Patent application title: MAMMALIAN GENES INVOLVED IN VIRAL INFECTION AND TUMOR SUPPRESSION
Inventors:
Donald H. Rubin (Nashville, TN, US)
Edward L. Organ (Nashville, TN, US)
Raymond N. Dubois (Franklin, TN, US)
IPC8 Class: AA61K39395FI
USPC Class:
4241301
Class name: Drug, bio-affecting and body treating compositions immunoglobulin, antiserum, antibody, or antibody fragment, except conjugate or complex of the same with nonimmunoglobulin material
Publication date: 2009-04-09
Patent application number: 20090092594
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Patent application title: MAMMALIAN GENES INVOLVED IN VIRAL INFECTION AND TUMOR SUPPRESSION
Inventors:
Donald H. Rubin
Edward L. Organ
Raymond N. Dubois
Agents:
Ballard Spahr Andrews & Ingersoll, LLP
Assignees:
Origin: ATLANTA, GA US
IPC8 Class: AA61K39395FI
USPC Class:
4241301
Abstract:
The present invention provides methods of identifying cellular genes
necessary for viral growth and cellular genes that function as tumor
suppressors. Thus, the present invention provides nucleic acids related
to and methods of reducing or preventing viral infection or cancer. The
invention also provides methods of producing substantially virus-free
cell cultures and methods for screening for additional such genes.Claims:
1. An isolated nucleic acid comprising a nucleotide sequence set forth in
SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, 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:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ
ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID
NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID
NO:35, SEQ ID NO:36, 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:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID
NO:51, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID
NO:59, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:66, SEQ ID
NO:67, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:73, SEQ ID
NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID
NO:80, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID
NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:91, SEQ ID
NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID
NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID
NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ
ID NO:112, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123,
SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, and SEQ ID NO:127.
2-5. (canceled)
6. A host cell containing the nucleic acid of claim 1.
7. A nucleic acid comprising a nucleic acid that selectively hybridizes under stringent conditions with the nucleic acid of claim 1.
8-13. (canceled)
14. A polypeptide comprising the amino acid sequence encoded by the nucleic acid of claim 1.
15-16. (canceled)
17. A method of reducing or inhibiting a viral infection in a subject, comprising administering to the subject an amount of a composition that inhibits expression or functioning of a gene product encoded by a gene comprising the nucleic acid set forth 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: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:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, 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:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82; SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, or SEQ ID NO:127 or a homolog thereof, thereby treating the viral infection.
18-23. (canceled)
24. A method of screening a compound for effectiveness in treating or preventing a viral infection, comprising administering the compound to a cell containing a cellular gene comprising the nucleic acid set forth 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: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:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, 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:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82; SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, or SEQ ID NO:127, or a homolog thereof, and functionally encoding a gene product necessary for reproduction of the virus in the cell but not necessary for survival of the cell and detecting the level and/or activity of the gene product produced, a decrease or elimination of the gene product and/or gene product activity indicating a compound effective for treating or preventing the viral infection.
25-29. (canceled)
Description:
[0001]This application is a continuation of U.S. application Ser. No.
10/877,807, filed Jun. 25, 2004 which is a continuation of U.S.
application Ser. No. 09/509,712, filed Mar. 31, 2000 (now U.S. Pat. No.
6,777,177) which is the National Stage of International Application No.
PCT/US98/21276, filed Oct. 8, 1998 which is a continuation of U.S.
Application No. 60/062,021, filed Oct. 10, 1997 and also a
continuation-in-part of U.S. application Ser. No. 10/228,794 filed Aug.
27, 2002 which is a divisional of U.S. application Ser. No. 09/171,209
(now U.S. Pat. No. 6,448,000) filed Mar. 8, 1999 which is the National
Stage of International Application No. PCT/US97/06067 filed Apr. 11,
1997, which is a continuation of U.S. Application No. 60/015,334 filed
Apr. 15, 1996 which are all hereby incorporated by reference in their
entireties.
BACKGROUND
[0003]1. Field of the Invention
[0004]The present invention provides methods of identifying cellular genes used for viral growth or for tumor progression. Thus, the present invention relates to nucleic acids related to and methods of reducing or preventing viral infection and for suppressing tumor progression. The invention also relates to methods for screening for additional such genes.
[0005]2. Background Art
[0006]Various projects have been directed toward isolating and sequencing the genome of various animals, notably the human. However, most methodologies provide nucleotide sequences for which no function is linked or even suggested, thus limiting the immediate usefulness of such data.
[0007]The present invention, in contrast, provides methods of screening only for nucleic acids that are involved in a specific process, i.e., viral infection or tumor progression. For viral infection, the nucleic acids isolated are useful in treatments for these processes because by this method only nucleic acids which are also nonessential to the cell are isolated. Such methods are highly useful, since they ascribe a function to each isolated gene, and thus the isolated nucleic acids can immediately be utilized in various specific methods and procedures.
[0008]For, example, the present invention provides methods of isolating nucleic acids encoding gene products used for viral infection, but nonessential to the cell. Viral infections are significant causes of human morbidity and mortality. Understanding the molecular mechanisms of such infections will lead to new approaches in their treatment and control.
[0009]Viruses can establish a variety of types of infection. These infections can be generally classified as lytic or persistent, though some lytic infections are considered persistent. Generally, persistent infections fall into two categories: (1) chronic (productive) infection, i.e., infection wherein infectious virus is present and can be recovered by traditional biological methods and (2) latent infection, i.e., infection wherein viral genome is present in the cell but infectious virus is generally not produced except during intermittent episodes of reactivation. Persistence generally involves stages of both productive and latent infection.
[0010]Lytic infections can also persist under conditions where only a small fraction of the total cells are infected (smoldering (cycling) infection). The few infected cells release virus and are killed, but the progeny virus again only infect a small number of the total cells. Examples of such smoldering infections include the persistence of lactic dehydrogenase virus in mice (Mahy, B. W. J., Br. Med. Bull. 41: 50-55 (1985)) and adenovirus infection in humans (Porter, D. D. pp. 784-790 in Baron, S., ed. Medical Microbiology 2d ed. (Addison-Wesley, Menlo Park, Calif. 1985)).
[0011]Furthermore, a virus may be lytic for some cell types but not for others. For example, evidence suggests that human immunodeficiency virus (HIV) is more lytic for T cells than for monocytes/macrophages, and therefore can result in a productive infection of T cells that can result in cell death, whereas HIV-infected mononuclear phagocytes may produce virus for considerable periods of time without cell lysis. (Klatzmann, et al. Science 225:59-62 (1984); Koyanagi, et al. Science 241:1673-1675 (1988); Sattentau, et al. Cell 52:631-633 (1988)).
[0012]Traditional treatments for viral infection include pharmaceuticals aimed at specific virus derived proteins, such as HIV protease or reverse transcriptase, or recombinant (cloned) immune modulators (host derived), such as the interferons. However, the current methods have several limitations and drawbacks which include high rates of viral mutations which render anti-viral pharmaceuticals ineffective. For immune modulators, limited effectiveness, limiting side effects, a lack of specificity all limit the general applicability of these agents. Also the rate of success with current antivirals and immune-modulators has been disappointing.
[0013]One aspect of the current invention focuses on isolating genes that are not essential for cellular survival when disrupted in one or both alleles, but which are required for virus replication. This may occur with a dose effect, in which one allele knock-out may confer the phenotype of virus resistance for the cell. As targets for therapeutic intervention, inhibition of these cellular gene products, including: proteins, parts of proteins (modification enzymes that include, but are not restricted to glycosylation, lipid modifiers [myriolate, etc.]), lipids, transcription elements and RNA regulatory molecules, may be less likely to have profound toxic side effects and virus mutation is less likely to overcome the `block` to replicate successfully.
[0014]The present invention provides a significant improvement over previous methods of attempted therapeutic intervention against viral infection by addressing the cellular genes required by the virus for growth. Therefore, the present invention also provides an innovative therapeutic approach to intervention in viral infection by providing methods to treat viruses by inhibiting the cellular genes necessary for viral infection. Because these genes, by virtue of the means by which they are originally detected, are nonessential to the cell's survival at a level of expression necessary to inhibit virus replication, these treatment methods can be used in a subject without serious detrimental effects to the subject, as has been found with previous methods. The present invention also provides the surprising discovery that virally infected cells are dependent upon a factor in serum to survive. Therefore, the present invention also provides a method for treating viral infection by inhibiting this serum survival factor. Finally, these discoveries also provide a novel method for removing virally infected cells from a cell culture by removing, inhibiting or disrupting this serum survival factor in the culture so that non-infected cells selectively survive.
[0015]The selection of tumor suppressor gene(s) has become an important area in the discovery of new target for therapeutic intervention of cancer. Since the discovery that cells are restricted from promiscuous entry into the cell cycle by specific genes that are capable of suppressing a `transformed` phenotype, considerable time has been invested in the discovery of such genes. Some of these genes include the gene associated by rhabdomyosarcoma (Rb) and the p53 (apoptosis related) encoding gene. The present invention provides a method, using gene-trapping, to select cell lines that have a transformed phenotype from cells that are not transformed and to isolate from these cells a gene that can suppress a malignant, or transformed, phenotype. Thus, by the nature of the isolation process, a function is associated with the isolated genes. The capacity to select quickly tumor suppressor genes can provide unique targets in the process of treating or preventing, and even for diagnostic testing of, cancer.
DETAILED DESCRIPTION OF THE INVENTION
[0016]The present invention utilizes a "gene trap" method along with a selection process to identify and isolate nucleic acids from genes associated with a particular function. Specifically, it provides a means of isolating cellular genes necessary for viral infection but not essential for the cell's survival, and it provides a means of isolating cellular genes that suppress tumor progression.
[0017]The present invention also provides a core discovery that virally infected cells become dependent upon at least one factor present in serum for survival, whereas non-infected cells do not exhibit this dependence. This core discovery has been utilized in the present invention in several ways. First, inhibition of the "serum survival factor" can be utilized to eradicate persistently virally infected cells from populations of non-infected cells. Inhibition of this factor can also be used to treat virus infection in a subject, as further described herein. Additionally, inhibition of or withdrawal of the serum survival factor in tissue culture allows for the detection of cellular genes required for viral replication yet nonessential for an uninfected cell to survive. The present invention further provides several such cellular genes, as well as methods of treating viral infections by inhibiting the functioning of such genes.
[0018]The invention also provides cellular genes whose overexpression is associated with inhibition of viral growth and/or reproduction.
[0019]The present method provides several cellular genes that are necessary for viral growth in the cell but are not essential for the cell to survive. These genes are important for lytic and persistent infection by viruses. These genes were isolated by generating gene trap libraries by infecting cells with a retrovirus gene trap vector, selecting for cells in which a gene trap event occurred (i.e., in which the vector had inserted such that the promoterless marker gene was inserted such that a cellular promoter promotes transcription of the marker gene, i.e., inserted into a functioning gene), starving the cells of serum, infecting the selected cells with the virus of choice while continuing serum starvation, and adding back serum to allow visible colonies to develop, which colonies were cloned by limiting dilution. Genes into which the retrovirus gene trap vector inserted were then isolated from the colonies using probes specific for the retrovirus gene trap vector. Thus nucleic acids isolated by this method are isolated portions of genes. Additionally, utilizing this method, several cellular genes were isolated whose overexpression prevents viral infection or tumor growth, and they provide methods of treating viral infection or tumor growth/suppression by overexpression of these genes.
[0020]Thus the present invention provides a method of identifying a cellular gene necessary for viral growth in a cell and nonessential for cellular survival, comprising (a) transferring into a cell culture, e.g. growing in serum-containing medium, a vector encoding a selective marker gene lacking a functional promoter, (b) selecting cells expressing the marker gene, (c) removing serum from the culture medium, (d) infecting the cell culture with the virus, and (e) isolating from the surviving cells a cellular gene within which the marker gene is inserted, thereby identifying a gene necessary for viral growth in a cell and nonessential for cellular survival. The present invention also provides a method of identifying a cellular gene used for viral growth in a cell and nonessential for cellular survival, comprising (a) transferring into a cell culture growing in serum-containing medium a vector encoding a selective marker gene lacking a functional promoter, (b) selecting cells expressing the marker gene, (c) removing serum from the culture medium, (d) infecting the cell culture with the virus, and (e) isolating from the surviving cells a cellular gene within which the marker gene is inserted, thereby identifying a gene necessary for viral growth in a cell and nonessential for cellular survival or a gene whose overexpression prevents viral reproduction but is not fatal to the survival to the cell. In any selected cell type, such as Chinese hamster ovary cells, one can readily determine if serum starvation is required for selection. If it is not, serum starvation may be eliminated from the steps.
[0021]Alternatively, instead of removing serum from the culture medium, a serum factor required by the virus for growth can be inhibited, such as by the administration of an antibody that specifically binds that factor. Furthermore, if it is believed that there are no persistently infected cells in the culture, the serum starvation step can be eliminated and the cells grown in usual medium for the cell type. If serum starvation is used, it can be continued for a time after the culture is infected with the virus. Serum can then be added back to the culture. If some other method is used to inactivate the factor, it can be discontinued, inactivated or removed (such as removing the anti-factor antibody, e.g., with a bound antibody directed against that antibody) prior to adding fresh serum back to the culture. Cells that survive are mutants having an inactivating insertion in a gene necessary for growth of the virus. The genes having the insertions can then be isolated by isolating sequences having the marker gene sequences. This mutational process disturbs a wild type function. A mutant gene may produce at a lower level a normal product, it may produce a normal product not normally found in these cells, it may cause the overproduction of a normal product, it may produce an altered product that has some functions but not others, or it may completely disrupt a gene function. Additionally, the mutation may disrupt an RNA that has a function but is never translated into a protein. For example, the alpha-tropomyosin gene has a 3' RNA that is very important in cell regulation but never is translated into protein. (Cell 75 pg 1107-1117, Dec. 17, 1993).
[0022]As used herein, a cellular gene "nonessential for cellular survival" means a gene for which disruption of one or both alleles results in a cell viable for at least a period of time which allows viral replication to be inhibited for preventative or therapeutic uses or use in research. A gene "necessary for viral growth" means the gene product, either protein or RNA, secreted or not, is necessary or beneficial, either directly or indirectly in some way for the virus to grow, and therefore, in the absence of that gene product (i.e., a functionally available gene product), the virus does not spread. For example, such genes can encode cell cycle regulatory proteins, proteins affecting the vacuolar hydrogen pump, or proteins involved in protein folding and protein modification, including but not limited to: phosphorylation, methylation, glycosylation, myristylation or other lipid moiety, or protein processing via enzymatic processing. Some examples of such genes include vacuolar H+ATPase, alpha tropomyosin, gas5 gene, ras complex, N-acetyl-glucosaminy-1-transferase I mRNA, annexin II, c-golgi CM130 and calcyclin.
[0023]Any virus capable of infecting the cell can be used for this method. Virus can be selected based upon the particular infection desired to study. However, it is contemplated by the present invention that many viruses will be dependent upon the same cellular genes for survival; thus a cellular gene isolated using one virus can be used as a target for therapy for other viruses as well. Any cellular gene can be tested for relevancy to any desired virus using the methods set forth herein, i.e., in general, by inhibiting the gene or its gene product in a cell and determining if the desired virus can grow in that cell. Some examples of viruses include HIV (including HIV-1 and HIV-2); parvovirus; papillomaviruses; hantaviruses; influenza viruses (e.g., influenza A, B and C viruses); hepatitis viruses A to G; caliciviruses; astroviruses; rotaviruses; coronaviruses, such as human respiratory coronavirus; picornaviruses, such as human rhinovirus and enterovirus; ebola virus; human herpesvirus (e.g., HSV-1-9); human adenovirus; for animal, the animal counterpart to any above listed human virus, animal retroviruses, such as simian immunodeficiency virus, avian immunodeficiency virus, bovine immunodeficiency virus, feline immunodeficiency virus, equine infectious anemia virus, caprine arthritis encephalitis virus, arenaviruses, arvoviruses, tickborne viruses or visna virus.
