Arg Gly Ile Leu Val 85 90
95 Ala Ser Asp Ser Gly Glu Ser Leu Ser His Tyr Pro Pro Pro Pro Pro
100 105 110 Gly Gly
Thr Val Glu Trp Arg Leu Gly Val Pro 115 120
151303PRTHomo Sapiens 151Met Arg Lys Glu Thr Pro Pro Pro Leu Val
Pro Pro Ala Ala Arg Glu 1 5 10
15 Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys Met Glu Arg Gln Leu
Glu 20 25 30 Ala
Ala Arg Tyr Arg Ser Asp Gly Ala Leu Leu Leu Gly Ala Ser Ser 35
40 45 Leu Ser Gly Arg Cys Trp
Ala Gly Ser Leu Trp Leu Phe Lys Asp Pro 50 55
60 Cys Ala Ala Pro Asn Glu Gly Phe Cys Ser Ala
Gly Val Gln Thr Glu 65 70 75
80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Glu Arg Gly Ile Leu Val
85 90 95 Ala Ser
Asp Ser Gly Ala Val Glu Leu Trp Glu Leu Asp Glu Asn Glu 100
105 110 Thr Leu Ile Val Ser Lys Phe
Cys Lys Tyr Glu His Asp Asp Ile Val 115 120
125 Ser Thr Val Ser Val Leu Ser Ser Gly Thr Gln Ala
Val Ser Gly Ser 130 135 140
Lys Asp Ile Cys Ile Lys Val Trp Asp Leu Ala Gln Gln Val Val Leu 145
150 155 160 Ser Ser Tyr
Arg Ala His Ala Ala Gln Val Thr Cys Val Ala Ala Ser 165
170 175 Pro His Lys Asp Ser Val Phe Leu
Ser Cys Ser Glu Asp Asn Arg Ile 180 185
190 Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro Ala Ser Gln
Ile Gly Cys 195 200 205
Ser Ala Pro Gly Tyr Leu Pro Thr Ser Leu Ala Trp His Pro Gln Gln 210
215 220 Ser Glu Val Phe
Val Phe Gly Asp Glu Asn Gly Thr Val Ser Leu Val 225 230
235 240 Asp Thr Lys Ser Thr Ser Cys Val Leu
Ser Ser Ala Val His Ser Gln 245 250
255 Cys Val Thr Gly Leu Val Phe Ser Pro His Ser Val Pro Phe
Leu Ala 260 265 270
Ser Leu Ser Glu Asp Cys Ser Leu Ala Val Leu Asp Ser Ser Leu Ser
275 280 285 Glu Leu Ala Gly
Ser Cys Ala Glu Thr Pro Arg Trp Cys Cys Pro 290 295
300 15272PRTHomo Sapiens 152Met Arg Lys Glu Thr
Pro Pro Pro Leu Val Pro Pro Ala Ala Arg Glu 1 5
10 15 Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys
Met Glu Arg Gln Leu Glu 20 25
30 Ala Ala Arg Tyr Arg Ser Gly Glu Pro Arg Ser Arg Ala Trp Glu
Leu 35 40 45 Pro
Tyr Pro Gly Pro Gly Arg Pro Ser Pro Glu Thr Asp Pro Pro Ser 50
55 60 Pro Ser Pro Pro Cys Met
Leu Ser 65 70 15337PRTHomo Sapiens 153Met Arg
Lys Glu Thr Pro Pro Pro Leu Val Pro Pro Ala Ala Arg Glu 1 5
10 15 Trp Asn Leu Pro Pro Asn Ala
Pro Ala Cys Met Glu Arg Arg Phe Ser 20 25
30 Ser Gly Pro Pro Ala 35
154308PRTHomo Sapiens 154Met Pro Gly Gln Glu Leu Arg Thr Leu Asn Gly Ser
Gln Met Leu Leu 1 5 10
15 Val Leu Leu Val Leu Ser Trp Leu Pro His Gly Gly Ala Leu Ser Leu
20 25 30 Ala Glu Ala
Ser Arg Ala Ser Phe Pro Gly Pro Ser Glu Leu His Thr 35
40 45 Glu Asp Ser Arg Phe Arg Glu Leu
Arg Lys Arg Tyr Glu Asp Leu Leu 50 55
60 Thr Arg Leu Arg Ala Asn Gln Ser Trp Glu Asp Ser Asn
Thr Asp Leu 65 70 75
80 Val Pro Ala Pro Ala Val Arg Ile Leu Thr Pro Glu Val Arg Leu Gly
85 90 95 Ser Gly Gly His
Leu His Leu Arg Ile Ser Arg Ala Ala Leu Pro Glu 100
105 110 Gly Leu Pro Glu Ala Ser Arg Leu His
Arg Ala Leu Phe Arg Leu Ser 115 120
125 Pro Thr Ala Ser Arg Ser Trp Asp Val Thr Arg Pro Leu Arg
Arg Gln 130 135 140
Leu Ser Leu Ala Arg Pro Gln Ala Pro Ala Leu His Leu Arg Leu Ser 145
150 155 160 Pro Pro Pro Ser Gln
Ser Asp Gln Leu Leu Ala Glu Ser Ser Ser Ala 165
170 175 Arg Pro Gln Leu Glu Leu His Leu Arg Pro
Gln Ala Ala Arg Gly Arg 180 185
190 Arg Arg Ala Arg Ala Arg Asn Gly Asp His Cys Pro Leu Gly Pro
Gly 195 200 205 Arg
Cys Cys Arg Leu His Thr Val Arg Ala Ser Leu Glu Asp Leu Gly 210
215 220 Trp Ala Asp Trp Val Leu
Ser Pro Arg Glu Val Gln Val Thr Met Cys 225 230
235 240 Ile Gly Ala Cys Pro Ser Gln Phe Arg Ala Ala
Asn Met His Ala Gln 245 250
255 Ile Lys Thr Ser Leu His Arg Leu Lys Pro Asp Thr Val Pro Ala Pro
260 265 270 Cys Cys
Val Pro Ala Ser Tyr Asn Pro Met Val Leu Ile Gln Lys Thr 275
280 285 Asp Thr Gly Val Ser Leu Gln
Thr Tyr Asp Asp Leu Leu Ala Lys Asp 290 295
300 Cys His Cys Ile 305 155331PRTHomo
Sapiens 155Met Thr Pro Gly Pro Arg Ser Cys Arg Asn Ala Thr Arg Thr Phe
Arg 1 5 10 15 Ala
Pro Val Arg Gln Gly Glu Pro Gly Gly Ala Gly Pro Gln Pro His
20 25 30 Pro Lys Ala Gln Met
Leu Leu Val Leu Leu Val Leu Ser Trp Leu Pro 35
40 45 His Gly Gly Ala Leu Ser Leu Ala Glu
Ala Ser Arg Ala Ser Phe Pro 50 55
60 Gly Pro Ser Glu Leu His Ser Glu Asp Ser Arg Phe Arg
Glu Leu Arg 65 70 75
80 Lys Arg Tyr Glu Asp Leu Leu Thr Arg Leu Arg Ala Asn Gln Ser Trp
85 90 95 Glu Asp Ser Asn
Thr Asp Leu Val Pro Ala Pro Ala Val Arg Ile Leu 100
105 110 Thr Pro Glu Val Arg Leu Gly Ser Gly
Gly His Leu His Leu Arg Ile 115 120
125 Ser Arg Ala Ala Leu Pro Glu Gly Leu Pro Glu Ala Ser Arg
Leu His 130 135 140
Arg Ala Leu Phe Arg Leu Ser Pro Thr Ala Ser Arg Ser Trp Asp Val 145
150 155 160 Thr Arg Pro Leu Arg
Arg Gln Leu Ser Leu Ala Arg Pro Gln Ala Pro 165
170 175 Ala Leu His Leu Arg Leu Ser Pro Pro Pro
Ser Gln Ser Asp Gln Leu 180 185
190 Leu Ala Glu Ser Ser Ser Ala Arg Pro Gln Leu Glu Leu His Leu
Arg 195 200 205 Pro
Gln Ala Ala Arg Gly Arg Arg Arg Ala Arg Ala Arg Asn Gly Asp 210
215 220 His Cys Pro Leu Gly Pro
Gly Arg Cys Cys Arg Leu His Thr Val Arg 225 230
235 240 Ala Ser Leu Glu Asp Leu Gly Trp Ala Asp Trp
Val Leu Ser Pro Arg 245 250
255 Glu Val Gln Val Thr Met Cys Ile Gly Ala Cys Pro Ser Gln Phe Arg
260 265 270 Ala Ala
Asn Met His Ala Gln Ile Lys Thr Ser Leu His Arg Leu Lys 275
280 285 Pro Asp Thr Val Pro Ala Pro
Cys Cys Val Pro Ala Ser Tyr Asn Pro 290 295
300 Met Val Leu Ile Gln Lys Thr Asp Thr Gly Val Ser
Leu Gln Thr Tyr 305 310 315
320 Asp Asp Leu Leu Ala Lys Asp Cys His Cys Ile 325
330 15694PRTHomo Sapiens 156Met Pro Gly Gln Glu Leu Arg
Thr Val Asn Gly Ser Gln Met Leu Leu 1 5
10 15 Val Leu Leu Val Leu Ser Trp Leu Pro His Gly
Gly Ala Leu Ser Leu 20 25
30 Ala Glu Ala Ser Arg Ala Ser Phe Pro Gly Pro Ser Glu Leu His
Ser 35 40 45 Glu
Asp Ser Arg Phe Arg Glu Leu Arg Lys Arg Tyr Glu Asp Leu Leu 50
55 60 Thr Arg Leu Arg Ala Asn
Gln Ser Trp Glu Asp Ser Asn Thr Asp Leu 65 70
75 80 Val Pro Ala Pro Ala Val Arg Ile Leu Thr Pro
Glu Gly Lys 85 90
157129PRTHomo Sapiens 157Met Ala Arg Gly Ser Leu Arg Arg Leu Leu Arg Leu
Leu Val Leu Gly 1 5 10
15 Leu Trp Leu Ala Leu Leu Arg Ser Val Ala Gly Glu Gln Ala Pro Gly
20 25 30 Thr Ala Pro
Cys Ser Arg Gly Ser Ser Trp Ser Ala Asp Leu Asp Lys 35
40 45 Cys Met Asp Cys Ala Ser Cys Arg
Ala Arg Pro His Ser Asp Phe Cys 50 55
60 Leu Gly Cys Ala Ala Ala Pro Pro Ala Pro Phe Arg Leu
Leu Trp Pro 65 70 75
80 Ile Leu Gly Gly Ala Leu Ser Leu Thr Phe Val Leu Gly Leu Leu Ser
85 90 95 Gly Phe Leu Val
Trp Arg Arg Cys Arg Arg Arg Glu Lys Phe Thr Thr 100
105 110 Pro Ile Glu Glu Thr Gly Gly Glu Gly
Cys Pro Ala Val Ala Leu Ile 115 120
125 Gln 158121PRTHomo Sapiens 158Met Ala Arg Gly Ser Leu
Arg Arg Leu Leu Arg Leu Leu Val Leu Gly 1 5
10 15 Leu Trp Leu Ala Leu Leu Arg Ser Val Ala Gly
Glu Gln Ala Pro Gly 20 25
30 Thr Arg Asp Ser Gly Val Gly Glu Pro Arg Ala Gly Ala Arg Glu
Pro 35 40 45 Asp
Trp Val Ser Gly Glu Gln Arg Arg Thr Gly Gly Thr Gly Gly Cys 50
55 60 Gly Asp Leu Gly Ser Gly
Gly Leu Gln Thr Ala Arg Ser Arg Leu Trp 65 70
75 80 Glu Val Pro Ser Leu Ser Lys Leu His Ser Gln
Ser Gly Pro Gln Phe 85 90
95 Leu Pro Pro Ser Asn Trp Gly Trp Gly Gly Ser Ser Val Pro Gln Val
100 105 110 Arg Ser
Thr Ser Asn Gly Glu Arg Lys 115 120
15994PRTHomo Sapiens 159Met Ala Arg Gly Ser Leu Arg Arg Leu Leu Arg Leu
Leu Val Leu Gly 1 5 10
15 Leu Trp Leu Ala Leu Leu Arg Ser Val Ala Gly Glu Gln Ala Pro Ala
20 25 30 Ser Asp Pro
Arg Pro Pro Pro Gln Ala Pro Pro Pro Ala Pro Ala Ala 35
40 45 Ala Pro Gly Ala Arg Thr Trp Thr
Ser Ala Trp Thr Ala Arg Leu Ala 50 55
60 Gly Arg Asp Arg Thr Ala Thr Ser Ala Trp Ala Ala Leu
Gln His Leu 65 70 75
80 Leu Pro Pro Ser Gly Cys Phe Gly Pro Ser Leu Gly Ala Leu
85 90 160250PRTHomo Sapiens 160Met
Ala Arg Gly Ser Leu Arg Arg Leu Leu Arg Leu Leu Val Leu Gly 1
5 10 15 Leu Trp Leu Ala Leu Leu
Arg Ser Val Ala Gly Glu Gln Ala Pro Gly 20
25 30 Thr Ala Pro Cys Ser Arg Gly Ser Ser Trp
Ser Ala Asp Leu Asp Lys 35 40
45 Cys Met Asp Cys Ala Ser Cys Arg Ala Arg Pro His Ser Asp
Phe Cys 50 55 60
Leu Gly Cys Glu Trp Gly Ala Gly Pro Val Ala Ser Gly Pro Gln Thr 65
70 75 80 Gly Arg Glu Gly Gly
Trp Cys Ala Glu Arg Gly Arg Glu Leu Cys Ile 85
90 95 Trp Glu Ile Ile Arg Glu Glu Val Gly Ala
Gly Arg Gly Leu Arg Ser 100 105
110 Gly Arg Arg Pro Arg Leu Gly Glu Gly Arg Arg Leu Ser Leu Arg
Gly 115 120 125 Arg
Gly Trp Pro Gly Glu Gly Arg Gly Leu Thr Pro Ser Pro Ala Pro 130
135 140 Arg Arg Cys Ser Thr Ser
Cys Pro Leu Pro Ala Ala Leu Ala His Pro 145 150
155 160 Trp Gly Arg Ser Glu Pro Asp Leu Arg Ala Gly
Ala Ala Phe Trp Leu 165 170
175 Phe Gly Leu Glu Thr Met Pro Gln Glu Arg Glu Val His His Pro His
180 185 190 Arg Gly
Asp Arg Arg Arg Gly Leu Pro Ser Cys Gly Ala Asp Pro Val 195
200 205 Thr Met Cys Pro Leu Pro Ala
Gly Ala Arg Pro Leu Ile Ile His Ser 210 215
220 Ser Ile Leu Glu Pro Val Ser Ala Ser Gln Thr Arg
Arg Glu Pro Ser 225 230 235
240 Ser Ser Asn His Lys Gly Gly Gly Gly Arg 245
250 161295PRTHomo Sapiens 161Met Ile Glu Val Leu Thr Thr Thr Asp
Ser Gln Lys Leu Leu His Gln 1 5 10
15 Leu Asn Ala Leu Leu Glu Gln Glu Ser Arg Cys Gln Pro Lys
Val Cys 20 25 30
Gly Leu Arg Leu Ile Glu Ser Ala His Asp Asn Gly Leu Arg Met Thr
35 40 45 Ala Arg Leu Arg
Asp Phe Glu Val Lys Asp Leu Leu Ser Leu Thr Gln 50
55 60 Phe Phe Gly Phe Asp Thr Glu Thr
Phe Ser Leu Ala Val Asn Leu Leu 65 70
75 80 Asp Arg Phe Leu Ser Lys Met Lys Val Gln Pro Lys
His Leu Gly Cys 85 90
95 Val Gly Leu Ser Cys Phe Tyr Leu Ala Val Lys Ser Ile Glu Glu Glu
100 105 110 Arg Asn Val
Pro Leu Ala Thr Asp Leu Ile Arg Ile Ser Gln Tyr Arg 115
120 125 Phe Thr Val Ser Asp Leu Met Arg
Met Glu Lys Ile Val Leu Glu Lys 130 135
140 Val Cys Trp Lys Val Lys Ala Thr Thr Ala Phe Gln Phe
Leu Gln Leu 145 150 155
160 Tyr Tyr Ser Leu Leu Gln Glu Asn Leu Pro Leu Glu Arg Arg Asn Ser
165 170 175 Ile Asn Phe Glu
Arg Leu Glu Ala Gln Leu Lys Ala Cys His Cys Arg 180
185 190 Ile Ile Phe Ser Lys Ala Lys Pro Ser
Val Leu Ala Leu Ser Ile Ile 195 200
205 Ala Leu Glu Ile Gln Ala Gln Lys Cys Val Glu Leu Thr Glu
Gly Ile 210 215 220
Glu Cys Leu Gln Lys His Ser Lys Ile Asn Gly Arg Asp Leu Thr Phe 225
230 235 240 Trp Gln Glu Leu Val
Ser Lys Cys Leu Thr Glu Tyr Ser Ser Asn Lys 245
250 255 Cys Ser Lys Pro Asn Val Gln Lys Leu Lys
Trp Ile Val Ser Gly Arg 260 265
270 Thr Ala Arg Gln Leu Lys His Ser Tyr Tyr Arg Ile Thr His Leu
Pro 275 280 285 Thr
Ile Pro Glu Met Val Pro 290 295 162114PRTHomo Sapiens
162Met Ile Glu Val Leu Thr Thr Thr Asp Ser Gln Lys Leu Leu His Gln 1
5 10 15 Leu Asn Ala Leu
Leu Glu Gln Glu Ser Arg Cys Gln Pro Lys Val Cys 20
25 30 Gly Leu Arg Leu Ile Glu Ser Ala His
Asp Asn Gly Leu Arg Met Thr 35 40
45 Ala Arg Leu Arg Asp Phe Glu Val Lys Asp Leu Leu Ser Leu
Thr Gln 50 55 60
Phe Phe Gly Phe Asp Thr Glu Thr Phe Ser Leu Ala Val Asn Leu Leu 65
70 75 80 Asp Arg Phe Leu Ser
Lys Met Lys Val Cys Leu Lys Leu His Phe Cys 85
90 95 Asn Phe Ala Gln Cys Val Leu Glu Met Glu
Leu Leu Pro Phe Gly Trp 100 105
110 Tyr Ser 163181PRTHomo Sapiens 163Met Ala Gly Ser Arg Glu
Val Val Ala Met Asp Cys Glu Met Val Gly 1 5
10 15 Leu Gly Pro His Arg Glu Ser Gly Leu Ala Arg
Cys Ser Leu Val Asn 20 25
30 Val His Gly Ala Val Leu Tyr Asp Lys Phe Ile Arg Pro Glu Gly
Glu 35 40 45 Ile
Thr Asp Tyr Arg Thr Arg Val Ser Gly Val Thr Pro Gln His Met 50
55 60 Val Gly Ala Thr Pro Phe
Ala Val Ala Arg Leu Glu Ile Leu Gln Leu 65 70
75 80 Leu Lys Gly Lys Leu Val Val Gly His Asp Leu
Lys His Asp Phe Gln 85 90
95 Ala Leu Lys Glu Asp Met Ser Gly Tyr Thr Ile Tyr Asp Thr Ser Thr
100 105 110 Asp Arg
Leu Leu Trp Arg Glu Ala Lys Leu Asp His Cys Arg Arg Val 115
120 125 Ser Leu Arg Val Leu Ser Glu
Arg Leu Leu His Lys Ser Ile Gln Asn 130 135
140 Ser Leu Leu Gly His Ser Ser Val Glu Asp Ala Arg
Ala Thr Met Glu 145 150 155
160 Leu Tyr Gln Ile Ser Gln Arg Ile Arg Ala Arg Arg Gly Leu Pro Arg
165 170 175 Leu Ala Val
Ser Asp 180 164125PRTHomo Sapiens 164Met Ser His Ser Arg
Gly Arg Gly Thr Gly Ile Phe Val His Gln Phe 1 5
10 15 Pro Ser Ala Thr Ser Cys Cys Cys Ser Cys
Ala Leu Ile Pro Gln His 20 25
30 Phe Trp Leu Val Gly Lys Ala Gly Arg Lys Arg His Thr Asp Met
Gly 35 40 45 Gly
Trp Glu Phe Thr Leu Trp Glu Gly Gln Arg Glu Arg Arg Gln Thr 50
55 60 Leu Arg Ala Arg Ala Val
His Arg Asp Pro Ser Gly Gln Gln Leu Phe 65 70
75 80 Ile Lys His Leu Leu Pro Ala Leu Gly Gln Ile
Leu Glu Thr Gln Gly 85 90
95 Glu Gln Asp Pro Ser Leu Ser Leu Ser Ser Trp Leu Val Gly Arg Trp
100 105 110 Pro Leu
Thr Arg Ser Ser Ala His Met Val Arg Ser Val 115
120 125 165203PRTHomo Sapiens 165Met Ala Lys Ala Tyr Asp
His Leu Phe Lys Leu Leu Leu Ile Gly Asp 1 5
10 15 Ser Gly Val Gly Lys Thr Cys Leu Ile Ile Arg
Phe Ala Glu Asp Asn 20 25
30 Phe Asn Asn Thr Tyr Ile Ser Thr Ile Gly Ile Asp Phe Lys Ile
Arg 35 40 45 Thr
Val Asp Ile Glu Gly Lys Lys Ile Lys Leu Gln Val Trp Asp Thr 50
55 60 Ala Gly Gln Glu Arg Phe
Lys Thr Ile Thr Thr Ala Tyr Tyr Arg Gly 65 70
75 80 Ala Met Gly Ile Ile Leu Val Tyr Asp Ile Thr
Asp Glu Lys Ser Phe 85 90
95 Glu Asn Ile Gln Asn Trp Met Lys Ser Ile Lys Glu Asn Ala Ser Ala
100 105 110 Gly Val
Glu Arg Leu Leu Leu Gly Asn Lys Cys Asp Met Glu Ala Lys 115
120 125 Arg Lys Val Gln Lys Glu Gln
Ala Asp Lys Leu Ala Arg Glu His Gly 130 135
140 Ile Arg Phe Phe Glu Thr Ser Ala Lys Ser Ser Met
Asn Val Asp Glu 145 150 155
160 Ala Phe Ser Ser Leu Ala Arg Asp Ile Leu Leu Lys Ser Gly Gly Arg
165 170 175 Arg Ser Gly
Asn Gly Asn Lys Pro Pro Ser Thr Asp Leu Lys Thr Cys 180
185 190 Asp Lys Lys Asn Thr Asn Lys Cys
Ser Leu Gly 195 200 166122PRTHomo
Sapiens 166Met Gly Ile Ile Leu Val Tyr Asp Ile Thr Asp Glu Lys Ser Phe
Glu 1 5 10 15 Asn
Ile Gln Asn Trp Met Lys Ser Ile Lys Glu Asn Ala Ser Ala Gly
20 25 30 Val Glu Arg Leu Leu
Leu Gly Asn Lys Cys Asp Met Glu Ala Lys Arg 35
40 45 Lys Val Gln Lys Glu Gln Ala Asp Lys
Leu Ala Arg Glu His Gly Ile 50 55
60 Arg Phe Phe Glu Thr Ser Ala Lys Ser Ser Met Asn Val
Asp Glu Ala 65 70 75
80 Phe Ser Ser Leu Ala Arg Asp Ile Leu Leu Lys Ser Gly Gly Arg Arg
85 90 95 Ser Gly Asn Gly
Asn Lys Pro Pro Ser Thr Asp Leu Lys Thr Cys Asp 100
105 110 Lys Lys Asn Thr Asn Lys Cys Ser Leu
Gly 115 120 167166PRTHomo Sapiens 167Met
Ala Lys Ala Tyr Asp His Leu Phe Lys Leu Leu Leu Ile Gly Asp 1
5 10 15 Ser Gly Val Gly Lys Thr
Cys Leu Ile Ile Arg Phe Ala Glu Asp Asn 20
25 30 Phe Asn Asn Thr Tyr Ile Ser Thr Ile Gly
Ile Asp Phe Lys Ile Arg 35 40
45 Thr Val Asp Ile Glu Gly Lys Lys Ile Lys Leu Gln Val Trp
Asp Thr 50 55 60
Ala Gly Gln Glu Arg Phe Lys Thr Ile Thr Thr Ala Tyr Tyr Arg Gly 65
70 75 80 Ala Met Gly Ile Ile
Leu Val Tyr Asp Ile Thr Asp Glu Lys Ser Phe 85
90 95 Glu Asn Ile Gln Asn Trp Met Lys Ser Ile
Lys Glu Asn Ala Ser Ala 100 105
110 Gly Val Glu Arg Leu Leu Leu Gly Asn Lys Cys Asp Met Glu Ala
Lys 115 120 125 Arg
Lys Val Gln Lys Glu Gln Ala Asp Lys Val Arg Ala Arg Leu Ser 130
135 140 Asn Val Leu Glu Leu Gly
Trp Glu Gly Gln Asp Arg Leu His Cys Arg 145 150
155 160 Gly Leu Gly Cys Cys Pro 165
16872PRTHomo Sapiens 168Met Ala Lys Ala Tyr Asp His Leu Phe Lys Leu
Leu Leu Ile Gly Asp 1 5 10
15 Ser Gly Val Gly Lys Thr Cys Leu Ile Ile Arg Phe Ala Glu Asp Asn
20 25 30 Phe Asn
Asn Thr Tyr Ile Ser Thr Ile Gly Glu Pro Ala Gly His Val 35
40 45 Pro Asp Pro Asp Ser Pro Val
Thr Ser Phe Ser Gly Ser Arg Ile Thr 50 55
60 Ser Asp Pro Thr Phe Gln Ser Pro 65
70 169184PRTHomo Sapiens 169Met Ala Lys Ala Tyr Asp His Leu
Phe Lys Leu Leu Leu Ile Gly Asp 1 5 10
15 Ser Gly Val Gly Lys Thr Cys Leu Ile Ile Arg Phe Ala
Glu Asp Asn 20 25 30
Phe Asn Asn Thr Tyr Ile Ser Thr Ile Gly Ile Asp Phe Lys Ile Arg
35 40 45 Thr Val Asp Ile
Glu Gly Lys Lys Ile Lys Leu Gln Val Trp Asp Thr 50
55 60 Ala Gly Gln Glu Arg Phe Lys Thr
Ile Thr Thr Ala Tyr Tyr Arg Gly 65 70
75 80 Ala Met Gly Ile Ile Leu Val Tyr Asp Ile Thr Asp
Glu Lys Ser Phe 85 90
95 Glu Asn Ile Gln Asn Trp Met Lys Ser Ile Lys Glu Asn Ala Ser Ala
100 105 110 Gly Val Glu
Arg Leu Leu Leu Gly Asn Lys Cys Asp Met Glu Ala Lys 115
120 125 Arg Lys Val Gln Lys Glu Gln Ala
Asp Lys Leu Ala Arg Glu His Gly 130 135
140 Ile Arg Phe Phe Glu Thr Ser Ala Lys Ser Ser Met Asn
Val Asp Glu 145 150 155
160 Phe Pro Gly Pro Gly His Leu Ala Gln Val Arg Arg Pro Glu Ile Arg
165 170 175 Lys Arg Gln Gln
Ala Ser Gln Tyr 180 170164PRTHomo Sapiens
170Met Ser Glu Pro Ala Gly Asp Val Arg Gln Asn Pro Cys Gly Ser Lys 1
5 10 15 Ala Cys Arg Arg
Leu Phe Gly Pro Val Asp Ser Glu Gln Leu Ser Arg 20
25 30 Asp Cys Asp Ala Leu Met Ala Gly Cys
Ile Gln Glu Ala Arg Glu Arg 35 40
45 Trp Asn Phe Asp Phe Val Thr Glu Thr Pro Leu Glu Gly Asp
Phe Ala 50 55 60
Trp Glu Arg Val Arg Gly Leu Gly Leu Pro Lys Leu Tyr Leu Pro Thr 65
70 75 80 Gly Pro Arg Arg Gly
Arg Asp Glu Leu Gly Gly Gly Arg Arg Pro Gly 85
90 95 Thr Ser Pro Ala Leu Leu Gln Gly Thr Ala
Glu Glu Asp His Val Asp 100 105
110 Leu Ser Leu Ser Cys Thr Leu Val Pro Arg Ser Gly Glu Gln Ala
Glu 115 120 125 Gly
Ser Pro Gly Gly Pro Gly Asp Ser Gln Gly Arg Lys Arg Arg Gln 130
135 140 Thr Ser Met Thr Asp Phe
Tyr His Ser Lys Arg Arg Leu Ile Phe Ser 145 150
155 160 Lys Arg Lys Pro 171163PRTHomo Sapiens
171Ser Glu Pro Ala Gly Asp Val Arg Gln Asn Pro Cys Gly Ser Lys Ala 1
5 10 15 Cys Arg Arg Leu
Phe Gly Pro Val Asp Ser Glu Gln Leu Ser Arg Asp 20
25 30 Cys Asp Ala Leu Met Ala Gly Cys Ile
Gln Glu Ala Arg Glu Arg Trp 35 40
45 Asn Phe Asp Phe Val Thr Glu Thr Pro Leu Glu Gly Asp Phe
Ala Trp 50 55 60
Glu Arg Val Arg Gly Leu Gly Leu Pro Lys Leu Tyr Leu Pro Thr Gly 65
70 75 80 Pro Arg Arg Gly Arg
Asp Glu Leu Gly Gly Gly Arg Arg Pro Gly Thr 85
90 95 Ser Pro Ala Leu Leu Gln Gly Thr Ala Glu
Glu Asp His Val Asp Leu 100 105
110 Ser Leu Ser Cys Thr Leu Val Pro Arg Ser Gly Glu Gln Ala Glu
Gly 115 120 125 Ser
Pro Gly Gly Pro Gly Asp Ser Gln Gly Arg Lys Arg Arg Gln Thr 130
135 140 Ser Met Thr Asp Phe Tyr
His Ser Lys Arg Arg Leu Ile Phe Ser Lys 145 150
155 160 Arg Lys Pro 172200PRTHomo Sapiens 172Met
Ser Glu Pro Ala Gly Asp Val Arg Gln Asn Pro Cys Gly Ser Lys 1
5 10 15 Ala Cys Arg Arg Leu Phe
Gly Pro Val Asp Ser Glu Gln Leu Ser Arg 20
25 30 Asp Cys Asp Ala Leu Met Ala Gly Cys Ile
Gln Glu Ala Arg Glu Arg 35 40
45 Trp Asn Phe Asp Phe Val Thr Glu Thr Pro Leu Glu Gly Asp
Phe Ala 50 55 60
Trp Glu Arg Val Arg Gly Leu Gly Leu Pro Lys Leu Tyr Leu Pro Thr 65
70 75 80 Gly Pro Arg Arg Gly
Arg Asp Glu Leu Gly Gly Gly Arg Arg Pro Gly 85
90 95 Thr Ser Pro Ala Leu Leu Gln Gly Thr Ala
Glu Glu Asp His Val Asp 100 105
110 Leu Ser Leu Ser Cys Thr Leu Val Pro Arg Ser Gly Glu Gln Ala
Glu 115 120 125 Gly
Ser Pro Gly Gly Pro Gly Asp Ser Gln Gly Arg Lys Arg Arg Gln 130
135 140 Thr Ser Met Thr Gly Ala
Asp Met Cys Thr Glu Gly Leu Cys Lys Gly 145 150
155 160 Pro Gly Phe Ser Glu Ser Met Val Gln Gly Leu
Thr Cys Leu Val Leu 165 170
175 Val Gln His Ala Pro Gly Arg Arg Lys Gln Ala Gln Arg Gly Glu Ala
180 185 190 Thr Ser
Leu Arg Ser His Ser Lys 195 200 173970PRTHomo
Sapiens 173Met Asp Ala Ala Glu Pro Gly Leu Pro Pro Gly Pro Glu Gly Arg
Lys 1 5 10 15 Arg
Tyr Ser Asp Ile Phe Arg Ser Leu Asp Asn Leu Glu Ile Ser Leu
20 25 30 Gly Asn Val Thr Leu
Glu Met Leu Ala Gly Asp Pro Leu Leu Ser Glu 35
40 45 Asp Pro Glu Pro Asp Lys Thr Pro Thr
Ala Thr Val Thr Asn Glu Ala 50 55
60 Ser Cys Trp Ser Gly Pro Ser Pro Glu Gly Pro Val Pro
Leu Thr Gly 65 70 75
80 Glu Glu Leu Asp Leu Arg Leu Ile Arg Thr Lys Gly Gly Val Asp Ala
85 90 95 Ala Leu Glu Tyr
Ala Lys Thr Trp Ser Arg Tyr Ala Lys Glu Leu Leu 100
105 110 Ala Trp Thr Glu Lys Arg Ala Ser Tyr
Glu Leu Glu Phe Ala Lys Ser 115 120
125 Thr Met Lys Ile Ala Glu Ala Gly Lys Val Ser Ile Gln Gln
Gln Ser 130 135 140
His Met Pro Leu Gln Tyr Ile Tyr Thr Leu Phe Leu Glu His Asp Leu 145
150 155 160 Ser Leu Gly Thr Leu
Ala Met Glu Thr Val Ala Gln Gln Lys Arg Asp 165
170 175 Tyr Tyr Gln Pro Leu Ala Ala Lys Arg Thr
Glu Ile Glu Lys Trp Arg 180 185
190 Lys Glu Phe Lys Glu Gln Trp Met Lys Glu Gln Lys Arg Met Asn
Glu 195 200 205 Ala
Val Gln Ala Leu Arg Arg Ala Gln Leu Gln Tyr Val Gln Arg Ser 210
215 220 Glu Asp Leu Arg Ala Arg
Ser Gln Gly Ser Pro Glu Asp Ser Ala Pro 225 230
235 240 Gln Ala Ser Pro Gly Pro Ser Lys Gln Gln Glu
Arg Arg Arg Arg Ser 245 250
255 Arg Glu Glu Ala Gln Ala Lys Ala Gln Glu Ala Glu Ala Leu Tyr Gln
260 265 270 Ala Cys
Val Arg Glu Ala Asn Ala Arg Gln Gln Asp Leu Glu Ile Ala 275
280 285 Lys Gln Arg Ile Val Ser His
Val Arg Lys Leu Val Phe Gln Gly Asp 290 295
300 Glu Val Leu Arg Arg Val Thr Leu Ser Leu Phe Gly
Leu Arg Gly Ala 305 310 315
320 Gln Ala Glu Arg Gly Pro Arg Ala Phe Ala Ala Leu Ala Glu Cys Cys
325 330 335 Ala Pro Phe
Glu Pro Gly Gln Arg Tyr Gln Glu Phe Val Arg Ala Leu 340
345 350 Arg Pro Glu Ala Pro Pro Pro Pro
Pro Pro Ala Phe Ser Phe Gln Glu 355 360
365 Phe Leu Pro Ser Leu Asn Ser Ser Pro Leu Asp Ile Arg
Lys Lys Leu 370 375 380
Ser Gly Pro Leu Pro Pro Arg Leu Asp Glu Asn Ser Ala Glu Pro Gly 385
390 395 400 Pro Trp Glu Asp
Pro Gly Thr Gly Trp Arg Trp Gln Gly Thr Pro Gly 405
410 415 Pro Thr Pro Gly Ser Asp Val Asp Ser
Val Gly Gly Gly Ser Glu Ser 420 425
430 Arg Ser Leu Asp Ser Pro Thr Ser Ser Pro Gly Ala Gly Thr
Arg Gln 435 440 445
Leu Val Lys Ala Ser Ser Thr Gly Thr Glu Ser Ser Asp Asp Phe Glu 450
455 460 Glu Arg Asp Pro Asp
Leu Gly Asp Gly Leu Glu Asn Gly Leu Gly Ser 465 470
475 480 Pro Phe Gly Lys Trp Thr Leu Ser Ser Ala
Ala Gln Thr His Gln Leu 485 490
495 Arg Arg Leu Arg Gly Pro Ala Lys Cys Arg Glu Cys Glu Ala Phe
Met 500 505 510 Val
Ser Gly Thr Glu Cys Glu Glu Cys Phe Leu Thr Cys His Lys Arg 515
520 525 Cys Leu Glu Thr Leu Leu
Ile Leu Cys Gly His Arg Arg Leu Pro Ala 530 535
540 Arg Thr Pro Leu Phe Gly Val Asp Phe Leu Gln
Leu Pro Arg Asp Phe 545 550 555
560 Pro Glu Glu Val Pro Phe Val Val Thr Lys Cys Thr Ala Glu Ile Glu
565 570 575 His Arg
Ala Leu Asp Val Gln Gly Ile Tyr Arg Val Ser Gly Ser Arg 580
585 590 Val Arg Val Glu Arg Leu Cys
Gln Ala Phe Glu Asn Gly Arg Ala Leu 595 600
605 Val Glu Leu Ser Gly Asn Ser Pro His Asp Val Ser
Ser Val Leu Lys 610 615 620
Arg Phe Leu Gln Glu Leu Thr Glu Pro Val Ile Pro Phe His Leu Tyr 625
630 635 640 Asp Ala Phe
