Materials and methods for assaying for methylation of CpG islands associated with genes in the evaluation of cancer

Abstract

Provided are methods, reagents, and kits for evaluating cancer, such as prostate cancer, in a subject. Disclosed methods of evaluating cancer include methods of diagnosing cancer, methods of prognosticating cancer and methods of assessing the efficacy of cancer treatment. The methods include assaying a biological sample for methylation of a CpG island associated with specified genes. Provided reagents and kits include primers suitable for amplifying at least a portion of a target CpG islands associated with specified genes.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]This patent application is a continuation of International Patent Application No. PCT/US2006/060685, filed Nov. 8, 2006, designating the United States, which claims the benefit of U.S. Provisional Patent Application No. 60/734,577, filed Nov. 8, 2005, which are incorporated by reference herein in their entirety.

INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ELECTRONICALLY

[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 214,875 Byte ASCII (Text) file named "702375_ST25.TXT," created on May 2, 2008.

BACKGROUND OF THE INVENTION

[0003]Phosphate linked cytosine-guanine (CpG) dinucleotides are statistically underrepresented in the genomes of higher eukaryotes, including mammals. The dinucleotide is reportedly found at only 5-10% of its predicted frequency. The majority of CpG dinucleotides that do remain in the human genome are normally located within repetitive sequences that are characterized by low gene expression levels and exhibit methylation at the cytosine residues.

[0004]CpG islands, on the other hand, represent genomic sequences that contain clusters of CpG dinucleotide. CpG islands may be associated with the promoter region or 5' end of coding sequences or may be present within introns or in genomic regions that are not known to be associated with coding sequences. They may be unmethylated or methylated in normal tissues and the methylation pattern may be used to control tissue specific expression and the expression of imprinted genes. Methylation of CpG islands within promoter regions can result in the downregulation or silencing of the associated gene. An increase in methylation of normally unmethylated islands is observed in aging tissues even as the overall methylcytosine content of the DNA is reduced. The aberrant methylation pattern is more pronounced in cancer cells with increased methylation or hypermethylation detected in various cancer tissues. CpG islands may be methylated to varying densities within the same tissue. Thus, aberrant methylation of cytosines within CpG islands can be a primary epigenetic event that acts to suppress the expression of genes involved in critical cellular processes, such as DNA damage repair, hormone response, cell-cycle control, and tumor-cell adhesion/metastasis, leading to tumor initiation, progression and metastasis (Li et al., Biochim. Biophys. Acta, 1704: 87-102 (2004)). It has been proposed that a unique profile of promoter hypermethylation exists for each human cancer in which some gene changes are shared and other gene changes are cancer-type specific (Esteller et al., Cancer Res., 61: 3225-3229 (2001)). Given that aberrant methylation represents new information not normally present in genomic DNA and that aberrant methylation is a common DNA modification and affects a large number of genomic targets, it is feasible to develop diagnostic and prognostic tests based on information obtained from multiple target CpGs. Such tests may be based on CpGs that are aberrantly hypermethylated or hypomethylated in the diseased tissues. They may also be based on changes in methylation density in CpG islands as long as the changes corrolate with the presence of cancer.

[0005]Prostate cancer, for example, which is the most common malignancy and the second leading cause of death among men in the U.S. (Li et al. (2004), supra), has been found to be associated with the methylation of CpG islands in the promoters of over 30 genes, in particular the CpG island of the glutathione S-transferase P1 (GSTP1) gene. GSTP1 methylation has been detected in over 50% of DNA recovered from urine and plasma of prostate cancer patients (Goessl et al., Ann. N.Y. Acad. Sci., 945: 51-58 (2001); Cairns et al., Clin. Cancer Res., 7: 2727-2730 (2001); Jeronimo et al., Urology, 60: 1131-1135 (2002); and Gonzalgo et al., Clin. Cancer Res., 9: 2673-2677 (2003)). However, if diagnosis of prostate cancer relied solely on the detection of the methylation of the CpG island in the GSTP1 gene, the theoretical limit of the sensitivity of such a test would only be approximately 90%. GSTP1 is also methylated in prostatic intraepithelial lesions (PIN) which may lead to a false positive diagnosis. Some CpG islands are methylated in prostate cancer and other diseases of the prostate, such as benign prostatic hyperplasia (BPH). They may even exhibit some degree of methylation in normal aging prostates. Such markers may not be suitable individually for prostate cancer diagnosis. Therefore, a panel of markers is required to achieve the sensitivity and specificity needed for a clinical test.

[0006]The prostate-specific antigen or PSA test continues to be widely used in the early detection of prostate cancer. While the PSA test has resulted in the majority of prostate cancer cases being diagnosed in asymptomatic men (Mettlin et al., Cancer, 83(8): 1679-1684 (1998a); Mettlin et al., Cancer, 82(2): 249-251 (1998b); Humphrey et al., J. Urol., 155: 816-820 (1996); and Grossfeld et al., Epidemiol. Rev., 23(1): 173-180 (2001)), the PSA test suffers from poor specificity, which can be as low as 33% when a PSA cut-off level of 2.6 ng/ml is used (Thompson et al., N. Engl. J. Med., 350: 2239-2246 (2004)), even though the sensitivity can be as high as 83%. The poor specificity of the PSA test is a direct result of increased secretion of PSA in other diseases of the prostate, such as BPH and prostatitis. Thus, an elevated PSA level indicates the need for additional screening in the form of needle biopsy. Ultimately, the results of needle biopsies lead to the diagnoses of prostate cancer.

[0007]Over 1 million needle biopsies of prostates are performed each year at a cost of about $1,500 each and much discomfort to the patient. However, less than 200,000 of these result in a diagnosis of prostate cancer. Therefore, the majority of needle biopsies are being performed needlessly.

[0008]In view of the above, there is a need for non-invasive methods of diagnosing and prognosticating cancer, such as prostate cancer, that reduce the cost and suffering associated with currently available cancer screening methods. It is an object of the invention to provide materials and methods for non-invasive diagnosis and prognosis of cancer, such as prostate cancer. This and other objects and advantages, as well as additional inventive features, will become apparent from the detailed description provided herein.

BRIEF SUMMARY OF THE INVENTION

[0009]The invention provides materials and methods for evaluating cancer. Methods of evaluating can include methods of diagnosing and prognosticating cancer as well as methods of assessing the efficacy of cancer treatment. Generally, the methods provided involve assaying for methylation of CpG islands associated with specific genes. The invention also provides pairs of isolated or purified primers that can be used in the methods of the invention, for example, to amplify and/or detect the methylation state of the CpG islands associated with specific genes. The invention also provides kits comprising one or more pairs of primers useful in the disclosed methods.

[0010]The invention provides methods of diagnosing cancer by assaying for one or more methylated CpG islands that are indicative of cancer. Generally, the method comprises providing a biological sample from a subject in need of cancer diagnosis and assaying the sample for methylation of one or more CpG islands associated with at least one gene selected from the group consisting of: neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidyl-inositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (predicted protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1A), ring finger protein 180 (LOG 285671 or RNF180), EGFR-co-amplified and overexpressed (DKFZP564K0822 or ECOP), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC286097 or EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-β signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2) Kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49).

[0011]The invention also provides a method of diagnosing prostate cancer in a male mammal by assaying for one or more methylated CpG islands that are indicative of prostate cancer. The method can include providing a biological sample from a subject in need of cancer diagnosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, ECOP, ZNF596, LOC441320, TDH, FLJ36980, EFHA2, ASAH1, NODAL, LOC399783, ISL2, MMP9, TNFSF11, RHOD or LRRC49. Kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), Ras association (RalGDS/AF-6) domain family 5 (RASSF5), and HtrA serine peptidase 4 (HTRA4). Optionally, the method of diagnosing prostate cancer can also include assaying for methylation of one or more CpG island associated with at least one gene that is known to be methylated in prostate cancer but is known not to be detectably methylated or is methylated at a lower level (e.g., about 50% or less, about 40% or less, 30% or less, about 20% or less, or about 10% or less) in BPH.

[0012]The invention also provides methods of prognosticating cancer by assaying for the methylation of one or more genes that are indicative of the grade or stage of the cancer, and/or the length of disease-free survival following treatment for cancer. Generally, the method comprises providing a biological sample from a subject in need of cancer prognosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD and LRRC49.

[0013]Further provided by the invention is a method of prognosticating prostate cancer in a male mammal by assaying for one or more methylated CpG islands that are indicative of the grade or stage of prostate cancer, and/or the length of disease-free survival following treatment of prostate cancer. The method comprises providing a biological sample from the male mammal and assaying the sample for methylation of a CpG island associated with at least one of the following genes: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, GPR62, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD or LRRC49. Optionally, the method of prognosticating prostate cancer can also include assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be methylated in prostate cancer but is known not to be detectably methylated or is methylated at a lower level (e.g., about 50% or less, about 40% or less, 30% or less, about 20% or less, or about 10% or less) in BPH. Methylation of the CpG islands associated with the genes is indicative of the grade or stage of the cancer, and/or the length of disease-free survival following treatment.

[0014]Furthermore, the invention provides methods of assessing the efficacy of treatment of cancer by assaying for the reduced methylation of CpG islands that indicates efficacy of treatment. Generally, the method comprises providing a first and a second biological sample from a subject in need of assessing the efficacy of treatment of cancer and assaying the samples for a change in methylation level of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD and LRRC49. The first biological sample is taken before the second biological sample, and the second biological sample is taken during or after a course of treatment. A decrease or absence of methylation of the assayed one or more CpG islands in the second sample (i.e., following the course of treatment) indicates that the treatment is effective. Alternatively, the maintenance or increase of methylation in the assayed CpG islands in the second sample can indicate a reduction or absence of treatment efficacy.

[0015]Also provided is a method of assessing the efficacy of treatment of prostate cancer in a male mammal by assaying biological samples, which are taken from the male mammal periodically during the course of treatment, for methylation of a CpG island and wherein a decrease or absence of methylation of the CpG islands following the course of treatment indicates that the treatment is effective. The method comprises (a) providing a first and a second biological sample from a subject undergoing a course of cancer treatment, wherein the first sample is taken at an earlier time than the second sample, and the second sample is taken during or following a course of treatment and (b) assaying the samples for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD and LRRC49. Optionally, this method can also include assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be methylated in prostate cancer but is known not to be detectably methylated or is methylated at a lower level (e.g. about 50% or less, about 40% or less, 30% or less, about 20% or less, or about 10% or less in BPH.

[0016]In preferred embodiments, the aforementioned methods of diagnosing, prognosticating and assessing the efficacy of treatment of cancer can further include assaying the biological sample for methylation of multiple CpG islands, for example, CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more genes.

[0017]Additionally, the invention provides a terminator-coupled linear amplification method of determining the methylation status of a CpG island. Generally, the method includes providing a DNA sample for terminator-coupled linear amplification and then incubating the DNA sample under deaminating conditions to thereby produce a deaminated DNA sample. Optionally, the deaminated DNA sample can be purified. The deaminated sample is used as template to amplify a target sequence or target sequences that include one or more CpG islands or portions of one or more CpG islands thereby producing one or more amplified target sequences. Optionally, the one or more amplified target sequences are purified. One or more sequences in the amplified target sequences are linearly amplified in the presence of a primer and a dideoxynucleotide to generate one or more fragments of different lengths, wherein each length corresponds to the distance in bases from the 5' end of the primer to the position where the dideoxynucleotide is incorporated. Optionally, the one or more fragments is purified. The one or more fragments are analyzed to determine their lengths. The lengths of the fragments can be used to determine the methylation status of methylated cytosines within the one or more amplified target sequences.

[0018]The invention also provides pairs of primers suitable for amplifying a CpG-island associated with genes described herein. Primers can include isolated or purified nucleic acid molecules suitable for amplifying a CpG island containing target sequence. Target sequences can include genomic sequence that has been fully methylated and fully deaminated such as those in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54.

[0019]Exemplary primer pairs include SEQ ID NOS: 55 and 56, SEQ ID NOS: 57 and 58, SEQ ID NOS: 59 and 60, SEQ ID NOS: 61 AND 62, SEQ ID NOS: 63 and 64, SEQ ID NOS: 65 and 66, SEQ ID NOS: 67 and 68, SEQ ID NOS: 69 and 70, SEQ ID NOS: 71 and 72, SEQ ID NOS: 73 and 74, SEQ ID NOS: 77 and 78, SEQ ID NOS: 79 and 80, SEQ ID NOS: 81 and 82, SEQ ID NOS: 83 and 84, SEQ ID NOS: 87 and 88, SEQ ID NOS: 89 and 90, SEQ ID NOS: 91 and 92, SEQ ID NOS: 93 and 94, SEQ ID NOS: 95 and 96, SEQ ID NOS: 97 and 98, SEQ ID NOS: 103 and 104, SEQ ID NOS: 105 and 106, SEQ ID NOS: 107 and 108, SEQ ID NOS: 109 and 110, SEQ ID NOS: 111 and 112, SEQ ID NOS: 113 and 114, SEQ ID NOS: 115 and 116, SEQ ID NOS: 117 and 118, SEQ ID NOS: 199 and 200, SEQ ID NOS: 201 and 202, SEQ ID NOS: 203 and 204, SEQ ID NOS: 205 and 206, SEQ ID NOS: 207 and 208, SEQ ID NOS: 209 and 210, SEQ ID NOS: 211 and 212, SEQ ID NOS: 213 and 214, SEQ ID NOS: 215 and 216, SEQ ID NOS: 217 and 218, SEQ ID NOS: 219 and 220, SEQ ID NOS: 221 and 222, SEQ ID NOS: 224 and 225, SEQ ID NOS: 227 and 228, SEQ ID NOS: 227 and 228, SEQ ID NOS: 230 and 231.

[0020]Also provided are kits that include one or more of the aforementioned pairs of primers.

BRIEF DESCRIPTION OF THE FIGURES

[0021]FIGS. 1A-1DD set forth the nucleotide sequences for SEQ ID NOS: 1-54. Sequences are presented in accordance with convention from left to right and top to bottom.

[0022]FIGS. 2A-2KK set forth the nucleotide sequences for SEQ ID NOS: 119-198. Sequences are presented in accordance with convention from left to right and top to bottom.

DETAILED DESCRIPTION OF THE INVENTION

[0023]The invention provides a method of diagnosing cancer by assaying for the methylation of one or more CpG islands that are indicative of cancer. Cancer can include, for example, lung, liver, pancreas, head and neck, throat, thyroid, esophagus, brain, ovarian, kidney, skin, colorectal, and hematopoeietic (e.g., lymphomas and leukemic) cancer. Generally, the method comprises providing a biological sample from a subject in need of cancer diagnosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD or LRRC49. In preferred embodiments, the method can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Methylation of the CpG islands associated with these genes is indicative of cancer.

[0024]The invention further provides a method of diagnosing prostate cancer by assaying for the methylation of one or more CpG islands that are indicative of prostate cancer in a male mammal. In one embodiment, the method comprises providing a biological sample from a male mammal in need of cancer diagnosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD and LRRC49. For example, the method of diagnosing prostate cancer includes assaying the biological sample for methylation of a CpG island associated with NRG1, KIF13B, or both. In another example, the method includes assaying for methylation of a CpG island associated with at least one gene selected from the group consisting of: TDH, ASAH1, FGF20, HEMK1, PALD NEUROG, EFHA2, KIFC2, GFRA1, DKK2, TNFSF11, NTN1, and RHOD. In preferred embodiments, the method of diagnosing prostate cancer can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Methylation of the CpG islands associated with these genes is indicative of cancer.

[0025]The foregoing method of diagnosing prostate cancer can optionally include, in combination with assaying for methylation of CpG islands associated with the foregoing genes, further assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be (i) methylated in prostate cancer and (ii) not detectably methylated or methylated at a lower level (e.g., about 50% or less, about 40% or less, about 30% or less, about 20% or less, or less than about 10%) in BPH. In this regard, when the method includes assaying for at least one CpG island that is known to be methylated in prostate cancer but is known not to be detectably methylated or methylated at a lower level in BPH, the method preferably includes assaying the biological sample for methylation of CpG islands associated with at least three different genes. Examples of CpG islands known to be methylated in prostate cancer but not detectably methylated or methylated at a lower level in BPH include CpG islands associated with glutathione S-transferase P1 (GSTP 1), glutathione peroxidase 3 (GPX3), glutathione S-transferase M1 (GSTM1), glutathione S-transferase M4 (GSTM4), Cub and Sushi multiple domains1 (CSMD1), tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), tumor necrosis factor receptor superfamily 10D (TNFRSF10D), secreted frizzled-related protein 1 (SFRP1), secreted frizzled-related protein 2 (SFRP2), dickkopf homolog 3 (DKK3), prostaglandin-endoperoxide synthase 2 (PTGS2), cyclin-dependent kinase inhibitor 1C (CDKN1C/p57), Ras association (RalGDS/AF-6) domain family 1 (RASSF1), and G-protein coupled receptor 62 (GPR62).

[0026]The invention also provides a method of prognosticating cancer by assaying for the methylation of one or more genes that are indicative of the grade or stage of the cancer, and/or the length of disease-free survival following treatment for cancer. Generally, the method comprises providing a biological sample from a subject in need of cancer prognosis and assaying the sample for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD and LRRC49. In preferred embodiments, the method can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Methylation of the CpG islands associated with these genes is indicative of the grade or stage of the cancer, and/or the length of disease-free survival following treatment for cancer.

[0027]The invention also provides a method of prognosticating prostate cancer in a male mammal by assaying for the methylation of one or more CpG islands that are indicative of the grade or stage of the prostate cancer, and/or the length of disease-free survival following treatment for prostate cancer. In one embodiment, the method comprises assaying a biological sample from the male mammal for methylation of a CpG island associated with at least one of the following genes: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTRIA, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, or ISL2. In addition to or instead of the foregoing, the method can include assaying the biological sample for methylation of a CpG island associated with at least one of the following genes: KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD or LRRC49. For example, the method of diagnosing prostate cancer includes assaying the biological sample for methylation of a CpG island associated with NRG1, KIF13B, or both. In another example, the method includes assaying for at least one of the following genes: TDH, ASAH1, FGF20, HEMK1, PALD NEUROG, EFHA2, KIFC2, GFRA1, DKK2, TNFSF11, NTN1, or RHOD. In preferred embodiments, the method of diagnosing prostate can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Methylation of the CpG islands associated with these genes is indicative of the grade or stage of prostate cancer, and/or the length of disease-free survival following treatment for prostate cancer.

[0028]The foregoing method of prognosticating prostate cancer can optionally include, in combination with assaying for methylation of CpG islands associated with the foregoing genes, further assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be (i) methylated in prostate cancer and (ii) not detectably methylated or methylated at a lower level (e.g., about 50% or less, about 40% or less, about 30% or less, about 20% or less, or less than about 10%) in BPH. Percent methylation level in BPH refers to the percent of patients that exhibit some detectable level of methylation at that locus. In this regard, when the method includes assaying for methylation of at least one CpG island that is known to be methylated in prostate cancer but is known not to be detectably methylated or is methylated at a lower level in BPH, the method preferably includes assaying the biological sample for methylation of CpG islands associated with at least three different genes. Examples of CpG islands known to be methylated in prostate cancer but not detectably methylated or methylated at a lower level in BPH include CpG islands associated with GSTP1, GPX3, GSTM1, GSTM4, CSMD1, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, SFRP1, SFRP2, DKK3, PTGS2, CDKN1C/p57, RASSF1, and GPR62. Methylation of CpG islands associated with the genes is indicative of the grade or stage of the prostate cancer, and/or the length of disease-free survival following treatment for prostate cancer.

[0029]Obtaining information about the aggressiveness of the cancer, its grade, and its stage is helpful when choosing a course of treatment. The patterns of CpG methylation may be correlated to the pathological stage and grade of the tumor. For example, in prostate cancer, patterns of CpG methylation may be correlated to the Gleason score of the primary tumor. The molecular information derived from CpG methylation may also be correlated to the likelihood of survival and the length of disease-free survival following treatment. The above prognostic methods can enable the prediction of the course of the cancer, as well as the prediction of the best approach to treatment.

[0030]Also provided are methods of assessing the efficacy of treatment of cancer by assaying for the reduced methylation of CpG islands that indicates efficacy of treatment. Generally, the method comprises providing a first and a second biological sample from a subject in need of assessing the efficacy of treatment of cancer and assaying the samples for a change in methylation level of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, ISL2, KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, MMP9, TNFSF11, RHOD and LRRC49. Generally, the first biological sample is taken (e.g, prior to commencing treatment or during treatment) before the second biological sample, and the second biological sample is taken after a course of treatment. In preferred embodiments, the method includes assaying for a change in methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. A decrease or absence of methylation of the assayed one or more CpG islands in the second sample (i.e., following the course of treatment) indicates that the treatment is effective. Alternatively, the maintenance or increase of methylation in the assayed CpG islands in the second sample can indicate a reduction or absence of treatment efficacy.

[0031]The invention provides a method of assessing the efficacy of treatment of prostate cancer in a male mammal by assaying for the reduced methylation of CpG islands that indicate efficacy of treatment of prostate cancer. In one embodiment, the method comprises assaying biological samples, which are taken from the male mammal periodically during the course of treatment, for methylation of a CpG island associated with at least one gene selected from the group consisting of: NRG1, ADRB3, GFRA2, KIF13B, RET, GPR147, NEUROG3, PALD, HEMK1, FGF4, HTR1A, RNF180, DKFZP5640822, ZNF596, LOC441320, TDH, FLJ36980, FGF20, EFHA2, ASAH1, NODAL, LOC399783, and ISL2. In addition to or instead of the foregoing, the method can include assaying the biological samples for methylation of a CpG island associated with at least one gene selected from the group consisting of: KIFC2, C20orf23, GFRA1, GPX7, DKK2, NTN1, RASSF5, HTRA4, MMP9, TNFSF11, RHOD and LRRC49. For example, the method of assessing the efficacy of treatment of prostate cancer includes assaying the biological sample for methylation of a CpG island associated with NRG1, KIF13B, or both. In another example, the method includes assaying for a CpG island associated with at least one gene selected from the group consisting of: TDH, ASAH1, FGF20, HEMK1, PALD NEUROG, EFHA2, KIFC2, GFRA1, DKK2, TNFSF11, NTN1, and RHOD. In preferred embodiments, the method can include assaying for methylation of CpG islands associated with two, three, four, five, six, seven, eight, nine, ten, eleven, or more of the foregoing genes. Generally, the assayed biological samples in the method include a first and a second biological sample. The first biological sample can be taken, for example, prior to commencing treatment or during treatment, though in any event prior to taking the second biological sample. The second biological sample is taken during or after a course of treatment. A decrease or absence of methylation of the assayed one or more CpG islands in the second sample (i.e., following the course of treatment) as compared to the first sample indicates that the treatment is effective. Alternatively, the maintenance or increase of methylation in the assayed CpG islands in the second sample as compared to the first sample can indicate a reduction in or absence of treatment efficacy.

[0032]The foregoing method of assessing the efficacy of prostate cancer treatment can optionally include, in combination with assaying for methylation of CpG islands associated with the foregoing genes, further assaying the biological sample for reduced methylation of a CpG island associated with at least one gene that is known to be (i) methylated in prostate cancer and (ii) not detectably methylated or methylated at a lower level (e.g., about 50% or less, about 40% or less, about 30% or less, about 20% or less, or less than about 10%) in BPH. In this regard, when the method includes assaying the biological samples for methylation of at least one CpG island that is known to be methylated in prostate cancer but known not to be detectably methylated or methylated at a lower level in BPH, the method preferably includes assaying for methylation of CpG islands associated with at least three different genes. Examples of CpG islands known not to be methylated in prostate cancer but not detectably methylated or methylated at a lower level in BPH include GSTP1, GPX3, GSTM1, GSTM4, CSMD1, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, SFRP1, SFRP2, DKK3, PTGS2, CDKN1C/p57, RASSF1, and GPR62. A decrease or absence of methylation of the CpG islands associated with the assayed genes in the second sample as compared to the first sample following some or all of the course of treatment indicates that the treatment is effective. Alternatively, the maintenance or increase of methylation in the assayed CpG islands in the second sample as compared to the first sample can indicate a reduction or absence of treatment efficacy.

[0033]CpG islands (Bird, Nature 321: 209-213 (1986); and Gardiner-Garden et al., J. Molec. Biol. 196: 261-282 (1987)) comprise about 1% of vertebrate genomes and account for about 15% of the total number of CpG dinucleotides. CpG islands typically are between about 0.2 and about 2.0 kb in length. They can be located upstream of (e.g., in a promoter or enhancer region) of the coding sequence of the associated genes or they may also extend into or be found within gene-coding regions of their associated genes. A gene-coding region can include exons and introns. Use of the phrase "associated with" to describe a CpG island's relation to a gene, is intended to encompass CpG islands that are upstream of gene coding sequences as well as internal CpG islands. For example, the CpG island associated with the RET gene is internal and not expected to affect the expression of the RET gene when methylated. Some CpG islands are associated with the promoter of two genes and it can affect the expression of both genes. CpGs were labeled based on their location with respect to the nearest gene. In some cases, a CpG island may be located near the promoter of two different genes and may in this case influence the expression of both genes. In such case, the CpG island was named after one of the genes. For example, the LRRC49 CpG island is also associated with the THAP domain containing 10 (THAP10) gene. A CpG island can also be associated with a pseudogene or be located in a genomic region that includes no known genes or pseudogenes. The CpG island can still be of interest so long as its methylation status correlates with a disease status.

[0034]A CpG island can be separated by up to 25 kilobases (kb) (e.g., up to 20 kb, up to 19 kb, up to 18, kb, up to 17 kb, up to 16 kb, up to 15 kb, up to 10 kb, up to 9 kb, up to 8 kb, up to 7 kb, up to 6 kb, up to 5 kb, up to 4 kb, up to 3 kb, up to 2 kb, or up to 1 kb) from the transcription start site for the nearest gene and still be considered "associated with" the gene. Preferably, CpG islands associated with at least three genes are assayed. However, CpG islands associated with 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or even more genes can be assayed.

[0035]Methods of identifying CpG islands have been described (e.g., Takai et al., Proc. Nat'l. Assoc. Sci. USA, 99:3740-3745 (2002)). For example, genomic sequences can be analyzed to identify segments containing CpG islands that are at least 200 bp in length, have at least a 60% GC content, and contain at least 7% CpG dinucleotides. Preferred sequences are at least 250 bp in length, are at least 60% GC rich, and contain at least 7% CpG dinucleotides. Moreover, undesirable highly repetitive sequences can be screened out using a repeat masker that filters out sequences. Desirable sequences contain less than 50% repeats (i.e., a sequence of reduced complexity or a sequence that is present at multiple genomic locations) within the length of the identified CpG island. Preferably, the CpG island is no more than 45%, 40%, 35%, 30%, 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, or 11% repetitive. Most desirable sequences are no more than 10% repetitive. Examples of repetitive sequences are available, for example, at the web site for National Center for Biotechnology Information (NCBI).

[0036]Biological sample" is intended to encompass any suitable sample that enables accurate assay of CpG island methylation. Examples of suitable biological samples include, but are not limited to, whole blood, blood plasma, blood serum, urine, saliva, cells (e.g., cells obtained from blood, such as epithelial cells), and tissue. Such samples are obtained in accordance with methods known in the art. When the biological sample is whole blood, blood plasma, or urine, preferably, CpG islands associated with more than three genes are assayed.

[0037]A CpG island is "not detectably methylated" when it is not methylated or it is methylated at a level below the level of sensitivity of the assay method employed.

[0038]Noncancerous" tissue can be benign or normal. Alternatively, but not preferably, the tissue can be diseased, as long as it is not cancerous.

[0039]Methods of assaying methylation of CpG islands are known in the art and include, for example, restriction enzyme-based technology, such as one that employs digestion with a methylation-sensitive restriction endonuclease coupled with Southern blot analysis, methylation-sensitive enzymes and polymerase chain reaction (PCR), such as methylation-sensitive arbitrarily primed PCR (AP-PCR; see, e.g., Gonzalgo et al., Cancer Res., 57: 594-599 (1997)), restriction landmark genomic scanning (RLGS; see, e.g., Plass et al., Genomic 58: 254-262 (1999)), methylated CpG island amplification (MCA; see, e.g., Toyota et al., Cancer Res., 59: 2307-2312 (1999)), differential methylation hybridization (DMH; see, e.g., Huang et al., Human Mol. Genet., 8: 459-470 (1999)), and Not I-based differential methylation hybridization (see, e.g., International Patent Publication No. WO 02/086163). Other methods are described in U.S. Pat. App. Pub. No. 2003/0170684 and International Patent Publication No. WO 04/05122.

[0040]Alternatively, cytosine conversion-based technology can be used. Such technology relies on methylation status-dependent chemical modification of CpG islands (i.e., deamination of unmethylated cytosines in CpG islands) within isolated genomic DNA or fragments thereof followed by DNA sequence analysis. Such methods employ reagents like hydrazine and bisulfite. Bisulfite treatment followed by alkaline hydrolysis is described by Olek et al., Nucl. Acids Res., 24: 5064-5066 (1996); and Frommer et al., PNAS USA, 89: 1827-1831 (1992). The use of methylation-sensitive primers to assay methylation of CpG islands in isolated genomic DNA is described by Herman et al., PNAS USA, 93: 9821-9826 (1996), and in U.S. Pat. Nos. 5,786,146 and 6,265,171. Bisulfite-treated DNA can be subsequently analyzed by conventional molecular techniques, such as PCR amplification, fluorescence-based, real-time PCR (see, e.g., Eads et al., Cancer Res., 59: 2302-2306 (1999); Heid et al., Genome Res., 6: 986-994 (1996); and U.S. Pat. No. 6,331,393), sequencing, oligonucleotide hybridization detection, and methylation-sensitive single nucleotide primer extension (Ms-SNuPE; see, e.g., Gonzalgo et al., Nucl. Acids Res., 25: 2529-2531 (1997); and U.S. Pat. No. 6,251,594).

[0041]A preferred method of assaying for methylation of a CpG island includes isolating genomic DNA (and/or fragments thereof) from a biological sample, treating the DNA under deaminating conditions that convert unmethylated cytosines to uracil, using the treated DNA as a template in a PCR reaction to amplify a target sequence that includes the CpG-island of interest, thereby producing an amplified sequence. Unmethylated cytosines in the target sequence, which are converted to uracils by the deaminating treatment, are amplified as thymines in the corresponding position of the amplified sequence. Since the sequence of the forward and the reverse strand of the CpG island lose their complimentarity after the deamination reaction, the methylation status of the CpG island can be determined by assaying one or both of the original strands by utilizing primers capable of annealing to the strand of interest.

[0042]The deamination reaction may not proceed to completion, which results in false positives. For example, deamination of DNA sequences using bisulfite salt is sensitive to the purity of the DNA, length of incubation, and the secondary structure of the denatured templates. Quantitative PCR methods can be used to assay for the efficiency of deamination. However, quantitative PCR methods are limited to assaying the conversion status within the sites where the primers and probes anneal to the template.

[0043]Quantitative PCR methods are also limited to assaying for the methylation of cytosines within the sites where the primers and probes anneal to the template. The primers and the probe only anneal efficiently to the templates that are fully converted and contain methylation at the appropriate cytosine nucleotides. Thus, they fail to provide methylation information for CpG dinucleotides that are not assayed for. The CpG islands may also be analyzed using direct sequencing following the deamination treatment. However, due to the heterogeneity of the methylation pattern within a CpG island and the presence of homopolymeric stretches within the sequence, direct sequencing of CpG islands can yield a sequencing pattern that is too noisy and complex for the available sequencing software.

[0044]To overcome these disadvantages and to minimize the overall cost of analysis for a clinical test, we developed a method to analyze the amplified sequences by termination-coupled linear amplification. The DNA is linearly amplified using a forward or a reverse primer in the presence of dNTPs and one or two dideoxynucleotides such as dideoxycytidine or dideoxyguanine. The amplified sequence can, optionally, be analyzed using only thymine and/or cytosine terminators when assaying for a methylated CpG dinucleotide (or adenine and/or guanine terminators when analyzing the amplified strand opposite to the CpG dinucleotide of interest) to make extension reaction products that terminate at thymines and/or cytosines nucleotides (or at guanine and/or adenine when assaying the opposite strand). The amplification reaction results in the generation of fragments with multiple lengths, each length of which corresponds to the distance in bases between the primer used for amplification and the position within the target sequence of a nucleotide that is complementary to the dideoxynucleotide added to the amplification reaction. Such amplification can result in the generation of 10 to 20 fragments from an average CpG island-containing amplicon of 100 to 150 bp. The extension products can be separated by size on an acrylamide gel and compared to (a) a size standard and/or (b) by comparing the fragments to those generated when fully unmethylated (PCR generated template or clones in E. coli) or fully methylated (enzymatically methylated in vitro) template to thereby determine the presence of cytosine (or guanine on the opposite strand) or the presence of thymine (or adenine on the opposite strand) in the amplified CpG island-containing sequence. When bisulfite is used as the deaminating agent, the amplified sequence may contain large stretches of thymine or adenine which may result in additional fragments due to the DNA polymerase slippage during amplification. Such "stutter" patterns may be minimized by selectively analyzing segments of the CpG islands that have shorter homopolymeric sequences. Stutter fragments can also be identified by analyzing the control templates.

[0045]When a fluoresent label is used to tag the primers or the dideoxynucleotides used in the terminator-coupled linear amplification, the resulting fragments may be analyzed using automated sequencing machines and software designed for determining the size of DNA fragments. In this regard, commercially available software such as GENESCAN (Applied Biosystems, Foster City, Calif.) and GENEMAPPER (Applied Biosystems) are trained to recognize and account for stutter patterns due to DNA polymerase slippage during the amplification of microsatellite repeats. Such software may also be used to account for the stutter pattern that is observed when amplifying homopolymeric stretches of DNA, as might be seen after bisulfite conversion of CpG islands. There are a number of fluorescent dyes available for the automated analysis of DNA such as but not limited to 6-carboxyfluorescein (6-FAM), Hexachlorofluorescein (HEX), VIC dye, 5-carboxytetramethylrhodamine (TAMRA), 5-carboxy-X-rhodamine, succinimidyl ester (5-ROX), 6-carboxy-2',4,7,7'-tetrachlorofluorescein (TET). The methods and equipment to determine amplicon size have been available for over a decade and in use for genetic linkage mapping, DNA identity, and forensic. For example, Applied Biosystems has a set of 5 dyes that can be used to multiplex fragments from 4 separate amplification reaction and one standard for use in linkage mapping on the ABI sequencers. Four different CpG islands from a single individual can be linearly amplified using fluorescently tagged primers, and the products pooled before analysis. Alternatively, different CpG islands from different individuals can be linearly amplified using fluorescently tagged primers, and the products pooled before analysis.

[0046]Since methylation of a particular CpG dinucleotide is not always complete in a sample, i.e., the CpG sequence is heterogenous, the methods provided herein can be advantageously used to analyze the extent of or percent methylation of a particular CpG dinucleotide site within a sample. In a preferred method, two different fluorescent-dye terminators are used for thymine and cytosine, respectively (or adenine and guanine, respectively, when analyzing the opposite strand) in a fluorescent dideoxy sequencing reaction. The relative abundance of the two dyes in same-size extension products are indicative of the relative abundance of the two nucleotides at a particular sequence position, and can thereby indicate the percent methylation of a particular CpG dinucleotide site within a CpG island. To determine the expected relative abundance of the two dyes, control reactions with a range of known ratios of fully methylated to fully unmethlylated templates can be used. The data obtained from the control reactions can be used as a reference to estimate relative abundance of methylated and unmethylated cytosines in a sample.

[0047]The levels of methylation or patterns of methylation at given CpG islands can be assayed as appropriate. The assay can employ the use of a reference standard when appropriate to enable the determination of abnormal methylation. A reference standard can be determined based on reference samples obtained from age-matched noncancerous classes of adjacent tissues, and with normal peripheral blood lymphocytes. When, for example, efficacy of treatment is being assessed, the assay results of biological samples taken over the course of treatment can be compared without the use of a reference standard.

[0048]When the DNA obtained from a biological sample is in limited quantities and is not sufficient for the analysis of multiple markers, the methods described herein can include amplifying the DNA from the sample. Amplification can be done using PCR amplification or isothermal amplification methods, for example, those described in U.S. Pat. Nos. 5,854,033; 6,124,120; 6,143,495; 6,210,884; 6,642,034; 6,280,949; 6,632,609; and 6,642,034; and U.S. Pat. App. Pub. Nos. 2003/0032024; 2003/0143536; 2003/0235849; 2004/0063144; and 2004/0265897, which are incorporated herein by reference in their entirety. Isothermal amplification can include rolling circle or strand displacement amplification. Methods that combine PCR and isothermal amplification have also been described (U.S. Pat. Nos. 6,777,187; and 6,828,098; and U.S. Pat. App. Pub. Nos. 2004/0209298; 2005/0032104; and 2006/0068394, each of which is incorporated herein by reference in its entirety). U.S. Pat. App. Pub. No. 2005/0202490, which is incorporated herein by reference in its entirety, describes the use of such methods in combination with methylation-sensitive restriction enzymes to study the methylation pattern of DNA. DNA amplification can also include methylation-coupled whole genomic amplification to generate the DNA needed, such as described in U.S. Pat. App. Pub. No. 2006/0257905, which is incorporated by reference herein in its entirety. The methylation-coupled whole genomic amplification can be especially advantageous when DNA is recovered from minute biological samples or from bodily fluids such as urine or plasma.

[0049]Skilled artisans will appreciate that the various amplification methods described herein, e.g., the PCR amplification, isothermal amplification, and termination-coupled linear amplification method, can employ nucleotides, nucleotide analogues, nucleotide or nucleotide analogue derivatives, and/or combinations thereof.

[0050]If desired, mRNA and protein levels can be assayed, and alterations in their expression levels can be indicative of a change in the level of methylation or the patterns of methylation at given CpG islands. Such methods of assaying mRNA and protein levels are also within the skill in the art. For example, the mRNA assay methods described in U.S. Provisional Patent Application No. 60/705,964 filed on Aug. 5, 2005 and International Patent Publication No. WO 2007/019444, which are hereby incorporated by reference, can be used. Such methods are particularly useful if a degraded tissue sample is used as the biological sample. Alternatively, reverse transcription with gene-specific primers can be used to assay mRNA levels. Proteins levels can be assayed, for example, using antibody and staining techniques.

[0051]It is important to note that even though aberrant methylation of a CpG island can affect expression of the associated gene, the methods described herein are not dependent on a biological role for the hypermethylation. That is a hypermethylated CpG island can be useful in the methods of the invention regardless of its effect on gene expression. Accordingly, the only requirement is that there be a correlation between the methylated state of a CpG island and the presence of cancer.

[0052]The invention further provides target sequences and corresponding primers or probes that are useful in the above methods. The target sequences provide the context for the selection of CpG islands to assay for methylation. If a given target sequence contains more than one CpG island, all or less than all of the CpG islands, even one CpG dinucleotide, can be assayed for methylation with respect to that particular target sequence. In this regard, a target sequence can include a genomic sequence that is fully methylated and fully deaminated such as SEQ ID NO: 1 or 2 [NRG1], SEQ ID NO: 3 or 4 [ADRB3], SEQ ID NO: 5 or 6 [GFRA2], SEQ ID NO: 7 or 8 [KIF13B], SEQ ID NO: 9 or 10 [RET], SEQ ID NO: 11 or 12 [GPR147], SEQ ID NO: 13 or 14 [NEUROG3], SEQ ID NO: 15 or 16 [PALD], SEQ ID NO: 17 or 18 [HEMK1], SEQ ID NO: 19 or 20 [FGF4], SEQ ID NO: 23 or 24 [HTR1A], SEQ ID NO: 25 or 26 [RNF180], SEQ ID NO: 27 or 28 [ECOP], SEQ ID NO: 29 or 30 [ZNF596], SEQ ID NO: 33 or 34 [LOC441320], SEQ ID NO: 35 or 36 [TDH], SEQ ID NO: 37 or 38 [FLJ36980], SEQ ID NO: 39 or 40 [FGF20], SEQ ID NO: 41 or 42 [EFHA2], SEQ ID NO: 43 or 44 [ASAH1], SEQ ID NO: 45 or 46 SEQ ID NO: 49 or 50 [NODAL], SEQ ID NO: 51 or 52 [LOC399783], SEQ ID NO: 53 or 54 [ISL2]. These fully methylated and deaminated sequences are used for illustrative purposed and do not exclude the use of partially methylated and deaminated sequences in the methods of the invention. A target sequence can include a genomic sequence that is partially methylated, such as in DNA obtained from a tumor, and then deaminated such that the target differs from the sequence listed above. Persons of skill in the art will appreciate that a target sequence that includes a partially methylated and deaminated CpG island will result in a population of DNA molecules that differ at one or more positions that correspond to the cytosine residues in one or more CpG dinucleotides. Thus, a target sequence can include a variety of partially methylated and deaminated sequences based on the following genomic sequences SEQ ID NOS: 119 or 220 [KIFC2], SEQ ID NOS: 121 or 122 [C20ORF23], SEQ ID NOS: 123 or 124 [GFRA1], SEQ ID NOS: 129 or 130 [DKK2], SEQ ID NOS: 133 or 134 [RASSF5], SEQ ID NOS: 135 or 136 [NTN1], SEQ ID NOS: 139 or 140 [GPR147], SEQ ID NOS: 141 or 142 [NEUROG3], SEQ ID NOS: 143 or 144 [NODAL], SEQ ID NOS: 145 or 146 [PALD], SEQ ID NOS: 147 or 148 [LOC399783], SEQ ID NOS: 151 or 152 [LOC441320], SEQ ID NOS: 153 or 154 [ZNF596], SEQ ID NOS: 155 or 156 [TDH], SEQ ID NOS: 157 or 158 [ASAH1], SEQ ID NOS: 159 or 160 [FGF20], SEQ ID NOS: 161 or 162 [FLJ36980], SEQ ID NOS: 163 or 164 [GFRA2], SEQ ID NOS: 165 or 166 [EFHA2], SEQ ID NOS: 171 or 172 [KIF13B], SEQ ID NOS: 173 or 174 [ADRB3], SEQ ID NOS: 175 or 176 [NRG1], SEQ ID NOS: 177 or 178 [ECOP], SEQ ID NOS: 179 or 180 [HTR1A], SEQ ID NOS: 181 or 182 [ISL2], SEQ ID NOS: 183 or 184 [LOC285671], SEQ ID NOS: 185 or 186 [FGF4], SEQ ID NOS: 189 or 190, [HEMK1], SEQ ID NOS: 191 or 192 [RET] SEQ ID NOS: 193 or 194 [HTRA4], SEQ ID NO: 195 [RHOD], SEQ ID NO: 196[TNFSF11], SEQ ID NO: 197 [MMP9], and SEQ ID NO: 198 [LRRC49].

[0053]These targets can be used in combination with known targets (for example known CpG islands associated with GSTP1, GPX3, GSTM1, GSTM4, CSMD1, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, SFRP1, SFRP2, DKK3, PTGS2, CDKN1C/p57, RASSF1, and GPR62. For example, fully methylated and deaminated sequences for some of these genes are provided in SEQ ID NO: 31 or 32 [CSMD1], SEQ ID NO: 45 or 46 [TNFRSF10C], SEQ ID NO: 47 or 48 [TNFRSF10B] SEQ ID NO: 21 and 22 [GPR62]. Also for example, a target sequence can include fully or partially methylated and (subsequently) deaminated sequences based on the following genomic sequences SEQ ID NOS: 131 or 132 [GPX3], SEQ ID NOS: 125 or 126 [GPX7], SEQ ID NOS: 127 or 128 [GSTM4], SEQ ID NOS: 137 or 138 [SFRP2], SEQ ID NOS: 149 or 150 [CSMD1], SEQ ID NOS: 167 or 168 [TNFRSF10B], SEQ ID NOS: 169 or 170 [TNFRSF10C], and SEQ ID NOS: 187 or 188 [GPR62]. Such target sequences can be isolated or purified in accordance with methods known in the art.