[0024]The nucleic acids comprising cellular genes of this invention were isolated by the above method and as set forth in the examples. The invention includes a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, 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:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, 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:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, and SEQ ID NO: 127 (this list is sometimes referred to herein as "SEQ LIST 1" for brevity). Thus these nucleic acids can contain, in addition to the nucleotides set forth in each SEQ ID NO in the sequence listing, additional nucleotides at either end of the molecule. Such additional nucleotides can be added by any standard method, as known in the art, such as recombinant methods and synthesis methods. Examples of such nucleic acids comprising the nucleotide sequence set forth in any entry of the sequence listing contemplated by this invention include, but are not limited to, for example, the nucleic acid placed into a vector; a nucleic acid having one or more regulatory region (e.g., promoter, enhancer, polyadenylation site) linked to it, particularly in functional manner, i.e. such that an mRNA or a protein can be produced; a nucleic acid including additional nucleic acids of the gene, such as a larger or even full length genomic fragment of the gene, a partial or full length cDNA, a partial or full length RNA. Making and/or isolating such larger nucleic acids is further described below and is well known and standard in the art.
[0025]Also provided in this invention are the double-stranded nucleic acids corresponding to the nucleic acid sequences set forth in SEQ ID 1 through SEQ ID 136, inclusive. It is recognized that "nucleic acid" as used herein, can refer to either or both strands of such double-stranded nucleic acids, such strands often referred to as the "positive" and "negative" strands. Either strand of such double-stranded nucleic acids may encode the polypeptides of this invention, and the coding sequences for such polypeptides may be translated in either direction along the strand. Examples of polypeptides encoded by either strand are disclosed herein.
[0026]The invention also provides a nucleic acid encoding the protein encoded by the gene comprising the nucleotide sequence set forth in any of the sequences listed in SEQ LIST 1, as well as allelic variants and homologs of each such gene. The gene is readily obtained using standard methods, as described below and as is known and standard in the art. The present invention also contemplates any unique fragment of these genes or of the nucleic acids set forth in any of the sequences listed in SEQ LIST 1. Examples of inventive fragments of the inventive genes can include the nucleic acids whose sequence is set forth in any of the sequences listed in SEQ LIST 1. To be unique, the fragment must be of sufficient size to distinguish it from other known sequences, most readily determined by comparing any nucleic acid fragment to the nucleotide sequences of nucleic acids in computer databases, such as GenBank. Such comparative searches are standard in the art. Typically, a unique fragment useful as a primer or probe will be at least about 20 to about 25 nucleotides in length, depending upon the specific nucleotide content of the sequence. Additionally, fragments can be, for example, at least about 30, 40, 50, 75, 100, 200 or 500 nucleotides in length. The nucleic acids can be single or double stranded, depending upon the purpose for which it is intended.
[0027]The present invention further provides a nucleic acid comprising the regulatory region of a gene comprising any one of the nucleotide sequences set forth in SEQ LIST 1, as well as homologs of each such gene. Additionally provided is a construct comprising such a regulatory region functionally linked to a reporter gene. Such reporter gene constructs can be used to screen for compounds and compositions that affect expression of the gene comprising the nucleic acids whose sequence is set forth in SEQ LIST 1, or any homologs thereof.
[0028]The nucleic acids set forth in the sequence listing are gene fragments; the entire coding sequence and the entire gene that comprises each fragment are both contemplated herein and are readily obtained by standard methods, given the nucleotide sequences presented in the sequence listing (see. e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989; DNA cloning. A Practical Approach, Volumes I and II, Glover, D. M. ed., IRL Press Limited, Oxford, 1985). To obtain the entire genomic gene, briefly, a nucleic acid whose sequence is set forth in any of SEQ ID NO: 1 through SEQ ID NO: 127, or preferably in any of the sequences listed in SEQ LIST 1, or a smaller fragment thereof, is utilized as a probe to screen a genomic library under high stringency conditions, and isolated clones are sequenced. Once the sequence of the new clone is determined, a probe can be devised from a portion of the new clone not present in the previous fragment and hybridized to the library to isolate more clones containing fragments of the gene. In this manner, by repeating this process in organized fashion, one can "walk" along the chromosome and eventually obtain nucleotide sequence for the entire gene. Similarly, one can use portions of the present fragments, or additional fragments obtained from the genomic library, that contain open reading frames to screen a cDNA library to obtain a cDNA having the entire coding sequence of the gene. Repeated screens can be utilized as described above to obtain the complete sequence from several clones if necessary. The isolates can then be sequenced to determine the nucleotide sequence by standard means such as dideoxynucleotide sequencing methods (see, e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989).
[0029]The present genes were isolated from rat; however, homologs in any desired species, preferably mammalian, such as human, can readily be obtained by screening a human library, genomic or cDNA, with a probe comprising sequences of the nucleic acids set forth in the sequence listing herein, or fragments thereof, and isolating genes specifically hybridizing with the probe under preferably relatively high stringency hybridization conditions. For example, high salt conditions (e.g., in 6×SSC or 6×SSPE) and/or high temperatures of hybridization can be used. For example, the stringency of hybridization is typically about 5° C. to 20° C. below the Tm (the melting temperature at which half of the molecules dissociate from its partner) for the given chain length. As is known in the art, the nucleotide composition of the hybridizing region factors in determining the melting temperature of the hybrid. For 20 mer probes, for example, the recommended hybridization temperature is typically about 55-58° C. Additionally, the rat sequence can be utilized to devise a probe for a homolog in any specific animal by determining the amino acid sequence for a portion of the rat protein, and selecting a probe with optimized codon usage to encode the amino acid sequence of the homolog in that particular animal. Any isolated gene can be confirmed as the targeted gene by sequencing the gene to determine it contains the nucleotide sequence listed herein as comprising the gene. Any homolog can be confirmed as a homolog by its functionality.
[0030]Additionally contemplated by the present invention are nucleic acids, from any desired species, preferably mammalian and more preferably human, having 98%, 95%, 90%, 85%, 80%, 70%, 60%, or 50% homology, or greater, in the region of homology, to a region in an exon of a nucleic acid encoding the protein encoded by the gene comprising the nucleotide sequence set forth in any of the sequences listed in SEQ LIST 1 or to homologs thereof. Also contemplated by the present invention are nucleic acids, from any desired species, preferably mammalian and more preferably human, having 98%, 95%, 90%, 85%, 80%, 70%, 60%, or 50% homology, or greater, in the region of homology, to a region in an exon of a nucleic acid comprising the nucleotide sequence set forth in any of the sequences listed in SEQ LIST 1 or to homologs thereof. These genes can be synthesized or obtained by the same methods used to isolate homologs, with stringency of hybridization and washing, if desired, reduced accordingly as homology desired is decreased, and further, depending upon the G-C or A-T richness of any area wherein variability is searched for. Allelic variants of any of the present genes or of their homologs can readily be isolated and sequenced by screening additional libraries following the protocol above. Methods of making synthetic genes are described in U.S. Pat. No. 5,503,995 and the references cited therein.
[0031]The nucleic acid encoding any selected protein of the present invention can be any nucleic acid that functionally encodes that protein. For example, to functionally encode, i.e., allow the nucleic acid to be expressed, the nucleic acid can include, for example, exogenous or endogenous expression control sequences, such as an origin of replication, a promoter, an enhancer, and necessary information processing sites, such as ribosome binding sites, RNA splice sites, polyadenylation sites, and transcriptional terminator sequences. Preferred expression control sequences can be promoters derived from metallothionine genes, actin genes, immunoglobulin genes, CMV, SV40, adenovirus, bovine papilloma virus, etc. Expression control sequences can be selected for functionality in the cells in which the nucleic acid will be placed. A nucleic acid encoding a selected protein can readily be determined based upon the amino acid sequence of the selected protein, and, clearly, many nucleic acids will encode any selected protein.
[0032]The present invention additionally provides a nucleic acid that selectively hybridizes under stringent conditions with a nucleic acid set forth in SEQ LIST 1 or with a nucleic acid encoding the protein encoded by the gene comprising the nucleotide sequence set forth in any sequence listed in SEQ LIST 1. This hybridization can be specific. The degree of complementarity between the hybridizing nucleic acid and the sequence to which it hybridizes should be at least enough to exclude hybridization with a nucleic acid encoding an unrelated protein. Thus, a nucleic acid that selectively hybridizes with a nucleic acid of the present protein coding sequence will not selectively hybridize under stringent conditions with a nucleic acid for a different, unrelated protein, and vice versa. Typically, the stringency of hybridization to achieve selective hybridization involves hybridization in high ionic strength solution (6×SSC or 6×SSPE) at a temperature that is about 12-25° C. below the Tm (the melting temperature at which half of the molecules dissociate from its partner) followed by washing at a combination of temperature and salt concentration chosen so that the washing temperature is about 5° C. to 20° C. below the Tm of the hybrid molecule. The temperature and salt conditions are readily determined empirically in preliminary experiments in which samples of reference DNA immobilized on filters are hybridized to a labeled nucleic acid of interest and then washed under conditions of different stringencies. Hybridization temperatures are typically higher for DNA-RNA and RNA-RNA hybridizations. The washing temperatures can be used as described above to achieve selective stringency, as is known in the art. (Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989; Kunkel et al. Methods Enzymol. 1987:154:367, 1987). Nucleic acid fragments that selectively hybridize to any given nucleic acid can be used, e.g., as primers and or probes for further hybridization or for amplification methods (e.g., polymerase chain reaction (PCR), ligase chain reaction (LCR)). A preferable stringent hybridization condition for a DNA:DNA hybridization can be at about 68° C. (in aqueous solution) in 6×SSC or 6×SSPE followed by washing at 68° C.
[0033]The present invention additionally provides a polypeptide comprising the amino acid sequence encoded by the gene comprising the nucleotide sequence set forth in SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, 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:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, 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:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, and SEQ ID NO: 127 (i.e., SEQ LIST 1). Additionally, polypeptides comprising the amino acid sequence encoded by a nucleic acid that selectively hybridizes under stringent conditions with a nucleic acid in SEQ LIST 1 are provided. Further, polypeptides comprising the amino acid sequence encoded by a nucleic acid having a region within an exon wherein the region has at least 50, 60, 70, 80, 90, or 95% homology with a nucleic acid in SEQ LIST 1. These polypeptides can be readily obtained by any of several means. For example, the nucleotide sequence of coding regions of the gene can be translated and then the corresponding polypeptide can be synthesized mechanically by standard methods. Additionally, the coding regions of the genes can be expressed or synthesized, an antibody specific for the resulting polypeptide can be raised by standard methods (see, e.g., Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1988), and the protein can be isolated from other cellular proteins by selective hybridization with the antibody. This protein can be purified to the extent desired by standard methods of protein purification (see, e.g., Sambrook et al., Molecular Cloning. A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989). The amino acid sequence of any protein, polypeptide or peptide of this invention can be deduced from the nucleic acid sequence, or it can be determined by sequencing an isolated or recombinantly produced protein.
[0034]The terms "peptide," "polypeptide" and "protein" can be used interchangeably herein and refer to a polymer of amino acids and includes full-length proteins and fragments thereof. As used in the specification and in the claims, "a" can mean one or more, depending upon the context in which it is used. An amino acid residue is an amino acid formed upon chemical digestion (hydrolysis) of a polypeptide at its peptide linkages. The amino acid residues described herein are preferably in the L isomeric form. However, residues in the D isomeric form can be substituted for any L-amino acid residue, as long as the desired functional property is retained by the polypeptide. Standard polypeptide nomenclature (described in J. Biol. Chem., 243:3552-59 (1969) and adopted at 37 CFR § 1.822(b)) is used herein.
[0035]As will be appreciated by those skilled in the art, the invention also includes those polypeptides having slight variations in amino acid sequences or other properties. Amino acid substitutions can be selected by known parameters to be neutral (see, e.g., Robinson W E Jr, and Mitchell W M., AIDS 4:S151-S162 (1990)). Such variations may arise naturally as allelic variations (e.g., due to genetic polymorphism) or may be produced by human intervention (e.g., by mutagenesis of cloned DNA sequences), such as induced point, deletion, insertion and substitution mutants. Minor changes in amino acid sequence are generally preferred, such as conservative amino acid replacements, small internal deletions or insertions, and additions or deletions at the ends of the molecules. Substitutions may be designed based on, for example, the model of Dayhoff, et al. (in Atlas of Protein Sequence and Structure 1978, Nat'l Biomed. Res. Found., Washington, D.C.). These modifications can result in changes in the amino acid sequence, provide silent mutations, modify a restriction site, or provide other specific mutations. Likewise, such amino acid changes result in a different nucleic acid encoding the polypeptides and proteins. Thus, alternative nucleic acids are also contemplated by such modifications.
[0036]The present invention also provides cells containing a nucleic acid of the invention. A cell containing a nucleic acid encoding a protein typically can replicate the DNA and, further, typically can express the encoded protein. The cell can be a prokaryotic cell, particularly for the purpose of producing quantities of the nucleic acid, or a eukaryotic cell, particularly a mammalian cell. The cell is preferably a mammalian cell for the purpose of expressing the encoded protein so that the resultant produced protein has mammalian protein processing modifications.
[0037]Nucleic acids of the present invention can be delivered into cells by any selected means, in particular depending upon the purpose of the delivery of the compound and the target cells. Many delivery means are well-known in the art. For example, electroporation, calcium phosphate precipitation, microinjection, cationic or anionic liposomes, and liposomes in combination with a nuclear localization signal peptide for delivery to the nucleus can be utilized, as is known in the art.
[0038]The present invention also contemplates that the mutated cellular genes necessary for viral growth, produced by the present method, as well as cells containing these mutants can also be useful. These mutated genes and cells containing them can be isolated and/or produced according to the methods herein described and using standard methods.
[0039]It should be recognized that the sequences set forth herein may contain minor sequencing errors. Such errors can be corrected, for example, by using the hybridization procedure described above with various probes derived from the described sequences such that the coding sequence can be reisolated and resequenced.
[0040]As described in the examples, the present invention provides the discovery of a "serum survival factor" present in serum that is necessary for the survival of persistently virally infected cells. Isolation and characterization of this factor have shown it to be a protein, to have a molecular weight of between about 50 kD and 100 kD, to resist inactivation in low pH (e.g., pH2) and chloroform extraction, to be inactivated by boiling for about 5 minutes and in low ionic strength solution (e.g., about 10 mM to about 50 mM). The present invention thus provides a purified mammalian serum protein having a molecular weight of between about 50 kD and 100 kD which resists inactivation in low pH and resists inactivation by chloroform extraction, which inactivates when boiled and inactivates in low ionic strength solution, and which when removed from a cell culture comprising cells persistently infected with reovirus selectively substantially prevents survival of cells persistently infected with reovirus. The factor, fitting the physical characteristics described above, can readily be verified by adding it to non-serum-containing medium (which previously could not support survival of persistently virally infected cells) and determining whether this medium with the added putative factor can now support persistently virally infected cells, particularly cells persistently infected with reovirus. As used herein, a "purified" protein means the protein is at least of sufficient purity such that an approximate molecular weight can be determined.