Ile Ser Leu Ala Lys Thr Leu His Ala Asp Pro Gly Asp 645
650 655 Asp Pro Gly Thr Pro Ser Pro Ser
Pro Asp Val Ile Arg Ser Leu Lys 660 665
670 Thr Leu Leu Val Gln Leu Pro Asp Ser Asn Tyr Asn Thr
Leu Arg His 675 680 685
Leu Val Ala His Leu Phe Arg Val Ala Ala Arg Phe Met Glu Asn Lys 690
695 700 Met Ser Ala Asn
Asn Leu Gly Ile Val Phe Gly Pro Thr Leu Leu Arg 705 710
715 720 Pro Pro Asp Gly Pro Arg Ala Ala Ser
Ala Ile Pro Val Thr Cys Leu 725 730
735 Leu Asp Ser Gly His Gln Ala Gln Leu Val Glu Phe Leu Ile
Val His 740 745 750
Tyr Glu Gln Ile Phe Gly Met Asp Glu Leu Pro Gln Ala Thr Glu Pro
755 760 765 Pro Pro Gln Asp
Phe Ser Pro Ala Pro Gly Pro Leu Thr Thr Ser Ser 770
775 780 Gln Pro Pro Pro Pro His Leu Asp
Pro Asp Ser Gln Pro Pro Val Leu 785 790
795 800 Ala Ser Asp Pro Gly Pro Asp Pro Gln His His Ser
Thr Leu Glu Gln 805 810
815 His Pro Thr Ala Thr Pro Thr Glu Ile Pro Thr Pro Gln Ser Asp Gln
820 825 830 Arg Glu Asp
Val Ala Glu Asp Thr Lys Asp Gly Gly Gly Glu Val Ser 835
840 845 Ser Gln Gly Pro Glu Asp Ser Leu
Leu Gly Thr Gln Ser Arg Gly His 850 855
860 Phe Ser Arg Gln Pro Cys Lys Tyr Pro Arg Gly Gly Val
Arg Pro Val 865 870 875
880 Thr His Gln Leu Ser Ser Leu Ala Leu Val Ala Ser Lys Leu Cys Glu
885 890 895 Glu Thr Pro Ile
Thr Ser Val Pro Arg Gly Ser Leu Arg Gly Arg Gly 900
905 910 Pro Ser Pro Ala Ala Ala Ser Pro Glu
Gly Ser Pro Leu Arg Arg Thr 915 920
925 Pro Leu Pro Lys His Phe Glu Ile Thr Gln Glu Thr Ala Arg
Leu Leu 930 935 940
Ser Lys Leu Asp Ser Glu Ala Val Pro Arg Ala Thr Cys Cys Pro Asp 945
950 955 960 Val Gln Pro Glu Glu
Ala Glu Asp His Leu 965 970 174474PRTHomo
Sapiens 174Met Asp Ala Ala Glu Pro Gly Leu Pro Pro Gly Pro Glu Gly Arg
Lys 1 5 10 15 Arg
Tyr Ser Asp Ile Phe Arg Ser Leu Asp Asn Leu Glu Ile Ser Leu
20 25 30 Gly Asn Val Thr Leu
Glu Met Leu Ala Gly Asp Pro Leu Leu Ser Glu 35
40 45 Asp Pro Glu Pro Asp Lys Thr Pro Thr
Ala Thr Val Thr Asn Glu Ala 50 55
60 Ser Cys Trp Ser Gly Pro Ser Pro Glu Gly Pro Val Pro
Leu Thr Gly 65 70 75
80 Glu Glu Leu Asp Leu Arg Leu Ile Arg Thr Lys Gly Gly Val Asp Ala
85 90 95 Ala Leu Glu Tyr
Ala Lys Thr Trp Ser Arg Tyr Ala Lys Glu Leu Leu 100
105 110 Ala Trp Thr Glu Lys Arg Ala Ser Tyr
Glu Leu Glu Phe Ala Lys Ser 115 120
125 Thr Met Lys Ile Ala Glu Ala Gly Lys Val Ser Ile Gln Gln
Gln Ser 130 135 140
His Met Pro Leu Gln Tyr Ile Tyr Thr Leu Phe Leu Glu His Asp Leu 145
150 155 160 Ser Leu Gly Thr Leu
Ala Met Glu Thr Val Ala Gln Gln Lys Arg Asp 165
170 175 Tyr Tyr Gln Pro Leu Ala Ala Lys Arg Thr
Glu Ile Glu Lys Trp Arg 180 185
190 Lys Glu Phe Lys Glu Gln Trp Met Lys Glu Gln Lys Arg Met Asn
Glu 195 200 205 Ala
Val Gln Ala Leu Arg Arg Ala Gln Leu Gln Tyr Val Gln Arg Ser 210
215 220 Glu Asp Leu Arg Ala Arg
Ser Gln Gly Ser Pro Glu Asp Ser Ala Pro 225 230
235 240 Gln Ala Ser Pro Gly Pro Ser Lys Gln Gln Glu
Arg Arg Arg Arg Ser 245 250
255 Arg Glu Glu Ala Gln Ala Lys Ala Gln Glu Ala Glu Ala Leu Tyr Gln
260 265 270 Ala Cys
Val Arg Glu Ala Asn Ala Arg Gln Gln Asp Leu Glu Ile Ala 275
280 285 Lys Gln Arg Ile Val Ser His
Val Arg Lys Leu Val Phe Gln Gly Asp 290 295
300 Glu Val Leu Arg Arg Val Thr Leu Ser Leu Phe Gly
Leu Arg Gly Ala 305 310 315
320 Gln Ala Glu Arg Gly Pro Arg Ala Phe Ala Ala Leu Ala Glu Cys Cys
325 330 335 Ala Pro Phe
Glu Pro Gly Gln Arg Tyr Gln Glu Phe Val Arg Ala Leu 340
345 350 Arg Pro Glu Ala Pro Pro Pro Pro
Pro Pro Ala Phe Ser Phe Gln Glu 355 360
365 Phe Leu Pro Ser Leu Asn Ser Ser Pro Leu Asp Ile Arg
Lys Lys Leu 370 375 380
Ser Gly Pro Leu Pro Pro Arg Leu Asp Glu Asn Ser Ala Glu Pro Gly 385
390 395 400 Pro Trp Glu Asp
Pro Gly Thr Gly Trp Arg Trp Gln Gly Thr Pro Gly 405
410 415 Pro Thr Pro Gly Ser Asp Val Asp Ser
Val Gly Gly Gly Ser Glu Ser 420 425
430 Arg Ser Leu Asp Ser Pro Thr Ser Ser Pro Gly Ala Gly Thr
Arg Gln 435 440 445
Leu Val Lys Ala Ser Ser Thr Gly Thr Glu Ser Ser Asp Asp Phe Glu 450
455 460 Glu Arg Asp Pro Gly
Glu Ala Glu Ala Gly 465 470 17536PRTHomo
Sapiens 175Met Asp Ala Ala Glu Pro Gly Leu Pro Pro Gly Pro Glu Gly Arg
Lys 1 5 10 15 Arg
Tyr Ser Asp Ile Phe Arg Ser Leu Asp Asn Leu Glu Ile Ser Leu
20 25 30 Gly Asn Asp Pro
35 176694PRTHomo Sapiens 176Met Asp Ala Ala Glu Pro Gly Leu Pro
Pro Gly Pro Glu Gly Arg Lys 1 5 10
15 Arg Tyr Ser Asp Ile Phe Arg Ser Leu Asp Asn Leu Glu Ile
Ser Leu 20 25 30
Gly Asn Val Thr Leu Glu Met Leu Ala Gly Asp Pro Leu Leu Ser Glu
35 40 45 Asp Pro Glu Pro
Asp Lys Thr Pro Thr Ala Thr Val Thr Asn Glu Ala 50
55 60 Ser Cys Trp Ser Gly Pro Ser Pro
Glu Gly Pro Val Pro Leu Thr Gly 65 70
75 80 Glu Glu Leu Asp Leu Arg Leu Ile Arg Thr Lys Gly
Gly Val Asp Ala 85 90
95 Ala Leu Glu Tyr Ala Lys Thr Trp Ser Arg Tyr Ala Lys Glu Leu Leu
100 105 110 Ala Trp Thr
Glu Lys Arg Ala Ser Tyr Glu Leu Glu Phe Ala Lys Ser 115
120 125 Thr Met Lys Ile Ala Glu Ala Gly
Lys Val Ser Ile Gln Gln Gln Ser 130 135
140 His Met Pro Leu Gln Tyr Ile Tyr Thr Leu Phe Leu Glu
His Asp Leu 145 150 155
160 Ser Leu Gly Thr Leu Ala Met Glu Thr Val Ala Gln Gln Lys Arg Asp
165 170 175 Tyr Tyr Gln Pro
Leu Ala Ala Lys Arg Thr Glu Ile Glu Lys Trp Arg 180
185 190 Lys Glu Phe Lys Glu Gln Trp Met Lys
Glu Gln Lys Arg Met Asn Glu 195 200
205 Ala Val Gln Ala Leu Arg Arg Ala Gln Leu Gln Tyr Val Gln
Arg Ser 210 215 220
Glu Asp Leu Arg Ala Arg Ser Gln Gly Ser Pro Glu Asp Ser Ala Pro 225
230 235 240 Gln Ala Ser Pro Gly
Pro Ser Lys Gln Gln Glu Arg Arg Arg Arg Ser 245
250 255 Arg Glu Glu Ala Gln Ala Lys Ala Gln Glu
Ala Glu Ala Leu Tyr Gln 260 265
270 Ala Cys Val Arg Glu Ala Asn Ala Arg Gln Gln Asp Leu Glu Ile
Ala 275 280 285 Lys
Gln Arg Ile Val Ser His Val Arg Lys Leu Val Phe Gln Gly Asp 290
295 300 Glu Val Leu Arg Arg Val
Thr Leu Ser Leu Phe Gly Leu Arg Gly Ala 305 310
315 320 Gln Ala Glu Arg Gly Pro Arg Ala Phe Ala Ala
Leu Ala Glu Cys Cys 325 330
335 Ala Pro Phe Glu Pro Gly Gln Arg Tyr Gln Glu Phe Val Arg Ala Leu
340 345 350 Arg Pro
Glu Ala Pro Pro Pro Pro Pro Pro Ala Phe Ser Phe Gln Glu 355
360 365 Phe Leu Pro Ser Leu Asn Ser
Ser Pro Leu Asp Ile Arg Lys Lys Leu 370 375
380 Ser Gly Pro Leu Pro Pro Arg Leu Asp Glu Asn Ser
Ala Glu Pro Gly 385 390 395
400 Pro Trp Glu Asp Pro Gly Thr Gly Trp Arg Trp Gln Gly Thr Pro Gly
405 410 415 Pro Thr Pro
Gly Ser Asp Val Asp Ser Val Gly Gly Gly Ser Glu Ser 420
425 430 Arg Ser Leu Asp Ser Pro Thr Ser
Ser Pro Gly Ala Gly Thr Arg Gln 435 440
445 Leu Val Lys Ala Ser Ser Thr Gly Thr Glu Ser Ser Asp
Asp Phe Glu 450 455 460
Glu Arg Asp Pro Asp Leu Gly Asp Gly Leu Glu Asn Gly Leu Gly Ser 465
470 475 480 Pro Phe Gly Lys
Trp Thr Leu Ser Ser Ala Ala Gln Thr His Gln Leu 485
490 495 Arg Arg Leu Arg Gly Pro Ala Lys Cys
Arg Glu Cys Glu Ala Phe Met 500 505
510 Val Ser Gly Thr Glu Cys Glu Glu Cys Phe Leu Thr Cys His
Lys Arg 515 520 525
Cys Leu Glu Thr Leu Leu Ile Leu Cys Gly His Arg Arg Leu Pro Ala 530
535 540 Arg Thr Pro Leu Phe
Gly Val Asp Phe Leu Gln Leu Pro Arg Asp Phe 545 550
555 560 Pro Glu Glu Val Pro Phe Val Val Thr Lys
Cys Thr Ala Glu Ile Glu 565 570
575 His Arg Ala Leu Asp Val Gln Gly Ile Tyr Arg Val Ser Gly Ser
Arg 580 585 590 Val
Arg Val Glu Arg Leu Cys Gln Ala Phe Glu Asn Gly Arg Ala Leu 595
600 605 Val Glu Leu Ser Gly Asn
Ser Pro His Asp Val Ser Ser Val Leu Lys 610 615
620 Arg Phe Leu Gln Glu Gly Gly Cys Thr Ile Tyr
Gly Lys Gln Asp Val 625 630 635
640 Cys Gln Gln Pro Gly His Cys Val Trp Ala Asp Thr Ala Ala Ala Ala
645 650 655 Gly Arg
Pro Ala Gly Ser Gln Arg His Pro Cys His Leu Pro Ala Gly 660
665 670 Leu Trp Ala Ser Gly Pro Ala
Cys Gly Val Pro His Arg Ala Leu Arg 675 680
685 Ala Asp Leu Trp Asp Gly 690
1771977DNAMus Musculus 177ctgggattgg taacctggag ttaagcgggc tccctgccaa
cgcgagggct ttaaaagggg 60tgatgcaacg cgctcccagc cacagtctca ctcagcgaga
cgccgcgcac ggtgcttccc 120cagtggagcc aatcggctaa cccgcgctcc ggcagagtcc
ttggcgctcg cccgccggcg 180ggacagacca cccgcctctg gccgctctct ggaccctggc
cgccccgagc gaagactgga 240gcaaaatgat gcttcaacat ccaggccagg tctctgcctc
agaagtcagt gcgaccgcca 300ttgtcccctg cctctcacct cctgggtcac tggtatttga
ggattttgct aacctgacac 360cctttgtcaa ggaagagctg agattcgcca tccagaataa
acacctctgc catcggatgt 420cctctgcgct ggagtcagtt accgtcaaca acagacccct
ggagatgtca gtcaccaagt 480ctgaggcggc ccctgaagaa gatgagagga aaaggaggcg
gcgagaaaga aataaaattg 540ctgctgccaa gtgtcgaaac aagaaaaagg agaagacaga
gtgcctgcag aaagagtcag 600agaaactgga gagtgtgaat gctgagctga aggcccagat
tgaggagctg aagaatgaga 660aacagcattt gatatacatg ctcaacctgc accggcccac
ctgcatcgtc cgggctcaga 720atggacggac accggaagac gagaggaacc tctttatcca
acagataaaa gaaggaacat 780tgcagagcta agcagaggtg gcacggaggc aattggggag
ttcttactga atcctccttt 840tccaccccac accctgaagc cattggaaaa ctggcttcct
gtgcacttct agaatcccag 900cagccaagag ccgttggggc aggagggcct gtggtgacct
actgcattga cccactctgc 960ccccgagtga accgtggagc aggcaggagc atcctttgtc
tcaccaattc caggatttag 1020gccttatcat cccggccagt ctcagatgac ctagctggcc
ccaggctggg gtcctatgca 1080aagcaggatc ccactaatgg gattcaggca gaagtgtcta
ccttgatagg tggggtggga 1140ccacatcctc cactgtggct gacaacgccc ttccaaggga
atatggaatg agaacattca 1200ttattgaggt tgtccaatgg ccagggtatg ctttctagaa
aatatgctgt tctgtcccag 1260aatgactgtg catagggtat ccgtttcaga gcctggtgtt
gtgctattta gatgtttgtc 1320ttgcacaaca ttggcatgat ttttccggga gtttcatcag
atctgatttc tgagagtctg 1380gggatctgcc atggtggaaa gtgcccctca aaagcatttg
tgtggccaca tgaactggct 1440ggcaccaggg gagtgaaact ggctgatgac cagctgagcc
actttgtgcc aacagaggat 1500ggacgacacc tttccctgta cccactgcag aggaagaacc
ctgggcacag cagctttgtc 1560cttggctaca aactgttaca acgtcacaca atgaaggcac
aaagtccaac tttcaaaggg 1620tgtaggactc catactcagt gacagggcag gaagagccaa
agataaccac agccacagcc 1680tgtggagacc agggttggaa gccaggtgca gggccaggca
tctgcattgt gggatgttaa 1740tggcactttt gtcttgtagc tattttgaga tgtggtccag
agcatttcag ctgggagatc 1800tccctctggc caccaggact ctggctactg ttaaaatcct
gatgtttctg tggaatcctc 1860agtgtttaat cccactcaat agtatcatta cagttttctg
taagagaaaa tattacttat 1920ttatcccagt attcctagcc tgtcaacata ataaatatcg
gaacaaaacc tggtaaa 19771781871DNAMus Musculus 178ctgggattgg
taacctggag ttaagcgggc tccctgccaa cgcgagggct ttaaaagggg 60tgatgcaacg
cgctcccagc cacagtctca ctcagcgaga cgccgcgcac ggtgcttccc 120cagtggagcc
aatcggctaa cccgcgctcc ggcagagtcc ttggcgctcg cccgccggcg 180ggacagacca
cccgcctctg gccgctctct ggaccctggc cgccccgagc gaagactgga 240gcaaaatgat
gcttcaacat ccaggccaga gctgagattc gccatccaga ataaacacct 300ctgccatcgg
atgtcctctg cgctggagtc agttaccgtc aacaacagac ccctggagat 360gtcagtcacc
aagtctgagg cggcccctga agaagatgag aggaaaagga ggcggcgaga 420aagaaataaa
attgctgctg ccaagtgtcg aaacaagaaa aaggagaaga cagagtgcct 480gcagaaagag
tcagagaaac tggagagtgt gaatgctgag ctgaaggccc agattgagga 540gctgaagaat
gagaaacagc atttgatata catgctcaac ctgcaccggc ccacctgcat 600cgtccgggct
cagaatggac ggacaccgga agacgagagg aacctcttta tccaacagat 660aaaagaagga
acattgcaga gctaagcaga ggtggcacgg aggcaattgg ggagttctta 720ctgaatcctc
cttttccacc ccacaccctg aagccattgg aaaactggct tcctgtgcac 780ttctagaatc
ccagcagcca agagccgttg gggcaggagg gcctgtggtg acctactgca 840ttgacccact
ctgcccccga gtgaaccgtg gagcaggcag gagcatcctt tgtctcacca 900attccaggat
ttaggcctta tcatcccggc cagtctcaga tgacctagct ggccccaggc 960tggggtccta
tgcaaagcag gatcccacta atgggattca ggcagaagtg tctaccttga 1020taggtggggt
gggaccacat cctccactgt ggctgacaac gcccttccaa gggaatatgg 1080aatgagaaca
ttcattattg aggttgtcca atggccaggg tatgctttct agaaaatatg 1140ctgttctgtc
ccagaatgac tgtgcatagg gtatccgttt cagagcctgg tgttgtgcta 1200tttagatgtt
tgtcttgcac aacattggca tgatttttcc gggagtttca tcagatctga 1260tttctgagag
tctggggatc tgccatggtg gaaagtgccc ctcaaaagca tttgtgtggc 1320cacatgaact
ggctggcacc aggggagtga aactggctga tgaccagctg agccactttg 1380tgccaacaga
ggatggacga cacctttccc tgtacccact gcagaggaag aaccctgggc 1440acagcagctt
tgtccttggc tacaaactgt tacaacgtca cacaatgaag gcacaaagtc 1500caactttcaa
agggtgtagg actccatact cagtgacagg gcaggaagag ccaaagataa 1560ccacagccac
agcctgtgga gaccagggtt ggaagccagg tgcagggcca ggcatctgca 1620ttgtgggatg
ttaatggcac ttttgtcttg tagctatttt gagatgtggt ccagagcatt 1680tcagctggga
gatctccctc tggccaccag gactctggct actgttaaaa tcctgatgtt 1740tctgtggaat
cctcagtgtt taatcccact caatagtatc attacagttt tctgtaagag 1800aaaatattac
ttatttatcc cagtattcct agcctgtcaa cataataaat atcggaacaa 1860aacctggtaa a
18711793932DNAMus
Musculus 179ggggcgacac cactgggtcg gcagaggcag gaaatcgggc tggtcccggg
cggcgcgcag 60ccctgtccct ttctcagcat tgccgcgcgt tccccacccc accccctgcc
cccgggcatc 120gccatggact cagcggagac agagctaacc ccagctcctg agggcaggaa
gagatacagt 180gacatcttcc agagcctgga caacctcgag atatcattgg ggaacgtaac
ttttgatccc 240ctggctggag accctgtacg cagagaagac ctggagcctg acaaagctga
cacagccaca 300gtggtgactg aggagaacag tgaagccagt agttggcggg atctctcccc
agaaggtcct 360gcacccctca cagaggaaga actggatttg cgactcattc ggaccaaggg
tggtgtagat 420gctgccctgg agtatgctaa agcatggagc cgctatgcca aggaactgct
ggcctggaca 480gacaagagag ccaactacga gctcgagttt gctaagagta tcatgaagct
cgctgaggct 540ggcaaggtgt ccattctcca gcagagccaa atgccactcc agtacatcta
caccttgttt 600ctggagcatg acctcagcct gggagccctg gccctggaga cagtggccca
acagaagaga 660gactactacc agcctctggc ggccaaaagg atggaaattg agaagtggag
gaaggaattc 720aaggaacagt ggctgaagga gcagaagcgc atgaatgagg cagtgcaggc
actgcggcgc 780tccgagctcc agtacattca acgcagagag gacctgaggg cacgctccca
ggggtcccct 840gaggaccctc cttcccaggc atctcctgga tccaacaagc aacaggagcg
cagacggcgc 900tcccgagagg aggcacaggc caaggcgcat gaggcggagg ctctgtacca
ggcctgtgtc 960cgggaggcca attctcgcca gcaggatctg gagaccacca agcggcggat
agtgtcacat 1020gtgcgcaagc tggtgctgca aggagacgaa gtgcttaggc gggtgacgct
gggtctgttt 1080gagctgcgag gggcgcaggc agagcgagga ccccgctcct tctctgctct
ggctgagtgc 1140tgtgtgccct ttgaacctgg ccagcgctac caggagtttg ttcggacact
gcagcctggg 1200gccccaccgc cgccatctcc ggccttctgc ttccaggagt tcacagctgt
ggtgcacagt 1260ttccctcagg acacaaaaaa gaagttttcg gggcctctac ctccaaggct
ggaggaggag 1320ggttcccctg agcctggccc ttgggaggtt gccagcttag gcagccaggg
aatcccaggc 1380agtgatgtgg acagtgtagg tggtggcagt gagtcccggt ctttggattc
tcccacttcc 1440agcccaggtg ctggggcccg ccgacttgta aaggcttcgt ccacaggcac
ggagtcctcc 1500gatgactttg aggagcgaga ccctgatctg ggggatggga tagagaatgg
agtaggcagc 1560ccgttcagga agtggacact gtccacagct gctcaaaccc accgactgcg
gcggctgcgg 1620ggcccagcca agtgcagaga atgtgaagcc ttcatggtca gcgggacaga
atgtgaagag 1680tgctttttga cctgtcacaa gcgctgcctg gagaccctcc tcatcctttg
tggacaccgg 1740cggcttccgg cccggatgtc cctctttggg gttgacttcc tacagctccc
cagagatttc 1800cctgaggagg ttccctttgt gattaccaga tgcacagctg agatagagca
ccgtgccctg 1860ggcttgcagg gtatctatcg ggtcagcggg tctcgggtac gtgtggagcg
gctgtgccag 1920gcctttgaga atggccgagc actggtcgag ctgtccggga actctcctca
cgatatcacc 1980agcgttctca agcgatttct tcaggagctc actgatcccg tggtcccctt
ccacttgtac 2040gacgccttca tctctctggc aaagaccctg catgcagacc ctggggacga
ccctgggacc 2100cccaacccca gccctgagat tattcgctcg ctgaagaccc tcttggtgca
gctgcctgac 2160tctaactaca gtaccctgcg acacctggtg gcccatctgt tcagggtggc
tgctcggttt 2220gaagaaaaca agatgtctgc caacaatctg ggaattgtat ttgggcctac
actgctgcgg 2280ccaccagatg gacccagggc caccggtgcc agccctgtgg cctgtctgct
ggactccggt 2340caccaggctc agctggttga gttcctcatt gtgcactatg agcagatctt
tggaatggat 2400gagctccctc tggcctcgga gcctctgacc caagaccctg gcttggctcc
tgcatgcctt 2460gaatccagtc cccagcaccc agcctcactt cttgcccaag acacacagcc
cctgaccata 2520gccttggatt ccagcccaga ccccaaacac cacagtgcct tggagaagtg
ccccgaggtc 2580acacctcctg agcttgcaac tctgcagagg gaccagaggg aggaggaggt
ggaagacacc 2640agagatgggg caggggatgg gtccagccac tgccctgagg acttggccct
gggagcacaa 2700tcccggggcc acttcagccg ccagccagtg aagtattccc ggggaggtgt
gaggccagtt 2760actcatcaac tctccagcct ggctctggtg gcctccaagc tgtgtgagga
gactcctgtc 2820actgtctcag cagtgcaccg aggtagtttg agggtacgag gtttgggccc
tgctgctgcc 2880tgccctgaag gcagccccct gcgccggaac cctctgccca agcactttga
gatcacccag 2940gagacagccc gacttctctc caagctgaac agtgatgctg tgtccaggac
cacctgttgt 3000gctgacccag agcctgagga gtctgaagag cacctctgac cacctaccat
cctgagggac 3060ccagaactga attgatggtc cctgacccaa cctggtgacc aaaccaattc
agtggggtgt 3120ggggagagac ggggttacca gtgagttccg gtaatgaaga ttacctacct
gtgggagtcc 3180caagacactt ggttgaagtg tcccatcatc tccctgccag aggagattta
aacagctagg 3240caacacaggt gcaggtgttt cggggtcaag actcaatggt caatacagat
cagtagatcc 3300ttggggacta cccgagtctc tgacctctga gacgggtgtc ttgactattt
cagtcataat 3360ggctcctggc cctactacac ttgcagcagt aacagactcc caagttagca
ggtggctgca 3420gcccagccct gtctcctttt aatttgtttg tttgtttgtt tgttttaagc
taagtctcac 3480tgtgtagctc tggctggtct ggagctccct ttgtgagcca caaatcctct
gcctcccaag 3540tgctggctaa atctgtgttc ttacaacctc caaataaaac catatcctgc
tgccggcagg 3600agggctgacc gcagtggtgc ttgctgtaaa gcctcacatt tgttggacct
cccagagcca 3660cttagtggaa ggagagagcc catccctaca aattgtctga cctgtgcaca
tgcacaaata 3720aaagaaaatt ttaatttaaa aaaaaaaatc cgctgggcgg tagtgccaca
cacctctact 3780tgatcctagc actcaggaga tagaggcagg aggatctctg agttttatgc
cagccaggtg 3840tacagagaaa gttccaggac agccagggct acacagagaa accctgtttc
agaaaaacaa 3900aataaaataa gataaatctt gtctgttctt gc
39321803922DNAMus Musculus 180ggggcgacac cactgggtcg gcagaggcag
gaaatcgggc tggtcccggg cggcgcgcag 60ccctgtccct ttctcagcat tgccgcgcgt
tccccacccc accccctgcc cccgggcatc 120gccatggact cagcggagac agagctaacc
ccagctcctg agggcaggaa gagatacagt 180gacatcttcc agagcctgga caacctcgag
atatcattgg ggaacgtaac ttttgatccc 240ctggctggag accctgtacg cagagaagac
ctggagcctg acaaagctga cacagccaca 300gtggtgactg aggagaacag tgaagccagt
agttggcggg atctctcccc agaaggtcct 360gcacccctca cagaggaaga actggatttg
cgactcattc ggaccaaggg tggtgtagat 420gctgccctgg agtatgctaa agcatggagc
cgctatgcca aggaactgct ggcctggaca 480gacaagagag ccaactacga gctcgagttt
gctaagagta tcatgaagct cgctgaggct 540ggcaaggtgt ccattctcca gcagagccaa
atgccactcc agtacatcta caccttgttt 600ctggagcatg acctcagcct gggagccctg
gccctggaga cagtggccca acagaagaga 660gactactacc agcctctggc ggccaaaagg
atggaaattg agaagtggag gaaggaattc 720aaggaacagt ggctgaagga gcagaagcgc
atgaatgagg cagtgcaggc actgcggcgc 780tccgagctcc agtacattca acgcagagag
gacctgaggg cacgctccca ggggtcccct 840gaggaccctc cttcccaggc atctcctgga
tccaacaagc aacaggagcg cagacggcgc 900tcccgagagg aggcacaggc caaggcgcat
gaggcggagg ctctgtacca ggcctgtgtc 960cgggaggcca attctcgcca gcaggatctg
gagaccacca agcggcggat agtgtcacat 1020gtgcgcaagc tggtgctgca aggagacgaa
gtgcttaggc gggtgacgct gggtctgttt 1080gagctgcgag gggcgcaggc agagcgagga
ccccgctcct tctctgctct ggctgagtgc 1140tgtgtgccct ttgaacctgg ccagcgctac
caggagtttg ttcggacact gcagcctggg 1200gccccaccgc cgccatctcc ggccttctgc
ttccaggagt tcacagctgt ggtgcacagg 1260acacaaaaaa gaagttttcg gggcctctac
ctccaaggct ggaggaggag ggttcccctg 1320agcctggccc ttgggaggtt gccagcttag
gcagccaggg aatcccaggc agtgatgtgg 1380acagtgtagg tggtggcagt gagtcccggt
ctttggattc tcccacttcc agcccaggtg 1440ctggggcccg ccgacttgta aaggcttcgt
ccacaggcac ggagtcctcc gatgactttg 1500aggagcgaga ccctgatctg ggggatggga
tagagaatgg agtaggcagc ccgttcagga 1560agtggacact gtccacagct gctcaaaccc
accgactgcg gcggctgcgg ggcccagcca 1620agtgcagaga atgtgaagcc ttcatggtca
gcgggacaga atgtgaagag tgctttttga 1680cctgtcacaa gcgctgcctg gagaccctcc
tcatcctttg tggacaccgg cggcttccgg 1740cccggatgtc cctctttggg gttgacttcc
tacagctccc cagagatttc cctgaggagg 1800ttccctttgt gattaccaga tgcacagctg
agatagagca ccgtgccctg ggcttgcagg 1860gtatctatcg ggtcagcggg tctcgggtac
gtgtggagcg gctgtgccag gcctttgaga 1920atggccgagc actggtcgag ctgtccggga
actctcctca cgatatcacc agcgttctca 1980agcgatttct tcaggagctc actgatcccg
tggtcccctt ccacttgtac gacgccttca 2040tctctctggc aaagaccctg catgcagacc
ctggggacga ccctgggacc cccaacccca 2100gccctgagat tattcgctcg ctgaagaccc
tcttggtgca gctgcctgac tctaactaca 2160gtaccctgcg acacctggtg gcccatctgt
tcagggtggc tgctcggttt gaagaaaaca 2220agatgtctgc caacaatctg ggaattgtat
ttgggcctac actgctgcgg ccaccagatg 2280gacccagggc caccggtgcc agccctgtgg
cctgtctgct ggactccggt caccaggctc 2340agctggttga gttcctcatt gtgcactatg
agcagatctt tggaatggat gagctccctc 2400tggcctcgga gcctctgacc caagaccctg
gcttggctcc tgcatgcctt gaatccagtc 2460cccagcaccc agcctcactt cttgcccaag
acacacagcc cctgaccata gccttggatt 2520ccagcccaga ccccaaacac cacagtgcct
tggagaagtg ccccgaggtc acacctcctg 2580agcttgcaac tctgcagagg gaccagaggg
aggaggaggt ggaagacacc agagatgggg 2640caggggatgg gtccagccac tgccctgagg
acttggccct gggagcacaa tcccggggcc 2700acttcagccg ccagccagtg aagtattccc
ggggaggtgt gaggccagtt actcatcaac 2760tctccagcct ggctctggtg gcctccaagc
tgtgtgagga gactcctgtc actgtctcag 2820cagtgcaccg aggtagtttg agggtacgag
gtttgggccc tgctgctgcc tgccctgaag 2880gcagccccct gcgccggaac cctctgccca
agcactttga gatcacccag gagacagccc 2940gacttctctc caagctgaac agtgatgctg
tgtccaggac cacctgttgt gctgacccag 3000agcctgagga gtctgaagag cacctctgac
cacctaccat cctgagggac ccagaactga 3060attgatggtc cctgacccaa cctggtgacc
aaaccaattc agtggggtgt ggggagagac 3120ggggttacca gtgagttccg gtaatgaaga
ttacctacct gtgggagtcc caagacactt 3180ggttgaagtg tcccatcatc tccctgccag
aggagattta aacagctagg caacacaggt 3240gcaggtgttt cggggtcaag actcaatggt
caatacagat cagtagatcc ttggggacta 3300cccgagtctc tgacctctga gacgggtgtc
ttgactattt cagtcataat ggctcctggc 3360cctactacac ttgcagcagt aacagactcc
caagttagca ggtggctgca gcccagccct 3420gtctcctttt aatttgtttg tttgtttgtt
tgttttaagc taagtctcac tgtgtagctc 3480tggctggtct ggagctccct ttgtgagcca
caaatcctct gcctcccaag tgctggctaa 3540atctgtgttc ttacaacctc caaataaaac
catatcctgc tgccggcagg agggctgacc 3600gcagtggtgc ttgctgtaaa gcctcacatt
tgttggacct cccagagcca cttagtggaa 3660ggagagagcc catccctaca aattgtctga
cctgtgcaca tgcacaaata aaagaaaatt 3720ttaatttaaa aaaaaaaatc cgctgggcgg
tagtgccaca cacctctact tgatcctagc 3780actcaggaga tagaggcagg aggatctctg
agttttatgc cagccaggtg tacagagaaa 3840gttccaggac agccagggct acacagagaa
accctgtttc agaaaaacaa aataaaataa 3900gataaatctt gtctgttctt gc
39221813865DNAMus Musculus 181ggggcgacac
cactgggtcg gcagaggcag gaaatcgggc tggtcccggg cggcgcgcag 60ccctgtccct
ttctcagcat tgccgcgcgt tccccacccc accccctgcc cccgggcatc 120gccatggact
cagcggagac agagctaacc ccagctcctg agggcaggaa gagatacagt 180gacatcttcc
agagcctgga caacctcgag atatcattgg ggaacgtaac ttttgatccc 240ctggctggag