[0054]Also provided are isolated or purified primers derived from and suitable for amplifying sequences internal to the above isolated or purified nucleic acid molecules. The isolated or purified primers can be DNA, RNA, PNA, and the like. It will be understood by one of ordinary skill in the art, however, that one type of nucleic acid can be preferred over another, depending on the particular biological sample, the methodology employed in assaying CpG islands for methylation, and the ability of the particular type of nucleic acid to detect methylation. One or more (e.g., two, three four, four, five, six, seven, eight, nine ten or more) isolated pairs of primers can be provided. Optionally, primers are provided as part of a kit useful in the methods disclosed herein. The pair of primers can consist essentially of SEQ ID NOS: 55 and 56, SEQ ID NOS: 57 and 58, SEQ ID NOS: 59 and 60, SEQ ID NOS: 61 AND 62, SEQ ID NOS: 63 and 64, SEQ ID NOS: 65 and 66, SEQ ID NOS: 67 and 68, SEQ ID NOS: 69 and 70, SEQ ID NOS: 71 and 72, SEQ ID NOS: 73 and 74, SEQ ID NOS: 75 and 76, SEQ ID NOS: 77 and 78, SEQ ID NOS: 79 and 80, SEQ ID NOS: 81 and 82, SEQ ID NOS: 83 and 84, SEQ ID NOS: 85 and 86, SEQ ID NOS: 87 and 88, SEQ ID NOS: 89 and 90, SEQ ID NOS: 91 and 92, SEQ ID NOS: 93 and 94, SEQ ID NOS: 95 and 96, SEQ ID NOS: 97 and 98, SEQ ID NOS: 99 and 100, SEQ ID NOS: 101 and 102, SEQ ID NOS: 103 and 104, SEQ ID NOS: 105 and 106, or SEQ ID NOS: 107 and 108. It is understood that these primer pairs are examples of suitable primers for use in the context of the invention. For example, each primer can be between 10 and 40 nucleotides and together the pair of primers can flank a region of at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 120, 130, 140, 150, 200, 250, 300 bp in length that includes one or more CpG dinucloetides in a CpG island of interest. Primer pairs can be modified in various ways, such as by chemical modification of a base, and still be useful in the context of the invention. Other primers derived from the target sequences, namely SEQ ID NOS: 1-54 and 119-198, and variants thereof, also can be used in the context of the invention. The only requirement is that such primers function to assay for methylation of a given CpG island. Thus, for example, alternate primers can be selected or the provided primers can be modified or provided in degenerate form to account for target sequence polymorphisms within a given population, so long as the primers are still suitable for assaying modification of CpG islands associated with the genes disclosed herein.

[0055]Like the target sequences, the primer pairs can be isolated or purified in accordance with methods known in the art. Alternatively, they can be synthesized using routine methods.

[0056]The primers can be part of a kit. Preferably, the kit comprises at least three pairs of primers, wherein each primer pair is specific for a CpG island associated with a different gene. However, the kit can comprise additional primer pairs, such as primer pairs for other CpG islands associated with the same gene or primer pairs for amplifying CpG islands associated with four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or even more genes. The kit can further comprise one or more reagents for assaying for methylation of CpG islands, instructions for use, and/or other components as are typically found in kits. For example, the kit can comprise a buffer suitable for (a) isolating genomic DNA comprising a target sequence from a biological sample, (b) amplifying a portion of the target sequence, and/or (c) deaminating a target sequence. In embodiments directed to the evaluation of prostate cancer, a kit can comprise one or more buffers suitable for preparing genomic DNA from serum and/or urine samples.

EXAMPLES

[0057]The following examples serve to illustrate the invention. The examples are not intended to limit the scope of the invention.

Example 1

[0058]This example demonstrates the determination of the methylation status of markers based on methylation-specific PCR amplification. Paraffin-embedded prostate tissues were obtained following radical prostatectomies. The tissue samples were sectioned into 23 10-micron sections and slide 1, 12, and 23 were stained using hematoxylin and eosin (H&E). Using the H&E slides as guide, the areas corresponding to the tumor tissues were microdissected from the unstained slides. The remaining tissues were recovered to use as a normal paired sample. Following deparaffinization using two xylene extractions and two ethanol washes, the DNA was isolated from the tumor tissue and surrounding normal tissues using standard proteinase K digest for 5 days at 50° C., extraction with phenol/chloroform and ethanol precipitation (Current Protocols in Molecular Biology, edited by Ausubel, et al., Wiley-Interscience (New York 1988, revised 1988-2006)). The DNA was resuspended in TE8 and the quality and quantity of the DNA was assessed by agarose gel electrophoresis using concentration and size standards as reference. Following denaturation in the presence of 0.3 M NaOH, the DNA was treated with 2.5 M sodium metabisulfite, pH 5.5, in the presence of 1 mM hydroquinone at a concentration of 1 μg of DNA/500 μl. The reaction was incubated in a thermocycler for a total of 8 cycles (95° C. for 5 minutes; 55° C. for 115 minutes).

[0059]Following bisulfite treatment, the DNA was purified using the QIAEX II purification kit (Qiagen, Valencia, Calif.) according to the manufacturer's recommendations and eluted in 50 μl of TE8. Sodium hydroxide (5.5 μl of 2 N) was added, and the DNA was incubated at RT for 15 min. The DNA was then precipitated with 3 volumes of ethanol and 0.3 volumes of 5 M NH₄OAC. The DNA was resuspended in 50 μl of TE8 and stored at -20° C.

[0060]In order to determine if a specific CpG position is methylated in genomic DNA isolated from tumor tissue, methylation-specific polymerase chain reaction (PCR) was performed, using primers designed to overlap the position of the CpG island of interest. All PCR reactions were performed in a MASTERCYCLER thermocycler (Eppendorf, Westbury, N.Y.) for 42 cycles of 95° C. for 15 seconds, 63° C. for 30 seconds, and 72° C. for 10 seconds. Each reaction was carried out in 30 μl of 1× PLATINUM Taq PCR buffer containing 1.5 mM magnesium chloride, 0.25 mM dNTPS, 12.5 pmoles of each primer, and 0.5 units of PLATINUM Taq enzyme (Invitrogen, Carlsbad Calif.). The primers used for each CpG island and the size of the product are shown in Table 1, wherein "F" indicates forward primer, "R" indicates reverse primer, "m" indicates methylated, and "u" indicates unmethylated.

TABLE-US-00001 TABLE 1 An- neal- ing Gene as- temp- Pro- sociated era- duct with CpG ture size island Primer sequences (° C.) (bp) NIRG1 mF: GAGCGGGTAGCGAGAGTTTCGG 63 119 [SEQ ID NO: 55] mR: TAACGACGCGACTACCGAAAACC [SEQ ID NO: 56] ADRB3 mF: GATTAACGTGTTCGTGATTTCGTT 63 102 [SEQ ID NO: 57] mR: CAACGACCAATAACCAATCAACGCC [SEQ ID NO: 58] GFRA2 mF: ATACGTCGGTGAGTTCGGTTTATC 63 101 [SEQ ID NO: 59] mR: ACTCCCGACTCCCTAAACTCCGAA [SEQ ID NO: 60] KIF13b mF: TGAATCGGCGAGGTGAGAGTCG 65 179 [SEQ ID NO: 61] mR: ACCGAACGTCTCAACGCGAAAACG [SEQ ID NO: 62] RET mF: TATCGTTAGCGTCGTGGTGGAGTT 63 120 [SEQ ID NO: 63] mR: CTACACGAACACTAAACCGACCGA [SEQ ID NO: 64] GPR147 mF: TCGGTCGTTACGTTGATCGTTATTC 63 119 [SEQ ID NO: 65] mR: ACCCTACGCATACCCTTCTCGAAC [SEQ ID NO: 66] NEUROG3 mF: GTTTCGAGGAAGTTTCGGGTACGG 63 103 [SEQ ID NO: 67] mR: GATCGTTAACCTTCTTTCGCCGAC [SEQ ID NO: 68] PALD mF: CGAAGTTGGGAGGAGCGAGTT 63 115 [SEQ ID NO: 69] mR: AAACATCCGTACTCCTACGACCGA [SEQ ID NO: 70] HEMK [tiF: 63 99 CGTATTAGTCGTATTCGCGAGCGT [SEQ ID NO: 71] mR: CGAAACTACTCGACCCGACCC [SEQ ID NO: 72] FGF4 mF: TAACGGTACGTTGGAGGTCGAGTT 63 102 [SEQ ID NO: 73] mR: ACGACCGCCTCCTTAAACTACGCT [SEQ ID NO: 74] GPR62 mR: TATCGTGTATTCGTTGCGGTTAGG 63 120 [SEQ ID NO: 75] mR: AACGATACGAACGACGTACCGAA [SEQ ID NO: 76] HTR1A mF: TACGTGAATAAGAGGACGTTTCGG 63 115 [SEQ ID NO: 77] mR: AACGATCTTCCGAAATACGCCAA [SEQ ID NO: 78] RNF180 mF: TCGTCGAATCGGTATCGTCGTC 63 118 [SEQ ID NO: 79] mR: ACCTATATCCACGTCCCGAAACCT [SEQ ID NO: 80] ECOP mF: CGGTTGTAGTTTGTTCGTTCGTTTC 63 108 [SEQ ID NO: 81] mR: CTAACGCCTCATAACTCCTCGCGT [SEQ ID NO: 82] ZNF596 mF: GCGTCGATTCGGGAGTAGTATCGT 63 96 [SEQ ID NO: 83] mR: ATACCGTAAATCCGCGCTACTTCC [SEQ ID NO: 84] CSMD1 mF: CGTTGAGGTCGAATGAAGCGTAGT 63 96 [SEQ ID NO: 85] mR: AACCGAAACTAAACACGACGCAA [SEQ ID NO: 86] LOC441320 mF: AAGCGTATAGTTCGAGGATTGCGA 63 107 [SEQ ID NO: 87] mR: CCGCGTCACTTACTCCTCTACGA [SEQ ID NO: 88] TDH mF: CGTTGGGTGCGTAGGAAGGTTAGT 63 120 [SEQ ID NO: 89] mR: GACCGACCCTAAACAACCCGCT [SEQ ID NO: 90] FLJ36980 mF: GTTGCGGGATAGCGTTGTGATT 63 96 [SEQ ID NO: 91] mR: ACCATTATCAATACTCCGATCGCC [SEQ ID NO: 92] FGF20 mF: TTTGTTTGTTAAGGGCGTTATCGT 63 105 [SEQ ID NO: 93] mR: CCGCGACTACTCTAACCAACCC [SEQ ID NO: 94] EFHA2 mF: GGGCGTTGAGTTTAGTTCGGAGA 63 108 [SEQ ID NO: 95] mR: ACGAACACAACCGAATCAACGTAA [SEQ ID NO: 96] ASHA1 mF: GGCGTTGGTTGTTAGAGCGATG 63 114 [SEQ ID NO: 97] mR: GACTCAAACTCACTCACCGACGAC [SEQ ID NO: 98] TNFRSF10C mF: GGTGCGATTTAGGATTTAGGACGG 63 115 [SEQ ID NO: 99] mR: GCGACCGAAACTCACTAACAACAA [SEQ ID NO: 100] TNFRSF10B mF: GCGATTTGGGTCGTTAGGGAATAG 63 119 [SEQ ID NO: 101] mR: ACCTCTCCGTAACTTCACGCAACTT [SEQ ID NO: 102] NODAL mF: GGTAGTCGCGGTCGTTTACGTT 63 111 [SEQ ID NO: 103] mR: ACGAACAAACGACAAATCGAATCA [SEQ ID NO: 104] LOC399783 mF: TACGTTGAGTTCGGTTTGGTTTGT 63 103 [SEQ ID NO: 105] mR: CGCGCCTCCGTAATCTAAACTAA [SEQ ID NO: 106] ISL2 mF: GTGCGTGTTGACGTTATGTTGCGT 63 99 [SEQ ID NO: 107] mR: CGCCCGACCTCGACTCTTTACT [SEQ ID NO: 108] GSTP1 mF: CGGCGATTTCGGGGATTTTAGGGC 63 109 [SEQ ID NO: 109] mR: GACCGCTCTTCTAAAAAATCCCGC G [SEQ ID NO: 110] GSTP1 mF: ACGTTCGGGGTGTAGCGGTCGTC 63 93 [SEQ ID NO: 111] mR: CCCCAATACTAAATCACGACGCCG [SEQ ID NO: 112] GSTP1 mF: GGTCGGCGTCGTGATTTAGTATTGG 63 99 [SEQ ID NO: 113] mR: ACTACGACGACGAAACTCCAACGA [SEQ ID NO: 114] GSTP1 uF: 63 113 TGTGGTGATTTTGGGGATTTTAGGGT [SEQ ID NO: 115] uR: CCAACCACTCTTCTAAAAAATCCCACA [SEQ ID NO: 116] GSTP1 uF: GATGTTTGGGGTGTAGTGGTTGTTG 63 99 [SEQ ID NO: 117] uR: CTCCACCCCAATACTAAATCACAACA [SEQ ID NO: 118] KIFC2 mF: TGATGGTCGTATTGCGGGTTTATC 62 91 [SEQ ID NO: 199] mR: ATACCTAAACCCAACGCCGACTAC [SEQ ID NO: 200] C20orf23 mF: CGCGATTTGAGTAGTTAGCGTCGT 62 90 [SEQ ID NO: 201] mR: AACCAACGCGACGACCTAACTAAC [SEQ ID NO: 202] GFRA1 mF: TAGATTTCGGTGTTTCGGGCGTT 62 98 [SEQ ID NO: 203] mR: CCGCTAATTCCCAATCGTACTACTCA [SEQ ID NO: 204] GPX7 mF: TTCGTTTCGTTCGGTCGTGATT 62 116 [SEQ ID NO: 205] mR: GACTACGAACGCTTCGAATTCCTC [SEQ ID NO: 206] DKK2 mF: GTTGCGTTGGTAGCGATTCGTTGT 62 117 [SEQ ID NO: 207] mR: CCCGAACCGAATCCTCGAAATCT [SEQ ID NO: 208] NTN1 mF: 62 103 GACGTAGTATGATGCGCGTAGTGTG [SEQ ID NO: 209] mR: GCGAACATACTAAACCCGAACCC [SEQ ID NO: 210] HTRA4 mF: GGATTACGTCGGTGTTCGATTTGT 62 95 [SEQ ID NO: 211] mR: AACGCACGATTAACCCTACGCC [SEQ ID NO: 212] MMP9 mF: TCGGATTAAGGTAGGCGTGGTTTC 62 102 [SEQ ID NO: 213] mR: AACGTAAACGCCGAACCGAAC [SEQ ID NO: 214] RHOD mF: GGAAGACGTCGTTGTTGATGGTTT 62 120 [SEQ ID NO: 215] mR: ACCGCTCCGACACGAACCTATAC [SEQ ID NO: 216] TNSF11 mF: AGCGTTATGCGTCGCGTTAGTAG 62 116 [SEQ ID NO: 217] mR: GCAAACGACGACGAAACGTACA [SEQ ID NO: 218] SFRP2 mF: GAAGAGAGCGGGTTCGGGATAAG 62 101 [SEQ ID NO: 219] mR: CTACAACATCGTAAACGCGCGAC [SEQ ID NO: 220]

[0061]The products of the PCR reactions were separated on 8% acrylamide gel. Only templates that exhibited methylation at all of the CpG islands that were present within the primers could serve as efficient templates for the amplification reactions. Control reactions were performed using fully methylated templates that were methylated in vitro using SS1 (CpG) methylase (NEB, Beverly, Mass.) according to the manufacturer's protocol. All primer pairs listed in Table 1 yielded a product of the correct size from fully methylated control template. Two negative controls (water and DNA isolated from white blood cells) were included for each target PCR amplification, which did not yield a PCR product. When a CpG island is methylated in a DNA sample, an amplification product of the expected size is obtained. This example demonstrates that the above primers can be used to assay for methylation of CpG islands in prostate cancer and that the CpG islands exhibit methylation in prostate cancer.

Example 2

[0062]This example demonstrates the determination of the methylation status of CpG islands at the ADRB3 locus by DNA sequencing. DNA is obtained from tumor samples and treated with sodium bisulfite as described in example 1. Two microliters of the bisulfite treated DNA are amplified with the following primers: ADRB3-F1: GAGAAGAGGAAGGTAGAAGGAG [SEQ ID NO: 221] and ADRB3-R1: CTACCTAACTATAACCAACCC [SEQ ID NO: 222] for 40 cycles as described in example 1 except for the annealing temperature, which is lowered to 55° C. The amplified 250 bp product is purified using QIAquick PCR purification kit (Qiagen, Valencia Calif.) and recovered in TE8. Fifty nanograms of the ADRB3 amplified product is sequenced using 1.25 pmole of ADRB3-F2:ACGGAGGAGGATAGTAGTACG [SEQ ID NO: 223] using BigDye Terminator v3.1 cycle sequencing kit (Applied Biosystems) and the sequencing reaction is purified using Centri-Sep columns (Applied Biosystems) according to the manufacturer's protocols. The products of the sequencing reaction are analyzed using an ABI 3700 sequencer according to manufacturer's specification. The resulting DNA sequence shows one or more sequence peaks corresponding to cytosine base or a mixed cytosine/thymidine base at the cytosine residue position of CpG dinucleotides that are fully or partially methylated in the original tumor DNA.

[0063]Alternatively, a more detailed sequence analysis is obtained by cloning the product of the amplification reaction using a TOPO TA cloning kit (Invitrogen, Carlsbad Calif.) according to supplier's protocol. Approximately 20 colonies are chosen for further analysis. Each colony is grown in 3 ml of LB media for 16 hours. DNA is isolated from 1.5 ml aliquot using plasmid preparation kit from Qiagen. The plasmid DNA is quantitated using spectrophotometer and 1 microgram aliquot is sequenced as described above. The sequence of the 20 individual clones is compared to determine which cytosines are methylated and to provide an estimate of their rate of methylation in the tumor sample. This example shows that the methylation status of cytosines within CpG islands can be determined using a sequencing approach.

Example 3

[0064]This example demonstrates the determination of the methylation pattern of multiple CpG islands associated with KIFC2, GFRA1 and GPX7 using terminator-coupled linear amplification. From DNA from tumor samples prepared as described in example 1, fragments of the CpG islands associated with KIFC2, GFRA1, GPX7 are amplified individually using the mF1 and mR1 primers shown below for each CpG island. The amplification reactions are performed for 42 cycles as described in example 1 except for the annealing temperature, which was lowered to 58° C. An aliquot of the amplification reaction is separated on an 8% acrylamide gel to verify that fragments of the appropriate length are obtained (264 bp for KIFC2, 326 bp for GFRA1, 367 bp for GPX7). The product of the PCR reaction were purified using QIAQUICK PCR purification kit (Qiagen).

[0065]Each amplification product (25 nanograms) is subjected to linear terminator-coupled amplification using 1.5 pmoles of the fluorescently labeled F2 primer shown below for the corresponding amplicon. The amplification reaction includes 1× VentR (exo-) DNA polymerase (New England Biolabs, Beverly Mass.), 30 μM dATP, 37 μM dCTP, 100 μM dGTP, 100 M dTTP, 480 μM ddCTP and 2 units of VentR (exo-) DNA polymerase. Reactions are performed in an MASTERCYCLER thermocycler (Eppendorf) for 30 cycles of 95° C. for 15 seconds, 58° C. for 30 seconds, and 72° C. for 30 seconds. Following amplification, the reaction products are pooled into a single tube and purified using Centri-Sep columns (Applied Biosystems) according to the manufacturer's protocols. One microliter of GENESCAN 500 LIZ standard (Applied Biosystems) is added to one tenth of the purified fragment and the DNA separated using the ABI Prism 3100 Genetic Analyzer (Applied Biosystems) according to manufacture's instructions. The data is analyzed using the GENESCAN and the GENEMAPPER software (Applied Biosystems).

[0066]The following primers are used for the amplifications:

TABLE-US-00002 KIFC2-F1: AGGTA(C/T)GTTGTATTTGGTGGATTTGG [SEQ ID NO: 224] KIFC2-R1: CCCACCTACAACAACAACACC [SEQ ID NO: 225] KIFC2-F2: 6FAM-GAACGCGTACGGAAGGTAGG [SEQ ID NO: 226] GFRA1-F1: GTGATAGGTTTGTAGATTTGATAGTTG [SEQ ID NO: 227] GFRA1-R1: AACTAACCTCCATTTTAACTATTTC [SEQ ID NO: 228] GFRA1-F2: NED-GAGAGATGAATTTGGATATTAGT [SEQ ID NO: 229] GPX7-F1: GGTAAATTGGTGT(C/T)GTTGGAGAAG [SEQ ID NO: 230] GPX7-R1: ACTAAACAATAATACCC(A/G)ACCTC [SEQ ID NO: 231] GPX7-F2: VIC-GTCGTTGGGTTCGGTTTCGTTTTG [SEQ ID NO: 232]

[0067]The F1 and R1 primers are used for the amplification of a fragment of a CpG island from the tumor DNA. The F2 primers are used for termination-coupled linear amplification.

[0068]This example shows that termination-coupled linear amplification fragment lengths can be analyzed to (i) determine the presence and/or the positions of methylated cytosines in CpG islands in a sequence of interest as well as (ii) provide information about the efficiency of the deamination reaction, since incomplete deamination results in fragments with length that differ than what is expected from the positions of the CpG dinucleotides within the sequence.

Example 4

[0069]This example demonstrates the use of methylation-coupled whole genome amplification on DNA recovered from urine samples to increase the amount of DNA available for CpG island marker assays. Urine samples were obtained from 4 patients that were recently diagnosed with prostate cancer. 50 ml samples were spun down at 4000 rpm for 15 min, transferred to 1.5 ml tubes and washed twice with PBS. The DNA was extracted using proteinase K digest (100 μl of 25 mM Tris pH8.0, 100 mM NaCL, 1% SDS, 5 mM EDTA and 10 μg of Proteinase K followed by phenol/chloroform extraction and ethanol precipitation. The DNA was resuspended in 10 μl TE8 buffer (10 mM Tris, pH 8.0, 1 mM EDTA).

[0070]A partially random primer with the sequence GGGN₆ (50 ng) was added to 5 μl of DNA. 12 μl of a denaturing solution (50 mM KOH, 0.1 mM EDTA) was added to the DNA/random primer mix. After a five-minute incubation at room temperature, 12 μl of a neutralization solution (60 mM Tris (pH 7.5), 50 mM HCl) was added to neutralize the reaction. The DNA/primer mix was denatured at 94° C. for 5 minutes, incubated at room temperature for 10 minutes, and then placed on ice.

[0071]The amplification reaction was set up in a final volume of 30 μl. The following reagents were added to give the indicated final concentrations: (a) 1×NEB buffer 2 (1×NEB buffer 2: 50 mM NaCl, 10 mM Tris-HCl, pH 7.9, 10 mM MgCl₂, 1 mM dithiothreitol), 333 μM dATP, dCTP, dGTP, dTTP, 160 μM S-adenosylmethionine, and 10 ng/μl of bovine serum albumin (BSA) were combined and to which was added (b) DNA methyltransferase enzyme 1 (0.15 units/μl) (New England Biolabs) and incubated at 37° C. for 10 minutes, and followed by (c) adding Klenow polymerase to a final concentration of 0.167 units/μl, and Klenow exo- to a final concentration of 0.167 units/μl (New England Biolabs).

[0072]The reaction was incubated at 37° C. for 16 hours, and the reaction was stopped by the addition of EDTA to a final concentration of 5 mM, phenol/chloroform extracted, and ethanol precipitated. The DNA was resuspended in 40 μl of TE8 and 2 μl were separated on agarose gel to verify the presence of DNA.

[0073]The DNA was treated with sodium bisulfite and analyzed by methylation specific PCR as described in Example 1 using the GPR147 and RET assays. The presence of a band of the expected size for either marker indicated the methylation of the associated marker in the input DNA.

[0074]All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

[0075]The use of the terms "a," "an," "the," and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0076]Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. It should be understood that the illustrated embodiments are exemplary only, and should not be taken as limiting the scope of the invention.

Sequence CWU 1

23211600DNAHomo sapiens 1gagtttattt tcgtttgcgt gcgatagggt ttttgtattt aagtgagtta aggaatgaat 60ttcgaatttt tttgggaaag ttattaacgt ttttttcgta ttttttttag ggtttttgat 120tacggagatt ttgtttgggg tataggtgtg ggagtcgtaa attttttttt gcgtcgtttt 180ttttcgcgtg gaatgggacg gagtagtttt tttaggcgtt gtttggttgc ggaggggagc 240gggtagcgag agtttcgggt tttcgtttgg gttttcgggt tttcggggcg ttggtttcgg 300ttttcgcgta gcgtttagcg atttttgtcg ggggttttcg gtagtcgcgt cgttattttt 360cgttcggtta gcgcgggagg aaaaggggtt gcgttcggga gcgtcgagtt taggtttttt 420tcggtggcgt gttcgcgttt cggggtgggg gtgtggtggg gaagagggag ggggcgaggt 480taggggaggg tgcgaaggag gcgtttgttt ttaatttgcg ggcgggaggt gggtggttgc 540ggggtaattg aaaaagagtc ggcgaggagt ttttcgaaat ttgttggaat ttcgggttcg 600cgcggaggtt aggagttgag cggcggcggt tgtcggacga tgggagcgtg agtaggacgg 660tgataatttt ttttcgatcg ggttgcgagg gcgtcgggta gaggttagga cgcgagtcgt 720tagcggtggg atttatcgac gatttttcgg ggcgatagga gtagtttcga gagttagggc 780gagcgttcgt tttaggtggt cggatcgttc gtcgcgttcg cgtcgcgttt tttgtaggta 840acgggagacg ttttcgcgta gcgcgagcgt tttagcgcgg tcgttcgttt tttttttcga 900gggataaatt ttttttaaat tcgattcgag tttttggatt aaattcgttt gcgtcgagag 960tcgttcgcgt agagcgtttc gttttcggcg agatgttcga gcgtaaagaa ggtagaggta 1020aagggaaggg taagaagaag gagcgaggtt tcggtaagaa gtcggagttc gcggcgggta 1080gttagagttt aggtgggtgc gtagcgcggt tcgggtttta cgattttttt tttgtttttt 1140ttattttttt tttttttcgg atgtcgtggt tttttttttt tttttttttt cgttcgtttt 1200tttcgttttg cgttttgagc gttcgttgag tcgcgcggtg tttttttttt tgggggtcgt 1260cgtttatttg ggcgtcgagt tttatcgggc gtttacgttt agagtttagg gtaagggata 1320gtagtttcgg tcgtattttt ttagagtttc gggagcgttt cgttttttgg tacggttttt 1380ttttagcgtt ttagcggttg agtttagttc gggagtggga tttgggttat aggagtcgag 1440gttgcgtgcg cgcgtgtttc gcgttataag cgttttgtac gggggtcgtg tgttttttag 1500cgggaaacgt tggaatgggt cgtttggagg gagagtcggt tttttcggtg tgtttggtag 1560cgtagaagtg ggtggtcgag taagaggtcg cgtgggaagt 160021600DNAHomo sapiens 2attttttacg cggttttttg ttcgattatt tatttttgcg ttgttaggta tatcgagggg 60atcggttttt tttttaggcg gtttatttta gcgtttttcg ttagagggta tacggttttc 120gtgtaaagcg tttatggcgc ggggtacgcg cgtacgtagt ttcgattttt atagtttagg 180ttttattttc gggttgggtt tagtcgttaa ggcgttgggg aggggtcgtg ttagggagcg 240aagcgttttc gggattttgg gagggtgcgg tcgggattgt tgttttttgt tttgagtttt 300gggcgtaggc gttcggtagg attcggcgtt taggtgagcg gcggttttta ggaggggaag 360tatcgcgcga tttaacgggc gtttagagcg tagggcgaag aggacgggcg agggagaggg 420ggagggagag gttacggtat tcgaggagga ggaggagtag gaggagtagg aggaggatcg 480tggggttcgg gtcgcgttgc gtatttattt gggttttggt tgttcgtcgc ggatttcggt 540tttttgtcgg agtttcgttt tttttttttg tttttttttt tgtttttgtt ttttttgcgt 600tcggatattt cgtcggagac ggagcgtttt acgcggacgg ttttcggcgt aggcgagttt 660ggtttaaggg ttcggatcgg gtttgggaaa agtttgtttt tcgaggggga gagcgagcgg 720tcgcgttgag gcgttcgcgt tgcgcggggg cgtttttcgt tgtttgtagg gagcgcggcg 780cggacgcggc gggcggttcg gttatttgga acgggcgttc gttttggttt tcggggttgt 840ttttgtcgtt tcgggaagtc gtcgatgggt tttatcgttg gcggttcgcg ttttggtttt 900tgttcggcgt tttcgtaatt cgatcgggga gaggttatta tcgttttgtt tacgttttta 960tcgttcggta gtcgtcgtcg tttagttttt ggttttcgcg cgagttcgga gttttaataa 1020gtttcgggga atttttcgtc ggtttttttt taattgtttc gtagttattt atttttcgtt 1080cgtaggttgg aggtaggcgt ttttttcgta tttttttttg gtttcgtttt tttttttttt 1140tttattatat ttttatttcg aggcgcggat acgttatcgg gaggagtttg ggttcggcgt 1200tttcgggcgt agtttttttt tttttcgcgt tggtcgggcg gggggtggcg gcgcggttgt 1260cgggaatttt cgataggggt cgttggacgt tgcgcggaga tcgaggttag cgtttcggag 1320attcgggaat ttaggcggag attcgaggtt ttcgttgttc gttttttttc gtagttaggt 1380agcgtttggg agggttgttt cgttttattt tacgcggaaa aggacggcgt agagaaaagt 1440ttgcgatttt tatatttgtg ttttaagtag agttttcgtg gttaggaatt ttgggagggg 1500tgcgggggga acgttggtgg tttttttaga agagttcggg gtttattttt taatttattt 1560aagtataaaa gttttgtcgt acgtaggcga aaataaattt 160031350DNAHomo sapiens 3attttggcgt ttaatatcgt taatattagt gggttgttag gggtttcgtg ggaggcggtt 60ttagtcgggg ttttgttggc gttggcggtg ttggttatcg tgggaggtaa tttgttggtt 120atcgtggtta tcgtttggat ttcgagattt tagattatga ttaacgtgtt cgtgatttcg 180ttggtcgtag tcgatttggt gatgggattt ttggtggtgt cgtcggcggt tattttggcg 240ttgattggtt attggtcgtt gggcgttatt ggttgcgagt tgtggatttc ggtggacgtg 300ttgtgtgtga tcgttagtat cgaaattttg tgcgttttgg tcgtggatcg ttatttggtt 360gtgattaatt cgttgcgtta cggcgtattg gttattaagc gttgcgttcg gatagttgtg 420gttttggtgt gggtcgtgtc ggtcgcggtg tcgtttgcgt ttattatgag ttagtggtgg 480cgcgtagggg tcgacgtcga ggcgtagcgt tgttatttta attcgcgttg ttgtgttttc 540gtttttaata tgttttacgt gttgttgttt tttttcgttt ttttttattt tttttttttc 600gtgatgtttt tcgtttacgc gcgggttttc gtggtggtta cgcgttagtt gcgtttgttg 660cgcggggagt tgggtcgttt ttcgttcgag gagttttcgt cggcgtcgtc gcgttttttg 720gtttcggttt cggtggggac gtgcgtttcg ttcgaagggg tgttcgtttg cggtcggcgg 780ttcgcgcgtt ttttgttttt tcgggaatat cgggttttgt gtattttggg ttttattatg 840ggtattttta ttttttgttg gttgtttttt tttttggtta acgtgttgcg cgttttgggg 900ggtttttttt tagtttcggg ttcggttttt tttgttttga attggttagg ttatgttaat 960tttgttttta attcgtttat ttattgtcgt agttcggatt ttcgtagcgt ttttcgtcgt 1020tttttgtgtc gttgcggtcg tcgtttgttt tcggagtttt gcgtcgtcgt tcgttcggtt 1080tttttttttt cgggcgtttt tgcggttcgg agtagtttag cgtagtttag gttttgttaa 1140cggttcgacg ggtaggtaat cggggtagag ggatcggcgg tttagggtcg ggaagtatgc 1200gatgtgttcg tgggttaatt ttttgagtgt ggagtttatt aagagaaggt gggatggttt 1260tgtttggaga gaaaagggaa cgaggagtag cgaattaaaa tgggatttag ggtttttttt 1320ttttcggatt tagttattag ggtagaagta 135041350DNAHomo sapiens 4tgtttttatt ttagtgattg gattcggaaa gaaaaggatt ttgggtttta ttttggttcg 60ttatttttcg tttttttttt tttttaagta aagttatttt attttttttt aataaatttt 120atatttaaaa agttgattta cggatatatc gtatgttttt cgattttgag tcgtcggttt 180ttttgtttcg gttatttatt cgtcgagtcg ttggtaaagt ttgggttgcg ttgggttgtt 240tcgggtcgta ggaacgttcg aggggaagag ggtcgggcgg gcggcggcgt agggtttcgg 300aggtaggcga cggtcgtagc ggtatagaag acggcggaag gcgttgcgaa agttcgggtt 360gcggtagtag atgagcgggt tgaaggtaga attggtataa tttagttagt ttagggtaag 420gaaagtcggg ttcgggatta gagaggggtt ttttagggcg cgtagtacgt tggttagaaa 480gaagggtaat tagtagagag tgaaggtgtt tatgatgaga tttaaggtgt atagggttcg 540gtgttttcgg agaggtagga ggcgcgcggg tcgtcggtcg taggcgggta ttttttcggg 600cggagcgtac gtttttatcg gggtcggggt tagagagcgc gacggcgtcg gcggagattt 660ttcgggcgga aagcggttta gtttttcgcg tagtaagcgt agttggcgcg tagttattac 720gaaaattcgc gcgtagacga agagtattac gagaagagga aggtagaagg agacggagga 780ggatagtagt acgtagggta tgttggaggc gaaggtatag tagcgcgggt tggagtggta 840gcgttgcgtt tcggcgtcgg tttttacgcg ttattattgg tttatgatgg gcgtaaacga 900tatcgcggtc gatacgattt atattaggat tatagttgtt cgggcgtagc gtttggtgat 960tagtgcgtcg taacgtagcg ggttggttat agttaggtag cggtttacgg ttagggcgta 1020tagggtttcg atgttggcgg ttatatatag tacgtttatc gaggtttata gttcgtagtt 1080agtggcgttt aacggttagt ggttagttag cgttaaggtg gtcgtcggcg gtattattag 1140gagttttatt attaggtcgg ttgcggttag cgaagttacg aatacgttgg ttatggtttg 1200gagtttcgga gtttaggcga tggttacgat gattagtagg ttgtttttta cggtggttag 1260tatcgttagc gttagtaggg tttcggttag ggtcgttttt tacggaattt ttggtagttt 1320attggtgttg gcggtattgg gcgttagggt 135051600DNAHomo sapiens 5cgaaaagttt ttgaggcgtt gcgtgtattt tattttagga tatcgtgtgt gcgcgtcgag 60ttgagtgcga ggaacgtggc gcgagggtcg ggggatgtcg ggttgcgtgg gtgtgagttt 120tcgcgcgatc gcgatttcgc gtttttttcg ttttcgtcgg aacgtgatcg tagtcgtatt 180ttttttttag ttttttttta gttagacgtt tttttttagg tttttttggg cgtttattgt 240aaattttgcg attaaaatac gtcggtgagt tcggtttatc gatagatgga ttaatcgttt 300ttttttcggt taggggagga ggaatttttt aatttcggag tttagggagt cgggagttgt 360ttcgggacga gtttttcgga gtttagtcgg ttgcggagtt tcggttcggg tcggtttcgg 420ggtttttttg tcggggtggg gtgcgagttt ttgttcgatt tttttggggc ggtttaggta 480ggtttgtcgg ttttcgagga ggtggttagg gcgttttggt ttagtaggtt ttttttcgag 540tcggggggag gggagatcgg ttggggaagg ggtatttcga aggggtggag gtcggggcgg 600gcgggaggta agcgcgtcgc gggcgtgagg gtaaagtttt cgaggttcgc gcggagagta 660tacgtgtatg tgcgcgcggg gttaggtcgg ggtcggtagg atgcgttggg ttcgggggcg 720cgcggggtcg gcgtcgaagg ggataatttt tttttttggt attatcgggg agacgttttg 780tcggtttcgg tttttgggcg tagggacgtt ttagtttacg gagggtggag ttttttttag 840attcgggtta tcggttgggg tttttttaac gttttgtttt tcgagttttc ggatggttcg 900ggttttacgg atttcgcgtt ttttagtttt agtttagttt tttaggtttt ttagatttag 960cggcgtaggg ggcgggggta ggggtagtgg gggttggagg gcgtagtcgg tttttagggt 1020ggggagagtt gcggggggag gaggaggagg gtgtcgacgt ttgagtgggt tcgagttcga 1080gtcgtagtcg ggggagttag ttagttttcg gttaaggtag taggttagtt ttaggaaggg 1140cgggcgattg agtcgaggga gtcggcggtt gggttttttt ttcggttcgc gattttcggc 1200gtcgtcgtcg tcgttatcgt tatcgttatc gttttcgttt tgtcgtcgtc gtcgttgtag 1260agtatcgtag tttcgtcgcg ttttcgcgtt tcgcgtttcg cgtcgttagt cgtttgggag 1320ttcgagcgtc gagttcgggg cggaggagag gggcgttggc gcgagagttc gggcgaggga 1380gtcgcgaagg gagaaggggg cgggcggagg gaggagtagg gagagtggga gaagggggag 1440ggagagagga gagcgaggga gagttggaga gagcgagagt aaagagcgag cgagggagag 1500gagagagaga gagaggagag agaaagatat acgtacgtag agatatacgg ttattggaat 1560tttattagaa aaaagtgagt cgagtaaggg ttagcgggag 160061545DNAHomo sapiens 6ttttcgttaa tttttgttcg gtttattttt ttttaatgga attttagtga tcgtgtgttt 60ttgcgtgcgt gtgttttttt tttttttttt tttttttttt ttttttttcg ttcgtttttt 120gttttcgttt tttttagttt tttttcgttt tttttttttt gcggtttttt cgttcgggtt 180ttcgcgttag cgtttttttt tttcgtttcg ggttcggcgt tcgggttttt aggcggttgg 240cggcgcgggg cgcggggcgc gggagcgcgg cggagttacg atgttttgta gcggcggcgg 300cgataaggcg aaggcggtgg cggtggcggt ggcggcggcg gcggcgtcgg ggatcgcggg 360tcgagaggag agtttagtcg tcggtttttt cggtttaatc gttcgttttt tttgggattg 420atttgttgtt ttggtcggaa attgattggt tttttcggtt acggttcggg ttcgaattta 480tttaagcgtc ggtatttttt tttttttttt ttcgtagttt tttttatttt ggggatcggt 540tgcgtttttt aatttttatt gtttttgttt tcgttttttg cgtcgttggg tttgggaagt 600ttggggagtt gagttgaggt tggagggcgc ggagttcgtg gggttcgagt tattcggggg 660ttcggggggt agggcgttag aaaaatttta gtcggtggtt cgggtttgag gggggtttta 720tttttcgtgg gttaaggcgt ttttgcgttt aggagtcgag gtcgataaag cgttttttcg 780atggtgttag ggaaaggaat tatttttttc ggcgtcggtt tcgcgcgttt tcgaatttaa 840cgtattttgt cggtttcggt ttagtttcgc gcgtatatat acgtgtgttt ttcgcgcgga 900tttcgggaat tttgttttta cgttcgcggc gcgtttgttt ttcgttcgtt tcggttttta 960ttttttcgag atgttttttt tttagtcggt tttttttttt ttcggttcgg gaagaagttt 1020gttgggttag ggcgttttga ttattttttc ggaggtcggt aaatttgttt gaatcgtttt 1080agaggaatcg ggtaggggtt cgtattttat ttcggtagga gggtttcgag atcgattcgg 1140gtcggggttt cgtagtcggt tgggtttcga ggagttcgtt tcgaggtagt tttcggtttt 1200ttaggtttcg gggttggggg gttttttttt ttttagtcgg gaagggggcg attgatttat 1260ttgtcggtgg gtcgggttta tcggcgtgtt ttagtcgtag aatttataat aaacgtttag 1320aaggatttaa aaggaagcgt ttggttggga aagggttgga ggagaggtgc ggttgcggtt 1380acgtttcggc gagagcggga gaggcgcggg gtcgcggtcg cgcgagggtt tatatttacg 1440tagttcggta tttttcggtt ttcgcgttac gtttttcgta tttagttcgg cgcgtatata 1500cggtgttttg gggtggggta tacgtagcgt tttagaaatt tttcg 154571100DNAHomo sapiens 7gaggtattag tttttgaagg tttatttttt aatattggtt gcgagagtaa gaatggtgtg 60taatttataa aagtcgttat tgttgtaggt aagttgtagt aaacgattcg cgttcgagta 120ttttcgtttt cgttttcgtt gcggtttcgt ttacgacgat tttggggaat tataagtttc 180gttatatagc ggggagcgtt cggagttcgc gtcggtttcg tttttagttc ggtttttatt 240ttcggtttcg ttttcggttt tttttcgtcg ggttaatttc gaagagtcgt cggtggtcgc 300ggtagacgga agtcgaacga gtttttcggc ggttgtagga tgggggattt taaagtgaaa 360gtggcggtgc ggatacgatt tatgaatcgg cgaggtgaga gtcgagtttt tttgggtcgt 420cggggcggag gcggtaggtg tttggcgcgt ttttttttcg gtcgtcgtgg ggggttcggc 480ggtttcgttt ttatagttag cggcggggcg cgaggagggg ttcggggatt ttgaaattcg 540ttttcgcgtt gagacgttcg gttttttttt tttttttttt tttttttttg gttagtttcg 600tttttggcgt cgtcgggttt ttcgtgtcgg tttcgttgtt tttttcgttt gcgttcgttt 660cgtttttgcg tttttttgtt ttttcgtttt tttcggaggt tttcgagggc gttttcggtt 720ttcgcgttta gtttcgtttt ggttttttag tttcgttttt ttttcgttag ttgttatcgt 780cgttttcgcg cgcgggtcgt tagtttttgt agttcgtttc gggatcgttc gggatttttc 840gggatttcgc gtttcgttcg ggtcgtttaa gtttgtatcg ttttggttcg cggcgggaag 900aagggtaggg ggttaggcgg gtgtttcgcg gcgagttttt tttatttggg cgttttgaga 960ttggggttag gtggaggaga tgtttttttc gttgtttttg gatagttgag aaagttttgg 1020ttttgtttga agttttattt attatttttt aataaatagt taaagtgtta agatttttgt 1080ggaattgtat ttttttgata 110081100DNAHomo sapiens 8tgttagaaag atataatttt ataagaattt tggtatttta gttatttatt gagagatgat 60gaatgagatt ttaggtaaaa ttaaaatttt tttaattgtt taaaaataac gaaaagggta 120ttttttttat ttgattttaa ttttaggacg tttaggtgga aggaattcgt cgcggggtat 180tcgtttggtt ttttgttttt tttttcgtcg cgggttaagg cggtgtaggt ttgggcgatt 240cgggcgagac gcggggtttc ggggggtttc gggcggtttc gaggcgggtt gtaggggttg 300gcgattcgcg cgcgggggcg acgatgatag ttggcgggga aggagcgagg ttgaggggtt 360aggacgaggt tgggcgcgag ggtcgagggc gttttcggga attttcgggg gagacgagag 420ggtaaaaggg cgtaggggcg gggcgggcgt aggcggaagg ggtagcgggg tcggtacgag 480gggttcgacg gcgttaggga cggggttggt taggggggaa gggaggggag aagagggagt 540cgggcgtttt agcgcgggag cgggttttag ggttttcggg ttttttttcg cgtttcgtcg 600ttgattatag gggcggggtc gtcggatttt ttacggcggt cgagggaagg gcgcgttagg 660tatttgtcgt tttcgtttcg gcggtttagg agggttcggt ttttatttcg tcggtttatg 720ggtcgtattc gtatcgttat ttttattttg gagtttttta ttttgtagtc gtcgaggaat 780tcgttcggtt ttcgtttgtc gcggttatcg gcgatttttc ggggttgatt cggcgggagg 840gggtcggggg cggagtcggg ggtggggatc gggttggggg cggggtcggc gcgagtttcg 900ggcgtttttc gttgtatggc gggatttgta gttttttagg gtcgtcgtgg gcggggtcgt 960agcgaaggcg ggggcgggaa tgttcgggcg cgagtcgttt gttataattt atttatagta 1020atgacggttt ttgtaaatta tatattattt ttgttttcgt agttagtatt gagaagtaag 1080tttttaagag ttgatatttt 11009850DNAHomo sapiens 9ttgtggagcg gaggagggga ggtttggggt cgcggcggtg tgcgtttcgt tttgatcgta 60gagttttttt ttcgaggaaa gcggttggtt cggtttcggt tggtgattac gcggggtttt 120tgtttgtttg gtgcgtaggt gagggtttgt tttttcgttg cgtttcggat agtttggagg 180tgagtacgcg ttgggttttg gatcgcgagt agcgggagaa gtacgagttg gtggtcgtgt 240gtatcgtgta cgtcggcgcg cgcgaggagg tggtgatggt gtttttttcg gtgatcgtgt 300acgacgagga cgattcggcg tttatttttt tcgcgggcgt cgatatcgtt agcgtcgtgg 360tggagtttaa gcggaaggag gtgtttgttc gcgcgtgttg tggtttattt agtgtttgtt 420ttcggttata gttcgttttt cggtcggttt agtgttcgtg tagttattta atcgtgtggt 480cgattattcg cgtttttatt tgtttttcgt tttcgtttgc gtcgtttgtt ttagggggag 540gggaaggggg agttttgtta gtatttagtt gggttttgtt tcgggaggta aggattagga 600cgaggttcga gggttcgcgt ttggggtata tttgtgtcgt tgtaggcggg cgcggcgcgt 660tgttcgggcg gggagtattt gtcgggaggg tatttttttt tattagtagt tagtttttaa 720cgggagggtt tttgagtgat tacgagtaga gtcggggatt ggagaaggac gggaaggcgg 780attattttcg gcgtcgttcg tttcgttttt tttcggttcg cgttggtgga gcgcgatcgt 840tatttgttgg 85010798DNAHomo sapiens 10ttagtaggtg gcggtcgcgt tttattagcg cgagtcggag aagggcgggg cgggcggcgt 60cggaggtgat tcgttttttc gttttttttt aattttcggt tttgttcgtg gttatttaag 120ggttttttcg ttgggggtta attgttggtg ggagggagtg ttttttcggt agatgttttt 180cgttcgggta gcgcgtcgcg ttcgtttgta gcggtataag tatgttttag acgcgagttt 240tcgggtttcg ttttgttttt ttttttagga tagacggcgt agacggaggc gaaggataaa 300tgaaagcgcg aatggtcggt tatacggttg ggtggttata cggatattaa atcgatcgag 360aaacgaattg tggtcggaga tagatattgg gtagattata gtacgcgcgg ataagtattt 420tttttcgttt gaattttatt acggcgttgg cggtgtcgac gttcgcgggg aaggtgggcg 480tcgagtcgtt ttcgtcgtat acggttatcg ggaagggtat tattattatt ttttcgcgcg 540cgtcggcgtg tacggtgtat acggttatta gttcgtattt ttttcgttgt tcgcggttta 600gggtttagcg cgtgtttatt tttaggttgt tcggggcgta gcggaagggt agatttttat 660ttgcgtatta agtagatagg ggtttcgcgt gattattagt cgggatcggg ttagtcgttt 720ttttcgggaa gggggttttg cggttagagc ggggcgtata tcgtcgcggt tttaggtttt 780ttttttttcg ttttatag 79811850DNAHomo sapiens 11atcgtttttt cgtaggggtt ttaggattta tttagatttc gtttgttttt tttttcgcgg 60taggtttcgt tgtatcgtgt atttttttcg cgagaagttg attttgcgga aggcgttcgt 120tattatcgtc gttatttggg ttttggcgtt gtttattatg tgtttttcgg tcgttacgtt 180gatcgttatt cgtgaggagt attattttat ggtggacgtt cgtaatcgtt tttattcgtt 240ttatttttgt tgggaggttt ggttcgagaa gggtatgcgt agggtttata ttattgtgtt 300tttttcgtat atttatttgg cgtcgttggc gtttatcgtg gttatgtacg ttcgtatcgc 360gcgtaagttt tgttaggttt cgggttcggt tttcgggggc gaggaggttg cggattcgcg 420agtatcgcgg cgtagagcgc gcgtggtgta tatgttggtt atggtggcgt tgttttttac 480gttgttttgg ttgtcgtttt gggcgttgtt gttgtttatc gattacgggt agtttagcgc 540gtcgtagttg tatttggtta tcgtttacgt tttttttttc gcgtattggt tggttttttt 600taatagtagc gttaatttta ttatttacgg ttattttaac gagaattttc gtcgcggttt 660ttaggtcgtt tttcgcgttc gtttttgttc gcgttcgtcg gggagttata aggaggttta 720tttcgagcgg ttcggcgggt ttttgtatag gcgggttttc gtggtggtgc ggtttagcga 780tttcgggttg ttttttgagt cgggttttag tagtggggtt tttaggttcg gtcgtttttc 840gttgcggaat 85012850DNAHomo sapiens 12atttcgtagc gggaggcggt cgggtttggg ggttttattg ttagggttcg atttagaggg 60tagttcggag tcgttgggtc gtattattac gaagattcgt ttgtgtagaa gttcgtcggg 120tcgttcggag taggtttttt tgtggttttt cgacgggcgc gggtagaggc gggcgcggaa 180ggcggtttgg aagtcgcggc ggaagttttc gttgaagtag tcgtagatga tggggttggc 240gttgttgttg aagaaggtta gttagtgcgc gaaggggaag gcgtagacgg tgattaggtg 300tagttgcggc gcgttgagtt gttcgtagtc gatgagtagt agtagcgttt agagcggtag 360ttaggatagc gtgaagaata gcgttattat gattagtatg tgtattacgc gcgttttgcg 420tcgcgatgtt cgcgggttcg tagttttttc gttttcgggg gtcgggttcg gggtttggta 480gagtttgcgc gcgatgcggg cgtatatgat tacgatgagc gttagcggcg ttaggtagat 540gtgcgagaag agtatagtgg tgtagatttt gcgtatgttt ttttcgggtt aggtttttta 600gtaggagtag agcgggtagg agcggttgcg ggcgtttatt atgaagtggt gttttttacg 660ggtgacggtt agcgtgacgg tcgagggata tatgatgagt agcgttaggg tttagatgac