[0041]The amino acid sequence of the protein can be elucidated by standard methods. For example, an antibody to the protein can be raised and used to screen an expression library to obtain nucleic acid sequence coding the protein. This nucleic acid sequence is then simply translated into the corresponding amino acid sequence. Alternatively, a portion of the protein can be directly sequenced by standard amino acid sequencing methods (amino-terminus sequencing). This amino acid sequence can then be used to generate an array of nucleic acid probes that encompasses all possible coding sequences for a portion of the amino acid sequence. The array of probes is used to screen a cDNA library to obtain the remainder of the coding sequence and thus ultimately the corresponding amino acid sequence.
[0042]The present invention also provides methods of detecting and isolating additional serum survival factors. For example, to determine if any known serum components are necessary for viral growth, the known components can be inhibited in, or eliminated from, the culture medium, and it can be observed whether viral growth is inhibited by determining if persistently infected cells do not survive. One can add the factor back (or remove the inhibition) and determine whether the factor allows for viral growth.
[0043]Additionally, other, unknown serum components can also be found to be essential for growth. Serum can be fractionated by various standard means, and fractions added to serum free medium to determine if a factor is present in a reaction that allows growth previously inhibited by the lack of serum. Fractions having this activity can then be further fractionated until the factor is relatively free of other components. The factor can then be characterized by standard methods, such as size fractionation, denaturation and/or inactivation by various means, etc. Preferably, once the factor has been purified to a desired level of purity, it is added to cells in serum free medium to confirm that it bestows the function of allowing virus to grow when serum-free medium alone did not. This method can be repeated to confirm the requirement for the specific factor for any desired virus, since each serum factor found to be required by any one virus can also be required by many other viruses. In general, the closer the viruses are related and the more similar the infection modes of the viruses, the more likely that a factor required by one virus will be required by the other.
[0044]The present invention also provides methods of treating virus infections utilizing applicants' discoveries. The subject of any of the herein described methods can be any animal, preferably a mammal, such as a human, a veterinary animal, such as a cat, dog, horse, pig, goat, sheep, or cow, or a laboratory animal, such as a mouse, rat, rabbit, or guinea pig, depending upon the virus.
[0045]The present invention provides a method of reducing or inhibiting, and thereby treating, a viral infection in a subject, comprising administering to the subject an inhibiting amount of a composition that inhibits functioning of the serum protein described herein, i.e. the serum protein having a molecular weight of between about 50 kD and 100 kD which resists inactivation in low pH and resists inactivation by chloroform extraction, which inactivates when boiled and inactivates in low ionic strength solution, and which when removed from a cell culture comprising cells persistently infected with the virus prevents survival of at least some cells persistently infected with the virus, thereby treating the viral infection. The composition can comprise, for example, an antibody that specifically binds the serum protein, or an antisense RNA that binds an RNA encoded by a gene functionally encoding the serum protein.
[0046]Any virus capable of infecting the selected subject to be treated can be treated by the present methods. As described above, any serum protein or survival factor found by the present methods to be necessary for growth of cells infected with any one virus can be found to be necessary for growth of the cells infected with many other viruses. For any given cell-virus combination, the serum protein or factor can be confirmed to be required for growth by the methods described herein. The cellular genes identified by the examples using reovirus, a mammalian pathogen, and a rat cell system have general applicability to other virus infections that include all of the known as well as yet to be discovered human pathogens, including, but not limited to: human immunodeficiency viruses (e.g., HIV-1, HIV-2); parvovirus; papillomaviruses; hantaviruses; influenza viruses (e.g., influenza A, B and C viruses); hepatitis viruses A to G; caliciviruses; astroviruses; rotaviruses; coronaviruses, such as human respiratory coronavirus; picornaviruses, such as human rhinovirus and enterovirus; ebola virus; human herpesvirus (e.g., HSV-1-9); human adenovirus; hantaviruses; for animal, the animal counterpart to any above listed human virus, animal retroviruses, such as simian immunodeficiency virus, avian immunodeficiency virus, bovine immunodeficiency virus, feline immunodeficiency virus, equine infectious anemia virus, caprine arthritis encephalitis virus, arenaviruses, arvoviruses, tickborne virus or visna virus.
[0047]A protein inhibiting amount of the composition can be readily determined, such as by administering varying amounts to cells or to a subject and then adjusting the effective amount for inhibiting the protein according to the volume of blood or weight of the subject. Compositions that bind to the protein can be readily determined by running the putatively bound protein on a protein gel and observing an alteration in the protein's migration through the gel. Inhibition of the protein can be determined by any desired means such as adding the inhibitor to complete media used to maintain persistently infected cells and observing the cells' viability. The composition can comprise, for example, an antibody that specifically binds the serum protein. Specific binding by an antibody means that the antibody can be used to selectively remove the factor from serum or inhibit the factor's biological activity and can readily be determined by radio immune assay (RIA), bioassay, or enzyme-linked immunosorbant (ELISA) technology. The composition can comprise, for example, an antisense RNA that specifically binds an RNA encoded by the gene encoding the serum protein. Antisense RNAs can be synthesized and used by standard methods (e.g., Antisense RNA and DNA, D. A. Melton, Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1988)).
[0048]The present methods provide a method of screening a compound for effectiveness in treating or preventing a viral infection, comprising administering the compound to a cell containing a cellular gene functionally encoding a gene product necessary for reproduction of the virus in the cell but not necessary for survival of the cell and detecting the level and/or activity (i.e. function) of the gene product produced, a decrease or elimination of the gene product and/or the gene product activity indicating a compound for treating or preventing the viral infection. The cellular gene can be, for example, a nucleic acid set forth 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: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:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, 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:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82; SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, or SEQ ID NO:127 (herein sometimes referred to as SEQ LIST 2, for brevity), any homolog thereof, or any other gene obtained using the methods provided herein for obtaining such genes. It is understood that the cellular gene can be present naturally in the cell being screened, or it can be introduced into the cell in a suitable expression vector, as are well known in the art. The level of the gene product can be measured by any standard means, such as by detection with an antibody specific for the protein. The level of gene product can be compared to the level of the gene product in a control cell not contacted with the compound. The level of gene product can be compared to the level of the gene product in the same cell prior to addition of the compound. Activity, or function, can be measured by any standard means, such as by enzymatic assays that measure the conversion of a substrate to a product or binding assays that measure the binding of a protein to a nucleic acid, for example. Examples of gene products disclosed herein whose activity/function can be measured include tristetraprolin (human ZFP-36), 6-pyruvoyl-tetrahydropterin synthase, a eukaryotic DnaJ-like protein, ID3 (inhibitor of DNA binding 3), N-acetylglucos-aminyltransferase I (mGAT-1), cleavage stimulation factor (CSTF2), TAK1 binding protein, human zinc transcription factor ZPF207, D1x2, Smad7 (Mad-related protein), and P-glycoprotein (mdr1b). The activity can be compared to the activity in a control cell not contacted with the compound or in the same cell prior to addition of the compound. Relatedly, the regulatory region of the gene can be functionally linked to a reporter gene and compounds can be screened for inhibition of the reporter gene. Such reporter constructs are described herein.
[0049]The present invention also provides a method of screening a compound for effectiveness in treating or preventing a viral infection comprising contacting the compound with the gene product of a cellular gene comprising a nucleic acid of SEQ LIST 2, or any homolog thereof, and detecting the function of the gene product, a decrease or elimination of the function indicating a compound effective for treating or preventing viral infection. Examples of gene products disclosed herein that can be utilized in this method include tristetraprolin (human ZFP-36), 6-pyruvoyl-tetrahydropterin synthase, a eukaryotic DnaJ-like protein, ID3 (inhibitor of DNA binding 3), N-acetylglucos-aminyltransferase I (mGAT-1), cleavage stimulation factor (CSTF2), TAK1 binding protein, human zinc transcription factor ZPF207, D1x2, Smad7 (Mad-related protein), and P-glycoprotein (mdr1b).
[0050]The present invention provides a method of selectively eliminating cells persistently infected with a virus from an animal cell culture capable of surviving for a first period of time in the absence of serum, comprising propagating the cell culture in the absence of serum for a second time period during which a persistently infected cell cannot survive without serum, thereby selectively eliminating from the cell culture cells persistently infected with the virus. The second time period should be shorter than the first time period. Thus one can simply eliminate serum from a standard culture medium composition for a period of time (e.g. by removing serum containing medium from the culture container, rinsing the cells, and adding serum-free medium back to the container), then, after a time of serum starvation, return serum to the culture medium. Alternatively, one can inhibit a serum survival factor from the culture in place of the step of serum starvation. Furthermore, one can instead interfere with the virus-factor interaction. Such a viral elimination method can periodically be performed for cultured cells to ensure that they remain virus-free. The time period of serum removal can greatly vary, with a typical range being about 1 to about 30 days; a preferable period can be about 3 to about 10 days, and a more preferable period can be about 5 days to about 7 days. This time period can be selected based upon ability of a specific cell to survive without serum as well as the life cycle of the target virus, e.g., for reovirus, which has a life cycle of about 24 hours, 3 days' starvation of cells provides dramatic results.
[0051]Furthermore, the time period can be shortened by also passaging the cells during the starvation; in general, increasing the number of passages can decrease the time of serum starvation (or serum factor inhibition) needed to get full clearance of the virus from the culture. While passaging, the cells typically are exposed briefly to serum (typically for about 3 to about 24 hours). This exposure both stops the action of the trypsin used to dislodge the cells and stimulates the cells into another cycle of growth, thus aiding in this selection process. Thus a starvation/serum cycle can be repeated to optimize the selective effect. Other standard culture parameters, such as confluency of the cultures, pH, temperature, etc. can be varied to alter the needed time period of serum starvation (or serum survival factor inhibition). This time period can readily be determined for any given viral infection by simply removing the serum for various periods of time, then testing the cultures for the presence of the infected cells (e.g., by ability to survive in the absence of serum and confirmed by quantitating virus in cells by standard virus titration and immunohistochemical techniques) at each tested time period, and then detecting at which time periods of serum deprivation the virally infected cells were eliminated. It is preferable that shorter time periods of serum deprivation that still provide elimination of the persistently infected cells be used. Furthermore, the cycle of starvation, then adding back serum and determining amount of virus remaining in the culture can be repeated until no virtually infected cells remain in the culture.
[0052]Thus, the present method can further comprise passaging the cells, i.e., transferring the cell culture from a first container to a second container. Such transfer can facilitate the selective lack of survival of virally infected cells. Transfer can be repeated several times. Transfer is achieved by standard methods of tissue culture (see, e.g., Freshney, Culture of Animal Cells, A Manual of Basic Technique, 2nd Ed. Alan R. Liss, Inc., New York, 1987).
[0053]The present method further provides a method of selectively eliminating from a cell culture cells persistently infected with a virus, comprising propagating the cell culture in the absence of a functional form of the serum protein having a molecular weight of between about 50 kD and 100 kD which resists inactivation in low pH and resists inactivation by chloroform extraction, which inactivates when boiled and inactivates in low ionic strength solution, and which when removed from a cell culture comprising cells persistently infected with reovirus substantially prevents survival of cells persistently infected with reovirus. The absence of the functional form can be achieved by any of several standard means, such as by binding the protein to an antibody selective for it (binding the antibody in serum either before or after the serum is added to the cells; if before, the serum protein can be removed from the serum by, e.g., binding the antibody to a column and passing the serum over the column and then administering the survival protein-free serum to the cells), by administering a compound that inactivates the protein, or by administering a compound that interferes with the interaction between the virus and the protein.
[0054]Thus, the present invention provides a method of selectively eliminating from a cell culture propagated in serum-containing medium cells persistently infected with a virus, comprising inhibiting in the serum the protein having a molecular weight of between about 50 kD and 100 kD which resists inactivation in low pH and resists inactivation by chloroform extraction, which inactivates when boiled and inactivates in low ionic strength solution, and which when removed from a cell culture comprising cells persistently infected with reovirus substantially prevents survival of cells persistently infected with reovirus. Alternatively, the interaction between the virus and the serum protein can be disrupted to selectively eliminate cells persistently infected with the virus.
[0055]Any virus capable of some form of persistent infection may be eliminated from a cell culture utilizing the present elimination methods, including removing, inhibiting or otherwise interfering with a serum protein, such as the one exemplified herein, and also including removing, inhibiting or otherwise interfering with a gene product from any cellular gene found by the present method to be necessary for viral growth yet nonessential to the cell. For example, DNA viruses or RNA viruses can be targeted. One can readily determine whether cells infected with a selected virus can be selectively removed from a culture through removal of serum by starving cells permissive to the virus of serum (or inhibiting the serum survival factor), adding the selected virus to the cells, adding serum to the culture, and observing whether infected cells die (i.e., by titering levels of virus in the surviving cells with an antibody specific for the virus).
[0056]A culture of any animal cell (i.e., any cell that is typically grown and maintained in culture in serum) that can be maintained for a period of time in the absence of serum, can be purified from viral infection utilizing the present method. For example, primary cultures as well as established cultures and cell lines can be used. Furthermore, cultures of cells from any animal and any tissue or cell type within that animal that can be cultured and that can be maintained for a period of time in the absence of serum can be used. For example, cultures of cells from tissues typically infected, and particularly persistently infected, by an infectious virus could be used.
[0057]As used in the claims "in the absence of serum" means at a level at which persistently virally infected cells do not survive. Typically, the threshold level is about 1% serum in the media. Therefore, about 1% serum or less can be used, such as about 1%, 0.75%, 0.50%. 0.25% 0.1% or no serum can be used.
[0058]As used herein, "selectively eliminating" cells persistently infected with a virus means that substantially all of the cells persistently infected with the virus are killed such that the presence of virally infected cells cannot be detected in the culture immediately after the elimination procedure has been performed. Furthermore, "selectively eliminating" includes that cells not infected with the virus are generally not killed by the method. Some surviving cells may still produce virus but at a lower level, and some may be defective in pathways that lead to death by the virus. Typically, for cells persistently infected with virus to be substantially all killed, more than about 90% of the cells, and more preferably more than about 95%, 98%, 99%, or 99.99% of virus-containing cells in the culture are killed.
[0059]The present method also provides a nucleic acid comprising the regulatory region of any of the genes. Such regulatory regions can be isolated from the genomic sequences isolated and sequenced as described above and identified by any characteristics observed that are characteristic for regulatory regions of the species and by their relation to the start codon for the coding region of the gene. The present invention also provides a construct comprising the regulatory region functionally linked to a reporter gene. Such constructs are made by routine subcloning methods, and many vectors are available into which regulatory regions can be subcloned upstream of a marker gene. Marker genes can be chosen for ease of detection of marker gene product.
[0060]The present method therefore also provides a method of screening a compound for treating a viral infection, comprising administering the compound to a cell containing any of the above-described constructs, comprising a regulatory region of one of the genes comprising any of the nucleotide sequences set forth in SEQ LIST 2, or any homologs thereof, whose inhibition or reduction in expression causes inhibition of viral replication wherein the region is functionally linked to a reporter gene, and detecting the level of the reporter gene product produced, a decrease or elimination of the reporter gene product indicating a compound for treating the viral infection. Compounds detected by this method would inhibit transcription of the gene from which the regulatory region was isolated, and thus, in treating a subject, would inhibit the production of the gene product produced by the gene, and thus treat the viral infection.
[0061]Some genes when disrupted by the present method of retrovirus insertion, resulted in over expression of the gene product, and this overexpression inhibited viral replication. Thus the present invention provides a method of screening a compound for effectiveness in treating a viral infection, comprising administering the compound to a cell containing a cellular gene functionally encoding a gene product whose overexpression inhibits reproduction of the virus but does not prevent survival of the cell and detecting the level of the gene product produced, an increase in the gene product indicating a compound effective for treating the viral infection. Typically, an increase will be a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, 300%, 400%, 500% or higher increase over gene product produced when the compound is not present.