accctgtacg cagagaagac ctggagcctg acaaagctga cacagccaca 300gtggtgactg
aggagaacag tgaagccagt agttggcggg atctctcccc agaaggtcct 360gcacccctca
cagaggaaga actggatttg cgactcattc ggaccaaggg tggtgtagat 420gctgccctgg
agtatgctaa agcatggagc cgctatgcca aggaactgct ggcctggaca 480gacaagagag
ccaactacga gctcgagttt gctaagagta tcatgaagct cgctgaggct 540ggcaaggtgt
ccattctcca gcagagccaa atgccactcc agtacatcta caccttgttt 600ctggagcatg
acctcagcct gggagccctg gccctggaga cagtggccca acagaagaga 660gactactacc
agcctctggc ggccaaaagg atggaaattg agaagtggag gaaggaattc 720aaggaacagt
ggctgaagga gcagaagcgc atgaatgagg cagtgcaggc actgcggcgc 780tccgagctcc
agtacattca acgcagagag gacctgaggg cacgctccca ggggtcccct 840gaggaccctc
cttcccaggc atctcctgga tccaacaagc aacaggagcg cagacggcgc 900tcccgagagg
aggcacaggc caaggcgcat gaggcggagg ctctgtacca ggcctgtgtc 960cgggaggcca
attctcgcca gcaggatctg gagaccacca agcggcggat agtgtcacat 1020gtgcgcaagc
tggtgctgca aggagacgaa gtgcttaggc gggtgacgct gggtctgttt 1080gagctgcgag
gggcgcaggc agagcgagga ccccgctcct tctctgctct ggctgagtgc 1140tgtgtgccct
ttgaacctgg ccagcgctac caggagtttg ttcggacact gcagcctggg 1200gccccaccgc
cgccatctcc ggccttctgc ttccaggagt tcacagctgt ggtgcacagt 1260ttccctcagg
acacaaaaaa gaagttttcg gggcctctac ctccaaggct ggaggaggag 1320ggttcccctg
agcctggccc ttgggaggtt gccagcttag gcagccaggg aatcccaggc 1380agtgatgtgg
acagtgtagg tggtggcagt gagtcccggt ctttggattc tcccacttcc 1440agcccaggtg
ctggggcccg ccgacttgta aaggcttcgt ccacaggcac ggagtcctcc 1500gatgactttg
aggagcgaga ccctgatctg ggggatggga tagagaatgg agtaggcagc 1560ccgttcagga
agtggacact gtccacagct gctcaaaccc accgactgcg gcggctgcgg 1620ggcccagcca
agtgcagaga atgtgaagcc ttcatggtca gcgggacaga atgtgaagag 1680tgctttttga
cctgtcacaa gcgctgcctg gagaccctcc tcatcctttg tggacaccgg 1740cggcttccgg
cccggatgtc cctctttggg gttgacttcc tacagctccc cagagatttc 1800cctgaggagg
ttccctttgt gattaccaga tgcacagctg agatagagca ccgtgccctg 1860ggcttgcagg
gtatctatcg ggtcagcggg tctcgggtac gtgtggagcg gctgtgccag 1920gcctttgaga
atggccgagc actggtcgag ctgtccggga actctcctca cgatatcacc 1980agcgttctca
agcgatttct tcaggagctc actgatcccg tggtcccctt ccacttgtac 2040gacgccttca
tctctctggc aaagaccctg catgcagacc ctggggacga ccctgggacc 2100cccaacccca
gccctgagat tattcgctcg ctgaagaccc tcttggtgca gctgcctgac 2160tctaactaca
gtaccctgcg acacctggtg gcccatctgt tcagggtggc tgctcggttt 2220gaagaaaaca
agatgtctgc caacaatctg ggaattgtat ttgggcctac actgctgcgg 2280ccaccagatg
gacccagggc caccggtgcc agccctgtgg cctgtctgct ggactccggt 2340caccaggctc
agctggttga gttcctcatt gtgcactatg agcagatctt tggaatggat 2400gagctccctc
tggcctcgga gcctctgacc caagaccctg gcttggctcc tgcatgcctt 2460gaatccagtc
cccagcaccc agcctcactt cttgcccaag acacacagcc cctgaccata 2520gccttggatt
ccagcccaga ccccaaacac cacagtgcct tggagaagtg ccccgaggtc 2580acacctcctg
agggtccagc cactgccctg aggacttggc cctgggagca caatcccggg 2640gccacttcag
ccgccagcca gtgaagtatt cccggggagg tgtgaggcca gttactcatc 2700aactctccag
cctggctctg gtggcctcca agctgtgtga ggagactcct gtcactgtct 2760cagcagtgca
ccgaggtagt ttgagggtac gaggtttggg ccctgctgct gcctgccctg 2820aaggcagccc
cctgcgccgg aaccctctgc ccaagcactt tgagatcacc caggagacag 2880cccgacttct
ctccaagctg aacagtgatg ctgtgtccag gaccacctgt tgtgctgacc 2940cagagcctga
ggagtctgaa gagcacctct gaccacctac catcctgagg gacccagaac 3000tgaattgatg
gtccctgacc caacctggtg accaaaccaa ttcagtgggg tgtggggaga 3060gacggggtta
ccagtgagtt ccggtaatga agattaccta cctgtgggag tcccaagaca 3120cttggttgaa
gtgtcccatc atctccctgc cagaggagat ttaaacagct aggcaacaca 3180ggtgcaggtg
tttcggggtc aagactcaat ggtcaataca gatcagtaga tccttgggga 3240ctacccgagt
ctctgacctc tgagacgggt gtcttgacta tttcagtcat aatggctcct 3300ggccctacta
cacttgcagc agtaacagac tcccaagtta gcaggtggct gcagcccagc 3360cctgtctcct
tttaatttgt ttgtttgttt gtttgtttta agctaagtct cactgtgtag 3420ctctggctgg
tctggagctc cctttgtgag ccacaaatcc tctgcctccc aagtgctggc 3480taaatctgtg
ttcttacaac ctccaaataa aaccatatcc tgctgccggc aggagggctg 3540accgcagtgg
tgcttgctgt aaagcctcac atttgttgga cctcccagag ccacttagtg 3600gaaggagaga
gcccatccct acaaattgtc tgacctgtgc acatgcacaa ataaaagaaa 3660attttaattt
aaaaaaaaaa atccgctggg cggtagtgcc acacacctct acttgatcct 3720agcactcagg
agatagaggc aggaggatct ctgagtttta tgccagccag gtgtacagag 3780aaagttccag
gacagccagg gctacacaga gaaaccctgt ttcagaaaaa caaaataaaa 3840taagataaat
cttgtctgtt cttgc
38651822764DNAMus Musculus 182ggggcgacac cactgggtcg gcagaggcag gaaatcgggc
tggtcccggg cggcgcgcag 60ccctgtccct ttctcagcat tgccgcgcgt tccccacccc
accccctgcc cccgggcatc 120gccatggact cagcggagac agagctaacc ccagctcctg
agggcaggaa gagatacagt 180gacatcttcc agagcctgga caacctcgag atatcattgg
ggaacgtaac ttttgatccc 240ctggctggag accctgtacg cagagaagac ctggagcctg
acaaagctga cacagccaca 300gtggtgactg aggagaacag tgaagccagt agttggcggg
atctctcccc agaaggtcct 360gcacccctca cagaggaaga actggatttg cgactcattc
ggaccaaggg tggtgtagat 420gctgccctgg agtatgctaa agcatggagc cgctatgcca
aggaactgct ggcctggaca 480gacaagagag ccaactacga gctcgagttt gctaagagta
tcatgaagct cgctgaggct 540ggcaaggtgt ccattctcca gcagagccaa atgccactcc
agtacatcta caccttgttt 600ctggagcatg acctcagcct gggagccctg gccctggaga
cagtggccca acagaagaga 660gactactacc agcctctggc ggccaaaagg atggaaattg
agaagtggag gaaggaattc 720aaggaacagt ggctgaagga gcagaagcgc atgaatgagg
cagtgcaggc actgcggcgc 780tccgagctcc agtacattca acgcagagag gacctgaggg
cacgctccca ggggtcccct 840gaggaccctc cttcccaggc atctcctgga tccaacaagc
aacaggagcg cagacggcgc 900tcccgagagg aggcacaggc caaggcgcat gaggcggagg
ctctgtacca ggcctgtgtc 960cgggaggcca attctcgcca gcaggatctg gagaccacca
agcggcggat agtgtcacat 1020gtgcgcaagc tggtgctgca aggagacgaa gtgcttaggc
gggtgacgct gggtctgttt 1080gagctgcgag gggcgcaggc agagcgagga ccccgctcct
tctctgctct ggctgagtgc 1140tgtgtgccct ttgaacctgg ccagcgctac caggagtttg
ttcggacact gcagcctggg 1200gccccaccgc cgccatctcc ggccttctgc ttccaggagt
tcacagctgt ggtgcacagt 1260ttccctcagg acacaaaaaa gaagttttcg gggcctctac
ctccaaggct ggaggaggag 1320ggttcccctg agcctggccc ttgggaggtt gccagcttag
gcagccaggg aatcccaggc 1380agtgatgtgg acagtgtagg tggtggcagt gagtcccggt
ctttggattc tcccacttcc 1440agcccaggtg ctggggcccg ccgacttgta aaggcttcgt
ccacaggcac ggagtcctcc 1500gatgactttg aggagcgaga ccctgatctg ggggatggga
tagagaatgg agtaggcagc 1560ccgttcagga agtggacact gtccacagct gctcaaaccc
accgactgcg gcggctgcgg 1620ggcccagcca agtgcagaga atgtgaagcc ttcatggtca
gcgggacaga atgtgaagag 1680tgctttttga cctgtcacaa gcgctgcctg gagaccctcc
tcatcctttg tggacaccgg 1740cggcttccgg cccggatgtc cctctttggg gttgacttcc
tacagctccc cagagatttc 1800cctgaggagg ttccctttgt gattaccaga tgcacagctg
agatagagca ccgtgccctg 1860ggcttgcagg gtatctatcg ggtcagcggg tctcgggtac
gtgtggagcg gctgtgccag 1920gcctttgaga atggccgagc actggtcgag ctgtccggga
actctcctca cgatatcacc 1980agcgttctca agcgatttct tcaggagctc actgatcccg
tggtcccctt ccacttgtac 2040gacgccttca tctctctggc aaagaccctg catgcagacc
ctggggacga ccctgggacc 2100cccaacccca gccctgagat tattcgctcg ctgaagaccc
tcttggtgca gctgcctgac 2160tctaactaca gtaccctgcg acacctggtg gcccatctgt
tcagggtggc tgctcggttt 2220gaagaaaaca agatgtctgc caacaatctg ggaattgtat
ttgggcctac actgctgcgg 2280ccaccagatg gacccagggc caccggtgcc agccctgtgg
cctgtctgct ggactccggt 2340caccaggctc agctggttga gttcctcatt gtgcactatg
agcagatctt tggaatggat 2400gagctccctc tggcctcgga gcctctgacc caagaccctg
gcttggctcc tgcatgcctt 2460gaatccagtc cccagcaccc agcctcactt cttgcccaag
acacacagcc cctgaccata 2520gccttggatt ccagcccaga ccccaaacac cacagtgcct
tggagaagtg ccccgaggtc 2580acacctcctg agttttggtt tttcgagaca gggtttctct
gtgtagccct ggctgtcctg 2640gaactcactc tgtagaccag gctggcctcg aactcaaaaa
tctgcctgcc tctgcctccc 2700gagtgctggg attaaaggcc tgcgccacca ccgcccagct
gttctgttgt tttatctgac 2760tttg
27641833735DNAMus Musculus 183ggggcgacac cactgggtcg
gcagaggcag gaaatcgggc tggtcccggg cggcgcgcag 60ccctgtccct ttctcagcat
tgccgcgcgt tccccacccc accccctgcc cccgggcatc 120gccatggact cagcggagac
agagctaacc ccagctcctg agggcaggaa gagatacagt 180gacatcttcc agagcctgga
caacctcgag atatcattgg ggaacgtaac ttttgatccc 240ctggctggag accctgtacg
cagagaagac ctggagcctg acaaagctga cacagccaca 300gtggtgactg aggagaacag
tgaagccagt agttggcggg atctctcccc agaaggtcct 360gcacccctca cagaggaaga
actggatttg cgactcattc ggaccaaggg tggtgtagat 420gctgccctgg agtatgctaa
agcatggagc cgctatgcca aggaactgct ggcctggaca 480gacaagagag ccaactacga
gctcgagttt gctaagagta tcatgaagct cgctgaggct 540ggcaaggtgt ccattctcca
gcagagccaa atgccactcc agtacatcta caccttgttt 600ctggagcatg acctcagcct
gggagccctg gccctggaga cagtggccca acagaagaga 660gactactacc agcctctggc
ggccaaaagg atggaaattg agaagtggag gaaggaattc 720aaggaacagt ggctgaagga
gcagaagcgc atgaatgagg cagtgcaggc actgcggcgc 780tccgagctcc agtacattca
acgcagagag gacctgaggg cacgctccca ggggtcccct 840gaggaccctc cttcccaggc
atctcctgga tccaacaagc aacaggagcg cagacggcgc 900tcccgagagg aggcacaggc
caaggcgcat gaggcggagg ctctgtacca ggcctgtgtc 960cgggaggcca attctcgcca
gcaggatctg gagaccacca agcggcggat agtgtcacat 1020gtgcgcaagc tggtgctgca
aggagacgaa gtgcttaggc gggtgacgct gggtctgttt 1080gagctgcgag gggcgcaggc
agagcgagga ccccgctcct tctctgctct ggctgagtgc 1140tgtgtgccct ttgaacctgg
ccagcgctac caggagtttg ttcggacact gcagcctggg 1200gccccaccgc cgccatctcc
ggccttctgc ttccaggagt tcacagctgt ggtgcacagt 1260ttccctcagg acacaaaaaa
gaagttttcg gggcctctac ctccaaggct ggaggaggag 1320ggttcccctg agcctggccc
ttgggaggtt gccagcttag gcagccaggg aatcccaggc 1380agtgatgtgg acagtgtagg
tggtggcagt gagtcccggt ctttggattc tcccacttcc 1440agcccaggtg ctggggcccg
ccgacttgta aaggcttcgt ccacaggcac ggagtcctcc 1500gatgactttg aggagcgaga
ccctgatctg ggggatggga tagagaatgg agtaggcagc 1560ccgttcagga agtggacact
gtccacagct gctcaaaccc accgactgcg gcggctgcgg 1620ggcccagcca agtgcagaga
atgtgaagcc ttcatggtca gcgggacaga atgtgaagag 1680tgctttttga cctgtcacaa
gcgctgcctg gagaccctcc tcatcctttg tggacaccgg 1740cggcttccgg cccggatgtc
cctctttggg gttgacttcc tacagctccc cagagatttc 1800cctgaggagg ttccctttgt
gattaccaga tgcacagctg agatagagca ccgtgccctg 1860ggcttgcagg gtatctatcg
ggtcagcggg tctcgggtac gtgtggagcg gctgtgccag 1920gcctttgaga atggccgagc
actggtcgag ctgtccggga actctcctca cgatatcacc 1980agcgttctca agcgatttct
tcaggagggt ggctgctcgg tttgaagaaa acaagatgtc 2040tgccaacaat ctgggaattg
tatttgggcc tacactgctg cggccaccag atggacccag 2100ggccaccggt gccagccctg
tggcctgtct gctggactcc ggtcaccagg ctcagctggt 2160tgagttcctc attgtgcact
atgagcagat ctttggaatg gatgagctcc ctctggcctc 2220ggagcctctg acccaagacc
ctggcttggc tcctgcatgc cttgaatcca gtccccagca 2280cccagcctca cttcttgccc
aagacacaca gcccctgacc atagccttgg attccagccc 2340agaccccaaa caccacagtg
ccttggagaa gtgccccgag gtcacacctc ctgagcttgc 2400aactctgcag agggaccaga
gggaggagga ggtggaagac accagagatg gggcagggga 2460tgggtccagc cactgccctg
aggacttggc cctgggagca caatcccggg gccacttcag 2520ccgccagcca gtgaagtatt
cccggggagg tgtgaggcca gttactcatc aactctccag 2580cctggctctg gtggcctcca
agctgtgtga ggagactcct gtcactgtct cagcagtgca 2640ccgaggtagt ttgagggtac
gaggtttggg ccctgctgct gcctgccctg aaggcagccc 2700cctgcgccgg aaccctctgc
ccaagcactt tgagatcacc caggagacag cccgacttct 2760ctccaagctg aacagtgatg
ctgtgtccag gaccacctgt tgtgctgacc cagagcctga 2820ggagtctgaa gagcacctct
gaccacctac catcctgagg gacccagaac tgaattgatg 2880gtccctgacc caacctggtg
accaaaccaa ttcagtgggg tgtggggaga gacggggtta 2940ccagtgagtt ccggtaatga
agattaccta cctgtgggag tcccaagaca cttggttgaa 3000gtgtcccatc atctccctgc
cagaggagat ttaaacagct aggcaacaca ggtgcaggtg 3060tttcggggtc aagactcaat
ggtcaataca gatcagtaga tccttgggga ctacccgagt 3120ctctgacctc tgagacgggt
gtcttgacta tttcagtcat aatggctcct ggccctacta 3180cacttgcagc agtaacagac
tcccaagtta gcaggtggct gcagcccagc cctgtctcct 3240tttaatttgt ttgtttgttt
gtttgtttta agctaagtct cactgtgtag ctctggctgg 3300tctggagctc cctttgtgag
ccacaaatcc tctgcctccc aagtgctggc taaatctgtg 3360ttcttacaac ctccaaataa
aaccatatcc tgctgccggc aggagggctg accgcagtgg 3420tgcttgctgt aaagcctcac
atttgttgga cctcccagag ccacttagtg gaaggagaga 3480gcccatccct acaaattgtc
tgacctgtgc acatgcacaa ataaaagaaa attttaattt 3540aaaaaaaaaa atccgctggg
cggtagtgcc acacacctct acttgatcct agcactcagg 3600agatagaggc aggaggatct
ctgagtttta tgccagccag gtgtacagag aaagttccag 3660gacagccagg gctacacaga
gaaaccctgt ttcagaaaaa caaaataaaa taagataaat 3720cttgtctgtt cttgc
37351843874DNAMus Musculus
184ggggcgacac cactgggtcg gcagaggcag gaaatcgggc tggtcccggg cggcgcgcag
60ccctgtccct ttctcagcat tgccgcgcgt tccccacccc accccctgcc cccgggcatc
120gccatggact cagcggagac agagctaacc ccagctcctg agggcaggaa gagatacagt
180gacatcttcc agagcctgga caacctcgag atatcattgg ggaacgtaac ttttgatccc
240ctggctggag accctgtacg cagagaagac ctggagcctg acaaagctga cacagccaca
300gtggtgactg aggagaggaa gaactggatt tgcgactcat tcggaccaag ggtggtgtag
360atgctgccct ggagtatgct aaagcatgga gccgctatgc caaggaactg ctggcctgga
420cagacaagag agccaactac gagctcgagt ttgctaagag tatcatgaag ctcgctgagg
480ctggcaaggt gtccattctc cagcagagcc aaatgccact ccagtacatc tacaccttgt
540ttctggagca tgacctcagc ctgggagccc tggccctgga gacagtggcc caacagaaga
600gagactacta ccagcctctg gcggccaaaa ggatggaaat tgagaagtgg aggaaggaat
660tcaaggaaca gtggctgaag gagcagaagc gcatgaatga ggcagtgcag gcactgcggc
720gctccgagct ccagtacatt caacgcagag aggacctgag ggcacgctcc caggggtccc
780ctgaggaccc tccttcccag gcatctcctg gatccaacaa gcaacaggag cgcagacggc
840gctcccgaga ggaggcacag gccaaggcgc atgaggcgga ggctctgtac caggcctgtg
900tccgggaggc caattctcgc cagcaggatc tggagaccac caagcggcgg atagtgtcac
960atgtgcgcaa gctggtgctg caaggagacg aagtgcttag gcgggtgacg ctgggtctgt
1020ttgagctgcg aggggcgcag gcagagcgag gaccccgctc cttctctgct ctggctgagt
1080gctgtgtgcc ctttgaacct ggccagcgct accaggagtt tgttcggaca ctgcagcctg
1140gggccccacc gccgccatct ccggccttct gcttccagga gttcacagct gtggtgcaca
1200gtttccctca ggacacaaaa aagaagtttt cggggcctct acctccaagg ctggaggagg
1260agggttcccc tgagcctggc ccttgggagg ttgccagctt aggcagccag ggaatcccag
1320gcagtgatgt ggacagtgta ggtggtggca gtgagtcccg gtctttggat tctcccactt
1380ccagcccagg tgctggggcc cgccgacttg taaaggcttc gtccacaggc acggagtcct
1440ccgatgactt tgaggagcga gaccctgatc tgggggatgg gatagagaat ggagtaggca
1500gcccgttcag gaagtggaca ctgtccacag ctgctcaaac ccaccgactg cggcggctgc
1560ggggcccagc caagtgcaga gaatgtgaag ccttcatggt cagcgggaca gaatgtgaag
1620agtgcttttt gacctgtcac aagcgctgcc tggagaccct cctcatcctt tgtggacacc
1680ggcggcttcc ggcccggatg tccctctttg gggttgactt cctacagctc cccagagatt
1740tccctgagga ggttcccttt gtgattacca gatgcacagc tgagatagag caccgtgccc
1800tgggcttgca gggtatctat cgggtcagcg ggtctcgggt acgtgtggag cggctgtgcc
1860aggcctttga gaatggccga gcactggtcg agctgtccgg gaactctcct cacgatatca
1920ccagcgttct caagcgattt cttcaggagc tcactgatcc cgtggtcccc ttccacttgt
1980acgacgcctt catctctctg gcaaagaccc tgcatgcaga ccctggggac gaccctggga
2040cccccaaccc cagccctgag attattcgct cgctgaagac cctcttggtg cagctgcctg
2100actctaacta cagtaccctg cgacacctgg tggcccatct gttcagggtg gctgctcggt
2160ttgaagaaaa caagatgtct gccaacaatc tgggaattgt atttgggcct acactgctgc
2220ggccaccaga tggacccagg gccaccggtg ccagccctgt ggcctgtctg ctggactccg
2280gtcaccaggc tcagctggtt gagttcctca ttgtgcacta tgagcagatc tttggaatgg
2340atgagctccc tctggcctcg gagcctctga cccaagaccc tggcttggct cctgcatgcc
2400ttgaatccag tccccagcac ccagcctcac ttcttgccca agacacacag cccctgacca
2460tagccttgga ttccagccca gaccccaaac accacagtgc cttggagaag tgccccgagg
2520tcacacctcc tgagcttgca actctgcaga gggaccagag ggaggaggag gtggaagaca
2580ccagagatgg ggcaggggat gggtccagcc actgccctga ggacttggcc ctgggagcac
2640aatcccgggg ccacttcagc cgccagccag tgaagtattc ccggggaggt gtgaggccag
2700ttactcatca actctccagc ctggctctgg tggcctccaa gctgtgtgag gagactcctg
2760tcactgtctc agcagtgcac cgaggtagtt tgagggtacg aggtttgggc cctgctgctg
2820cctgccctga aggcagcccc ctgcgccgga accctctgcc caagcacttt gagatcaccc
2880aggagacagc ccgacttctc tccaagctga acagtgatgc tgtgtccagg accacctgtt
2940gtgctgaccc agagcctgag gagtctgaag agcacctctg accacctacc atcctgaggg
3000acccagaact gaattgatgg tccctgaccc aacctggtga ccaaaccaat tcagtggggt
3060gtggggagag acggggttac cagtgagttc cggtaatgaa gattacctac ctgtgggagt
3120cccaagacac ttggttgaag tgtcccatca tctccctgcc agaggagatt taaacagcta
3180ggcaacacag gtgcaggtgt ttcggggtca agactcaatg gtcaatacag atcagtagat
3240ccttggggac tacccgagtc tctgacctct gagacgggtg tcttgactat ttcagtcata
3300atggctcctg gccctactac acttgcagca gtaacagact cccaagttag caggtggctg
3360cagcccagcc ctgtctcctt ttaatttgtt tgtttgtttg tttgttttaa gctaagtctc
3420actgtgtagc tctggctggt ctggagctcc ctttgtgagc cacaaatcct ctgcctccca
3480agtgctggct aaatctgtgt tcttacaacc tccaaataaa accatatcct gctgccggca
3540ggagggctga ccgcagtggt gcttgctgta aagcctcaca tttgttggac ctcccagagc
3600cacttagtgg aaggagagag cccatcccta caaattgtct gacctgtgca catgcacaaa
3660taaaagaaaa ttttaattta aaaaaaaaaa tccgctgggc ggtagtgcca cacacctcta
3720cttgatccta gcactcagga gatagaggca ggaggatctc tgagttttat gccagccagg
3780tgtacagaga aagttccagg acagccaggg ctacacagag aaaccctgtt tcagaaaaac
3840aaaataaaat aagataaatc ttgtctgttc ttgc
3874185845DNAMus Musculus 185agcagttaaa gagcactagc tttgctttca gaggactcag
atttggttct tagcatccac 60atggtggttc acagtcatca gtgactctag tcccagggga
ttaaataccc tttcagacct 120ccatgggcac tgactgcagg cacatggtga aggaaaaaca
cttccataca taaaaataat 180tactacaatt taagctaaaa gggcaccaaa cactttatag
atcttgatga gaggctatat 240caaattttat acattgtgac accggttttt tatagatttt
ctagcatata ttttagatct 300atttatcatc tatctatcta tctatctatc tatctttcta
tcatctatct tatataaaat 360aaagtctgac ctaaatatga gaccctgtat ggttgtctaa
aaacatactg ttagctcctt 420cagtcacacc tgtttggggc tggctggtga atcagaagga
accttgttgg gtctgctgct 480caccacctat ggggctgtgg gcatggtggc agcagcagtt
gttgccactt ctgctttggc 540caagcacagt aggtgatcct gatagtcagc agcacagatt
cccattgatt ctagtctatg 600tatttgctta tggttggtac aatatttaat gtatataggc
agaagtatta tagggtcttt 660aaatatgtga acatatgtag cactgctttt aaacttaaaa
cggatatgat atttttcata 720tgtcaagaca cactggtaaa tttctgttac atattgtttt
caagttttct gttagtcttg 780tttctatgag gtacttttat tgtaacttaa aattcttaga
aattaaagtt ctgagaaaaa 840cctta
8451861871DNAMus Musculus 186gtcttcccca gaggccctaa
ctacagccac taccctttca gggcccaggc tgaccgtgga 60tggggctcct ggcaccttca
tcctcctcct ccatcttcta tctgagcctg agacgaactg 120cccaccccct ccagccacct
gccgcctcct gtttggaagg aggcccgcag cagatttcct 180cttccctcca ttcccaagag
gaacccctgg tctggggata ctgaggcagg cacagggcag 240ggcacgtgtg agcatccagt
catcctgaaa ggtaaatctg gttcctgaag cgacaactgt 300tcgtacaggg ttttgaagga
ttggtaggag ttccacagag gacaccgaag aggtgcagtc 360cctggtttgt ccttatgtcc
cagcccattt gggcacagct gtaatgtcta ctcctgggtc 420actgaggcat aggggtgact
tgcctgaact tgccttttct aggttttcct tggcttcacc 480tttgatgggg gtggagggag
gagggaggga aagaggagga aagagagagg gagagagtcc 540tggtcccaag aggaaggaag
aagccacttg aacttcagtc tggactccat cacatgttct 600gtggggacgg tcagccctca
ctcaagtccc agacccggcg gtttccctcc ctcccacccc 660ctccccctgc ggagccctgg
gattcccgcc cgaattagcc tggtcacccg agttggcatc 720gcacacgggg gcggagcgga
cagagtccag tgggtataaa ggcagctgca gagggcttaa 780ctcaaagaca cactcaggac
acaagcgaca tggccccgcc cgcgctccag gcccagcctc 840caggcggctc tcaactgagg
ttcctgctgt tcctgctgct gttgctgctg ctgctgtcat 900ggccatcgca gggggacgcc
ctggcaatgc ctgaacagcg accctccggc cctgagtccc 960aactcaacgc cgacgagcta
cggggtcgct tccaggacct gctgagccgg ctgcatgcca 1020accagagccg agaggactcg
aactcagaac caagtcctga cccagctgtc cggatactca 1080gtccagaggt gagattgggg
tcccacggcc agctgctact ccgcgtcaac cgggcgtcgc 1140tgagtcaggg tctccccgaa
gcctaccgcg tgcaccgagc gctgctcctg ctgacgccga 1200cggcccgccc ctgggacatc
actaggcccc tgaagcgtgc gctcagcctc cagggacccc 1260gtgctcccgc attacgcctg
cgcctgacgc cgcctccgga cctggctatg ctgccctctg 1320gcggcacaca gctggaactg
cgcttacggg tagccgccgg cagggggcgc cgaagcgcgc 1380atgcgcaccc aagagactcg
tgcccactgg gtccggggcg ctgctgtcac ctggagactg 1440tgcaggcaac tcttgaagac
ttgggctgga gcgactgggt gctgtccccg cgccagctgc 1500agctgagcat gtgcgtgggc
gagtgtcccc acctgtatcg ctccgcgaac acgcatgcgc 1560agatcaaagc acgcctgcat
ggcctgcagc ctgacaaggt gcctgccccg tgctgtgtcc 1620cctccagcta caccccggtg
gttcttatgc acaggacaga cagtggtgtg tcactgcaga 1680cttatgatga cctggtggcc
cggggctgcc actgcgcttg agcaccgggc cctgctcctc 1740acctacactc cccttcaagg
atgctattta tatttgtatt tattaatatt attaatttat 1800tggggtcggg ctgggtggat
ggattgtgta tttatttaaa actctgctaa taaaggtgag 1860cttggtttct a
18711871916DNAMus Musculus
187tgcagcagcc gagaggtgtg agccgccgcg gtgtcagagt ctaggggaat tggagtcagg
60cgcagatcca cagcgatatc cagacattca gagccacagg caccatgtcc aatcctggtg
120atgtccgacc tgttccgcac aggagcaaag tgtgccgttg tctcttcggt cccgtggaca
180gtgagcagtt gcgccgtgat tgcgatgcgc tcatggcggg ctgtctccag gaggcccgag
240aacggtggaa ctttgacttc gtcacggaga cgccgctgga gggcaacttc gtctgggagc
300gcgttcggag cctagggctg cccaaggtct acctgagccc tgggtcccgc agccgtgacg
360acctgggagg ggacaagagg cccagtactt cctctgccct gctgcagggg ccagctccgg
420aggaccacgt ggccttgtcg ctgtcttgca ctctggtgtc tgagcggcct gaagattccc
480cgggtgggcc cggaacatct cagggccgaa aacggaggca gaccagcctg acagatttct
540atcactccaa gcgcagattg gtcttctgca agagaaaacc ctgaagtgcc cacgggagcc
600ccgccctctt ctgctgtggg tcaggaggcc tcttccccat cttcggcctt agccctcact
660ctgtgtgtct taattattat ttgtgtttta atttaaacgt ctcctgtata tacgctgcct
720gccctctccc agtctccaaa cttaaagtta tttaaaaaaa gaacaaaaca aaacaaaaaa
780aaccaaaaca aaacaaacct aaattagtag gacggtaggg cccttagtgt gggggatttc
840tattatgtag attattatta tttaagcccc tcccaaccca agctctgtgt ttcctatacc
900ggaggaacag tcctactgat atcaacccat ctgcatccgt ttcacccaac ccccctcccc
960ccattccctg cctggttcct tgccacttct tacctggggg tgatcctcag acctgaatag
1020cactttggaa aaatgagtag gactttgggg tctccttgtc acctctaagg ccagctagga
1080tgacagtgaa gcagtcacag cctagaacag ggatggcagt taggactcaa ccgtaatatc
1140ccgactcttg acattgctca gacctgtgaa gacaggaatg gtccccactc tggatcccct
1200ttgccactcc tggggagccc acctctcctg tgggtctctg ccagctgccc ctctattttg
1260gagggttaat ctggtgatct gctgctcttt tcccccaccc catacttccc cttctgcagg
1320tcggcaggag gcatatctag gcacttgccc cacagctcag tggactggaa gggaatgtat
1380atgcagggta cactaagtgg gattccctgg tcttacctta ggcagctcca gtggcaaccc
1440cctgcattgt gggtctaggg tgggtccttg gtggtgagac aggcctccca gagcattcta