720ggcgatggtg acgagcgttt ttcgtagggt tagtttttcg cggaaagggt gtacgatgta 780gcggaatttg tcgcggggag agagataggc gggatttggg tgggttttag ggtttttgcg 840aggggacggt 85013600DNAHomo sapiens 13tttagtttcg gaatcgcgga ttgcgtttag tgacggattt aaatttattt ttttttttga 60tttcgtcgta ggatgacgtt ttaattttcg ggtgcgttta ttgtttaagt gattcgtgag 120acggagcggt ttttttttag agtttcggaa gacgaagtga tttgttttac gttcgtttcg 180tttagtttta ttcgtatacg ggggaattgc gtagaggcgg aagagggagg ttgtcgaggg 240gtttcgagga agtttcgggt acggcgcggg ggacgtagtc ggtttaagag cgagttggta 300ttgagtaagt agcgacggag tcggcgaaag aaggttaacg atcgcgagcg taatcgaatg 360tataatttta attcggtatt ggacgttttg cgcggtgttt tgtttatttt tttagacgac 420gcgaagttta ttaagatcga gacgttgcgt ttcgtttata attatatttg ggcgttgatt 480taaacgttgc gtatagcgga ttatagtttg tacgcgttgg agtcgtcggc gtcgtattgc 540ggggagttgg gtagtttagg cggttttttc ggggattggg ggttttttta ttttttagtt 60014600DNAHomo sapiens 14gattggggag tagagggatt tttagttttc gggggaatcg tttgggttgt ttagtttttc 60gtagtgcggc gtcggcggtt ttagcgcgta taagttgtgg ttcgttatgc gtagcgtttg 120agttagcgtt tagatgtagt tgtgggcgaa gcgtagcgtt tcgattttgg tgagtttcgc 180gtcgtttggg aaggtgggta ggatatcgcg tagggcgttt agtgtcgagt tgaggttgtg 240tattcgattg cgttcgcggt cgttggtttt ttttcgtcga tttcgtcgtt gtttgtttag 300tgttaattcg tttttaggtc ggttgcgttt ttcgcgtcgt gttcggagtt ttttcggggt 360ttttcggtag tttttttttt tcgtttttgc gtagtttttt cgtgtgcgag tggggttggg 420cggggcggac gtggggtagg ttatttcgtt tttcgaggtt ttggggaagg atcgtttcgt 480tttacgggtt atttggatag tgggcgtatt cgagggttga ggcgttattt tacggcgggg 540ttagagggaa gggtaagttt gagttcgtta ttgggcgtag ttcgcgattt cgaggttagg 60015850DNAHomo sapiens 15ttagtttcgg tcgtattgta tagcgaggtc ggttcggagt tcggatgttg ggttcggttt 60cgtcgaggtt cggtttggtt gtaaagtaga ggggggcgag ggaagtcggg ttagcgggtg 120tcgcgggtag tcggcgttcg ggacggggtg tggcgtttag agcgttgttg tttttcgtag 180ttaggaggtt ggatgtcggg tttgggtgtt ttttagaagg agtcgtatta gcgacgaggg 240aagaggaatt ggtttttcgg gtagtttttt tcgttttaaa tttttttttt tcgcggaggg 300tgggcgggcg gagggaggaa gcgtagtcgg ggaacgtggc gttcgcgttt ttttcgttcg 360ggggttgcgg ttgggttgag tgtgttttta aatttgagtt tttcgttttt cgcggtgggg 420tcgggattcg cggttcgggc gggggcgggc gcggtgattg gcggtcgggt cgggttcgtt 480tttcggcgtt gggtagcggg gcgttgggga gtagcgcggc gcgtacgggt cggggcgcgt 540aggtttcgtc gtcggtgagt acgggttttt tttcgcgtgg tttcgtcggg ttcgtttggt 600ttgtttattt tcggagttat ttttgttttc gtatgggttg gcgaagttgg gaggagcgag 660ttggagttag agcgcgcgtc gggcgcgttt cgtcgttgtt tgattcggcg ttcgtagttc 720gggcgtagta cgtcggtcgt aggagtacgg atgtttttcg gagtcgcggg ttggtaggta 780tcgaagtgtt ttgttttggg gttggcgagg ggagggtaaa tttggaattt ttcgggtatt 840ttttagttcg 85016850DNAHomo sapiens 16cgggttgggg ggtgttcggg ggattttaga tttgtttttt tttcgttagt tttagggtag 60gatatttcgg tatttgttag ttcgcggttt cggggggtat tcgtgttttt gcggtcggcg 120tgttgcgttc gaattgcggg cgtcgagtta ggtagcgacg gggcgcgttc ggcgcgcgtt 180ttggttttag ttcgtttttt ttaatttcgt tagtttatgc gggggtagag gtggtttcgg 240aggtgggtag gttaggcgga ttcggcgagg ttacgcgaga gggagttcgt gtttatcggc 300gacgggattt gcgcgtttcg gttcgtgcgc gtcgcgttgt tttttagcgt ttcgttattt 360aacgtcgagg ggcggattcg attcggtcgt taattatcgc gttcgttttc gttcggatcg 420cgagtttcgg ttttatcgcg aggggcgggg ggtttagatt taaagatata tttagtttag 480tcgtagtttt cgggcgggag gaacgcgggc gttacgtttt tcggttgcgt tttttttttt 540cgttcgttta tttttcgcga ggaggaaaag tttggggcgg gggagattgt tcgggaagtt 600agtttttttt ttttcgtcgt tagtgcggtt ttttttggaa gatatttaaa ttcgatattt 660agttttttgg ttgcgagagg tagtagcgtt ttgggcgtta tatttcgttt cggacgtcgg 720ttattcgcga tattcgttgg ttcggttttt ttcgtttttt tttgttttat agttaggtcg 780agtttcggcg ggatcgagtt tagtattcgg gtttcgggtc ggtttcgttg tgtagtgcgg 840tcggagttgg 85017600DNAHomo sapiens 17ttttgtatag gagtagtgat tttagtattt atttaatttt ttttcggcgt cgagtttagt 60tggagaggtt aggggtggta gtgattggta ggaggtcggg gcggggggaa tttttaagtt 120cggcgtttgg ggttgcgggt tcgattcgag attcgttttt tttgtaagtt tcgagtcgtt 180ggttaggttc gttattgcgt attagtcgta ttcgcgagcg ttggttttgt cggtttgagt 240tagggtgggt agggtcggga tttacggcgg aggtggggtc gggtcgagta gtttcggggg 300attttcgaag ttatagcgtt ttgttttttt gtacgtttcg cgttttcggt tttcgattgg 360ttgtcgggtt tagagttcgt ttagaattgg atcgttcgtt tgtcgttcgg gtttggtttt 420atttttagag ggagtttaga atttggtcgt agtttttaga gattattttt atttcgtggt 480ttgcgtcgaa gttgggcgga ggatagtggg tggttaggtt ttttcgggtt agaattcggg 540atttttgtta gttattcgtg ttaggataga tttaagtttt taaaacgcgg atggatgtat 60018600DNAHomo sapiens 18gtatatttat tcgcgttttg ggggtttgag tttgttttgg tacgggtagt tggtaggggt 60ttcgagtttt ggttcggaag ggtttggtta tttattgttt ttcgtttaat ttcggcgtag 120gttacggggt gagggtagtt tttaaaaatt gcgattaggt tttaggtttt ttttgggggt 180ggagttagat tcgagcgata agcgaacggt ttaattttgg gcgggtttta ggttcgatag 240ttaatcggag gtcgggggcg cggagcgtgt agggaggtaa ggcgttgtag tttcggggat 300ttttcgaggt tgttcggttc ggttttattt tcgtcgtggg tttcggtttt atttatttta 360gtttaggtcg gtagagttag cgttcgcgga tgcggttggt gcgtagtagc gggtttggtt 420agcggttcgg ggtttgtagg gagggcggat ttcgggtcgg attcgtagtt ttagacgtcg 480ggtttggggg tttttttcgt ttcggttttt tgttagttat tattattttt agttttttta 540attgagttcg gcgtcgggag aggattaagt aagtgttgag gttattgttt ttgtgtaaga 600191548DNAHomo sapiens 19aggtagggat aaagtgtaag aggtaaaatt ggttgaaaag tagaagtgta ggagtcgtta 60aggggcggga cgaataggtt cgtgggtcgg gcggagttaa gggtgggggt cggggttttt 120ttaggtggta ttcgcggcgt tagtttttaa acgttatagc gtttcgggcg tttaggagaa 180cgcgaacggt ttttcgcggg agcgggcgag taggaggggg cgtcgggtta tatatatagc 240ggttcggttt cgggcgggtt tggcgtttag ggaggcgcgt attgtttttt agagttttag 300ttttagtcgc gcgtttttcg ttcggttcgt cgttttatgt agtcggggta gagttcggcg 360ttcgggggtt tcgtcgtttg tttttcgtat tttttcggtt gcgtattttt gttcgaggtc 420ggtcgtgcgt tttcgcggga cgttataggc gtagttttgt tttttagttt ttcgggcgta 480ttgatcgttt gatcgacgta cggttttcgg gtcgggatgt cggggttcgg gacggtcgcg 540gtagcgttgt tttcggcggt tttgttggtt ttgttggcgt tttgggcggg tcgagggggc 600gtcgtcgtat ttattgtatt taacggtacg ttggaggtcg agttggagcg tcgttgggag 660agtttggtgg cgttttcgtt ggcgcgtttg tcggtggtag cgtagtttaa ggaggcggtc 720gtttagagcg gcgtcggcga ttatttgttg ggtattaagc ggttgcggcg gttttattgt 780aacgtgggta tcggttttta tttttaggcg tttttcgacg gtcgtatcgg cggcgcgtac 840gcggatattc gcgatagtga gtggcgcggt taggcgcgaa ggggcggggg cggggggtaa 900cggtcgtcgg gttaattcgt ttagttatat tttgagattt tcggcgggta tttgttcggg 960ggtttcggga atcggggcgg attcgggttt cggttttttt tgacgcgggg ttggggacgt 1020agatattttt ggtttcggta gtttagcgta atttttgagg tcgggcgtcg tttttcgttt 1080ttagaaattc gggtttcgag cgtcgaattt tagcgttttc gttcgtgggt atagggcgcg 1140cggtgtagtt atagggggtt cgagatacgc gtttcggttt ggtttaggtt ggggaatcgt 1200tggggtcggg ttcgcgtttg aaggttcggg attgggtgcg gtcgtcgggg gttttttata 1260taggtaagtt aatttgagtt agcgtaggtt tgggtttcgg aggttttaga gggtagtttg 1320ggttttggag gtttttgggg gcggttgcgt cgggaatttt ggttttttat ttttaatttt 1380attttagaaa tagggttttc ggaggcgaat aagtcgaggg gcggagtggg ttagggatta 1440tttgtttcgt aatgatttgc gtttcgtttt taggtttgtt ggagttttcg ttcgtggagc 1500ggggcgtggt gagtattttc ggcgtggtta gtcggttttt cgtggtta 1548201600DNAHomo sapiens 20tggttacgaa gaatcggttg gttacgtcga agatgtttat tacgtttcgt tttacgggcg 60agagttttag taggtttggg ggcggggcgt aggttattgc ggggtaggtg atttttggtt 120tatttcgttt ttcggtttgt tcgttttcgg ggattttatt tttggggtgg ggttggggat 180aaagggttag ggttttcggc gtagtcgttt ttaagggttt ttagagttta agttgttttt 240tagggttttc ggagtttaag tttgcgttag tttagattag tttgtttgtg taggggattt 300tcggcggtcg tatttagttt cggattttta gacgcgagtt cgattttagc ggttttttag 360tttgggttag gtcggggcgc gtgtttcggg ttttttgtgg ttgtatcgcg cgttttgtgt 420ttacgggcga aggcgttgga attcggcgtt cggagttcga gtttttgaag gcgggaggcg 480gcgttcgatt ttaggggttg cgttgggttg tcggagttaa gagtgtttgc gtttttagtt 540tcgcgttaga agggatcgga gttcgagttc gtttcggttt tcggggtttt cgagtaggtg 600ttcgtcgagg gttttagagt gtgattgagc gggttggttc ggcggtcgtt gtttttcgtt 660ttcgtttttt cgcgtttggt cgcgttattt attgtcgcgg gtgttcgcgt gcgcgtcgtc 720gatgcggtcg tcggggagcg tttggaggtg gaagtcgatg tttacgttgt agtagagtcg 780tcgtagtcgt ttgatgttta gtaggtagtc gtcggcgtcg ttttggacgg tcgttttttt 840gggttgcgtt gttatcggta ggcgcgttaa cgagagcgtt attaggtttt tttagcggcg 900ttttagttcg gtttttagcg tgtcgttggg tgtagtgggt gcggcggcgt tttttcggtt 960cgtttagggc gttagtaagg ttagtaggat cgtcgggagt agcgttatcg cggtcgtttc 1020gggtttcgat atttcggttc gagggtcgtg cgtcggttag gcggttagtg cgttcgggaa 1080gttggggggt agagttgcgt ttgtggcgtt tcgcgggagc gtacggtcga tttcgggtag 1140gagtgcgtaa tcgaggaggt gcgggaggta agcgacgggg ttttcgggcg tcgggtttta 1200tttcggttgt atggagcggc gagtcgggcg gaaagcgcgc ggttggagtt gggattttga 1260ggagtagtgc gcgttttttt gagcgttagg ttcgttcgag gtcgagtcgt tatatatata 1320gttcggcgtt tttttttatt cgttcgtttt cgcggggggt cgttcgcgtt tttttgggcg 1380ttcggggcgt tgtggcgttc gcggttggtc gtaggtcgtt tgttaattag ggtcggggga 1440agggaggagg ttggggatta gcgtcgcgag tgttatttgg agggatttcg gtttttattt 1500ttggtttcgt tcggtttacg gatttgttcg tttcgttttt tggcggtttt tatatttttg 1560ttttttagtt agttttgttt tttgtatttt gtttttgttt 1600211100DNAHomo sapiens 21agggtgaagt ttgagagttt aaatggttaa ttttataggg ttgaacgttt tagaagtcgt 60aggttcgttg gggttgattt tggtagttgt cgtggaggtg ggggtattgt tgggtaacgg 120cgcgttgttg gtcgtggtgt tgcgtacgtc gggattgcgc gacgcgtttt atttggcgta 180tttgtgcgtc gtggatttgt tggcggtcgt ttttattatg tcgttgggtt tgttggtcgt 240atcgtcgttc gggttgggtc gcgtgcgttt gggtttcgcg ttatgtcgcg tcgttcgttt 300ttttttcgtc gttttgttgt cggtttgtac gttcggggtg gtcgtatttg gtttggtacg 360ttatcgtttt atcgtgtatt cgttgcggtt aggttcgcgg tcgtcgtttg tgttcgtgtt 420tatcgtcgtg tgggtcgcgg cgggattgtt gggcgcgttt tttttgttcg gtacgtcgtt 480cgtatcgttt tttgtttttg ttcgttgttc ggttttggtt gggggtttcg ggttttttcg 540gtcgttttgg gttttgttgg ttttcgcgtt gttcgttttt ttgttgttcg gcgtttacgg 600cggtattttc gtggtggcgc gtcgcgttgt tttgaggttt ttacggtcgg cgcgcgggtt 660tcgattttat tcggattttt tggatagtcg tttttttatt ttgtcgtcgt ttcggtttcg 720tttgttcggg ggtaaggcgg ttttggtttt agcgttggtc gtgggttaat ttgtagtttg 780ttggttgttt tatggttgcg cgtgtttggc gttcgtagcg cgggtcgcgg aagtcgaagc 840ggttgttatt tgggtcgttt attcggtttt cgcggtttat ttttttttgt acgggttgtt 900gtagcgtttc gtgcgtttgg tattgggtcg tttttttcgt cgtgtattgt ttggatttgt 960gcgggtttgt atttcgtaag tttggtattc gcgggtattt ttgtaatgtt tttagagatt 1020tttagagggt tttgtcgtag gtttttttga ggttttagaa tagattttcg agttggtagg 1080agggcggagt ttcgtatatt 1100221100DNAHomo sapiens 22ggtatgcggg gtttcgtttt tttgttaatt cgggggtttg ttttggagtt ttagaagggt 60ttacggtagg gttttttggg ggtttttgga ggtattgtaa gagtgttcgc gggtgttagg 120tttgcggagt gtaggttcgt ataggtttag gtagtgtacg gcgagagagg cggtttagtg 180ttaagcgtac ggggcgttgt agtagttcgt ataggaaggg gtgagtcgcg aaggtcgagt 240aggcgattta ggtgatagtc gtttcggttt tcgcggttcg cgttgcgggc gttaggtacg 300cgtagttata aggtagttag taggttgtaa attggtttac ggttagcgtt ggggttaggg 360tcgttttgtt ttcgggtagg cgaggtcgga gcggcggtaa gatggaaagg cggttattta 420gagagttcga gtggagtcgg gattcgcgcg tcggtcgtgg gggttttagg gtagcgcgac 480gcgttattac gaagatgtcg tcgtaggcgt cgagtagtag gagggcgggt agcgcgaagg 540ttagtagggt ttagagcggt cggaagggtt cgaggttttt agttaggatc gagtagcgag 600taggagtagg gggcggtgcg ggcggcgtgt cgagtaggga gagcgcgttt agtagtttcg 660tcgcggttta tacggcggtg agtacgagta taggcggcgg tcgcgagttt ggtcgtagcg 720ggtgtacgat gaggcggtag cgtgttaggt taagtgcggt tatttcgagc gtgtaggtcg 780gtagtagagc ggcggagagg aagcgagcgg cgcggtatgg cgcggggttt aggcgtacgc 840ggtttagttc gggcggcggt gcggttagta ggtttagcgg tatgatggag gcggtcgtta 900gtaggtttac gacgtatagg tgcgttaggt agagcgcgtc gcgtagtttc ggcgtgcgta 960gtattacgat tagtagcgcg tcgttgttta gtagtgtttt tatttttacg atagttgtta 1020ggattaattt taacgagttt gcgatttttg aggcgtttag ttttgtggag ttggttattt 1080gggtttttag gttttatttt 110023600DNAHomo sapiens 23ggtgtcggtg ttggtgttgt ttatggtcgc gttgtattag gtgtttaata agtggatatt 60gggttaggta atttgcgatt tgtttatcgt tttcgacgtg ttgtgttgta ttttatttat 120tttgtatttg tgcgttatcg cgttggatag gtattgggtt attacggatt ttatcgatta 180cgtgaataag aggacgtttc ggcgcgtcgt tgcgtttatt tcgtttattt ggtttattgg 240tttttttatt tttatttcgt ttatgttggg ttggcgtatt tcggaagatc gttcggattt 300cgacgtatgt attattagta aggattatgg ttatattatt tattttattt ttggagtttt 360ttatatttcg ttgttgttta tgttggtttt ttatgggcgt atatttcgag ttgcgcgttt 420tcgtattcgt aagacggtta aaaaggtgga gaagatcgga gcggatattc gttatggagt 480atttttcgtt tcgtagttta agaagagtgt gaatggagag tcggggagta ggaattggag 540gttgggcgtg gagagtaagg ttgggggtgt tttgtgcgtt aatggcgcgg tgaggtaagg 60024600DNAHomo sapiens 24ttttgtttta tcgcgttatt ggcgtataga gtatttttag ttttgttttt tacgtttagt 60ttttagtttt tgtttttcga ttttttattt atattttttt tgggttgcgg ggcgggagat 120gttttatggc gggtgttcgt ttcggttttt tttatttttt tgatcgtttt gcggatgcgg 180aagcgcgtag ttcggaatat gcgtttatag agaattagta tgagtagtag cgggatgtag 240aaagttttaa aggtggaata gatagtgtag ttatgatttt tgttaatggt gtatgcgtcg 300gggttcgagc ggtttttcgg ggtgcgttag tttagtatgg gcgggataga gatgaggaag 360ttaataagtt aagtgagcga gatgagcgta gcggcgcgtc ggggcgtttt tttgtttacg 420tagtcgatgg ggttcgtgat ggtttagtat ttgtttagcg cgatggcgta taggtgtaag 480atggatgagg tgtagtatag tacgtcgagg gcgatgaata ggtcgtaggt tatttggttt 540agtgtttatt tgttgagtat ttgatatagc gcggttatgg gtagtattaa tatcgatatt 60025850DNAHomo sapiens 25gggatgataa gggagaaaaa tttttttacg gtttcgtttg gttcgcggcg tttgtttgtt 60tgcgcggggt taaagttcgg cgtcgtttac gcgcggttcg ggtgggaatt cgtagacgtg 120gggcgagtag ggtcgttggt tgtggcgggc gagcgtcggg gcgttacgtt cgaggtcgcg 180gggtcggggt tgtaggtata gttcgagcgt ttttcgcggg gtttggtttt tgtcgttttt 240cgtttcgtcg aatcggtatc gtcgtcgtcg gagtcgtagc gagtttttag agtttggttg 300ttggcggtcg ggagcgtcgg gacggggcgc gaagtcggag gtttcgggac gtggatatag 360gtaaaggtcg gcgggtcgga gtcgggcggg gcgcggcggc ggcgtttttc ggagggattt 420ggtttcggtc gggttttatt tagtcgcggt ggttcgggtt tttacgttgg tttaggcggg 480gacgtgttaa ggggttgggt tagggttgtc gttggtttgg tcgtttttcg ttcggcgggt 540tttaggtgac gcggtcgcgg tttaattttc gtatttgagg ttttcggagc ggtttcgggg 600cgcgtttatt tggaggttgg aattatatag ggtcgaaaaa gttgagtttt ggaggcgagg 660cgttgtaggt gtggcggagg aggtcgggga aggtggggtg ggtgttaggg gtttagtatt 720gaattttttt taggtttgag gtggggaatt gcgttttgtt taatttcgga gtttgtgggg 780attatatagt tttttttacg gtcgattttt tttgtacggt tttatttttt tttgtttagt 840ttattttagt 85026850DNAHomo sapiens 26attgaaatgg gttagataaa ggaaagtgga atcgtgtaga gggaatcggt cgtggaaggg 60gttgtgtggt ttttataagt ttcgaaatta aataagacgt agttttttat tttagatttg 120gagagggttt agtattggat ttttggtatt tattttattt ttttcggttt ttttcgttat 180atttatagcg tttcgttttt aggatttagt tttttcgatt ttgtgtaatt ttaattttta 240ggtgggcgcg tttcgaggtc gtttcgagag ttttaggtgc gaaagttaag tcgcggtcgc 300gttatttgag gttcgtcggg cgagaggcgg ttaggttagc ggtaatttta gtttagtttt 360ttggtacgtt ttcgtttggg ttaacgtggg ggttcgggtt atcgcggttg ggtagggttc 420ggtcgaggtt aggttttttc gagaggcgtc gtcgtcgcgt ttcgttcgat ttcgattcgt 480cggtttttat ttgtatttac gtttcggagt tttcggtttc gcgtttcgtt tcggcgtttt 540cggtcgttag tagttaggtt ttgaggattc gttgcggttt cggcggcggc gatgtcggtt 600cggcgagacg ggaagcgata ggagttaaat ttcgcggaaa gcgttcgagt tgtgtttgta 660gtttcgattt cgcggtttcg gacgtggcgt ttcggcgttc gttcgttata gttagcggtt 720ttgttcgttt tacgtttgcg ggtttttatt cgagtcgcgc gtgggcggcg tcgggttttg 780atttcgcgta ggtagataag cgtcgcgggt tagacggaat cgtgggaaag tttttttttt 840ttgttatttt 850271350DNAHomo sapiens 27tgaggtgtgg ggattattta tttcggtggg tttttttatt tttaggtcgg tttttttatt 60acgcgtgggt gtgggggtat tgttttcgtt gcgcgtagga atagcgggga gagttaggag 120cggagcggtt tcgggatgtt agattgagta gtgggttcgt ttgcggttat tttttaggga 180ataagttttt tttcgcggag attttgtttt ttttaaaagt ttttttgggt ttagtttagg 240gcgataggac gatttttttt gggaagggag agtttgttag tttttttttt attcgttagg 300cggtgtagtt ttttttttcg ttcggggcgc gcgtatttta gcgtcgcggg tttagcgttt 360agtagtcgcg ttttaggtcg ggtttcgggt ttcgggagtt cgtaggcgcg cgttcggtcg 420ggcgtgtcgg gagcgcgcgg cggtcggggg cggagcgtag ttagggttgc gcggcgcgtt 480tcggttttcg ttcgttttta gtcgggtttt ttagcggtcg gcgggacggt tttcggttgt 540agtttgttcg ttcgtttcgc gcgggggtcg agtcgcgaag cgcgtttgcg attcggcgtt 600cgggcgcgtt ggagaggacg cgaggagtta tgaggcgtta gtttgcgaag gtggcggcgt 660tgttgttcgg gttgtttttg gaggtagggg tcggggatcg ggtgttgtcg gaggcgcggc 720gtttattatg ttggcggttg ggggcgcgta gtttcgaggc gttttagagg attttgtttg 780ggagcgtaga cggtggagcg acggggagtt atagttttgc gcgtttttcg gagttgggag 840gtgcgggatt ttggtgacgg ggaggttttc gtttcggttc gcgtttttcg tcgttttttc 900ggttttcgta tttcgttttt attttgcggg tgagcgcgtt tttcgcgtcg atcgttttcg 960ttagttcggg gtgatttttg tgtatcgttc gttttttttt ttcgtcgtag agggtcgagg 1020atcggatgga ttcggggttg ggcgggggtg gttttcgggc gcggcgtagg cgcggagagt 1080tcggggcgtc gggtagtttg gggttaggaa aggatgggtg tcgagtcggg gtgaggggag 1140cgggcggagg ggattgtggg gaagtgtcgc gggagtgtcg ggagttgtgg aggtgagtag 1200cgggaggagg cgttttcgcg tgtgaaaatg aagtgtagtt tttaggtgcg gggaggaaat 1260tttgcggaga gtttggttgg gtgggggtgc ggagtcgaag tcggcgggga atttgttgag 1320cggttttcgg gtgcgagcgt tcgtgatcgt 1350281350DNAHomo sapiens 28gcggttacgg gcgttcgtat tcggaagtcg tttaataagt ttttcgtcgg tttcggtttc 60gtatttttat ttagttaggt ttttcgtaga attttttttt cgtatttaaa ggttgtattt 120tatttttata cgcgggaacg ttttttttcg ttgtttattt ttataatttt cggtattttc 180gcgatatttt tttatagttt ttttcgttcg ttttttttat ttcggttcgg tatttatttt 240tttttaattt taaattgttc ggcgtttcgg gtttttcgcg tttgcgtcgc gttcgaggat 300tattttcgtt taatttcggg tttattcgat tttcggtttt ttgcggcggg gagagggggc 360ggacggtgta taaaggttat ttcgagttaa cggaggcggt cggcgcggga aacgcgttta 420ttcgtagggt gggggcgggg tgcgaaaatc gaaggaacga cggaaggcgc ggatcggggc 480gggagttttt tcgttattag ggtttcgtat tttttagttt