[0062]The present invention additionally provides a method of reducing or inhibiting a viral infection in a subject, comprising administering to the subject an amount of a composition that inhibits expression or functioning of a gene product encoded by a gene comprising the nucleic acid set forth in any of SEQ LIST 2, or a homolog thereof, thereby treating the viral infection. Reducing or inhibiting viral infection naturally can include both the initial infection of the subject and the infection of uninfected cells within an already infected subject, e.g. inhibiting viral replication in cells of the subject. The composition can comprise, for example, an antibody that binds a protein encoded by the gene. The composition can also comprise an antibody that binds a receptor for a protein encoded by the gene. Such an antibody can be raised against the selected protein by standard methods as set forth above, and can be either polyclonal or monoclonal, though monoclonal is preferred. Alternatively, the composition can comprise an antisense RNA that binds an RNA encoded by the gene, as described above. Examples of antisense RNA useful therapeutically include the fragments of the nucleic acids described above. Furthermore, the composition can comprise a nucleic acid functionally encoding an antisense RNA that binds an RNA encoded by the gene. Other useful compositions will be readily apparent to the skilled artisan.
[0063]The present invention also provides a method of treating a viral infection in a subject comprising administering to the subject a treatment effective amount of a composition that increases expression of a gene whose over expression reduces or inhibits viral replication. Typically, an increase will be a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, 300%, 400%, 500% or higher increase over gene product produced when the composition is not present.
[0064]The present invention further provides a method of reducing or inhibiting a viral infection in a subject comprising mutating ex vivo in a selected cell, for example from the subject or from an allogenic source, an endogenous gene comprising a nucleic acid set forth in SEQ LIST 2 whose inhibition or reduction in expression causes inhibition of viral replication, or a homolog thereof, to a gene form incapable of producing a functional gene product of the gene or a gene form producing a reduced amount of a functional gene product of the gene, and placing (or replacing, in the case of the subject's own cells) the cell in the subject, thereby reducing viral infection of cells in the subject. The cell can be selected according to the typical target cell of the specific virus whose infection is to be reduced, prevented or inhibited. A preferred cell for several viruses is a hematopoietic cell. When the selected cell is a hematopoietic cell, viruses which can be reduced or inhibited from infection can include, for example, HIV, including HIV-1 and HIV-2. However, many other virus-cell combinations will be apparent to the skilled artisan.
[0065]The invention also includes a method of reducing or inhibiting viral infection in a subject comprising mutating ex vivo in a selected cell, for example from a subject or an allogenic source, an endogenous gene comprising a nucleic acid set forth in SEQ LIST 2 whose overexpression causes inhibition of viral replication, or a homolog thereof, to a gene form that expresses the gene at a higher level than the endogenous gene, and placing or replacing the cell in the subject. Typically, a higher level can be 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 125%, 150%, 175%, 200%, 300%, 400%, 500% or higher than the non-mutated, endogenous gene. The cell can be selected according to the typical target cell of the specific virus whose infection is to be reduced, prevented or inhibited. A preferred cell for several viruses is a hematopoietic cell. When the selected cell is a hematopoietic cell, viruses which can be reduced or inhibited from infection can include, for example, HIV, including HIV-1 and HIV-2. However, many other virus-cell combinations will be apparent to the skilled artisan.
[0066]The present invention additionally provides a method of increasing viral infection resistance in a subject comprising mutating ex vivo in a selected cell, for example from the subject or from an allogenic source, an endogenous gene comprising a nucleic acid set forth in SEQ LIST 2, whose inhibition or reduction in expression increases viral infection resistance, said endogenous gene being mutated to a mutated gene form incapable of producing a functional gene product of the gene or a gene form producing a reduced amount of a functional gene product of the gene, and placing the cell in the subject, thereby increasing viral infection resistance of cells in the subject. The virus can be HIV, particularly when the cell is a hematopoietic cell. However, many other virus-cell combinations will be apparent to the skilled artisan.
[0067]Furthermore, the present invention provides a method for isolation of cellular genes utilized in tumor progression. The present invention provides a method of identifying a cellular gene that can suppress a malignant phenotype in a cell, comprising (a) transferring into a cell culture incapable of growing well in soft agar or Matrigel a vector encoding a selective marker gene lacking a functional promoter, (b) selecting cells expressing the marker gene, and (c) isolating from selected cells which are capable of growing in soft agar or Matrigel a cellular gene within which the marker gene is inserted, thereby identifying a gene that can suppress a malignant phenotype in a cell. This method can be performed using any selected non-transformed cell line, of which many are known in the art.
[0068]The present invention additionally provides a method of identifying a cellular gene that can suppress a malignant phenotype in a cell, comprising (a) transferring into a cell culture of non-transformed cells a vector encoding a selective marker gene lacking a functional promoter, (b) selecting cells expressing the marker gene, and (c) isolating from selected and transformed cells a cellular gene within which the marker gene is inserted, thereby identifying a gene that can suppress a malignant phenotype in a cell. A non-transformed phenotype can be determined by any of several standard methods in the art, such as the exemplified inability to grow in soft agar, or inability to grow in Matrigel.
[0069]The present invention further provides a method of screening for a compound for suppressing a malignant phenotype in a cell comprising administering the compound to a cell containing a cellular gene functionally encoding a gene product involved in establishment of a malignant phenotype in the cell and detecting the level of the gene product produced, a decrease, inhibition or elimination of the gene product indicating a compound effective for suppressing the malignant phenotype. Detection of the level, or amount, of gene product produced can be measured, directly or indirectly, by any of several methods standard in the art (e.g., protein gel, antibody-based assay, detecting labeled RNA) for assaying protein levels or amounts, and selected based upon the specific gene product.
[0070]The present invention also provides a method of screening for a compound for suppressing a malignant phenotype in a cell comprising administering the compound to a cell containing a cellular gene functionally encoding a gene product whose overexpression is involved in suppressing a malignant phenotype in the cell and detecting the level of the gene product produced, an increase in the gene product indicating a compound effective for suppressing the malignant phenotype.
[0071]The present invention further provides a method of suppressing a malignant phenotype in a cell in a subject, comprising administering to the subject an amount of a composition that inhibits expression or functioning of a gene product encoded by a gene comprising the nucleic acid set forth in SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:36 or SEQ ID NO:94, or a homolog thereof, or any gene whose overexpression is found by the present method to be involved in suppressing a malignant phenotype in the cell (e.g., any clone designated herein with an "x") thereby suppressing a malignant phenotype. The composition can, for example, comprise an antibody that binds a protein encoded by the gene. The composition can, as another example, comprise an antibody that binds a receptor for a protein encoded by the gene. The composition can comprise an antisense RNA that binds an RNA encoded by the gene. Further, the composition can comprise a nucleic acid functionally encoding an antisense RNA that binds an RNA encoded by the gene.
[0072]The present invention further provides a method of suppressing a malignant phenotype in a cell in a subject, comprising administering to the subject an amount of a composition that increases expression of a gene product whose overexpression is involved in suppressing a malignant phenotype in the cell. The gene product can be the product of a gene wherein disruption of an upstream gene by the present vector resulted in overexpression of the downstream gene, and the overexpression of the downstream gene demonstrated a transformed phenotype. The composition can be, for example, an inhibitor, such as a small molecule inhibitor, of the COX 2 enzyme.
[0073]Diagnostic or therapeutic agents of the present invention can be administered to a subject or an animal model by any of many standard means for administering therapeutics or diagnostics to that selected site or standard for administering that type of functional entity. For example, an agent can be administered orally, parenterally (e.g., intravenously), by intramuscular injection, by intraperitoneal injection, topically, transdermally, or the like. Agents can be administered, e.g., as a complex with cationic liposomes, or encapsulated in anionic liposomes. Compositions can include various amounts of the selected agent in combination with a pharmaceutically acceptable carrier and, in addition, if desired, may include other medicinal agents, pharmaceutical agents, carriers, adjuvants, diluents, etc. Parental administration, if used, is generally characterized by injection. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. Depending upon the mode of administration, the agent can be optimized to avoid degradation in the subject, such as by encapsulation, etc.
[0074]Dosages will depend upon the mode of administration, the disease or condition to be treated, and the individual subject's condition, but will be that dosage typical for and used in administration of antiviral or anticancer agents. Dosages will also depend upon the composition being administered, e.g., a protein or a nucleic acid. Such dosages are known in the art. Furthermore, the dosage can be adjusted according to the typical dosage for the specific disease or condition to be treated. Furthermore, viral titers in culture cells of the target cell type can be used to optimize the dosage for the target cells in vivo, and transformation from varying dosages achieved in culture cells of the same type as the target cell type can be monitored. Often a single dose can be sufficient; however, the dose can be repeated if desirable. The dosage should not be so large as to cause adverse side effects. Generally, the dosage will vary with the age, condition, sex and extent of the disease in the patient and can be determined by one of skill in the art. The dosage can also be adjusted by the individual physician in the event of any complication.
[0075]For administration to a cell in a subject, the composition, once in the subject, will of course adjust to the subject's body temperature. For ex vivo administration, the composition can be administered by any standard methods that would maintain viability of the cells, such as by adding it to culture medium (appropriate for the target cells) and adding this medium directly to the cells. As is known in the art, any medium used in this method can be aqueous and non-toxic so as not to render the cells non-viable. In addition, it can contain standard nutrients for maintaining viability of cells, if desired. For in vivo administration, the complex can be added to, for example, a blood sample or a tissue sample from the patient, or to a pharmaceutically acceptable carrier, e.g., saline and buffered saline, and administered by any of several means known in the art. Examples of administration include parenteral administration, e.g., by intravenous injection including regional perfusion through a blood vessel supplying the tissues(s) or organ(s) having the target cell(s), or by inhalation of an aerosol, subcutaneous or intramuscular injection, topical administration such as to skin wounds and lesions, direct transfection into, e.g., bone marrow cells prepared for transplantation and subsequent transplantation into the subject, and direct transfection into an organ that is subsequently transplanted into the subject. Further administration methods include oral administration, particularly when the composition is encapsulated, or rectal administration, particularly when the composition is in suppository form. A pharmaceutically acceptable carrier includes any material that is not biologically or otherwise undesirable, i.e., the material may be administered to an individual along with the selected complex without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the pharmaceutical composition in which it is contained.
[0076]Specifically, if a particular cell type in vivo is to be targeted, for example, by regional perfusion of an organ or tumor, cells from the target tissue can be biopsied and optimal dosages for import of the complex into that tissue can be determined in vitro, as described herein and as known in the art, to optimize the in vivo dosage, including concentration and time length. Alternatively, cultured cells of the same cell type can also be used to optimize the dosage for the target cells in vivo.
[0077]For either ex vivo or in vivo use, the complex can be administered at any effective concentration. An effective concentration is that amount that results in reduction, inhibition or prevention of the viral infection or in reduction or inhibition of the transformed phenotype of the cells.
[0078]A nucleic acid can be administered in any of several means, which can be selected according to the vector utilized, the organ or tissue, if any, to be targeted, and the characteristics of the subject. The nucleic acids, if desired in a pharmaceutically acceptable carrier such as physiological saline, can be administered systemically, such as intravenously, intraarterially, orally, parenterally, subcutaneously. The nucleic acids can also be administered by direct injection into an organ or by injection into the blood vessel supplying a target tissue. For an infection of cells of the lungs or trachea, it can be administered intratracheally. The nucleic acids can additionally be administered topically, transdermally, etc.
[0079]The nucleic acid or protein can be administered in a composition. For example, the composition can comprise other medicinal agents, pharmaceutical agents, carriers, adjuvants, diluents, etc. Furthermore, the composition can comprise, in addition to the vector, lipids such as liposomes, such as cationic liposomes (e.g., DOTMA, DOPE, DC-cholesterol) or anionic liposomes. Liposomes can further comprise proteins to facilitate targeting a particular cell, if desired. Administration of a composition comprising a vector and a cationic liposome can be administered to the blood afferent to a target organ or inhaled into the respiratory tract to target cells of the respiratory tract. Regarding liposomes, see, e.g., Brigham et al. Am. J. Resp. Cell. Mol. Biol. 1:95-100 (1989); Felgner et al. Proc. Natl. Acad. Sci. USA 84:7413-7417 (1987); U.S. Pat. No. 4,897,355.
[0080]For a viral vector comprising a nucleic acid, the composition can comprise a pharmaceutically acceptable carrier such as phosphate buffered saline or saline. The viral vector can be selected according to the target cell, as known in the art. For example, adenoviral vectors, in particular replication-deficient adenoviral vectors, can be utilized to target any of a number of cells, because of its broad host range. Many other viral vectors are available, and their target cells are known.
[0081]Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
EXAMPLES
Selective Elimination of Virally Infected Cells from a Cell Culture
[0082]Rat intestinal cell line-1 cells (RIE-1 cells) were standardly grown in Dulbecco's modified Eagle's medium, high glucose, supplemented with 10% fetal bovine serum. To begin the experiment, cells persistently infected with reovirus were grown to near confluence, then serum was removed from the growth medium by removing the medium, washing the cells in PBS, and returning to the flask medium not supplemented with serum. Typically, the serum content was reduced to 1% or less. The cells are starved for serum for several days, or as long as about a month, to bring them to quiescence or growth arrest. Media containing 10% serum is then added to the quiescent cells to stimulate growth of the cells. Surviving cells are found to not be persistently infected cells by immunohistochemical techniques used to establish whether cells contain any infectious virus (sensitivity to 1 infectious virus per ml of homogenized cells).
Cellular Genomic DNA Isolation
[0083]Gene Trap Libraries: The libraries are generated by infecting the RIE-1 cells with a retrovirus vector (U3 gene-trap) at a ratio of less than one retrovirus for every ten cells. When a U3 gene trap retrovirus integrates within an actively transcribed gene, the neomycin resistance gene that the U3 gene trap retrovirus encodes is also transcribed, thus conferring resistance to the cell to the antibiotic neomycin. Cells with gene trap events are able to survive exposure to neomycin while cells without a gene trap event die. The various cells that survive neomycin selection are then propagated as a library of gene trap events. Such libraries can be generated with any retrovirus vector that has the properties of expressing a reporter gene from a transcriptionally active cellular promoter that tags the gene for later identification.
[0084]Reovirus selection: Reovirus infection is typically lethal to RIE-1 cells but can result in the development of persistently infected cells. These cells continue to grow while producing infective reovirus particles. For the identification of gene trap events that confer reovirus resistance to cells, the persistently infected cells must be eliminated or they will be scored as false positives. We have found that RIE-1 cells persistently infected with reovirus are very poorly tolerant to serum starvation, passaging and plating at low density. Thus, we have developed protocols for the screening of the RIE-1 gene trap libraries that select against both reovirus sensitive cells and cells that are persistently infected with reovirus. [0085]1. RIE-1 library cells are grown to near confluence and then the serum is removed from the media. The cells are starved for serum for several days to bring them to quiescent or growth arrest. [0086]2. The library cells are infected with reovirus at a titer of greater than ten reovirus per cell and the serum starvation is continued for several more days. [0087]3. The infected cells are passaged, (a process in which they are exposed to serum for three to six hours) and then starved for serum for several more days. [0088]4. The surviving cells are then allowed to grow in the presence of serum until visible colonies develop at which point they are cloned by limiting dilution.MEDIA: DULBECCO'S MODIFIED EAGLE'S MEDIUM, HIGH GLUCOSE (DME/HIGH) Hyclone Laboratories cat. no. SH30003.02.NEOMYCIN: The antibiotic used to select against the cells that did not have a U3 gene trap retrovirus, e.g. GENETICIN, from Sigma. [cat. no. G9516].RAT INTESTINAL CELL LINE-1 CELLS (RIE-1 CELLS): These cells are from the laboratory of Dr. Ray Dubois (VAMC). They are typically cultured in Dulbecco's Modified Eagle's Medium supplemented with 10% fetal calf serum.REOVIRUS: Laboratory strains of either serotype 1 or serotype 3 are used. They were originally obtained from the laboratories of Bernard N. Fields (deceased). These viruses have been described in detail.RETROVIRUS: The U3 gene trap retrovirus used here were developed by Dr. Earl Ruley (VAMC) and the libraries were produced using a general protocol suggested by him.SERUM: FETAL BOVINE SERUM Hyclone Laboratories cat. no. A-1115-L.