1500tggtgtgtgg tggtgggggt gggcttatct gggatgggga ccccagttgg ggttctcagt
1560gacttctccc atttcttagt agcagttgta caaggagcca ggccaagatg gtgtcttggg
1620ggctaaggga gctcacagga cactgagcaa tggctgatcc tttctcagtg ttgaataccg
1680tgggtgtcaa agcacttagt gggtctgact ccagccccaa acatccctgt ttctgtaaca
1740tcctggtctg gactgtctac ccttagcccg caccccaaga acatgtattg tggctccctc
1800cctgtctcca ctcagattgt aagcgtctca cgagaaggga cagcaccctg cattgtcccg
1860agtcctcaca cccgacccca aagctggtgc tcaataaata cttctcgatg atttat
19161883512DNAMus Musculus 188agagaccatc catcaaaaga accacaccaa tcagcgacgt
agatgcgtcc cagctagaga 60gccaggtctc cagcttgttc ccccactgcc cggcgcagtc
cttcgctgcg cgctgacccc 120gaggaaggca gtacttggtc agggcgctga gggaccctcc
accgggacgc cggcccctcc 180ccgggcctct gctcacttga cccccactcc ctagtccgtc
cccttagtag gcctgtcgga 240tcggggacgt ggggcgagct gagagcaggc ccggggtggg
tggtcaccgt ggtgaagacg 300tggctgtcaa gatgatagaa gtactgacaa ctgactctca
gaaactgcta caccagctga 360acaccctgtt ggaacaggag tctagatgtc agccaaaggt
ctgcggcttg aaactaattg 420agtcggccca tgataatggc ctcagaatga ctgcaagatt
acgggacttt gaagtaaaag 480atctacttag tctaactcag ttctttggct ttgacacgga
gacattttcc ctagctgtga 540atttactgga cagattcttg tctaaaatga aggtacaggc
gaagcatctt gggtgtgttg 600gactgagctg cttttatttg gctgtgaaag cgactgaaga
ggaaaggaat gtcccactgg 660cgactgattt gatccgaata agtcagtata ggttcacggt
ttcagacctg atgagaatgg 720agaagattgt gttggagaaa gtgtgttgga aagtcaaagc
tactactgcc tttcaatttc 780tgcagctcta ttattcactc gttcacgaca ccttgccatt
tgagaggaga aacgatctga 840attttgaaag actagaagcc caacttaagg cctgccactg
caggatcata ttttctaagg 900caaagccttc tgtgctggcg ctatctatcc ttgcgttgga
gatccaagca ctgaaatacg 960tagagttaac agaaggagta gaatgtattc agaaacattc
caagataagt ggccgagatt 1020tgaccttctg gcaagagctt gtttccaagt gtttaactga
atattcatca aacaagtgct 1080ccaaacctaa cggtcagaag ttgaaatgga ttgtgtctgg
acgcactgca cggcaactga 1140agcacagtta ttatagaata actcacctcc caacgattcc
tgagaccatt tgttagttga 1200taaatctggt tgttattctc tgtatacaga aaattttcca
gtatgatcat tttctgctac 1260aactgaagaa ttgaaatact atcttcaata taaagaatat
gggatgaaaa cataaaggaa 1320aagtgaattg ttgactggtc tagatagaga atactggaag
gcattcactg tgtacagtgc 1380gtagcagttt taagagaaaa gacatatcaa acccctagat
atacgctaat acttttcatc 1440aaaagattag cgtagtagca aagagaatac tttaaactcg
aattttaaaa gtagttactg 1500aaatagcact tctttaaatt acgtaccacc ccactgtagc
ttatttaaag ttgcataagc 1560ccatgcagaa caacaagcaa tgtgacccat atatgaacaa
attttaatct gcccatcgac 1620tatgaaaatg aagtacaaac ctgggtgatg gacttacaaa
gtaatatagg gcatgcccat 1680gttaggtttc tggaaactgc cagagtgtct taattctata
gctagtattt tacctctata 1740gcatttggac taatacaaag taattatatg catgaaaata
taaaattggt ctctgataca 1800tacacatttt tgacatctaa atttcttaat catagcaaag
atttatcttt ttatgattaa 1860aaacaatttt ttccttaatg catggcagca catgccttta
atcccagcac tagagaggca 1920gagacaggta gatctctgag ttcaaagcca ggctggtcta
cacagtgagt tccaagacag 1980ctagagacct tgtctcaaaa acactcaaaa caaccaaaca
ccaggggtaa atgttgctgg 2040gaagtcaggg aagatggttt agaagggaag cctgacaacc
tgacttcatt cttcaggacc 2100cacatgatgg aaggagagaa cgaagaactc ccaagttctc
tcacatatgc acatacctca 2160ccaccccccg caggaaatac atgatcatgc gtctgagata
tcaccagttc acctttagca 2220gctcgcagtt tgtaggcaga tttctgttaa gttgggtctg
tgttgtttgc ctatgtagca 2280ggattacagc agcagcaaaa acggtccctc aagtctttct
gccactctga cctgagtttc 2340ctacggtaca ggatttactc tgagaaacct cagcaccttg
ccacagtagc cttggcagaa 2400tggcctcacg gttagggaaa ctcctgattc taagcttggg
agagctacgc ttagatttga 2460attcacccag gaagcattca aatcaaggct aaagacataa
atgtgaaata aaactgtgaa 2520ccttcattct aaagttcatc tgacttccca gatttgatca
atatattctt aggtggtatt 2580aaaaatggta aactgcttaa tttaaatctc aaaatttaaa
ttatgaggtt tacataaaaa 2640ccaacatttc atgaatgcac ttttaaggta ttaaaagggg
tacttaagcg gtaaatggtt 2700tcttggcacc cataaccaag taatagttaa tttacaggtg
ggattttttt ttattgctat 2760gagaattaca tttaaaattg tgggtgtttt atataaagca
gatatcacaa gttttgaaaa 2820tttgttacct ttaatatttc ttctagagaa taggtgtttg
tatccataat aaaagaaaaa 2880tttgtcagaa ctgctgcttc aatctaatcc catttgagag
aattgtcttt actgtcttaa 2940taactggatg aattatcact ctgaaaatgt atttattgca
ctaaagttag tttaggcttg 3000ataaaacact ccagacattt ttactacaga ctgtttctat
aaaactgcca ttgcttctaa 3060tggagaattt tattttaaaa gaaataaaat tgctgagttt
atctgcaaaa cctttctcta 3120agtcttatgg gacgtaagga gacacctcca taattataag
agccgttgtg ctcagagtct 3180ccatgctggc ttgaatgtat gatccacact gttaaaacat
aggcagcagc tcagggccct 3240ggacagcctg agtcaaccta gagtagctgg aaccattttg
acatgtaatg gataagaaaa 3300ttatccattg agaagctgaa caataaacca aagaacgggt
gtattttatc cttaacctct 3360gtaaaccacg ttacactgag aacacttcag ttcttcctaa
aggttgatag gcttcagtct 3420gaaaacaata ttgatttgga gtggacagaa gttaactaac
caactaccat tatgttttga 3480atacaccttt caataaaatg attgaaatgc aa
35121893433DNAMus Musculus 189agagaccatc catcaaaaga
accacaccaa tcagcgacgt agatgcgtcc cagctagaga 60gccaggtctc cagcttgttc
ccccactgcc cggcgcagtc cttcgctgcg cgctgacccc 120gaggaaggca gtacttggtc
agggcgctga gggaccctcc accgggacgc cggcccctcc 180ccgggcctct gctcacttga
cccccactcc ctagtccgtc cccttagtag gcctgtcgga 240tcggggacgt ggggcgagct
gagagcaggc ccggggtggg tggtcaccgt ggtgaagacg 300tggctgtcaa gatgatagaa
gtactgacaa ctgactctca gaaactgcta caccagctga 360acaccctgtt ggaacaggag
tctagatgtc agccaaaggt ctgcggcttg aaactaattg 420agtcggccca tgataatggc
ctcagaatga ctgcaagatt acgggacttt gaagtaaaag 480atctacttag tctaactcag
ttctttggct ttgacacgga gacattttcc ctagctgtga 540atttactgga cagattcttg
tctaaaatga aggtacaggc gaagcatctt gggtgtgttg 600gactgagctg cttttatttg
gctgtgaaag cgactgaaga ggaaaggaat gtcccactgg 660cgactgattt gatccgaata
agtcagtata ggttcacggt ttcagacctg atgagaatgg 720agaagattgt gttggagaaa
gtgtgttgga aagtcaaagc tactactgcc tttcaatttc 780tgcagctcta ttattcactc
gttcacgaca ccttgccatt tgagagcctt ctgtgctggc 840gctatctatc cttgcgttgg
agatccaagc actgaaatac gtagagttaa cagaaggagt 900agaatgtatt cagaaacatt
ccaagataag tggccgagat ttgaccttct ggcaagagct 960tgtttccaag tgtttaactg
aatattcatc aaacaagtgc tccaaaccta acggtcagaa 1020gttgaaatgg attgtgtctg
gacgcactgc acggcaactg aagcacagtt attatagaat 1080aactcacctc ccaacgattc
ctgagaccat ttgttagttg ataaatctgg ttgttattct 1140ctgtatacag aaaattttcc
agtatgatca ttttctgcta caactgaaga attgaaatac 1200tatcttcaat ataaagaata
tgggatgaaa acataaagga aaagtgaatt gttgactggt 1260ctagatagag aatactggaa
ggcattcact gtgtacagtg cgtagcagtt ttaagagaaa 1320agacatatca aacccctaga
tatacgctaa tacttttcat caaaagatta gcgtagtagc 1380aaagagaata ctttaaactc
gaattttaaa agtagttact gaaatagcac ttctttaaat 1440tacgtaccac cccactgtag
cttatttaaa gttgcataag cccatgcaga acaacaagca 1500atgtgaccca tatatgaaca
aattttaatc tgcccatcga ctatgaaaat gaagtacaaa 1560cctgggtgat ggacttacaa
agtaatatag ggcatgccca tgttaggttt ctggaaactg 1620ccagagtgtc ttaattctat
agctagtatt ttacctctat agcatttgga ctaatacaaa 1680gtaattatat gcatgaaaat
ataaaattgg tctctgatac atacacattt ttgacatcta 1740aatttcttaa tcatagcaaa
gatttatctt tttatgatta aaaacaattt tttccttaat 1800gcatggcagc acatgccttt
aatcccagca ctagagaggc agagacaggt agatctctga 1860gttcaaagcc aggctggtct
acacagtgag ttccaagaca gctagagacc ttgtctcaaa 1920aacactcaaa acaaccaaac
accaggggta aatgttgctg ggaagtcagg gaagatggtt 1980tagaagggaa gcctgacaac
ctgacttcat tcttcaggac ccacatgatg gaaggagaga 2040acgaagaact cccaagttct
ctcacatatg cacatacctc accacccccc gcaggaaata 2100catgatcatg cgtctgagat
atcaccagtt cacctttagc agctcgcagt ttgtaggcag 2160atttctgtta agttgggtct
gtgttgtttg cctatgtagc aggattacag cagcagcaaa 2220aacggtccct caagtctttc
tgccactctg acctgagttt cctacggtac aggatttact 2280ctgagaaacc tcagcacctt
gccacagtag ccttggcaga atggcctcac ggttagggaa 2340actcctgatt ctaagcttgg
gagagctacg cttagatttg aattcaccca ggaagcattc 2400aaatcaaggc taaagacata
aatgtgaaat aaaactgtga accttcattc taaagttcat 2460ctgacttccc agatttgatc
aatatattct taggtggtat taaaaatggt aaactgctta 2520atttaaatct caaaatttaa
attatgaggt ttacataaaa accaacattt catgaatgca 2580cttttaaggt attaaaaggg
gtacttaagc ggtaaatggt ttcttggcac ccataaccaa 2640gtaatagtta atttacaggt
gggatttttt tttattgcta tgagaattac atttaaaatt 2700gtgggtgttt tatataaagc
agatatcaca agttttgaaa atttgttacc tttaatattt 2760cttctagaga ataggtgttt
gtatccataa taaaagaaaa atttgtcaga actgctgctt 2820caatctaatc ccatttgaga
gaattgtctt tactgtctta ataactggat gaattatcac 2880tctgaaaatg tatttattgc
actaaagtta gtttaggctt gataaaacac tccagacatt 2940tttactacag actgtttcta
taaaactgcc attgcttcta atggagaatt ttattttaaa 3000agaaataaaa ttgctgagtt
tatctgcaaa acctttctct aagtcttatg ggacgtaagg 3060agacacctcc ataattataa
gagccgttgt gctcagagtc tccatgctgg cttgaatgta 3120tgatccacac tgttaaaaca
taggcagcag ctcagggccc tggacagcct gagtcaacct 3180agagtagctg gaaccatttt
gacatgtaat ggataagaaa attatccatt gagaagctga 3240acaataaacc aaagaacggg
tgtattttat ccttaacctc tgtaaaccac gttacactga 3300gaacacttca gttcttccta
aaggttgata ggcttcagtc tgaaaacaat attgatttgg 3360agtggacaga agttaactaa
ccaactacca ttatgttttg aatacacctt tcaataaaat 3420gattgaaatg caa
34331904172DNAMus Musculus
190agccctgctt ctccttctaa caacaccttt cccaccaccg tgtcaggctc catctgtggt
60gtgggtgctc tacctctctg gtcctcagct tgggggtggg gtggaagtgg ggggagcctc
120aggccaccaa cttcagacgg aagtcaggtg gggggcaggg tgaggagcca acgccagagg
180agcctcagga ggagagggaa gcagaggggc ccaacaacga tggtgtcacc ctgaagactg
240gacaactgtg cagactgtgg agggctgcga gaccacggct ccagtatata aatcaggcaa
300attccccatt tgagcatgaa cttctgaaaa cggcctgcat ctaaggtctc ctccaaggcc
360ctctggagtc cagcccataa tgaaggtctt ggccgcaggg attgtgccct tactgctgct
420ggttctgcac tggaaacacg gggcagggag ccctcttccc atcacccctg taaatgccac
480ctgtgccata cgccacccat gccacggcaa cctcatgaac cagatcaaga atcaactggc
540acagctcaat ggcagcgcca atgctctctt catttcctat tacacagctc aaggggagcc
600gtttcccaac aacgtggaaa agctatgtgc gcctaacatg acagacttcc catctttcca
660tggcaacggg acagagaaga ccaagttggt ggagctgtat cggatggtcg catacctgag
720cgcctccctg accaatatca cccgggacca gaaggtcctg aaccccactg ccgtgagcct
780ccaggtcaag ctcaatgcta ctatagacgt catgaggggc ctcctcagca atgtgctttg
840ccgtctgtgc aacaagtacc gtgtgggcca cgtggatgtg ccacctgtcc ccgaccactc
900tgacaaagaa gccttccaaa ggaaaaagtt gggttgccag cttctgggga catacaagca
960agtcataagt gtggtggtcc aggccttcta gagaggaggt cttgaatgta ccatggactg
1020agggacctca ggagcaggat ccggaggtgg ggagggggct caaaatgtgc tggggtttgg
1080gacattgtta aatgcaaaac ggggctgctg gcagacccca gggatttcca ggtactcact
1140gcactctggg ctgggccatg atggaatctg gcaaagttga aacttccata ggcagagctt
1200ctatacagcc cagcaccagc tagaaatggc aatgagggtg ttggtctgag agatttctgt
1260ctcactcact cactcactca ctctcactca ctcactcact cactcactca gccccttgct
1320tgctgggtgt atgaacaagc tgcacaagtt gtctacagca gacagcaaag ggctgggaag
1380tgtcctagac ccctacagag tcaccatcat ctggtccttt gctgtctctc agagaaactt
1440tggaaggctt ggttgggatg tgagagagct aaggggactg ggatccagaa ggaatccttt
1500tattttattt tattttattt tattttattt tattttataa gttttgtggg tggaagggta
1560ccctggggtg gaatgatgga atgtgtcttc tcttgagttg gatgagagag ttcaggctta
1620gagactgtca gatggaagag tctaggtcac cagtgttcag gctcccacag aagcacagcg
1680gccagcttcc agttgtcaaa gcctgacgaa ctcggttagc ttctatgcag ttccccccac
1740agcctggcgt ggttggggtc tgccagctgg acctagaggt gaggtgtgtg caggcaggaa
1800gaggcaggct gcaaaggcag gttcccagag tcctcccggg gaaggacctc taactgtcta
1860ggagtcaggg aaggagcaag gcagccagcc attgctgagg cagtagccga ctgcagctct
1920catctgcttc tcaacccctg agaacaggtg atcttgagca gacagacagg tagcataaag
1980tagaatgtcg ggtctgaggc cccggaggtc gcaaaggtac ttgaagggga ccagagggct
2040gtcttgggtc cctggagcat ggagaagcag aacttgaggt cagggtctca gggaagatga
2100ggcccagagt gctgtgtttg atccagcaca gctgtctatt tattactatg tcctatttat
2160attaacttat tggtgcttta aatggcaaag ttaattcccc gaaatggtat gaggctcctt
2220ccatgggagc tggggccgag actctccacc tagtggggcc tggtctggag gcacatgatt
2280gttacaggtg cagctcatgg gtcaaatcag agagctggct agctcctctg tctcccactg
2340tgactcactt ttagggtgtc agggtccccc agaaaaagct gggccagttt gtctctctgc
2400ttctgtctct gtctctccga gtctgtctct gtctgtctct gtgtctctgt ctctttgtct
2460ctctctgtct ctgtctctct ctctctctcc ccgccccccc cccttctccc tctggtctcc
2520aagggggtgg aacagtttct tgttgttttg tcccactgag ctctctggca ccccctagat
2580tcctgctatg cggtgcacca ttcataatga agtgaatggc tctggaacct tgggcaaaac
2640tgattccttc ctcaaatcgt agctgaggag tgctgaaaca tcctgacccg gcacccagcg
2700tgctttcgac cagcatggaa gctcctcggg tggcccgaac acccacagag ggtgaataca
2760ggaggttgga gcagtgcagg ccctgaactg ggcctgaaca gctgcccagt gcgccagaga
2820aggggagatc aaggcccgag acgcctggga cacagaccag gaagctgtgg tccttgcttc
2880atcgctgcct tcccactccc gcccatgtct gggctcccag gcagggaatc cgatctgatc
2940tctcctttgt gctgaggcca ggcaagcaga ggaacgccct cgatctggga gcagggtagg
3000gaggaaggca gccaagctgg ggcagtggct gactacagag ctagctgcct gcctctcagg
3060ctctgaacag ggcggtcctt agcagttcag cagtgggatt ctgcttcacg cggttttgca
3120cctttctctg tcactctcta agcactttac ctggacggca ggtggacagg ccctggagct
3180ctggcttagg aaaggcctgg aaccatagat gcagcaagga gactatggtg ggggccacgc
3240gtgtcagcga caaagttact ccaccgtact cctgttgctg cgtcaggctc atctcaggac
3300tggctgccct tctccaagct gagagtcaat ttgtctaaaa gccaagatga tgccacagcc
3360tggggcctgt tgggctttgt catcacttca catttgtatg gacttggact ctctgggctc
3420cgcccacctg gcagctttga aggctcaggg accaatggac tctctccgtg cacgcccccg
3480tccccccaac gcaaccacct acctgcgtct tactccatca gttgcccagc atcccagaac
3540cattgagcct ttggggaaaa cagactttag gggcaggtag ttgctcacct gacatctttc
3600acctggaagc attgacttcc accgagcata gtaggtagtg tgtctggacc agagaaaaag
3660ggatggggca ttttgcagtt tatccagaga gaagcaaagg ggcctttatt tattatttaa
3720aacttcaaac ctgaaagcac tgagagttta ctggtctgcc cccctccccc cactcttgtc
3780tatttctgtg tccttgatcc cgactcaagc aacccagctc tgctttgcct gctctctgga
3840gcagacatgg tatgtgggcc aggaccccgg agtcttgcat ggtagcggct tcagaaggga
3900aatgatatgg ctgtctgcat tcggatgact ccccagtccc agcccagcct ctcctttgca
3960ctgctgctct ccctctttcc tttcctttgg aagggacttg gccttgggtg acaaattcct
4020ctttgatgaa tgtaccctgt gggaatgttt catactgaca gattattttt atttattcaa
4080tgtcatattt aaaatattta ttttttatac tgaaggagtg tctttttttt tttaaagaaa
4140aaatgaaata ataaagaact cattcttgtt ga
41721912111DNAMus Musculus 191ggtggggctg agggagggaa acaaacaaaa tcccgctgcg
gggacaggag acggaaaagc 60aggctggaag ggtagacaca attctcgcga gaagtagagc
gaattccctc ggagaggggc 120ggttgcgcag aggtacacca cgtgtgcggt ccctccggcg
ccgagtcagg gtctctcgtc 180gagtctgggt ctaggttaga tttggaatcg tggagatgcg
gaaggacacc cctcctccgc 240tcgtgccccc ggcggcccgc gagtggaacc tgccccccaa
tgcgcccgca tgcatggaac 300gtcaattgga ggctgcacgg taccggtctg atggttccct
tctgctcggg gtctccagcc 360tgagtggtcg ctgctgggta ggttctctgt ggtttttcaa
ggatcctagt gcggccccca 420acgaaggttt ctgctctgct ggcgtccaga ccgaggctgg
agtagctgac ctcacttggg 480tgggggacaa aggtatccta gtggcttctg attcaggtgc
tgttgaattg tgggagctag 540atgagaacga gacacttata gtcagcaagt tctgcaagta
tgagcatgat gacattgtgt 600ctactgtcac tgtcctgagc tctggcacac aagctgtcag
tggtagcaaa gactgctgca 660tcaaaatttg ggacctggct cagcaggtat cactgaattc
ataccgagct cacgctggac 720aggttacctg tgttgctgcc tctccccaca aagactctgt
gtttctttca tgtagtgagg 780acagtagaat tttgctctgg gatacccgct gtcccaagcc
ggcatcacag atggcctgca 840atgcctctgg ctacctccct accgctttgg cttggcatcc
tcagcagagt gaagtctttg 900tttttggtga cgagaatgga tctgtctccc ttgtggacac
caagaatgca agctgtaccc 960tcagctcagc tgtgcactcc cagggtgtca ctagactggt
attctcccca cacagtgtcc 1020ccctcctgac ttctctcagt gaagactgtt cacttgctgt
gctggattca agcctttctg 1080aggtgtttag aagtcgagcc cacagagact ttgtgagaga
tgctacgtgg tctccactca 1140atcactccct tcttaccaca gttggctggg accatcaggt
catccaccat gttgtgccct 1200tagagcctct cccaaaccct ggacctgaca gtgttgtgga
gtagaatgga tttcagaaaa 1260accaaaacaa gccctccgtc tgtaagcgac tactcgattg
cccctgcctt ccatgtgtga 1320gagcacagga gccttgtaga gcatgtttcc tccctagccc
cgtgcagtaa caggcagatt 1380ctcagcctga gggaggctgc atcccatagt gactcagagg
aagaaacttc ctctgtaaat 1440ggatgtatgt gagtacacgt gtgagtgcgg tatatagttt
ggagtggaga aaattattct 1500tcagctttcc caaagcaatg ctctttaccc ctgacaaagt
gaccagagga ttttaatgct 1560tcccatgtct gggaattggc gatgttaggg atatggaatg
tgggtatccc tagatttttg 1620ggaatacttc atactactca gaggtgcgta acttattttt
atatagagtt taattcacta 1680ttatgggaat tacttccata tacaaaagtc tagcccactg
taccttgaga agacaaaaca 1740gttttgtaca agtccctgtt atactgagtc aaatccattt
tctgggtgaa taaatttggc 1800cctgcagtgt agctcttgtt caccctttcc ttccttggtg
ttgtgtgtga gagatgagtg 1860ttttcctgtc ctagatttca cagataagtt gtagggatga
tggaccactt aaaagtgttt 1920cagtgaagtg ggaaaattga catggattgt tacagagaaa
tctgtcattt ttcccaccta 1980aaaattgatc tgggtacctt cctctggaga gctgaagtct
gaatgtattt ttggactcct 2040aagatttgag atccagcatc agggaaactg tcggaaatac
taaaaggtga aataaagact 2100tttatccttg a
21111922594DNAMus Musculus 192ggtggggctg agggagggaa
acaaacaaaa tcccgctgcg gggacaggag acggaaaagc 60aggctggaag ggtagacaca
attctcgcga gaagtagagc gaattccctc ggagaggggc 120ggttgcgcag aggtacacca
cgtgtgcggt ccctccggcg ccgagtcagg gtctctcgtc 180gagtctgggt ctaggttaga
tttggaatcg tggagatgcg gaaggacacc cctcctccgc 240tcgtgccccc ggcggcccgc
gagtggaacc tgccccccaa tgcgcccgca tgcatggaac 300gtcaattgga ggctgcacgg
taccggtctg atggttccct tctgctcggg gtctccagcc 360tgagtggtcg ctgctgggta
ggttctctgt ggtttttcaa ggatcctagt gcggccccca 420acgaaggttt ctgctctgct
ggcgtccaga ccgaggctgg agtagctgac ctcacttggg 480tgggggacaa aggtatccta
gtggcttctg attcaggtgc tgttgaattg tgggagctag 540atgagaacga gacacttata
gtcagcaagt tctgcaagta tgagcatgat gacattgtgt 600ctactgtcac tgtcctgagc
tctggcacac aagctgtcag tggtagcaaa gactgctgca 660tcaaaatttg ggacctggct
cagcaggtat cactgaattc ataccgagct cacgctggac 720aggttacctg tgttgctgcc
tctccccaca aagactctgt gtttctttca tgtagtgagg 780acagtagaat tttgctctgg
gatacccgct gtcccaagcc ggcatcacag atggcctgca 840atgcctctgg ctacctccct
accgctttgg cttggcatcc tcagcagagt gaagtctttg 900tttttggtga cgagaatgga
tctgtctccc ttgtggacac caagaatgca agctgtaccc 960tcagctcagc tgtgcactcc
cagggtgtca ctagactggt attctcccca cacaggtgct 1020gtgtgtcacc aggaacttgg
aagggatggg tggggacagt ggtgaaggag taggaatgga 1080gtgacacagg gaggaggtat
ctatttggca aagctgcttc cattggtcct tagctggggc 1140agtactctaa cttggctttc
ccaagcttgt cagtgtagtc tttatttggt ttgtatagtt 1200tgagaagacc taaaatataa
tctcattcct gctcaaagcc tgtgagtctg agtaactgtt 1260gctaatgtag agaaggagcc
attgggctgg tgggctgcta gtgtggtttc tgtgagccct 1320gttccatttt ctttgccttt
ccttgggatt gtaatggtag taagacctaa acctcaagtg 1380gccatcagga tgccttctcc
cctgtctcag tttacagtgg ggtcagggct ggccctgata 1440gattttggtt gtggaatcta
tggactttat cttcttttcc ttttgtgtcc tctcctagtg 1500tccccctcct gacttctctc
agtgaagact gttcacttgc tgtgctggat tcaagccttt 1560ctgaggtgtt tagaagtcga
gcccacagag actttgtgag agatgctacg tggtctccac 1620tcaatcactc ccttcttacc
acagttggct gggaccatca ggtcatccac catgttgtgc 1680ccttagagcc tctcccaaac
cctggacctg acagtgttgt ggagtagaat ggatttcaga 1740aaaaccaaaa caagccctcc
gtctgtaagc gactactcga ttgcccctgc cttccatgtg 1800tgagagcaca ggagccttgt
agagcatgtt tcctccctag ccccgtgcag taacaggcag 1860attctcagcc tgagggaggc
tgcatcccat agtgactcag aggaagaaac ttcctctgta 1920aatggatgta tgtgagtaca
cgtgtgagtg cggtatatag tttggagtgg agaaaattat 1980tcttcagctt tcccaaagca
atgctcttta cccctgacaa agtgaccaga ggattttaat 2040gcttcccatg tctgggaatt
ggcgatgtta gggatatgga atgtgggtat ccctagattt 2100ttgggaatac ttcatactac
tcagaggtgc gtaacttatt tttatataga gtttaattca 2160ctattatggg aattacttcc
atatacaaaa gtctagccca ctgtaccttg agaagacaaa 2220acagttttgt acaagtccct
gttatactga gtcaaatcca ttttctgggt gaataaattt 2280ggccctgcag tgtagctctt
gttcaccctt tccttccttg gtgttgtgtg tgagagatga 2340gtgttttcct gtcctagatt
tcacagataa gttgtaggga tgatggacca cttaaaagtg 2400tttcagtgaa gtgggaaaat
tgacatggat tgttacagag aaatctgtca tttttcccac 2460ctaaaaattg atctgggtac
cttcctctgg agagctgaag tctgaatgta tttttggact 2520cctaagattt gagatccagc
atcagggaaa ctgtcggaaa tactaaaagg tgaaataaag 2580acttttatcc ttga
25941932723DNAMus Musculus
193ggtggggctg agggagggaa acaaacaaaa tcccgctgcg gggacaggag acggaaaagc
60aggctggaag ggtagacaca attctcgcga gaagtagagc gaattccctc ggagaggggc
120ggttgcgcag aggtacacca cgtgtgcggt ccctccggcg ccgagtcagg gtctctcgtc
180gagtctgggt ctaggttaga tttggaatcg tggagatgcg gaaggacacc cctcctccgc
240tcgtgccccc ggcggcccgc gagtggaacc tgccccccaa tgcgcccgca tgcatggaac
300gtcaattgga ggctgcacgg taccggtctg atggttccct tctgctcggg gtctccagcc
360tgagtggtcg ctgctgggta ggttctctgt ggtttttcaa ggatcctagt gcggccccca
420acgaaggttt ctgctctgct ggcgtccaga ccgaggctgg agtagctgac ctcacttggg
480tgggggacaa aggtatccta gtggcttctg attcaggtgc tgttgaattg tgggagctag
540atgagaacga gacacttata gtcagcaagt tctgcaagta tgagcatgat gacattgtgt
600ctactgtcac tgtcctgagc tctggcacac aagctgtcag tggtagcaaa gactgctgca
660tcaaaatttg ggacctggct cagcaggtat cactgaattc ataccgagct cacgctggac
720aggttacctg tgttgctgcc tctccccaca aagactctgt gtttctttca tgtagtgagg
780acagtagaat tttgctctgg gatacccgct gtcccaagcc ggcatcacag atggcctgca
840atgcctctgg ctacctccct accgctttgg cttggcatcc tcagcagagt gaagtctttg
900tttttggtaa ggcagcatga cgtaccgtag actctgggaa tggggaggat gacaaagtgc
960taccttcaat ggagtacatg cccctgtcag cacatgcagg cactgcatga attatgccag
1020tttgaggtag ctatggagag catctttttt tccctagtgg gtttgtttcc tcattgttcc
1080agcttcttta ttctgggcat ggttagaagt cagtgagctg tggagcaagt gcttgctgtt
1140atggaattat gttctgctgt ggtgtgactg catatggtaa gagtttgtag ttaattgtcc
1200cagccacata gtgacttact gattctatac cacaaaggaa actgttgtct acattttgag
1260agactaggat tcattcaaat ccaggtctgg ctcacatcaa agtatggttt ttgttgttgt
1320tttttttttt tttcttcctc aagacagggt ctgtatgaag tttgggctgt cttagaacct
1380gatgagtaga ccaggctgac cttgaactca aagatccttc tgcttcagcc tcccacatac
1440tagaattaaa ggtgtatact atacttagcc aggagcgtga attcttagcc actgtgacgt
1500gctttatttc ttctgcaggt gacgagaatg gatctgtctc ccttgtggac accaagaatg
1560caagctgtac cctcagctca gctgtgcact cccagggtgt cactagactg gtattctccc
1620cacacagtgt ccccctcctg acttctctca gtgaagactg ttcacttgct gtgctggatt
1680caagcctttc tgaggtgttt agaagtcgag cccacagaga ctttgtgaga gatgctacgt
1740ggtctccact caatcactcc cttcttacca cagttggctg ggaccatcag gtcatccacc
1800atgttgtgcc cttagagcct ctcccaaacc ctggacctga cagtgttgtg gagtagaatg
1860gatttcagaa aaaccaaaac aagccctccg tctgtaagcg actactcgat tgcccctgcc
1920ttccatgtgt gagagcacag gagccttgta gagcatgttt cctccctagc cccgtgcagt
1980aacaggcaga ttctcagcct gagggaggct gcatcccata gtgactcaga ggaagaaact