cgggaggcgc gtagggttgt 540ggtttttcgt cgttttatcg tttgcgtttt taggtaaggt tttttggggc gtttcggaat 600tgcgcgtttt tagtcgttag tatggtgggc gtcgcgtttt cggtagtatt cggttttcgg 660tttttatttt taagagtagt tcgagtagta gcgtcgttat tttcgtaggt tggcgtttta 720tggtttttcg cgtttttttt agcgcgttcg gacgtcgggt cgtaggcgcg tttcgcgatt 780cggttttcgc gcggggcggg cgggtagatt gtagtcggga gtcgtttcgt cgatcgttgg 840ggggttcggt tgggagcggg cgggagtcgg ggcgcgtcgc gtagttttgg ttgcgtttcg 900ttttcggtcg tcgcgcgttt tcgatacgtt cggtcgggcg cgcgtttgcg ggttttcgga 960attcgaggtt cggtttgggg cgcggttgtt gggcgttagg ttcgcgacgt tgaggtgcgc 1020gcgtttcggg cgggaggagg ggttgtatcg tttggcgaat gggaggggga ttggtaggtt 1080tttttttttt aagggaggtc gttttgtcgt tttagattaa atttaggaag gtttttaaaa 1140gaagtagagt tttcgcgggg ggaagtttgt tttttgagag gtggtcgtag acgaatttat 1200tgtttagttt ggtatttcga agtcgtttcg tttttggttt ttttcgttgt ttttgcgcgt 1260agcgggggta gtgtttttat atttacgcgt gatgggaagg tcggtttggg ggtgggaagg 1320tttatcgaaa tagatggttt ttatatttta 1350291100DNAHomo sapiens 29aatttagaaa taaataaata tatatgtata cgtatataaa tatattttaa attaaaaaat 60atttttagat agtggtatgt attatattta gaaattaata acgaagtaaa ttatgggatg 120ttatttacgt ttgttttaaa ggtatcgaat ttataaatta ttttaggtgc ggagtaggat 180aggttgaaaa taggaatgat atgaattcgc gcggaatagt tgtcggcgcg gtgtttaggg 240cggtatttcg ttcggtttcg gtttttttag ttttgggttc gatttttatt acgtttttgt 300ttcgacgcga acgcggagtt cgagcgcgcg ttacgtcgtg tggggtcgaa gaggttgtta 360tttagaggcg gagtgcgggt tcgcgagggt ttttattcga ttttcgtttt cgttagtatt 420tacggattcg cgttttcgtc gcgcgtcgat tcgggagtag tatcgttttc ggtataggag 480ttttacgcgt tttttattta ataggaagtt gggtggaagt agcgcggatt tacggtatat 540cgaacgtatt ttaatagaat tcgacgtaga tacgcgtttt taatcggcgg agatattggt 600agggttagaa acgcgcgtag cgggggcggg aggtcggtaa gtttttcgtt tttgttcgag 660atttcgtttc ggttcggttt cgtttttttt tttgtttttt ttttttgtac gtacgggttt 720cgtttttcgc gcgacgtttt ttgttgattc ggaaacggat ttttcggagt cgaggttcgt 780tcgggtgagt gtttttcgtt ttttgtggtt aaatttagtt acgtagtttt ttttttgcgg 840cgttttttat attcggggtt tgttggtttt cgcggatgtt ataggttcgg taatcgtttt 900tttgtcggcg gggagtttcg cgacgttcgg aaatgtttcg aagtttgtcg tttagttgtt 960agatttgcgt ttgtgttcgg tttcgttatt gaggtcgttt ttgttcggtt tttttatttt 1020agtttttttt atcgttcgtt tattttatcg cgcgcggttt taggtttcga ttcggtatgt 1080ggtttgtttt ttatcgtttt 1100301100DNAHomo sapiens 30gggacgatgg aagataagtt atatgtcgaa tcgggatttg aggtcgcgcg cgataggatg 60ggcggacggt gaagagaatt agggtggaag ggtcggatag gggcgatttt agtgacggaa 120tcggatatag acgtagattt ggtagttggg cgataggttt cggagtattt tcgggcgtcg 180cgggattttt cgtcgatagg agggcggttg tcgagtttgt gatattcgcg gagattagta 240gatttcgggt gtggaggacg tcgtaggaag ggaattgcgt ggttgggttt ggttataaaa 300agcggagggt atttattcga gcggatttcg gtttcggaga attcgttttc gggttaataa 360aaaacgtcgc gcgaggggcg gggttcgtac gtgtagggag gggaggtaga gaaaaaggcg 420gggtcgggtc ggggcggggt ttcgggtagg ggcggggagt ttatcgattt ttcgttttcg 480ttgcgcgcgt ttttggtttt gttagtgttt tcgtcggttg aaagcgcgtg tttgcgtcgg 540gttttgttgg agtgcgttcg gtgtgtcgtg ggttcgcgtt gtttttattt aattttttgt 600taggtaagag gcgcgtgagg tttttgtgtc gggggcggtg ttgttttcga gtcggcgcgc 660ggcggggacg cgagttcgta ggtgttggcg ggagcgagag tcgggtgggg attttcgcga 720gttcgtattt cgtttttggg tagtagtttt ttcggtttta tacggcgtga cgcgcgttcg 780ggtttcgcgt tcgcgtcgag gtagaggcgt agtaggggtc gggtttaggg ttggaggggt 840cgggatcggg cggggtgtcg ttttggatat cgcgtcggta gttgtttcgc gcgggtttat 900gttattttta tttttaattt gttttgtttc gtatttgaga tgatttataa attcggtatt 960tttgggatag gcgtggatga tattttataa tttatttcgt tattaatttt taaatgtaat 1020atatattatt atttaaaagt attttttaat ttgaaatata tttgtatacg tatatatgta 1080tatttattta tttttgaatt 1100311350DNAHomo sapiens 31tgcgcgttgt tgcgttgagg tcgaatgaag cgtagtacgg tgcgggtagt tcgaggtttc 60gaggttgggt tttgtttgtt tgggattgcg tcgtgtttag tttcggtttt ttttttgtgg 120gtaaggatgg ttgagtttag tttttacggt agcggttttt tgtgttatta gtagtttttt 180ttttgcgttt ttcgtttttt ttttttagat tggatttttt ttttttttcg cgtttttttt 240ttcgtatttt ttattcgttg gttttttttt tagttgtttt ttttttaggt tttttttggt 300tgcgcgcgtt ttttttttcg tttttttttt tttcgtagtt tcgtcgtttt ggtgtttttt 360tgttcggttc ggtcggcgtt cgttttcggt ttcggtttcg ttagttcggg ttttcgcgtt 420cggagtagtt tagttttgta gtggttcggg attcgatgtt atgagaggga agcgagtcgg 480gcgtttagat ttttaggagg cgtcggatgc gcggcgggtt ttgggatcgg gttttttttt 540cggttcgttt tgttttcggg tgattatttg gtttcgttta tagttttgtt tttttcggag 600gagttatcgg tgtcgcgtgc gtgtggagta tttgtagata tgattgcgtg gaggagattt 660tagtcgttgt ttttgttttt cgggttgttg gtgttgtgcg cgaggttttt tattgtagcg 720aagggtaaga cggatttgtt tttggtcggg gaggcggtag agttttcgga ggtttcgtgt 780gcggacgcga gtgtgcgttt tggggatcgt agggtacgga gtggtcgttt ttgttcggcg 840ttgttttatc gtcgaagttc ggggaacgcg atgtacggga gggagttttt atcgcgtttt 900ttttagtttt tttgggtttt cgttttattt cgttattttt tttttttttt ttgggtttat 960aggagagatt tttttttttc ggtagtatag ggtgttaagg agaaaggaat ttaatacgag 1020ttgggttgga attgtgtttc gtcggggcgg tgttgttttt ttcgagacgt ggattttacg 1080ggtcggggtg gttgaggggt agtttttagg attttttttt cggattcgac gcgtttggga 1140aagcgtttcg ggtgaagtcg gtttggaaag ttcgggtttt ttacgggggt tttggtatta 1200ataggtaaag gttttcgtcg gttcggtttt ttcgtattta tatattttat tttttttttt 1260tttttttttt ttttaacgtt tttagtcggc gaggagtagt tgtttttaga aggtcgtttt 1320cgtttttttt tttttcggat ttcgtttttt 1350321350DNAHomo sapiens 32aaggagcgaa gttcggggga gaggaaagcg ggggcgattt tttagaggta gttatttttc 60gtcggttgag gacgttggag agggaaggag gagaggagga atggggtgta tgggtgcgag 120gaggtcgggt cggcggagat ttttgtttat tggtattaaa attttcgtag agagttcgaa 180ttttttaggt cggttttatt cgggacgttt ttttaggcgc gtcgggttcg gggagaaagt 240tttgggaatt gttttttagt tatttcgatt cgtggagttt acgtttcgga ggaggtaata 300tcgtttcggc ggagtatagt tttagtttaa ttcgtattgg gttttttttt ttttgatatt 360ttgtattgtc gagaaaaaga gatttttttt gtgagtttaa gagaggggga aggaatggcg 420gggtggggcg ggggtttagg agggttgggg agagcgcgat ggaagttttt tttcgtgtat 480cgcgtttttc gagtttcggc gatggagtag cgtcgggtag aggcggttat ttcgtatttt 540gcggttttta aaacgtatat tcgcgttcgt atacggggtt ttcgagggtt ttatcgtttt 600ttcggttagg agtaagttcg ttttattttt cgttgtagtg aggagtttcg cgtatagtat 660tagtagttcg agaagtagga gtagcgattg gaattttttt tacgtagtta tgtttgtaga 720tattttatac gtacgcgata tcgatggttt tttcgaggaa ggtagggtta tgagcggagt 780taaataatta ttcgagggta aggcgagtcg gagagagagt tcggttttaa gattcgtcgc 840gtattcgacg ttttttgaag gtttgggcgt tcggttcgtt ttttttttat agtatcgggt 900ttcgagttat tgtagggttg agttgtttcg agcgcggaga ttcgggttgg cggggtcggg 960gtcggggacg agcgtcggtc gagtcgggta ggaaggtatt aaggcggcga ggttgcggga 1020gggggagaag cggggagagg agcgcgcgta gttaggagag atttggagag gaggtagttg 1080gagagagagt tagcgagtgg gagatgcggg gaggggggcg cgggggggag gagagattta 1140gtttagagag aaaaggcgga gagcgtagaa gaagggttgt tagtggtata aggagtcgtt 1200gtcgtggagg ttggatttaa ttatttttat ttatagagag gggatcgagg ttgggtacgg 1260cgtagtttta gatagataga gtttagtttc ggggtttcgg gttgttcgta tcgtgttgcg 1320ttttattcgg ttttagcgta gtagcgcgta 135033850DNAHomo sapiens 33gattttttgg gttaggatat gtgagagttg cgtaggtttg ggttcggcgt ggcggaggtg 60cgcgagagcg gttagaagag ggcgttagag agttaggcgc ggttcgcgga ggagttcgcg 120tcggttttta tatttagttt cgcgtcgcgc ggatttatcg agttcgcgtt tagacgtttt 180agttttatcg agaggtcgtt cgggtcgtgt tttttttttt ttttaggtgt aggtagagtt 240ttcgagttat ggttagtttt ttcggtagtt tcgaagttat tggtaagttt cgaggtaggg 300atggtcggtt taggagggag gaggacgacg tttttttcga agagaagagg ttggggttgt 360agttggaggg gggaagcgta tagttcgagg attgcgagaa cggggaggac gcgtcgcggt 420taggtaggga ggagatcggt atttagatag gtggcgatcg tagaggagta agtgacgcgg 480gcgttggggt tcgggggtgt cgggggcgtc ggtaggggcg gcgggaggtt tcgtggtcgg 540tttcgggttg aagttggtat tttagcggta atttcgaagg gcgcggagtg atagcgcgtg 600acggttttcg agacgttagt tgtcgttttt cggttgtgtg gttttgattt tttgattttt 660ttacgacgtc gttggttggg agatttattg gattttgcgg ttggttaaaa agagaggggt 720agtttcgcgt tttgggggtt tttagtaggg gaagtggcgg gtgttgcgtt gggtattttg 780tttggggtat ttgtttggga ttttgttggt gttttttatt tggcgagggg ttagtggtgg 840gggtaggggg 85034850DNAHomo sapiens 34ttttttattt ttattattgg tttttcgtta ggtgagaggt attaataggg ttttagatag 60atgttttaga taggatgttt agcgtaatat tcgttatttt ttttgttagg ggtttttagg 120acgcggggtt gttttttttt ttttggttag tcgtagagtt tagtgggttt tttagttagc 180gacgtcgtgg gagaattagg aagttaaagt tatatagtcg agaagcggta gttggcgttt 240cggaggtcgt tacgcgttgt tatttcgcgt ttttcggagt tgtcgttaaa atattaattt 300taattcgggg tcggttacgg agtttttcgt cgtttttatc ggcgttttcg gtattttcgg 360attttagcgt tcgcgttatt tatttttttg cggtcgttat ttgtttgggt gtcggttttt 420tttttgtttg gtcgcggcgc gtttttttcg ttttcgtagt tttcgggttg tgcgtttttt 480ttttttagtt atagttttag tttttttttt tcgggaggga cgtcgttttt tttttttttg 540ggtcggttat ttttgtttcg gggtttgtta gtggtttcgg agttgtcgga agggttggtt 600atggttcggg ggttttgttt gtatttggag aagaggaagg atacggttcg agcggttttt 660cggtggagtt ggggcgtttg agcgcgggtt cggtgggttc gcgcggcgcg gagttgggta 720taggggtcgg cgcgggtttt ttcgcgggtc gcgtttggtt ttttggcgtt tttttttggt 780cgttttcgcg tattttcgtt acgtcgggtt taggtttgcg tagtttttat atgttttggt 840ttaggaggtt 850351100DNAHomo sapiens 35tcggcgttta ggtgacgttg attttgttgg tttatcgttt tgggggttat ttaatttttt 60agcgatgttt tttagttggg gaggttaaga agtgtttcgt ttaaggtttt ttaatattcg 120atttttagat ttttaatttt gggttagtta tatcgtaaat ttttttagtt gttttttttg 180cgttttgcgt ttttttttta cgttatttgt tagggagtcg ttaaatagta agatcgcgcg 240ttttgcggtt ttagagtgcg gatttcggtc gcgtgcggtt ttgatcgcgt cgttttattt 300ttggcggggt tacgtacgga cgttatggtt ggcgtcgcgg agtcgggcga tgcgcgcgga 360ttttttcggg gttttgattg tttttgagtt ttttttgcgg ggggcgtgcg cggttcgttt 420ttcgcggcgt tacgcggttt tttttcggtc ggggattggt gcgtcgggcg gggcggggcg 480gggcgggata aaggcgcggg gtttggttgc gcggggtttg cgggtagttt taattttggg 540ttcgtagttt gcgttgggtg cgtaggaagg ttagtgtggg ggtcgttcga tatttttttt 600tcgcggaggt gggagtcgag ttatattttg gagtggggat tggtcgcgga gcgggttgtt 660tagggtcggt cgaggtcggg gcgagttttg cgcggcgttg gagattttgt attttcgggc 720gcgcgtaggg ttttcggtcg tggtcgtaga gttaggaggg gcggtttcgg agttcggcgc 780ggggagggtt taggcgtagt cggggttggt agggcgcgat attcgttttt ttttattttt 840gaaagggttt tttacgtcga gaagaggggc gggtatggtc ggttcggcga aatcggtttg 900tatagatttt gggaagttat cgtttgcgga gggtgggatt ttatagtttg tttatttgtt 960taggttgaga tttcgtgttt tagttttgga tgttttacgg gtttttcgtt tcgggtagcg 1020gcgtacggga ggagaagatt ttcggtttgt agttagattt ttttttgaga ttttttttag 1080tttaggttta gagttttggg 1100361100DNAHomo sapiens 36tttaaagttt taagtttgag ttagggaggg ttttagaggg aggtttgatt gtagatcggg 60agtttttttt tttcgtgcgt cgttgttcgg gacgagaaat tcgtggggta tttaggatta 120ggatacgagg ttttagtttg ggtaggtgga taagttgtgg ggttttattt ttcgtaggcg 180atggtttttt aaagtttgta taaatcggtt tcgtcgggtc ggttatgttc gttttttttt 240tcggcgtggg aagttttttt aaaagtggag gggagcgagt gtcgcgtttt gttaatttcg 300attgcgtttg ggtttttttc gcgtcgggtt tcggagtcgt tttttttgat tttgcgatta 360cggtcgggga ttttgcgcgc gttcgggaat gtagagtttt tagcgtcgcg tagggttcgt 420ttcgatttcg gtcggttttg ggtaattcgt ttcgcggtta gtttttattt taagatgtgg 480ttcggttttt attttcgcgg gggggaaatg tcgggcgatt tttatattga tttttttgcg 540tatttagcgt aaattacgaa tttagagttg gagttgttcg tagatttcgc gtagttagat 600ttcgcgtttt tatttcgttt cgtttcgttt cgttcggcgt attaattttc ggtcgaggag 660gggtcgcgtg gcgtcgcggg gggcgggtcg cgtacgtttt tcgtagggag gatttaggga 720tagttagggt ttcgggagag ttcgcgcgta tcgttcggtt tcgcggcgtt agttatggcg 780ttcgtgcgtg gtttcgttag ggatggggcg acgcggttag agtcgtacgc gatcgaaatt 840cgtattttgg agtcgtagag cgcgcggttt tgttgtttag cggttttttg gtaagtgacg 900tggggaagaa acgtagggcg taggagagat agttggaaag gtttgcggtg tagttggttt 960aggattgagg gtttggaggt cgggtgttgg aagattttga gcgaggtatt ttttggtttt 1020tttagttggg aggtatcgtt gaaaaattag gtgattttta agacggtaga ttagtagagt 1080tagcgttatt tgggcgtcgg 1100371100DNAHomo sapiens 37aaagttaagc gtcgtcgtta tttaaggtat tgcgttgatg cgttgcgggt cgattaggtg 60ttttcgtcgg ggcgtttttt tttacgtagg aagggttacg tcgagagagg taggtaataa 120gggtacggtt ggaggtcgga aggttatttc gttttcggcg gggcgggcgc ggtttagttt 180tatttttcgg gtacgttcgg gcggggcgat tgtagggaac ggggcgggga ggcgatagtt 240ttcggtttcg tcgcgcgtta gttcgttttc gttgttcgga ggcgtcgtag gtttgggttt 300tcggatagtt gagttcgagc gtcgtttttc gaaaggtgaa ggcggttcgg ggaggcgggg 360acggtgacgg gggcgggggt cgcgggcggt ttttcgacgg ttgtcgcggg gttagtttaa 420agttttcgat tttcggtagt tgcgtttttc gcgcggggcg tcggagtagg gcgggttaag 480ttggtttgcg gtcgcggcgg gaagaagggt tagcgaagta ttttcgatcg ggtttaggcg 540tcggacgtcg gggggcgttt cgttgtaatt tttttttgga agtttcgata cgagtttcgg 600ttcgcgcgcg cgttttttta cggttacgcg cgtattttgt cgttcgtatt ttcgcgcgtt 660tttcgtttat tttttttttt tttttttatt tttatatttt aaaataggtt aaggggtgga 720agttatattt ggtgtagttt tcggttttga tgtaaaagta gtttttgttt ttggttgcgg 780gatagcgttg tgattattcg taacgggaga gttgttgtta gtcgttatat cgtgcggaaa 840gcgtcggcga tcggagtatt gataatggtt tgtatagggg agcggagaga agtttttgtt 900gcgttttaga ttcgttgttt cggcgttcgt tcgtagggag gagggggcgc gataggtcgt 960ttagcgcgtg tttcggagtt cgcgttcggg tttggtcgtt tgggtgagtt tttgttcgtt 1020ttttgttttt ttagtagttc ggggtggttg tttattttgt aaatagtttt gtaatacgat 1080taaaataggc gagatagtta 1100381100DNAHomo sapiens 38tggttgtttc gtttgttttg atcgtattgt aaggttgttt gtaaggtaaa tagttatttc 60gggttattgg aaaggtaggg gacgagtagg aatttattta ggcggttaga ttcgggcgcg 120ggtttcgggg tacgcgttag acgatttgtc gcgttttttt ttttttgcgg gcgggcgtcg 180aggtagcgga tttagggcgt aatagaagtt ttttttcgtt tttttatgta gattattgtt 240agtgtttcgg tcgtcggcgt ttttcgtacg gtgtggcgat tggtagtagt tttttcgttg 300cgagtagtta tagcgttgtt tcgtagttag gggtaaaagt tgtttttgta ttagagtcga 360gggttgtatt aggtgtaatt tttatttttt gatttatttt agagtgtgag gatgaaagga 420agaggaaaaa atagacggag ggcgcgcggg ggtgcgggcg gtagggtgcg cgcgtggtcg 480tgggggagcg cgcgcgcggg tcggggttcg tgtcggggtt tttaaagaga agttgtagcg 540aggcgttttt cggcgttcgg cgtttgggtt cggtcggggg tgtttcgtta gttttttttt 600tcgtcgcggt cgtaggttag tttggttcgt tttatttcgg cgtttcgcgc gggaagcgta 660gttatcgggg atcgggggtt ttgggttggt ttcgcgatag tcgtcgggag atcgttcgcg 720gttttcgttt tcgttatcgt tttcgttttt tcgggtcgtt tttatttttc gggaggcggc 780gttcgggttt agttgttcgg gaatttaggt ttgcggcgtt ttcgggtagc gaaggcgggt 840tggcgcgcgg cggagtcggg gattgtcgtt ttttcgtttc gttttttgta atcgtttcgt 900tcgaacgtgt tcgggaagtg aggttgggtc gcgttcgttt cgtcggggac ggggtgattt 960ttcggttttt agtcgtgttt ttgttgtttg tttttttcgg cgtggttttt tttgcgtagg 1020agaagacgtt tcggcgggag tatttggtcg gttcgtagcg tattagcgta gtattttggg 1080tgacgacgac gtttggtttt 110039600DNAHomo sapiens 39gcgattttag aggagtaatc gggttttaat tttttgcgtt cgttttgtta taattttttt 60ttatttattt ttattttatt tttataatat tttttattgg gggggttttt tgtgtttcgg 120attttttttt ttatggtttt tttagtcgaa gtcgggggtt ttttgggcgg tttggagggt 180ttgggttagt aggtgggttc gtattttttg ttgttttttg tcggggagcg gtcgtcgttg 240ttgggcgagc gtaggagcgc ggcggagcgg agcgcgcgcg gcgggtcggg ggttgcgtag 300ttggcgtatt tgtacggtat tttgcgtcgt cggtagtttt attgtcgtat cggtttttat 360ttgtagattt tgttcgacgg tagcgtgtag ggtattcggt aggattatag ttttttcggt 420acgtattagt atttcgattt tatttttatt tgcgttttag ttcggttttt cgtttttttt 480ttttgtattt ttttttttgt ttgttaaggg cgttatcgtc gcgcggagtt cggagttttt 540ttggatttat tcggtgtaag acgtaggttg gggttgaagg gttggttaga gtagtcgcgg 60040600DNAHomo sapiens 40tcgcggttgt tttggttagt tttttagttt tagtttgcgt tttgtatcgg atgggtttag 60gggagtttcg ggtttcgcgc ggcgatgacg tttttggtag gtaaagaggg aggtgtaagg 120ggagggaacg aggagtcgag ttggggcgta gatgggggtg gggtcgggat gttagtacgt 180atcgaagagg ttgtggtttt gtcgggtgtt ttgtacgttg tcgtcgggta ggatttgtag 240gtggaagtcg gtgcggtaat agagttgtcg gcggcgtagg atgtcgtgta ggtgcgttag 300ttgcgtagtt ttcggttcgt cgcgcgcgtt tcgtttcgtc gcgtttttgc gttcgtttag 360tagcggcggt cgtttttcgg taggaggtaa taggaaatgc gaatttattt gttggtttaa 420gttttttagg tcgtttagaa agttttcgat ttcggttaag ggagttatgg agggggagat 480tcggaatata aaagattttt ttagtaaaga gtgttgtggg ggtgggatgg aggtggatag 540agaaaaatta tagtaaaacg agcgtaaaaa gttaaggttc ggttattttt ttgaggtcgt 600411100DNAHomo sapiens 41tatattttat ttgtgtcgta tatgtgaaga tataattgta aatcgtttac gattttgagt 60taagattttg agttttttga ggttaggaga tcgttaggga atgtgagtgt tttagacggg 120cgttgagttt agttcggaga tttatttcgt tcgtagtagc ggcgcgggtt ttagagagtt 180tcgtattcgg tcgcgtttta gttacgttga ttcggttgtg ttcgtagtgt cgcgttgtcg 240cgtagttagg tgtcgtcggg ttggcgcggt tatttatgat tgcgtggttg ggttgggggt 300tcggggtcgg ggagtagtcg ggattcgtcg ttttttttat gattttttcg ggtcgaatta 360cgggatcgtt acgttgaagg tggcgtcgcg ggttttcggg gtcgcgcgag tgtaggggtc 420gttttcggtc ggtcgcgaag ttcgcggtat cgatttttcg cgagatttcg gcgatttttt 480ttttcgtttt cgttttttcg ttttttgttt ttttttagtt ttggtgtggg cggttttcgt 540tatggttgcg ttgcgaaggt ttttgtggtc gttatttcgg gtgttttttt tattttgcgt 600ttattagttt ttttttgggt cgtgggggcg gtttgcggtg attattttgg gtttttttgg 660tcggtttttt ttttttcgag aggatgagga gagggttgtg gcggaggcgg tatggaggcg 720gcggcggcgt tggggggagt tgagcgtggc ggcggcggtc ggcggggggt tggtcggttt 780ggtatgttat tagttgtacg gggattttag ggtcggttcg tcggcgatcg ggcgattttt 840aaagagcgcg gttacggagt tcgaggattc gtttcgcggt cgggggatgt tgtttatttt 900agtggcggtt gttaaggaga cggtgagtgc gcgagcgcgc gttatatttg cgcgggggat 960gtgattttcg tgtcgggtac gtaggatttt ggaggttgtg gggacggtgt aagcgttgtg 1020gtcgcgggtg aggaattttt cgtgagcgag gttgatattt aggtcggata gtttaggatt 1080cggttattta cgtattggga 1100421100DNAHomo sapiens 42ttttaatacg tgggtgatcg gattttaggt tgttcggttt aggtgttagt ttcgtttacg 60ggaagttttt tattcgcggt tatagcgttt gtatcgtttt tatagttttt agggttttgc 120gtattcggta cgaaggttat atttttcgcg taggtgtgac gcgcgttcgc gtatttatcg

180tttttttggt agtcgttatt gggatgggta gtatttttcg gtcgcggggc gggttttcgg 240gtttcgtggt cgcgtttttt gagggtcgtt cggtcgtcgg cgagtcggtt ttggggtttt 300cgtatagttg gtagtatatt aggtcgatta gtttttcgtc ggtcgtcgtc gttacgttta 360gtttttttta gcgtcgtcgt cgtttttatg tcgttttcgt tatagttttt tttttatttt 420ttcgggagga gaagggtcgg ttaggaaggt ttagggtggt tatcgtaggt cgtttttacg 480gtttaaggag gggttggtga gcgtagagtg gaggagatat tcggggtggc ggttataaga 540gttttcgtag cgtagttata gcggaggtcg tttatattag agttgggagg gggtagagaa 600cggaggggcg ggggcggggg ggggggtcgt cgaaatttcg cgagaagtcg gtgtcgcgag 660tttcgcggtc ggtcgagagc gatttttata ttcgcgcggt ttcggggatt cgcgacgtta 720tttttagcgt agcggtttcg tggttcggtt cgggaagatt atggaagagg cggcggattt 780cggttgtttt tcggtttcga atttttagtt taattacgta gttataaata atcgcgttag 840ttcggcgata tttggttacg cgatagcgcg atattgcggg tatagtcgag ttagcgtaat 900tgaggcgcgg tcgagtgcgg ggttttttgg ggttcgcgtc gttgttacgg gcggggtggg 960ttttcgagtt gggtttagcg ttcgtttggg atatttatat tttttaacgg ttttttgatt 1020ttaggaaatt taaggttttg atttaaggtc gtgaacgatt tgtaattgta tttttatata 1080tacgatataa atgaggtata 110043600DNAHomo sapiens 43gtttgggtac gcgggatagg ttgtattcgt ttgttagagg cgttttatcg aggcgttacg 60ggtgaagttt tcggttttat ttacggggcg gggtttcggt tcggttcgat tattgttcgc 120ggtgggggag ggggatggat tacgttacgc gttaaaggcg atcgcgattt tttttttgta 180ggtagtttgg aaggtttttt tttttttttt acgttatttt tttcgtggta ttgaaaagtt 240tcgttttttt tttttagttt cgtttttttc gagcgttttt tttattgttt ggaatggtgc 300ggttttaggt cgcgggttac gcggcggagg gggcgtggtt tgttttcggt ttagtcggtt 360tttttttgtt tttgttggag ttcggggagt ggcgttggtt gttagagcga tgtcgggtcg 420gagttgcgtc gttttagttt ttttggttgt cgtcgttagt tgtgtcgtcg cgtagtacgc 480gtcgtcggtg agtgagtttg agtcgaggcg tagagagggg cgtgtaggtg cgggcgcgga 540tggaggcgta ggtgtggcgg cgcgagcggg tataaggaat atttcgtgtt gggtagtttt 60044600DNAHomo sapiens 44gaagttgttt agtacgaggt gttttttgta ttcgttcgcg tcgttatatt tgcgttttta 60ttcgcgttcg tatttgtacg tttttttttg cgtttcggtt taagtttatt tatcggcggc 120gcgtgttgcg cgacggtata gttgacggcg gtagttagga ggattaaggc gacgtaattt 180cggttcggta tcgttttagt agttaacgtt atttttcgga ttttagtaga ggtaaagaag 240agtcggttgg gtcgggggta ggttacgttt ttttcgtcgc gtgattcgcg atttgggatc 300gtattatttt aggtagtagg gggaacgttc ggaggaggcg ggattgggag gagaggacgg 360ggttttttag tgttacgaaa agggtggcgt agagaaagag agagagtttt ttaggttatt 420tgtagaagga gagtcgcgat cgtttttggc gcgtggcgtg atttattttt tttttttatc 480gcgggtaata gtcggatcga gtcggagttt cgtttcgtag gtggggtcgg gagttttatt 540cgtggcgttt cgatggggcg tttttagtag gcgggtgtag tttgtttcgc gtatttaggt 60045600DNAHomo sapiens 45ggtagtgtag ttgtgggaat ttttttacgc gtacgaattt agttaacgat ttttgataga 60tttttgggag tttgattaga gatgtaaggg gtgaaggagc gttttttatc gttagggaat 120tttggggata gagcgtttcg gtcgtttgat ggtcgaggta gggtgcgatt taggatttag 180gacggcgtcg ggaattatat tatggttcgg atttttaaga ttttaaagtt cgtcgtcgtt 240atcgtcgcgg ttttgttgtt agtgagtttc ggtcgcggtt tttggttggg gaagagcgta 300tttggcgtcg ggagggggta gggagacggg gatacggtag ggatgtttgg ttttggttat 360ttgcggtcgg gtatgttcgg gtaggacgaa ttcgtcgtcg gagttagggg aagaattggg 420ttttcgggtt gggtaggagg gattcggtcg cgagggagta gagaggcggt ttttttggtt 480gtttcgagtt cgcgaaggga gggaagtttt agaatcgaga gagggaggga gttaaggtgg 540aatttataga gtgagttttt tgaagatata gagcggttgt tttttttatt aattaattaa 60046600DNAHomo sapiens 46ttaattaatt aatgagagag gtaatcgttt tgtgttttta ggaggtttat tttatgggtt 60ttattttgat tttttttttt tttcgatttt ggaatttttt ttttttcgcg ggttcggggt 120agttaggggg atcgtttttt tgttttttcg cggtcgggtt ttttttgttt agttcgggga 180tttagttttt tttttgattt cgacggcgag ttcgttttgt tcggatatgt tcggtcgtag 240gtgattaggg ttaggtattt ttgtcgtgtt ttcgtttttt tgtttttttt cggcgttagg 300tgcgtttttt tttagttagg gatcgcggtc gggatttatt ggtagtagga tcgcgacgat 360gacgacgacg aattttaggg ttttggggat tcgggttatg gtatggtttt cgacgtcgtt 420ttgggttttg ggtcgtattt tgtttcggtt attaggcggt cggggcgttt tgtttttaga 480gttttttaac ggtaggaagc gtttttttat tttttgtatt tttggttaaa tttttaaaaa 540tttattagaa atcgttggtt gagttcgtgc gcgtggagag gtttttatag ttgtattgtt 600471100DNAHomo sapiens 47cgtttgcgga ggattgcgtt gacgagattt ttatttattg ttattaattt gtggtggaat 60ttgtagttgt atattggatt tgattcgttt cgtttcgaat gacgtttgtt cggaggtagt 120gaaagtatag tcgcgtcgtt ttaagttagt ttggatatat aaattagtac gcggtcggag 180aatttcgtaa tttttgcgtt tataaaatat atcgacgatg ttcgatttat tttaagggtt 240gaaatttacg ggtttgagag attataagag cgttttttat cgttatggaa taacggggat 300agaacgtttc ggtcgtttcg ggggttcgga aaaggtacgg tttaggattt agggaggcgc 360ggggagttag gtttgggttt cgggttttta agatttttgt gttcgttgtc gtcgcggttt 420tgttgttggt gagttttcgt cgcggttttt ggttggggaa gagcgtgttt ggcgtttgga 480gagggtaggg agagaggggg atacggcggg ggtgcgtggt tcgggtcgtt tgcggtcggg 540tatgttcggg taagacgtat tagtcgtcgg agtcggggga agagatgggt tttcgggttg 600ggtaggagcg atttgggtcg ttagggaata gagcgcgcgt tttatttggt gtaaattttc 660gaatttagtg ggggagggcg ataaggaggg aattttcgag taagttgcgt gaagttacgg 720agaggtcgtc ggattttgat tttgtttttt ttttttattt tttgtttttt tttttttttt 780tttttttttt tttttttttt tttttttttt tttcgtttag tttttgtttt aatttttttt 840ttttttgcgt tttcgaatga atttttaaag gcgtttattg tagatcgttt tgaatttgcg 900gtcggcgaag aatttttttg tggtcgttgc ggtttagtgg tttcgtttcg tgcgcgggag 960tcgtcgcggg cgtagttgga gaggtttttt ttttttttta gcggttgcgt ttttacgcgt 1020gcggggtcgt ttatcgttaa tgttattgtt tggggttttt tgggaaaacg agatttagga 1080gaagggagtt gtggtatttg 1100481048DNAHomo sapiens 48taagtgttat aatttttttt ttttaaattt cgttttttta aggaatttta aataatggta 60ttggcgatga gcggtttcgt acgcgtaggg gcgtagtcgt taaggagggg aaggggtttt 120tttagttgcg ttcgcgacga ttttcgcgta cggaacggaa ttattgggtc gtagcgatta 180taggggagtt tttcgtcggt cgtaggttta aagcgatttg taatgagcgt ttttaggaat 240ttattcgaag gcgtaaaaga aaaagaaatt aaggtaggaa ttgagcgagg aaggaaggga 300gggaaagaaa ggaagaaaga gaaaaagaga aagaaataga aagtaaggaa agaaaataaa 360attaaagttc gacgattttt tcgtggtttt acgtagttta ttcgggaatt ttttttttgt 420cgtttttttt tattggattc gggaatttat attaagtgga gcgcgcgttt tgttttttgg 480cggtttaggt cgtttttgtt taattcgggg atttattttt tttttcgatt tcgacgattg 540gtgcgttttg ttcggatatg ttcggtcgta ggcgattcgg gttacgtatt ttcgtcgtgt 600ttttttttgc ggggatttat taatagtagg atcgcggcga taacgagtat aagggttttg 660gggattcggg gtttaggttt ggtttttcgc gtttttttgg gttttgggtc gtgttttttt 720cgggttttcg aagcggtcgg ggcgttttgt tttcgttgtt ttatggcggt agggaacgtt 780tttatagttt tttaggttcg tgggttttag tttttaaagt agatcgggta tcgtcggtgt 840attttgtggg cgtagagatt gcggggtttt tcggtcgcgt gttgatttat gtgtttaggt 900tgatttgggg cggcgcggtt gtatttttat tgttttcggg taggcgttat tcggggcggg 960gcgaattaga tttaatgtgt aattgtaaat tttattatag gttggtgata ataaataaga 1020gtttcgttaa cgtaattttt cgtaagcg 1048491299DNAHomo sapiens 49tgtacgttta ttgtttgttt ttttttttgt acgtttggtg ggttttattt taggcgggtg 60ttgcgacggt ggttattgcg tttttgcgta cgcgggggta gttttcgtcg ttattttttt 120tggcgtatat gttgagtttt tatcgcgatt cgttgtcgag ggtagatatt attcgtagtt 180tataggtaga aggtaggtag tgtcgcgtgt cgcgttttgt tgggtatttt cggggcgttt 240tcgtcgcgtt tagttagcgg attcgggaag tgttgtgggt tgggggttgc ggtttcgagt 300cgggtttgta gtcgttcggg cgtttcgagt ttagggttta gttttgcggg tgttttcgcg 360ttagtaggtt cggggtgtag cgttggtggt tgggggcgta tttacggtcg agtcgggaag 420ggattttagc gtttagggtg tgttttcgac ggggattatt gtttttgggt tttggtttgg 480gattgcgcgg agcgtagcgc ggaagggtgg gagtttttaa tttttagttt tgtgaagttg 540tttatttcgg agtttgggtt tgcgtatttg taggataggt gtaataaata atatttcgtt 600tattagattg tggaaagcgc gagatgataa tgcgcgcgaa acgtttagcg tagtattcgg 660tatagttata gttaacggtc gttggtatta ttgtaatggt ttggttttgg cgcgggagta 720tcggtagttg agttggtaat atcggggatt cgggtttacg gttcggagat tagggatggg 780ttgtttcgaa gtcgcgaatt gtggtagttt tgggtttttt agtcgcgtcg gggaagtgtt 840aagtgtttcg tttaatttcg ggttcggggt tatgatttgt aggggagtgg gtgttaagga 900cggtagggat ttgagggtat cgttttcgag gatttggtag cgcgttttgg gtatttagcg 960cggcgagtag gtgggtgttg cggagaggga gtttttttcg cgttttaatt tatattttgt 1020cgtttgggta gtcgcggtcg tttacgtttt ttttcgtttg cgggggttag acggtttttt 1080ttggggtcgg ggcgtaattt ataaacgtta atttgattcg atttgtcgtt tgttcgtttt 1140ttgtgatttg gtgtcggggg tttttcgttt tcgcgtttgg ggttagatag tcggtgattt 1200ttttcggaag ggttatttgg ggattagtta gattagggga tattttcggg ggcggggtaa 1260tgagaaattt gttggagtgt tcggtttttt aatcgaaaa 1299501350DNAHomo sapiens 50ttttcggttg aggggtcgag tattttagta aattttttat tgtttcgttt tcgagggtgt 60tttttggttt ggttggtttt tagatgattt tttcggagag ggttatcggt tgtttgattt 120taggcgcggg agcgaagggt tttcggtatt aggttataag gggcgggtag gcggtaggtc 180ggattagatt agcgtttgtg gattgcgttt cggttttagg gagggtcgtt tggttttcgt 240aggcggaggg aggcgtgggc ggtcgcggtt gtttaggcgg tagaatgtgg attgaggcgc 300ggaaggggtt tttttttcgt agtatttatt tgttcgtcgc gttgggtgtt tagaacgcgt 360tgttaggttt tcgagggcga tatttttaga tttttgtcgt ttttgatatt tatttttttg 420taaattatgg tttcgaattc ggggttaagc gagatatttg atattttttc ggcgcggttg 480gaggatttaa ggttgttata gttcgcgatt tcgggatagt ttatttttga ttttcgggtc 540gtgagttcga attttcgatg ttattagttt agttgtcgat attttcgacg ttatatttcg 600ggatttattt atttttattc gtagaaagaa aaaaaaatcg ttaagattaa attattatag 660taatattaac gatcgttgat tgtggttgtg tcgggtattg cgttgagcgt ttcgcgcgta 720ttgttatttc gcgtttttta tagtttgata ggcgaggtgt tatttattat atttatttta 780tagatgcgta gatttaggtt tcgggataag taattttata agattggaga ttagaagttt 840ttattttttc gcgttgcgtt tcgcgtaatt ttaaattaaa atttagagat aatggttttc 900gtcgaggata tattttgaac gttagaattt tttttcgatt cggtcgtgga tacgttttta 960gttattaacg ttgtatttcg agtttgttga cgcggagata ttcgtagagt taggttttgg 1020gttcgggacg ttcgggcggt tgtaaattcg gttcggagtc gtagttttta atttatagta 1080tttttcgagt tcgttggttg gacgcggcgg aggcgtttcg ggggtgttta gtagggcgcg 1140gtacgcggta ttgtttattt tttgtttgta ggttgcggat gatgtttgtt ttcggtagcg 1200ggtcgcggta gaggtttagt atgtacgtta gaggggatgg cgacgagggt tgttttcgcg 1260tacgtaggag cgtagtggtt atcgtcgtag tattcgtttg gagtagggtt tattaggcgt 1320gtagaaggaa gggtaggtag tgggcgtgta 135051350DNAHomo sapiens 51ttttgaaggg cggcggattt tagggttatg ttggttgttt ttagaaagta ggagttcgaa 60atcgcggggt taacgaacgt ttatattttt tgttataatt tcgttatttt tttgcgtttt 120tttttttgtt ttttgttttt ataggtaacg tttagaacga gtgttttttt cggtggggta 180ttgaggagtt tgggttgtag ttgtcgagtc gttatagtta cgttgagttc ggtttggttt 240gtatattggc gttatcgttt ggcggggagc gggattgacg cgtttttttt tttttttttt 300agtttagatt acggaggcgc ggagttttat tttttgtttt gggcgagggg 35052350DNAHomo sapiens 52tttttcgttt agggtaggag atggagtttc gcgttttcgt gatttgggtt ggaggagagg 60gagaggagcg cgttagtttc gtttttcgtt aggcggtggc gttagtgtgt aggttaggtc 120gggtttagcg tggttgtggc ggttcggtag ttgtagttta ggttttttag tattttatcg 180ggagaagtat tcgttttggg cgttatttgt gggggtaggg ggtaagggga gaggcgtagg 240ggagtggcga ggttgtagta gagaatgtgg gcgttcgttg gtttcgcggt ttcgggtttt 300tgttttttgg ggatagttag tatggttttg aagttcgtcg ttttttagag 35053350DNAHomo sapiens 53taattagggt tggtttattt ttttttagtt aatttttttt tatttttagt ttttaattta 60atttatttcg tttattagtt tttggatttt tattattttt ttcgtatttt cggtagtttt 120ggggaagttt cgtgacgtta taggtttcgt ttttagtttc ggttcggggt tagtgcgtgt 180tgacgttatg ttgcgtgcgg gtcggtgcgg aatcgttttt ttaatttcgc ggggtagtag 240gagttagtta gtaaagagtc gaggtcgggc gcgcgatttt cgtttttttg tttttggtcg 300tatattttgc gtatattttt ttttttgtat ggtggatatt attttttatt 35054350DNAHomo sapiens 54aatgaaaaat aatatttatt atgtagaaaa agagatgtgc gtaaagtgtg cggttagggg 60tagaaggacg agggtcgcgc gttcggtttc ggttttttgt taattaattt ttattgtttc 120gcggagttga aggagcgatt tcgtatcggt tcgtacgtag tatgacgtta atacgtatta 180gtttcgggtc ggagttgggg gcgggatttg tggcgttacg aagttttttt agaattgtcg 240gggatgcggg ggaggtgatg gggatttagg ggttgatggg cggggtgggt tgggttggag 300gttgggggtg aagggagatt ggttgggagg aagtgggtta attttgattg 3505522DNAArtificialPrimer 55gagcgggtag cgagagtttc gg 225623DNAArtificialPrimer 56taacgacgcg actaccgaaa acc 235724DNAArtificialPrimer 57gattaacgtg ttcgtgattt cgtt 245825DNAArtificialPrimer 58caacgaccaa taaccaatca acgcc 255924DNAArtificialPrimer 59atacgtcggt gagttcggtt tatc 246024DNAArtificialPrimer 60actcccgact ccctaaactc cgaa 246122DNAArtificialPrimer 61tgaatcggcg aggtgagagt cg 226224DNAArtificialPrimer 62accgaacgtc tcaacgcgaa aacg 246324DNAArtificialPrimer 63tatcgttagc gtcgtggtgg agtt 246424DNAArtificialPrimer 64ctacacgaac actaaaccga ccga 246525DNAArtificialPrimer 65tcggtcgtta cgttgatcgt tattc 256624DNAArtificialPrimer 66accctacgca tacccttctc gaac 246724DNAArtificialPrimer 67gtttcgagga agtttcgggt acgg 246824DNAArtificialPrimer 68gatcgttaac cttctttcgc cgac 246921DNAArtificialPrimer 69cgaagttggg aggagcgagt t 217024DNAArtificialPrimer 70aaacatccgt actcctacga ccga 247124DNAArtificialPrimer 71cgtattagtc gtattcgcga gcgt 247221DNAArtificialPrimer 72cgaaactact cgacccgacc c 217324DNAArtificialPrimer 73taacggtacg ttggaggtcg agtt 247424DNAArtificialPrimer 74acgaccgcct ccttaaacta cgct 247524DNAArtificialPrimer 75tatcgtgtat tcgttgcggt tagg 247623DNAArtificialPrimer 76aacgatacga acgacgtacc gaa 237724DNAArtificialPrimer 77tacgtgaata agaggacgtt tcgg 247823DNAArtificialPrimer 78aacgatcttc cgaaatacgc caa 237922DNAArtificialPrimer 79tcgtcgaatc ggtatcgtcg tc 228024DNAArtificialPrimer 80acctatatcc acgtcccgaa acct 248125DNAArtificialPrimer 81cggttgtagt ttgttcgttc gtttc 258224DNAArtificialPrimer 82ctaacgcctc ataactcctc gcgt 248324DNAArtificialPrimer 83gcgtcgattc gggagtagta tcgt 248424DNAArtificialPrimer 84ataccgtaaa tccgcgctac ttcc 248524DNAArtificialPrimer 85cgttgaggtc gaatgaagcg tagt 248623DNAArtificialPrimer 86aaccgaaact aaacacgacg caa 238724DNAArtificialPrimer 87aagcgtatag ttcgaggatt gcga 248823DNAArtificialPrimer 88ccgcgtcact tactcctcta cga 238924DNAArtificialPrimer 89cgttgggtgc gtaggaaggt tagt 249022DNAArtificialPrimer 90gaccgaccct aaacaacccg ct 229122DNAArtificialPrimer 91gttgcgggat agcgttgtga tt 229224DNAArtificialPrimer 92accattatca atactccgat cgcc 249324DNAArtificialPrimer 93tttgtttgtt aagggcgtta tcgt 249422DNAArtificialPrimer 94ccgcgactac tctaaccaac cc 229523DNAArtificialPrimer 95gggcgttgag tttagttcgg aga 239624DNAArtificialPrimer 96acgaacacaa ccgaatcaac gtaa 249722DNAArtificialPrimer 97ggcgttggtt gttagagcga tg 229824DNAArtificialPrimer 98gactcaaact cactcaccga cgac 249924DNAArtificialPrimer 99ggtgcgattt aggatttagg acgg 2410024DNAArtificialPrimer 100gcgaccgaaa ctcactaaca acaa 2410124DNAArtificialPrimer 101gcgatttggg tcgttaggga atag 2410225DNAArtificialPrimer 102acctctccgt aacttcacgc aactt 2510322DNAArtificialPrimer 103ggtagtcgcg gtcgtttacg tt 2210424DNAArtificialPrimer 104acgaacaaac gacaaatcga atca 2410524DNAArtificialPrimer 105tacgttgagt tcggtttggt ttgt 2410623DNAArtificialPrimer 106cgcgcctccg taatctaaac taa 2310724DNAArtificialPrimer 107gtgcgtgttg acgttatgtt gcgt 2410822DNAArtificialPrimer 108cgcccgacct cgactcttta ct 2210924DNAArtificialPrimer 109cggcgatttc ggggatttta gggc 2411025DNAArtificialPrimer 110gaccgctctt ctaaaaaatc ccgcg 2511123DNAArtificialPrimer 111acgttcgggg tgtagcggtc gtc 2311224DNAArtificialPrimer 112ccccaatact aaatcacgac gccg 2411325DNAArtificialPrimer 113ggtcggcgtc gtgatttagt attgg 2511424DNAArtificialPrimer 114actacgacga cgaaactcca acga 2411526DNAArtificialPrimer 115tgtggtgatt ttggggattt tagggt 2611627DNAArtificialPrimer 116ccaaccactc