Identification Tags for Isolated Nucleic Acids
[0089]Genomic sequences, tagged with a vector, such as the U3 gene trap vector, are given a number corresponding to the genomic library of mutant cells from which the sequence was isolated., and a letter indicating a unique member of the library. More than one sequence with the same number and letter indicates multiple, unique sequences obtained from the genome surrounding the vector insert that "tagged" the gene. Such genomic sequences are obtained using vector-based primers, from which sequencing occurs 3' to 5' or 5' to 3'. In the former case, to recover the orientation of the gene into which the vector inserted, the sequence derived from the vector primer must be reversed and complemented. Such reverse complement sequences are designated "rE". In the case of genome sequencing from a primer that occurs 5' to 3' (i.e. the primer is at the 3' end of the vector), no changes are needed, since the derived sequence is the sequence as it appears in the gene disrupted. Such sequences are designated "B4". Homologies indicated below each genomic sequence are in the positive direction, unless explicitly noted to be on the negative strand. As an example, SEQ ID NO. 27 comprises a nucleic acid sequence encoding a novel polypeptide on the positive strand, while the negative strand encodes ferritin.
SEQ ID NO: Lab Designation
1 32-3-2#1E/-rE
2 L191B2E#1-RE
3 L191B2E#3+-rE
4 21-5-9E-RE
[0090]homology to: emb/AL021154/HS15005 human DNA sequence
5 14A14E-rE
[0091]6 4cx-b47 5a-b4
8 6BSA12-B4
9 X7B/B4
[0092]10 x27b4f--1
11 12C#A-rE
[0093]12 10-3b(May 2, 1996)/-rE
13 10--4B--4-rE
14 6BE60-rE
[0094]homology to: alpha-trophomyosin
15 19D3E-rE
16 L19D16E-rE
[0095]17 2b_rE18 14--24--#6-rE
19 7A7'-rE
[0096]homology to: annexin II/dynein I20 L12cx#6-rEhomology to: gb:X51760 human zinc finger protein ZFP-3621 L12cx#11-rE
22 19D5E-rE
[0097]homology to: 6-pyruvoyl-tetrahydropterin synthase (gb/M77850/RAT6PTHS)23 12--3b#7-rE
24 12--3B#8--RE
[0098]homology to: gb/AA871174/vq32a08.r1 Barskad bowel MPLRBg Mus musculus cDNA clone 10959265'
25 9B27-2-E
[0099]homology to: RAT LOCUS RNU53922 4 May 1996; Rattus norvegicus DnaJ-like protein (RDJ1) mRNA, complete Cds, ACCESSION U53922 (on negative strand)26 x15-rE
27 X11-rE
[0100]homology to: ferritin H (on the negative strand)
28 X20-rE
[0101]homology to: LOCUS RATGL5A Rat NICER element (GL5-14)5' long terminal repeat, Acc. No. M59028 M33535N1D
29 X4-rE
30 14A7E-rE
[0102]homology to: MMSMAD7 3681 bp mRNA ROD 31 Jul. 1998 DEFINITION Mus musculus mRNA for Mad-related protein Smad7, 149 bases
31 14A13E-rE
32 14--7#2E-rE
[0103]homology to: N-acetylglucosaminyltransferase I
33 12CX#6-rE
[0104]homology to: gb|AA522204|AA522204 vf98g09_r1 Soares mouse mammary gland NbMMG Mus musculus cDNA clone 851872; also 5' similar to gb X51760 zinc finger protein ZFP-36 (HUMAN), gb L20450 Mus musculus DNA-binding protein mRNA, complete cds (MOUSE); Length=442, 925 bases (shares homology with SEQ ID NO:20)
34 12C--2B#9E-rE
35 12CX#11E-rE
[0105]36 x5-rE
37 8C5--11-rE
38 191E2E-rE
39 19--7AE-rE
40 19--9BE-rE
[0106]homology to: LOCUS HS347M6 56583 bp DNA PRI 14 Jan. 1998 Human DNA sequence from PAC 347M6 on chromosome Xq22, CSTF2 (Cleavage Stimulation Factor, CF-1, Polyadenylation Factor) 64 kD subunit gene
41 191E9E-rE
42 191E8E-rE
43 14C--2E/-rE
[0107]homology to: gb/H31084/EST104778 Rattus sp. cDNA-5' end similar to signal recognition particle subunit(19 kDa) (on negative strand)
44 14H1E-rE
45 14G3E-rE
46 14G--2E-rE
47 6--3--6--2E/-rE
[0108]homology to: Rattus norvegicus cis-golgi gp130 (on negative strand); and a HUMAN EST (on positive strand) AI127398; qb70g11.x1 Soares fetal heart NbHH19W Homo sapiens cDNA clone (1705508 3' mRNA sequence)
48 14H4E/-rE
49 18A--8--4E-rE
50 18A--8--1E-rE
51 SCB2--19E-rE
52 L197B3E-rE
53 L195C5E-rE
[0109]homology to: H. pylori and C. jeuni
54 21--5--7E-rE
[0110]homology to: id3 gene; emb|AL021154|HS150O5 Human DNA sequence from clone 150O5; HTGS phase 1 [Homo sapiens]; containing the E2F2 gene for transcription factor E2F-2 and the ID3 gene for Inhibitor of DNA binding 3 (dominant negative helix-loop-helix protein), 1R2, Length=133667, 971 bases
55 L195B1E-rE
[0111]homology to: vK72b07.s1 Knowles Solter mouse 2 cell Mus musculus cDNA clone 960181 5'56 L194c4E-rE
57 L193A1E#A-rE
58 L192A3E-rE
59 L1739E-rE
60 L192B3E#13-rE
[0112]contains sequence identical to: insulin growth factorII/mannose-6-phosphate receptor61-3 2 4rElocated in the same region of the genome as calcyclin, but the gene is "read" in the opposite direction62 36 7 1a-rE63 36 5 1 4a-rE64 34 25 5a-rErat satellite DNA (RATRSSID 93 bp, ROD 12 Mar. 1984)65 34 24-126/rEhomology to:HSU49928 (3096 bp mRNA) PRI 6 Apr. 1998, Homo sapiens TAK1 binding protein (TAB1) mRNA, complete cds, ACCESSION U49928 NID g1401125, and HS333H23 (142274 bp DNA) HTG 17 Jul. 1998 Human DNA sequence66 34 23-1/rE67 36 5 2-6/rE68 3652-196/rE69 34 23-3/rEhomology to: gb|L16546|RATAP1X Rat P-glycoprotein (mdr1b) gene70 34 25 23-rE71 36 5 2-196/rE72 31 3 9/rEhomology to: AA798638 568 bp mRNA EST 10-FEB-1998, vw34b06.r1 Soares mouse mammary gland NbMMG Mus musculus cDNA clone 1245683 5, mRNA sequence, 824 bases.73 31 3 6-2-rE74 31 3 17-rE75 31 3 5-rEhomology to: AF046001 2347 bp mRNA PRI 19 Feb. 1998, Homo sapiens zinc finger transcription factor (ZNF207) mRNA, complete Cds, 833 bases.76 31 3 15#1/rE77 24 3 5#1/rE78 31 44#1/rE79 31 3 19#2/rE80 31 4 5#1/rE81 24 9 3#2/rE
82 L24--26--1-BL
[0113]homology to: AI045472 396 bp mRNA EST 6 Jul. 1998, UI-R--C1-jz-h-09-0-UI.s2 UI-R--C1 Rattus norvegicus cDNA cloneUI-R-C1-jz-h-09-0-UI 3', mRNA sequence.
83 L24--26--1-B4
84 L22--5A1/rE
85 L24--3--2B/rE
86 L24 4-2/rE
87 L24 5-2/rE
88 L24 5-3/rE
89 (15-)L28AP/rE
90 L24 26-10/rE
[0114]homology to: LOCUS R06687 403 bp mRNA EST 3 Apr. 1995; yf10a10.r1 Soares fetal liver spleen 1NFLS Homo sapiens cDNA clone 126426 5'
91 L24 26-2A/rE
92 L24 26-2B/rE
[0115]homology to: gb|AA5900261|AA590026 vm22g03.r1 Knowles Solter mouse blastocyst B1 Mus musculus cDNA clone 990964, 459 bases, 139A; and Rattus norvegicus Eker rat-associated intracisternal-A particle element
93 14 7#2E-rE
[0116]homology to: N-acetylglucosaminyltransferase I; this sequence shares homology with SEQ ID NO:32.94 x1895 31--3--9-rE96 31--3--6--2-rE97 31--3--17-rE98 31--3--15#1-rE99 24--3--5#1-rE100 31--4--4# 1-rE101 31--3--19#2-rE102 31--4--5#1-rE103 24--9--3#2-rE
104 14XD#12E-rE
105 70A-rE
[0117]106 31-3-4-rE
107 3--6--9-NeoG-rE
[0118]108 31--4--2-rE109 3--2--13-rEhomology to: calcyclin
110 3--2--4-E
[0119]homology to: pist1re-alpha 1 (with homology to calcyclin on negative strand)
111 L25-10/-rE
[0120]homology to: calcyclin
112 L24-4-3/-rE
113 L24-9-1-rE
[0121]rat id sequence
114 17-L25-27#7-rE
[0122]homology to: calcyclin
115 L21C1E-rE
[0123]homology to: calcyclin
116 L24-5-3BE-rE.
[0124]homology to:LOCUS H32572 310 bp mRNA EST 8 Sep. 1995 EST107805 Rat PC-12 cells, untreated Rattus sp cDNA 5' end, ACCESSION H32572, andLOCUS AA858747 470 bp mRNA EST 10 Mar. 1998 UI-R-A0-bb-e-01-0-UI.s1 UI-R-A0 Rattus norvegicus cDNA clone UI-R-A0-bb-e-01-0-UI, 3' similar to gb|AA473081|AA473081 vd44b07-r1 Barstead MPLRB1 Mus musculus cDNA clone 803413 5' mRNA sequence
117 L24-4-2BE-rE
[0125]homology to: LOCUS MMU51002 6495 bp DNA ROD 16 Jan. 1997 Mus musculus D1x-2 gene, complete cds, ACCESSION U51002 NID g1477589
118 17-3-3B-B4
119 L24-26-3/-rE
[0126]homology to: RNU23776, DNA ROD 10 Aug. 1995, Rattus norvegicus Eker rat-associated intracisternal-A particle element
120 12--2B#2-rE
121 05-17-3-3He-1-T7
122 21--5--8E-rE
[0127]homology to: emb|AL021154|HS150O5 Human DNA sequence from clone 150O5; 1p36--13-36--22, contains the E2F2 gene for transcription factor E2F-2 and the ID3 gene for Inhibitor of DNA binding 3 (dominant negative helix-loop-helix protein, 1R2, Length=133667, 971 bases
123 X18H-t7
124 18A--8--4E-rE
125 L24-5-2BE-rE
126 L24-4-2AE-rE
127 L24-10-1BE-rE
Genes Necessary for Viral Infection
[0128]Some of the isolated sequences disclosed here comprise sequence encoding the following proteins: tristetraprolin (human ZFP-36), 6-pyruvoyltetrahydropterin synthase, a eukaryotic DnaJ-like protein, ID3 (inhibitor of DNA binding 3), N-acetylglucos-aminyltransferase I (mGAT-1), cleavage stimulation factor (CSTF2), TAK1 binding protein, human zinc transcription factor ZPF207, D1x2, Smad7 (Mad-related protein), and P-glycoprotein (mdr1b).
Isolation of Cellular Genes that Suppress a Malignant Phenotype
[0129]We have utilized a gene-trap method of selecting cell lines that have a transformed phenotype (are potentially tumor cells) from a population of cells (RIE-1 parentals) that are not transformed. The parental cell line, RIE-1 cells, does not have the capacity to grow in soft agar or to produce tumors in mice. Following gene-trapping, cells were screened for their capacity to grow in soft agar. These cells were cloned and genomic sequences were obtained 5' or 3' of the retrovirus vector, i.e. SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:36 or SEQ ID NO:94; sequences designated with an "x" in the clone name). All of the cell lines behave as if they are tumor cell lines, as they also induce tumors in mice.
[0130]Of the cell lines, two are associated with the enhanced expression of the prostaglandin synthetase gene II or COX 2. It has been shown that disruption of gene function by retroviral targeting of an upstream gene has lead to increased expression of a downstream gene product, COX 2. When a small molecule inhibitor of COX 2 enzyme was added, reversion of the transformed phenotype occurred. The COX 2 gene has been found to be increased in pre-malignant adenomas in humans and overexpressed in human colon cancer. Inhibitors of COX 2 expression also arrests the growth of the tumor. One of the cell lines, x18 (SEQ ID NO:94), has disrupted a gene that is now represented in the EST (dbest) database, but the gene is not known (not present in GenBank).
[0131]Each of the genes from which the provided nucleotide sequences is isolated (and all clones designated with an "x") represents a tumor suppressor gene. The mechanism by which the disrupted genes may suppress a transformed phenotype is at present unknown. However, each one represents a tumor suppressor gene that is potentially unique, as none of the genomic sequences correspond to a known gene. The capacity to select quickly tumor suppressor genes may provide unique targets in the process of treating or preventing (potential for diagnostic testing) cancer.
Isolation of Entire Genomic Genes
[0132]An isolated nucleic acid of this invention (whose sequence is set forth in any of SEQ ID NO:1 through SEQ ID NO:127), or a smaller fragment thereof, is labeled by a detectable label and utilized as a probe to screen a rat genomic library (lambda phage or yeast artificial chromosome vector library) under high stringency conditions, i.e., high salt and high temperatures to create hybridization and wash temperature 5-20° C. Clones are isolated and sequenced by standard Sanger dideoxynucleotide sequencing methods. Once the entire sequence of the new clone is determined, it is aligned with the probe sequence and its orientation relative to the probe sequence determined. A second and third probe is designed using sequences from either end of the combined genomic sequence, respectively. These probes are used to screen the library, isolate new clones, which are sequenced. These sequences are aligned with the previously obtained sequences and new probes designed corresponding to sequences at either end and the entire process repeated until the entire gene is isolated and mapped. When one end of the sequence cannot isolate any new clone, a new library can be screened. The complete sequence includes regulatory regions at the 5' end and a polyadenylation signal at the 3' end.
Isolation of cDNAs
[0133]An isolated nucleic acid (whose sequence is set forth in any of SEQ ID NO:1 through SEQ ID NO:127), or a smaller fragment thereof, or additional fragments obtained from the genomic library, that contain open reading frames, is labeled by a detectable label and utilized as a probe to screen a portions of the present fragments, to screen a cDNA library. A rat cDNA library obtains rat cDNA; a human cDNA library obtains a human cDNA. Repeated screens can be utilized as described above to obtain the complete coding sequence of the gene from several clones if necessary. The isolates can then be sequenced to determine the nucleotide sequence by standard means such as dideoxynucleotide sequencing methods.