2040tcctctgtaa atggatgtat gtgagtacac gtgtgagtgc ggtatatagt ttggagtgga
2100gaaaattatt cttcagcttt cccaaagcaa tgctctttac ccctgacaaa gtgaccagag
2160gattttaatg cttcccatgt ctgggaattg gcgatgttag ggatatggaa tgtgggtatc
2220cctagatttt tgggaatact tcatactact cagaggtgcg taacttattt ttatatagag
2280tttaattcac tattatggga attacttcca tatacaaaag tctagcccac tgtaccttga
2340gaagacaaaa cagttttgta caagtccctg ttatactgag tcaaatccat tttctgggtg
2400aataaatttg gccctgcagt gtagctcttg ttcacccttt ccttccttgg tgttgtgtgt
2460gagagatgag tgttttcctg tcctagattt cacagataag ttgtagggat gatggaccac
2520ttaaaagtgt ttcagtgaag tgggaaaatt gacatggatt gttacagaga aatctgtcat
2580ttttcccacc taaaaattga tctgggtacc ttcctctgga gagctgaagt ctgaatgtat
2640ttttggactc ctaagatttg agatccagca tcagggaaac tgtcggaaat actaaaaggt
2700gaaataaaga cttttatcct tga
27231942094DNAMus Musculus 194ggtggggctg agggagggaa acaaacaaaa tcccgctgcg
gggacaggag acggaaaagc 60aggctggaag ggtagacaca attctcgcga gaagtagagc
gaattccctc ggagaggggc 120ggttgcgcag aggtacacca cgtgtgcggt ccctccggcg
ccgagtcagg gtctctcgtc 180gagtctgggt ctaggttaga tttggaatcg tggagatgcg
gaaggacacc cctcctccgc 240tcgtgccccc ggcggcccgc gagtggaacc tgccccccaa
tgcgcccgca tgcatggaac 300gtcaattgga ggctgcacgg taccggtctg atggttccct
tctgctcggg gtctccagcc 360tgagtggtcg ctgctgggta ggttctctgt ggtttttcaa
ggatcctagt gcggccccca 420acgaaggttt ctgctctgct ggcgtccaga ccgaggctgg
agtagctgac ctcacttggg 480tgggggacaa aggtatccta gtggcttctg attcaggtgc
tgttgaattg tgggagctag 540atgagaacga gacacttata gtcagcaagt tctgcaagta
tgagcatgat gacattgtgt 600ctactgtcac tgtcctgagc tctggcacac aagctgtcag
tggtagcaaa gactgctgca 660tcaaaatttg ggacctggct cagcaggtat cactgaattc
ataccgagct cacgctggac 720aggttacctg tgttgctgcc tctccccaca aagactctgt
gtttctttca tgtagtgagg 780acagtagaat tttgctctgg gatacccgct gtcccaagcc
ggcatcacag atggcctgca 840atgcctctgg ctacctccct accgctttgg cttggcatcc
tcagcagagt gaagtctttg 900tttttggtga cgagaatgga tctgtctccc ttgtggacac
caagaatgca agctgtaccc 960tcagctcagc tgtgcactcc cagggtgtca ctagactgtg
tccccctcct gacttctctc 1020agtgaagact gttcacttgc tgtgctggat tcaagccttt
ctgaggtgtt tagaagtcga 1080gcccacagag actttgtgag agatgctacg tggtctccac
tcaatcactc ccttcttacc 1140acagttggct gggaccatca ggtcatccac catgttgtgc
ccttagagcc tctcccaaac 1200cctggacctg acagtgttgt ggagtagaat ggatttcaga
aaaaccaaaa caagccctcc 1260gtctgtaagc gactactcga ttgcccctgc cttccatgtg
tgagagcaca ggagccttgt 1320agagcatgtt tcctccctag ccccgtgcag taacaggcag
attctcagcc tgagggaggc 1380tgcatcccat agtgactcag aggaagaaac ttcctctgta
aatggatgta tgtgagtaca 1440cgtgtgagtg cggtatatag tttggagtgg agaaaattat
tcttcagctt tcccaaagca 1500atgctcttta cccctgacaa agtgaccaga ggattttaat
gcttcccatg tctgggaatt 1560ggcgatgtta gggatatgga atgtgggtat ccctagattt
ttgggaatac ttcatactac 1620tcagaggtgc gtaacttatt tttatataga gtttaattca
ctattatggg aattacttcc 1680atatacaaaa gtctagccca ctgtaccttg agaagacaaa
acagttttgt acaagtccct 1740gttatactga gtcaaatcca ttttctgggt gaataaattt
ggccctgcag tgtagctctt 1800gttcaccctt tccttccttg gtgttgtgtg tgagagatga
gtgttttcct gtcctagatt 1860tcacagataa gttgtaggga tgatggacca cttaaaagtg
tttcagtgaa gtgggaaaat 1920tgacatggat tgttacagag aaatctgtca tttttcccac
ctaaaaattg atctgggtac 1980cttcctctgg agagctgaag tctgaatgta tttttggact
cctaagattt gagatccagc 2040atcagggaaa ctgtcggaaa tactaaaagg tgaaataaag
acttttatcc ttga 20941952596DNAMus Musculus 195ggaagtgctc
ctgcggctcc ggttgccggc gtgactttga gctcttcccg ctctgctgcc 60ggcgctgagc
acaaccgatc acctcagagc aggagccttg gaagtggctg ttccaggctt 120gccatgcggc
tgctgcgggt cgccgcagcc ctggggcgtg gaccgttccc tcgggtccct 180gcagtcctgg
gctggcaggg gaagcaggct gattggaaga cccgccgatg gtgttcgtca 240gggccagttc
ccaatgaaaa aatacggaac attgggatct cagctcacat tgattctggg 300aagacgacgc
taacagaacg ggtgctatac tacactggca ggattgccac gatgcacgag 360gtgaaaggta
aagatggagt tggcgctgtc atggattcca tggagctgga gaggcagcga 420gggatcacga
tccagtcagc agctacgtat accatgtgga aagacatcaa tatcaacatc 480atagacacgc
caggccacgt ggactttacc atagaagtgg aaagagccct gcgggtcctg 540gacggtgcag
tccttgttct ctgtgcggtt ggcggagtcc agtgccagac catgacagtc 600agtcgtcaga
tgaagcgcta caacgttccc tttttaacct tcattaacaa actggaccga 660atgggctcta
acccatccag ggccctccaa caaatgagat ctaaactaaa tcacaatgct 720gcatttgtac
aaatacccat tggtttagag ggtgatttta agggaattat agacctcatt 780gaagaacgag
ctatttactt tgatggagac tttggtcaga ttgtccgata tgacgagatt 840ccggctggat
tgcgggccgc agccgctgac caccggcagg agctcattga gtgcgttgct 900aactcagatg
agcagcttgg tgagctcttc ctggaagaaa agatcccctc agtttccgac 960ttaaagcgag
caatccggag agctactctg agtcgatcct tcactcctgt atttttggga 1020agtgctttga
aaaacaaagg agttcaacct cttttggacg ctgttttaga atacctgccc 1080aatccatctg
aggtccagaa ttacgctata ctcaatcaga atgactcaaa agagaagacc 1140aaaatcttaa
tgaaccccca aagagatgat tcgcacccat ttgtaggcct ggcttttaaa 1200ctggaggcgg
gccgttttgg acagctgact tatgtccgaa attatcaagg tgaactgaag 1260aagggaagca
ccatctacaa cacgaggacc gggaagaaag tgcgcgtgca gcggctagtg 1320cgcatgcacg
ccgacatgat ggaggatgtt gaagaagtat atgctggaga catctgtgca 1380ttgtttggca
ttgactgtgc aagtggagat acattcacaa acaaagataa cagtgacctt 1440tctatggaat
cgattcatgt tcctgagcct gtcatttcaa tagcaatgag gccttctaac 1500aagaatgatc
tggagaaatt ttccaaaggt attggcaggt ttacacggga agaccccaca 1560tttaaagtcc
actttgaccc tgagagcaag gagaccattg tgtcagggat gggagagctg 1620cacctggaaa
tctatgctca gagaatggag agagaatatg gctgcccttg tatcacagga 1680aaacccaaag
tagcctttag agagaccatt gttgccccag tgccgtttga ttttacacat 1740aaaaagcagt
cgggtggtgc cggccagttt ggaaaagtaa taggagtgct ggagcccttg 1800cccccagagg
actacacgaa gttggagttt tctgatgaga catttgggtc caatgttcca 1860aagcagtttg
tccccgctgt tgaaaagggg tttctggatg cctgcgaaaa aggccctctt 1920tctggtcaca
agctttctgg gctacggttt gttctgcaag atggagcaca ccacatggtt 1980gattcgaatg
aaatctcttt catccgagct ggagaaggtg ctcttaaaca agccttggca 2040aatggcacac
tatgtattat tgagcctatt atgtctgtgg aagttatagc ccccaatgaa 2100ttccagggaa
cagtgttcgc agggattaac cggcggcatg gagtgattac agggcaggac 2160ggcattgagg
actacttcac actgtatgca gatgttcccc taaataatat gtttggttat 2220tccactgagc
ttaggtcttg cacagaggga aaaggagagt acacgatgga gtactgcagg 2280taccagccgt
gttcaccatc cacacaggaa gagctcatca ataagtattt ggaagctaca 2340ggtcagcttc
ccgtaaaaaa agggaaagcc aagaactgac tctcctcact caggatatac 2400tgactatttg
actaccacac ttggggatga tggagtctgc ttgaatgaat tctgacggca 2460gaaacaaatt
taggagcccc tgctggccca cgttcaggag cttctgtatg tacgccaagg 2520ataactgtgt
atttaaactg tattgactat ttttattgtt tagtaaaaga ccttaaataa 2580aattatatta
ttactg
25961961971DNAMus Musculus 196ggaagtgctc ctgcggctcc ggttgccggc gtgactttga
gctcttcccg ctctgctgcc 60ggcgctgagc acaaccgatc acctcagagc aggagccttg
gaagtggctg ttccaggctt 120gccatgcggc tgctgcgggt cgccgcagcc ctggggcgtg
gaccgttccc tcgggtccct 180gcagtcctgg gctggcaggg gaagcaggct gattggaaga
cccgccgatg gtgttcgtca 240gggccagttc ccaatgaaaa aatacggaac attgggatct
cagctcacat tgattctggg 300aagacgacgc taacagaacg ggtgctatac tacactggca
ggattgccac gatgcacgag 360gtgaaaggta aagatggagt tggcgctgtc atggattcca
tggagctgga gaggcagcga 420gggatcacga tccagtcagc agctacgtat accatgtgga
aagacatcaa tatcaacatc 480atagacacgc caggccacgt ggactttacc atagaagtgg
aaagagccct gcgggtcctg 540gacggtgcag tccttgttct ctgtgcggtt ggcggagtcc
agtgccagac catgacagtc 600agtcgtcaga tgaagcgcta caacgttccc tttttaacct
tcattaacaa actggaccga 660atgggctcta acccatccag ggccctccaa caaatgagat
ctaaactaaa tcacaatgct 720gcatttgtac aaatacccat tggtttagag ggtgatttta
agggaattat agacctcatt 780gaagaacgag ctatttactt tgatggagac tttggtcaga
ttgtccgata tgacgagatt 840ccggctggat tgcgggccgc agccgctgac caccggcagg
agctcattga gtgcgttgct 900aactcagatg agcagcttgg tgagctcttc ctggaagaaa
agatcccctc agtttccgac 960ttaaagcgag caatccggag agctactctg agtcgatcct
tcactcctgt atttttggga 1020agtgctttga aaaacaaagg agttcaacct cttttggacg
ctgttttaga atacctgccc 1080aatccatctg aggtccagaa ttacgctata ctcaatcaga
atgactcaaa agagaagacc 1140aaaatcttaa tgaaccccca aagagatgat tcgcacccat
ttgtaggcct ggcttttaaa 1200ctggaggcgg gccgttttgg acagctgact tatgtccgaa
attatcaagg tgaactgaag 1260aagggaagca ccatctacaa cacgaggacc gggaagaaag
tgcgcgtgca gcggctagtg 1320cgcatgcacg ccgacatgat ggaggatgtt gaagaagtat
atgctggaga catctgtgca 1380ttgtttggca ttgactgtgc aagtggagat acattcacaa
acaaagataa cagtgacctt 1440tctatggaat cgattcatgt tcctgagcct gtcatttcaa
tagcaatgag gccttctaac 1500aagaatgatc tggagaaatt ttccaaaggt attggcaggt
ttacacggga agaccccaca 1560tttaaagtcc actttgaccc tgagagcaag gagaccattg
tgtcagggat gggagagctg 1620cacctggaaa tctatgctca gagaatggag agagaatatg
gctgcccttg tatcacagga 1680aaacccaaag tagcctttag agagaccatt gttgccccag
tgccagtggc atcaaataaa 1740gaaaagttgt atatgttacc tgcgatgcaa tgtcgtggag
tagaatggtg taatctaact 1800caatgaagtc atcgtttctt tgctacaaca acaacaacaa
caacaaaatg cttagacaac 1860atcatggcaa aaatgacatc ttaatttctt ttttgcatta
atgttgattt attcacttca 1920ggttagcctg gcagaaaact agtttcttaa aataataaca
attcttcttt c 19711971001DNAMus Musculus 197agccctgagt
ctggcttgcg ggtggtggga gcagacagtt cttgcctcgg gaccggcaat 60catggcttcg
gcttggccgc ggtctctgcc gcagatcctc gtgttgggat tcggcttggt 120gttgatgcgc
gccgcggccg gggagcaagc accaggcacc tccccatgct ctagcggcag 180ctcctggagc
gcggacctcg acaagtgcat ggactgcgct tcttgtccag cgcgaccaca 240cagcgacttc
tgcctgggat gcgccgcagc acctcctgcc cacttcaggc tactgtggcc 300cattctgggg
ggcgctctta gtctggtcct ggttttggcg ctggtttcta gtttcctggt 360ctggagaaga
tgccgccgga gagaaaagtt tactaccccc atagaggaga ctggtggaga 420gggctgccca
ggtgtggcac tgatccagtg aggagcaccc gcgctggggc ccactcgtcg 480tccattcatt
cattctggag tcagcctggc cttccagaca gaagccgagc cagactcttt 540caaccacaag
ggggtggggc gaggtggtga ttcacctcca aggactgggc ttagagttca 600gggagccttc
caaggtgtcc aattgcccta tctctgggtc tggggcagac agagagcctc 660aatctgggtc
acaaagcgac ccatactaag gaactgcagc atttgcacaa gggaatctct 720tgttccccac
aagtcctggc agtctggctg acttgagggg cagacacaac actgggtccc 780acccactcgg
aggggctata atgccactcc ctgagtttta gccctaggag tgggtcagat 840tgacagacct
gttcttaaca ctaagggggc tggccctctg ggagggctgg ccccagtaca 900cacggaaaca
accatctccc aaggggggtg atatttattg tggggataat gtttggaggg 960gagggagact
tattaataaa agaatcttta actttaagat a
10011981078DNAMus Musculus 198agccctgagt ctggcttgcg ggtggtggga gcagacagtt
cttgcctcgg gaccggcaat 60catggcttcg gcttggccgc ggtctctgcc gcagatcctc
gtgttgggat tcggcttggt 120gttgatgcgc gccgcggccg gggagcaagc accaggcagc
aagttccaag tgggaaaggt 180ctcaagtttt atccgcagtc cgagcttcag tttcgctacc
tgtccaattg aggcacctcc 240ccatgctcta gcggcagctc ctggagcgcg gacctcgaca
agtgcatgga ctgcgcttct 300tgtccagcgc gaccacacag cgacttctgc ctgggatgcg
ccgcagcacc tcctgcccac 360ttcaggctac tgtggcccat tctggggggc gctcttagtc
tggtcctggt tttggcgctg 420gtttctagtt tcctggtctg gagaagatgc cgccggagag
aaaagtttac tacccccata 480gaggagactg gtggagaggg ctgcccaggt gtggcactga
tccagtgagg agcacccgcg 540ctggggccca ctcgtcgtcc attcattcat tctggagtca
gcctggcctt ccagacagaa 600gccgagccag actctttcaa ccacaagggg gtggggcgag
gtggtgattc acctccaagg 660actgggctta gagttcaggg agccttccaa ggtgtccaat
tgccctatct ctgggtctgg 720ggcagacaga gagcctcaat ctgggtcaca aagcgaccca
tactaaggaa ctgcagcatt 780tgcacaaggg aatctcttgt tccccacaag tcctggcagt
ctggctgact tgaggggcag 840acacaacact gggtcccacc cactcggagg ggctataatg
ccactccctg agttttagcc 900ctaggagtgg gtcagattga cagacctgtt cttaacacta
agggggctgg ccctctggga 960gggctggccc cagtacacac ggaaacaacc atctcccaag
gggggtgata tttattgtgg 1020ggataatgtt tggaggggag ggagacttat taataaaaga
atctttaact ttaagata 1078199910DNAMus Musculus 199agccctgagt
ctggcttgcg ggtggtggga gcagacagtt cttgcctcgg gaccggcaat 60catggcttcg
gcttggccgc ggtctctgcc gcagatcctc gtgttgggat tcggcttggt 120gttgatgcgc
gccgcggccg gggagcaagc accaggcacc tccccatgct ctagcggcag 180ctcctggagc
gcggacctcg acaagtgcat ggactgcgct tcttgtccag cgcgaccaca 240cagcgacttc
tgcctgggat tttcctggtc tggagaagat gccgccggag agaaaagttt 300actaccccca
tagaggagac tggtggagag ggctgcccag gtgtggcact gatccagtga 360ggagcacccg
cgctggggcc cactcgtcgt ccattcattc attctggagt cagcctggcc 420ttccagacag
aagccgagcc agactctttc aaccacaagg gggtggggcg aggtggtgat 480tcacctccaa
ggactgggct tagagttcag ggagccttcc aaggtgtcca attgccctat 540ctctgggtct
ggggcagaca gagagcctca atctgggtca caaagcgacc catactaagg 600aactgcagca
tttgcacaag ggaatctctt gttccccaca agtcctggca gtctggctga 660cttgaggggc
agacacaaca ctgggtccca cccactcgga ggggctataa tgccactccc 720tgagttttag
ccctaggagt gggtcagatt gacagacctg ttcttaacac taagggggct 780ggccctctgg
gagggctggc cccagtacac acggaaacaa ccatctccca aggggggtga 840tatttattgt
ggggataatg tttggagggg agggagactt attaataaaa gaatctttaa 900ctttaagata
910200952DNAMus
Musculus 200gacgcacgac acaacctctc gattccggac gtgcctgatg gtggctcttc
tcgttacgcc 60ccaagaccta gcactgcctg tcgcccagca actaaggcgg caggtccgtg
ctgtctcgaa 120ccacagaaac ctaggagaac tacacgaagc acccttatgc taaaaagcgc
ccagaactat 180ccagccacgc cggatcccct cccccaccgc gccgacctgt cccgccttct
aacctctaac 240ctgattcctg tcttccgcgc ctgcgtaaaa cgtctccagt gcgcacgccg
gtaggcccgc 300ccctcgcgct gtaccacgcc ctcaaaggct ccgcctctgc tgcttgaatc
ccacccctct 360atctgcagga ccctgagccg taatgatcct gcaacagccc ctggagcgag
gtcccccaag 420tcgggaccca cgggccacca ctggggtaac tcgcggccta aacgccagtc
tttcccccag 480ggaacctttg cacaagcagt tcctgtctga ggagaacatg gccacccatt
tctcccgact 540cagcctacat aatgaccacc cctactgcag cccccctgtg acttttcccg
aagccctgcc 600accactcagg agcccttgcc cagagctgct tctctggcgc tatcccggga
gcctgattcc 660tgaagccctc aggctgctga ggctggggga tacccccagt ccctactacc
ctgcgtcccc 720agctggggat atcgtggagc tctgagtatt gatggcctgt gtccctccct
atcttctttc 780tgacaacaaa gaccagcaac tcccagaaag ggatgaagtc cttctgcaaa
cctggccacc 840aggaccttcc ctctgacaag aggacactag ctcggtggaa ccctcagtga
aaggcagcct 900gggaaaggga aaatgttacc ccattagtga ataaagacct gtgagcagtt
ga 9522011108DNAMus Musculus 201gggaggaaaa cttcctggct
gggactccgg cggtttctgc ctgccaaccc tcggatcccg 60cctaccagtg ttggctcttc
ccgacccctc ccccggcgcc cccagtgtcc gccatggcca 120aagcctacga ccacctcttc
aagttgctgc tcatcgggga ctcgggggtg ggcaagactt 180gtctgatcat tcgctttgca
gaggacaact tcaacagcac ttacatctct accatcggaa 240ttgatttcaa gatccgaacc
gtggacatag aggggaagag gatcaaactg caagtgtggg 300acacggctgg ccaagaacga
ttcaagacaa taactaccgc ctattaccgt ggagccatgg 360gcattatcct cgtatatgac
atcacagatg agaaatcctt cgagaatatt cagaactgga 420tgaaaagcat caaagagaat
gcctctgcgg gagtggagcg cctcctgctg ggaaacaagt 480gtgacatgga ggccaagcgg
caggtgcaga gagagcaggc ggagaagttg gctcgagagc 540acagaatccg attttttgag
acgagtgcca aatccagtgt gaatgtggat gaggctttca 600gttccctggc ccgtgacatc
ttgctcaaga caggaggccg gagatcggga accaacagta 660agccctcaag cactggcctg
aaaacatctg acaagaagaa gaacaagtgc ttgttaggct 720gagagcattt cttgcctcct
attcaccctg aacctggagg ctagacctga gggagtcgga 780ctgagggatt gcagatggga
gaactgtggt ggcacctcaa ggggagatga ggggaataag 840gagaccggcg aggacgagac
ggaagaaagg ggcagggaaa ggagggggag gaaccaagga 900tgtgaaaggt gaacagaagg
gatttgagaa gaggaaagga agaagaaatg aatggctcag 960gccttggaca gtccaacatt
aaagtcaaca tgctgatctc tccattcctg gttcagggtt 1020agggtcctga gaggctggct
cggcactact ccgagggtcc ctcactctac aaggtctttg 1080ttagtattaa aggccactgt
tttgcatg 11082021037DNAMus Musculus
202gaaagggagg agtagggcag ggccagagga gggacagcct gacgcggcca ccagccctga
60ctcaacctgc cagccccctt acctggccag ccttgaggag atggaacagc ccaggctaca
120aggcctgccc ccactcctca acttcccttg ataatgaacc agaaactgaa actaaaacag
180gcaggctccc cgttagagat gagtcacttc ccaaagtgac tgaagtagcc gagaagtgga
240aacagagggg cagaagagaa cccagggcac tgagacaggg ctttctgagg gtcgccaagg
300agcatggcag gcatcccaga ggtggtggcc atggactgtg agatggtggg gcttgggcct
360caaagggtga gtggcctcgc ccgctgcagc attgtgaaca tccatggcgc agtcctgtat
420gacaagtaca tccgacccga gggagagatc acggactaca gaacccaagt cagcggggtc
480acgcctcagc acatggtgag ggccacgcca tttggtgaag ccaggctaga gatcctgcag
540cttctgaaag gcaagctggt ggtgggccat gacctgaagc acgacttcaa tgccctgaag
600gaggatatga gcaagtacac catctatgac acgtccacag acaggctgct gtggcatgag
660gccaagctgc agtactacag ccgagtgtcc ctgaggctgc tgtgtaagcg cctgctacac
720aagaacatcc agaacaactg gcggggccac tgctctgtgg aagatgccag ggccacaatg
780gagctctaca aaatctctca gcgactcaga gcccagcgag ggctgccttg ccctgggacg
840tcagactgaa cttcatcctc atccagggtt agaagctgcc actcctcaag ttctccatga
900atgagacctg tttctaacaa ccactgccac caaccaccgc aatgtgtaaa accaagaaca
960ctcccccatt acagcaactc tcttgctttg aggcaaaaac aacaacaaca acaacaacaa
1020caacaacagc aaaacca
10372031017DNAMus Musculus 203gaaagggagg agtagggcag ggccagagga gggacagcct
gacgcggcca ccagccctga 60ctcaacctgc cagccccctt acctggccag ccttgaggag
atggaacagc ccaggctaca 120aggcctgccc ccactcctca acttcccttg ataatgaacc
agaaactgaa actaaaacag 180gcaggctccc cgttagagat gagtcacttc ccaaagtgac
tgaagtagcc gagaagtgga 240aacagagggg cagaagagaa cccagggcac tgagacaggg
ctttctgagg gtcgccaagg 300agcatggcag gcatcccaga ggtggtggcc atggactgtg
agatggtggg gcttgggcct 360caaagggtga gtggcctcgc ccgctgcagc attgtgaaca
tccatggcgc agtcctgtat 420gacaagtaca tccgacccga gggagagatc acggactaca
gaacccaagt cagcggggtc 480acgcctcagc acatggtgag ggccacgcca tttggtgaag
ccaggctaga gatcctgcag 540cttctgaaag gcaagctggt ggtgggccat gacctgaagc
acgacttcaa tgccctgaag 600gaggatatga gcaagtacac catctatgac acgtccacag
acaggctgct gtggcatgag 660gccaagctgc agtactacag ccgagtgtcc ctgaggctgc
tgtgtaagcg cctgctacac 720aagaacatcc aggtgaggag tctcccggcc cccatgaccc
ttcttgtctc tctctcttct 780ccctcctccc tctcgttctc cctcttccca ctcagatgct
ctttctcttt ctccttcctc 840tcctactcct ccaagcaagg agttctcctc ctttcttcct
tagtcctccc tctccttcct 900tgcttctaaa agtgagggtc ttcctctccc tcctccccac
actcccactc ctcccaaggg 960cagatcagtc ccacctgcct aagctggctc caggtaagga
acctctgcag cctgctg 10172041164DNAMus Musculus 204agaacccagg
aggaagaaca gcctggcttg aggccctcta aaggtctgct gctgtttgtc 60aactctccca
gggctttctg agggtcgcca aggagcatgg caggcatccc agaggtggtg 120gccatggact
gtgagatggt ggggcttggg cctcaaaggg tgagtggcct cgcccgctgc 180agcattgtga
acatccatgg cgcagtcctg tatgacaagt acatccgacc cgagggagag 240atcacggact
acagaaccca agtcagcggg gtcacgcctc agcacatggt gagggccacg 300ccatttggtg
aagccaggct agagatcctg cagcttctga aaggcaagct ggtggtgggc 360catgacctga
agcacgactt caatgccctg aaggaggata tgagcaagta caccatctat 420gacacgtcca
cagacaggct gctgtggcat gaggccaagc tgcagtacta cagccgagtg 480tccctgaggc
tgctgtgtaa gcgcctgcta cacaagaaca tccaggtcct gcctggcagc 540ctcttggggg
ttggaggatg catcttgcca ggcactgaca tccttcatct tctgctctat 600gtcggaatgg
tcaggattgc tgatctccgc ttgctgacgc cctttctacc tccgagctgc 660ctcgcttgcc
cactgctccc ggagagtctt gcttctgctc gctcgcacgc tgttatttct 720gccctgtcca
gctctagtca cctgctgaca cccctcccaa acccgagtca gggacctcag 780ggacacgtgg
acagactgag cggccagctc caggactggg gaggcagccc cttagctcct 840gctctccctg
tgtctgcaga acaactggcg gggccactgc tctgtggaag atgccagggc 900cacaatggag
ctctacaaaa tctctcagcg actcagagcc cagcgagggc tgccttgccc 960tgggacgtca
gactgaactt catcctcatc cagggttaga agctgccact cctcaagttc 1020tccatgaatg
agacctgttt ctaacaacca ctgccaccaa ccaccgcaat gtgtaaaacc 1080aagaacactc
ccccattaca gcaactctct tgctttgagg caaaaacaac aacaacaaca 1140acaacaacaa
caacagcaaa acca
11642052224DNAMus Musculus 205agcgaccggc aggctgcccg cccgacttcc cagctgcccc
gtgcggcccg ggcatgccca 60gtgtgggcgc agccccggct ctccgagcgc ccgggcggag
cgggcagccg ggcgcggagc 120aggcgaaccg agcctcggtg ggcgagcgcc ctggctggag
ccgcggcggt agggtggcgg 180ggccctccat gatgaatggt ttgggggcac ttccctctcg
ctgtatttga tagtctgggc 240agtggagaga tggctgacag tgtcaaaacc tttctgcagg
accttggcag gggaatcaaa 300gactccatct ggggcatctg taccatctca aagctagatg
ctcggatcca gcagaagaga 360gaggaacagc gtcgaagaag ggcaagtagc ctcttggccc
agaggagacc ccagagtgta 420gagcggaagc aagagagtga accacgtatt gttagtagaa
ttttccagtg ttgtgcttgg 480aatggtggag tattctggtt cagtctcctc ttgttttatc
gagtgtttat tcctgtactt 540cagtcagtaa cagcccggat tattggagat ccatcacttc
atggagatgt ttggtcatgg 600ctggaattct tcctcacatc aattttcagt gctctttggg
tgctccccct gtttgtgctt 660agcaaagttg tgaatgccat ttggttccaa gatatagctg
acttggcatt tgaagtatca 720gggaggaaac ctcatccatt ccccagtgtc agcaaaataa
ttgctgacat gctcttcaac 780cttttgctac aggcactttt ccttattcag gggatgtttg
tgagtctctt ccccatccat 840cttgtgggtc agctggttag tctgctgcat atgtctcttc
tctattcact gtactgcttt 900gagtaccgtt ggttcaacaa aggaattgaa atgcaccagc
gattgtcgaa catagaaagg 960aattggcctt actactttgg gtttggcttg cccttggctt
tcctcacagc aatgcaatcc 1020tcctacatta tcagtggctg cctcttttct atcctgtttc
ctttattcat catcagcgcc 1080aatgaagcaa agactcctgg aaaagcatat cttttccagt
tgcgcctatt ctccttggtg 1140gtctttttaa gcaacagact tttccacaag accgtctacc
tgcagtcagc cctgagcagc 1200tcgtcctctg cagagaaatt cccttcgcca catccttctc
ctgccaaact gaaagctgct 1260gcaggccact gagccctgct gtcaaagggg tgggtgggac
tgggtggagg atgtggcagc 1320tcttttctct gttttcctcc ccctgccgtg gaaggcagaa
cccactgcca agggccctct 1380gcatagtccc ttgtctttga attggaatct tcctgactcc
agtatatgga tttttaccac 1440caccctaggt ctgtaaggac cagagttttc cagctgtttt
tttagcactt gccagctcct 1500gtgcctggac tgattgattt gagtactttt ttcccccttt
ccttgtgtca tttaccctcc 1560cacttcctcc tgccttccag cacccctgga tgaatgggct
ttgtaatttt aactgttgta 1620ttttgtgaat ttgttgttac tgtttttctg tgaagcacat
acattgtatg tgggaggtaa 1680aggggcattc cagttgctcc agtcactccc tctatagcca
tcactgtctt gttttctgta 1740actcaggtta ggttttggtc tctattgctc tgctgcagaa
aaggaaagaa aggagtgggg 1800gaaatggagc ctgaagagtt ggggcagata gacctcagcc
aaactggctg ggttttgagg 1860agtcatgttc tttcttcccc ttgaagggga aagagttttt
tccactggtc catttaaagt 1920ttcccagcta tggggtggta ccagttctgg acaagtgcca
ctgcatcata gtatgctcgg 1980agaatctgaa ccttactctg aagatgaaat ttactgttgg
ccactgccag gtcagactgg 2040tgttttaagg aatactgggt gcttcatata ggaactgaag
gggtaaactt actaaaccat 2100tcaacctgtg attggtgatg ttttcctgtc attttaagag
tcgacacatg ggtggggggg 2160cagatgtaaa aaaacttgta caattttaaa atatcacaat
taaacgtgag ctggtttccc 2220aaaa
22242062144DNAMus Musculus 206agcgaccggc aggctgcccg
cccgacttcc cagctgcccc gtgcggcccg ggcatgccca 60gtgtgggcgc agccccggct
ctccgagcgc ccgggcggag cgggcagccg ggcgcggagc 120aggcgaaccg agcctcggtg
ggcgagcgcc ctggctggag ccgcggcggt agggtggcgg 180ggccctccat gatgaatggt
ttgggggcac ttccctctcg ctgtatttga tagtctgggc 240agtggagaga tggctgacag
tgtcaaaacc tttctgcagg accttggcag gggaatcaaa 300gactccatct ggggcatctg