ttctaaaaaa tcccaca 2711725DNAArtificialPrimer 117gatgtttggg gtgtagtggt tgttg 2511826DNAArtificialPrimer 118ctccacccca atactaaatc acaaca 261191300DNAHomo sapiens 119gtcaggtggg ctactccacc agggaggcct tctccccacc cctggcccag ggcccttccg 60gatttccaga gaattctgga accaagacct tcccctttct caccagggac ctccttgctc 120cagggcctcc cgagcgcctg gccgtgaggc agggcccaga aggccagggc gggatccagg 180tggctggcct cacccactgg gacgtgccca acctggagac attgcaccag gtagggctgc 240accgctctcc gagaccccgc cccgtgcttc cacttggggg cggggaccct gcacctgacc 300agcccttcgc cccgccttcc agatgctgaa actggggagg agcaaccggg ccaccgccgc 360caccgccatg aaccagcgca gctcccgctc gcatgccctg gtcacgctga cgctgcgcgc 420ggcgtctcca ccgcgcgctc caggcaccgc aggtaccacg gccggtgcct gagccctgcg 480gagtctccag agcacccgag gcccggcctt cccccatgtc gggctcgctc gcccctctag 540gcacgctgca cctggtggac ctggcgggat ccgaacgcgc acggaaggca ggggcggccg 600gcccgccgcg gggagaccca gacggcgccc ggcgcctgcg ggaggcccag accataaacc 660gctcgctgct ggcgctagga ggcgtgatgg ccgcactgcg ggcccaccgg ccgcacgtgc 720ccttccgcga ctcgcagctc acgcgactgc tgcagccggc gctgggccca ggcaccaccg 780cggtgctgct gctgcaggtg ggcgccgggg cggggcaggt gtgtgcgtgc cggtcgccgc 840ccacccgggc ccgcccaccc gcgcctcttg cccgcagatc tccacgcggc cggaggatct 900cggggagaca gtctgctccc tcaagttcgc cgaccgagtg ggtcaagtgg agctggggcc 960agcccggcgc cgcagggtcc cgcgctcctc cgggacgcct tcttccctca gcaccgacac 1020tccgctcacc gggaccccct gcacccctac gccgtcccct ggcagtcctc catgccccag 1080tcccgacaac ggctcgggct cggctctcgc gcccgcagag ggcctgcccc tctagtcctg 1140ggtcgcggcc ctgcccatgg ggtctcaggc caggtctctg ctggcagagg cggtagtaaa 1200gtccctgtac cccgtctccc agggcacaag ctccctagcc tctttggatc cattgcccct 1260gagctcccag agtcacccct ccacctccgc agccagtgaa 13001201300DNAHomo sapiens 120ttcactggct gcggaggtgg aggggtgact ctgggagctc aggggcaatg gatccaaaga 60ggctagggag cttgtgccct gggagacggg gtacagggac tttactaccg cctctgccag 120cagagacctg gcctgagacc ccatgggcag ggccgcgacc caggactaga ggggcaggcc 180ctctgcgggc gcgagagccg agcccgagcc gttgtcggga ctggggcatg gaggactgcc 240aggggacggc gtaggggtgc agggggtccc ggtgagcgga gtgtcggtgc tgagggaaga 300aggcgtcccg gaggagcgcg ggaccctgcg gcgccgggct ggccccagct ccacttgacc 360cactcggtcg gcgaacttga gggagcagac tgtctccccg agatcctccg gccgcgtgga 420gatctgcggg caagaggcgc gggtgggcgg gcccgggtgg gcggcgaccg gcacgcacac 480acctgccccg ccccggcgcc cacctgcagc agcagcaccg cggtggtgcc tgggcccagc 540gccggctgca gcagtcgcgt gagctgcgag tcgcggaagg gcacgtgcgg ccggtgggcc 600cgcagtgcgg ccatcacgcc tcctagcgcc agcagcgagc ggtttatggt ctgggcctcc 660cgcaggcgcc gggcgccgtc tgggtctccc cgcggcgggc cggccgcccc tgccttccgt 720gcgcgttcgg atcccgccag gtccaccagg tgcagcgtgc ctagaggggc gagcgagccc 780gacatggggg aaggccgggc ctcgggtgct ctggagactc cgcagggctc aggcaccggc 840cgtggtacct gcggtgcctg gagcgcgcgg tggagacgcc gcgcgcagcg tcagcgtgac 900cagggcatgc gagcgggagc tgcgctggtt catggcggtg gcggcggtgg cccggttgct 960cctccccagt ttcagcatct ggaaggcggg gcgaagggct ggtcaggtgc agggtccccg 1020cccccaagtg gaagcacggg gcggggtctc ggagagcggt gcagccctac ctggtgcaat 1080gtctccaggt tgggcacgtc ccagtgggtg aggccagcca cctggatccc gccctggcct 1140tctgggccct gcctcacggc caggcgctcg ggaggccctg gagcaaggag gtccctggtg 1200agaaagggga aggtcttggt tccagaattc tctggaaatc cggaagggcc ctgggccagg 1260ggtggggaga aggcctccct ggtggagtag cccacctgac 1300121550DNAHomo sapiens 121aacacgtgta ggttgttgga attacattaa cgaatgaatg agcaaaacct tctaaaccac 60cgaccaatga aaccccgata cagaaaatcg ctgtcatgag taagttagca ctcctgaaga 120gtttgaatac tgaactggcc agagtctgcg cgccgacgcc ccccaggtgg ccggagtgac 180ccggagcagg cgtggctgtc tctcagaccc gcgcgttggg cccgaacagt ttgtccccac 240gcagctccca tataaggcgg gcccctcccc tgccccagcc agctaggtcg ccgcgctggc 300tccctggcgg cttctcaaac caacccgccg ctactgcgca tgcttggcaa gctcgcccgc 360tccttaatat cctgctccgg ctgttcctgc cacccgttgg tcaaattcgc acccagctct 420gctccagaca gagggaaaac ccagtgattt ccgggctcta gaaacaaagg gaggctatga 480ttccctgctg gccctagggg tccagggaag gttatggaaa gataattctt tgtgtaagcg 540ggttgcgtac 550122550DNAHomo sapiens 122gtacgcaacc cgcttacaca aagaattatc tttccataac cttccctgga cccctagggc 60cagcagggaa tcatagcctc cctttgtttc tagagcccgg aaatcactgg gttttccctc 120tgtctggagc agagctgggt gcgaatttga ccaacgggtg gcaggaacag ccggagcagg 180atattaagga gcgggcgagc ttgccaagca tgcgcagtag cggcgggttg gtttgagaag 240ccgccaggga gccagcgcgg cgacctagct ggctggggca ggggaggggc ccgccttata 300tgggagctgc gtggggacaa actgttcggg cccaacgcgc gggtctgaga gacagccacg 360cctgctccgg gtcactccgg ccacctgggg ggcgtcggcg cgcagactct ggccagttca 420gtattcaaac tcttcaggag tgctaactta ctcatgacag cgattttctg tatcggggtt 480tcattggtcg gtggtttaga aggttttgct cattcattcg ttaatgtaat tccaacaacc 540tacacgtgtt 550123550DNAHomo sapiens 123cagccgaggg gcgcgcctgg ctgatgtgtg gttgaatgga gagcggccca accctcctcc 60ttcctcctct tcttctcccc gccctgacac ccgggcctca aacttcaacc aaagcccgtg 120cccttttcaa tttacccccc tcgatcaaaa tgagccattc ttgtctgtcc tccgcggcgg 180cccattgtct ggcgtgatag gtttgcagat ttgacagctg ggcgcacgca gatttgattc 240aaactcggtc tccccgagag atgaacttgg acatcagcaa agatcccgag cactgccggc 300tggctcctag accggtctcc cgacccagtg tagacttcgg tgccccgggc gccccccggc 360gtgcgggaag gggagcgtgt gtcaggcgtg gggggcgggg ggtgagcagc acgactggga 420accagcggtc ccaggggttg gggcgaaggg ctgtgtacat gttaggcttt ttttgttgtt 480gttaatttac tctcgaaaca gccaaaatgg aggtcagctt ataaattttc taaagccagg 540tctggccggg 550124550DNAHomo sapiens 124cccggccaga cctggcttta gaaaatttat aagctgacct ccattttggc tgtttcgaga 60gtaaattaac aacaacaaaa aaagcctaac atgtacacag cccttcgccc caacccctgg 120gaccgctggt tcccagtcgt gctgctcacc ccccgccccc cacgcctgac acacgctccc 180cttcccgcac gccggggggc gcccggggca ccgaagtcta cactgggtcg ggagaccggt 240ctaggagcca gccggcagtg ctcgggatct ttgctgatgt ccaagttcat ctctcgggga 300gaccgagttt gaatcaaatc tgcgtgcgcc cagctgtcaa atctgcaaac ctatcacgcc 360agacaatggg ccgccgcgga ggacagacaa gaatggctca ttttgatcga ggggggtaaa 420ttgaaaaggg cacgggcttt ggttgaagtt tgaggcccgg gtgtcagggc ggggagaaga 480agaggaggaa ggaggagggt tgggccgctc tccattcaac cacacatcag ccaggcgcgc 540ccctcggctg 5501251050DNAHomo sapiens 125agaaactgag gtcggagtgg gggcgtgacc aggccagcct aaggccgctg cactaatgag 60aagctgagct ctcagatttt tgcctccctg tccctgccaa gtcgctgttt cctgggacaa 120gagggagcct cactgaaacg aactccggtc tcaggggaca gaatcctgaa accctggctc 180tggggtccgg ggcaggggtg cgctgcctca ggacagacgg tgaaactgag gtccagagcc 240ggacatccac cgcctgcgga gggaacgaga acgcggcgcg tcctgccttg cgggccgagc 300ggcgccagag ccgcctcctc ccgccccccg cgctagatcc ccccgccccg tctttgccct 360cgcgacgccg ccacctccgg aacaagccat ggtggcggcg acggtggcag cggcgtggct 420gctcctgtgg gctgcggcct gcgcgcagca ggagcaggac ttctacgact tcaaggcggt 480caacatccgg ggcaaactgg tgtcgctgga gaagtaccgc ggatcggtga gtgcgcgggg 540tctggcggcg ccgctgggcc cggcctcgcc ctggcggggc ctgctgggga cgccccgcag 600cccggtcccc cgcgcggtgt ggctccgagg acgctccagc cgcgcggccg ccaaaccccg 660gcccccgccc cgctcggccg tgacctctgg cgcggcgccc ccatcccgcg cccggcccgg 720cccggcccgc ggctacgtgg cacggccttg gcgcggagga acccgaagcg ctcgcagtcg 780gcgcccactt cgctaccggc acctttgggc agcggggtcc agaccttcgc cgggaggccg 840ggcaccactg cccagccttt gccattcacg ggtgaaaaaa gtaaccgtag catcgtgcgg 900cctttccctc tcccgtcctc attttctgca tctggaacgg ggagtggctg attcggagtc 960cagtgaagaa cactgtggag atcaatgtgc agggcagaga gagagttatt tcagatgcac 1020ggagacctca cacggatcat ccctgggaga 10501261050DNAHomo sapiens 126tctcccaggg atgatccgtg tgaggtctcc gtgcatctga aataactctc tctctgccct 60gcacattgat ctccacagtg ttcttcactg gactccgaat cagccactcc ccgttccaga 120tgcagaaaat gaggacggga gagggaaagg ccgcacgatg ctacggttac ttttttcacc 180cgtgaatggc aaaggctggg cagtggtgcc cggcctcccg gcgaaggtct ggaccccgct 240gcccaaaggt gccggtagcg aagtgggcgc cgactgcgag cgcttcgggt tcctccgcgc 300caaggccgtg ccacgtagcc gcgggccggg ccgggccggg cgcgggatgg gggcgccgcg 360ccagaggtca cggccgagcg gggcgggggc cggggtttgg cggccgcgcg gctggagcgt 420cctcggagcc acaccgcgcg ggggaccggg ctgcggggcg tccccagcag gccccgccag 480ggcgaggccg ggcccagcgg cgccgccaga ccccgcgcac tcaccgatcc gcggtacttc 540tccagcgaca ccagtttgcc ccggatgttg accgccttga agtcgtagaa gtcctgctcc 600tgctgcgcgc aggccgcagc ccacaggagc agccacgccg ctgccaccgt cgccgccacc 660atggcttgtt ccggaggtgg cggcgtcgcg agggcaaaga cggggcgggg ggatctagcg 720cggggggcgg gaggaggcgg ctctggcgcc gctcggcccg caaggcagga cgcgccgcgt 780tctcgttccc tccgcaggcg gtggatgtcc ggctctggac ctcagtttca ccgtctgtcc 840tgaggcagcg cacccctgcc ccggacccca gagccagggt ttcaggattc tgtcccctga 900gaccggagtt cgtttcagtg aggctccctc ttgtcccagg aaacagcgac ttggcaggga 960cagggaggca aaaatctgag agctcagctt ctcattagtg cagcggcctt aggctggcct 1020ggtcacgccc ccactccgac ctcagtttct 1050127550DNAHomo sapiens 127ttctcttacg atctggcttt actctcacgc gcacagccga gtccctgggg acccagcaga 60ggtccgaagc ggagcggggc ggggcggggc tacggaagct ggcgaggccg agcccctcct 120agtgcttccg gaccttgctc cctgaacact cggaggtggc ggtggatctt actccttcca 180gccagtgagg atccagcaac ctgctccgtg cctcccgcgc ctgttggttg gaagtgacga 240ccttgaagat cggccggttg gaagtgacga ccttgaagat cggcgggcgc agcggggccg 300agggggcggg tctggcgcta ggtccagccc ctgcgtgccg ggaaccccag aggaggtcgc 360agttcagccc agctgaggcc tgtctgcaga atcgacacca accagcatca tgtccatgac 420actggggtac tgggacatcc gcggggtgag tgagggtccg ctgcactgtg ggaccgggcg 480cgtgggcggg aagtgccgag cggctgggga ccggctctag ggacggttcc ctccttaggg 540ctatctctca 550128550DNAHomo sapiens 128tgagagatag ccctaaggag ggaaccgtcc ctagagccgg tccccagccg ctcggcactt 60cccgcccacg cgcccggtcc cacagtgcag cggaccctca ctcaccccgc ggatgtccca 120gtaccccagt gtcatggaca tgatgctggt tggtgtcgat tctgcagaca ggcctcagct 180gggctgaact gcgacctcct ctggggttcc cggcacgcag gggctggacc tagcgccaga 240cccgccccct cggccccgct gcgcccgccg atcttcaagg tcgtcacttc caaccggccg 300atcttcaagg tcgtcacttc caaccaacag gcgcgggagg cacggagcag gttgctggat 360cctcactggc tggaaggagt aagatccacc gccacctccg agtgttcagg gagcaaggtc 420cggaagcact aggaggggct cggcctcgcc agcttccgta gccccgcccc gccccgctcc 480gcttcggacc tctgctgggt ccccagggac tcggctgtgc gcgtgagagt aaagccagat 540cgtaagagaa 550129550DNAHomo sapiens 129tcttgaattg ggggcggagg taaaaaaaaa aaaaaagtcc tcactgtggg aagctataaa 60aagcaaagag gactggggag agagcagaga gagagaaagc gggagcccgc ggcgagcgta 120gcgcaagtcc gctccctagg catcgctgcg ctggcagcga ttcgctgtct cttgtgagtc 180aggggacaac gcttcggggc aactgtgagt gcgcgtgtgg gggacctcga ttctcttcag 240atctcgagga ttcggtccgg ggacgtctcc tgatccccta ctaaagcgcc tgctaacttt 300gaaaaggagc actgtgtcct gcaaagtttg acacataaag gataggaaaa gagaggagag 360aaaagcaact gagttgaagg agaaggagct gatgcgggcc tcctgatcaa ttaagaggag 420agttaaaccg ccgagatccc ggcgggacca aggaggtgcg gggcaagaag gaacggaagc 480ggtgcgatcc acagggctgg gttttcttgc accttgggtc acgcctcctt ggcgagaaag 540cgcctcgcat 550130550DNAHomo sapiens 130atgcgaggcg ctttctcgcc aaggaggcgt gacccaaggt gcaagaaaac ccagccctgt 60ggatcgcacc gcttccgttc cttcttgccc cgcacctcct tggtcccgcc gggatctcgg 120cggtttaact ctcctcttaa ttgatcagga ggcccgcatc agctccttct ccttcaactc 180agttgctttt ctctcctctc ttttcctatc ctttatgtgt caaactttgc aggacacagt 240gctccttttc aaagttagca ggcgctttag taggggatca ggagacgtcc ccggaccgaa 300tcctcgagat ctgaagagaa tcgaggtccc ccacacgcgc actcacagtt gccccgaagc 360gttgtcccct gactcacaag agacagcgaa tcgctgccag cgcagcgatg cctagggagc 420ggacttgcgc tacgctcgcc gcgggctccc gctttctctc tctctgctct ctccccagtc 480ctctttgctt tttatagctt cccacagtga ggactttttt ttttttttta cctccgcccc 540caattcaaga 550131550DNAHomo sapiens 131cgattggctg caagggtctc ggcttggccg cggattggtc acacccgagg gcttgaaagg 60tggctgggag cgccggacac ctcagacgga cggtggccag ggatcaggca gcggctcagg 120cgaccctgag tgtgccccca ccccgccatg gcccggctgc tgcaggcgtc ctgcctgctt 180tccctgctcc tggccggctt cgtctcgcag agccggggac aagagaagtc gaaggtgagt 240gagcctccgg gccgggggcc gggagaaaaa acctagcccc tcggtgtcca gcgctcagtg 300caatgcaccc cttttcccag gctccccgcc agatgggcaa tccccaggtg cgagagacct 360cctgaacccc ttttgccgcc ccctccgccg ccgggacccc gcccccgacc gtcgtcgtct 420cgtagttcca tctgttggag agccgagacc tggtgcttca ggcgggcaga atgactaagg 480gaggaaggtc tctctccccg agctcgcact ttctccccac tgccacctcg agggtcgcct 540tgctacatct 550132550DNAHomo sapiens 132agatgtagca aggcgaccct cgaggtggca gtggggagaa agtgcgagct cggggagaga 60gaccttcctc ccttagtcat tctgcccgcc tgaagcacca ggtctcggct ctccaacaga 120tggaactacg agacgacgac ggtcgggggc ggggtcccgg cggcggaggg ggcggcaaaa 180ggggttcagg aggtctctcg cacctgggga ttgcccatct ggcggggagc ctgggaaaag 240gggtgcattg cactgagcgc tggacaccga ggggctaggt tttttctccc ggcccccggc 300ccggaggctc actcaccttc gacttctctt gtccccggct ctgcgagacg aagccggcca 360ggagcaggga aagcaggcag gacgcctgca gcagccgggc catggcgggg tgggggcaca 420ctcagggtcg cctgagccgc tgcctgatcc ctggccaccg tccgtctgag gtgtccggcg 480ctcccagcca cctttcaagc cctcgggtgt gaccaatccg cggccaagcc gagacccttg 540cagccaatcg 550133550DNAHomo sapiens 133aggggaactg gtatctccac agtaattact agagcagctc tggggaacgg agggttggct 60aaggaagaaa agctccccca acccttgggg cgagggagcg ttctctcaat ggagcccccc 120caactcccct ccacccccca ccagtcttcc aggaaagagg aataccctac ccggcagggc 180tgcgaaggaa ggggaaatcc aaccagagcg aaagtcgcac gcggacagct ctgccagccc 240ttggaggcat ccggcggtca cccacgggac aaagcgcggc tgcgggagcg cgcgcggggc 300attccggacc cgcgtcgagc tccgctctag agggggcggc gggcggcgac aagccggaga 360gaggaagggc caaggagcac ggccctcctg tcggcaccat cagcgggaga gtggcgagcg 420gacgcctaga cggaggggcc ctactcagac cccatcgagc cagttcccaa gcttttccct 480ccgacctgct ccctcccggg gcgcgtgagg gtgcgggtcg ggggtgaacc tggtgttggg 540gaaagtgatt 550134550DNAHomo sapiens 134aatcactttc cccaacacca ggttcacccc cgacccgcac cctcacgcgc cccgggaggg 60agcaggtcgg agggaaaagc ttgggaactg gctcgatggg gtctgagtag ggcccctccg 120tctaggcgtc cgctcgccac tctcccgctg atggtgccga caggagggcc gtgctccttg 180gcccttcctc tctccggctt gtcgccgccc gccgccccct ctagagcgga gctcgacgcg 240ggtccggaat gccccgcgcg cgctcccgca gccgcgcttt gtcccgtggg tgaccgccgg 300atgcctccaa gggctggcag agctgtccgc gtgcgacttt cgctctggtt ggatttcccc 360ttccttcgca gccctgccgg gtagggtatt cctctttcct ggaagactgg tggggggtgg 420aggggagttg ggggggctcc attgagagaa cgctccctcg ccccaagggt tgggggagct 480tttcttcctt agccaaccct ccgttcccca gagctgctct agtaattact gtggagatac 540cagttcccct 5501352800DNAHomo sapiens 135cgggcaaaaa tggagagcag gcagaggtca catcctcctc ctcttcctca cgctcccggg 60ctgcgtgccc acaggggcac agccctgtgc gcggtgccac cgggggccat caggctgggt 120tagaggaagg cccgacctcc gcgcagcaaa gaaaacaaac acagatgtgt ttggctggga 180ccgggaggga gaaagtggcc cccttccccc gcccgcgcgc tcccccgggc gtgaggctct 240ccgggcggcg cggggcgcgg gcgaggctga cagtccccgg cggcccctcc tcccccacgg 300ggtgcgcgcc tggcccggcc cagccccctc tccggggttt ccccgggtgc tctcctcgct 360ttctctttgt ctctgctgtt ctttctcggg ctcccgggtt cccacccgcc tgtgctctcc 420ctctcgggcg tccgggccgg ttccctttaa ctttcttctt tcccggggtg aaaactttgc 480tcggagctgg cggcagctcg cggacgttat tggccggcgc cccgcccggc ggccccgccc 540cccgcccccg cgctcccctc cgcccctcac tcccagcgcg agtggcggcg gcggcggagc 600cttcgggggc gagcgcgcgt gtgtgtgagt gcgcgccggc cagcgtgagt gtgtgtgcgc 660cccgggcgcg ggcagggcag cactccgagc tcggcgggag cggcgggagc cgggcggccg 720cgtagtcact cgggcgagag aggcggcggc ggggccggga ccggggctgg ggctggggca 780gcggcggccg cgccgggcat ggagctggca agcccgcgct gaggcgggac gcgcctgcta 840gcagcgagcg agaggctctc cggcgaccgg cgcgcgggct ccccggaggg gccaggcaaa 900cttttctttc tcttttgccc cctccagagg taaagtcccg aacgcggact ttccggcggg 960gacgcgatcg gggggcatct gagagggacc ccgggctgcg agacgaaggg gcgcgggccg 1020tgcagagtcg gggtccccca gctctcctgc gcccgaaact tggggtgcga ggggggctgg 1080tcgcggacgg ggagaccggc tcaggcatgc ccctcgggcg gcgtgggggc ggcggtggcg 1140gggaagcaga gcgttctccc gccgggcggg gaagaagggg cgcgagcggt gcggacttgg 1200agggccccgg cttcgccgcc cgcgggactt tgggggagag aggcgggcag tcggctgcgg 1260ggtgggtgcc caggaagccg ggcgttctcc cgcatctccg ctcgccaccc cgccgagagc 1320tggagggcgc ggggcgggct ggctgagcgc agctcccttc tctccgcagg cgccttctgc 1380ggcaggcgga cagatcctcg gcgcggcagg gccggggcaa gctggacgca gcatgatgcg 1440cgcagtgtgg gaggcgctgg cggcgctggc ggcggtggcg tgcctggtgg gcgcggtgcg 1500cggcgggccc gggctcagca tgttcgcggg ccaggcggcg cagcccgatc cctgctcgga 1560cgagaacggc cacccgcgcc gctgcatccc ggactttgtc aatgcggcct tcggcaagga 1620cgtgcgcgtg tccagcacct gcggccggcc cccggcgcgc tactgcgtgg tgagcgagcg 1680cggcgaggag cggctgcgct cgtgccacct ctgcaacgcg tccgacccca agaaggcgca 1740cccgcccgcc ttcctcaccg acctcaacaa cccgcacaac ctgacgtgct ggcagtccga 1800gaactacctg cagttcccgc acaacgtcac gctcacactg tccctcggca agaagttcga 1860agtgacctac gtgagcctgc agttctgctc gccgcggccc gagtccatgg ccatctacaa 1920gtccatggac tacgggcgca cgtgggtgcc cttccagttc tactccacgc agtgccgcaa 1980gatgtacaac cggccgcacc gcgcgcccat caccaagcag aacgagcagg aggccgtgtg 2040caccgactcg cacaccgaca tgcgcccgct ctcgggcggc ctcatcgcct tcagcacgct 2100ggacgggcgg ccctcggcgc acgacttcga caactcgccc gtgctgcagg actgggtcac 2160ggccacagac atccgcgtgg ccttcagccg cctgcacacg ttcggcgacg agaacgagga 2220cgactcggag ctggcgcgcg actcgtactt ctacgcggtg tccgacctgc aggtgggcgg 2280ccggtgcaag tgcaacggcc acgcggcccg ctgcgtgcgc gaccgcgacg acagcctggt 2340gtgcgactgc aggcacaaca cggccggccc ggagtgcgac cgctgcaagc ccttccacta 2400cgaccggccc tggcagcgcg ccacagcccg cgaagccaac gagtgcgtgg gtgagtgggg 2460tgcggcggcg gagccggcgg

cgggtggggc cgcgggcggg agctgctggg cctcgcagcg 2520gcgagttcat aggagcgcgg gtcgagggaa cggcgggagg cgcgttcgcc gatgcccggg 2580acccgggagg gctcagagca ggtccactcg ctcgcgtggc gctcgtggtg gacgcccgaa 2640tttgcgccca gtgctctctg cgaagccaag aagcagcagg agaaatgttc ccgggagggg 2700gtttggcaga acatttgcag ataggtctcc gctaaccctg gatccaaacg caaacattca 2760ttgccttccc cctcgttggg ttggacgctg ggattcacct 28001362800DNAHomo sapiens 136aggtgaatcc cagcgtccaa cccaacgagg gggaaggcaa tgaatgtttg cgtttggatc 60cagggttagc ggagacctat ctgcaaatgt tctgccaaac cccctcccgg gaacatttct 120cctgctgctt cttggcttcg cagagagcac tgggcgcaaa ttcgggcgtc caccacgagc 180gccacgcgag cgagtggacc tgctctgagc cctcccgggt cccgggcatc ggcgaacgcg 240cctcccgccg ttccctcgac ccgcgctcct atgaactcgc cgctgcgagg cccagcagct 300cccgcccgcg gccccacccg ccgccggctc cgccgccgca ccccactcac ccacgcactc 360gttggcttcg cgggctgtgg cgcgctgcca gggccggtcg tagtggaagg gcttgcagcg 420gtcgcactcc gggccggccg tgttgtgcct gcagtcgcac accaggctgt cgtcgcggtc 480gcgcacgcag cgggccgcgt ggccgttgca cttgcaccgg ccgcccacct gcaggtcgga 540caccgcgtag aagtacgagt cgcgcgccag ctccgagtcg tcctcgttct cgtcgccgaa 600cgtgtgcagg cggctgaagg ccacgcggat gtctgtggcc gtgacccagt cctgcagcac 660gggcgagttg tcgaagtcgt gcgccgaggg ccgcccgtcc agcgtgctga aggcgatgag 720gccgcccgag agcgggcgca tgtcggtgtg cgagtcggtg cacacggcct cctgctcgtt 780ctgcttggtg atgggcgcgc ggtgcggccg gttgtacatc ttgcggcact gcgtggagta 840gaactggaag ggcacccacg tgcgcccgta gtccatggac ttgtagatgg ccatggactc 900gggccgcggc gagcagaact gcaggctcac gtaggtcact tcgaacttct tgccgaggga 960cagtgtgagc gtgacgttgt gcgggaactg caggtagttc tcggactgcc agcacgtcag 1020gttgtgcggg ttgttgaggt cggtgaggaa ggcgggcggg tgcgccttct tggggtcgga 1080cgcgttgcag aggtggcacg agcgcagccg ctcctcgccg cgctcgctca ccacgcagta 1140gcgcgccggg ggccggccgc aggtgctgga cacgcgcacg tccttgccga aggccgcatt 1200gacaaagtcc gggatgcagc ggcgcgggtg gccgttctcg tccgagcagg gatcgggctg 1260cgccgcctgg cccgcgaaca tgctgagccc gggcccgccg cgcaccgcgc ccaccaggca 1320cgccaccgcc gccagcgccg ccagcgcctc ccacactgcg cgcatcatgc tgcgtccagc 1380ttgccccggc cctgccgcgc cgaggatctg tccgcctgcc gcagaaggcg cctgcggaga 1440gaagggagct gcgctcagcc agcccgcccc gcgccctcca gctctcggcg gggtggcgag 1500cggagatgcg ggagaacgcc cggcttcctg ggcacccacc ccgcagccga ctgcccgcct 1560ctctccccca aagtcccgcg ggcggcgaag ccggggccct ccaagtccgc accgctcgcg 1620ccccttcttc cccgcccggc gggagaacgc tctgcttccc cgccaccgcc gcccccacgc 1680cgcccgaggg gcatgcctga gccggtctcc ccgtccgcga ccagcccccc tcgcacccca 1740agtttcgggc gcaggagagc tgggggaccc cgactctgca cggcccgcgc cccttcgtct 1800cgcagcccgg ggtccctctc agatgccccc cgatcgcgtc cccgccggaa agtccgcgtt 1860cgggacttta cctctggagg gggcaaaaga gaaagaaaag tttgcctggc ccctccgggg 1920agcccgcgcg ccggtcgccg gagagcctct cgctcgctgc tagcaggcgc gtcccgcctc 1980agcgcgggct tgccagctcc atgcccggcg cggccgccgc tgccccagcc ccagccccgg 2040tcccggcccc gccgccgcct ctctcgcccg agtgactacg cggccgcccg gctcccgccg 2100ctcccgccga gctcggagtg ctgccctgcc cgcgcccggg gcgcacacac actcacgctg 2160gccggcgcgc actcacacac acgcgcgctc gcccccgaag gctccgccgc cgccgccact 2220cgcgctggga gtgaggggcg gaggggagcg cgggggcggg gggcggggcc gccgggcggg 2280gcgccggcca ataacgtccg cgagctgccg ccagctccga gcaaagtttt caccccggga 2340aagaagaaag ttaaagggaa ccggcccgga cgcccgagag ggagagcaca ggcgggtggg 2400aacccgggag cccgagaaag aacagcagag acaaagagaa agcgaggaga gcacccgggg 2460aaaccccgga gagggggctg ggccgggcca ggcgcgcacc ccgtggggga ggaggggccg 2520ccggggactg tcagcctcgc ccgcgccccg cgccgcccgg agagcctcac gcccggggga 2580gcgcgcgggc gggggaaggg ggccactttc tccctcccgg tcccagccaa acacatctgt 2640gtttgttttc tttgctgcgc ggaggtcggg ccttcctcta acccagcctg atggcccccg 2700gtggcaccgc gcacagggct gtgcccctgt gggcacgcag cccgggagcg tgaggaagag 2760gaggaggatg tgacctctgc ctgctctcca tttttgcccg 28001371300DNAHomo sapiens 137gcagtcctgt gtgactggtg agactcttgt aggggcgttt ctacaacgac gaaacccttc 60ctaggcactc actccaacag aataacaagc ccattttatt agtatttcgt tttccatgta 120aagttctgct catacgaata tatttataat tctgattttt ttacggcatt ggggagcaca 180ccgacaggct gctgaacggt ggctggagat tcgagggaaa acgaagttcg ccgaggcggc 240ctcgggcggg caggtcccgg gctccatcac agggcacacg cggctaccag ggacgcagcc 300ccccaacaca cacacacaca cacacacaca cacacacaca cacacacaca ccctctccca 360ctcatgcctg gcaacccagc agaaacttcg gactggggca aaacaagccc gggccccggc 420ggcacgcggg gctaggcgcg ttcccgccag tacctggtcg cgaggccgct cgcggggtgc 480cctgcgtgcc ccccactccc gcagcccgcg ccctgctcgc tcactgtggg ggcgcagcgg 540ccaggcttct ctgtttgttg tttaaagaaa tcctagggcg ggcgagcggc ggcatctagg 600ggagggggcg cagccagaat tcccttccag caagcgcgtg aggggcattc tcaacgcaaa 660accagaccca gaaagtagtg accagccctc ctcggattac ccttcattgg ctcctccctt 720gctcccccca ccctccagat ttgcataaaa aaggccaaga aaactctggc tgtgccccag 780caacggctca ttctgctccc ccgggtcgga gccccccgga gctgcgcgcg ggcttgcagc 840gcctcgcccg cgctgtcctc ccggtgtccc gcttctccgc gccccagccg ccggctgcca 900gcttttcggg gccccgagtc gcacccagcg aagagagcgg gcccgggaca agctcgaact 960ccggccgcct cgcccttccc cggctccgct ccctctgccc cctcggggtc gcgcgcccac 1020gatgctgcag ggccctggct cgctgctgct gctcttcctc gcctcgcact gctgcctggg 1080ctcggcgcgc gggctcttcc tctttggcca gcccgacttc tcctacaagc gcagcaattg 1140caagcccatc cctgccaacc tgcagctgtg ccacggcatc gaataccaga acatgcggct 1200gcccaacctg ctgggccacg agaccatgaa ggaggtgctg gagcaggccg gcgcttggat 1260cccgctggtc atgaagcagt gccacccgga caccaagaag 13001381300DNAHomo sapiens 138cttcttggtg tccgggtggc actgcttcat gaccagcggg atccaagcgc cggcctgctc 60cagcacctcc ttcatggtct cgtggcccag caggttgggc agccgcatgt tctggtattc 120gatgccgtgg cacagctgca ggttggcagg gatgggcttg caattgctgc gcttgtagga 180gaagtcgggc tggccaaaga ggaagagccc gcgcgccgag cccaggcagc agtgcgaggc 240gaggaagagc agcagcagcg agccagggcc ctgcagcatc gtgggcgcgc gaccccgagg 300gggcagaggg agcggagccg gggaagggcg aggcggccgg agttcgagct tgtcccgggc 360ccgctctctt cgctgggtgc gactcggggc cccgaaaagc tggcagccgg cggctggggc 420gcggagaagc gggacaccgg gaggacagcg cgggcgaggc gctgcaagcc cgcgcgcagc 480tccggggggc tccgacccgg gggagcagaa tgagccgttg ctggggcaca gccagagttt 540tcttggcctt ttttatgcaa atctggaggg tggggggagc aagggaggag ccaatgaagg 600gtaatccgag gagggctggt cactactttc tgggtctggt tttgcgttga gaatgcccct 660cacgcgcttg ctggaaggga attctggctg cgccccctcc cctagatgcc gccgctcgcc 720cgccctagga tttctttaaa caacaaacag agaagcctgg ccgctgcgcc cccacagtga 780gcgagcaggg cgcgggctgc gggagtgggg ggcacgcagg gcaccccgcg agcggcctcg 840cgaccaggta ctggcgggaa cgcgcctagc cccgcgtgcc gccggggccc gggcttgttt 900tgccccagtc cgaagtttct gctgggttgc caggcatgag tgggagaggg tgtgtgtgtg 960tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgttgggg ggctgcgtcc ctggtagccg 1020cgtgtgccct gtgatggagc ccgggacctg cccgcccgag gccgcctcgg cgaacttcgt 1080tttccctcga atctccagcc accgttcagc agcctgtcgg tgtgctcccc aatgccgtaa 1140aaaaatcaga attataaata tattcgtatg agcagaactt tacatggaaa acgaaatact 1200aataaaatgg gcttgttatt ctgttggagt gagtgcctag gaagggtttc gtcgttgtag 1260aaacgcccct acaagagtct caccagtcac acaggactgc 13001391034DNAHomo sapiens 139gctgcctttg ttctttgact actcagccaa ttcaggtctg agctgttctt cgacgccgcc 60ctagatgcga tgatgaaggt caggtgcccg catcccaccc accgtcccct cgcaggggcc 120ctaggaccca cccagatccc gcctgtctct ctccccgcgg caggttccgc tgcatcgtgc 180accctttccg cgagaagctg accctgcgga aggcgctcgt caccatcgcc gtcatctggg 240ccctggcgct gctcatcatg tgtccctcgg ccgtcacgct gaccgtcacc cgtgaggagc 300accacttcat ggtggacgcc cgcaaccgct cctacccgct ctactcctgc tgggaggcct 360ggcccgagaa gggcatgcgc agggtctaca ccactgtgct cttctcgcac atctacctgg 420cgccgctggc gctcatcgtg gtcatgtacg cccgcatcgc gcgcaagctc tgccaggccc 480cgggcccggc ccccgggggc gaggaggctg cggacccgcg agcatcgcgg cgcagagcgc 540gcgtggtgca catgctggtc atggtggcgc tgttcttcac gctgtcctgg ctgccgctct 600gggcgctgct gctgctcatc gactacgggc agctcagcgc gccgcagctg cacctggtca 660ccgtctacgc cttccccttc gcgcactggc tggccttctt caacagcagc gccaacccca 720tcatctacgg ctacttcaac gagaacttcc gccgcggctt ccaggccgcc ttccgcgccc 780gcctctgccc gcgcccgtcg gggagccaca aggaggccta ctccgagcgg cccggcgggc 840ttctgcacag gcgggtcttc gtggtggtgc ggcccagcga ctccgggctg ccctctgagt 900cgggccctag cagtggggcc cccaggcccg gccgcctccc gctgcggaat gggcgggtgg 960ctcaccacgg cttgcccagg gaagggcctg gctgctccca cctgcccctc accattccag 1020cctgggatat ctga 10341401034DNAHomo sapiens 140tcagatatcc caggctggaa tggtgagggg caggtgggag cagccaggcc cttccctggg 60caagccgtgg tgagccaccc gcccattccg cagcgggagg cggccgggcc tgggggcccc 120actgctaggg cccgactcag agggcagccc ggagtcgctg ggccgcacca ccacgaagac 180ccgcctgtgc agaagcccgc cgggccgctc ggagtaggcc tccttgtggc tccccgacgg 240gcgcgggcag aggcgggcgc ggaaggcggc ctggaagccg cggcggaagt tctcgttgaa 300gtagccgtag atgatggggt tggcgctgct gttgaagaag gccagccagt gcgcgaaggg 360gaaggcgtag acggtgacca ggtgcagctg cggcgcgctg agctgcccgt agtcgatgag 420cagcagcagc gcccagagcg gcagccagga cagcgtgaag aacagcgcca ccatgaccag 480catgtgcacc acgcgcgctc tgcgccgcga tgctcgcggg tccgcagcct cctcgccccc 540gggggccggg cccggggcct ggcagagctt gcgcgcgatg cgggcgtaca tgaccacgat 600gagcgccagc ggcgccaggt agatgtgcga gaagagcaca gtggtgtaga ccctgcgcat 660gcccttctcg ggccaggcct cccagcagga gtagagcggg taggagcggt tgcgggcgtc 720caccatgaag tggtgctcct cacgggtgac ggtcagcgtg acggccgagg gacacatgat 780gagcagcgcc agggcccaga tgacggcgat ggtgacgagc gccttccgca gggtcagctt 840ctcgcggaaa gggtgcacga tgcagcggaa cctgccgcgg ggagagagac aggcgggatc 900tgggtgggtc ctagggcccc tgcgagggga cggtgggtgg gatgcgggca cctgaccttc 960atcatcgcat ctagggcggc gtcgaagaac agctcagacc tgaattggct gagtagtcaa 1020agaacaaagg cagc 1034141800DNAHomo sapiens 141agaaaggtaa tatttggagg cctccgaggg acgggcaggg gaaagaggga tcctctgacc 60cagcgggggc tgggaggatg gctgtttttg ttttttccca cctagcctcg gaatcgcgga 120ctgcgcccag tgacggactc aaacttaccc ttccctctga ccccgccgta ggatgacgcc 180tcaaccctcg ggtgcgccca ctgtccaagt gacccgtgag acggagcggt ccttccccag 240agcctcggaa gacgaagtga cctgccccac gtccgccccg cccagcccca ctcgcacacg 300ggggaactgc gcagaggcgg aagagggagg ctgccgaggg gccccgagga agctccgggc 360acggcgcggg ggacgcagcc ggcctaagag cgagttggca ctgagcaagc agcgacggag 420tcggcgaaag aaggccaacg accgcgagcg caatcgaatg cacaacctca actcggcact 480ggacgccctg cgcggtgtcc tgcccacctt cccagacgac gcgaagctca ccaagatcga 540gacgctgcgc ttcgcccaca actacatctg ggcgctgact caaacgctgc gcatagcgga 600ccacagcttg tacgcgctgg agccgccggc gccgcactgc ggggagctgg gcagcccagg 660cggttccccc ggggactggg ggtccctcta ctccccagtc tcccaggctg gcagcctgag 720tcccgccgcg tcgctggagg agcgacccgg gctgctgggg gccacctttt ccgcctgctt 780gagcccaggc agtctggctt 800142800DNAHomo sapiens 142aagccagact gcctgggctc aagcaggcgg aaaaggtggc ccccagcagc ccgggtcgct 60cctccagcga cgcggcggga ctcaggctgc cagcctggga gactggggag tagagggacc 120cccagtcccc gggggaaccg cctgggctgc ccagctcccc gcagtgcggc gccggcggct 180ccagcgcgta caagctgtgg tccgctatgc gcagcgtttg agtcagcgcc cagatgtagt 240tgtgggcgaa gcgcagcgtc tcgatcttgg tgagcttcgc gtcgtctggg aaggtgggca 300ggacaccgcg cagggcgtcc agtgccgagt tgaggttgtg cattcgattg cgctcgcggt 360cgttggcctt ctttcgccga ctccgtcgct gcttgctcag tgccaactcg ctcttaggcc 420ggctgcgtcc cccgcgccgt gcccggagct tcctcggggc ccctcggcag cctccctctt 480ccgcctctgc gcagttcccc cgtgtgcgag tggggctggg cggggcggac gtggggcagg 540tcacttcgtc ttccgaggct ctggggaagg accgctccgt ctcacgggtc acttggacag 600tgggcgcacc cgagggttga ggcgtcatcc tacggcgggg tcagagggaa gggtaagttt 660gagtccgtca ctgggcgcag tccgcgattc cgaggctagg tgggaaaaaa caaaaacagc 720catcctccca gcccccgctg ggtcagagga tccctctttc ccctgcccgt ccctcggagg 780cctccaaata ttacctttct 8001431550DNAHomo sapiens 143taaagcttcc ccagagggag gaaaggtggg ggcggggcgg ctgctgaggc ccaggatata 60agggctggag gtgctgcttt caggcctggc cagcccacca tgcacgccca ctgcctgccc 120ttccttctgc acgcctggtg ggccctactc caggcgggtg ctgcgacggt ggccactgcg 180ctcctgcgta cgcgggggca gccctcgtcg ccatcccctc tggcgtacat gctgagcctc 240taccgcgacc cgctgccgag ggcagacatc atccgcagcc tacaggcaga aggtaggcag 300tgccgcgtgc cgcgccctgc tgggcacccc cggggcgcct ccgccgcgtc cagccagcgg 360actcgggaag tgctgtgggt tgggggctgc ggctccgagc cgggtttgca gccgcccggg 420cgtcccgagc ccagggccta gctctgcggg tgtctccgcg tcagcaggct cggggtgcag 480cgttggtggc tgggggcgta tccacggccg agtcgggaag ggattctagc gttcagggtg 540tgtcctcgac ggggaccatt gtctctgggt tttggtttgg gattgcgcgg agcgcagcgc 600ggaagggtgg gagcttctaa tctccagtct tgtgaagttg cttatcccgg agcctgggtc 660tgcgcatctg taggataggt gtaataaata acacctcgcc tatcagactg tggaaagcgc 720gagatgacaa tgcgcgcgaa acgctcagcg cagtacccgg cacagccaca gtcaacggtc 780gttggtatta ctgtaatggt ttggtcttgg cgattttttt ttctttctgc gagtgagggt 840gaatgggtcc cggggtgtga cgtcgggagt atcggcagct gagctggtaa catcggggat 900tcgggctcac ggcccggaga tcagggatgg gctgtcccga agtcgcgaac tgtggcagcc 960ttgggtcctc cagccgcgcc ggggaagtgt caagtgtctc gcttaacccc gggttcgggg 1020ccatgatttg caggggagtg ggtgtcaagg acggcaggga tctgagggta tcgccctcga 1080ggacctggca gcgcgttctg ggcacccagc gcggcgagca ggtgggtgct gcggagaggg 1140agccccttcc gcgcctcaat ccacattctg ccgcctgggc agccgcggcc gcccacgcct 1200ccctccgcct gcgggggcca gacggccctc cctggggccg gggcgcaatc cacaaacgct 1260aatctgatcc gacctgccgc ctgcccgccc cttgtgacct ggtgccgggg gcccttcgct 1320cccgcgcctg gggtcagaca gccggtgacc ctctccggaa gggtcatctg gggaccagcc 1380agaccagggg acaccctcgg gggcggggca atgagaaatt tgctggagtg ctcggcccct 1440caaccgaaaa gcggccgggg atgggagggg gcaaagaagg gagggagcgc ttttccagtt 1500cactcccttc tggaaagttc gagatgtgtg cggtgatgga caggcatctg 15501441550DNAHomo sapiens 144cagatgcctg tccatcaccg cacacatctc gaactttcca gaagggagtg aactggaaaa 60gcgctccctc ccttctttgc cccctcccat ccccggccgc ttttcggttg aggggccgag 120cactccagca aatttctcat tgccccgccc ccgagggtgt cccctggtct ggctggtccc 180cagatgaccc ttccggagag ggtcaccggc tgtctgaccc caggcgcggg agcgaagggc 240ccccggcacc aggtcacaag gggcgggcag gcggcaggtc ggatcagatt agcgtttgtg 300gattgcgccc cggccccagg gagggccgtc tggcccccgc aggcggaggg aggcgtgggc 360ggccgcggct gcccaggcgg cagaatgtgg attgaggcgc ggaaggggct ccctctccgc 420agcacccacc tgctcgccgc gctgggtgcc cagaacgcgc tgccaggtcc tcgagggcga 480taccctcaga tccctgccgt ccttgacacc cactcccctg caaatcatgg ccccgaaccc 540ggggttaagc gagacacttg acacttcccc ggcgcggctg gaggacccaa ggctgccaca 600gttcgcgact tcgggacagc ccatccctga tctccgggcc gtgagcccga atccccgatg 660ttaccagctc agctgccgat actcccgacg tcacaccccg ggacccattc accctcactc 720gcagaaagaa aaaaaaatcg ccaagaccaa accattacag taataccaac gaccgttgac 780tgtggctgtg ccgggtactg cgctgagcgt ttcgcgcgca ttgtcatctc gcgctttcca 840cagtctgata ggcgaggtgt tatttattac acctatccta cagatgcgca gacccaggct 900ccgggataag caacttcaca agactggaga ttagaagctc ccacccttcc gcgctgcgct 960ccgcgcaatc ccaaaccaaa acccagagac aatggtcccc gtcgaggaca caccctgaac 1020gctagaatcc cttcccgact cggccgtgga tacgccccca gccaccaacg ctgcaccccg 1080agcctgctga cgcggagaca cccgcagagc taggccctgg gctcgggacg cccgggcggc 1140tgcaaacccg gctcggagcc gcagccccca acccacagca cttcccgagt ccgctggctg 1200gacgcggcgg aggcgccccg ggggtgccca gcagggcgcg gcacgcggca ctgcctacct 1260tctgcctgta ggctgcggat gatgtctgcc ctcggcagcg ggtcgcggta gaggctcagc 1320atgtacgcca gaggggatgg cgacgagggc tgcccccgcg tacgcaggag cgcagtggcc 1380accgtcgcag cacccgcctg gagtagggcc caccaggcgt gcagaaggaa gggcaggcag 1440tgggcgtgca tggtgggctg gccaggcctg aaagcagcac ctccagccct tatatcctgg 1500gcctcagcag ccgccccgcc cccacctttc ctccctctgg ggaagcttta 15501451050DNAHomo sapiens 145accccggggc gtgggagaag cccctgcttg gggggaccgt ctgctgttta ggggctcccc 60ttcgacacgt gggaggcaaa agtgcagagc gcaccatcat ccagctccgg ccgcactgca 120cagcgaggcc ggcccggagc ccggatgctg ggctcggtcc cgccgaggct cggcctggct 180gtaaagcaga ggggggcgag ggaagccggg ccagcgggtg tcgcgggtag ccggcgtccg 240ggacggggtg tggcgcccag agcgctgctg cctctcgcag ccaggaggct ggatgtcggg 300tttgggtgtc ttccagaagg agccgcacta gcgacgaggg aagaggaact ggcttcccgg 360gcagtctccc ccgccccaaa cttttcctcc tcgcggaggg tgggcgggcg gagggaggaa 420gcgcagccgg ggaacgtggc gcccgcgttc ctcccgcccg ggggctgcgg ctgggctgag 480tgtgtcttta aatctgagcc ccccgcccct cgcggtgggg ccgggactcg cggtccgggc 540gggggcgggc gcggtgattg gcggccgggt cgggtccgcc cctcggcgtt gggtagcggg 600gcgctgggga gcagcgcggc gcgcacgggc cggggcgcgc aggtcccgtc gccggtgagc 660acgggctccc tctcgcgtgg cctcgccggg tccgcctggc ctgcccacct ccggagccac 720ctctgccccc gcatgggctg gcgaagttgg gaggagcgag ctggagccag agcgcgcgcc 780gggcgcgccc cgtcgctgcc tgactcggcg cccgcagttc gggcgcagca cgccggccgc 840aggagcacgg atgccccccg gagccgcggg ctggcaggta ccgaagtgtc ctgccctggg 900gctggcgagg ggagggcaaa tctggaatcc cccgggcacc ccccagcccg aggctgctcc 960agacaccaac tccccatcct ttggagaggt gaggtcctgg gccttcaccc cacacccgct 1020caggattggt ccctgggagg caagagggac 10501461050DNAHomo sapiens 146gtccctcttg cctcccaggg accaatcctg agcgggtgtg gggtgaaggc ccaggacctc 60acctctccaa aggatgggga gttggtgtct ggagcagcct cgggctgggg ggtgcccggg 120ggattccaga tttgccctcc cctcgccagc cccagggcag gacacttcgg tacctgccag 180cccgcggctc cggggggcat ccgtgctcct gcggccggcg tgctgcgccc gaactgcggg 240cgccgagtca ggcagcgacg gggcgcgccc ggcgcgcgct ctggctccag ctcgctcctc 300ccaacttcgc cagcccatgc gggggcagag gtggctccgg aggtgggcag gccaggcgga 360cccggcgagg ccacgcgaga gggagcccgt gctcaccggc gacgggacct gcgcgccccg 420gcccgtgcgc gccgcgctgc tccccagcgc cccgctaccc aacgccgagg ggcggacccg 480acccggccgc caatcaccgc gcccgccccc gcccggaccg cgagtcccgg ccccaccgcg 540aggggcgggg ggctcagatt taaagacaca ctcagcccag ccgcagcccc cgggcgggag 600gaacgcgggc gccacgttcc ccggctgcgc ttcctccctc cgcccgccca ccctccgcga 660ggaggaaaag tttggggcgg gggagactgc ccgggaagcc agttcctctt ccctcgtcgc 720tagtgcggct ccttctggaa gacacccaaa cccgacatcc agcctcctgg ctgcgagagg 780cagcagcgct ctgggcgcca caccccgtcc cggacgccgg ctacccgcga cacccgctgg 840cccggcttcc ctcgcccccc tctgctttac agccaggccg agcctcggcg ggaccgagcc 900cagcatccgg gctccgggcc ggcctcgctg tgcagtgcgg ccggagctgg atgatggtgc 960gctctgcact tttgcctccc