[0134]Serum Survival Factor Isolation and Characterization
[0135]The lack of tolerance to serum starvation is due to the acquired dependence of the persistently infected cells for a serum factor (survival factor) that is present in serum. The serum survival factor for persistently infected cells has a molecular weight between 50 and 100 kD and resists inactivation in low pH (pH2) and chloroform extraction. It is inactivated by boiling for 5 minutes [once fractionated from whole serum (50 to 100 kD fraction)], and in low ionic strength solution [10 to 50 mM].
[0136]The factor was isolated from serum by size fraction using centriprep molecular cut-off filters with excluding sizes of 30 and 100 kd (Millipore and Amnicon), and dialysis tubing with a molecular exclusion of 50 kd. Polyacrylamide gel electrophoresis and silver staining was used to determine that all of the resulting material was between 50 and 100 kd, confirming the validity of the initial isolation. Further purification was performed on using ion exchange chromatography, and heparin sulfate adsorption columns, followed by HPLC. Activity was determined following adjusting the pH of the serum fraction (30 to 100 kd fraction) to different pH conditions using HCl and readjusting the pH to pH 7.4 prior to assessment of biologic activity. Low ionic strength sensitivity was determined by dialyzing the fraction containing activity into low ionic strength solution for various lengths of time and readjusting ionic strength to physiologic conditions prior to determining biologic activity by dialyzing the fraction against the media. The biologic activity was maintained in the aqueous solution following chloroform extraction, indicating the factor is not a lipid. The biologic activity was lost after the 30 to 100 kd fraction was placed in a 100° C. water bath for 5 minutes.
Isolated Nucleic Acids
[0137]Tagged genomic DNAS isolated were sequenced by standard methods using Sanger dideoxynucleotide sequencing. The sequences were run through computer databanks in a homology search. These genes can be therapy targets particularly because disruption of one or both alleles results in a viable cell.
Sequence CWU
1
1271925DNARattus norvegicusmisc_feature1- 925n = g, a, c or t(u)
1gggggaaaac cnggnaattg ttttttgacg anccaaaaag gggncnagna gcnnttntcc
60tanatggggn cgggatcntn tccnaggana gattnatgga gtatnccttt tttgcncnaa
120ggttgattgc tcttgaaagg ntttgaggtg naattcctcc gtnagtttga ccgtagtcgg
180atntgaagag ggattgttna gcagncataa tttcattccc tgnacaccca gtaacnnttt
240accgtcattt ggttgggaat tgatntcggg aggtancaan ggccacagtt atttattgtt
300ncggaggatt gcaccaattn ggccggctgc ctctganatc tgtttctcat ccatgccggt
360tcacccagac gaaagccgaa agcntcggga gtcctaactn tagtccntga aagtcattcc
420cagctgcgta attgggctgt gcagagtccc agctcggtaa atatttgccc cgtgactgag
480ctggagagaa tgctcctttc ttggtcctgg gcagctcttg gcagctcaca tgcactgttt
540acctatcctc ccacattccc ccctgaggaa tcatcgtgcc tcggttccct taagtcctct
600caacagaaaa caaggcagag tggaacgaag gaaagtgcgt ggccgttaga aagcctgtct
660cgaatctgtc ccacgtgcct caggtagcgt tccaaacagc aaagattcta gtgaagaaaa
720ataccgtccg gtcaattagt caggtggaca gagcaggacc cggtgtcttg gaagcctcgt
780ccattcctct ggggaaggtg ggggggggcg tgtaatgcag ctctcaagaa gaaggtattt
840ttgttttcct ggagaaactg ccatcccagg agctgagagt ggatcagtag gaaggcctgt
900gacaggaagc agggaggttc agcng
9252554DNARattus norvegicusmisc_feature1- 554n = g, a, c or t(u)
2caagatngan ggggcggcgg ttcgnccaga gagcgggtag ggaagggaac gcgccggatg
60agccngggtg cgganagcca gaccccaggc gtgggaaggg gagagagata gagcggccgg
120ttgggaagag gaggaccgtg gttnataaat aacagaaagc ccagagggac gtanccatcc
180gggatggaga gaggtaggga atccagntgt aagtcccaaa ctgccaccac cttcatnaga
240actgcttcgt gtaaggtcac gcaccgggcc agctgtccng agtggcggtc ctggcgtgtt
300aagttagcta aagtnactgc aactccgnct gtgcagactg ntcgtaaatt ctctctgtcc
360gccaaattct ccctcctatt aaacttttca cttcctttca cttagtttcc tnacttcttt
420caaacggaag ctgtaactga gcctgccacc cnganacntt gtggttgcca tttttatgct
480aaagtaatcg tgttttttat gcctgtcaac tcccttttca tntaaagcag ggcntaccct
540attataactc tgcc
5543891DNARattus norvegicusmisc_feature1- 878n = g, a, c or t(u)
3ttngaaanaa tttccgtnaa ggtcngnaat nggccccgga aaaaatgngt tcctccccac
60cttcattggn gcggatcctg ccngggaggc caatggttta acaaataatc tttnggagnt
120ntggtngggg ggggagggac ncccacagan tcatgnggtg gttngggngg ngggcatcgt
180tnngatatta tcacattntg ngaanctatg tnggggcttc ctttcngaca ggtggtggtt
240nnacangngg atgtgtgctt cttttttcag cagtggtgga cccggattct aagaccctta
300cngtaacaat gccctntttt cctaagccta accagtcctt tangaggant gctcttgggn
360acccatgctg nntcacctag ccttggntca catnttnnac acaggaaaag gcagcatgtc
420ttntnggagc tcagcttatt cccttcccnt cccatccagn atctccctgg gntggatgag
480gtggatgacg catcttcaaa gcaccccacg tntcatggga tgtgcacagg agcttcgttg
540gaaatgtgtt gcgcgaccag gcttgtgtag gaaacaacag actactcgaa attaaagtcn
600taccttgcag ggttctcaga ggcttttacg cattaataaa catttgaatc ntaagaaggg
660agcacagcat gtaatattnt tcaaattatc aggcnttgca accttcatta gtttctctta
720cgcagctggg ngtggtggtg tgtaccttta atctcagcac tgaggaggca cngatatctc
780catctctgtg acttccagac cggcntcgcc agagcaagtt ccaggccacc cagatgagat
840gctcacagag gggacctttt tntgatgacc aacgnagnat gcaagtaagg a
8914974DNARattus norvegicusmisc_feature1- 974n = g, a, c or t(u)
4aaaanaanat attccgnntc tnntagcnna gaagttntnc gagcnntccc ccgtnttttt
60aaaaacccnc ggattccggn nntcgggntt taanngnttt tttaanggcc cnaagncccn
120nttattgccg ncntttcccc cccgctnttg cnccccttta cttngagant ngtgntncna
180agatttnaag gttnttgccc ccccggcttt tnttcccctn nttttccccn nagntttaaa
240accggtntgg gttncnantt nnttgnancc nccnattggg gtttccgntt accngggttt
300ttccccatgn ccgttccctc caatnttgna cttcccnggt cngggtccna atnccnngna
360acngntcnan ccttattgac aattaatttt tccttgngna ntctgncccc cngnantttg
420gggttcttgg gngcagggcc tttttttcnt tggnngcaan cncataaatn ttaccagntt
480gattgctaag gaagtancca tggttgngaa cccccccttn ttntctccca gatggaaccc
540aggattttgg aactgcagag gcttcagggt cttgggaagc ggaggcagnn aaagattgga
600gtgcactgtc cttttgcaat atggggtttg cctgcctgct ggctcntctc ctgctntntc
660agatggtgac tgaggctact tcngcaggac tnggaataat catgtccagg tggctgccct
720tccgagcaga aagggacaga cgtggggcga tgaagttgct atcgtttntt tttttttctg
780cacagactgc aaagtgtgca gagggaggga ggctgtgcaa aaaaaaaaaa aaaaaaaaaa
840aaaaaaaaaa ccgaggacgc agaagttaga ctgctgaccc atttggtgca tgtgtgccca
900tggagggagg ggaccttntt taaagggttc acgcggcacg cantgggnaa nngnncctnt
960acgnnnctcc caga
9745850DNARattus norvegicusmisc_feature1- 850n = g, a, c or t(u)
5anttttccct caagnaaant ntggtttggg caacttgaag acgcttnnac cnaaaaccct
60tgnggagntt ggngaccttn ttaccgnaan gagtgggaaa cgttttcctc cgggttnang
120gttaggggga cccgnnggaa aattttaaaa ccnngngggc tttttcgaat taaggggaaa
180ngcggtttng gtnnntgaag ggcgggnggt tggagtcnna gtccagagtt gatttccacc
240cacaaatntg ggaggtgncg gggaatgntg ncnttttctt gngatgaggg ntgccgtncc
300ggantaacag ngnttgcntt gtntngcnaa acgaagagtn tcctgnttgg aataggngtt
360cngttcgang ganccagatt tangngntgg agnaaggatt nggcagataa angcntgaga
420natgnancnt ggancaggtc nggncnnagn ntacagatga tgnncccana canganataa
480ntncagatca cagtcgtacc cgnggctggg ccatgaanag ggcatcccca gacnnacaca
540ngccttnana antgntcaga gaaccancag tggntanggg ntgcccnnnn naccagggaa
600gacccggggc gtgncggata ttgacacanc agatnncatt tggggncggt tcgagggttn
660atgntcnccg agtacnagan angatcntcc aacccggaat ncggtgctcc ngtcgtccga
720tgnaatgagt cgnccggnaa cctcatatcc aagaaacnat acagcagtgg nntccgagtc
780tcgtatantc nttgcgggng gaggctatnt tcagaggnca agattaccgt tagcgggana
840aagtngaana
8506531DNARattus norvegicusmisc_feature1- 531n = g, a, c or t(u)
6ttgnggcngg gtctcctctg ngtgngngtn tccccnanag ggggggtctc acagtgtnng
60ngtctnntgt ctgtgtngtg cccctgtccn catctctcac nccagggaga gagatgtgag
120ananacatca gagatctctn gnacagtgtt tcacaagagt ctatcncana gagcacatct
180gcccggggng anacacaact ctaaatgtgt ctcanntgat ctctctnttg tgtctctnac
240atatgnggac atgctctcag agtatnggnt ctcttgngcn cttntgcaca cacacacaca
300cacacacaca cacacacaca cacncttctc tctggcacag ggntatggca nagcacatnt
360tnngagntca nagctntata tgagtgtgtg gcgaaaggng tnatnanann gacnncccca
420gcnnatatag gggggngnnc tctngggctc tcttnggnaa tntgngggng agtctgcnca
480cacaggcgct cnnacccanc nnnttggggc cccccaggng tttttcnccc c
5317572DNARattus norvegicusmisc_feature1- 572n = g, a, c or t(u)
7tttttntgtg gccctttaaa ctctgngtgn ccgtntnccc nagagggggg gtctcacaag
60gagacancgg nnacacagag gttttgngnn tattgngagt ctctgcgcac nccananttt
120aaccncgggg nctcntgttt tattttaaaa aaaaagagtc ncatgtntat ttctctnatg
180tgaaaatcnc attcanagtt ntggggtttc ccntgaggag anatagagtt tcacactctt
240ctctccgagg ggtcntcnca tgtntctccc caatgtgngn ggnacacaca tgnggccccn
300agggggtgng ctctctctgc ncagggcncc ccccaanang tagaganaca ntgtggtgtt
360tcacaacaca attcncgaga nattntgttc cncantggnn gtctnagntc ncatgttgtg
420gngacangtt agnncncccc atnttcnccc ccctttcaca ctgccccnag agagagaaan
480tctnggcccc ctctanannt ntttttaaat cnccccnnac cacaggtntt cccagggtat
540gngacntcnc cnnccccncn aaagatntgc nc
5728906DNARattus norvegicusmisc_feature1- 906n = g, a, c or t(u)
8tgggagtctc tctcatatgg cgcnttcncc aaaggggngt ctctntccng agncgcanac
60gcgagaanac tctgtnnant ngtctccccc cncnccnaca gngtganant caaaacctct
120agagcccccc agaaancccc tntctcaaan aaagagaaag agaagancga gnagnagaga
180gananagaga gagagagtgt gganctntnt cctcngancc ccannnanan ngtgnggcnc
240actcncnngt gnngngnacc ccnggggatt tncgcgtgtc cccttgngct ctgtntanga
300gananatatg tntagtctct ctntcgcccc ctccgntgtc acgtgtgcgg ggcccnngag
360acacagacac ntctctcang gggaacacat anngactcnc acntgtgttt atattcnccc
420ctcccnctca cacanacaca cacacagnag atattnngct actctctctc tgtcacaggg
480gtacanattt antctnggcc anacccctct cngaagngng ggcanngtaa accccgcccc
540ctctcngaga angngagggc gntttacntt cccngtggcg tgtncgngcc cccgagactc
600cccttngnac ccccctntna accctctntt tgaacncaac ncaccntccc cnttttctcg
660gggnnggncc ngcncccnct ctcncaaaaa aaattnnaan ttngtcccct nccccnttnt
720ttcnggnana aaccgtgtcc ggggggggan nactcttttt tgnccttaaa atcaantttt
780ttcccctttt ccnggggacc cccgnnttcc tttttaaaaa aaaanaaccc tttctccctt
840ttaaaagnac ccnttttttc naaaaccgtt ccgnatttaa ttcctaaatt cccttccccn
900ncccgg
9069914DNARattus norvegicusmisc_feature1- 914n = g, a, c or t(u)
9gggatgngcc ctcagatcaa tacacccctc ngggggngtc tctctctatc tcccncagna
60gactcccatc tctntntntn cccccaganc tggngaacgg ngtgtggnga nccntntctg
120ttctcnantc tctaaaagng cnaaaagcgc ananacacgn gcctctctat anatctcacg
180tgtcccnngn nctctcngac ccctnntctg tntgagagac accctntctc aaaatatagt
240gtacacgngc tttgnggctc tccccttttc tctccactnt tgagngngaa acgcggngtt
300ntctctgaga tgtaganagn gtcccctnct cnatatatgt gttncccact ccnnagggng
360tctcataaaa atcncntntc tcaacaccac cncctcnacc ccccncacga gaacacntcn
420ccaccncnan gacacaaana naaggngtnn anaaccccan aaaaactnng ntntcngntt
480tacacacaca cacacncacn ctcncncaca cccccacnna aatgggagaa aaaacagaga
540ggngtgggtg ttngnntcaa caccntntta cctctctgnt gnnanttgag aaaatatttc