taccatctca aagctagatg ctcggatcca gcagaagaga 360gaggaacagc gtcgaagaag
ggcaagtagc ctcttggccc agaggagacc ccagagtgta 420gagcggaagc aagagagtga
accacgtatt gttagtagaa ttttccagtg ttgtgcttgg 480aatggtggag tattctggtt
cagtctcctc ttgttttatc gagtgtttat tcctgtactt 540cagtcagtaa cagcccggat
tattggagat ccatcacttc atggagatgt ttggtcatgg 600ctggaattct tcctcacatc
aattttcagt gctctttggg tgctccccct gtttgtgctt 660agcaaagttg tgaatgccat
ttggttccaa gatatagctg acttggcatt tgaagtatca 720gggaggaaac ctcatccatt
ccccagtgtc agcaaaataa ttgctgacat gctcttcaac 780cttttgctac aggcactttt
ccttattcag gggatgtttg tgagtctctt ccccatccat 840cttgtgggtc agctggttag
tctgctgcat atgtctcttc tctattcact gtactgcttt 900gagtaccgtt ggttcaacaa
aggaattgaa atgcaccagc gattgtcgaa catagaaagg 960aattggcctt actactttgg
gtttggcttg cccttggctt tcctcacagc aatgcaatcc 1020tcctacatta tcagtggctg
cctcttttct atcctgtttc ctttattcat catcagcgcc 1080aatgaagcaa agactcctgg
aaaagcatat cttttccagt tgcgcctatt ctccttggtg 1140gtctttttaa gcaacagact
tttccacaag accgtctacc tgcagccact gagccctgct 1200gtcaaagggg tgggtgggac
tgggtggagg atgtggcagc tcttttctct gttttcctcc 1260ccctgccgtg gaaggcagaa
cccactgcca agggccctct gcatagtccc ttgtctttga 1320attggaatct tcctgactcc
agtatatgga tttttaccac caccctaggt ctgtaaggac 1380cagagttttc cagctgtttt
tttagcactt gccagctcct gtgcctggac tgattgattt 1440gagtactttt ttcccccttt
ccttgtgtca tttaccctcc cacttcctcc tgccttccag 1500cacccctgga tgaatgggct
ttgtaatttt aactgttgta ttttgtgaat ttgttgttac 1560tgtttttctg tgaagcacat
acattgtatg tgggaggtaa aggggcattc cagttgctcc 1620agtcactccc tctatagcca
tcactgtctt gttttctgta actcaggtta ggttttggtc 1680tctattgctc tgctgcagaa
aaggaaagaa aggagtgggg gaaatggagc ctgaagagtt 1740ggggcagata gacctcagcc
aaactggctg ggttttgagg agtcatgttc tttcttcccc 1800ttgaagggga aagagttttt
tccactggtc catttaaagt ttcccagcta tggggtggta 1860ccagttctgg acaagtgcca
ctgcatcata gtatgctcgg agaatctgaa ccttactctg 1920aagatgaaat ttactgttgg
ccactgccag gtcagactgg tgttttaagg aatactgggt 1980gcttcatata ggaactgaag
gggtaaactt actaaaccat tcaacctgtg attggtgatg 2040ttttcctgtc attttaagag
tcgacacatg ggtggggggg cagatgtaaa aaaacttgta 2100caattttaaa atatcacaat
taaacgtgag ctggtttccc aaaa 21442072507DNAMus Musculus
207agcgaccggc aggctgcccg cccgacttcc cagctgcccc gtgcggcccg ggcatgccca
60gtgtgggcgc agccccggct ctccgagcgc ccgggcggag cgggcagccg ggcgcggagc
120aggcgaaccg agcctcggtg ggcgagcgcc ctggctggag ccgcggcggt agggtggcgg
180ggccctccat gatgaatggt ttgggggcac ttccctctcg ctgtatttga tagtctgggc
240agtggagaga tggctgacag tgtcaaaacc tttctgcagg accttggcag gggaatcaaa
300gactccatct ggggcatctg taccatctca aagctagatg ctcggatcca gcagaagaga
360gaggaacagc gtcgaagaag ggcaagtagc ctcttggccc agaggagacc ccagagtgta
420gagcggaagc aagagagtga accacgtatt gttagtagaa ttttccagtg ttgtgcttgg
480aatggtggag tattctggtt cagtctcctc ttgttttatc gagtgtttat tcctgtactt
540cagtcagtaa cagcccggat tattggagat ccatcacttc atggagatgt ttggtcatgg
600ctggaattct tcctcacatc aattttcagt gctctttggg tgctccccct gtttgtgctt
660agcaaagttg tgaatgccat ttggttccaa gtaggtgcag gacaaaatgg aactgggttc
720tacatgctgg gttgactagg ttacacattt tagcctatga agttagtggc ctataaaact
780taatccttaa cgtttttaag ccaagcagtc aggtaatatt tgtggttttg taaaatgaaa
840ttactgtctt gggttactga gacagacttt tctcacctgg cagttctagc agcaaaccag
900tggccttaac tctggggatg aacactggga ttatttaatc catattttgc tatattattg
960ttctttgttt caggatatag ctgacttggc atttgaagta tcagggagga aacctcatcc
1020attccccagt gtcagcaaaa taattgctga catgctcttc aaccttttgc tacaggcact
1080tttccttatt caggggatgt ttgtgagtct cttccccatc catcttgtgg gtcagctggt
1140tagtctgctg catatgtctc ttctctattc actgtactgc tttgagtacc gttggttcaa
1200caaaggaatt gaaatgcacc agcgattgtc gaacatagaa aggaattggc cttactactt
1260tgggtttggc ttgcccttgg ctttcctcac agcaatgcaa tcctcctaca ttatcagtgg
1320ctgcctcttt tctatcctgt ttcctttatt catcatcagc gccaatgaag caaagactcc
1380tggaaaagca tatcttttcc agttgcgcct attctccttg gtggtctttt taagcaacag
1440acttttccac aagaccgtct acctgcagtc agccctgagc agctcgtcct ctgcagagaa
1500attcccttcg ccacatcctt ctcctgccaa actgaaagct gctgcaggcc actgagccct
1560gctgtcaaag gggtgggtgg gactgggtgg aggatgtggc agctcttttc tctgttttcc
1620tccccctgcc gtggaaggca gaacccactg ccaagggccc tctgcatagt cccttgtctt
1680tgaattggaa tcttcctgac tccagtatat ggatttttac caccacccta ggtctgtaag
1740gaccagagtt ttccagctgt ttttttagca cttgccagct cctgtgcctg gactgattga
1800tttgagtact tttttccccc tttccttgtg tcatttaccc tcccacttcc tcctgccttc
1860cagcacccct ggatgaatgg gctttgtaat tttaactgtt gtattttgtg aatttgttgt
1920tactgttttt ctgtgaagca catacattgt atgtgggagg taaaggggca ttccagttgc
1980tccagtcact ccctctatag ccatcactgt cttgttttct gtaactcagg ttaggttttg
2040gtctctattg ctctgctgca gaaaaggaaa gaaaggagtg ggggaaatgg agcctgaaga
2100gttggggcag atagacctca gccaaactgg ctgggttttg aggagtcatg ttctttcttc
2160cccttgaagg ggaaagagtt ttttccactg gtccatttaa agtttcccag ctatggggtg
2220gtaccagttc tggacaagtg ccactgcatc atagtatgct cggagaatct gaaccttact
2280ctgaagatga aatttactgt tggccactgc caggtcagac tggtgtttta aggaatactg
2340ggtgcttcat ataggaactg aaggggtaaa cttactaaac cattcaacct gtgattggtg
2400atgttttcct gtcattttaa gagtcgacac atgggtgggg gggcagatgt aaaaaaactt
2460gtacaatttt aaaatatcac aattaaacgt gagctggttt cccaaaa
2507208181PRTMus Musculus 208Met Met Leu Gln His Pro Gly Gln Val Ser Ala
Ser Glu Val Ser Ala 1 5 10
15 Thr Ala Ile Val Pro Cys Leu Ser Pro Pro Gly Ser Leu Val Phe Glu
20 25 30 Asp Phe
Ala Asn Leu Thr Pro Phe Val Lys Glu Glu Leu Arg Phe Ala 35
40 45 Ile Gln Asn Lys His Leu Cys
His Arg Met Ser Ser Ala Leu Glu Ser 50 55
60 Val Thr Val Asn Asn Arg Pro Leu Glu Met Ser Val
Thr Lys Ser Glu 65 70 75
80 Ala Ala Pro Glu Glu Asp Glu Arg Lys Arg Arg Arg Arg Glu Arg Asn
85 90 95 Lys Ile Ala
Ala Ala Lys Cys Arg Asn Lys Lys Lys Glu Lys Thr Glu 100
105 110 Cys Leu Gln Lys Glu Ser Glu Lys
Leu Glu Ser Val Asn Ala Glu Leu 115 120
125 Lys Ala Gln Ile Glu Glu Leu Lys Asn Glu Lys Gln His
Leu Ile Tyr 130 135 140
Met Leu Asn Leu His Arg Pro Thr Cys Ile Val Arg Ala Gln Asn Gly 145
150 155 160 Arg Thr Pro Glu
Asp Glu Arg Asn Leu Phe Ile Gln Gln Ile Lys Glu 165
170 175 Gly Thr Leu Gln Ser 180
209971PRTMus Musculus 209Met Asp Ser Ala Glu Thr Glu Leu Thr Pro Ala
Pro Glu Gly Arg Lys 1 5 10
15 Arg Tyr Ser Asp Ile Phe Gln Ser Leu Asp Asn Leu Glu Ile Ser Leu
20 25 30 Gly Asn
Val Thr Phe Asp Pro Leu Ala Gly Asp Pro Val Arg Arg Glu 35
40 45 Asp Leu Glu Pro Asp Lys Ala
Asp Thr Ala Thr Val Val Thr Glu Glu 50 55
60 Asn Ser Glu Ala Ser Ser Trp Arg Asp Leu Ser Pro
Glu Gly Pro Ala 65 70 75
80 Pro Leu Thr Glu Glu Glu Leu Asp Leu Arg Leu Ile Arg Thr Lys Gly
85 90 95 Gly Val Asp
Ala Ala Leu Glu Tyr Ala Lys Ala Trp Ser Arg Tyr Ala 100
105 110 Lys Glu Leu Leu Ala Trp Thr Asp
Lys Arg Ala Asn Tyr Glu Leu Glu 115 120
125 Phe Ala Lys Ser Ile Met Lys Leu Ala Glu Ala Gly Lys
Val Ser Ile 130 135 140
Leu Gln Gln Ser Gln Met Pro Leu Gln Tyr Ile Tyr Thr Leu Phe Leu 145
150 155 160 Glu His Asp Leu
Ser Leu Gly Ala Leu Ala Leu Glu Thr Val Ala Gln 165
170 175 Gln Lys Arg Asp Tyr Tyr Gln Pro Leu
Ala Ala Lys Arg Met Glu Ile 180 185
190 Glu Lys Trp Arg Lys Glu Phe Lys Glu Gln Trp Leu Lys Glu
Gln Lys 195 200 205
Arg Met Asn Glu Ala Val Gln Ala Leu Arg Arg Ser Glu Leu Gln Tyr 210
215 220 Ile Gln Arg Arg Glu
Asp Leu Arg Ala Arg Ser Gln Gly Ser Pro Glu 225 230
235 240 Asp Pro Pro Ser Gln Ala Ser Pro Gly Ser
Asn Lys Gln Gln Glu Arg 245 250
255 Arg Arg Arg Ser Arg Glu Glu Ala Gln Ala Lys Ala His Glu Ala
Glu 260 265 270 Ala
Leu Tyr Gln Ala Cys Val Arg Glu Ala Asn Ser Arg Gln Gln Asp 275
280 285 Leu Glu Thr Thr Lys Arg
Arg Ile Val Ser His Val Arg Lys Leu Val 290 295
300 Leu Gln Gly Asp Glu Val Leu Arg Arg Val Thr
Leu Gly Leu Phe Glu 305 310 315
320 Leu Arg Gly Ala Gln Ala Glu Arg Gly Pro Arg Ser Phe Ser Ala Leu
325 330 335 Ala Glu
Cys Cys Val Pro Phe Glu Pro Gly Gln Arg Tyr Gln Glu Phe 340
345 350 Val Arg Thr Leu Gln Pro Gly
Ala Pro Pro Pro Pro Ser Pro Ala Phe 355 360
365 Cys Phe Gln Glu Phe Thr Ala Val Val His Ser Phe
Pro Gln Asp Thr 370 375 380
Lys Lys Lys Phe Ser Gly Pro Leu Pro Pro Arg Leu Glu Glu Glu Gly 385
390 395 400 Ser Pro Glu
Pro Gly Pro Trp Glu Val Ala Ser Leu Gly Ser Gln Gly 405
410 415 Ile Pro Gly Ser Asp Val Asp Ser
Val Gly Gly Gly Ser Glu Ser Arg 420 425
430 Ser Leu Asp Ser Pro Thr Ser Ser Pro Gly Ala Gly Ala
Arg Arg Leu 435 440 445
Val Lys Ala Ser Ser Thr Gly Thr Glu Ser Ser Asp Asp Phe Glu Glu 450
455 460 Arg Asp Pro Asp
Leu Gly Asp Gly Ile Glu Asn Gly Val Gly Ser Pro 465 470
475 480 Phe Arg Lys Trp Thr Leu Ser Thr Ala
Ala Gln Thr His Arg Leu Arg 485 490
495 Arg Leu Arg Gly Pro Ala Lys Cys Arg Glu Cys Glu Ala Phe
Met Val 500 505 510
Ser Gly Thr Glu Cys Glu Glu Cys Phe Leu Thr Cys His Lys Arg Cys
515 520 525 Leu Glu Thr Leu
Leu Ile Leu Cys Gly His Arg Arg Leu Pro Ala Arg 530
535 540 Met Ser Leu Phe Gly Val Asp Phe
Leu Gln Leu Pro Arg Asp Phe Pro 545 550
555 560 Glu Glu Val Pro Phe Val Ile Thr Arg Cys Thr Ala
Glu Ile Glu His 565 570
575 Arg Ala Leu Gly Leu Gln Gly Ile Tyr Arg Val Ser Gly Ser Arg Val
580 585 590 Arg Val Glu
Arg Leu Cys Gln Ala Phe Glu Asn Gly Arg Ala Leu Val 595
600 605 Glu Leu Ser Gly Asn Ser Pro His
Asp Ile Thr Ser Val Leu Lys Arg 610 615
620 Phe Leu Gln Glu Leu Thr Asp Pro Val Val Pro Phe His
Leu Tyr Asp 625 630 635
640 Ala Phe Ile Ser Leu Ala Lys Thr Leu His Ala Asp Pro Gly Asp Asp
645 650 655 Pro Gly Thr Pro
Asn Pro Ser Pro Glu Ile Ile Arg Ser Leu Lys Thr 660
665 670 Leu Leu Val Gln Leu Pro Asp Ser Asn
Tyr Ser Thr Leu Arg His Leu 675 680
685 Val Ala His Leu Phe Arg Val Ala Ala Arg Phe Glu Glu Asn
Lys Met 690 695 700
Ser Ala Asn Asn Leu Gly Ile Val Phe Gly Pro Thr Leu Leu Arg Pro 705
710 715 720 Pro Asp Gly Pro Arg
Ala Thr Gly Ala Ser Pro Val Ala Cys Leu Leu 725
730 735 Asp Ser Gly His Gln Ala Gln Leu Val Glu
Phe Leu Ile Val His Tyr 740 745
750 Glu Gln Ile Phe Gly Met Asp Glu Leu Pro Leu Ala Ser Glu Pro
Leu 755 760 765 Thr
Gln Asp Pro Gly Leu Ala Pro Ala Cys Leu Glu Ser Ser Pro Gln 770
775 780 His Pro Ala Ser Leu Leu
Ala Gln Asp Thr Gln Pro Leu Thr Ile Ala 785 790
795 800 Leu Asp Ser Ser Pro Asp Pro Lys His His Ser
Ala Leu Glu Lys Cys 805 810
815 Pro Glu Val Thr Pro Pro Glu Leu Ala Thr Leu Gln Arg Asp Gln Arg
820 825 830 Glu Glu
Glu Val Glu Asp Thr Arg Asp Gly Ala Gly Asp Gly Ser Ser 835
840 845 His Cys Pro Glu Asp Leu Ala
Leu Gly Ala Gln Ser Arg Gly His Phe 850 855
860 Ser Arg Gln Pro Val Lys Tyr Ser Arg Gly Gly Val
Arg Pro Val Thr 865 870 875
880 His Gln Leu Ser Ser Leu Ala Leu Val Ala Ser Lys Leu Cys Glu Glu
885 890 895 Thr Pro Val
Thr Val Ser Ala Val His Arg Gly Ser Leu Arg Val Arg 900
905 910 Gly Leu Gly Pro Ala Ala Ala Cys
Pro Glu Gly Ser Pro Leu Arg Arg 915 920
925 Asn Pro Leu Pro Lys His Phe Glu Ile Thr Gln Glu Thr
Ala Arg Leu 930 935 940
Leu Ser Lys Leu Asn Ser Asp Ala Val Ser Arg Thr Thr Cys Cys Ala 945
950 955 960 Asp Pro Glu Pro
Glu Glu Ser Glu Glu His Leu 965 970
210408PRTMus Musculus 210Met Asp Ser Ala Glu Thr Glu Leu Thr Pro Ala Pro
Glu Gly Arg Lys 1 5 10
15 Arg Tyr Ser Asp Ile Phe Gln Ser Leu Asp Asn Leu Glu Ile Ser Leu
20 25 30 Gly Asn Val
Thr Phe Asp Pro Leu Ala Gly Asp Pro Val Arg Arg Glu 35
40 45 Asp Leu Glu Pro Asp Lys Ala Asp
Thr Ala Thr Val Val Thr Glu Glu 50 55
60 Asn Ser Glu Ala Ser Ser Trp Arg Asp Leu Ser Pro Glu
Gly Pro Ala 65 70 75
80 Pro Leu Thr Glu Glu Glu Leu Asp Leu Arg Leu Ile Arg Thr Lys Gly
85 90 95 Gly Val Asp Ala
Ala Leu Glu Tyr Ala Lys Ala Trp Ser Arg Tyr Ala 100
105 110 Lys Glu Leu Leu Ala Trp Thr Asp Lys
Arg Ala Asn Tyr Glu Leu Glu 115 120
125 Phe Ala Lys Ser Ile Met Lys Leu Ala Glu Ala Gly Lys Val
Ser Ile 130 135 140
Leu Gln Gln Ser Gln Met Pro Leu Gln Tyr Ile Tyr Thr Leu Phe Leu 145
150 155 160 Glu His Asp Leu Ser
Leu Gly Ala Leu Ala Leu Glu Thr Val Ala Gln 165
170 175 Gln Lys Arg Asp Tyr Tyr Gln Pro Leu Ala
Ala Lys Arg Met Glu Ile 180 185
190 Glu Lys Trp Arg Lys Glu Phe Lys Glu Gln Trp Leu Lys Glu Gln
Lys 195 200 205 Arg
Met Asn Glu Ala Val Gln Ala Leu Arg Arg Ser Glu Leu Gln Tyr 210
215 220 Ile Gln Arg Arg Glu Asp
Leu Arg Ala Arg Ser Gln Gly Ser Pro Glu 225 230
235 240 Asp Pro Pro Ser Gln Ala Ser Pro Gly Ser Asn
Lys Gln Gln Glu Arg 245 250
255 Arg Arg Arg Ser Arg Glu Glu Ala Gln Ala Lys Ala His Glu Ala Glu
260 265 270 Ala Leu
Tyr Gln Ala Cys Val Arg Glu Ala Asn Ser Arg Gln Gln Asp 275
280 285 Leu Glu Thr Thr Lys Arg Arg
Ile Val Ser His Val Arg Lys Leu Val 290 295
300 Leu Gln Gly Asp Glu Val Leu Arg Arg Val Thr Leu
Gly Leu Phe Glu 305 310 315
320 Leu Arg Gly Ala Gln Ala Glu Arg Gly Pro Arg Ser Phe Ser Ala Leu
325 330 335 Ala Glu Cys
Cys Val Pro Phe Glu Pro Gly Gln Arg Tyr Gln Glu Phe 340
345 350 Val Arg Thr Leu Gln Pro Gly Ala
Pro Pro Pro Pro Ser Pro Ala Phe 355 360
365 Cys Phe Gln Glu Phe Thr Ala Val Val His Arg Thr Gln
Lys Arg Ser 370 375 380
Phe Arg Gly Leu Tyr Leu Gln Gly Trp Arg Arg Arg Val Pro Leu Ser 385
390 395 400 Leu Ala Leu Gly
Arg Leu Pro Ala 405 211846PRTMus Musculus
211Met Asp Ser Ala Glu Thr Glu Leu Thr Pro Ala Pro Glu Gly Arg Lys 1
5 10 15 Arg Tyr Ser Asp
Ile Phe Gln Ser Leu Asp Asn Leu Glu Ile Ser Leu 20
25 30 Gly Asn Val Thr Phe Asp Pro Leu Ala
Gly Asp Pro Val Arg Arg Glu 35 40
45 Asp Leu Glu Pro Asp Lys Ala Asp Thr Ala Thr Val Val Thr
Glu Glu 50 55 60
Asn Ser Glu Ala Ser Ser Trp Arg Asp Leu Ser Pro Glu Gly Pro Ala 65
70 75 80 Pro Leu Thr Glu Glu
Glu Leu Asp Leu Arg Leu Ile Arg Thr Lys Gly 85
90 95 Gly Val Asp Ala Ala Leu Glu Tyr Ala Lys
Ala Trp Ser Arg Tyr Ala 100 105
110 Lys Glu Leu Leu Ala Trp Thr Asp Lys Arg Ala Asn Tyr Glu Leu
Glu 115 120 125 Phe
Ala Lys Ser Ile Met Lys Leu Ala Glu Ala Gly Lys Val Ser Ile 130
135 140 Leu Gln Gln Ser Gln Met
Pro Leu Gln Tyr Ile Tyr Thr Leu Phe Leu 145 150
155 160 Glu His Asp Leu Ser Leu Gly Ala Leu Ala Leu
Glu Thr Val Ala Gln 165 170
175 Gln Lys Arg Asp Tyr Tyr Gln Pro Leu Ala Ala Lys Arg Met Glu Ile
180 185 190 Glu Lys
Trp Arg Lys Glu Phe Lys Glu Gln Trp Leu Lys Glu Gln Lys 195
200 205 Arg Met Asn Glu Ala Val Gln
Ala Leu Arg Arg Ser Glu Leu Gln Tyr 210 215
220 Ile Gln Arg Arg Glu Asp Leu Arg Ala Arg Ser Gln
Gly Ser Pro Glu 225 230 235
240 Asp Pro Pro Ser Gln Ala Ser Pro Gly Ser Asn Lys Gln Gln Glu Arg
245 250 255 Arg Arg Arg
Ser Arg Glu Glu Ala Gln Ala Lys Ala His Glu Ala Glu 260
265 270 Ala Leu Tyr Gln Ala Cys Val Arg
Glu Ala Asn Ser Arg Gln Gln Asp 275 280
285 Leu Glu Thr Thr Lys Arg Arg Ile Val Ser His Val Arg
Lys Leu Val 290 295 300
Leu Gln Gly Asp Glu Val Leu Arg Arg Val Thr Leu Gly Leu Phe Glu 305
310 315 320 Leu Arg Gly Ala
Gln Ala Glu Arg Gly Pro Arg Ser Phe Ser Ala Leu 325
330 335 Ala Glu Cys Cys Val Pro Phe Glu Pro
Gly Gln Arg Tyr Gln Glu Phe 340 345
350 Val Arg Thr Leu Gln Pro Gly Ala Pro Pro Pro Pro Ser Pro
Ala Phe 355 360 365
Cys Phe Gln Glu Phe Thr Ala Val Val His Ser Phe Pro Gln Asp Thr 370
375 380 Lys Lys Lys Phe Ser
Gly Pro Leu Pro Pro Arg Leu Glu Glu Glu Gly 385 390
395 400 Ser Pro Glu Pro Gly Pro Trp Glu Val Ala
Ser Leu Gly Ser Gln Gly 405 410
415 Ile Pro Gly Ser Asp Val Asp Ser Val Gly Gly Gly Ser Glu Ser
Arg 420 425 430 Ser
Leu Asp Ser Pro Thr Ser Ser Pro Gly Ala Gly Ala Arg Arg Leu 435
440 445 Val Lys Ala Ser Ser Thr
Gly Thr Glu Ser Ser Asp Asp Phe Glu Glu 450 455
460 Arg Asp Pro Asp Leu Gly Asp Gly Ile Glu Asn
Gly Val Gly Ser Pro 465 470 475
480 Phe Arg Lys Trp Thr Leu Ser Thr Ala Ala Gln Thr His Arg Leu Arg
485 490 495 Arg Leu
Arg Gly Pro Ala Lys Cys Arg Glu Cys Glu Ala Phe Met Val 500
505 510 Ser Gly Thr Glu Cys Glu Glu
Cys Phe Leu Thr Cys His Lys Arg Cys 515 520
525 Leu Glu Thr Leu Leu Ile Leu Cys Gly His Arg Arg
Leu Pro Ala Arg 530 535 540
Met Ser Leu Phe Gly Val Asp Phe Leu Gln Leu Pro Arg Asp Phe Pro 545
550 555 560 Glu Glu Val
Pro Phe Val Ile Thr Arg Cys Thr Ala Glu Ile Glu His 565
570 575 Arg Ala Leu Gly Leu Gln Gly Ile
Tyr Arg Val Ser Gly Ser Arg Val 580 585
590 Arg Val Glu Arg Leu Cys Gln Ala Phe Glu Asn Gly Arg
Ala Leu Val 595 600 605
Glu Leu Ser Gly Asn Ser Pro His Asp Ile Thr Ser Val Leu Lys Arg 610
615 620 Phe Leu Gln Glu
Leu Thr Asp Pro Val Val Pro Phe His Leu Tyr Asp 625 630
635 640 Ala Phe Ile Ser Leu Ala Lys Thr Leu
His Ala Asp Pro Gly Asp Asp 645 650
655 Pro Gly Thr Pro Asn Pro Ser Pro Glu Ile Ile Arg Ser Leu
Lys Thr 660 665 670
Leu Leu Val Gln Leu Pro Asp Ser Asn Tyr Ser Thr Leu Arg His Leu
675 680 685 Val Ala His Leu
Phe Arg Val Ala Ala Arg Phe Glu Glu Asn Lys Met 690
695 700 Ser Ala Asn Asn Leu Gly Ile Val
Phe Gly Pro Thr Leu Leu Arg Pro 705 710
715 720 Pro Asp Gly Pro Arg Ala Thr Gly Ala Ser Pro Val
Ala Cys Leu Leu 725 730
735 Asp Ser Gly His Gln Ala Gln Leu Val Glu Phe Leu Ile Val His Tyr
740 745 750 Glu Gln Ile
Phe Gly Met Asp Glu Leu Pro Leu Ala Ser Glu Pro Leu 755
760 765 Thr Gln Asp Pro Gly Leu Ala Pro
Ala Cys Leu Glu Ser Ser Pro Gln 770 775
780 His Pro Ala Ser Leu Leu Ala Gln Asp Thr Gln Pro Leu
Thr Ile Ala 785 790 795
800 Leu Asp Ser Ser Pro Asp Pro Lys His His Ser Ala Leu Glu Lys Cys
805 810 815 Pro Glu Val Thr
Pro Pro Glu Gly Pro Ala Thr Ala Leu Arg Thr Trp 820
825 830 Pro Trp Glu His Asn Pro Gly Ala Thr
Ser Ala Ala Ser Gln 835 840 845
212843PRTMus Musculus 212Met Asp Ser Ala Glu Thr Glu Leu Thr Pro Ala
Pro Glu Gly Arg Lys 1 5 10
15 Arg Tyr Ser Asp Ile Phe Gln Ser Leu Asp Asn Leu Glu Ile Ser Leu
20 25 30 Gly Asn
Val Thr Phe Asp Pro Leu Ala Gly Asp Pro Val Arg Arg Glu 35
40 45 Asp Leu Glu Pro Asp Lys Ala
Asp Thr Ala Thr Val Val Thr Glu Glu 50 55
60 Asn Ser Glu Ala Ser Ser Trp Arg Asp Leu Ser Pro
Glu Gly Pro Ala 65 70 75
80 Pro Leu Thr Glu Glu Glu Leu Asp Leu Arg Leu Ile Arg Thr Lys Gly
85 90 95 Gly Val Asp
Ala Ala Leu Glu Tyr Ala Lys Ala Trp Ser Arg Tyr Ala 100
105 110 Lys Glu Leu Leu Ala Trp Thr Asp
Lys Arg Ala Asn Tyr Glu Leu Glu 115 120
125 Phe Ala Lys Ser Ile Met Lys Leu Ala Glu Ala Gly Lys
Val Ser Ile 130 135 140
Leu Gln Gln Ser Gln Met Pro Leu Gln Tyr Ile Tyr Thr Leu Phe Leu 145
150 155 160 Glu His Asp Leu
Ser Leu Gly Ala Leu Ala Leu Glu Thr Val Ala Gln 165
170 175 Gln Lys Arg Asp Tyr Tyr Gln Pro Leu
Ala Ala Lys Arg Met Glu Ile 180 185
190 Glu Lys Trp Arg Lys Glu Phe Lys Glu Gln Trp Leu Lys Glu
Gln Lys 195 200 205
Arg Met Asn Glu Ala Val Gln Ala Leu Arg Arg Ser Glu Leu Gln Tyr 210
215 220 Ile Gln Arg Arg Glu
Asp Leu Arg Ala Arg Ser Gln Gly Ser Pro Glu 225 230
235 240 Asp Pro Pro Ser Gln Ala Ser Pro Gly Ser
Asn Lys Gln Gln Glu Arg 245 250
255 Arg Arg Arg Ser Arg Glu Glu Ala Gln Ala Lys Ala His Glu Ala
Glu 260 265 270 Ala
Leu Tyr Gln Ala Cys Val Arg Glu Ala Asn Ser Arg Gln Gln Asp 275
280 285 Leu Glu Thr Thr Lys Arg
Arg Ile Val Ser His Val Arg Lys Leu Val 290 295
300 Leu Gln Gly Asp Glu Val Leu Arg Arg Val Thr
Leu Gly Leu Phe Glu 305 310 315
320 Leu Arg Gly Ala Gln Ala Glu Arg Gly Pro Arg Ser Phe Ser Ala Leu
325 330 335 Ala Glu
Cys Cys Val Pro Phe Glu Pro Gly Gln Arg Tyr Gln Glu Phe 340
345 350 Val Arg Thr Leu Gln Pro Gly
Ala Pro Pro Pro Pro Ser Pro Ala Phe 355 360
365 Cys Phe Gln Glu Phe Thr Ala Val Val His Ser Phe
Pro Gln Asp Thr 370 375 380
Lys Lys Lys Phe Ser Gly Pro Leu Pro Pro Arg Leu Glu Glu Glu Gly 385
390 395 400 Ser Pro Glu
Pro Gly Pro Trp Glu Val Ala Ser Leu Gly Ser Gln Gly 405
410 415 Ile Pro Gly Ser Asp Val Asp Ser
Val Gly Gly Gly Ser Glu Ser Arg 420 425
430 Ser Leu Asp Ser Pro Thr Ser Ser Pro Gly Ala Gly Ala
Arg Arg Leu 435 440 445
Val Lys Ala Ser Ser Thr Gly Thr Glu Ser Ser Asp Asp Phe Glu Glu 450
455 460 Arg Asp Pro Asp
Leu Gly Asp Gly Ile Glu Asn Gly Val Gly Ser Pro 465 470
475 480 Phe Arg Lys Trp Thr Leu Ser Thr Ala
Ala Gln Thr His Arg Leu Arg 485 490
495 Arg Leu Arg Gly Pro Ala Lys Cys Arg Glu Cys Glu Ala Phe
Met Val 500 505 510
Ser Gly Thr Glu Cys Glu Glu Cys Phe Leu Thr Cys His Lys Arg Cys
515 520 525 Leu Glu Thr Leu
Leu Ile Leu Cys Gly His Arg Arg Leu Pro Ala Arg 530
535 540 Met Ser Leu Phe Gly Val Asp Phe
Leu Gln Leu Pro Arg Asp Phe Pro 545 550
555 560 Glu Glu Val Pro Phe Val Ile Thr Arg Cys Thr Ala
Glu Ile Glu His 565 570
575 Arg Ala Leu Gly Leu Gln Gly Ile Tyr Arg Val Ser Gly Ser Arg Val
580 585 590 Arg Val Glu
Arg Leu Cys Gln Ala Phe Glu Asn Gly Arg Ala Leu Val 595
600 605 Glu Leu Ser Gly Asn Ser Pro His
Asp Ile Thr Ser Val Leu Lys Arg 610 615
620 Phe Leu Gln Glu Leu Thr Asp Pro Val Val Pro Phe His
Leu Tyr Asp 625 630 635
640 Ala Phe Ile Ser Leu Ala Lys Thr Leu His Ala Asp Pro Gly Asp Asp
645 650 655 Pro Gly Thr Pro
Asn Pro Ser Pro Glu Ile Ile Arg Ser Leu Lys Thr 660
665 670 Leu Leu Val Gln Leu Pro Asp Ser Asn
Tyr Ser Thr Leu Arg His Leu 675 680
685 Val Ala His Leu Phe Arg Val Ala Ala Arg Phe Glu Glu Asn
Lys Met 690 695 700
Ser Ala Asn Asn Leu Gly Ile Val Phe Gly Pro Thr Leu Leu Arg Pro 705
710 715 720 Pro Asp Gly Pro Arg
Ala Thr Gly Ala Ser Pro Val Ala Cys Leu Leu 725
730 735 Asp Ser Gly His Gln Ala Gln Leu Val Glu
Phe Leu Ile Val His Tyr 740 745
750 Glu Gln Ile Phe Gly Met Asp Glu Leu Pro Leu Ala Ser Glu Pro
Leu 755 760 765 Thr
Gln Asp Pro Gly Leu Ala Pro Ala Cys Leu Glu Ser Ser Pro Gln 770
775 780 His Pro Ala Ser Leu Leu
Ala Gln Asp Thr Gln Pro Leu Thr Ile Ala 785 790
795 800 Leu Asp Ser Ser Pro Asp Pro Lys His His Ser
Ala Leu Glu Lys Cys 805 810
815 Pro Glu Val Thr Pro Pro Glu Phe Trp Phe Phe Glu Thr Gly Phe Leu
820 825 830 Cys Val
Ala Leu Ala Val Leu Glu Leu Thr Leu 835 840
213633PRTMus Musculus 213Met Asp Ser Ala Glu Thr Glu Leu Thr Pro
Ala Pro Glu Gly Arg Lys 1 5 10
15 Arg Tyr Ser Asp Ile Phe Gln Ser Leu Asp Asn Leu Glu Ile Ser
Leu 20 25 30 Gly
Asn Val Thr Phe Asp Pro Leu Ala Gly Asp Pro Val Arg Arg Glu 35
40 45 Asp Leu Glu Pro Asp Lys
Ala Asp Thr Ala Thr Val Val Thr Glu Glu 50 55
60 Asn Ser Glu Ala Ser Ser Trp Arg Asp Leu Ser
Pro Glu Gly Pro Ala 65 70 75
80 Pro Leu Thr Glu Glu Glu Leu Asp Leu Arg Leu Ile Arg Thr Lys Gly
85 90 95 Gly Val
Asp Ala Ala Leu Glu Tyr Ala Lys Ala Trp Ser Arg Tyr Ala 100
105 110 Lys Glu Leu Leu Ala Trp Thr
Asp Lys Arg Ala Asn Tyr Glu Leu Glu 115 120
125 Phe Ala Lys Ser Ile Met Lys Leu Ala Glu Ala Gly