acgtgtcgaa ggggagcccc taaacagcag acggtccccc 1020caagcagggg cttctcccac gccccggggt 1050147550DNAHomo sapiens 147ccgaaaggac ccgtcccagc gagccagggc ctggttttcc ttccgcagaa ggcggaggga 60ccggagcggg cgcgggcacc cctgggctct gaggggcgcg ctctgaaggg cggcggactt 120cagggccatg ctggctgtcc ccagaaagca ggagcccgaa accgcggggc caacgaacgc 180ccacattctc tgctacaacc tcgccactcc cctgcgcctc tccccttgcc ccctgccccc 240acaggtaacg cccagaacga gtgcttctcc cggtggggta ctgaggagcc tgggctgcag 300ctgccgagcc gccacagcca cgctgagccc ggcctggcct gcacactggc gccaccgcct 360ggcggggagc gggactgacg cgctcctctc cctctcctcc agcccagatc acggaggcgc 420ggagctccat ctcctgccct gggcgagggg agtgagggag acaaagactt tgggcacaac 480acccaccaca tagaacctat tctctagttg ggaaacaagt caaggcaaag gcgcacagag 540tgaaagtcag 550148550DNAHomo sapiens 148ctgactttca ctctgtgcgc ctttgccttg acttgtttcc caactagaga ataggttcta 60tgtggtgggt gttgtgccca aagtctttgt ctccctcact cccctcgccc agggcaggag 120atggagctcc gcgcctccgt gatctgggct ggaggagagg gagaggagcg cgtcagtccc 180gctccccgcc aggcggtggc gccagtgtgc aggccaggcc gggctcagcg tggctgtggc 240ggctcggcag ctgcagccca ggctcctcag taccccaccg ggagaagcac tcgttctggg 300cgttacctgt gggggcaggg ggcaagggga gaggcgcagg ggagtggcga ggttgtagca 360gagaatgtgg gcgttcgttg gccccgcggt ttcgggctcc tgctttctgg ggacagccag 420catggccctg aagtccgccg cccttcagag cgcgcccctc agagcccagg ggtgcccgcg 480cccgctccgg tccctccgcc ttctgcggaa ggaaaaccag gccctggctc gctgggacgg 540gtcctttcgg 5501491550DNAHomo sapiens 149ccctccagtt tgctggagtt gccggattac attgttcctc cccggtgtgc ggcgtgagct 60tcccccaccc gagcgcccaa caagtctcct ttctccagcc tgcgcgctgc tgcgctgagg 120ccgaatgaag cgcagcacgg tgcgggcagc ccgaggcccc gaggctgggc tctgtctgtc 180tgggactgcg ccgtgcccag cctcggtccc ctctctgtgg gtaaggatgg ttgagtccag 240cctccacggc agcggctcct tgtgccacta gcagcccttc ttctgcgctc tccgcctttt 300ctctctagac tggatctctc ctcccccccg cgcccccctc cccgcatctc ccactcgctg 360gctctctctc cagctgcctc ctctccaggt ctctcctggc tgcgcgcgct cctctccccg 420cttctccccc tcccgcagcc tcgccgcctt ggtgccttcc tgcccggctc ggccggcgct 480cgtccccggc cccggccccg ccagcccggg tctccgcgct cggagcagct cagccctgca 540gtggctcggg acccgatgct atgagaggga agcgagccgg gcgcccagac cttcaggagg 600cgtcggatgc gcggcgggtc ttgggaccgg gctctctctc cggctcgcct tgccctcggg 660tgattatttg gctccgctca tagccctgcc ttcctcggag gagccatcgg tgtcgcgtgc 720gtgtggagta tctgcagaca tgactgcgtg gaggagattc cagtcgctgc tcctgcttct 780cgggctgctg gtgctgtgcg cgaggctcct cactgcagcg aagggtaaga cggacttgct 840cctggccggg gaggcggtag agccctcgga ggccccgtgt gcggacgcga gtgtgcgttt 900tggggaccgc agggtacgga gtggccgcct ctgcccggcg ctgctccatc gccgaagctc 960ggggaacgcg atgcacggga gggagcttcc atcgcgctct ccccagccct cctgggcccc 1020cgccccaccc cgccattcct tccccctctc ttgggctcac aggagagatc tctttttctc 1080ggcagtacag ggtgtcaagg agaaaggaac ccaatacgag ttgggctgga actgtgctcc 1140gccggggcgg tgttgcctcc tccgagacgt ggactccacg ggtcggggtg gctgaggggc 1200agttcccagg actttctccc cggacccgac gcgcctggga aagcgtcccg ggtgaagccg 1260gcctggaaag ttcgggctct ctacgggggt tttggtacca ataggcaaag gtctccgccg 1320gcccggcctc ctcgcaccca tacaccccat tcctcctctc ctccttccct ctccaacgtc 1380ctcagccggc gaggagtagc tgcctctaga aggtcgcccc cgctttcctc tcccccggac 1440ttcgctcctt gcaagttgta aggtgttggc aaggtgcgtg aaacaggcta ggagttctgg 1500accggcttcc aagtcagata cattcactgt gggcgcacgg gtatcctcct 15501501550DNAHomo sapiens 150aggaggatac ccgtgcgccc acagtgaatg tatctgactt ggaagccggt ccagaactcc 60tagcctgttt cacgcacctt gccaacacct tacaacttgc aaggagcgaa gtccggggga 120gaggaaagcg ggggcgacct tctagaggca gctactcctc gccggctgag gacgttggag 180agggaaggag gagaggagga atggggtgta tgggtgcgag gaggccgggc cggcggagac 240ctttgcctat tggtaccaaa acccccgtag agagcccgaa ctttccaggc cggcttcacc 300cgggacgctt tcccaggcgc gtcgggtccg gggagaaagt cctgggaact gcccctcagc 360caccccgacc cgtggagtcc acgtctcgga ggaggcaaca ccgccccggc ggagcacagt 420tccagcccaa ctcgtattgg gttcctttct ccttgacacc ctgtactgcc gagaaaaaga 480gatctctcct gtgagcccaa gagaggggga aggaatggcg gggtggggcg ggggcccagg 540agggctgggg agagcgcgat ggaagctccc tcccgtgcat cgcgttcccc gagcttcggc 600gatggagcag cgccgggcag aggcggccac tccgtaccct gcggtcccca aaacgcacac 660tcgcgtccgc acacggggcc tccgagggct ctaccgcctc cccggccagg agcaagtccg 720tcttaccctt cgctgcagtg aggagcctcg cgcacagcac cagcagcccg agaagcagga 780gcagcgactg gaatctcctc cacgcagtca tgtctgcaga tactccacac gcacgcgaca 840ccgatggctc ctccgaggaa ggcagggcta tgagcggagc caaataatca cccgagggca 900aggcgagccg gagagagagc ccggtcccaa gacccgccgc gcatccgacg cctcctgaag 960gtctgggcgc ccggctcgct tccctctcat agcatcgggt cccgagccac tgcagggctg 1020agctgctccg agcgcggaga cccgggctgg cggggccggg gccggggacg agcgccggcc 1080gagccgggca ggaaggcacc aaggcggcga ggctgcggga gggggagaag cggggagagg 1140agcgcgcgca gccaggagag acctggagag gaggcagctg gagagagagc cagcgagtgg 1200gagatgcggg gaggggggcg cgggggggag gagagatcca gtctagagag aaaaggcgga 1260gagcgcagaa gaagggctgc tagtggcaca aggagccgct gccgtggagg ctggactcaa 1320ccatccttac ccacagagag gggaccgagg ctgggcacgg cgcagtccca gacagacaga 1380gcccagcctc ggggcctcgg gctgcccgca ccgtgctgcg cttcattcgg cctcagcgca 1440gcagcgcgca ggctggagaa aggagacttg ttgggcgctc gggtggggga agctcacgcc 1500gcacaccggg gaggaacaat gtaatccggc aactccagca aactggaggg 15501511050DNAHomo sapiens 151tcctccttga gcagggagac catcggggtg caacctggcc ggggcgggga ggaggtgcag 60ggcattgcca gagcgggcct gtccatgggc aagggacagc gacctcctgg gccaggacat 120gtgagagctg cgcaggcctg ggcccggcgt ggcggaggtg cgcgagagcg gccagaagag 180ggcgccagag agccaggcgc ggcccgcgga ggagcccgcg ccggccccta tacccagctc 240cgcgccgcgc ggacccaccg agcccgcgct cagacgcccc agctccaccg agaggccgct 300cgggccgtgt ccttcctctt ctccaggtgc aggcagagcc cccgagccat ggccagccct 360tccggcagct ccgaagccac tggcaagccc cgaggcaggg atggccggcc caggagggag 420gaggacgacg tccctcccga agagaagagg ctggggctgt agctggaggg gggaagcgca 480cagcccgagg actgcgagaa cggggaggac gcgccgcggc caggcaggga ggagaccggc 540acccagacag gtggcgaccg cagaggagta agtgacgcgg gcgctggggt ccgggggtgc 600cgggggcgcc ggtaggggcg gcgggaggct ccgtggccgg ccccgggttg aagttggtat 660tttagcggca actccgaagg gcgcggagtg acagcgcgtg acggcctccg agacgccagc 720tgccgcttct cggctgtgtg gctttgactt cctgattctc ccacgacgtc gctggctggg 780agacccactg gactctgcgg ctggccaaaa agagaggggc agccccgcgt cctgggggcc 840cctagcaggg gaagtggcgg gtgttgcgct gggcatcctg tctggggcat ctgtctggga 900ccctgttggt gcctctcacc tggcgagggg ccagtggtgg gggtaggggg gaagtccctg 960gcgccaggct tggccaagcc ctgcttggct ggactgcggg ctggcggcgc tcacccagct 1020cctcacctgt cccgcatctt cctgtttttc 10501521050DNAHomo sapiens 152gaaaaacagg aagatgcggg acaggtgagg agctgggtga gcgccgccag cccgcagtcc 60agccaagcag ggcttggcca agcctggcgc cagggacttc ccccctaccc ccaccactgg 120cccctcgcca ggtgagaggc accaacaggg tcccagacag atgccccaga caggatgccc 180agcgcaacac ccgccacttc ccctgctagg ggcccccagg acgcggggct gcccctctct 240ttttggccag ccgcagagtc cagtgggtct cccagccagc gacgtcgtgg gagaatcagg 300aagtcaaagc cacacagccg agaagcggca gctggcgtct cggaggccgt cacgcgctgt 360cactccgcgc ccttcggagt tgccgctaaa ataccaactt caacccgggg ccggccacgg 420agcctcccgc cgcccctacc ggcgcccccg gcacccccgg accccagcgc ccgcgtcact 480tactcctctg cggtcgccac ctgtctgggt gccggtctcc tccctgcctg gccgcggcgc 540gtcctccccg ttctcgcagt cctcgggctg tgcgcttccc ccctccagct acagccccag 600cctcttctct tcgggaggga cgtcgtcctc ctccctcctg ggccggccat ccctgcctcg 660gggcttgcca gtggcttcgg agctgccgga agggctggcc atggctcggg ggctctgcct 720gcacctggag aagaggaagg acacggcccg agcggcctct cggtggagct ggggcgtctg 780agcgcgggct cggtgggtcc gcgcggcgcg gagctgggta taggggccgg cgcgggctcc 840tccgcgggcc gcgcctggct ctctggcgcc ctcttctggc cgctctcgcg cacctccgcc 900acgccgggcc caggcctgcg cagctctcac atgtcctggc ccaggaggtc gctgtccctt 960gcccatggac aggcccgctc tggcaatgcc ctgcacctcc tccccgcccc ggccaggttg 1020caccccgatg gtctccctgc tcaaggagga 10501531300DNAHomo sapiens 153cccagtaagt caccaattaa gtctttacta cttaaaagca aaatccacct atgtcctgaa 60cagtatccac tttacgagcc tcattatatg tacgagataa aattcagaaa taaataaata 120tacatgtata cgtatacaaa tatatttcaa attaaaaaat acttttagat agtggtatgt 180attacattta gaaattaata acgaagtaaa ttatgggatg tcatccacgc ctgtcccaaa 240ggtaccgaat ttataaatca tctcaggtgc ggagcaggac aggttgaaaa taggaatgac 300atgaacccgc gcggaacagc tgccggcgcg gtgtccaggg cggcaccccg cccggtcccg 360gcccctccag ccctgggccc gacccctact acgcctctgc ctcgacgcga acgcggagcc 420cgagcgcgcg tcacgccgtg tggggccgaa gaggctgcta cccagaggcg gagtgcgggc 480tcgcgagggt ccccacccga ctctcgctcc cgccagcacc tacggactcg cgtccccgcc 540gcgcgccgac tcgggagcag caccgccccc ggcacaggag cctcacgcgc ctcttaccta 600acaggaagtt gggtggaagc agcgcggacc cacggcacac cgaacgcact ccaacagaac 660ccgacgcaga cacgcgcttt caaccggcgg agacactggc agggccagaa acgcgcgcag 720cgggggcggg aggtcggtaa gctccccgcc cctgcccgag accccgcccc ggcccggccc 780cgcctttttc tctgcctccc ctccctgcac gtacgggccc cgcccctcgc gcgacgtttt 840ttgttgaccc ggaaacggat tctccggagc cgaggtccgc tcgggtgagt gccctccgct 900ttttgtggcc aaacccagcc acgcagttcc cttcctgcgg cgtcctccac acccggggtc 960tgctggtctc cgcggatgtc acaggctcgg caaccgccct cctgtcggcg gggagtcccg 1020cgacgcccgg aaatgctccg aagcctgtcg cccagctgcc agatctgcgt ctgtgtccgg 1080ttccgtcact gaggtcgccc ctgtccggcc cttccaccct agttctcttc accgtccgcc 1140catcctatcg cgcgcggcct caggtcccga ttcggcatgt ggcttgtctt ccatcgtccc 1200caccctcgcc cctcttggcc cctcagggca gccctgggat tcggcagacg ccagtcctcc 1260ctgagatgct tccccatcct tccctccgcc aggccctacg 13001541300DNAHomo sapiens 154cgtagggcct ggcggaggga aggatgggga agcatctcag ggaggactgg cgtctgccga 60atcccagggc tgccctgagg ggccaagagg ggcgagggtg gggacgatgg aagacaagcc 120acatgccgaa tcgggacctg aggccgcgcg cgataggatg ggcggacggt gaagagaact 180agggtggaag ggccggacag gggcgacctc agtgacggaa ccggacacag acgcagatct 240ggcagctggg cgacaggctt cggagcattt ccgggcgtcg cgggactccc cgccgacagg 300agggcggttg ccgagcctgt gacatccgcg gagaccagca gaccccgggt gtggaggacg 360ccgcaggaag ggaactgcgt ggctgggttt ggccacaaaa agcggagggc actcacccga 420gcggacctcg gctccggaga atccgtttcc gggtcaacaa aaaacgtcgc gcgaggggcg 480gggcccgtac gtgcagggag gggaggcaga gaaaaaggcg gggccgggcc ggggcggggt 540ctcgggcagg ggcggggagc ttaccgacct cccgcccccg ctgcgcgcgt ttctggccct 600gccagtgtct ccgccggttg aaagcgcgtg tctgcgtcgg gttctgttgg agtgcgttcg 660gtgtgccgtg ggtccgcgct gcttccaccc aacttcctgt taggtaagag gcgcgtgagg 720ctcctgtgcc gggggcggtg ctgctcccga gtcggcgcgc ggcggggacg cgagtccgta 780ggtgctggcg ggagcgagag tcgggtgggg accctcgcga gcccgcactc cgcctctggg 840tagcagcctc ttcggcccca cacggcgtga cgcgcgctcg ggctccgcgt tcgcgtcgag 900gcagaggcgt agtaggggtc gggcccaggg ctggaggggc cgggaccggg cggggtgccg 960ccctggacac cgcgccggca gctgttccgc gcgggttcat gtcattccta ttttcaacct 1020gtcctgctcc gcacctgaga tgatttataa attcggtacc tttgggacag gcgtggatga 1080catcccataa tttacttcgt tattaatttc taaatgtaat acataccact atctaaaagt 1140attttttaat ttgaaatata tttgtatacg tatacatgta tatttattta tttctgaatt 1200ttatctcgta catataatga ggctcgtaaa gtggatactg ttcaggacat aggtggattt 1260tgcttttaag tagtaaagac ttaattggtg acttactggg 13001551300DNAHomo sapiens 155accggcgtcc cgctgggggc gcgcgagccc cacccccaga gatgctgact cagcaagtcg 60ggaggggttg ggggtgggac ctgccaatct gcatttccaa ccggcgccca ggtgacgctg 120actctgctgg tctaccgtct tgggggtcac ctaatttttc agcgatgcct cccagctggg 180gaggccaaga agtgcctcgc tcaaggtctt ccaacacccg acctccagac cctcaatcct 240gggccagcta caccgcaaac ctttccagct gtctctcctg cgccctgcgt ttcttcccca 300cgtcacttgc cagggagccg ctaaacagca agaccgcgcg ctctgcggct ccagagtgcg 360gatttcggtc gcgtgcggct ctgaccgcgt cgccccatcc ctggcggggc cacgcacgga 420cgccatggct ggcgccgcgg agccgggcga tgcgcgcgga ctctcccggg gccctgactg 480tccctgagtc ctccctgcgg ggggcgtgcg cggcccgccc cccgcggcgc cacgcggccc 540ctcctcggcc ggggattggt gcgccgggcg gggcggggcg gggcgggata aaggcgcggg 600gtctggctgc gcggggtctg cgggcagctc caactctggg ttcgtagttt gcgctgggtg 660cgcaggaagg tcagtgtggg ggtcgcccga catttccccc ccgcggaggt gggagccgag 720ccacatcttg gagtggggac tggccgcgga gcgggttgcc cagggccggc cgaggtcggg 780gcgagccctg cgcggcgctg gagactctgc attcccgggc gcgcgcaggg tccccggccg 840tggtcgcaga gtcaggaggg gcggctccgg agcccggcgc ggggagggcc caggcgcagt 900cggggttggc agggcgcgac actcgctccc ctccactttt gaaagggctt cccacgccga 960gaagaggggc gggcatggcc ggcccggcga aaccggtttg tacagacttt gggaagccat 1020cgcctgcgga gggtgggacc ccacagcttg tccacctgcc caggctgaga cctcgtgtcc 1080tagtcctgga tgccccacgg gtttctcgtc ccgggcagcg gcgcacggga ggagaagact 1140cccggtctgc agtcagacct ccctctgaga ccctccctag ctcaggctta gagctttggg 1200atttttctcg atcctttcta gctttcagat catccccacg taaagttcag actttaccag 1260cccagagagt ttaaaaaaaa aaaaagagag agagagaaag 13001561300DNAHomo sapiens 156ctttctctct ctctcttttt ttttttttaa actctctggg ctggtaaagt ctgaacttta 60cgtggggatg atctgaaagc tagaaaggat cgagaaaaat cccaaagctc taagcctgag 120ctagggaggg tctcagaggg aggtctgact gcagaccggg agtcttctcc tcccgtgcgc 180cgctgcccgg gacgagaaac ccgtggggca tccaggacta ggacacgagg tctcagcctg 240ggcaggtgga caagctgtgg ggtcccaccc tccgcaggcg atggcttccc aaagtctgta 300caaaccggtt tcgccgggcc ggccatgccc gcccctcttc tcggcgtggg aagccctttc 360aaaagtggag gggagcgagt gtcgcgccct gccaaccccg actgcgcctg ggccctcccc 420gcgccgggct ccggagccgc ccctcctgac tctgcgacca cggccgggga ccctgcgcgc 480gcccgggaat gcagagtctc cagcgccgcg cagggctcgc cccgacctcg gccggccctg 540ggcaacccgc tccgcggcca gtccccactc caagatgtgg ctcggctccc acctccgcgg 600gggggaaatg tcgggcgacc cccacactga ccttcctgcg cacccagcgc aaactacgaa 660cccagagttg gagctgcccg cagaccccgc gcagccagac cccgcgcctt tatcccgccc 720cgccccgccc cgcccggcgc accaatcccc ggccgaggag gggccgcgtg gcgccgcggg 780gggcgggccg cgcacgcccc ccgcagggag gactcaggga cagtcagggc cccgggagag 840tccgcgcgca tcgcccggct ccgcggcgcc agccatggcg tccgtgcgtg gccccgccag 900ggatggggcg acgcggtcag agccgcacgc gaccgaaatc cgcactctgg agccgcagag 960cgcgcggtct tgctgtttag cggctccctg gcaagtgacg tggggaagaa acgcagggcg 1020caggagagac agctggaaag gtttgcggtg tagctggccc aggattgagg gtctggaggt 1080cgggtgttgg aagaccttga gcgaggcact tcttggcctc cccagctggg aggcatcgct 1140gaaaaattag gtgaccccca agacggtaga ccagcagagt cagcgtcacc tgggcgccgg 1200ttggaaatgc agattggcag gtcccacccc caacccctcc cgacttgctg agtcagcatc 1260tctgggggtg gggctcgcgc gcccccagcg ggacgccggt 1300157800DNAHomo sapiens 157ctcatttcgg gccgcttttc tcagagggca aagatgggtc agggtgggat gttacattag 60tgttgagact ctttggatcc gtttcgtggg taccgaggac gcctgggtac gcgggacagg 120ctgcacccgc ctgctagagg cgccccatcg aggcgccacg ggtgaagctc ccggccccac 180ctacggggcg gggctccggc tcggtccgac tattgcccgc ggtgggggag ggggatggat 240cacgccacgc gccaaaggcg atcgcgactc tccttctgca ggtagcctgg aaggctctct 300ctctttctct acgccaccct tttcgtggca ctgaaaagcc ccgtcctctc ctcccagtcc 360cgcctcctcc gagcgttccc cctactgcct ggaatggtgc ggtcccaggt cgcgggtcac 420gcggcggagg gggcgtggcc tgcccccggc ccagccggct cttctttgcc tctgctggag 480tccggggagt ggcgttggct gctagagcga tgccgggccg gagttgcgtc gccttagtcc 540tcctggctgc cgccgtcagc tgtgccgtcg cgcagcacgc gccgccggtg agtgagcttg 600agccgaggcg cagagagggg cgtgcaggtg cgggcgcgga tggaggcgca ggtgtggcgg 660cgcgagcggg tacaaggaac acctcgtgct gggcagcttc tttacggggg tctgtggttt 720cgtgcacagg ggtgtgggtg cagagcgggc tggcgaaccc cgtcctcggt agattcggtg 780ctacctgcaa ctagaactcc 800158800DNAHomo sapiens 158ggagttctag ttgcaggtag caccgaatct accgaggacg gggttcgcca gcccgctctg 60cacccacacc cctgtgcacg aaaccacaga cccccgtaaa gaagctgccc agcacgaggt 120gttccttgta cccgctcgcg ccgccacacc tgcgcctcca tccgcgcccg cacctgcacg 180cccctctctg cgcctcggct caagctcact caccggcggc gcgtgctgcg cgacggcaca 240gctgacggcg gcagccagga ggactaaggc gacgcaactc cggcccggca tcgctctagc 300agccaacgcc actccccgga ctccagcaga ggcaaagaag agccggctgg gccgggggca 360ggccacgccc cctccgccgc gtgacccgcg acctgggacc gcaccattcc aggcagtagg 420gggaacgctc ggaggaggcg ggactgggag gagaggacgg ggcttttcag tgccacgaaa 480agggtggcgt agagaaagag agagagcctt ccaggctacc tgcagaagga gagtcgcgat 540cgcctttggc gcgtggcgtg atccatcccc ctcccccacc gcgggcaata gtcggaccga 600gccggagccc cgccccgtag gtggggccgg gagcttcacc cgtggcgcct cgatggggcg 660cctctagcag gcgggtgcag cctgtcccgc gtacccaggc gtcctcggta cccacgaaac 720ggatccaaag agtctcaaca ctaatgtaac atcccaccct gacccatctt tgccctctga 780gaaaagcggc ccgaaatgag 800159800DNAHomo sapiens 159ttctgcagag ccagcagccg gctcccacct acccaaggag agaagatcgc tccaagacag 60tgagagcttc cctgccattt cagtgcaaag tccctccgga gcgacctcag aggagtaacc 120gggccttaac tttttgcgct cgttttgcta taatttttct ctatccacct ccatcccacc 180cccacaacac tctttactgg gggggtcttt tgtgttccgg atctccccct ccatggctcc 240cttagccgaa gtcgggggct ttctgggcgg cctggagggc ttgggccagc aggtgggttc 300gcatttcctg ttgcctcctg ccggggagcg gccgccgctg ctgggcgagc gcaggagcgc 360ggcggagcgg agcgcgcgcg gcgggccggg ggctgcgcag ctggcgcacc tgcacggcat 420cctgcgccgc cggcagctct attgccgcac cggcttccac ctgcagatcc tgcccgacgg 480cagcgtgcag ggcacccggc aggaccacag cctcttcggt acgtactagc atcccgaccc 540cacccccatc tgcgccccag ctcggctcct cgttccctcc ccttgcacct ccctctttgc 600ctgccaaggg cgtcatcgcc gcgcggagcc cggagctccc ctggacccat ccggtgcaag 660acgcaggctg gggctgaagg gctggccaga gcagccgcgg ggagaaattt tcctgctggt 720ttgtcgccgc agcctctagc agggcagcag ctccagatgc tgggggcggg aggagaaagg 780gtgggcgctt cgcaagctcc 800160800DNAHomo sapiens 160ggagcttgcg aagcgcccac cctttctcct cccgccccca gcatctggag ctgctgccct 60gctagaggct gcggcgacaa accagcagga aaatttctcc ccgcggctgc tctggccagc 120ccttcagccc cagcctgcgt cttgcaccgg atgggtccag gggagctccg ggctccgcgc 180ggcgatgacg cccttggcag gcaaagaggg aggtgcaagg ggagggaacg aggagccgag 240ctggggcgca gatgggggtg gggtcgggat gctagtacgt accgaagagg ctgtggtcct 300gccgggtgcc ctgcacgctg ccgtcgggca ggatctgcag gtggaagccg gtgcggcaat 360agagctgccg gcggcgcagg atgccgtgca ggtgcgccag

ctgcgcagcc cccggcccgc 420cgcgcgcgct ccgctccgcc gcgctcctgc gctcgcccag cagcggcggc cgctccccgg 480caggaggcaa caggaaatgc gaacccacct gctggcccaa gccctccagg ccgcccagaa 540agcccccgac ttcggctaag ggagccatgg agggggagat ccggaacaca aaagaccccc 600ccagtaaaga gtgttgtggg ggtgggatgg aggtggatag agaaaaatta tagcaaaacg 660agcgcaaaaa gttaaggccc ggttactcct ctgaggtcgc tccggaggga ctttgcactg 720aaatggcagg gaagctctca ctgtcttgga gcgatcttct ctccttgggt aggtgggagc 780cggctgctgg ctctgcagaa 8001611300DNAHomo sapiens 161cttaaccccc ccatctccag ttatcccaat gaaccgaccc cgagggggca tttccgctga 60agtccggggc tgtaaaaaat taagtgagaa gagccgcgct aaagccaagc gtcgtcgtca 120cccaaggtac tgcgctgatg cgctgcgggc cgaccaggtg ctcccgccgg ggcgtcttct 180cctacgcagg aagggccacg ccgagagagg caggcaacaa gggcacggct ggaggccgga 240aggtcacccc gtccccggcg gggcgggcgc ggcccagcct cacttcccgg gcacgttcgg 300gcggggcgat tgcagggaac ggggcgggga ggcgacagtc cccggctccg ccgcgcgcca 360gcccgccttc gctgcccgga ggcgccgcag gcctgggttc ccggacagct gagcccgagc 420gccgcctccc gaaaggtgaa ggcggcccgg ggaggcgggg acggtgacgg gggcgggggc 480cgcgggcggt ctcccgacgg ctgtcgcggg gccagcccaa agcccccgat ccccggtagc 540tgcgcttccc gcgcggggcg ccggagtagg gcgggccaag ctggcctgcg gccgcggcgg 600gaagaagggc tagcgaagca cccccgaccg ggcccaggcg ccggacgccg gggggcgcct 660cgctgcaact tctctttgga agccccgaca cgagccccgg cccgcgcgcg cgctccccca 720cggccacgcg cgcaccctgc cgcccgcacc cccgcgcgcc ctccgtctat tttttcctct 780tcctttcatc ctcacactct aaaataggtc aaggggtgga agttacacct ggtgcagccc 840tcggctctga tgcaaaagca gcttttgccc ctggctgcgg gacagcgctg tgactactcg 900caacgggaga gctgctgcca gtcgccacac cgtgcggaaa gcgccggcga ccggagcact 960gacaatggtc tgcatagggg agcggagaga agcttctgtt gcgccctaga tccgctgcct 1020cggcgcccgc ccgcagggag gagggggcgc gacaggtcgt ctagcgcgtg ccccggagcc 1080cgcgcccggg tctggccgcc tgggtgagtt cctgctcgtc ccctgccttt ccagtagccc 1140ggggtggctg tttaccttgc aaacagcctt gcaatacgat caaaacaggc gagacagcca 1200tgcagtaagg gattgcggga tgtgctttgg gtgtgagatt ggataaatca gaattcagag 1260ataaaggaca tgtctagtgc cttaagggtt aaagtggatt 13001621300DNAHomo sapiens 162aatccacttt aacccttaag gcactagaca tgtcctttat ctctgaattc tgatttatcc 60aatctcacac ccaaagcaca tcccgcaatc ccttactgca tggctgtctc gcctgttttg 120atcgtattgc aaggctgttt gcaaggtaaa cagccacccc gggctactgg aaaggcaggg 180gacgagcagg aactcaccca ggcggccaga cccgggcgcg ggctccgggg cacgcgctag 240acgacctgtc gcgccccctc ctccctgcgg gcgggcgccg aggcagcgga tctagggcgc 300aacagaagct tctctccgct cccctatgca gaccattgtc agtgctccgg tcgccggcgc 360tttccgcacg gtgtggcgac tggcagcagc tctcccgttg cgagtagtca cagcgctgtc 420ccgcagccag gggcaaaagc tgcttttgca tcagagccga gggctgcacc aggtgtaact 480tccacccctt gacctatttt agagtgtgag gatgaaagga agaggaaaaa atagacggag 540ggcgcgcggg ggtgcgggcg gcagggtgcg cgcgtggccg tgggggagcg cgcgcgcggg 600ccggggctcg tgtcggggct tccaaagaga agttgcagcg aggcgccccc cggcgtccgg 660cgcctgggcc cggtcggggg tgcttcgcta gcccttcttc ccgccgcggc cgcaggccag 720cttggcccgc cctactccgg cgccccgcgc gggaagcgca gctaccgggg atcgggggct 780ttgggctggc cccgcgacag ccgtcgggag accgcccgcg gcccccgccc ccgtcaccgt 840ccccgcctcc ccgggccgcc ttcacctttc gggaggcggc gctcgggctc agctgtccgg 900gaacccaggc ctgcggcgcc tccgggcagc gaaggcgggc tggcgcgcgg cggagccggg 960gactgtcgcc tccccgcccc gttccctgca atcgccccgc ccgaacgtgc ccgggaagtg 1020aggctgggcc gcgcccgccc cgccggggac ggggtgacct tccggcctcc agccgtgccc 1080ttgttgcctg cctctctcgg cgtggccctt cctgcgtagg agaagacgcc ccggcgggag 1140cacctggtcg gcccgcagcg catcagcgca gtaccttggg tgacgacgac gcttggcttt 1200agcgcggctc ttctcactta attttttaca gccccggact tcagcggaaa tgccccctcg 1260gggtcggttc attgggataa ctggagatgg gggggttaag 13001631800DNAHomo sapiens 163ctagcattta ctggattcca gagtcttgtt atttaagaat gcatcttaaa cggtactatc 60aaattcatgt tacgtgcagc ccagattgtt ttgggcagca cgaaaagttt ctgaggcgct 120gcgtgtaccc caccccagga caccgtgtgt gcgcgccgag ctgagtgcga ggaacgtggc 180gcgagggccg ggggatgccg ggctgcgtgg gtgtgagccc tcgcgcgacc gcgaccccgc 240gcctctcccg ctctcgccgg aacgtgaccg cagccgcacc tctcctccag ccctttccca 300gccagacgct tccttttagg tccttctggg cgtttattgt aaattctgcg actaaaacac 360gccggtgagc ccggcccacc gacagatgga tcaatcgccc ccttcccggc taggggagga 420ggaacccccc aaccccggag cctagggagc cgggagctgc ctcgggacga gctcctcgga 480gcccagccgg ctgcggagcc ccggcccggg tcggtctcgg ggccctcctg ccggggtggg 540gtgcgagccc ctgcccgatt cctctggggc ggttcaggca ggtttgccgg cctccgagga 600ggtggtcagg gcgccctggc ccagcaggct tcttcccgag ccggggggag gggagaccgg 660ctggggaagg ggcatctcga aggggtggag gccggggcgg gcgggaggca agcgcgccgc 720gggcgtgagg gcaaagttcc cgaggtccgc gcggagagca cacgtgtatg tgcgcgcggg 780gctaggccgg ggccggcagg atgcgttggg ttcgggggcg cgcggggccg gcgccgaagg 840ggataattcc tttccctggc accatcgggg agacgctttg tcggcctcgg ctcctgggcg 900cagggacgcc ttagcccacg gagggtggag cccccctcag acccgggcca ccggctgggg 960tttttctaac gccctgcccc ccgagccccc ggatggctcg ggccccacgg actccgcgcc 1020ctccagcctc agctcagctc cccaggcttc ccagacccag cggcgcaggg ggcgggggca 1080ggggcagtgg gggttggagg gcgcagccgg tccccagggt ggggagagct gcggggggag 1140gaggaggagg gtgccgacgc ttgagtgggt tcgagcccga gccgtagccg ggggagccag 1200tcagtttccg gccaaggcag caggtcagtc ccaggaaggg cgggcgattg agccgaggga 1260gccggcggct gggctctcct ctcggcccgc gatccccggc gccgccgccg ccgccaccgc 1320caccgccacc gccttcgcct tgtcgccgcc gccgctgcag agcatcgtag ctccgccgcg 1380ctcccgcgcc ccgcgccccg cgccgccagc cgcctgggag cccgagcgcc gagcccgggg 1440cggaggagag gggcgctggc gcgagagccc gggcgaggga gccgcgaagg gagaaggggg 1500cgggcggagg gaggagcagg gagagtggga gaagggggag ggagagagga gagcgaggga 1560gagctggaga gagcgagagc aaagagcgag cgagggagag gagagagaga gagaggagag 1620agaaagacac acgcacgcag agacacacgg tcactggaat tccattagaa aaaagtgagc 1680cgagcaaggg ttagcgggag aagatttttt tgaatcttgt cttcgtcttg gtgcgaaaga 1740agcgactcca gtctctcgtc ctcgaagctc cgactggatt gttcttgggc gctgacaccc 18001641800DNAHomo sapiens 164gggtgtcagc gcccaagaac aatccagtcg gagcttcgag gacgagagac tggagtcgct 60tctttcgcac caagacgaag acaagattca aaaaaatctt ctcccgctaa cccttgctcg 120gctcactttt ttctaatgga attccagtga ccgtgtgtct ctgcgtgcgt gtgtctttct 180ctctcctctc tctctctctc ctctccctcg ctcgctcttt gctctcgctc tctccagctc 240tccctcgctc tcctctctcc ctcccccttc tcccactctc cctgctcctc cctccgcccg 300cccccttctc ccttcgcggc tccctcgccc gggctctcgc gccagcgccc ctctcctccg 360ccccgggctc ggcgctcggg ctcccaggcg gctggcggcg cggggcgcgg ggcgcgggag 420cgcggcggag ctacgatgct ctgcagcggc ggcggcgaca aggcgaaggc ggtggcggtg 480gcggtggcgg cggcggcggc gccggggatc gcgggccgag aggagagccc agccgccggc 540tccctcggct caatcgcccg cccttcctgg gactgacctg ctgccttggc cggaaactga 600ctggctcccc cggctacggc tcgggctcga acccactcaa gcgtcggcac cctcctcctc 660ctccccccgc agctctcccc accctgggga ccggctgcgc cctccaaccc ccactgcccc 720tgcccccgcc ccctgcgccg ctgggtctgg gaagcctggg gagctgagct gaggctggag 780ggcgcggagt ccgtggggcc cgagccatcc gggggctcgg ggggcagggc gttagaaaaa 840ccccagccgg tggcccgggt ctgagggggg ctccaccctc cgtgggctaa ggcgtccctg 900cgcccaggag ccgaggccga caaagcgtct ccccgatggt gccagggaaa ggaattatcc 960ccttcggcgc cggccccgcg cgcccccgaa cccaacgcat cctgccggcc ccggcctagc 1020cccgcgcgca catacacgtg tgctctccgc gcggacctcg ggaactttgc cctcacgccc 1080gcggcgcgct tgcctcccgc ccgccccggc ctccacccct tcgagatgcc ccttccccag 1140ccggtctccc ctccccccgg ctcgggaaga agcctgctgg gccagggcgc cctgaccacc 1200tcctcggagg ccggcaaacc tgcctgaacc gccccagagg aatcgggcag gggctcgcac 1260cccaccccgg caggagggcc ccgagaccga cccgggccgg ggctccgcag ccggctgggc 1320tccgaggagc tcgtcccgag gcagctcccg gctccctagg ctccggggtt ggggggttcc 1380tcctccccta gccgggaagg gggcgattga tccatctgtc ggtgggccgg gctcaccggc 1440gtgttttagt cgcagaattt acaataaacg cccagaagga cctaaaagga agcgtctggc 1500tgggaaaggg ctggaggaga ggtgcggctg cggtcacgtt ccggcgagag cgggagaggc 1560gcggggtcgc ggtcgcgcga gggctcacac ccacgcagcc cggcatcccc cggccctcgc 1620gccacgttcc tcgcactcag ctcggcgcgc acacacggtg tcctggggtg gggtacacgc 1680agcgcctcag aaacttttcg tgctgcccaa aacaatctgg gctgcacgta acatgaattt 1740gatagtaccg tttaagatgc attcttaaat aacaagactc tggaatccag taaatgctag 18001651300DNAHomo sapiens 165aaacagcatt agccttctcc catcaaaagt ccggaagctg cccttcagtc gtcaaagtgt 60ttgccttaat ttgcaatcgt tatgacttga gccaaatgct tatacctcat ttgtgtcgta 120tatgtgaaga tacaattgca aatcgttcac gaccttgagt caagaccttg agtttcctga 180ggtcaggaga ccgttaggga atgtgagtgt cccagacggg cgctgagccc agctcggaga 240cccaccccgc ccgtagcagc ggcgcgggcc ccagagagcc ccgcactcgg ccgcgcctca 300gttacgctga ctcggctgtg cccgcagtgt cgcgctgtcg cgtagccagg tgtcgccggg 360ctggcgcggt tatttatgac tgcgtggttg ggctgggggt tcggggccgg ggagcagccg 420ggatccgccg cctcttccat gatcttcccg ggccgaacca cgggaccgct acgctgaagg 480tggcgtcgcg ggtccccggg gccgcgcgag tgtaggggtc gctctcggcc ggccgcgaag 540ctcgcggcac cgacttctcg cgagatttcg gcgacccccc cccccgcccc cgcccctccg 600ttctctgccc cctcccagct ctggtgtggg cggcctccgc tatggctgcg ctgcgaaggc 660tcttgtggcc gccaccccgg gtgtctcctc cactctgcgc tcaccagccc ctccttgggc 720cgtgggggcg gcctgcggtg accaccctgg gccttcctgg ccggcccttc tcctcccgag 780aggatgagga gagggctgtg gcggaggcgg catggaggcg gcggcggcgc tggggggagc 840tgagcgtggc ggcggcggcc ggcggggggc tggtcggcct ggtatgctac cagctgtacg 900gggaccccag ggccggctcg ccggcgaccg ggcgaccctc aaagagcgcg gccacggagc 960ccgaggaccc gccccgcggc cgggggatgc tgcccatccc agtggcggct gccaaggaga 1020cggtgagtgc gcgagcgcgc gtcacacctg cgcgggggat gtgaccttcg tgccgggtac 1080gcaggaccct ggaggctgtg gggacggtgc aagcgctgtg gccgcgggtg aggaacttcc 1140cgtgagcgag gctgacacct aggccggaca gcctaggatc cggtcaccca cgtattggga 1200agaccagtga tgctgtccct gatgcatcag gaccttaaag gtggctgcag ctaccaagta 1260tcaatccaaa cccaaaacca acacccctcc ccctcttaca 13001661300DNAHomo sapiens 166tgtaagaggg ggaggggtgt tggttttggg tttggattga tacttggtag ctgcagccac 60ctttaaggtc ctgatgcatc agggacagca tcactggtct tcccaatacg tgggtgaccg 120gatcctaggc tgtccggcct aggtgtcagc ctcgctcacg ggaagttcct cacccgcggc 180cacagcgctt gcaccgtccc cacagcctcc agggtcctgc gtacccggca cgaaggtcac 240atcccccgcg caggtgtgac gcgcgctcgc gcactcaccg tctccttggc agccgccact 300gggatgggca gcatcccccg gccgcggggc gggtcctcgg gctccgtggc cgcgctcttt 360gagggtcgcc cggtcgccgg cgagccggcc ctggggtccc cgtacagctg gtagcatacc 420aggccgacca gccccccgcc ggccgccgcc gccacgctca gctcccccca gcgccgccgc 480cgcctccatg ccgcctccgc cacagccctc tcctcatcct ctcgggagga gaagggccgg 540ccaggaaggc ccagggtggt caccgcaggc cgcccccacg gcccaaggag gggctggtga 600gcgcagagtg gaggagacac ccggggtggc ggccacaaga gccttcgcag cgcagccata 660gcggaggccg cccacaccag agctgggagg gggcagagaa cggaggggcg ggggcggggg 720ggggggtcgc cgaaatctcg cgagaagtcg gtgccgcgag cttcgcggcc ggccgagagc 780gacccctaca ctcgcgcggc cccggggacc cgcgacgcca ccttcagcgt agcggtcccg 840tggttcggcc cgggaagatc atggaagagg cggcggatcc cggctgctcc ccggccccga 900acccccagcc caaccacgca gtcataaata accgcgccag cccggcgaca cctggctacg 960cgacagcgcg acactgcggg cacagccgag tcagcgtaac tgaggcgcgg ccgagtgcgg 1020ggctctctgg ggcccgcgcc gctgctacgg gcggggtggg tctccgagct gggctcagcg 1080cccgtctggg acactcacat tccctaacgg tctcctgacc tcaggaaact caaggtcttg 1140actcaaggtc gtgaacgatt tgcaattgta tcttcacata tacgacacaa atgaggtata 1200agcatttggc tcaagtcata acgattgcaa attaaggcaa acactttgac gactgaaggg 1260cagcttccgg acttttgatg ggagaaggct aatgctgttt 13001671300DNAHomo sapiens 167cctggcgcgg acaggaccca gaaacaaacc acagcccggg gcgcagccgc cagggcgaag 60gttagttccg gtcccttccc ctcccctccc cacttggacg cgcttgcgga ggattgcgtt 120gacgagactc ttatttattg tcaccaacct gtggtggaat ttgcagttgc acattggatc 180tgattcgccc cgccccgaat gacgcctgcc cggaggcagt gaaagtacag ccgcgccgcc 240ccaagtcagc ctggacacat aaatcagcac gcggccggag aaccccgcaa tctctgcgcc 300cacaaaatac accgacgatg cccgatctac tttaagggct gaaacccacg ggcctgagag 360actataagag cgttccctac cgccatggaa caacggggac agaacgcccc ggccgcttcg 420ggggcccgga aaaggcacgg cccaggaccc agggaggcgc ggggagccag gcctgggccc 480cgggtcccca agacccttgt gctcgttgtc gccgcggtcc tgctgttggt gagtccccgc 540cgcggtccct ggctggggaa gagcgtgcct ggcgcctgga gagggcaggg agagaggggg 600acacggcggg ggtgcgtggc ccgggtcgcc tgcggccggg catgtccggg caagacgcac 660cagtcgtcgg agtcggggga agagatgggt ccccgggttg ggcaggagcg acctgggccg 720ccagggaaca gagcgcgcgc tccacttggt gtaaattccc gaatccagtg ggggagggcg 780acaaggaggg aattcccgag taagctgcgt gaagccacgg agaggtcgtc ggactttgat 840tttgttttct ttccttactt tctgtttctt tctctttttc tctttcttcc tttctttccc 900tcccttcctt cctcgctcag ttcctgcctt aatttctttt tcttttgcgc cttcgaatga 960attcctaaag gcgctcattg cagatcgctt tgaacctgcg gccggcgaag aactcccctg 1020tggtcgctgc ggcccagtgg ttccgttccg tgcgcgggag tcgtcgcggg cgcagctgga 1080gaggcccctt cccctcctta gcggctgcgc ccctacgcgt gcggggccgc tcatcgccaa 1140tgccattgtt tggggttcct tgggaaaacg agatttagga gaagggagtt gtggcacttg 1200gggcctgacc tgcttgataa tagcagctgc attttggcct gggaagagcc tttcttgcca 1260cctcttggca agtatccgtg ataatgggga agggacaaag 13001681300DNAHomo sapiens 168ctttgtccct tccccattat cacggatact tgccaagagg tggcaagaaa ggctcttccc 60aggccaaaat gcagctgcta ttatcaagca ggtcaggccc caagtgccac aactcccttc 120tcctaaatct cgttttccca aggaacccca aacaatggca ttggcgatga gcggccccgc 180acgcgtaggg gcgcagccgc taaggagggg aaggggcctc tccagctgcg cccgcgacga 240ctcccgcgca cggaacggaa ccactgggcc gcagcgacca caggggagtt cttcgccggc 300cgcaggttca aagcgatctg caatgagcgc ctttaggaat tcattcgaag gcgcaaaaga 360aaaagaaatt aaggcaggaa ctgagcgagg aaggaaggga gggaaagaaa ggaagaaaga 420gaaaaagaga aagaaacaga aagtaaggaa agaaaacaaa atcaaagtcc gacgacctct 480ccgtggcttc acgcagctta ctcgggaatt ccctccttgt cgccctcccc cactggattc 540gggaatttac accaagtgga gcgcgcgctc tgttccctgg cggcccaggt cgctcctgcc 600caacccgggg acccatctct tcccccgact ccgacgactg gtgcgtcttg cccggacatg 660cccggccgca ggcgacccgg gccacgcacc cccgccgtgt ccccctctct ccctgccctc 720tccaggcgcc aggcacgctc ttccccagcc agggaccgcg gcggggactc accaacagca 780ggaccgcggc gacaacgagc acaagggtct tggggacccg gggcccaggc ctggctcccc 840gcgcctccct gggtcctggg ccgtgccttt tccgggcccc cgaagcggcc ggggcgttct 900gtccccgttg ttccatggcg gtagggaacg ctcttatagt ctctcaggcc cgtgggtttc 960agcccttaaa gtagatcggg catcgtcggt gtattttgtg ggcgcagaga ttgcggggtt 1020ctccggccgc gtgctgattt atgtgtccag gctgacttgg ggcggcgcgg ctgtactttc 1080actgcctccg ggcaggcgtc attcggggcg gggcgaatca gatccaatgt gcaactgcaa 1140attccaccac aggttggtga caataaataa gagtctcgtc aacgcaatcc tccgcaagcg 1200cgtccaagtg gggaggggag gggaagggac cggaactaac cttcgccctg gcggctgcgc 1260cccgggctgt ggtttgtttc tgggtcctgt ccgcgccagg 1300169800DNAHomo sapiens 169tgcccctttt ctgagtgctt ggaagtgact gctgcaagtg acaagtgacc acgccttttc 60ccccgcgggt ataaattcag aggcgctgcg ctccgattct ggcagtgcag ctgtgggaac 120ctctccacgc gcacgaactc agccaacgat ttctgataga tttttgggag tttgaccaga 180gatgcaaggg gtgaaggagc gcttcctacc gttagggaac tctggggaca gagcgccccg 240gccgcctgat ggccgaggca gggtgcgacc caggacccag gacggcgtcg ggaaccatac 300catggcccgg atccccaaga ccctaaagtt cgtcgtcgtc atcgtcgcgg tcctgctgcc 360agtgagtccc ggccgcggtc cctggctggg gaagagcgca cctggcgccg ggagggggca 420gggagacggg gacacggcag ggatgcctgg ccctggtcac ctgcggccgg gcatgtccgg 480gcaggacgaa ctcgccgtcg gagtcagggg aagaactggg tccccgggct gggcaggagg 540gacccggccg cgagggagca gagaggcggt ccccctggct gccccgagcc cgcgaaggga 600gggaagttcc agaatcgaga gagggaggga gtcaaggtgg aacccataga gtgagcctcc 660tgaagacaca gagcggttgc ctctctcatt aattaattaa ttagttaata aaattaaccc 720catgtttaca ttcttaaacg tgttccttgg agatcggttt aaccaacagc cagtgaaaaa 780acttttcagc gctgtcttta 800170800DNAHomo sapiens 170taaagacagc gctgaaaagt tttttcactg gctgttggtt aaaccgatct ccaaggaaca 60cgtttaagaa tgtaaacatg gggttaattt tattaactaa ttaattaatt aatgagagag 120gcaaccgctc tgtgtcttca ggaggctcac tctatgggtt ccaccttgac tccctccctc 180tctcgattct ggaacttccc tcccttcgcg ggctcggggc agccaggggg accgcctctc 240tgctccctcg cggccgggtc cctcctgccc agcccgggga cccagttctt cccctgactc 300cgacggcgag ttcgtcctgc ccggacatgc ccggccgcag gtgaccaggg ccaggcatcc 360ctgccgtgtc cccgtctccc tgccccctcc cggcgccagg tgcgctcttc cccagccagg 420gaccgcggcc gggactcact ggcagcagga ccgcgacgat gacgacgacg aactttaggg 480tcttggggat ccgggccatg gtatggttcc cgacgccgtc ctgggtcctg ggtcgcaccc 540tgcctcggcc atcaggcggc cggggcgctc tgtccccaga gttccctaac ggtaggaagc 600gctccttcac cccttgcatc tctggtcaaa ctcccaaaaa tctatcagaa atcgttggct 660gagttcgtgc gcgtggagag gttcccacag ctgcactgcc agaatcggag cgcagcgcct 720ctgaatttat acccgcgggg gaaaaggcgt ggtcacttgt cacttgcagc agtcacttcc 780aagcactcag aaaaggggca 8001711300DNAHomo sapiens 171gaaataactt gagccaggga tcaaacacta agattggcag gaaatgagca ggaagaggta 60gcggggtccc tgacgccatc tattcaattg tttttcagaa gaggtatcag ctcttgaagg 120cttacttctc aatactggct gcgagagcaa gaatggtgtg taatttacaa aagccgtcat 180tgctgtaggt aagttgtagc aaacgactcg cgcccgagca ttcccgcccc cgccttcgct 240gcggccccgc ccacgacgac cctggggaac tacaagtccc gccatacagc ggggagcgcc 300cggagctcgc gccggccccg cccccagccc ggtccccacc cccggctccg cccccggccc 360cctcccgccg ggtcaacccc gaagagtcgc cggtggccgc ggcagacgga agccgaacga 420gttcctcggc ggctgcagga tgggggactc caaagtgaaa gtggcggtgc ggatacgacc 480catgaaccgg cgaggtgaga gccgagccct cctgggccgc cggggcggag gcggcaggtg 540cctggcgcgc ccttccctcg gccgccgtgg ggggtccggc ggccccgccc ctatagtcag 600cggcggggcg cgaggagggg cccggggacc ctgaaacccg ctcccgcgct gagacgcccg 660gctccctctt ctcccctccc ttcccccctg gccagccccg tccctggcgc cgtcgggccc 720ctcgtgccgg ccccgctgcc ccttccgcct gcgcccgccc cgcccctgcg cccttttgcc 780ctctcgtctc ccccggaggt tcccgagggc gccctcggcc ctcgcgccca gcctcgtcct 840ggcccctcag cctcgctcct tccccgccag ctgtcatcgt cgcccccgcg cgcgggtcgc 900cagcccctgc agcccgcctc gggaccgccc gggacccccc gggaccccgc gtctcgcccg 960ggtcgcccaa gcctgcaccg ccttggcccg cggcgggaag aagggcaggg ggccaggcgg 1020gtgccccgcg gcgagttcct tccacctggg cgtcctgaga ttggggtcag gtggaggaga 1080tgcccttttc gttgtttttg gacagttgag aaagttttgg ttttgcctga agtctcattc 1140atcatctctc aataaatagc taaagtgcca agattcttgt