600tntncttacc cctctcccct ctctgtgtgt ngannatatc ngntctagat gtcctnaccc
660tccccaaacc tttctcnggn agagacntct ctntnttttt cccccncttc catttgaaan
720anangagaag gnccaaaaag gngggngtct tctcgggaat ncnccctttt ggccccccaa
780cctgggtttt tttccccctt ccttttaatn antttttcna nacaaanctt tnngngtttn
840ggaaaangcc tttnnctgnn nnttttttcc cttccccttt tnnangggnt tccccccccc
900ccngaatttt tttt
91410400DNARattus norvegicusmisc_feature1- 400n = g, a, c or t(u)
10ttcctgggtg cggtctcctc tgagatagtg tatcccctat agggggggtc tcactttagc
60acagtttatg aatattatta catatttcac aagactttat attgttataa tatgcctcat
120gtgagatata tgtgattctg tggtggtgtt ctcagagggg gtttgggtta ttggggataa
180tagtttgccc ctcgcggggt ctatatttat atatgtgaca caatatatta gagagatttt
240tggttatata tatttccctt cgcgggggtg gagatttatc acagggggag agcttttccc
300ttgttagcaa aagtccctgg tctcgtcccc catctcccaa aaaaaaaaaa atgtgaaaaa
360aaaaaaaaaa agggcccctc ttgagtgatg tccccttctt
40011880DNARattus norvegicusmisc_feature1- 880n = g, a, c or t(u)
11acccaatctt nanggtggca gtgnggnnga tcttaacggt ttttnagaaa aaaaantnct
60tcgctcncac ccccaagcct cccnttctta ncagcttttt tatangaaaa aagatgataa
120cgaaatttta aaaaccgtcg ttagaggaaa tgaaggttca gccgaccatt acctganagt
180aatgaaggtn ttccggaggg ttgccttcca atcccagatg gatttgagtt tcaggatcaa
240ttcagttacc gntgaccatc caccnncctc cngtataatc attngatgag gatgaatggt
300gagtgagtga tgatgatgat gatgatgatg aagggatgag aagnacacta tgataacaag
360tgtctcagtc cacattaagg tttgcctgna aattagtgca taagccatgg gagacaaatt
420cttttcnnac acaattaata gtntcttant ccttcccatc ttctctgccc cattctgttt
480tccaccacag gtctgcagcg ggctacagct tccagtctcc aagcaaatac cagaactgga
540ggagaaaatt ccagtccagt gagtcatggg cagggggagg ggtggggtaa gggcagtggc
600gctcattcct nacatggtgt cttctcttgc ctagcctggg atctgagggc aagagaacct
660gtaagcttga tttgatttcc actgctgact ggagtcactg ccaagggatt tgggacttct
720ccatctctct ctctaacctg aaatccttag gattctatta tttcaccgga ccagagctgt
780agcagagatg agctccaagt ttgaaatgag aaaggggaaa ttgagagcta tgagctaggn
840gcgaaagncc ccacaaagnn tttggcaagt agaaaagncg
88012909DNARattus norvegicusmisc_feature1- 909n = g, a, c or t(u)
12cgngagnngg cagggannna ggngggagcn ngagaggaga aggagaaggn nnggnaggng
60nngngagnaa cgggcgggan cnnnngacga gagaangggn aggggancga agngcggngg
120nagacggtgc nnggggggga ggggcaggag nggnagagag gcangagngg agnggggaca
180agcnnaaanc gaggaggnan gangngangg nnggngngnc gaaggcgcnn aagnnggtcg
240gngagcggna gnggnnaaac tggggaacga gacagacggc cccnncggng gcangnggga
300gagnnncgcc agngagagna gncagnanca gancanggga ggggggggan ncacnggcgg
360gagggncgan gacggnnngn annggnnaga ggcannnnnc gccnanagng ngaagngagg
420cangagtgnc gcnngagnag acaggcccgc gcnccggggg cagacnnngg ncaccaccga
480gggtgggngg ggcncggaga naagaccaga ggnnngaggg cganggcnng ggtnngcccg
540ggccncccna aaaaaanncc gaaaaaaaan aaggggcgcn gcngggcngg ggaggagcgc
600ntnncgtang tngantgacg gaggccngna atngggccgn gccanncnag ggcgnagagg
660cccaagngcg gnaggngnaa gnanagancc ngnnggtngg gagnganagn gcnnggnncc
720nacccccngn gttganggcn cccacgncgg ngcaggccgn nnaaagngag tccccnaaaa
780nntcgnggtn tnacancgnc ccggggncgc cgcngngtcc cgncacacng gannncggag
840anngcctnnt ntctncacan ggngccanac nngntgctat gcaaaagggg cgnacttcna
900gaaaaagnc
90913927DNARattus norvegicusmisc_feature1- 927n = g, a, c or t(u)
13cctttattcg gaggcaggga nnncttgtcc gggaangtta aacgtttttt aaaagggggn
60ncccnggggg gggggnttnt ccagggaant aaaanggtgn gttggggggn aaaaatttat
120tttnaaaaag ggcgnccnat ataaangacn ttcggggggg tttgaanagg gccggaancn
180tcgacgggtt tccgggnggg ganaaggana agggnacgca cgggatttct tncccttttt
240tngcaaattg cngcaggana ccaccgggtg gggnggtttt gttttccgtn aagaaagcgg
300gngtggaaaa acanggataa acgggaagan ggggttattt nggttagnaa ttgnttccag
360nggngccagg aaattggcct gtccaaaatt cttttcccng cttttaagac aggcaggtat
420tatttggcag caggttatta cnataggnaa gtaaataaca atgggtaagt gcctggcaca
480ggccagggta agtagggcat gtatggaatg ttaaacatta cccttcatcc tgagaaanaa
540aanacaagna anaaaggctg gtctcacata tcccaaagct ttatcttcnt aggtgcccca
600tggtgaacgt taagccaagc ntatgantca caagggacga catgggcagg ntagggtaca
660gaatcagtgn tcagagactc caggggcacc cctgattccc tttgctgtca cacagacact
720gctccaggga caaccctccg gatgtgagta tatgacttcc tgatggtgac gctgccgtga
780tgggacactc ntcgtggtag cacacattcc tcagtcagct tctgagcntc agggtcccag
840cagagcacag tggcaangac tttcattctt nttggncttt cccagggggc gtncccaaat
900ggaagatttg gcaagntaag gaagntc
92714848DNARattus norvegicusmisc_feature1- 848n = g, a, c or t(u)
14ttttccaagt aaancanggg anttcggtan aagaangttt aaanaagngt ccaggcancn
60gaaattttcg nggntttggt taacgangca accagggggg ggtttcaang ggtcttctaa
120tnatttnaan gggngtagtt tctggtnggt tcattccttn aaaaaaaaac aaaacaaaac
180aaaccgnagc ttctgcattg gccaccngtt gnggcaccaa cccttnangc attgcccttt
240ccttcctgcc gtgtcgggng gcgctaagcn gcccttgtca ccttccattt ntngatcatt
300ttccatgtcc ttgcacttct gcttccactt cntgttggta gacgagctgt atgntcagaa
360antgaagtac aaggccatca gcgaggagct ggaccacgct ctcaacgata tgacttccat
420gtaaatgttc atgcaccctg cctgcttgca ccctcaccnt catgcttgtg tgatgacctc
480accgtggctc ccccannann aaaananatc catgtctgca ccttttgttg gctttcttgc
540ataacctagg ataggttatc ttttccacgt tgcactaaca aggccacgcg cattcggtcc
600gtgaaaccac ctcggcatcc ttttatntca tagaggcaaa tntagcttgt ttctgccgag
660agatgacctg gactccgaat gggctctgag tatntccttt taaaacctta aaccagantc
720aagtaaagtt aggaagccat gaggcagtgg tgcaggaagt taggaagaaa naccgggttg
780ttggtttcct gggnctgggg tgagggacca ttgatagacc tttacgaaan ganccgcang
840atagaaaa
84815896DNARattus norvegicusmisc_feature1- 896n = g, a, c or t(u)
15agagaaaaag gaaanannga aagaaagagg agnaaaaana aagaggnggn aanaaagaan
60agangnanaa agaananant nngagattac gaantcgggg agagngaaag gaaacaaagn
120nggnggnaaa gagnnanttn tttcaagggt ccgnaacaaa aagttgagng angattccna
180acaagggntn nccacccaan ctgntaaagg gangatttgg ncaaacanaa accngtattg
240gggagttaaa aagagtcacc aaatagggaa aaaaagttng ggggagggnn aacnacnggg
300taaaggttcc aggaccagag ngttcagnac caagtttcag tattcaggag gacagagttc
360aggatcnntt tggaacattg gggtttgggt agcntggnaa cacgaaccct tttgttcata
420aaaaggaagg gaaaagaaag ggnngaagag tnttcccaga tgnattntga gcagagaatg
480cccgaccccc cgaatacgta gttccaaaat gggattgnac ctgtttcacc tcaaatttca
540ntcntccttc tngtggacag acgcagggat ggggtcgggg aaggggngaa gctggtgcgt
600gttctgtggt tgccggtgga tgntctgcag ctgtntaccc caccgaaaac gaatggatgg
660gatgtcactc ccaggcagta gggggcgcac gcgcattgtg ttntagagag anttccccag
720cctccccngg aannacaaca cgttntcttc ttcttaaggt ggtggtgggg ggggggggga
780agacctattg ctttccgaga ggatcggacc aaacagcaga ttntgctcaa ggcccttgaa
840ccctgntatc tcactaaaca tctgagatac tgacattaca gatacggata tcgtgg
89616858DNARattus norvegicusmisc_feature1- 858n = g, a, c or t(u)
16gccaatcaag ttncggttaa attttggaaa ngnggcgaat gcnntgtctt gnggattttg
60gagggnggaa ngtnggtnaa agagttttaa tgttcttggg atcgcaanta ttttcctggt
120tcgcgncttg tacattatga gggttgataa cngctgtttt tngattttgg ttaacanggg
180ngggngcntt tttnggntga cctntagtnc ntcngngccg ggcattttgg ntaccttttt
240atttttngaa gtncagggat gttgtgtact gggaatattc cttagaagtg accatgattt
300tatattttat taaatatata cttagattca ntctttgcct aagcctggat gttgttggtn
360tttgtttttg ttttgttgtt nggagagttn tcattttccc aagctggctt tgaacattca
420cttccacaca aacatgtcca cacacgggca aaggtgtatg cacagatatg gacataacac
480acacagagaa gaatnacaaa caaacaaaca aaatatttcn gacagaaaca antaaataca
540tccagaaggt agaatattct acaaggcatc aaatctgttc taaagaaaaa gttataataa
600agaaaaacat tgaaaggcag gtgaaggaga ttgaaggcca taggggccac aaaaaggttt
660aaacagcaaa gcaccaacgt agatatccgg aacgtgctaa atatggcaca cacaggatat
720ccgggaacga tgagtcagcc agcggcacat ataaccaacg atgtaatctg ttatgtaact
780atgaatcatc cctggcagag tgccaccttt gtgtgatttt tgtataaata tgcccctgag
840accagaagcc attgcctt
85817551DNARattus norvegicusmisc_feature1- 551n = g, a, c or t(u)
17ttntctgtac ccccttctca aaaaaagtgg ctggtgnctt ttctcngaag agaatcctca
60ccnccncana anaaatatct ctctcccccc cttgttgntt gtcncccnnc ccaaaantgt
120gngatctntc tctctgtgca cgaganattt tagaggggga tatccccggg gtgtngccng
180tgtctntcct ctcgcgaata tctttangag nctctctctc tcganccccc agngtaggnn
240gagngganaa catttttntg tggnggcccc ccacaananc acnaacaana tattttcgag
300aancncatgn ganaatcggg gggggggggg ccngtgttna cacnatancc ngggngatna
360nanagacacn nnatatntct gggntgtgna aanataanac aagancanac atgnggagan
420natgtgagan tgtgcacacc ctgttgtgac atgtgaggtg gggggctgat gatncctncc
480ttctacgtnn tntcttctcc tccncantga tagacnccac ctgctggagt gnctagctan
540ctggggtcgg t
55118888DNARattus norvegicusmisc_feature1- 888n = g, a, c or t(u)
18gttaaatatg aaaaagtggg ggtgacaggg ggtgataccc tttgcgccgg gctatggatt
60tttggcaccg ataagatttt caggtgacat ggaaggtggt tggggatggg ggaaagtttt
120gaggggccaa aaggataagg aggatgattg attggtttgg gagcagtact tggaaagagt
180gtgtttgatc ggtaaacaac cacgtgtagt gtgtttttgt tgcagcagag ataagtgaga
240aaaagatttc aggagatctt gatttttttc gggtcgagct atgttggggg atgtgagggt
300acaattcaca agatttgttc acagggagtt ctaggaggtg gtcccattag ccggtagggg
360ggttttctca ataaatgggt tcagtcaggt gtttgcctag atctttcatt agttcctccc
420ttcaaaggga ttttgaagga gtgctttgtc ctgtggagca attgactcaa tcaataaact
480taagtaatct cccggattac tgttgatgcg ttcccagaga ggtcccccgt agttaccagt
540gaatcacaat ttcctaacca tatgattttt gttaatctca ccacataaac ccacaattct
600cgcgtccttt gtgatggttt caaagtctgg aatatttttt cctccatccc tcctttcctt
660cctcctttta tccctccctt ccttttttcc tttcacagga tctcattatg cagcccagtc
720aggccttaaa cttgtgatcc tcctgtctca gcctcctagg tgttaagatg acccaaatgt
780aaaccatgtc cagttacttc ctcctaatcc catcttcaga tatcctttaa gaccaaatta
840aatattaact gaaagacccc accagtaggt ttggcaagct agcaaaga
88819867DNARattus norvegicusmisc_feature1- 867n = g, a, c or t(u)
19ctttttctaa attttttaac gggggaaatc aaacggcaaa aaagaggggg gaccacctca
60atcacccaca gtggaaaatt ggtgggtatc aatcaggtgt tattaggggg ggaggaatgt
120tggggaacaa aaaaaaaatt ttaaaaattt ccaggggggt tttgaaggca ggtgatttaa
180aaaccgcccg tcagttaagg gggttttatt tttttttaat aaaaaataaa attaggattc
240tggaatagaa tttttaattc agggatcctt atttttaatg tttccagggt aaaagggaga
300tattcttatc aggtttctgg aaaaagtttg cttggtttcc tttggcagga gagaggttta
360aaaaagactt catttgaact ttttgatcat tgtgtaaaac tttttttttt gaacaaaaca
420ataaaatgta aaaagatata gatcttaggt tttttaaaag acaaacatat aaaatattaa
480aacagattgt ctgtcccatg caaatgactg actgaccttg taacagctcc acagagtgtg
540taaaaacaaa aaaaagcccc ctgagagcct tgagccatca ggttaagtct catttattaa
600tattttcaag gccacaggag acactctgtt cccttcattt agggaggtgc tgaggcagcc
660atgttttccc agcagtgggg gttgggcaga gccactccag attggcttgg aggggtgtgt
720agctctcagt ctgcccggac ttggatggtt tattttctta aacgaaaaca cctgcctgag
780aaagagccct tttcacgggg tggccaagtc ccagcccgcc ctgggagcca aggtcaagtc
840ttagcttagc gttctaagga cacagat
86720897DNARattus norvegicusmisc_feature1- 897n = g, a, c or t(u)
20aaagggnanc aaaaccntaa nggggagggg nggggaaatg gccaaaantt ggggttaaaa
60aaagttagga tntggttgga tccnacccac aaggaatttg ttnttaattt tttaaaggna
120aatttgggca cttcnattgg gaaggttaaa acccaggcaa gtgntaccgg gntatgcaag
180tgaaacntga ttctggnggt ggagggaagg atantganat gtgagtgagt gcagttgagt
240gaggacttgt gagnacaggt catgcccacc aaagggagga gcaagggtgg gcagtggtag