Lys Val Ser Ile 130 135 140
Leu Gln Gln Ser Gln Met Pro Leu Gln Tyr Ile Tyr Thr Leu Phe Leu 145
150 155 160 Glu His Asp
Leu Ser Leu Gly Ala Leu Ala Leu Glu Thr Val Ala Gln 165
170 175 Gln Lys Arg Asp Tyr Tyr Gln Pro
Leu Ala Ala Lys Arg Met Glu Ile 180 185
190 Glu Lys Trp Arg Lys Glu Phe Lys Glu Gln Trp Leu Lys
Glu Gln Lys 195 200 205
Arg Met Asn Glu Ala Val Gln Ala Leu Arg Arg Ser Glu Leu Gln Tyr 210
215 220 Ile Gln Arg Arg
Glu Asp Leu Arg Ala Arg Ser Gln Gly Ser Pro Glu 225 230
235 240 Asp Pro Pro Ser Gln Ala Ser Pro Gly
Ser Asn Lys Gln Gln Glu Arg 245 250
255 Arg Arg Arg Ser Arg Glu Glu Ala Gln Ala Lys Ala His Glu
Ala Glu 260 265 270
Ala Leu Tyr Gln Ala Cys Val Arg Glu Ala Asn Ser Arg Gln Gln Asp
275 280 285 Leu Glu Thr Thr
Lys Arg Arg Ile Val Ser His Val Arg Lys Leu Val 290
295 300 Leu Gln Gly Asp Glu Val Leu Arg
Arg Val Thr Leu Gly Leu Phe Glu 305 310
315 320 Leu Arg Gly Ala Gln Ala Glu Arg Gly Pro Arg Ser
Phe Ser Ala Leu 325 330
335 Ala Glu Cys Cys Val Pro Phe Glu Pro Gly Gln Arg Tyr Gln Glu Phe
340 345 350 Val Arg Thr
Leu Gln Pro Gly Ala Pro Pro Pro Pro Ser Pro Ala Phe 355
360 365 Cys Phe Gln Glu Phe Thr Ala Val
Val His Ser Phe Pro Gln Asp Thr 370 375
380 Lys Lys Lys Phe Ser Gly Pro Leu Pro Pro Arg Leu Glu
Glu Glu Gly 385 390 395
400 Ser Pro Glu Pro Gly Pro Trp Glu Val Ala Ser Leu Gly Ser Gln Gly
405 410 415 Ile Pro Gly Ser
Asp Val Asp Ser Val Gly Gly Gly Ser Glu Ser Arg 420
425 430 Ser Leu Asp Ser Pro Thr Ser Ser Pro
Gly Ala Gly Ala Arg Arg Leu 435 440
445 Val Lys Ala Ser Ser Thr Gly Thr Glu Ser Ser Asp Asp Phe
Glu Glu 450 455 460
Arg Asp Pro Asp Leu Gly Asp Gly Ile Glu Asn Gly Val Gly Ser Pro 465
470 475 480 Phe Arg Lys Trp Thr
Leu Ser Thr Ala Ala Gln Thr His Arg Leu Arg 485
490 495 Arg Leu Arg Gly Pro Ala Lys Cys Arg Glu
Cys Glu Ala Phe Met Val 500 505
510 Ser Gly Thr Glu Cys Glu Glu Cys Phe Leu Thr Cys His Lys Arg
Cys 515 520 525 Leu
Glu Thr Leu Leu Ile Leu Cys Gly His Arg Arg Leu Pro Ala Arg 530
535 540 Met Ser Leu Phe Gly Val
Asp Phe Leu Gln Leu Pro Arg Asp Phe Pro 545 550
555 560 Glu Glu Val Pro Phe Val Ile Thr Arg Cys Thr
Ala Glu Ile Glu His 565 570
575 Arg Ala Leu Gly Leu Gln Gly Ile Tyr Arg Val Ser Gly Ser Arg Val
580 585 590 Arg Val
Glu Arg Leu Cys Gln Ala Phe Glu Asn Gly Arg Ala Leu Val 595
600 605 Glu Leu Ser Gly Asn Ser Pro
His Asp Ile Thr Ser Val Leu Lys Arg 610 615
620 Phe Leu Gln Glu Gly Gly Cys Ser Val 625
630 21478PRTMus Musculus 214Met Asp Ser Ala Glu Thr
Glu Leu Thr Pro Ala Pro Glu Gly Arg Lys 1 5
10 15 Arg Tyr Ser Asp Ile Phe Gln Ser Leu Asp Asn
Leu Glu Ile Ser Leu 20 25
30 Gly Asn Val Thr Phe Asp Pro Leu Ala Gly Asp Pro Val Arg Arg
Glu 35 40 45 Asp
Leu Glu Pro Asp Lys Ala Asp Thr Ala Thr Val Val Thr Glu Glu 50
55 60 Arg Lys Asn Trp Ile Cys
Asp Ser Phe Gly Pro Arg Val Val 65 70
75 215303PRTMus Musculus 215Met Ala Pro Pro Ala Leu Gln Ala
Gln Pro Pro Gly Gly Ser Gln Leu 1 5 10
15 Arg Phe Leu Leu Phe Leu Leu Leu Leu Leu Leu Leu Leu
Ser Trp Pro 20 25 30
Ser Gln Gly Asp Ala Leu Ala Met Pro Glu Gln Arg Arg Ser Gly Pro
35 40 45 Glu Ser Gln Leu
Asn Ala Asp Glu Leu Arg Gly Arg Phe Gln Asp Leu 50
55 60 Leu Ser Arg Leu His Ala Asn Gln
Ser Arg Glu Asp Ser Asn Ser Glu 65 70
75 80 Pro Ser Pro Asp Pro Ala Val Arg Ile Leu Ser Pro
Glu Val Arg Leu 85 90
95 Gly Ser His Gly Gln Leu Leu Leu Arg Val Asn Arg Ala Ser Leu Ser
100 105 110 Gln Gly Leu
Pro Glu Ala Tyr Arg Val His Arg Ala Leu Leu Leu Leu 115
120 125 Thr Pro Thr Thr Arg Pro Trp Asp
Ile Thr Arg Pro Leu Lys Arg Ala 130 135
140 Leu Ser Leu Gln Gly Pro Arg Ala Pro Ala Leu Arg Leu
Arg Leu Thr 145 150 155
160 Pro Pro Pro Asp Leu Ala Met Leu Pro Ser Gly Gly Ala Gln Leu Glu
165 170 175 Leu Arg Leu Arg
Val Ala Ala Gly Arg Gly Arg Arg Ser Ala His Ala 180
185 190 His Pro Arg Asp Ser Cys Pro Leu Gly
Pro Gly Arg Cys Cys His Leu 195 200
205 Glu Thr Val Gln Ala Thr Leu Glu Asp Leu Gly Trp Ser Asp
Trp Val 210 215 220
Leu Ser Pro Arg Gln Leu Gln Leu Ser Met Cys Val Gly Glu Cys Pro 225
230 235 240 His Leu Tyr Arg Ser
Ala Asn Thr His Ala Gln Ile Lys Ala Arg Leu 245
250 255 His Gly Leu Gln Pro Asp Lys Val Pro Ala
Pro Cys Cys Val Pro Ser 260 265
270 Ser Tyr Thr Pro Val Val Leu Met His Arg Thr Asp Ser Gly Val
Ser 275 280 285 Leu
Gln Thr Tyr Asp Asp Leu Val Ala Arg Gly Cys His Cys Ala 290
295 300 216159PRTMus Musculus 216Met
Ser Asn Pro Gly Asp Val Arg Pro Val Pro His Arg Ser Lys Val 1
5 10 15 Cys Arg Cys Leu Phe Gly
Pro Val Asp Ser Glu Gln Leu Arg Arg Asp 20
25 30 Cys Asp Ala Leu Met Ala Gly Cys Leu Gln
Glu Ala Arg Glu Arg Trp 35 40
45 Asn Phe Asp Phe Val Thr Glu Thr Pro Leu Glu Gly Asn Phe
Val Trp 50 55 60
Glu Arg Val Arg Ser Leu Gly Leu Pro Lys Val Tyr Leu Ser Pro Gly 65
70 75 80 Ser Arg Ser Arg Asp
Asp Leu Gly Gly Asp Lys Arg Pro Ser Thr Ser 85
90 95 Ser Ala Leu Leu Gln Gly Pro Ala Pro Glu
Asp His Val Ala Leu Ser 100 105
110 Leu Ser Cys Thr Leu Val Ser Glu Arg Pro Glu Asp Ser Pro Gly
Gly 115 120 125 Pro
Gly Thr Ser Gln Gly Arg Lys Arg Arg Gln Thr Ser Leu Thr Asp 130
135 140 Phe Tyr His Ser Lys Arg
Arg Leu Val Phe Cys Lys Arg Lys Pro 145 150
155 217294PRTMus Musculus 217Met Ile Glu Val Leu Thr
Thr Asp Ser Gln Lys Leu Leu His Gln Leu 1 5
10 15 Asn Thr Leu Leu Glu Gln Glu Ser Arg Cys Gln
Pro Lys Val Cys Gly 20 25
30 Leu Lys Leu Ile Glu Ser Ala His Asp Asn Gly Leu Arg Met Thr
Ala 35 40 45 Arg
Leu Arg Asp Phe Glu Val Lys Asp Leu Leu Ser Leu Thr Gln Phe 50
55 60 Phe Gly Phe Asp Thr Glu
Thr Phe Ser Leu Ala Val Asn Leu Leu Asp 65 70
75 80 Arg Phe Leu Ser Lys Met Lys Val Gln Ala Lys
His Leu Gly Cys Val 85 90
95 Gly Leu Ser Cys Phe Tyr Leu Ala Val Lys Ala Thr Glu Glu Glu Arg
100 105 110 Asn Val
Pro Leu Ala Thr Asp Leu Ile Arg Ile Ser Gln Tyr Arg Phe 115
120 125 Thr Val Ser Asp Leu Met Arg
Met Glu Lys Ile Val Leu Glu Lys Val 130 135
140 Cys Trp Lys Val Lys Ala Thr Thr Ala Phe Gln Phe
Leu Gln Leu Tyr 145 150 155
160 Tyr Ser Leu Val His Asp Thr Leu Pro Phe Glu Arg Arg Asn Asp Leu
165 170 175 Asn Phe Glu
Arg Leu Glu Ala Gln Leu Lys Ala Cys His Cys Arg Ile 180
185 190 Ile Phe Ser Lys Ala Lys Pro Ser
Val Leu Ala Leu Ser Ile Leu Ala 195 200
205 Leu Glu Ile Gln Ala Leu Lys Tyr Val Glu Leu Thr Glu
Gly Val Glu 210 215 220
Cys Ile Gln Lys His Ser Lys Ile Ser Gly Arg Asp Leu Thr Phe Trp 225
230 235 240 Gln Glu Leu Val
Ser Lys Cys Leu Thr Glu Tyr Ser Ser Asn Lys Cys 245
250 255 Ser Lys Pro Asn Gly Gln Lys Leu Lys
Trp Ile Val Ser Gly Arg Thr 260 265
270 Ala Arg Gln Leu Lys His Ser Tyr Tyr Arg Ile Thr His Leu
Pro Thr 275 280 285
Ile Pro Glu Thr Ile Cys 290 218187PRTMus Musculus
218Met Ile Glu Val Leu Thr Thr Asp Ser Gln Lys Leu Leu His Gln Leu 1
5 10 15 Asn Thr Leu Leu
Glu Gln Glu Ser Arg Cys Gln Pro Lys Val Cys Gly 20
25 30 Leu Lys Leu Ile Glu Ser Ala His Asp
Asn Gly Leu Arg Met Thr Ala 35 40
45 Arg Leu Arg Asp Phe Glu Val Lys Asp Leu Leu Ser Leu Thr
Gln Phe 50 55 60
Phe Gly Phe Asp Thr Glu Thr Phe Ser Leu Ala Val Asn Leu Leu Asp 65
70 75 80 Arg Phe Leu Ser Lys
Met Lys Val Gln Ala Lys His Leu Gly Cys Val 85
90 95 Gly Leu Ser Cys Phe Tyr Leu Ala Val Lys
Ala Thr Glu Glu Glu Arg 100 105
110 Asn Val Pro Leu Ala Thr Asp Leu Ile Arg Ile Ser Gln Tyr Arg
Phe 115 120 125 Thr
Val Ser Asp Leu Met Arg Met Glu Lys Ile Val Leu Glu Lys Val 130
135 140 Cys Trp Lys Val Lys Ala
Thr Thr Ala Phe Gln Phe Leu Gln Leu Tyr 145 150
155 160 Tyr Ser Leu Val His Asp Thr Leu Pro Phe Glu
Ser Leu Leu Cys Trp 165 170
175 Arg Tyr Leu Ser Leu Arg Trp Arg Ser Lys His 180
185 219203PRTMus Musculus 219Met Lys Val Leu Ala Ala
Gly Ile Val Pro Leu Leu Leu Leu Val Leu 1 5
10 15 His Trp Lys His Gly Ala Gly Ser Pro Leu Pro
Ile Thr Pro Val Asn 20 25
30 Ala Thr Cys Ala Ile Arg His Pro Cys His Gly Asn Leu Met Asn
Gln 35 40 45 Ile
Lys Asn Gln Leu Ala Gln Leu Asn Gly Ser Ala Asn Ala Leu Phe 50
55 60 Ile Ser Tyr Tyr Thr Ala
Gln Gly Glu Pro Phe Pro Asn Asn Val Glu 65 70
75 80 Lys Leu Cys Ala Pro Asn Met Thr Asp Phe Pro
Ser Phe His Gly Asn 85 90
95 Gly Thr Glu Lys Thr Lys Leu Val Glu Leu Tyr Arg Met Val Ala Tyr
100 105 110 Leu Ser
Ala Ser Leu Thr Asn Ile Thr Arg Asp Gln Lys Val Leu Asn 115
120 125 Pro Thr Ala Val Ser Leu Gln
Val Lys Leu Asn Ala Thr Ile Asp Val 130 135
140 Met Arg Gly Leu Leu Ser Asn Val Leu Cys Arg Leu
Cys Asn Lys Tyr 145 150 155
160 Arg Val Gly His Val Asp Val Pro Pro Val Pro Asp His Ser Asp Lys
165 170 175 Glu Ala Phe
Gln Arg Lys Lys Leu Gly Cys Gln Leu Leu Gly Thr Tyr 180
185 190 Lys Gln Val Ile Ser Val Val Val
Gln Ala Phe 195 200 220342PRTMus
Musculus 220Met Arg Lys Asp Thr Pro Pro Pro Leu Val Pro Pro Ala Ala Arg
Glu 1 5 10 15 Trp
Asn Leu Pro Pro Asn Ala Pro Ala Cys Met Glu Arg Gln Leu Glu
20 25 30 Ala Ala Arg Tyr Arg
Ser Asp Gly Ser Leu Leu Leu Gly Val Ser Ser 35
40 45 Leu Ser Gly Arg Cys Trp Val Gly Ser
Leu Trp Phe Phe Lys Asp Pro 50 55
60 Ser Ala Ala Pro Asn Glu Gly Phe Cys Ser Ala Gly Val
Gln Thr Glu 65 70 75
80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Asp Lys Gly Ile Leu Val
85 90 95 Ala Ser Asp Ser
Gly Ala Val Glu Leu Trp Glu Leu Asp Glu Asn Glu 100
105 110 Thr Leu Ile Val Ser Lys Phe Cys Lys
Tyr Glu His Asp Asp Ile Val 115 120
125 Ser Thr Val Thr Val Leu Ser Ser Gly Thr Gln Ala Val Ser
Gly Ser 130 135 140
Lys Asp Cys Cys Ile Lys Ile Trp Asp Leu Ala Gln Gln Val Ser Leu 145
150 155 160 Asn Ser Tyr Arg Ala
His Ala Gly Gln Val Thr Cys Val Ala Ala Ser 165
170 175 Pro His Lys Asp Ser Val Phe Leu Ser Cys
Ser Glu Asp Ser Arg Ile 180 185
190 Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro Ala Ser Gln Met Ala
Cys 195 200 205 Asn
Ala Ser Gly Tyr Leu Pro Thr Ala Leu Ala Trp His Pro Gln Gln 210
215 220 Ser Glu Val Phe Val Phe
Gly Asp Glu Asn Gly Ser Val Ser Leu Val 225 230
235 240 Asp Thr Lys Asn Ala Ser Cys Thr Leu Ser Ser
Ala Val His Ser Gln 245 250
255 Gly Val Thr Arg Leu Val Phe Ser Pro His Ser Val Pro Leu Leu Thr
260 265 270 Ser Leu
Ser Glu Asp Cys Ser Leu Ala Val Leu Asp Ser Ser Leu Ser 275
280 285 Glu Val Phe Arg Ser Arg Ala
His Arg Asp Phe Val Arg Asp Ala Thr 290 295
300 Trp Ser Pro Leu Asn His Ser Leu Leu Thr Thr Val
Gly Trp Asp His 305 310 315
320 Gln Val Ile His His Val Val Pro Leu Glu Pro Leu Pro Asn Pro Gly
325 330 335 Pro Asp Ser
Val Val Glu 340 221285PRTMus Musculus 221Met Arg Lys
Asp Thr Pro Pro Pro Leu Val Pro Pro Ala Ala Arg Glu 1 5
10 15 Trp Asn Leu Pro Pro Asn Ala Pro
Ala Cys Met Glu Arg Gln Leu Glu 20 25
30 Ala Ala Arg Tyr Arg Ser Asp Gly Ser Leu Leu Leu Gly
Val Ser Ser 35 40 45
Leu Ser Gly Arg Cys Trp Val Gly Ser Leu Trp Phe Phe Lys Asp Pro 50
55 60 Ser Ala Ala Pro
Asn Glu Gly Phe Cys Ser Ala Gly Val Gln Thr Glu 65 70
75 80 Ala Gly Val Ala Asp Leu Thr Trp Val
Gly Asp Lys Gly Ile Leu Val 85 90
95 Ala Ser Asp Ser Gly Ala Val Glu Leu Trp Glu Leu Asp Glu
Asn Glu 100 105 110
Thr Leu Ile Val Ser Lys Phe Cys Lys Tyr Glu His Asp Asp Ile Val
115 120 125 Ser Thr Val Thr
Val Leu Ser Ser Gly Thr Gln Ala Val Ser Gly Ser 130
135 140 Lys Asp Cys Cys Ile Lys Ile Trp
Asp Leu Ala Gln Gln Val Ser Leu 145 150
155 160 Asn Ser Tyr Arg Ala His Ala Gly Gln Val Thr Cys
Val Ala Ala Ser 165 170
175 Pro His Lys Asp Ser Val Phe Leu Ser Cys Ser Glu Asp Ser Arg Ile
180 185 190 Leu Leu Trp
Asp Thr Arg Cys Pro Lys Pro Ala Ser Gln Met Ala Cys 195
200 205 Asn Ala Ser Gly Tyr Leu Pro Thr
Ala Leu Ala Trp His Pro Gln Gln 210 215
220 Ser Glu Val Phe Val Phe Gly Asp Glu Asn Gly Ser Val
Ser Leu Val 225 230 235
240 Asp Thr Lys Asn Ala Ser Cys Thr Leu Ser Ser Ala Val His Ser Gln
245 250 255 Gly Val Thr Arg
Leu Val Phe Ser Pro His Arg Cys Cys Val Ser Pro 260
265 270 Gly Thr Trp Lys Gly Trp Val Gly Thr
Val Val Lys Glu 275 280 285
222234PRTMus Musculus 222Met Arg Lys Asp Thr Pro Pro Pro Leu Val Pro Pro
Ala Ala Arg Glu 1 5 10
15 Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys Met Glu Arg Gln Leu Glu
20 25 30 Ala Ala Arg
Tyr Arg Ser Asp Gly Ser Leu Leu Leu Gly Val Ser Ser 35
40 45 Leu Ser Gly Arg Cys Trp Val Gly
Ser Leu Trp Phe Phe Lys Asp Pro 50 55
60 Ser Ala Ala Pro Asn Glu Gly Phe Cys Ser Ala Gly Val
Gln Thr Glu 65 70 75
80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Asp Lys Gly Ile Leu Val
85 90 95 Ala Ser Asp Ser
Gly Ala Val Glu Leu Trp Glu Leu Asp Glu Asn Glu 100
105 110 Thr Leu Ile Val Ser Lys Phe Cys Lys
Tyr Glu His Asp Asp Ile Val 115 120
125 Ser Thr Val Thr Val Leu Ser Ser Gly Thr Gln Ala Val Ser
Gly Ser 130 135 140
Lys Asp Cys Cys Ile Lys Ile Trp Asp Leu Ala Gln Gln Val Ser Leu 145
150 155 160 Asn Ser Tyr Arg Ala
His Ala Gly Gln Val Thr Cys Val Ala Ala Ser 165
170 175 Pro His Lys Asp Ser Val Phe Leu Ser Cys
Ser Glu Asp Ser Arg Ile 180 185
190 Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro Ala Ser Gln Met Ala
Cys 195 200 205 Asn
Ala Ser Gly Tyr Leu Pro Thr Ala Leu Ala Trp His Pro Gln Gln 210
215 220 Ser Glu Val Phe Val Phe
Gly Lys Ala Ala 225 230 223269PRTMus
Musculus 223Met Arg Lys Asp Thr Pro Pro Pro Leu Val Pro Pro Ala Ala Arg
Glu 1 5 10 15 Trp
Asn Leu Pro Pro Asn Ala Pro Ala Cys Met Glu Arg Gln Leu Glu
20 25 30 Ala Ala Arg Tyr Arg
Ser Asp Gly Ser Leu Leu Leu Gly Val Ser Ser 35
40 45 Leu Ser Gly Arg Cys Trp Val Gly Ser
Leu Trp Phe Phe Lys Asp Pro 50 55
60 Ser Ala Ala Pro Asn Glu Gly Phe Cys Ser Ala Gly Val
Gln Thr Glu 65 70 75
80 Ala Gly Val Ala Asp Leu Thr Trp Val Gly Asp Lys Gly Ile Leu Val
85 90 95 Ala Ser Asp Ser
Gly Ala Val Glu Leu Trp Glu Leu Asp Glu Asn Glu 100
105 110 Thr Leu Ile Val Ser Lys Phe Cys Lys
Tyr Glu His Asp Asp Ile Val 115 120
125 Ser Thr Val Thr Val Leu Ser Ser Gly Thr Gln Ala Val Ser
Gly Ser 130 135 140
Lys Asp Cys Cys Ile Lys Ile Trp Asp Leu Ala Gln Gln Val Ser Leu 145
150 155 160 Asn Ser Tyr Arg Ala
His Ala Gly Gln Val Thr Cys Val Ala Ala Ser 165
170 175 Pro His Lys Asp Ser Val Phe Leu Ser Cys
Ser Glu Asp Ser Arg Ile 180 185
190 Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro Ala Ser Gln Met Ala
Cys 195 200 205 Asn
Ala Ser Gly Tyr Leu Pro Thr Ala Leu Ala Trp His Pro Gln Gln 210
215 220 Ser Glu Val Phe Val Phe
Gly Asp Glu Asn Gly Ser Val Ser Leu Val 225 230
235 240 Asp Thr Lys Asn Ala Ser Cys Thr Leu Ser Ser
Ala Val His Ser Gln 245 250
255 Gly Val Thr Arg Leu Cys Pro Pro Pro Asp Phe Ser Gln
260 265 224751PRTMus Musculus 224Met Arg
Leu Leu Arg Val Ala Ala Ala Leu Gly Arg Gly Pro Phe Pro 1 5
10 15 Arg Val Pro Ala Val Leu Gly
Trp Gln Gly Lys Gln Ala Asp Trp Lys 20 25
30 Thr Arg Arg Trp Cys Ser Ser Gly Pro Val Pro Asn
Glu Lys Ile Arg 35 40 45
Asn Ile Gly Ile Ser Ala His Ile Asp Ser Gly Lys Thr Thr Leu Thr
50 55 60 Glu Arg Val
Leu Tyr Tyr Thr Gly Arg Ile Ala Thr Met His Glu Val 65
70 75 80 Lys Gly Lys Asp Gly Val Gly
Ala Val Met Asp Ser Met Glu Leu Glu 85
90 95 Arg Gln Arg Gly Ile Thr Ile Gln Ser Ala Ala
Thr Tyr Thr Met Trp 100 105
110 Lys Asp Ile Asn Ile Asn Ile Ile Asp Thr Pro Gly His Val Asp
Phe 115 120 125 Thr
Ile Glu Val Glu Arg Ala Leu Arg Val Leu Asp Gly Ala Val Leu 130
135 140 Val Leu Cys Ala Val Gly
Gly Val Gln Cys Gln Thr Met Thr Val Ser 145 150
155 160 Arg Gln Met Lys Arg Tyr Asn Val Pro Phe Leu
Thr Phe Ile Asn Lys 165 170
175 Leu Asp Arg Met Gly Ser Asn Pro Ser Arg Ala Leu Gln Gln Met Arg
180 185 190 Ser Lys
Leu Asn His Asn Ala Ala Phe Val Gln Ile Pro Ile Gly Leu 195
200 205 Glu Gly Asp Phe Lys Gly Ile
Ile Asp Leu Ile Glu Glu Arg Ala Ile 210 215
220 Tyr Phe Asp Gly Asp Phe Gly Gln Ile Val Arg Tyr
Asp Glu Ile Pro 225 230 235
240 Ala Gly Leu Arg Ala Ala Ala Ala Asp His Arg Gln Glu Leu Ile Glu
245 250 255 Cys Val Ala
Asn Ser Asp Glu Gln Leu Gly Glu Leu Phe Leu Glu Glu 260
265 270 Lys Ile Pro Ser Val Ser Asp Leu
Lys Arg Ala Ile Arg Arg Ala Thr 275 280
285 Leu Ser Arg Ser Phe Thr Pro Val Phe Leu Gly Ser Ala
Leu Lys Asn 290 295 300
Lys Gly Val Gln Pro Leu Leu Asp Ala Val Leu Glu Tyr Leu Pro Asn 305
310 315 320 Pro Ser Glu Val
Gln Asn Tyr Ala Ile Leu Asn Gln Asn Asp Ser Lys 325
330 335 Glu Lys Thr Lys Ile Leu Met Asn Pro
Gln Arg Asp Asp Ser His Pro 340 345
350 Phe Val Gly Leu Ala Phe Lys Leu Glu Ala Gly Arg Phe Gly
Gln Leu 355 360 365
Thr Tyr Val Arg Asn Tyr Gln Gly Glu Leu Lys Lys Gly Ser Thr Ile 370
375 380 Tyr Asn Thr Arg Thr
Gly Lys Lys Val Arg Val Gln Arg Leu Val Arg 385 390
395 400 Met His Ala Asp Met Met Glu Asp Val Glu
Glu Val Tyr Ala Gly Asp 405 410
415 Ile Cys Ala Leu Phe Gly Ile Asp Cys Ala Ser Gly Asp Thr Phe
Thr 420 425 430 Asn
Lys Asp Asn Ser Asp Leu Ser Met Glu Ser Ile His Val Pro Glu 435
440 445 Pro Val Ile Ser Ile Ala
Met Arg Pro Ser Asn Lys Asn Asp Leu Glu 450 455
460 Lys Phe Ser Lys Gly Ile Gly Arg Phe Thr Arg
Glu Asp Pro Thr Phe 465 470 475
480 Lys Val His Phe Asp Pro Glu Ser Lys Glu Thr Ile Val Ser Gly Met
485 490 495 Gly Glu
Leu His Leu Glu Ile Tyr Ala Gln Arg Met Glu Arg Glu Tyr 500
505 510 Gly Cys Pro Cys Ile Thr Gly
Lys Pro Lys Val Ala Phe Arg Glu Thr 515 520
525 Ile Val Ala Pro Val Pro Phe Asp Phe Thr His Lys
Lys Gln Ser Gly 530 535 540
Gly Ala Gly Gln Phe Gly Lys Val Ile Gly Val Leu Glu Pro Leu Pro 545
550 555 560 Pro Glu Asp
Tyr Thr Lys Leu Glu Phe Ser Asp Glu Thr Phe Gly Ser 565
570 575 Asn Val Pro Lys Gln Phe Val Pro
Ala Val Glu Lys Gly Phe Leu Asp 580 585
590 Ala Cys Glu Lys Gly Pro Leu Ser Gly His Lys Leu Ser
Gly Leu Arg 595 600 605
Phe Val Leu Gln Asp Gly Ala His His Met Val Asp Ser Asn Glu Ile 610
615 620 Ser Phe Ile Arg
Ala Gly Glu Gly Ala Leu Lys Gln Ala Leu Ala Asn 625 630
635 640 Gly Thr Leu Cys Ile Ile Glu Pro Ile
Met Ser Val Glu Val Ile Ala 645 650
655 Pro Asn Glu Phe Gln Gly Thr Val Phe Ala Gly Ile Asn Arg
Arg His 660 665 670
Gly Val Ile Thr Gly Gln Asp Gly Ile Glu Asp Tyr Phe Thr Leu Tyr
675 680 685 Ala Asp Val Pro
Leu Asn Asn Met Phe Gly Tyr Ser Thr Glu Leu Arg 690
695 700 Ser Cys Thr Glu Gly Lys Gly Glu
Tyr Thr Met Glu Tyr Cys Arg Tyr 705 710
715 720 Gln Pro Cys Ser Pro Ser Thr Gln Glu Glu Leu Ile
Asn Lys Tyr Leu 725 730
735 Glu Ala Thr Gly Gln Leu Pro Val Lys Lys Gly Lys Ala Lys Asn
740 745 750 225560PRTMus
Musculus 225Met Arg Leu Leu Arg Val Ala Ala Ala Leu Gly Arg Gly Pro Phe
Pro 1 5 10 15 Arg
Val Pro Ala Val Leu Gly Trp Gln Gly Lys Gln Ala Asp Trp Lys
20 25 30 Thr Arg Arg Trp Cys
Ser Ser Gly Pro Val Pro Asn Glu Lys Ile Arg 35
40 45 Asn Ile Gly Ile Ser Ala His Ile Asp
Ser Gly Lys Thr Thr Leu Thr 50 55
60 Glu Arg Val Leu Tyr Tyr Thr Gly Arg Ile Ala Thr Met
His Glu Val 65 70 75
80 Lys Gly Lys Asp Gly Val Gly Ala Val Met Asp Ser Met Glu Leu Glu
85 90 95 Arg Gln Arg Gly
Ile Thr Ile Gln Ser Ala Ala Thr Tyr Thr Met Trp 100
105 110 Lys Asp Ile Asn Ile Asn Ile Ile Asp
Thr Pro Gly His Val Asp Phe 115 120
125 Thr Ile Glu Val Glu Arg Ala Leu Arg Val Leu Asp Gly Ala
Val Leu 130 135 140
Val Leu Cys Ala Val Gly Gly Val Gln Cys Gln Thr Met Thr Val Ser 145
150 155 160 Arg Gln Met Lys Arg
Tyr Asn Val Pro Phe Leu Thr Phe Ile Asn Lys 165
170 175 Leu Asp Arg Met Gly Ser Asn Pro Ser Arg
Ala Leu Gln Gln Met Arg 180 185
190 Ser Lys Leu Asn His Asn Ala Ala Phe Val Gln Ile Pro Ile Gly
Leu 195 200 205 Glu
Gly Asp Phe Lys Gly Ile Ile Asp Leu Ile Glu Glu Arg Ala Ile 210
215 220 Tyr Phe Asp Gly Asp Phe
Gly Gln Ile Val Arg Tyr Asp Glu Ile Pro 225 230
235 240 Ala Gly Leu Arg Ala Ala Ala Ala Asp His Arg
Gln Glu Leu Ile Glu 245 250
255 Cys Val Ala Asn Ser Asp Glu Gln Leu Gly Glu Leu Phe Leu Glu Glu
260 265 270 Lys Ile
Pro Ser Val Ser Asp Leu Lys Arg Ala Ile Arg Arg Ala Thr 275
280 285 Leu Ser Arg Ser Phe Thr Pro
Val Phe Leu Gly Ser Ala Leu Lys Asn 290 295
300 Lys Gly Val Gln Pro Leu Leu Asp Ala Val Leu Glu
Tyr Leu Pro Asn 305 310 315
320 Pro Ser Glu Val Gln Asn Tyr Ala Ile Leu Asn Gln Asn Asp Ser Lys
325 330 335 Glu Lys Thr
Lys Ile Leu Met Asn Pro Gln Arg Asp Asp Ser His Pro 340
345 350 Phe Val Gly Leu Ala Phe Lys Leu
Glu Ala Gly Arg Phe Gly Gln Leu 355 360
365 Thr Tyr Val Arg Asn Tyr Gln Gly Glu Leu Lys Lys Gly
Ser Thr Ile 370 375 380
Tyr Asn Thr Arg Thr Gly Lys Lys Val Arg Val Gln Arg Leu Val Arg 385
390 395 400 Met His Ala Asp
Met Met Glu Asp Val Glu Glu Val Tyr Ala Gly Asp 405
410 415 Ile Cys Ala Leu Phe Gly Ile Asp Cys
Ala Ser Gly Asp Thr Phe Thr 420 425
430 Asn Lys Asp Asn Ser Asp Leu Ser Met Glu Ser Ile His Val
Pro Glu 435 440 445
Pro Val Ile Ser Ile Ala Met Arg Pro Ser Asn Lys Asn Asp Leu Glu 450
455 460 Lys Phe Ser Lys Gly
Ile Gly Arg Phe Thr Arg Glu Asp Pro Thr Phe 465 470
475 480 Lys Val His Phe Asp Pro Glu Ser Lys Glu
Thr Ile Val Ser Gly Met 485 490
495 Gly Glu Leu His Leu Glu Ile Tyr Ala Gln Arg Met Glu Arg Glu
Tyr 500 505 510 Gly
Cys Pro Cys Ile Thr Gly Lys Pro Lys Val Ala Phe Arg Glu Thr 515
520 525 Ile Val Ala Pro Val Pro
Val Ala Ser Asn Lys Glu Lys Leu Tyr Met 530 535
540 Leu Pro Ala Met Gln Cys Arg Gly Val Glu Trp
Cys Asn Leu Thr Gln 545 550 555
560 226129PRTMus Musculus 226Met Ala Ser Ala Trp Pro Arg Ser Leu
Pro Gln Ile Leu Val Leu Gly 1 5 10
15 Phe Gly Leu Val Leu Met Arg Ala Ala Ala Gly Glu Gln Ala
Pro Gly 20 25 30
Thr Ser Pro Cys Ser Ser Gly Ser Ser Trp Ser Ala Asp Leu Asp Lys
35 40 45 Cys Met Asp Cys
Ala Ser Cys Pro Ala Arg Pro His Ser Asp Phe Cys 50
55 60 Leu Gly Cys Ala Ala Ala Pro Pro
Ala His Phe Arg Leu Leu Trp Pro 65 70
75 80 Ile Leu Gly Gly Ala Leu Ser Leu Val Leu Val Leu
Ala Leu Val Ser 85 90
95 Ser Phe Leu Val Trp Arg Arg Cys Arg Arg Arg Glu Lys Phe Thr Thr
100 105 110 Pro Ile Glu
Glu Thr Gly Gly Glu Gly Cys Pro Gly Val Ala Leu Ile 115
120 125 Gln 227139PRTMus Musculus
227Met Ala Ser Ala Trp Pro Arg Ser Leu Pro Gln Ile Leu Val Leu Gly 1
5 10 15 Phe Gly Leu Val
Leu Met Arg Ala Ala Ala Gly Glu Gln Ala Pro Gly 20
25 30 Ser Lys Phe Gln Val Gly Lys Val Ser
Ser Phe Ile Arg Ser Pro Ser 35 40
45 Phe Ser Phe Ala Thr Cys Pro Ile Glu Ala Pro Pro His Ala
Leu Ala 50 55 60
Ala Ala Pro Gly Ala Arg Thr Ser Thr Ser Ala Trp Thr Ala Leu Leu 65
70 75 80 Val Gln Arg Asp His
Thr Ala Thr Ser Ala Trp Asp Ala Pro Gln His 85
90 95 Leu Leu Pro Thr Ser Gly Tyr Cys Gly Pro
Phe Trp Gly Ala Leu Leu 100 105
110 Val Trp Ser Trp Phe Trp Arg Trp Phe Leu Val Ser Trp Ser Gly