ggaattgtat ctttctgaca 1200ttctcttaac tctgcaggga gtgtagagaa ggcagataaa ccgagtacat ttaaataatc 1260tgtagacccg gggagtggag agaaccccaa aagtcagggg 13001721300DNAHomo sapiens 172cccctgactt ttggggttct ctccactccc cgggtctaca gattatttaa atgtactcgg 60tttatctgcc ttctctacac tccctgcaga gttaagagaa tgtcagaaag atacaattcc 120acaagaatct tggcacttta gctatttatt gagagatgat gaatgagact tcaggcaaaa 180ccaaaacttt ctcaactgtc caaaaacaac gaaaagggca tctcctccac ctgaccccaa 240tctcaggacg cccaggtgga aggaactcgc cgcggggcac ccgcctggcc ccctgccctt 300cttcccgccg cgggccaagg cggtgcaggc ttgggcgacc cgggcgagac gcggggtccc 360ggggggtccc gggcggtccc gaggcgggct gcaggggctg gcgacccgcg cgcgggggcg 420acgatgacag ctggcgggga aggagcgagg ctgaggggcc aggacgaggc tgggcgcgag 480ggccgagggc gccctcggga acctccgggg gagacgagag ggcaaaaggg cgcaggggcg 540gggcgggcgc aggcggaagg ggcagcgggg ccggcacgag gggcccgacg gcgccaggga 600cggggctggc caggggggaa gggaggggag aagagggagc cgggcgtctc agcgcgggag 660cgggtttcag ggtccccggg cccctcctcg cgccccgccg ctgactatag gggcggggcc 720gccggacccc ccacggcggc cgagggaagg gcgcgccagg cacctgccgc ctccgccccg 780gcggcccagg agggctcggc tctcacctcg ccggttcatg ggtcgtatcc gcaccgccac 840tttcactttg gagtccccca tcctgcagcc gccgaggaac tcgttcggct tccgtctgcc 900gcggccaccg gcgactcttc ggggttgacc cggcgggagg gggccggggg cggagccggg 960ggtggggacc gggctggggg cggggccggc gcgagctccg ggcgctcccc gctgtatggc 1020gggacttgta gttccccagg gtcgtcgtgg gcggggccgc agcgaaggcg ggggcgggaa 1080tgctcgggcg cgagtcgttt gctacaactt acctacagca atgacggctt ttgtaaatta 1140cacaccattc ttgctctcgc agccagtatt gagaagtaag ccttcaagag ctgatacctc 1200ttctgaaaaa caattgaata gatggcgtca gggaccccgc tacctcttcc tgctcatttc 1260ctgccaatct tagtgtttga tccctggctc aagttatttc 13001731550DNAHomo sapiens 173accccctcct tccttctttc cctaccgccc cacgcgcgac ccggggatgg ctccgtggcc 60tcacgagaac agctctcttg ccccatggcc ggacctcccc accctggcgc ccaataccgc 120caacaccagt gggctgccag gggttccgtg ggaggcggcc ctagccgggg ccctgctggc 180gctggcggtg ctggccaccg tgggaggcaa cctgctggtc atcgtggcca tcgcctggac 240tccgagactc cagaccatga ccaacgtgtt cgtgacttcg ctggccgcag ccgacctggt 300gatgggactc ctggtggtgc cgccggcggc caccttggcg ctgactggcc actggccgtt 360gggcgccact ggctgcgagc tgtggacctc ggtggacgtg ctgtgtgtga ccgccagcat 420cgaaaccctg tgcgccctgg ccgtggaccg ctacctggct gtgaccaacc cgctgcgtta 480cggcgcactg gtcaccaagc gctgcgcccg gacagctgtg gtcctggtgt gggtcgtgtc 540ggccgcggtg tcgtttgcgc ccatcatgag ccagtggtgg cgcgtagggg ccgacgccga 600ggcgcagcgc tgccactcca acccgcgctg ctgtgccttc gcctccaaca tgccctacgt 660gctgctgtcc tcctccgtct ccttctacct tcctcttctc gtgatgctct tcgtctacgc 720gcgggttttc gtggtggcta cgcgccagct gcgcttgctg cgcggggagc tgggccgctt 780tccgcccgag gagtctccgc cggcgccgtc gcgctctctg gccccggccc cggtggggac 840gtgcgctccg cccgaagggg tgcccgcctg cggccggcgg cccgcgcgcc tcctgcctct 900ccgggaacac cgggccctgt gcaccttggg tctcatcatg ggcaccttca ctctctgctg 960gttgcccttc tttctggcca acgtgctgcg cgccctgggg ggcccctctc tagtcccggg 1020cccggctttc cttgccctga actggctagg ttatgccaat tctgccttca acccgctcat 1080ctactgccgc agcccggact ttcgcagcgc cttccgccgt cttctgtgcc gctgcggccg 1140tcgcctgcct ccggagccct gcgccgccgc ccgcccggcc ctcttcccct cgggcgttcc 1200tgcggcccgg agcagcccag cgcagcccag gctttgccaa cggctcgacg ggtaggtaac 1260cggggcagag ggaccggcgg ctcagggtcg ggaagcatgc gatgtgtccg tgggtcaact 1320ttttgagtgt ggagtttatt aagagaaggt gggatggctt tgcttggaga gaaaagggaa 1380cgaggagtag cgaaccaaaa tgggacccag ggtccttttc tttccggatc cagtcactag 1440ggtagaagca aaggagggcg agcgggccgt cgttcctcac ccaaggaccc aaggtgcgcc 1500accggaaagc gctgcggtgt cccgaggact ctcgcctcgc ctggtcggct 15501741550DNAHomo sapiens 174agccgaccag gcgaggcgag agtcctcggg acaccgcagc gctttccggt ggcgcacctt 60gggtccttgg gtgaggaacg acggcccgct cgccctcctt tgcttctacc ctagtgactg 120gatccggaaa gaaaaggacc ctgggtccca ttttggttcg ctactcctcg ttcccttttc 180tctccaagca aagccatccc accttctctt aataaactcc acactcaaaa agttgaccca 240cggacacatc gcatgcttcc cgaccctgag ccgccggtcc ctctgccccg gttacctacc 300cgtcgagccg ttggcaaagc ctgggctgcg ctgggctgct ccgggccgca ggaacgcccg 360aggggaagag ggccgggcgg gcggcggcgc agggctccgg aggcaggcga cggccgcagc 420ggcacagaag acggcggaag gcgctgcgaa agtccgggct gcggcagtag atgagcgggt 480tgaaggcaga attggcataa cctagccagt tcagggcaag gaaagccggg cccgggacta 540gagaggggcc ccccagggcg cgcagcacgt tggccagaaa gaagggcaac cagcagagag 600tgaaggtgcc catgatgaga cccaaggtgc acagggcccg gtgttcccgg agaggcagga 660ggcgcgcggg ccgccggccg caggcgggca ccccttcggg cggagcgcac gtccccaccg 720gggccggggc cagagagcgc gacggcgccg gcggagactc ctcgggcgga aagcggccca 780gctccccgcg cagcaagcgc agctggcgcg tagccaccac gaaaacccgc gcgtagacga 840agagcatcac gagaagagga aggtagaagg agacggagga ggacagcagc acgtagggca 900tgttggaggc gaaggcacag cagcgcgggt tggagtggca gcgctgcgcc tcggcgtcgg 960cccctacgcg ccaccactgg ctcatgatgg gcgcaaacga caccgcggcc gacacgaccc 1020acaccaggac cacagctgtc cgggcgcagc gcttggtgac cagtgcgccg taacgcagcg 1080ggttggtcac agccaggtag cggtccacgg ccagggcgca cagggtttcg atgctggcgg 1140tcacacacag cacgtccacc gaggtccaca gctcgcagcc agtggcgccc aacggccagt 1200ggccagtcag cgccaaggtg gccgccggcg gcaccaccag gagtcccatc accaggtcgg 1260ctgcggccag cgaagtcacg aacacgttgg tcatggtctg gagtctcgga gtccaggcga 1320tggccacgat gaccagcagg ttgcctccca cggtggccag caccgccagc gccagcaggg 1380ccccggctag ggccgcctcc cacggaaccc ctggcagccc actggtgttg gcggtattgg 1440gcgccagggt ggggaggtcc ggccatgggg caagagagct gttctcgtga ggccacggag 1500ccatccccgg gtcgcgcgtg gggcggtagg gaaagaagga aggagggggt 15501751800DNAHomo sapiens 175cgcagaccca gcaggagagc gcaacctagc atctttaagg ttcgcttagc ccttcctgtg 60cacctggaag gaagccttat cttaaactcc cttccaccta gagtttattt tcgcctgcgt 120gcgacagggc ttttgtactt aagtgagtta aggaatgaac cccgaactct tctgggaaag 180ccaccaacgt tccccccgca cccctcccag ggttcctgac cacggagact ctgcttgggg 240cacaggtgtg ggagtcgcaa acttttctct gcgccgtcct tttccgcgtg gaatgggacg 300gagcagccct cccaggcgct gcctggctgc ggaggggagc gggcagcgag agcctcgggt 360ctccgcctgg gttcccgggt ctccggggcg ctggcctcgg tctccgcgca gcgtccagcg 420acccctgtcg ggggttcccg gcagccgcgc cgccaccccc cgcccggcca gcgcgggagg 480aaaaggggct gcgcccggga gcgccgagcc caggctcctc ccggtggcgt gtccgcgcct 540cggggtgggg gtgtggtggg gaagagggag ggggcgaggc caggggaggg tgcgaaggag 600gcgcctgcct ccaacctgcg ggcgggaggt gggtggctgc ggggcaattg aaaaagagcc 660ggcgaggagt tccccgaaac ttgttggaac tccgggctcg cgcggaggcc aggagctgag 720cggcggcggc tgccggacga tgggagcgtg agcaggacgg tgataacctc tccccgatcg 780ggttgcgagg gcgccgggca gaggccagga cgcgagccgc cagcggtggg acccatcgac 840gacttcccgg ggcgacagga gcagccccga gagccagggc gagcgcccgt tccaggtggc 900cggaccgccc gccgcgtccg cgccgcgctc cctgcaggca acgggagacg cccccgcgca 960gcgcgagcgc ctcagcgcgg ccgctcgctc tccccctcga gggacaaact tttcccaaac 1020ccgatccgag cccttggacc aaactcgcct gcgccgagag ccgtccgcgt agagcgctcc 1080gtctccggcg agatgtccga gcgcaaagaa ggcagaggca aagggaaggg caagaagaag 1140gagcgaggct ccggcaagaa gccggagtcc gcggcgggca gccagagccc aggtgggtgc 1200gcagcgcggc ccgggcccca cgatcctcct cctgctcctc ctactcctcc tcctcctcgg 1260atgccgtggc ctctccctcc ccctctccct cgcccgtcct cttcgccctg cgctctgagc 1320gcccgttgag tcgcgcggtg cttcccctcc tgggggccgc cgctcacctg ggcgccgagt 1380cctaccgggc gcctacgccc agagctcagg gcaagggaca gcagtcccgg ccgcaccctc 1440ccagagtccc gggagcgctt cgctccctgg cacggcccct ccccagcgcc ttagcggctg 1500agcccagccc gggagtggga cctgggctat aggagtcgag gctgcgtgcg cgcgtgcccc 1560gcgccataag cgctttgcac gggggccgtg tgccctctag cgggaaacgc tggaatgggc 1620cgcctggagg gagagccggt cccctcggtg tgcctggcag cgcagaagtg ggtggtcgag 1680caagaggccg cgtgggaagt tagcttcggc gttttggggc acagggcaag cgatgtagag 1740tgcgcgccgg ttcatcttga ttcagtcctg tgctacggag actcaagagc agcggcaggg 18001761800DNAHomo sapiens 176ccctgccgct gctcttgagt ctccgtagca caggactgaa tcaagatgaa ccggcgcgca 60ctctacatcg cttgccctgt gccccaaaac gccgaagcta acttcccacg cggcctcttg 120ctcgaccacc cacttctgcg ctgccaggca caccgagggg accggctctc cctccaggcg 180gcccattcca gcgtttcccg ctagagggca cacggccccc gtgcaaagcg cttatggcgc 240ggggcacgcg cgcacgcagc ctcgactcct atagcccagg tcccactccc gggctgggct 300cagccgctaa ggcgctgggg aggggccgtg ccagggagcg aagcgctccc gggactctgg 360gagggtgcgg ccgggactgc tgtcccttgc cctgagctct gggcgtaggc gcccggtagg 420actcggcgcc caggtgagcg gcggccccca ggaggggaag caccgcgcga ctcaacgggc 480gctcagagcg cagggcgaag aggacgggcg agggagaggg ggagggagag gccacggcat 540ccgaggagga ggaggagtag gaggagcagg aggaggatcg tggggcccgg gccgcgctgc 600gcacccacct gggctctggc tgcccgccgc ggactccggc ttcttgccgg agcctcgctc 660cttcttcttg cccttccctt tgcctctgcc ttctttgcgc tcggacatct cgccggagac 720ggagcgctct acgcggacgg ctctcggcgc aggcgagttt ggtccaaggg ctcggatcgg 780gtttgggaaa agtttgtccc tcgaggggga gagcgagcgg ccgcgctgag gcgctcgcgc 840tgcgcggggg cgtctcccgt tgcctgcagg gagcgcggcg cggacgcggc gggcggtccg 900gccacctgga acgggcgctc gccctggctc tcggggctgc tcctgtcgcc ccgggaagtc 960gtcgatgggt cccaccgctg gcggctcgcg tcctggcctc tgcccggcgc cctcgcaacc 1020cgatcgggga gaggttatca ccgtcctgct cacgctccca tcgtccggca gccgccgccg 1080ctcagctcct ggcctccgcg cgagcccgga gttccaacaa gtttcgggga actcctcgcc 1140ggctcttttt caattgcccc gcagccaccc acctcccgcc cgcaggttgg aggcaggcgc 1200ctccttcgca ccctcccctg gcctcgcccc ctccctcttc cccaccacac ccccaccccg 1260aggcgcggac acgccaccgg gaggagcctg ggctcggcgc tcccgggcgc agcccctttt 1320cctcccgcgc tggccgggcg gggggtggcg gcgcggctgc cgggaacccc cgacaggggt 1380cgctggacgc tgcgcggaga ccgaggccag cgccccggag acccgggaac ccaggcggag 1440acccgaggct ctcgctgccc gctcccctcc gcagccaggc agcgcctggg agggctgctc 1500cgtcccattc cacgcggaaa aggacggcgc agagaaaagt ttgcgactcc cacacctgtg 1560ccccaagcag agtctccgtg gtcaggaacc ctgggagggg tgcgggggga acgttggtgg 1620ctttcccaga agagttcggg gttcattcct taactcactt aagtacaaaa gccctgtcgc 1680acgcaggcga aaataaactc taggtggaag ggagtttaag ataaggcttc cttccaggtg 1740cacaggaagg gctaagcgaa ccttaaagat gctaggttgc gctctcctgc tgggtctgcg 18001771550DNAHomo sapiens 177gggagggtgg cctgcaaggc ggggccggtt gcggtcaagt tcaagtaggg tcagagcagg 60agaacactgg cataaaaaat agccacatcc aaggaagcag tgaggtgtgg ggaccatcta 120tttcggtggg ccttcccacc cccaggccgg ccttcccatc acgcgtgggt gtgggggcac 180tgcccccgct gcgcgcagga acagcgggga gagccaggag cggagcggct tcgggatgcc 240agactgagca gtgggttcgt ctgcggccac ctctcaggga acaagcttcc ccccgcggag 300actctgcttc ttttaaaagc cttcctgggt ttagtctagg gcgacaggac gacctccctt 360gggaagggag agcctgccag tccccctccc attcgccagg cggtgcagcc cctcctcccg 420cccggggcgc gcgcacctca gcgtcgcggg cctagcgccc agcagccgcg ccccaggccg 480ggcctcgggt tccgggagcc cgcaggcgcg cgcccggccg ggcgtgtcgg gagcgcgcgg 540cggccggggg cggagcgcag ccagggctgc gcggcgcgcc ccggctcccg cccgctccca 600gccgggcccc ccagcggtcg gcgggacggc tcccggctgc agtctgcccg cccgccccgc 660gcgggggccg agtcgcgaag cgcgcctgcg acccggcgtc cgggcgcgct ggagaggacg 720cgaggagcca tgaggcgcca gcctgcgaag gtggcggcgc tgctgctcgg gctgctcttg 780gaggtagggg ccggggaccg ggtgctgccg gaggcgcggc gcccaccatg ctggcggctg 840ggggcgcgca gttccgaggc gccccagagg accttgcctg ggagcgcaga cggtggagcg 900acggggagcc acagccctgc gcgcctcccg gagctgggag gtgcgggacc ctggtgacgg 960ggaggctccc gccccggtcc gcgccttccg tcgttccttc ggttttcgca ccccgccccc 1020accctgcggg tgagcgcgtt tcccgcgccg accgcctccg ttagctcggg gtgacctttg 1080tgcaccgtcc gccccctctc cccgccgcag agggccgagg atcggatgga cccggggttg 1140ggcgggggtg gtcctcgggc gcggcgcagg cgcggagagc ccggggcgcc gggcagtttg 1200gggttaggaa aggatgggtg ccgagccggg gtgaggggag cgggcggagg ggactgtggg 1260gaagtgtcgc gggagtgccg ggagttgtgg aggtgagcag cgggaggagg cgttcccgcg 1320tgtgaaaatg aagtgcagcc tttaggtgcg gggaggaaat tctgcggaga gcctggctgg 1380gtgggggtgc ggagccgaag ccggcgggga acttgttgag cggcttccgg gtgcgagcgc 1440ccgtgaccgc atccctggcg gggaccgcgg ctgctcctgg ctgtgaaatt gcatcctcgg 1500atggggccac atacttctca ctaaagcagg ttccttaaaa tgcgaactag 15501781550DNAHomo sapiens 178ctagttcgca ttttaaggaa cctgctttag tgagaagtat gtggccccat ccgaggatgc 60aatttcacag ccaggagcag ccgcggtccc cgccagggat gcggtcacgg gcgctcgcac 120ccggaagccg ctcaacaagt tccccgccgg cttcggctcc gcacccccac ccagccaggc 180tctccgcaga atttcctccc cgcacctaaa ggctgcactt cattttcaca cgcgggaacg 240cctcctcccg ctgctcacct ccacaactcc cggcactccc gcgacacttc cccacagtcc 300cctccgcccg ctcccctcac cccggctcgg cacccatcct ttcctaaccc caaactgccc 360ggcgccccgg gctctccgcg cctgcgccgc gcccgaggac cacccccgcc caaccccggg 420tccatccgat cctcggccct ctgcggcggg gagagggggc ggacggtgca caaaggtcac 480cccgagctaa cggaggcggt cggcgcggga aacgcgctca cccgcagggt gggggcgggg 540tgcgaaaacc gaaggaacga cggaaggcgc ggaccggggc gggagcctcc ccgtcaccag 600ggtcccgcac ctcccagctc cgggaggcgc gcagggctgt ggctccccgt cgctccaccg 660tctgcgctcc caggcaaggt cctctggggc gcctcggaac tgcgcgcccc cagccgccag 720catggtgggc gccgcgcctc cggcagcacc cggtccccgg cccctacctc caagagcagc 780ccgagcagca gcgccgccac cttcgcaggc tggcgcctca tggctcctcg cgtcctctcc 840agcgcgcccg gacgccgggt cgcaggcgcg cttcgcgact cggcccccgc gcggggcggg 900cgggcagact gcagccggga gccgtcccgc cgaccgctgg ggggcccggc tgggagcggg 960cgggagccgg ggcgcgccgc gcagccctgg ctgcgctccg cccccggccg ccgcgcgctc 1020ccgacacgcc cggccgggcg cgcgcctgcg ggctcccgga acccgaggcc cggcctgggg 1080cgcggctgct gggcgctagg cccgcgacgc tgaggtgcgc gcgccccggg cgggaggagg 1140ggctgcaccg cctggcgaat gggaggggga ctggcaggct ctcccttccc aagggaggtc 1200gtcctgtcgc cctagactaa acccaggaag gcttttaaaa gaagcagagt ctccgcgggg 1260ggaagcttgt tccctgagag gtggccgcag acgaacccac tgctcagtct ggcatcccga 1320agccgctccg ctcctggctc tccccgctgt tcctgcgcgc agcgggggca gtgcccccac 1380acccacgcgt gatgggaagg ccggcctggg ggtgggaagg cccaccgaaa tagatggtcc 1440ccacacctca ctgcttcctt ggatgtggct attttttatg ccagtgttct cctgctctga 1500ccctacttga acttgaccgc aaccggcccc gccttgcagg ccaccctccc 1550179800DNAHomo sapiens 179tgctgggcaa tgcgtgcgtg gtggctgcca tcgccttgga gcgctccctg cagaacgtgg 60ccaattatct tattggctct ttggcggtca ccgacctcat ggtgtcggtg ttggtgctgc 120ccatggccgc gctgtatcag gtgctcaaca agtggacact gggccaggta acctgcgacc 180tgttcatcgc cctcgacgtg ctgtgctgca cctcatccat cttgcacctg tgcgccatcg 240cgctggacag gtactgggcc atcacggacc ccatcgacta cgtgaacaag aggacgcccc 300ggcgcgccgc tgcgctcatc tcgctcactt ggcttattgg cttcctcatc tctatcccgc 360ccatgctggg ctggcgcacc ccggaagacc gctcggaccc cgacgcatgc accattagca 420aggatcatgg ctacactatc tattccacct ttggagcttt ctacatcccg ctgctgctca 480tgctggttct ctatgggcgc atattccgag ctgcgcgctt ccgcatccgc aagacggtca 540aaaaggtgga gaagaccgga gcggacaccc gccatggagc atctcccgcc ccgcagccca 600agaagagtgt gaatggagag tcggggagca ggaactggag gctgggcgtg gagagcaagg 660ctgggggtgc tctgtgcgcc aatggcgcgg tgaggcaagg tgacgatggc gccgccctgg 720aggtgatcga ggtgcaccga gtgggcaact ccaaagagca cttgcctctg cccagcgagg 780ctggtcctac cccttgtgcc 800180800DNAHomo sapiens 180ggcacaaggg gtaggaccag cctcgctggg cagaggcaag tgctctttgg agttgcccac 60tcggtgcacc tcgatcacct ccagggcggc gccatcgtca ccttgcctca ccgcgccatt 120ggcgcacaga gcacccccag ccttgctctc cacgcccagc ctccagttcc tgctccccga 180ctctccattc acactcttct tgggctgcgg ggcgggagat gctccatggc gggtgtccgc 240tccggtcttc tccacctttt tgaccgtctt gcggatgcgg aagcgcgcag ctcggaatat 300gcgcccatag agaaccagca tgagcagcag cgggatgtag aaagctccaa aggtggaata 360gatagtgtag ccatgatcct tgctaatggt gcatgcgtcg gggtccgagc ggtcttccgg 420ggtgcgccag cccagcatgg gcgggataga gatgaggaag ccaataagcc aagtgagcga 480gatgagcgca gcggcgcgcc ggggcgtcct cttgttcacg tagtcgatgg ggtccgtgat 540ggcccagtac ctgtccagcg cgatggcgca caggtgcaag atggatgagg tgcagcacag 600cacgtcgagg gcgatgaaca ggtcgcaggt tacctggccc agtgtccact tgttgagcac 660ctgatacagc gcggccatgg gcagcaccaa caccgacacc atgaggtcgg tgaccgccaa 720agagccaata agataattgg ccacgttctg cagggagcgc tccaaggcga tggcagccac 780cacgcacgca ttgcccagca 800181550DNAHomo sapiens 181tgacgcaagg tccagtccag attgccaggc ccggggcatg agagaggatc cttgtaggtt 60tcggaggtgg gggggctgca ctccattgtt cactccgggc caatcagggt tggcccactt 120cctcccagcc aatctccctt cacccccagc ctccaaccca acccaccccg cccatcagcc 180cctggatccc catcacctcc cccgcatccc cggcagttct ggggaagctt cgtgacgcca 240caggtcccgc ccccagctcc ggcccggggc tagtgcgtgt tgacgtcatg ctgcgtgcgg 300gccggtgcgg aatcgctcct tcaactccgc ggggcagtag gagttagtta gcaaagagcc 360gaggccgggc gcgcgaccct cgtccttctg cccctggccg cacactttgc gcacatctct 420ttttctgcat ggtggatatt atttttcatt atccttttct gggtgctatg ggtgatcatt 480ccaagagtaa gtatttctgt gtgtgtgtgg ggtggggtgt gtgtgtatgc ttaatatgca 540aaatttctaa 550182550DNAHomo sapiens 182ttagaaattt tgcatattaa gcatacacac acaccccacc ccacacacac acagaaatac 60ttactcttgg aatgatcacc catagcaccc agaaaaggat aatgaaaaat aatatccacc 120atgcagaaaa agagatgtgc gcaaagtgtg cggccagggg cagaaggacg agggtcgcgc 180gcccggcctc ggctctttgc taactaactc ctactgcccc gcggagttga aggagcgatt 240ccgcaccggc ccgcacgcag catgacgtca acacgcacta gccccgggcc ggagctgggg 300gcgggacctg tggcgtcacg aagcttcccc agaactgccg gggatgcggg ggaggtgatg 360gggatccagg ggctgatggg cggggtgggt tgggttggag gctgggggtg aagggagatt 420ggctgggagg aagtgggcca accctgattg gcccggagtg aacaatggag tgcagccccc 480ccacctccga aacctacaag gatcctctct catgccccgg gcctggcaat ctggactgga 540ccttgcgtca 5501831050DNAHomo sapiens 183cagggaacag acccagtagt tggcttggat ctcttaactc cagaaaaggc cgagtgagga 60caagggagac cacagggata atttctgtgg ctctggtaag gggatgacaa gggagaaaaa 120ctttcccacg gttccgtctg gcccgcggcg cttgtctgcc tgcgcggggt caaagcccgg 180cgccgcccac gcgcggctcg ggtgggaacc cgcagacgtg gggcgagcag ggccgctggc 240tgtggcgggc gagcgccggg gcgccacgtc cgaggccgcg gggtcggggc tgcaggcaca 300gctcgagcgc tttccgcggg gtttggctcc tgtcgcttcc cgtctcgccg aaccggcatc 360gccgccgccg gagccgcagc gagtcctcag agcctggctg ctggcggccg ggagcgccgg 420gacggggcgc gaagccggag gctccgggac gtggatacag gtaaaggccg gcgggtcgga 480gtcgggcggg gcgcggcggc ggcgcctctc ggagggacct ggcctcggcc gggccctacc 540cagccgcggt ggcccgggcc cccacgttgg cccaggcggg

gacgtgccaa ggggctgggc 600tagggttgcc gctggcctgg ccgcctctcg cccggcgggc ctcaggtgac gcggccgcgg 660cttaactttc gcacctgagg ctctcggagc ggcctcgggg cgcgcccacc tggaggttgg 720aattacacag ggtcgaaaaa gctgagtcct ggaggcgagg cgctgtaggt gtggcggagg 780aggccgggga aggtggggtg ggtgccaggg gtccagtact gaaccctctc caggtctgag 840gtggggaact gcgtcttgtt taatttcgga gcttgtgggg accacacagc cccttccacg 900gccgattccc tctgcacggt tccactttcc tttgtctagc ccatttcagt atcggcgtcg 960cagtcgcttt tgttgcagcc ttgggtccgg agtgtacgac tttctgctag gcagaggtca 1020taagctctga aatccatcgg gcggaggtgg 10501841050DNAHomo sapiens 184ccacctccgc ccgatggatt tcagagctta tgacctctgc ctagcagaaa gtcgtacact 60ccggacccaa ggctgcaaca aaagcgactg cgacgccgat actgaaatgg gctagacaaa 120ggaaagtgga accgtgcaga gggaatcggc cgtggaaggg gctgtgtggt ccccacaagc 180tccgaaatta aacaagacgc agttccccac ctcagacctg gagagggttc agtactggac 240ccctggcacc caccccacct tccccggcct cctccgccac acctacagcg cctcgcctcc 300aggactcagc tttttcgacc ctgtgtaatt ccaacctcca ggtgggcgcg ccccgaggcc 360gctccgagag cctcaggtgc gaaagttaag ccgcggccgc gtcacctgag gcccgccggg 420cgagaggcgg ccaggccagc ggcaacccta gcccagcccc ttggcacgtc cccgcctggg 480ccaacgtggg ggcccgggcc accgcggctg ggtagggccc ggccgaggcc aggtccctcc 540gagaggcgcc gccgccgcgc cccgcccgac tccgacccgc cggcctttac ctgtatccac 600gtcccggagc ctccggcttc gcgccccgtc ccggcgctcc cggccgccag cagccaggct 660ctgaggactc gctgcggctc cggcggcggc gatgccggtt cggcgagacg ggaagcgaca 720ggagccaaac cccgcggaaa gcgctcgagc tgtgcctgca gccccgaccc cgcggcctcg 780gacgtggcgc cccggcgctc gcccgccaca gccagcggcc ctgctcgccc cacgtctgcg 840ggttcccacc cgagccgcgc gtgggcggcg ccgggctttg accccgcgca ggcagacaag 900cgccgcgggc cagacggaac cgtgggaaag tttttctccc ttgtcatccc cttaccagag 960ccacagaaat tatccctgtg gtctcccttg tcctcactcg gccttttctg gagttaagag 1020atccaagcca actactgggt ctgttccctg 10501851800DNAHomo sapiens 185ggcagcagcc gctggcttct gcgcccacta ggagcttcgg atgcccgagt tagggctgcg 60ccaaggcggc cggagcagag agggagacgg ggacggggac aggcagggac aaagtgcaag 120aggcaaaact ggctgaaaag cagaagtgta ggagccgcca aggggcggga cgaacaggtc 180cgtgggccgg gcggagccaa gggtgggggc cggggtccct ccaggtggca ctcgcggcgc 240tagtccccag cctcctccct tcccccggcc ctgattggca ggcggcctgc gaccagccgc 300gaacgccaca gcgccccggg cgcccaggag aacgcgaacg gccccccgcg ggagcgggcg 360agtaggaggg ggcgccgggc tatatatata gcggctcggc ctcgggcggg cctggcgctc 420agggaggcgc gcactgctcc tcagagtccc agctccagcc gcgcgctttc cgcccggctc 480gccgctccat gcagccgggg tagagcccgg cgcccggggg ccccgtcgct tgcctcccgc 540acctcctcgg ttgcgcactc ctgcccgagg tcggccgtgc gctcccgcgg gacgccacag 600gcgcagctct gccccccagc ttcccgggcg cactgaccgc ctgaccgacg cacggccctc 660gggccgggat gtcggggccc gggacggccg cggtagcgct gctcccggcg gtcctgctgg 720ccttgctggc gccctgggcg ggccgagggg gcgccgccgc acccactgca cccaacggca 780cgctggaggc cgagctggag cgccgctggg agagcctggt ggcgctctcg ttggcgcgcc 840tgccggtggc agcgcagccc aaggaggcgg ccgtccagag cggcgccggc gactacctgc 900tgggcatcaa gcggctgcgg cggctctact gcaacgtggg catcggcttc cacctccagg 960cgctccccga cggccgcatc ggcggcgcgc acgcggacac ccgcgacagt gagtggcgcg 1020gccaggcgcg aaggggcggg ggcggggggc aacggccgcc gggccaaccc gctcagtcac 1080actctgagac cctcggcggg cacctgctcg ggggccccgg gaaccggggc ggactcgggc 1140tccggtccct tctgacgcgg ggctggggac gcagacactc ttggctccgg cagcccagcg 1200caacccctga ggtcgggcgc cgcctcccgc cttcagaaac tcgggctccg agcgccgaat 1260tccagcgcct tcgcccgtgg gcacagggcg cgcggtgcag ccacaggggg cccgagacac 1320gcgccccggc ctggcccagg ctggggaacc gctggggtcg ggctcgcgtc tgaaggtccg 1380ggactgggtg cggccgccgg gggtccccta cacaggcaag ctaatctgag ctagcgcagg 1440cttgggctcc ggaggcccta gagggcagct tgggctctgg aggcccttgg gggcggctgc 1500gccgggaacc ctggcccttt atccccaacc ccaccccaga aatagggtcc ccggaggcga 1560acaagccgag gggcggagtg ggccagggat cacctgcccc gcaatgacct gcgccccgcc 1620cccaggcctg ctggagctct cgcccgtgga gcggggcgtg gtgagcatct tcggcgtggc 1680cagccggttc ttcgtggcca tgagcagcaa gggcaagctc tatggctcgg tgagtaccgc 1740aggggtctgg ctaggcacct agttgggaac agcggacatg gctagcaggc tcgtggcttc 18001861800DNAHomo sapiens 186gaagccacga gcctgctagc catgtccgct gttcccaact aggtgcctag ccagacccct 60gcggtactca ccgagccata gagcttgccc ttgctgctca tggccacgaa gaaccggctg 120gccacgccga agatgctcac cacgccccgc tccacgggcg agagctccag caggcctggg 180ggcggggcgc aggtcattgc ggggcaggtg atccctggcc cactccgccc ctcggcttgt 240tcgcctccgg ggaccctatt tctggggtgg ggttggggat aaagggccag ggttcccggc 300gcagccgccc ccaagggcct ccagagccca agctgccctc tagggcctcc ggagcccaag 360cctgcgctag ctcagattag cttgcctgtg taggggaccc ccggcggccg cacccagtcc 420cggaccttca gacgcgagcc cgaccccagc ggttccccag cctgggccag gccggggcgc 480gtgtctcggg ccccctgtgg ctgcaccgcg cgccctgtgc ccacgggcga aggcgctgga 540attcggcgct cggagcccga gtttctgaag gcgggaggcg gcgcccgacc tcaggggttg 600cgctgggctg ccggagccaa gagtgtctgc gtccccagcc ccgcgtcaga agggaccgga 660gcccgagtcc gccccggttc ccggggcccc cgagcaggtg cccgccgagg gtctcagagt 720gtgactgagc gggttggccc ggcggccgtt gccccccgcc cccgcccctt cgcgcctggc 780cgcgccactc actgtcgcgg gtgtccgcgt gcgcgccgcc gatgcggccg tcggggagcg 840cctggaggtg gaagccgatg cccacgttgc agtagagccg ccgcagccgc ttgatgccca 900gcaggtagtc gccggcgccg ctctggacgg ccgcctcctt gggctgcgct gccaccggca 960ggcgcgccaa cgagagcgcc accaggctct cccagcggcg ctccagctcg gcctccagcg 1020tgccgttggg tgcagtgggt gcggcggcgc cccctcggcc cgcccagggc gccagcaagg 1080ccagcaggac cgccgggagc agcgctaccg cggccgtccc gggccccgac atcccggccc 1140gagggccgtg cgtcggtcag gcggtcagtg cgcccgggaa gctggggggc agagctgcgc 1200ctgtggcgtc ccgcgggagc gcacggccga cctcgggcag gagtgcgcaa ccgaggaggt 1260gcgggaggca agcgacgggg cccccgggcg ccgggctcta ccccggctgc atggagcggc 1320gagccgggcg gaaagcgcgc ggctggagct gggactctga ggagcagtgc gcgcctccct 1380gagcgccagg cccgcccgag gccgagccgc tatatatata gcccggcgcc ccctcctact 1440cgcccgctcc cgcggggggc cgttcgcgtt ctcctgggcg cccggggcgc tgtggcgttc 1500gcggctggtc gcaggccgcc tgccaatcag ggccggggga agggaggagg ctggggacta 1560gcgccgcgag tgccacctgg agggaccccg gcccccaccc ttggctccgc ccggcccacg 1620gacctgttcg tcccgcccct tggcggctcc tacacttctg cttttcagcc agttttgcct 1680cttgcacttt gtccctgcct gtccccgtcc ccgtctccct ctctgctccg gccgccttgg 1740cgcagcccta actcgggcat ccgaagctcc tagtgggcgc agaagccagc ggctgctgcc 18001871300DNAHomo sapiens 187tgaggtgagg ggccggagga gcaagggaca agaggagcag aggacaggtg atggaaatcc 60tgcagcttta ggctccattc tgccatctac atcccagcgc agggtgaagc ctgagagccc 120aaatggccaa ctccacaggg ctgaacgcct cagaagtcgc aggctcgttg gggttgatcc 180tggcagctgt cgtggaggtg ggggcactgc tgggcaacgg cgcgctgctg gtcgtggtgc 240tgcgcacgcc gggactgcgc gacgcgctct acctggcgca cctgtgcgtc gtggacctgc 300tggcggccgc ctccatcatg ccgctgggcc tgctggccgc accgccgccc gggctgggcc 360gcgtgcgcct gggccccgcg ccatgccgcg ccgctcgctt cctctccgcc gctctgctgc 420cggcctgcac gctcggggtg gccgcacttg gcctggcacg ctaccgcctc atcgtgcacc 480cgctgcggcc aggctcgcgg ccgccgcctg tgctcgtgct caccgccgtg tgggccgcgg 540cgggactgct gggcgcgctc tccctgctcg gcacgccgcc cgcaccgccc cctgctcctg 600ctcgctgctc ggtcctggct gggggcctcg ggcccttccg gccgctctgg gccctgctgg 660ccttcgcgct gcccgccctc ctgctgctcg gcgcctacgg cggcatcttc gtggtggcgc 720gtcgcgctgc cctgaggccc ccacggccgg cgcgcgggtc ccgactccac tcggactctc 780tggatagccg cctttccatc ttgccgccgc tccggcctcg cctgcccggg ggcaaggcgg 840ccctggcccc agcgctggcc gtgggccaat ttgcagcctg ctggctgcct tatggctgcg 900cgtgcctggc gcccgcagcg cgggccgcgg aagccgaagc ggctgtcacc tgggtcgcct 960actcggcctt cgcggctcac cccttcctgt acgggctgct gcagcgcccc gtgcgcttgg 1020cactgggccg cctctctcgc cgtgcactgc ctggacctgt gcgggcctgc actccgcaag 1080cctggcaccc gcgggcactc ttgcaatgcc tccagagacc cccagagggc cctgccgtag 1140gcccttctga ggctccagaa cagacccccg agttggcagg agggcggagc cccgcatacc 1200aggggccacc tgagagttct ctctcctgag caggagaaag gagggtggtt tccgtggggg 1260ctcatccaac ccctgcacag gtcacagcag gtgccctgct 13001881300DNAHomo sapiens 188agcagggcac ctgctgtgac ctgtgcaggg gttggatgag cccccacgga aaccaccctc 60ctttctcctg ctcaggagag agaactctca ggtggcccct ggtatgcggg gctccgccct 120cctgccaact cgggggtctg ttctggagcc tcagaagggc ctacggcagg gccctctggg 180ggtctctgga ggcattgcaa gagtgcccgc gggtgccagg cttgcggagt gcaggcccgc 240acaggtccag gcagtgcacg gcgagagagg cggcccagtg ccaagcgcac ggggcgctgc 300agcagcccgt acaggaaggg gtgagccgcg aaggccgagt aggcgaccca ggtgacagcc 360gcttcggctt ccgcggcccg cgctgcgggc gccaggcacg cgcagccata aggcagccag 420caggctgcaa attggcccac ggccagcgct ggggccaggg ccgccttgcc cccgggcagg 480cgaggccgga gcggcggcaa gatggaaagg cggctatcca gagagtccga gtggagtcgg 540gacccgcgcg ccggccgtgg gggcctcagg gcagcgcgac gcgccaccac gaagatgccg 600ccgtaggcgc cgagcagcag gagggcgggc agcgcgaagg ccagcagggc ccagagcggc 660cggaagggcc cgaggccccc agccaggacc gagcagcgag caggagcagg gggcggtgcg 720ggcggcgtgc cgagcaggga gagcgcgccc agcagtcccg ccgcggccca cacggcggtg 780agcacgagca caggcggcgg ccgcgagcct ggccgcagcg ggtgcacgat gaggcggtag 840cgtgccaggc caagtgcggc caccccgagc gtgcaggccg gcagcagagc ggcggagagg 900aagcgagcgg cgcggcatgg cgcggggccc aggcgcacgc ggcccagccc gggcggcggt 960gcggccagca ggcccagcgg catgatggag gcggccgcca gcaggtccac gacgcacagg 1020tgcgccaggt agagcgcgtc gcgcagtccc ggcgtgcgca gcaccacgac cagcagcgcg 1080ccgttgccca gcagtgcccc cacctccacg acagctgcca ggatcaaccc caacgagcct 1140gcgacttctg aggcgttcag ccctgtggag ttggccattt gggctctcag gcttcaccct 1200gcgctgggat gtagatggca gaatggagcc taaagctgca ggatttccat cacctgtcct 1260ctgctcctct tgtcccttgc tcctccggcc cctcacctca 1300189800DNAHomo sapiens 189ccgcgacctt cgagaacccg catgctgttc tccaccaggt ctctcagtcc tccctgcccc 60aatccccatg cccgcctccg cgaccctgtg atgcctccct tcttgcacag gagcagtgac 120ctcagcactt acttaatcct ctcccggcgc cgagctcagt tggagaggct aggggtggta 180gtgactggca ggaggccggg gcggggggaa cccccaagcc cggcgtctgg ggctgcgggt 240ccgacccgag atccgccctc cctgcaagcc ccgagccgct ggccaggccc gctactgcgc 300accagccgca tccgcgagcg ctggctctgc cggcctgagc tagggtgggt agggccggga 360cccacggcgg aggtggggcc gggccgagca gcctcggggg atccccgaag ctacagcgcc 420ttgcctccct gcacgctccg cgcccccggc ctccgattgg ctgtcgggcc tagagcccgc 480ccagaattgg accgttcgct tgtcgctcgg gtctggctcc acccccagag ggagcctaga 540acctggtcgc agtttttaga gactaccctc accccgtggc ctgcgccgaa gttgggcgga 600ggacagtggg tggccaggcc cttccgggcc agaactcggg acccctgcca gctacccgtg 660ccaggacaga ctcaagcccc caaaacgcgg atggatgtac agaggagact tggggagagc 720actggactgg gagtccttgg gcctgcactg aactctggct gactttgtga ccttgaagaa 780actgcttttc ccttcctgaa 800190800DNAHomo sapiens 190ttcaggaagg gaaaagcagt ttcttcaagg tcacaaagtc agccagagtt cagtgcaggc 60ccaaggactc ccagtccagt gctctcccca agtctcctct gtacatccat ccgcgttttg 120ggggcttgag tctgtcctgg cacgggtagc tggcaggggt cccgagttct ggcccggaag 180ggcctggcca cccactgtcc tccgcccaac ttcggcgcag gccacggggt gagggtagtc 240tctaaaaact gcgaccaggt tctaggctcc ctctgggggt ggagccagac ccgagcgaca 300agcgaacggt ccaattctgg gcgggctcta ggcccgacag ccaatcggag gccgggggcg 360cggagcgtgc agggaggcaa ggcgctgtag cttcggggat cccccgaggc tgctcggccc 420ggccccacct ccgccgtggg tcccggccct acccacccta gctcaggccg gcagagccag 480cgctcgcgga tgcggctggt gcgcagtagc gggcctggcc agcggctcgg ggcttgcagg 540gagggcggat ctcgggtcgg acccgcagcc ccagacgccg ggcttggggg ttccccccgc 600cccggcctcc tgccagtcac taccacccct agcctctcca actgagctcg gcgccgggag 660aggattaagt aagtgctgag gtcactgctc ctgtgcaaga agggaggcat cacagggtcg 720cggaggcggg catggggatt ggggcaggga ggactgagag acctggtgga gaacagcatg 780cgggttctcg aaggtcgcgg 8001911050DNAHomo sapiens 191ctgcagcagg acgtaagcac agtcatcgct gcaaactgca aactcgtaag cacagtcatc 60gctgcaaact gcaaactcgt gctccgagcg ctgccctccc ctgtggagcg gaggagggga 120ggcctggggc cgcggcggtg tgcgccccgc tctgaccgca gagccccctt cccgaggaaa 180gcggctggcc cggtcccggc tggtgatcac gcggggcccc tgtctgcttg gtgcgcaggt 240gagggtctgc ccttccgctg cgccccggac agcctggagg tgagcacgcg ctgggccctg 300gaccgcgagc agcgggagaa gtacgagctg gtggccgtgt gcaccgtgca cgccggcgcg 360cgcgaggagg tggtgatggt gcccttcccg gtgaccgtgt acgacgagga cgactcggcg 420cccaccttcc ccgcgggcgt cgacaccgcc agcgccgtgg tggagttcaa gcggaaggag 480gtgcttgtcc gcgcgtgctg tggtctaccc agtgtctgtc tccggccaca gttcgtttct 540cggtcggttt agtgtccgtg tagccaccca accgtgtggc cgaccattcg cgctttcatt 600tgtccttcgc ctccgtctgc gccgtctgtc ctagggggag gggaaggggg agtcctgcca 660gcacccagct gggccttgcc tcgggaggca aggaccagga cgaggcccga gggctcgcgt 720ctggggcata cttgtgccgc tgcaggcggg cgcggcgcgc tgcccgggcg gggagcatct 780gccgggaggg cactccctcc caccagcagt tagcccccaa cgggagggcc cttgagtgac 840cacgagcaga gccggggatt ggagaaggac gggaaggcgg atcacctccg gcgccgcccg 900ccccgccctt ctccggctcg cgctggtgga gcgcgaccgc cacctgctgg gcctcggcct 960tcctgcagcc ggcccaccca gcaggggccg tgggagagtg ggcgtgggga ctgaggtagg 1020tagtacgttg ccttgttccg cttctctggg 10501921050DNAHomo sapiens 192cccagagaag cggaacaagg caacgtacta cctacctcag tccccacgcc cactctccca 60cggcccctgc tgggtgggcc ggctgcagga aggccgaggc ccagcaggtg gcggtcgcgc 120tccaccagcg cgagccggag aagggcgggg cgggcggcgc cggaggtgat ccgccttccc 180gtccttctcc aatccccggc tctgctcgtg gtcactcaag ggccctcccg ttgggggcta 240actgctggtg ggagggagtg ccctcccggc agatgctccc cgcccgggca gcgcgccgcg 300cccgcctgca gcggcacaag tatgccccag acgcgagccc tcgggcctcg tcctggtcct 360tgcctcccga ggcaaggccc agctgggtgc tggcaggact cccccttccc ctccccctag 420gacagacggc gcagacggag gcgaaggaca aatgaaagcg cgaatggtcg gccacacggt 480tgggtggcta cacggacact aaaccgaccg agaaacgaac tgtggccgga gacagacact 540gggtagacca cagcacgcgc ggacaagcac ctccttccgc ttgaactcca ccacggcgct 600ggcggtgtcg acgcccgcgg ggaaggtggg cgccgagtcg tcctcgtcgt acacggtcac 660cgggaagggc accatcacca cctcctcgcg cgcgccggcg tgcacggtgc acacggccac 720cagctcgtac ttctcccgct gctcgcggtc cagggcccag cgcgtgctca cctccaggct 780gtccggggcg cagcggaagg gcagaccctc acctgcgcac caagcagaca ggggccccgc 840gtgatcacca gccgggaccg ggccagccgc tttcctcggg aagggggctc tgcggtcaga 900gcggggcgca caccgccgcg gccccaggcc tcccctcctc cgctccacag gggagggcag 960cgctcggagc acgagtttgc agtttgcagc gatgactgtg cttacgagtt tgcagtttgc 1020agcgatgact gtgcttacgt cctgctgcag 1050193800DNAHomo sapiens 193gcgccgacgg gggcgggtgg taggggatgt acgggtgtgt atatgcagag gtatgccagg 60ctctgcccct taaagtttgg gggccggcgg aggcggcgcc gtggccggga gaaagtgtct 120ctcatttagg agggtttgca ggtccagagt aaagtcactg aagagtggaa gcgaggaagg 180aacaggatga ttagacctca gctgcggacc gcggggctgg gacgatgcct cctgccgggg 240ctgctgctgc tcctggtgcc cgtcctctgg gccggggctg aaaagctaca tacccagccc 300tcctgccccg cggtctgcca gcccacgcgc tgccccgcgc tgcccacctg cgcgctgggg 360accacgccgg tgttcgacct gtgccgctgt tgccgcgtct gccccgcggc cgagcgtgaa 420gtctgcggcg gggcgcaggg ccaaccgtgc gccccggggc tgcagtgcct ccagccgctg 480cgccccgggt tccccagcac ctgcggttgc ccgacgctgg gaggggccgt gtgcggcagc 540gacaggcgca cctaccccag catgtgcgcg ctccgggccg aaaaccgcgc cgcgcgccgc 600ctgggcaagg tcccggccgt gcctgtgcag tgggggaact gcggggatac aggtgagccg 660cgggggcgcg cgccctcgga acactttcta actctggagg agcgtaaagg aacaagacct 720cactgagacc gcacagttcg cgcctggtcc tcctgcgtca tttgcctcct ggattcgaca 780cctctgtgtt cctgatttcc 800194800DNAHomo sapiens 194ggaaatcagg aacacagagg tgtcgaatcc aggaggcaaa tgacgcagga ggaccaggcg 60cgaactgtgc ggtctcagtg aggtcttgtt cctttacgct cctccagagt tagaaagtgt 120tccgagggcg cgcgcccccg cggctcacct gtatccccgc agttccccca ctgcacaggc 180acggccggga ccttgcccag gcggcgcgcg gcgcggtttt cggcccggag cgcgcacatg 240ctggggtagg tgcgcctgtc gctgccgcac acggcccctc ccagcgtcgg gcaaccgcag 300gtgctgggga acccggggcg cagcggctgg aggcactgca gccccggggc gcacggttgg 360ccctgcgccc cgccgcagac ttcacgctcg gccgcggggc agacgcggca acagcggcac 420aggtcgaaca ccggcgtggt ccccagcgcg caggtgggca gcgcggggca gcgcgtgggc 480tggcagaccg cggggcagga gggctgggta tgtagctttt cagccccggc ccagaggacg 540ggcaccagga gcagcagcag ccccggcagg aggcatcgtc ccagccccgc ggtccgcagc 600tgaggtctaa tcatcctgtt ccttcctcgc ttccactctt cagtgacttt actctggacc 660tgcaaaccct cctaaatgag agacactttc tcccggccac ggcgccgcct ccgccggccc 720ccaaacttta aggggcagag cctggcatac ctctgcatat acacacccgt acatccccta 780ccacccgccc ccgtcggcgc 800195801DNAHomo sapiens 195ttgtcttctc ccttccgacc tcccgtggcc ccagcgcggc cagctcacag taggtgctcg 60ggcagcgttt cttcagggac ctagacggcc tggagaggaa gggccccagc ccagccgccc 120gggcctctca cctggctctc ggggcgcccg gctcgcactt cctcccgccg ccccgcccct 180tccacattcc tgccccgccg ggcctgcccc gcgcagtctg ggtctctgcg ccgcagccgc 240ccgcccgccc gctcagcgcc cggccccggg atgacggcgg cccaggccgc gggtgaggag 300gcgccaccag gcgtgcggtc cgtcaaggtg gtcctggtgg gcgacggcgg ctgcgggaag 360acgtcgctgc tgatggtctt cgccgatggg gccttccccg aggtgagtgc cccgcgcctc 420cgcctcgccc ggttccgctc gcgcgcccgg gtgtacaggt ccgtgccgga gcggcccagg 480ctgtgcgcct aacccggcct ccgaggggtg tcccagcggg gcctggggtc cagggcagag 540ttcttccgcc ccagccattg ggaatgaagg cctcagtgat gttatctgta aagccggagg 600aatggcatcc accggggaga ggtgtcacaa ggactgagtg aggcgacctg ggtgcacaca 660agatcctaag acagcacttg gccacacaat tccgctgagg gcctgagagc ttggaagcca 720gactgccgag gttcaaatta tggctttgcc tcttatagct gtgtgccctt gggtaagtcc 780cctaaccctg ctgtgcctgt g 8011961301DNAHomo sapiens 196attgagagag agggagggcg aaaggaagga aggggagcca gaggtgggag tggaagaggc 60agcctcgcct ggggctgatt ggctcccgag gccagggctc tccaagcggt ttataagagt 120tggggctgcc gggcgccctg cccgctcgcc cgcgcgcccc aggacccaaa gccgggctcc 180aagtcggcgc cccacgtcga ggctccgccg cagcctccgg agttggccgc agacaagaag 240gggagggagc gggagaggga ggagagctcc gaagcgagag ggccgagcgc catgcgccgc 300gccagcagag actacaccaa gtacctgcgt ggctcggagg agatgggcgg cggccccgga 360gccccgcacg agggccccct gcacgccccg ccgccgcctg cgccgcacca gccccctgcc 420gcctcccgct ccatgttcgt ggccctcctg gggctggggc tgggccaggt tgtctgcagc 480gtcgccctgt tcttctattt cagagcgcag gtgagtggcc accttcccag gggatcgcgg 540ctgagagcgc ccatctcctt cccccgcact tggaaactga gtctggcggc agggctgggc

600cacccagagc ttgcatattc cggaagggaa agtgactcca gaagggagag aggaagtgtt 660gagtttgggg acaacctggc gcagggctgt cgggcgcacc ctgctctctc tccgcccacg 720caccccagct tctcggtgct ctgggggcgg actcccctgg ccggacgatg ggtttgaatc 780tcaccccgtc ccttcgctgg gaaacaacac tggcctctca ccttttctgg tagtgattgc 840atactttttc tccctgtcat ttctcacttg aagttaagaa tcaacttctg ttcacgtagg 900aaaaaagatg agcgccttca cttgggcatc tacctttccc ttcccgccca ccacccggcg 960ggtttcggtt cctgcgcctg gctgctctgc aggtgtgctg gggccacggt gctggagggc 1020tgcgcggagc gggaggtcgc ggtgctcgtg cccaggtcgc ccaatgggtg ggcagaatga 1080cacggcgcga ccagagaggc gcgggctcgg gatgggggct ctgcggctgt ggcgctgtcc 1140tgtgggggtg aaggaagagg gacagcccca cgtgcctgct agggatgtgg gcggaggaag 1200gaagcgaggt gagtgtgatg gcacagtgtt actacagtct agcaaataac caaccttcgg 1260aaagatgaag aggttttttg cacgacggct aggaactgca g 13011974301DNAHomo sapiens 197gcaatttata gatgagagcg tggacggcag agagcattgt gtatgttgaa gtctctgcga 60tatggggtgt ccctgctgcc ccgctccagc ctttcacttc tgacctcctt cctctggctc 120ttacgctaca ggatccaaaa ctactcggaa gacttgccgc gggcggtgat tgacgacgcc 180tttgcccgcg ccttcgcact gtggagcgcg gtgacgccgc tcaccttcac tcgcgtgtac 240agccgggacg cagacatcgt catccagttt ggtgtcgcgg gtgagaacgt gaggagggaa 300aatccaagag acctgggcgg ggtcagggaa gggaggacca cggagagcgt ggaggcagca 360gtggccccgg cttcctcttg cctgcccgcg ctgccctggc ttatacggcc cctcctgcca 420gacagtgcac agggccaggg cgccaggctg ggagagcttc gcgcaggcgg gatttcagcc 480cgcacttatt tcggagccct tgccttgggc agcgcacaat ctgcgcagca gtactcggct 540aaccctcttc ctctcgacct gtttcttcag agcacggaga cgggtatccc ttcgacggga 600aggacgggct cctggcacac gcctttcctc ctggccccgg cattcaggga gacgcccatt 660tcgacgatga cgagttgtgg tccctgggca agggcgtcgg tgagattctg agtcctcctg 720gcccctgatt cccttcattc tctcccactc atcacccgcc gccctaactc cggtcccccc 780tcctcctgca gtggttccaa ctcggtttgg aaacgcagat ggcgcggcct gccacttccc 840cttcatcttc gagggccgct cctactctgc ctgcaccacc gacggtcgct ccgacggctt 900gccctggtgc agtaccacgg ccaactacga caccgacgac cggtttggct tctgccccag 960cgagagtgag tgagggggct cgccgagggc tgggggcgcc caccaccctt gatggtcctg 1020ggttctaatt ccagctctgc cactagtgct gtgtggcctg caattcaccc tcccgcactc 1080tgggcccaat tttctcatct gagaaatgat gagagatggg atgaactgca gaccatccat 1140gggtcaaaga acaggacaca cttgggggtt ataatgtgct gtctccgcct tctccccctt 1200tcccacatcc tcctcgcccc aggactctac acccaggacg gcaatgctga tgggaaaccc 1260tgccagtttc cattcatctt ccaaggccaa tcctactccg cctgcaccac ggacggtcgc 1320tccgacggct accgctggtg cgccaccacc gccaactacg accgggacaa gctcttcggc 1380ttctgcccga cccgaggtac ctccaccctg tctaccaggt tcagccccgc cctctcatca 1440tgtattggcc cccaaaacgc ggctcttccc tcccatcagt ttgtctttcc actctcattg 1500gtcctcagga cgaccgtgac tccgcccacc tacaccacat ttccaccact atccctgact 1560tccaatggcc ccgccccagc cactaaggtt cggccttttc tgcccagctg gccgcctctt 1620ccttggtctg gtgtcccagg caccgcccac gggtctagcc tcttctcagg agtgctctac 1680agcgccccct aggccaccaa gattgtttag ctccctgtcg ggtcggcccc tgactcctta 1740ttggactcat ccatctggct catccaaggc cttgggtctc tccagctgac tcgacggtga 1800tggggggcaa ctcggcgggg gagctgtgcg tcttcccctt cactttcctg ggtaaggagt 1860actcgacctg taccagcgag ggccgcggag atgggcgcct ctggtgcgct accacctcga 1920actttgacag cgacaagaag tggggcttct gcccggacca aggtaggcgt ggtcccgcgg 1980ctccggggct ggggttcccg gcagtggtgg tggtggggtg gccagggctg ggggctcggc 2040ccggcgctca cgtctcaggc tccctctccc tccaggatac agtttgttcc tcgtggcggc 2100gcatgagttc ggccacgcgc tgggcttaga tcattcctca gtgccggagg cgctcatgta 2160ccctatgtac cgcttcactg aggggccccc cttgcataag gacgacgtga atggcatccg 2220gcacctctat ggtgaggcag gggcagggat gggaggagga ggggaaaggg cgtggctgtg 2280ccacagtacc aaagaattgg gggttgggga tcgggggagg aacggggcgt gcaggagagg 2340tgggacctca acgtctgtct ggaagcagag cctgggccca gtcgctgcca tgtcagtgct 2400tagaggtggt gataaagaga ctctagagag agataggtgt gacttcaaaa gccagtctac 2460tctgggcatg gtggctcacg cctctaatcc cagggctttg ggagacccaa ggcgggagga 2520ttgcttaagc ccaggagttc cagaccagcc tcggcaacat agccagactc ccatctctac 2580aaaaaataaa tgagcaaggc gtgaaggcac atgtctgtag tcctagctac tctggaggct 2640gaggtgggag gatctcttga gcccaggagt tcgaggctgt agtgagctat gattgcacca 2700ctgcattcca tcctgggcca tagaggatgt cgcttaaaac gaaaaagaag aagaagaaag 2760tcctgtggtt tgggaaggga ggctgagtga ggaggggcct gtgtgccaga ggaggcttca 2820ctgagaagct taggggagca gatgttctag gggtacagag gtatgcagga ataggaagag 2880tctcaccccg tgtctctttt taggtcctcg ccctgaacct gagccacggc ctccaaccac 2940caccacaccg cagcccacgg ctcccccgac ggtctgcccc accggacccc ccactgtcca 3000cccctcagag cgccccacag ctggccccac aggtcccccc tcagctggcc ccacaggtcc 3060ccccactgct ggcccttcta cggccactac tgtgcctttg agtccggtgg acgatgcctg 3120caacgtgaac atcttcgacg ccatcgcgga gattgggaac cagctgtatt tgttcaagga 3180tgggtgagga ggcggggttg tgtggatgcg ggagggggct ttgcggaggg gctgcccgtc 3240ccttcccgcc cactggccct gtgtccaagg cttagagccc gtcctttccc tcctcgcttt 3300ctcaggaagt actggcgatt ctctgagggc agggggagcc ggccgcaggg ccccttcctt 3360atcgccgaca agtggcccgc gctgccccgc aagctggact cggtctttga ggagcggctc 3420tccaagaagc ttttcttctt ctctggttag ttacctactt tccctccccc gcccggtcaa 3480tccccatcag tcaaggaggc tcaagagacc atcgataacc cacgaaacgt cttgtgcgtt 3540ttagaaaaat acgccccctg gcggacgcag tttagcaaac gtaggggcgg ctgagtttct 3600gccccctcct ctccacgccc tcgcgtcgct ctacccagcg cctctgcccc tgggttgcag 3660ggactgcggg cacgcgggct aggaaaggcc tcgccggaat ctccctcctc gcgttctagg 3720agtacgtgct ccctctgcgc ccccaaaccg acgtgaccct cctcccctgc agggcgccag 3780gtgtgggtgt acacaggcgc gtcggtgctg ggcccgaggc gtctggacaa gctgggcctg 3840ggagccgacg tggcccaggt gaccggggcc ctccggagtg gcagggggaa gatgctgctg 3900ttcagcgggc ggcgcctctg gaggtgagcg ccgccgcggc cgccggcagg gggagcccgg 3960gcgccgtcgg tccgtccgct agccggctca gcacctgtct cctccgcgcc tgcccgcagg 4020ttcgacgtga aggcgcagat ggtggatccc cggagcgcca gcgaggtgga ccggatgttc 4080cccggggtgc ctttggacac gcacgacgtc ttccagtacc gaggtgaggg ctgaggagga 4140tcccttcgtg agacaccaca ctaagctcct cttagtgagt ggtcaaattc tgagcgagga 4200agaaaaagcc cttggaaatg gaaacaaatg ccccagcaca gacaagatcc cagcagaggc 4260agaggccttc tccaggtcat ttaggaagtc agggatgcaa c 4301198801DNAHomo sapiens 198caggaacttt cgagatgagg tgcctttccc aaggtgacac taagtggagg agcccagcca 60gagtccaggg gtccttacac aaccttcggt ggtctctctt tacctgtgaa gctgcagcct 120gcttcccagc tcgggggcgt gtacaggaga ctggacctgg ggcagcctca gaatgcctgg 180ctgcctggag ctctcctcgc gtgtccaggc ggcctgcttg gtctccctcc tctcccctct 240taggtgccgg ggcgggcacc cggtgcaggg tgggcacggc gcctgccacc agcctcaggc 300gctgggagaa gcgcaggttc ttctggataa ccgaagagac gtcaaaacag gctggggcaa 360agtggtcaga gcagatgacc gagcggtcat tgcctccgta ccagtcggcg cggcaacccc 420gcacgaagcg gtcccagagc agccgcacgg cccggtcctt gggaaagcgg aacagcgact 480tcccagactt ggtggtgttg ccgcagtggg cggccacaca acgggccggc atggcggccg 540tcttcggtgc gcgggagccg ggttccctgg accttcgccc ttgggcacgc tcctcgcagc 600ggcctcggcg aggcaagtcc tcccctcctc acctgtccac tccgggtcgg gattgtttcc 660ttccctacct ctggtcaccg gaagtggcga tctggggccc ccaatgggag ggctctttga 720tatcttcctc ctcctcctcc ctgcgctgct ccccaggagc cagtggacac aagcagaggg 780atacaaattt cgcgcgggca g 80119924DNAArtificialPrimer 199tgatggtcgt attgcgggtt tatc 2420024DNAArtificialPrimer 200atacctaaac ccaacgccga ctac 2420124DNAArtificialPrimer 201cgcgatttga gtagttagcg tcgt 2420224DNAArtificialPrimer 202aaccaacgcg acgacctaac taac 2420323DNAArtificialPrimer 203tagatttcgg tgtttcgggc gtt 2320426DNAArtificialPrimer 204ccgctaattc ccaatcgtac tactca 2620522DNAArtificialPrimer 205ttcgtttcgt tcggtcgtga tt 2220624DNAArtificialPrimer 206gactacgaac gcttcgaatt cctc 2420724DNAArtificialPrimer 207gttgcgttgg tagcgattcg ttgt 2420823DNAArtificialPrimer 208cccgaaccga atcctcgaaa tct 2320925DNAArtificialPrimer 209gacgtagtat gatgcgcgta gtgtg 2521023DNAArtificialPrimer 210gcgaacatac taaacccgaa ccc 2321124DNAArtificialPrimer 211ggattacgtc ggtgttcgat ttgt 2421222DNAArtificialPrimer 212aacgcacgat taaccctacg cc 2221324DNAArtificialPrimer 213tcggattaag gtaggcgtgg tttc 2421421DNAArtificialPrimer 214aacgtaaacg ccgaaccgaa c 2121524DNAArtificialPrimer 215ggaagacgtc gttgttgatg gttt 2421623DNAArtificialPrimer 216accgctccga cacgaaccta tac 2321723DNAArtificialPrimer 217agcgttatgc gtcgcgttag tag 2321822DNAArtificialPrimer 218gcaaacgacg acgaaacgta ca 2221923DNAArtificialPrimer 219gaagagagcg ggttcgggat aag 2322023DNAArtificialPrimer 220ctacaacatc gtaaacgcgc gac 2322122DNAArtificialPrimer 221gagaagagga aggtagaagg ag 2222221DNAArtificialPrimer 222ctacctaact ataaccaacc c 2122321DNAArtificialPrimer 223acggaggagg atagtagtac g 2122426DNAArtificialPrimer 224aggtaygttg tatttggtgg atttgg 2622521DNAArtificialPrimer 225cccacctaca acaacaacac c 2122620DNAArtificialPrimer 226gaacgcgtac ggaaggtagg 2022727DNAArtificialPrimer 227gtgataggtt tgtagatttg atagttg 2722825DNAArtificialPrimer 228aactaacctc cattttaact atttc 2522923DNAArtificialPrimer 229gagagatgaa tttggatatt agt 2323024DNAArtificialPrimer 230ggtaaattgg tgtygttgga gaag 2423123DNAArtificialPrimer 231actaaacaat aatacccrac ctc 2323224DNAArtificialPrimer 232gtcgttgggt tcggtttcgt tttg 24

Claims

1. A method of detecting the methylation status of one or more CpG islands indicative of cancer, which method comprises:providing a biological sample from a subject in need of cancer evaluation; andassaying the biological sample for methylation of a CpG island associated with at least one gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), kinesin family member 13B (KIF13B), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (predicted protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1A), ring finger protein 180 (RNF180), EGFR-co-amplified and overexpressed (DKFZP564K0822 or ECOP), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein C8orf79 (C8orf79/FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC286097/EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), matrix metallopeptidase 9 (MMP9), leucine rich repeat containing 49 (LRRC49), tumor necrosis factor (ligand) superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), Kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), wherein methylation of the assayed CpG island is indicative of cancer.

2. A method of detecting the methylation status of one or more CpG islands indicative of prostate cancer, which method comprisesproviding a biological sample from a male mammal in need of prostate cancer evaluation; andassaying the biological sample for methylation of a CpG island associated with at least one gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), kinesin family member 13B (KIF13B), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), flbroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671 or RNF180), EGFR-co-amplified and overexpressed (DKFZP5640822 or ECOP), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-.beta. signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), and transcription factor LIM homeodomain (ISL2), matrix metallopeptidase 9 (MMP9), leucine rich repeat containing 49 (LRRC49), tumor necrosis factor (ligand) superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), Kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), Ras association (RalGDS/AF-6) domain family 5 (RASSF5), and HtrA serine peptidase 4 (HTRA4); andoptionally, further assaying the biological sample for methylation of a CpG island associated with at least one gene that is known to be methylated in prostate cancer and that is known not to be detectably methylated or methylated at a lower level in benign prostate hyperplasia (BPH); wherein methylation of the assayed CpG island or islands is indicative of prostate cancer.

3. The method of claim 2, wherein the method comprises:assaying the biological sample for methylation of CpG islands associated with at least three genes, at least one of the genes being selected from the group consisting of neuregulin cell-surface ligand (NRG1), kinesin family member 13B (KIF13B), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671 or RNF180), EGFR-co-amplified and overexpressed (DKFZP5640822 or ECOP), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097 or EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-.beta. signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), and transcription factor LIM homeodomain (ISL2);the CpG island associated with a gene that is known to be methylated in prostate cancer is also known to be not methylated in BPH or methylated at a level of about 10% or less in BPH; andwherein methylation of the CpG islands associated with the at least three genes is indicative of prostate cancer;

4. The method of claim 2, wherein the at least one CpG island that is known to be methylated in prostate cancer and that is known to be unmethylated or methylated at a lower level in BPH is or includes one or more CpG island associated with glutathione S-transferase P1 (GSTP1), glutathione peroxidase 3 (GPX3), glutathione S-transferase M1 (GSTM1), Cub and Sushi multiple domains1 (CSMD1), tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), tumor necrosis factor receptor superfamily 10D (TNFRSF10D), secreted frizzled-related protein 1 (SFRP1), secreted frizzled-related protein 2 (SFRP2), dickkopf homolog 3 (DKK3), prostaglandin-endoperoxide synthase 2 (PTGS2), cyclin-dependent kinase inhibitor 1C (CDKN1C/p57), Ras association (RalGDS/AF-6) domain family 1 (RASSF1), G-protein coupled receptor 62 (GPR62).

5. The method of claim 4, wherein the at least one CpG island that is known to be methylated in prostate cancer and that is known to be unmethylated or methylated at a lower level in BPH is or includes one or more CpG island associated with glutathione S-transferase P1 (GSTP1).

6. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 4 genes.

7. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 5 genes.

8. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 6 genes.

9. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 7 genes.

10. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 8 genes.

11. The method of claim 1, wherein the method comprises assaying for methylation of CpG islands associated with at least 9 genes.

12. The method of claim 1, wherein the assaying for methylation of a CpG island comprises amplifying a target sequence that includes at least one CpG dinucleotide in a target sequence selected from the group consisting of (a) SEQ ID NO: 1 and 2 [NRG1], SEQ ID NO: 3 and 4 [ADRB3], SEQ ID NO: 5 and 6 [GFRA2], SEQ ID NO: 7 and 8 [KIF13B], SEQ ID NO: 9 and 10 [RET], SEQ ID NO: 11 and 12 [GPR147], SEQ ID NO: 13 and 14 [NEUROG3], SEQ ID NO: 15 and 16 [PALD], SEQ ID NO: 17 and 18 [HEMK1], SEQ ID NO: 19 and 20 [FGF4], SEQ ID NO: 21 and 22 [GPR62], SEQ ID NO: 23 and 24 [HTR1A], SEQ ID NO: 25 and 26 [RNF180], SEQ ID NO: 27 and 28 [DKFZP5640822], SEQ ID NO: 29 and 30 [ZNF596], SEQ ID NO: 33 and 34 [LOC441320], SEQ ID NO: 35 and 36 [TDK], SEQ ID NO: 37 and 38 [FLJ36980], SEQ ID NO: 39 and 40 [FGF20], SEQ ID NO: 41 and 42 [EFHA2], SEQ ID NO: 43 and 44 [ASAH1], SEQ ID NO: 49 and 50 [NODAL], SEQ ID NO: 51 and 52 [LOC399783], SEQ ID NO: 53 and 54 [ISL2] and (b) fully or partially methylated derivatives of (a).

13. The method of claim 1, wherein the assaying for methylation of a CpG island comprises amplifying a target sequence that includes at least one CpG dinucleotide or a deaminated derivative thereof in a target sequence selected from the group consisting of (a) SEQ ID NOS: 119 and 220 [KIFC2], SEQ ID NOS: 121 and 122 [C20ORF23], SEQ ID NOS: 123 and 124 [GFRA1], SEQ ID NOS: 129 and 130 [DKK2], SEQ ID NOS: 135 and 136 [NTN1], SEQ ID NO: 195 [RHOD], SEQ ID NO: 196[TNFSF11], SEQ ID NO: 197 [MMP9], and SEQ ID NO: 198 [LRRC49] (b) fully or partially methylated cytosine derivatives of (a), and (c) deaminated derivatives of (b).

14. The method of claim 2, wherein the assaying for methylation of a CpG island comprises amplifying a target sequence that includes at least one CpG dinucleotide or a deaminated derivative thereof in a target sequence selected from the group consisting of (a) SEQ ID NOS: 119 and 220 [KIFC2], SEQ ID NOS: 121 and 122 [C20ORF23], SEQ ID NOS: 123 and 124 [GFRA1], SEQ ID NOS: 129 and 130 [DKK2], SEQ ID NOS: 135 and 136 [NTN1], SEQ ID NOS: 133 and 134 [RASSF5] and SEQ ID NOS: 193 and 194 [HTRA4], (b) fully or partially methylated cytosine derivatives of (a), and (c) deaminated derivatives of (b).

15. The method of claim 12, wherein the assaying for methylation comprises performing terminator-coupled linear amplification in the presence of at least one dideoxynucleotide and determining the size of the amplified fragments to thereby determine the methylation status of the cytidine residues.

16. The method of claim 15, wherein the assaying comprises performing linear amplification in the presence of only one dideoxynucleotide.

17. The method of claim 15, wherein the assaying comprises performing linear amplification in the presence of only two dideoxynucleotides.

18. The method of claim 15, wherein the at least one dideoxynucleotide is chosen from the group consisting of dideoxyadenine, dideoxcytidine, dideoxguanine, and dideoxthymidine.

19. A terminator-coupled linear amplification method of determining the methylation status of a CpG island, wherein the method comprises(a) providing a DNA sample;(b) incubating the DNA sample under deaminating conditions to thereby produce a deaminated DNA sample;(c) optionally, purifying the deaminated DNA sample;(d) amplifying a target sequence or target sequences that include one or more CpG islands or portions of one or more CpG islands to thereby produce one or more amplified target sequences;(e) optionally, purifying the one or more amplified target sequences;(f) linearly amplifying the one or more amplified target sequences of step (d) or (e) in the presence of a primer and 1 to 3 dideoxynucleotides to generate one or more fragments of different lengths, wherein each length corresponds to the distance in bases from the 5' end of the primer to the position where the dideoxynucleotide was incorporated;(g) optionally, purifying the one or more fragments; and(h) analyzing the one or more fragments to determine their lengths and thereby determine the methylation status of methylated cytosines within the one or more amplified target sequences.

20. A pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49).

21. A set of primers comprising:(i) at least one pair of primers of claim 20; and(ii) at least one pair of primers suitable for amplifying at least a portion of a CpG island associated with at least one other gene that is known to be methylated in prostate cancer but not methylated or methylated at a low level in BPH.

22. A set of primers comprising:(i) a first pair of primers of claim 20; and(ii) a second pair of primers of claim 20, wherein the second pair of primers is suitable for amplifying at least a portion of a different CpG island than the first pair of primers.

23. The set of primers of claim 22, wherein the CpG island amplified by the first pair of primers is associated with a first gene, the CpG island amplified by the second pair of primers is associated with a second gene, and the first and second genes are different genes.

24. The set of primers of claim 21, wherein the set further comprises a third pair of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), flbroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer but not methylated or methylated at a low level in BPH, wherein the third pair of primers is suitable for amplifying a different CpG island than that suited for amplification by the first or second pair of primers.

25. The set of primers of claim 24, wherein the set further comprises a fourth pair of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer but not methylated or methylated at a low level in BPH, wherein the third pair of primers is suitable for amplifying a different CpG island than that suited for amplification by the first, second, or third pair of primers.

26. The set of primers of claim 25, wherein the set further comprises a fifth pair of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), flbroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), flbroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer but not methylated or methylated at a low level in BPH, wherein the third pair of primers is suitable for amplifying a different CpG island than that suited for amplification by the first, second, third, or fourth pair of primers.

27. The set of primers of claim 26, wherein the set further comprises a sixth pair of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), flbroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer, wherein the fourth pair of primers is suitable for amplifying a different CpG island than that suited for amplification by the first, second, third, fourth or fifth pair of primers.

28. The set of primers of claim 27, wherein the set further comprises from one to four additional pairs of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), fibroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), fibroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer, wherein each pair of primers in the set amplifies a different CpG island.

29. The set of primers of claim 28, wherein the set further comprises one or more additional pairs of primers selected from the group consisting of(i) a pair of primers suitable for amplifying at least a portion of one or more CpG-islands associated with a gene selected from the group consisting of neuregulin cell-surface ligand (NRG1), adrenergic B3 receptor (ADRB3), glycosylphosphatidylinositol cell-surface receptor (GFRA2), kinesin family member 13B (KIF13B), RET proto-oncogene (RET), G-protein-coupled protein receptor 147 (GPR147), neurogenin 3 transcription factor (NEUROG3), paladin (protein tyrosine phosphatase) (PALD), methyltransferase family member 1 (HEMK1), flbroblast growth factor 4 oncogene (FGF4), 5-hydroxytryptamine (serotonin) receptor 1A (HTR1 A), ring finger protein 180 (LOC 285671) (RNF180), EGFR-co-amplified and overexpressed (ECOP) (DKFZP5640822), zinc finger protein 596 (ZNF596), similar to 7 transmembrane helix receptor (LOC441320), L-threonine dehydrogenase (TDH), hypothetical protein FLJ36980 (FLJ36980), flbroblast growth factor receptor 20 (FGF20), EF-hand domain family member 2A (LOC2 86097) (EFHA2), N-acylsphingosine amidohydrolase (acid ceraminase) 1 (ASAH1), nodal homolog (TGF-B signaling pathway) (NODAL), hypothetical protein similar to zinc finger protein 532 (LOC399783), transcription factor LIM homeodomain (ISL2), kinesin family member C2 (KIFC2), chromosome 20 open reading frame 23 (Kinesin-like motor protein) (C20orf23), GDNF family receptor alpha 1 (GFRA1), Glutathione peroxidase 7 (GPX7), Dickkopf homolog 2 (DKK2), netrin 1 (NTN1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor superfamily member 11 (TNFSF11), ras homolog gene family member D (RHOD), and leucine rich repeat containing 49 (LRRC49), and(ii) a pair of primers suitable for amplifying a CpG island known to be methylated in prostate cancer, wherein each pair of primers in the set amplifies a different CpG island.

30. A pair of primers or set of primers of claim 20, wherein the pair or set of primers have sequences selected from the group consisting of SEQ ID NOs: 55 to 118.

31. The primer or set of primers of claim 20, wherein the pair of primers or the set of primers includes two primers suitable for amplifying a CpG island associated with NRG1 or KIF13b.

32. The primer or set of primers of claim 20, wherein the pair of primers or the set of primers includes two primers suitable for amplifying a CpG island associated with TDH, ASAH1, FGF20, HEMK1, PALD NEUROG, EFHA2, KIFC2, GFRA1, DKK2, TNFSF11, NTN1, or RHOD.

33. A kit for detecting the methylation status of a CpG island indicative of cancer, the kit comprising:(i) a pair of primers or set of primers of claim 20; and(ii) instructions for using the primers to amplify at least one CpG island from a biological sample.

34. The kit of claim 33, further comprising a buffer selected from the group consisting of (a) a buffer for amplifying genomic DNA, (b) a buffer for preparing genomic DNA from a biological sample, and (c) a buffer for preparing genomic DNA from plasma or urine.