Glu 115 120 125 Asp
Ala Ala Gly Glu Lys Ser Leu Leu Pro Pro 130 135
22883PRTMus Musculus 228Met Ala Ser Ala Trp Pro Arg Ser Leu Pro
Gln Ile Leu Val Leu Gly 1 5 10
15 Phe Gly Leu Val Leu Met Arg Ala Ala Ala Gly Glu Gln Ala Pro
Gly 20 25 30 Thr
Ser Pro Cys Ser Ser Gly Ser Ser Trp Ser Ala Asp Leu Asp Lys 35
40 45 Cys Met Asp Cys Ala Ser
Cys Pro Ala Arg Pro His Ser Asp Phe Cys 50 55
60 Leu Gly Phe Ser Trp Ser Gly Glu Asp Ala Ala
Gly Glu Lys Ser Leu 65 70 75
80 Leu Pro Pro 229120PRTMus Musculus 229Met Ile Leu Gln Gln Pro
Leu Glu Arg Gly Pro Pro Ser Arg Asp Pro 1 5
10 15 Arg Ala Thr Thr Gly Val Thr Arg Gly Leu Asn
Ala Ser Leu Ser Pro 20 25
30 Arg Glu Pro Leu His Lys Gln Phe Leu Ser Glu Glu Asn Met Ala
Thr 35 40 45 His
Phe Ser Arg Leu Ser Leu His Asn Asp His Pro Tyr Cys Ser Pro 50
55 60 Pro Val Thr Phe Pro Glu
Ala Leu Pro Pro Leu Arg Ser Pro Cys Pro 65 70
75 80 Glu Leu Leu Leu Trp Arg Tyr Pro Gly Ser Leu
Ile Pro Glu Ala Leu 85 90
95 Arg Leu Leu Arg Leu Gly Asp Thr Pro Ser Pro Tyr Tyr Pro Ala Ser
100 105 110 Pro Ala
Gly Asp Ile Val Glu Leu 115 120 230202PRTMus
Musculus 230Met Ala Lys Ala Tyr Asp His Leu Phe Lys Leu Leu Leu Ile Gly
Asp 1 5 10 15 Ser
Gly Val Gly Lys Thr Cys Leu Ile Ile Arg Phe Ala Glu Asp Asn
20 25 30 Phe Asn Ser Thr Tyr
Ile Ser Thr Ile Gly Ile Asp Phe Lys Ile Arg 35
40 45 Thr Val Asp Ile Glu Gly Lys Arg Ile
Lys Leu Gln Val Trp Asp Thr 50 55
60 Ala Gly Gln Glu Arg Phe Lys Thr Ile Thr Thr Ala Tyr
Tyr Arg Gly 65 70 75
80 Ala Met Gly Ile Ile Leu Val Tyr Asp Ile Thr Asp Glu Lys Ser Phe
85 90 95 Glu Asn Ile Gln
Asn Trp Met Lys Ser Ile Lys Glu Asn Ala Ser Ala 100
105 110 Gly Val Glu Arg Leu Leu Leu Gly Asn
Lys Cys Asp Met Glu Ala Lys 115 120
125 Arg Gln Val Gln Arg Glu Gln Ala Glu Lys Leu Ala Arg Glu
His Arg 130 135 140
Ile Arg Phe Phe Glu Thr Ser Ala Lys Ser Ser Val Asn Val Asp Glu 145
150 155 160 Ala Phe Ser Ser Leu
Ala Arg Asp Ile Leu Leu Lys Thr Gly Gly Arg 165
170 175 Arg Ser Gly Thr Asn Ser Lys Pro Ser Ser
Thr Gly Leu Lys Thr Ser 180 185
190 Asp Lys Lys Lys Asn Lys Cys Leu Leu Gly 195
200 231300PRTMus Musculus 231Met Ala Gly Ile Pro Glu Val
Val Ala Met Asp Cys Glu Met Val Gly 1 5
10 15 Leu Gly Pro Gln Arg Val Ser Gly Leu Ala Arg
Cys Ser Ile Val Asn 20 25
30 Ile His Gly Ala Val Leu Tyr Asp Lys Tyr Ile Arg Pro Glu Gly
Glu 35 40 45 Ile
Thr Asp Tyr Arg Thr Gln Val Ser Gly Val Thr Pro Gln His Met 50
55 60 Val Arg Ala Thr Pro Phe
Gly Glu Ala Arg Leu Glu Ile Leu Gln Leu 65 70
75 80 Leu Lys Gly Lys Leu Val Val Gly His Asp Leu
Lys His Asp Phe Asn 85 90
95 Ala Leu Lys Glu Asp Met Ser Lys Tyr Thr Ile Tyr Asp Thr Ser Thr
100 105 110 Asp Arg
Leu Leu Trp His Glu Ala Lys Leu Gln Tyr Tyr Ser Arg Val 115
120 125 Ser Leu Arg Leu Leu Cys Lys
Arg Leu Leu His Lys Asn Ile Gln Val 130 135
140 Leu Pro Gly Ser Leu Leu Gly Val Gly Gly Cys Ile
Leu Pro Gly Thr 145 150 155
160 Asp Ile Leu His Leu Leu Leu Tyr Val Gly Met Val Arg Ile Ala Asp
165 170 175 Leu Arg Leu
Leu Thr Pro Phe Leu Pro Pro Ser Cys Leu Ala Cys Pro 180
185 190 Leu Leu Pro Glu Ser Leu Ala Ser
Ala Arg Ser His Ala Val Ile Ser 195 200
205 Ala Leu Ser Ser Ser Ser His Leu Leu Thr Pro Leu Pro
Asn Pro Ser 210 215 220
Gln Gly Pro Gln Gly His Val Asp Arg Leu Ser Gly Gln Leu Gln Asp 225
230 235 240 Trp Gly Gly Ser
Pro Leu Ala Pro Ala Leu Pro Val Ser Ala Glu Gln 245
250 255 Leu Ala Gly Pro Leu Leu Cys Gly Arg
Cys Gln Gly His Asn Gly Ala 260 265
270 Leu Gln Asn Leu Ser Ala Thr Gln Ser Pro Ala Arg Ala Ala
Leu Pro 275 280 285
Trp Asp Val Arg Leu Asn Phe Ile Leu Ile Gln Gly 290
295 300 232181PRTMus Musculus 232Met Ala Gly Ile Pro Glu
Val Val Ala Met Asp Cys Glu Met Val Gly 1 5
10 15 Leu Gly Pro Gln Arg Val Ser Gly Leu Ala Arg
Cys Ser Ile Val Asn 20 25
30 Ile His Gly Ala Val Leu Tyr Asp Lys Tyr Ile Arg Pro Glu Gly
Glu 35 40 45 Ile
Thr Asp Tyr Arg Thr Gln Val Ser Gly Val Thr Pro Gln His Met 50
55 60 Val Arg Ala Thr Pro Phe
Gly Glu Ala Arg Leu Glu Ile Leu Gln Leu 65 70
75 80 Leu Lys Gly Lys Leu Val Val Gly His Asp Leu
Lys His Asp Phe Asn 85 90
95 Ala Leu Lys Glu Asp Met Ser Lys Tyr Thr Ile Tyr Asp Thr Ser Thr
100 105 110 Asp Arg
Leu Leu Trp His Glu Ala Lys Leu Gln Tyr Tyr Ser Arg Val 115
120 125 Ser Leu Arg Leu Leu Cys Lys
Arg Leu Leu His Lys Asn Ile Gln Asn 130 135
140 Asn Trp Arg Gly His Cys Ser Val Glu Asp Ala Arg
Ala Thr Met Glu 145 150 155
160 Leu Tyr Lys Ile Ser Gln Arg Leu Arg Ala Gln Arg Gly Leu Pro Cys
165 170 175 Pro Gly Thr
Ser Asp 180 233201PRTMus Musculus 233Met Ala Gly Ile Pro
Glu Val Val Ala Met Asp Cys Glu Met Val Gly 1 5
10 15 Leu Gly Pro Gln Arg Val Ser Gly Leu Ala
Arg Cys Ser Ile Val Asn 20 25
30 Ile His Gly Ala Val Leu Tyr Asp Lys Tyr Ile Arg Pro Glu Gly
Glu 35 40 45 Ile
Thr Asp Tyr Arg Thr Gln Val Ser Gly Val Thr Pro Gln His Met 50
55 60 Val Arg Ala Thr Pro Phe
Gly Glu Ala Arg Leu Glu Ile Leu Gln Leu 65 70
75 80 Leu Lys Gly Lys Leu Val Val Gly His Asp Leu
Lys His Asp Phe Asn 85 90
95 Ala Leu Lys Glu Asp Met Ser Lys Tyr Thr Ile Tyr Asp Thr Ser Thr
100 105 110 Asp Arg
Leu Leu Trp His Glu Ala Lys Leu Gln Tyr Tyr Ser Arg Val 115
120 125 Ser Leu Arg Leu Leu Cys Lys
Arg Leu Leu His Lys Asn Ile Gln Val 130 135
140 Arg Ser Leu Pro Ala Pro Met Thr Leu Leu Val Ser
Leu Ser Ser Pro 145 150 155
160 Ser Ser Leu Ser Phe Ser Leu Phe Pro Leu Arg Cys Ser Phe Ser Phe
165 170 175 Ser Phe Leu
Ser Tyr Ser Ser Lys Gln Gly Val Leu Leu Leu Ser Ser 180
185 190 Leu Val Leu Pro Leu Leu Pro Cys
Phe 195 200 234358PRTMus Musculus 234Met Val
Trp Gly His Phe Pro Leu Ala Val Phe Asp Ser Leu Gly Ser 1 5
10 15 Gly Glu Met Ala Asp Ser Val
Lys Thr Phe Leu Gln Asp Leu Gly Arg 20 25
30 Gly Ile Lys Asp Ser Ile Trp Gly Ile Cys Thr Ile
Ser Lys Leu Asp 35 40 45
Ala Arg Ile Gln Gln Lys Arg Glu Glu Gln Arg Arg Arg Arg Ala Ser
50 55 60 Ser Leu Leu
Ala Gln Arg Arg Pro Gln Ser Val Glu Arg Lys Gln Glu 65
70 75 80 Ser Glu Pro Arg Ile Val Ser
Arg Ile Phe Gln Cys Cys Ala Trp Asn 85
90 95 Gly Gly Val Phe Trp Phe Ser Leu Leu Leu Phe
Tyr Arg Val Phe Ile 100 105
110 Pro Val Leu Gln Ser Val Thr Ala Arg Ile Ile Gly Asp Pro Ser
Leu 115 120 125 His
Gly Asp Val Trp Ser Trp Leu Glu Phe Phe Leu Thr Ser Ile Phe 130
135 140 Ser Ala Leu Trp Val Leu
Pro Leu Phe Val Leu Ser Lys Val Val Asn 145 150
155 160 Ala Ile Trp Phe Gln Asp Ile Ala Asp Leu Ala
Phe Glu Val Ser Gly 165 170
175 Arg Lys Pro His Pro Phe Pro Ser Val Ser Lys Ile Ile Ala Asp Met
180 185 190 Leu Phe
Asn Leu Leu Leu Gln Ala Leu Phe Leu Ile Gln Gly Met Phe 195
200 205 Val Ser Leu Phe Pro Ile His
Leu Val Gly Gln Leu Val Ser Leu Leu 210 215
220 His Met Ser Leu Leu Tyr Ser Leu Tyr Cys Phe Glu
Tyr Arg Trp Phe 225 230 235
240 Asn Lys Gly Ile Glu Met His Gln Arg Leu Ser Asn Ile Glu Arg Asn
245 250 255 Trp Pro Tyr
Tyr Phe Gly Phe Gly Leu Pro Leu Ala Phe Leu Thr Ala 260
265 270 Met Gln Ser Ser Tyr Ile Ile Ser
Gly Cys Leu Phe Ser Ile Leu Phe 275 280
285 Pro Leu Phe Ile Ile Ser Ala Asn Glu Ala Lys Thr Pro
Gly Lys Ala 290 295 300
Tyr Leu Phe Gln Leu Arg Leu Phe Ser Leu Val Val Phe Leu Ser Asn 305
310 315 320 Arg Leu Phe His
Lys Thr Val Tyr Leu Gln Ser Ala Leu Ser Ser Ser 325
330 335 Ser Ser Ala Glu Lys Phe Pro Ser Pro
His Pro Ser Pro Ala Lys Leu 340 345
350 Lys Ala Ala Ala Gly His 355
235374PRTMus Musculus 235Met Val Trp Gly His Phe Pro Leu Ala Val Phe Asp
Ser Leu Gly Ser 1 5 10
15 Gly Glu Met Ala Asp Ser Val Lys Thr Phe Leu Gln Asp Leu Gly Arg
20 25 30 Gly Ile Lys
Asp Ser Ile Trp Gly Ile Cys Thr Ile Ser Lys Leu Asp 35
40 45 Ala Arg Ile Gln Gln Lys Arg Glu
Glu Gln Arg Arg Arg Arg Ala Ser 50 55
60 Ser Leu Leu Ala Gln Arg Arg Pro Gln Ser Val Glu Arg
Lys Gln Glu 65 70 75
80 Ser Glu Pro Arg Ile Val Ser Arg Ile Phe Gln Cys Cys Ala Trp Asn
85 90 95 Gly Gly Val Phe
Trp Phe Ser Leu Leu Leu Phe Tyr Arg Val Phe Ile 100
105 110 Pro Val Leu Gln Ser Val Thr Ala Arg
Ile Ile Gly Asp Pro Ser Leu 115 120
125 His Gly Asp Val Trp Ser Trp Leu Glu Phe Phe Leu Thr Ser
Ile Phe 130 135 140
Ser Ala Leu Trp Val Leu Pro Leu Phe Val Leu Ser Lys Val Val Asn 145
150 155 160 Ala Ile Trp Phe Gln
Asp Ile Ala Asp Leu Ala Phe Glu Val Ser Gly 165
170 175 Arg Lys Pro His Pro Phe Pro Ser Val Ser
Lys Ile Ile Ala Asp Met 180 185
190 Leu Phe Asn Leu Leu Leu Gln Ala Leu Phe Leu Ile Gln Gly Met
Phe 195 200 205 Val
Ser Leu Phe Pro Ile His Leu Val Gly Gln Leu Val Ser Leu Leu 210
215 220 His Met Ser Leu Leu Tyr
Ser Leu Tyr Cys Phe Glu Tyr Arg Trp Phe 225 230
235 240 Asn Lys Gly Ile Glu Met His Gln Arg Leu Ser
Asn Ile Glu Arg Asn 245 250
255 Trp Pro Tyr Tyr Phe Gly Phe Gly Leu Pro Leu Ala Phe Leu Thr Ala
260 265 270 Met Gln
Ser Ser Tyr Ile Ile Ser Gly Cys Leu Phe Ser Ile Leu Phe 275
280 285 Pro Leu Phe Ile Ile Ser Ala
Asn Glu Ala Lys Thr Pro Gly Lys Ala 290 295
300 Tyr Leu Phe Gln Leu Arg Leu Phe Ser Leu Val Val
Phe Leu Ser Asn 305 310 315
320 Arg Leu Phe His Lys Thr Val Tyr Leu Gln Pro Leu Ser Pro Ala Val
325 330 335 Lys Gly Val
Gly Gly Thr Gly Trp Arg Met Trp Gln Leu Phe Ser Leu 340
345 350 Phe Ser Ser Pro Cys Arg Gly Arg
Gln Asn Pro Leu Pro Arg Ala Leu 355 360
365 Cys Ile Val Pro Cys Leu 370
236179PRTMus Musculus 236Met Val Trp Gly His Phe Pro Leu Ala Val Phe Asp
Ser Leu Gly Ser 1 5 10
15 Gly Glu Met Ala Asp Ser Val Lys Thr Phe Leu Gln Asp Leu Gly Arg
20 25 30 Gly Ile Lys
Asp Ser Ile Trp Gly Ile Cys Thr Ile Ser Lys Leu Asp 35
40 45 Ala Arg Ile Gln Gln Lys Arg Glu
Glu Gln Arg Arg Arg Arg Ala Ser 50 55
60 Ser Leu Leu Ala Gln Arg Arg Pro Gln Ser Val Glu Arg
Lys Gln Glu 65 70 75
80 Ser Glu Pro Arg Ile Val Ser Arg Ile Phe Gln Cys Cys Ala Trp Asn
85 90 95 Gly Gly Val Phe
Trp Phe Ser Leu Leu Leu Phe Tyr Arg Val Phe Ile 100
105 110 Pro Val Leu Gln Ser Val Thr Ala Arg
Ile Ile Gly Asp Pro Ser Leu 115 120
125 His Gly Asp Val Trp Ser Trp Leu Glu Phe Phe Leu Thr Ser
Ile Phe 130 135 140
Ser Ala Leu Trp Val Leu Pro Leu Phe Val Leu Ser Lys Val Val Asn 145
150 155 160 Ala Ile Trp Phe Gln
Val Gly Ala Gly Gln Asn Gly Thr Gly Phe Tyr 165
170 175 Met Leu Gly 23720DNAArtificial
SequenceSynthetic polynucleotide 237gggaaatcgt gcgtgacatt
2023817DNAArtificial SequenceSynthetic
polynucleotide 238gcggcagtgg ccatctc
1723976DNAArtificial SequenceSynthetic polynucleotide
239gggaaatcgt gcgtgacatt aaagagaagc tgtgctatgt tgccctagac ttcgagcaag
60agatggccac tgccgc
7624020DNAArtificial SequenceSynthetic polynucleotide 240taccctattg
agcacggcat
2024120DNAArtificial SequenceSynthetic polynucleotide 241cgcagctcgt
tgtagaaggt
2024280DNAArtificial SequenceSynthetic polynucleotide 242taccccattg
aacacggcat catcacgaac tgggatgaca tggagaagat ctggcaccac 60tccttctaca
acgagctgcg
8024321DNAArtificial SequenceSynthetic polynucleotide 243gcgaaagtgg
aaaagccaag t
2124424DNAArtificial SequenceSynthetic polynucleotide 244gccacatcaa
caggactctt gtag
2424576DNAArtificial SequenceSynthetic polynucleotide 245gcgaaagtgg
aaaagccaag tacaaagcct aaaagacagc ggcaagttga atctacaaga 60gtcctgttga
tgtggc
7624623DNAArtificial SequenceSynthetic polynucleotide 246caagcatacc
aagaagcatt tga
2324718DNAArtificial SequenceSynthetic polynucleotide 247gggccagacc
cagtctga
1824876DNAArtificial SequenceSynthetic polynucleotide 248caagcatacc
aagaagcatt tgaaatcagc aaaaaggaga tgcagccgac acaccccatc 60agactgggtc
tggccc
7624920DNAArtificial SequenceSynthetic polynucleotide 249ccaaggactg
ggcttagggt
2025022DNAArtificial SequenceSynthetic polynucleotide 250agagattccc
ttgtgcaaat gc
22251144DNAArtificial SequenceSynthetic polynucleotide 251ccaaggactg
ggcttagggt tcaggggagc cttccagggt gtctaattgc cctgtctctg 60gttctggggc
agacagagag cctcaagcta ggtcacaaag cgactcatac taaggatctg 120cagcatttgc
acaagggaat ctct
14425222DNAArtificial SequenceSynthetic polynucleotide 252gatctgggta
ggtggttgtt gg
2225322DNAArtificial SequenceSynthetic polynucleotide 253cgcacaccct
tataaaagtc cc
22254102DNAArtificial SequenceSynthetic polynucleotide 254gatctgggta
ggtggttgtt ggggcagaaa ggaggtcgta gacttaggat ataggaaacc 60aggaaaaact
gactgaggaa gggactttta taagggtgtg cg
10225524DNAArtificial SequenceSynthetic polynucleotide 255atctcgatgg
taacgggtct aatc
2425620DNAArtificial SequenceSynthetic polynucleotide 256tttgtgctga
ccttcatgcc
20257124DNAArtificial SequenceSynthetic polynucleotide 257atctcgatgg
taacgggtct aatcagccca tgatcaacat aactgtggtg atatacattt 60ggtatttttt
aattttcgga tgccttcctc aacatagccg tcaaggcatg aaggtcagca 120caaa
12425821DNAArtificial SequenceSynthetic polynucleotide 258ccagcctagc
ctctcttttg c
2125923DNAArtificial SequenceSynthetic polynucleotide 259aacattccca
cagggtacat tca
23260121DNAArtificial SequenceSynthetic polynucleotide 260ccagcctagc
ctctcttttg cactgctggt tcagcccact gggcctccgt cctttcctct 60ggaagggact
tggccttggg tgacaaattc ctctttgatg aatgtaccct gtgggaatgt 120t
12126120DNAArtificial SequenceSynthetic polynucleotide 261gggccacaat
ggagctctac
2026226DNAArtificial SequenceSynthetic polynucleotide 262acaggtctca
ttcatggaaa actatg
26263151DNAArtificial SequenceSynthetic polynucleotide 263gggccacaat
ggagctctac aaaatctctc agcgactcag agcccagcga gggctgccct 60gcctgggaac
atcagcctga acttcatcct catccaggat cagaagcagc tactccttga 120aggaccatag
ttttccatga atgagacctg t
15126417DNAArtificial SequenceSynthetic polynucleotide 264ggaggagggc
agagcca
1726525DNAArtificial SequenceSynthetic polynucleotide 265tctggttcat
tatcaaggga agttg
25266151DNAArtificial SequenceSynthetic polynucleotide 266ggaggagggc
agagccagag gagggacagc ctgatgcaga cagccctgac tcaacctgcc 60agccccctta
cctgtcagcc ttgaggagat ggaacagccc agcctactag gcctgccccc 120actccccaac
ttcccttgat aatgaaccag a
15126722DNAArtificial SequenceSynthetic polynucleotide 267atcctgttgg
gtctgcttct ca
2226830DNAArtificial SequenceSynthetic polynucleotide 268cacaagtaaa
tacatagact ggaatcaatg
30269155DNAArtificial SequenceSynthetic polynucleotide 269atcctgttgg
gtctgcttct cacagcgtat ggggctgtgt gcttttactc atggtggcag 60cagcagttgt
tgtcacttct ttggccaggc acagtgggtg atccttacag agcagcacag 120attcccattg
attccagtct atgtatttac ttgtg
15527025DNAArtificial SequenceSynthetic polynucleotide 270tgtttaaaat
ctgggctctt gattc
2527131DNAArtificial SequenceSynthetic polynucleotide 271gtatttccaa
tagtcaatgc agtaactcta c
31272155DNAArtificial SequenceSynthetic polynucleotide 272tgtttaaaat
ctgggctctt gattcagacc gagttttaat actggatctc attcaatctt 60tgtgtttttt
ctttttcttt tctttttttt ccaatagtac ggcagtgcta atagcagtcc 120tttagtagag
ttactgcatt gactattgga aatac
15527321DNAArtificial SequenceSynthetic polynucleotide 273gccacagtag
aggctgcact t
2127424DNAArtificial SequenceSynthetic polynucleotide 274gaatcaactg
gaaatgttct aggg
24275137DNAArtificial SequenceSynthetic polynucleotide 275gccacagtag
aggctgcact tgccactgct gtgtagcggc actctcctga ctcacttaaa 60aattctctgg
aggtttaagt gaggacccag ttccatctct agatatccag gctccctaga 120acatttccag
ttgattc
13727620DNAArtificial SequenceSynthetic polynucleotide 276ctgcaactga
gcatgtgcgt
2027719DNAArtificial SequenceSynthetic polynucleotide 277tgcataagaa
ccaccgggg
19278155DNAArtificial SequenceSynthetic polynucleotide 278ctgcaactga
gcatgtgcgt gggcgagtgc ccccacctct accggtcggc caacacgcat 60gcgcagatca
aagcacgcct gcatggcctg cagcccgaca gagtgccggc cccgtgctgt 120gtcccctcca
gctacacccc ggtggttctt atgca
15527916DNAArtificial SequenceSynthetic polynucleotide 279ggacggccga
gcacaa
1628022DNAArtificial SequenceSynthetic polynucleotide 280gtgtgcatgt
gcataggtca ga
22281123DNAArtificial SequenceSynthetic polynucleotide 281ggacggccga
gcacaatggt gcttgctgta cagcctcata gaccttcctt ggatctccca 60gacacactta
gtggaaggag agaatccatt cttgcaaatt gtctgaccta tgcacatgca 120cac
12328226DNAArtificial SequenceSynthetic polynucleotide 282tactgtttcc
tgtgaagcac atacct
2628323DNAArtificial SequenceSynthetic polynucleotide 283gcagagcagt
aaagaccaaa acc
23284137DNAArtificial SequenceSynthetic polynucleotide 284tactgtttcc
tgtgaagcac ataccttgta tgtgggaggt aaaggagcac gccagctgct 60ccatgtcact
ccctctatag ccatcactgt cttgtttttt tgtaactcag gttaggtttt 120ggtctttact
gctctgc
13728521DNAArtificial SequenceSynthetic polynucleotide 285aatctaggct
gcctcctgga g
2128628DNAArtificial SequenceSynthetic polynucleotide 286aggtcaatta
tacaaggcat gactttag
28287101DNAArtificial SequenceSynthetic polynucleotide 287aatctaggct
gcctcctgga ggaagatact taggagttca gaagtgaaga gatgaggctt 60ataatacttt
ttcctaaagt catgccttgt ataattgacc t
10128820DNAArtificial SequenceSynthetic polynucleotide 288tcgtcagaat
tgctgcctca
2028924DNAArtificial SequenceSynthetic polynucleotide 289tctgtggtaa
aaacctcctg gagt
24290151DNAArtificial SequenceSynthetic polynucleotide 290tcgtcagaat
tgctgcctca atctagtccc atttgagaaa atttgtttct actgtctcaa 60taactggatg
aaatatcact ctgaaaactt gcctattgca ctaaagctag tttaggcttg 120ataaaacact
ccaggaggtt tttaccacag a
15129130DNAArtificial SequenceSynthetic polynucleotide 291ataaaatcaa
tcccactttc ttgttaaaag
3029226DNAArtificial SequenceSynthetic polynucleotide 292ctttgcctta
gaaaatatga tcctgc
26293109DNAArtificial SequenceSynthetic polynucleotide 293ataaaatcaa
tcccactttc ttgttaaaag gagaaacgat ctgaattttg aaagactaga 60agcccaactt
aaggcctgcc actgcaggat catattttct aaggcaaag
10929428DNAArtificial SequenceSynthetic polynucleotide 294gagatccaag
cactgaagta tgtagagt
2829528DNAArtificial SequenceSynthetic polynucleotide 295tcaggagtac
agtggataca tttctctt
28296134DNAArtificial SequenceSynthetic polynucleotide 296gagatccaag
cactgaagta tgtagagtta acagaaggag tagaatgtat tcagaaacat 60tccaaggtat
gccaaggtga tagcattgat cctattagca agctacaaga gaaatgtatc 120cactgtactc
ctga
13429721DNAArtificial SequenceSynthetic polynucleotide 297gggcactgca
tggattatgt c
2129821DNAArtificial SequenceSynthetic polynucleotide 298ccatgcccag
aataaaggag c
21299101DNAArtificial SequenceSynthetic polynucleotide 299gggcactgca
tggattatgt cggttttacc tagctttgga gaccatcatt ttttcctaat 60aggtttgctt
cattgtttca gctcctttat tctgggcatg g
10130024DNAArtificial SequenceSynthetic polynucleotide 300ctccgttagc
aattatgggt cagt
2430121DNAArtificial SequenceSynthetic polynucleotide 301gaagctcatg
gtccttcagg g
21302102DNAArtificial SequenceSynthetic polynucleotide 302ctccgttagc
aattatgggt cagtaactga tcttattaga gctttacaac tttggtttag 60gaaaagcaca
taaaatgggc gccctgaagg accatgagct tc
10230323DNAArtificial SequenceSynthetic polynucleotide 303ctgtcattgt
catttttccc acc
2330422DNAArtificial SequenceSynthetic polynucleotide 304atgccggatc
ttcaatctta gg
22305118DNAArtificial SequenceSynthetic polynucleotide 305ctgtcattgt
catttttccc acctaaaaat tccctgagga ctgatctggg tactttgctc 60tggagagctg
aagtctgagc gctgtatatt tggactccta agattgaaga tccggcat
11830621DNAArtificial SequenceSynthetic polynucleotide 306aactggctga
tgaccagctg t
2130717DNAArtificial SequenceSynthetic polynucleotide 307tgctgtgccc
gggttct
1730895DNAArtificial SequenceSynthetic polynucleotide 308aactggctga
tgaccagctg tgctactctg tgctgaccga ggactgatgc ctccttcccc 60tgtacccact
gctgaggaag aacccgggca cagca
9530917DNAArtificial SequenceSynthetic polynucleotide 309gtgagtcagg
ccgggct
1731023DNAArtificial SequenceSynthetic polynucleotide 310tcaaaaaatc
ggattctgtg ctc
23311115DNAArtificial SequenceSynthetic polynucleotide 311gtgagtcagg
ccgggctgct gtggccgaat gccttgcttc tgccctttat ccagctctct 60ccttcctacc
tcatccccta cagttggctc gagagcacag aatccgattt tttga
11531221DNAArtificial SequenceSynthetic polynucleotide 312ttctcctgaa
tctggctggg t
2131323DNAArtificial SequenceSynthetic polynucleotide 313tggaaaaagg
atgtccattc ttc
23314105DNAArtificial SequenceSynthetic polynucleotide 314ttctcctgaa
tctggctggg tcccccttcc ttaccccaac tctttaactg gtgatgaaaa 60cagcaaggag
aaagggcagc ctgaagaatg gacatccttt ttcca
10531525DNAArtificial SequenceSynthetic polynucleotide 315agaatccgat
tttttgagac aagtg
2531620DNAArtificial SequenceSynthetic polynucleotide 316gatctccggc
ctcctgtctt
20317104DNAArtificial SequenceSynthetic polynucleotide 317agaatccgat
tttttgagac aagtgccaaa tccagtgtga atgtggatga ggctttcagt 60tccctggccc
gtgacatctt gctcaagaca ggaggccgga gatc
10431820DNAArtificial SequenceSynthetic polynucleotide 318caagccctca
agcactgacc
2031921DNAArtificial SequenceSynthetic polynucleotide 319ggtctagcct
ccaggttcag g
21320113DNAArtificial SequenceSynthetic polynucleotide 320caagccctca
agcactgacc tgaaagtatc tgacaagaag aacagcaaca agtgctcctt 60gggctgagga
acatttcttg cctcctattc accctgaacc tggaggctag acc
11332119DNAArtificial SequenceSynthetic polynucleotide 321gggtggggga
atctagcct
1932220DNAArtificial SequenceSynthetic polynucleotide 322ccccagacaa
agggacatgt
20323106DNAArtificial SequenceSynthetic polynucleotide 323gggtggggga
atctagcctc tctagagccc tagccctctg acgaggagga ggtgtagtgc 60cctgtagctt
ttccccagga ctcgccacat gtccctttgt ctgggg
10632422DNAArtificial SequenceSynthetic polynucleotide 324cgctgaagtc
ctcagtgact tg
2232522DNAArtificial SequenceSynthetic polynucleotide 325cactaagtgc
ttcgacaccc ac
22326161DNAArtificial SequenceSynthetic polynucleotide 326cgctgaagtc
ctcagtgact tgtcccattt cttagtagtt gtacaaggag tcaggccaag 60atggtgcctc
gggggctgag ggagctcaca ggaactgagc agtgactggt cctttcccag 120tattgaatac
tgagcccctg tgggtgtcga agcacttagt g
16132719DNAArtificial SequenceSynthetic polynucleotide 327acagcctgat
gcagacagc
1932825DNAArtificial SequenceSynthetic polynucleotide 328tctggttcat
tatcaaggga agttg
25329127DNAArtificial SequenceSynthetic polynucleotide 329acagcctgat
gcagacagcc ctgactcaac ctgccagccc ccttacctgg ccagccttga 60ggagatggaa
cagcccaggc tacaaggcct gcccccactc ctcaacttcc cttgataatg 120aaccaga
12733025DNAArtificial SequenceSynthetic polynucleotide 330cagaattgct
gcctcaatct agtcc
2533124DNAArtificial SequenceSynthetic polynucleotide 331ggttttgcag
atgtactcgg ttcc
24332219DNAArtificial SequenceSynthetic polynucleotide 332cagaattgct
gcctcaatct agtcccattt gagaaaattt gtttctactg tctcaataac 60tggatgaaat
atcactctga aaacttgcct attgcactaa agctagttta ggcttgataa 120aacactccag
gaggttttta ccacagactg tttctattaa aactgctgct tctcatgtac 180aattttgttt
taaaaggaac cgagtacatc tgcaaaacc 219
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