300gtggtgtgtg gttcctttct gggggntggg cggggagaca gatgagaacg ntattggagg
360acaggnacaa gtgtactgaa atgcaaatcc ctgtagatct ggaaaaggtc tggnttcagg
420cttgatgctt gggccggcaa ctgtgnacct tccctgnacg ttcagccccc ccacccttac
480ggaagttttc gtcactgaag actagtggct aatcagagtc ttcaatggac ctgccaatca
540gaaaggaagg cgggntnttc cgggtgcnta ggtgtaggat tcgctcagta gttaagcagt
600cttaactggt tctggctgct gtgctntctg tcctgccgtt ggattntctg aggcatgttc
660aggcaagctc caaagttgcg acatggtgag cacaggggca gggggggcgg gcggacgggc
720aggggactga gcagtgggag ctggtgtggt gggtctttcc cggggctgag ttggaatccg
780cggctacccg tgaggtctta gccactcact agacccagcg gcagtttctg aataactttc
840nttgtagggg ttggnactcn gnaaagactt ccacnaaggn cttggcaagt agaaagg
89721435DNARattus norvegicusmisc_feature1- 435n = g, a, c or t(u)
21gattccagag agaggagtga actggcagat aaggcagtca gcataatggc ttagatacca
60tgtgctttcg ctcactatgc acccatgaca caagatcaca gggtacaggc ctggaccatg
120gcagagtata cactggttgg gtaaatgaag aggagagaca gagtgggaag tcggcttagt
180ggatatggac ttcaaatttg atgaacaagc aattcaaatg agtatcgtgg gcttgantgg
240tatgaagacc cgtttgcaaa gcagtggtca taagagagaa aagagagaga gagagagaga
300gagagagaga gagagagnaa gagagagagn gtgtgttgtt gttgttgttg ttgttgttta
360ttggttnata acaanatnta cctttgggcn ctttngaaag actntncaca aaggagcttg
420ncaagctaga aaggt
43522894DNARattus norvegicusmisc_feature1- 894n = g, a, c or t(u)
22gaaaaaaaaa aaannataat tttaattttt cccccatttn aagggaaatn ggaaattaaa
60natnggtttt nagcccaatg gaaattaaaa ttaagaaggt tgttttccaa aaacctttcc
120ctagaggana accggccnat aggngggggn agnatggaag gattttccag agaggaatca
180gtttggngag agaatttgat aaggagttcc ttggaaccaa ccnggagggg gttttggttt
240nngggattna tcangatggt tgtccttggg aagcataagg ntggtttatt attttggtta
300aaggggatga agtaccntgt gttgcacttg gtagcccaat gtcctgtcat tgtgctttgg
360atgtaggcag ctttgaaggg atttntcctg agaggatctt ccggatcaga gtatatcgcc
420ttttcttggt gaggccccat agtgggantc cgcacttcac catttctttt ccgcccgccc
480cagttcggtt ntaacccacc cgcgtggcca cgatcccagg gacatagcgg gacaggcccc
540gcagtgcggt gacacacgtg ggcacacccc acctgtgcag ccggtggctc gcgntgaagg
600acacgaggcg cgacaatcgc gcgcggcgcc gaaggccaac cgccgcgttc atggtnttca
660gaccaaagac ccacaagnta cgggttccgg tttccgggac ngaggccagc ccggttcccc
720cgcggntgcg cagtgcaaan tcggccttcc ccgccggaag tactcctggg agcggtttcg
780gcgcgtggca cttttcggtc cacctggagg caacactggc gccntttcct gtttcagtct
840ttgntaggct ataagtgaaa gaccccacan gtaggtttgg caagctagcn aaag
89423594DNARattus norvegicusmisc_feature1- 594n = g, a, c or t(u)
23ccattaatgg gggngggnaa agggataggg atttgggccn gnnggttant ggggaagtgg
60gattttaagg aattccccaa aaatattgat tcttccaaag tattttcctt catttcccaa
120nagagtaatt tcaaaagccc cagntttgtg gaatcanttt ttgaanatat gaaaaggccc
180taatggtttc ggcattatta aggcccgctg aggacactgn tcaagttact cttggaaggc
240gtttntggca gaaacagaac agccccgttg gcacggacag tgtccactgt ttatctataa
300atcttttcaa gcagatcttg cagccaacta ggtacaagag tcggatgggg atggggggcg
360gggagtcaga gaggtcggaa caatgaggcg gaaaccaaaa ntntgaaaca cgcccacctg
420aacaggacga aagggtgggg cttggtccac ccagaaggaa acctcgaact ccacntttca
480aggtatccgc tccgggttag cagccccggc caaacgcccc tgctggcttc taacccaacc
540agctacgaaa gcaggctnga ccactagctg ncctcgactt gaaagttccc acaa
59424586DNARattus norvegicusmisc_feature1- 586n = g, a, c or t(u)
24atccaatnat tgggagtagg acaggggatc gggattngag gccagttggg ntagtgggat
60gctgggaatc ttaaggaatc cccaanacat atggattctt ccaaagtatt ttccatcaat
120tccaaataga tgtatttcaa aagccccagc tttgtggatc agtttttgca ntatatgaaa
180aaggccttan tgnttcggga ttattaaggc ccgctgagga cactgttagg gcgcntcaag
240ttattcttgg aagggtttct ggcagaaaca gaacagcccc gttggcacgg acagtgtcca
300ctgtttatct ataaatcttt tcaagcagat cttgcagcca actaggtaca agagtcggat
360ggggatgggg ggcggggagt cagagaggtc ggaacaatga ggcggaaacc aaaantntga
420aacacgccca cctgaacagg angaaagggt ggggcttggt ccacccagaa ggaaacctcg
480aactccacnt tcaaggtatc cgctccgggt tagcagcccg ccaaacgccc tgctggnttc
540tacccaacca gctacgaaag caggcngacc actagctgac ctcgac
58625909DNARattus norvegicusmisc_feature1- 909n = g, a, c or t(u)
25ggggggttgn aaattgagaa gcccnccttt cntctttgtt gtgaanacat ttnccntncn
60gggggatccc tnggttccgg aagggccgcc ttagttnttc ttttcctcca cctatgaaag
120gggngggagc cgattaaaag aagggnggag cagngaggga agcggagctt cgcccgtttt
180ccgnaccctt aaccctgctt gttcgggggg ggagngtgcc accnacccgg gngnggtggc
240acggagatnt gagggggagg gatggtttgc cntggccgct ngtgggtggg cgggcaggcg
300ccggcattcc cggcaccttc ngaagacnga gccgggttca gggacnnaca ntccccgcca
360agngggacca accgcttcgg gtgggttccc cggttgtntg gtgcccaggc cgnacgccgn
420gacngaggga gacccaagga cntagantca ccggtgagcg ggccggcgcc ggagagcgga
480aagaggagcg tagcacagcg cagntcggcc agacgttgtt cttntaccac ccaccgagcg
540tttaaaaaaa anaaaaaaan cccgcggcag cggacttttt ttgtagcgga gcccgggcgn
600gtcacttgcc ggaagtcccg cccntcgttt ctgccaccgc ccntcggtta cctgggcaac
660ggcgcggggg cggagagtgg ntgcgcccaa gggcnttgtg ggggtggact caggcccggg
720ttcccgatcc tngtagaatn ttntagaggc tttttcttta tgcgaggtac cagagggcgg
780aagtcttgag gtggagaggt catgtcccag agccgtaagc cggggacgag tgctntcagg
840cnntgtgcan ttgggatcct nnggnccacc ntgagggtcn tcacaaanga agcngncnag
900taaaggagt
90926576DNARattus norvegicusmisc_feature1- 576n = g, a, c or t(u)
26ggcaccgggg taanangggg gggagtngtc ctgggnncct tgaacgctgg gggaggantg
60gtngggggct ccaagggggn nggggaganc tnaagntcnt caanntagag agggggaagc
120tccccactct acatctgttg tcggagcacc cccccaccca gagggcgctg tcagtcatag
180actagagacc tcccctcaag tgnctcnatc cttccaatag acgagccctc ttgacgcctt
240tttcagagaa ttctctaatc ctcgggtcac ttccgccccc ctgtcaagac ttcacatatg
300tcctccacgc gagggggtgt ctagaaccat cataagaatc tctctgtcct cgttctttcc
360tgtgataaaa gccgcgggag nttccttttg ggcgtctaga tctccgtgct gagtgtctcg
420ggagagcgcg cgacatcgcg tgtgaanngc gacctgtctc cgcggagaat gggagtgtct
480gtgtgcagat gtcatagtga gaaaccaccg ataagggtga tagggtaaaa gatacttaaa
540gggctatgaa gaaagtgggg aagggaggag gggaga
57627853DNARattus norvegicusmisc_feature1- 853n = g, a, c or t(u)
27aacncccctt ncggggggng gggaaaaana aagggggtng gnggaannta aaccctagtt
60taaaangggn tanangtntt taangggcna aaagnttggt ttnantccca ggngggtccc
120tcctttgaan acccngaaaa attcatttnc agaggggttg gaagggggag ccgaaaagaa
180accccaacna cttcgcaagt aacaangggc cnaagggagn cagccgcacc ttttttccnc
240cccgcccaaa ggccagccgc attcaccatg aacagataga ngtaggaggc aaacaattcc
300agttaatntg gcggttgatg gcancttcgg attcttggtg gtatttctgg cgnatttgcg
360agggagacgc ggtgttcatg atggcggctg ggngaggcgc ggaggcgacg ctggagcggc
420ggagcgacga agttgcaaag gntcaggttc aaagcgnccg gcggggtcgg aggggtcgag
480caccggttcc gttcaagcac tgttgaagca ggaaaccgcg gngantctgg gcgagaangt
540ctggcgtagg gaccagcggg ccgcacttta tagcgggatc ntgcgtcagg cgcgntccgg
600ccaatcagcg cggtgggccg cccagccccg cttnttcctg taggcgtgtt gcccaagcca
660gcagtgcgtg ggcggggagg agcctgtgtg attgtgaggc gantcttggg gttatgagct
720gntgcaagag cggtgcctgg caacaagcgg gacgtttntg tggcccgggg cggacgtagt
780tggaaccagc cgtactacag aggcattctg ggtcccagag agtatcgata aggttgattt
840ttaagtccca ccg
85328825DNARattus norvegicusmisc_feature1- 825n = g, a, c or t(u)
28ggnttncagg ggnacccccc ccccncttnn antttgtcca cgnaanattn nngccnnnna
60agganggggn ngggaagttt nagggcaang aaaagggaaa agtttngttt ggacaaacct
120tgaaaggggn tttatcgcaa nacnccgggg gggggttttt ttgaaagaga aggggaaaag
180attcggaanc ctgatttttt tggnttgagt naagnggggg angggnngna aaaattaaan
240ggattccngn gggggngact agtantttag gggggagaaa agggttttat aaggncccat
300aaagttcagc ggaaagccgg ntccggggaa gaccacccat gngttttaat tagagtgcaa
360cgggttgaag agcccaggaa gcccaganac tagggtgagt caccgngaaa ntaacagacc
420ataaaaggaa ggatgcagaa cagaccaggg tacnantcac aggccacttg gcaggaagag
480atagccccca gccccngaat ncagagcccc aacctgccaa tgnggtagnt ataccttatt
540acttcatcat gtgaatagcc aatcatatgt gaacatgtnt atgtgcttcg tttgaatcca
600ccaatcccng taantatgat ntgttctgna cgcccgnttn tgttccccaa tccntataaa
660agccccatgc tggagctgct gggcgcgcaa gtcntccgaa gagactgtgt gcccgcaggt
720acctgtgttt tccaataaac cctcttgctg attgcatccg agtggactcg gctcggtcat
780tgggcgcttg ggactcctcc tgagggaaag tcctctctgg ggtct
82529861DNARattus norvegicusmisc_feature1- 861n = g, a, c or t(u)
29anngaaacat ncccnncnnn ttnatccttt nggaaaaggg cancccaaag gnnnggaacg
60gatngaanaa ttctttcaaa aagaganatc gganggnnat cgnnnnggtt ttcaagtccc
120cccngagnan naaaattgag tcagtngggg gnaaccgacg nananaggaa caggtttccc
180gggagtcctt gggtntcngt tcgacccccg gaaaccgaac tnncgcnttt ncctttggga
240gnggggattt ntaaaggnna ncgggngtat ttccattcgg ntagttgttn gttcaagggg
300gntgccggac ggaccccctt tnagccagac ngngncccta tccgnaaaan tgttggggtc
360caacccggta agacagattt ntcgccantg ccagcagcca ntggtaacag gattagcaga
420gagaggtatg tagacngtgn acagattaag gaagtggtgg cgtaagnacg gacacattag
480naggacagta tgnggtatct gcnctcggtt gaagccagtt accttnggat aanganntgg
540tagntttnga tcccggcaga caaaccaccg ttggnagcgg tggntccttt gnntgnaagc
600agcagantan gcgcagaaaa aaaggatctc gagaagatcc tangatatnt tgttcggggt
660cagacgctna annggtntgg natnntganc ggntgaccat agagcacagt antgnngatt
720gcagtccgcc ccnaggacga naggagacca ggggcccang ctgnagtaac naatcaacta
780ccctnacnag atgnancaga gagagagagn accgtatant nantgnaaga gaggtcccgg
840tttcnagttc ccagnacgga a
86130149DNARattus norvegicusmisc_feature1- 149n = g, a, c or t(u)
30attngaggag atccggttac taaggatata gaagaaaaaa ataaatcgtg tgcctgcctt
60ttttttttta attgcctgct tctccccacc cccaaattaa gttgcttagc aagggggaaa
120gaggcttttc ctcccttcag taggtcagc
14931857DNARattus norvegicusmisc_feature1- 857n = g, a, c or t(u)
31gatctggtct tgcccnggan ganntcnntn ccgggggggn taaaaaagaa ttgntggngn
60tgacnagggg gganaccccn taccgngggn cnancggaan tnttggncac cgnaaaaaat
120ttccaggngn acangaacgg gtgcggnggg antaggggga aangtttgga gtgngccaaa
180acggaaaagn agacgnttgt angggttggg aaccagnacc ntggaaagan tgnagttctn
240atcngcaaca accaccggag gtagggggtt ttttgtngca gcacagatan gcgcagaaaa
300aaggatttca ggagatcctt tgatttttat tcgggtanga cgttcangtn gnggggattg
360ggagcggana accatttnna cacaggattn tatgaactat ggtcanttgc tttgttgtcc
420angtcgttgt gggattgctg tttttagtag ctgcaaacgg ttcgttttnt gctatctttg
480ttnngataaa tcagccccgg gcagangana ttcgaaagtt ccctttagga gcttatttan
540acgggctcaa ngccaccggt ttcgtttttn taggcacgtt ctgcgcattt tttttttttn
600gnatntttgg atcgcgtttc gtgggatctt aaaaaccgtt ttctgtgatt ggcacgcaag
660aaanactcat gagctggtcc ctgttgtgtc tctcaggacc aatcaaanac ccatttccaa
720cggctttata atgtctggtt ctgtttgcac aggaagcgaa gtcacggctt gcacccgtga
780agtctgggga ggttcagagc tgggaactgc ccagaggaag gggttcgggg ctacagccat
840caatcttcca gttgttt
857321630DNARattus norvegicusmisc_feature1- 1630n = g, a, c or t(u)
32cccccccccc ccccaaaaan aanaattacc nttttaccat tgnggttccc ngtccntgat
60aaatttttaa ccnncntttt tccttaaaaa ancgnatcct gangggattt ccgttnaatg
120gnnttaannc ttttngngaa tgttnacccc aatnttcccc tnaattttga gtnngataat
180tgcttanagg catttggaaa tttaacggnc acctgaggtt gattggttgn tattnaacgg
240acttngatnn gaggaaggcc cccaanattt tgttccattc cttntaagtt tgggacttgg
300aaatcccgtt gtttagatct tgaccgtaat caggagtcag cgtagaggag gccccggaag
360gagggcccag cgcggattcg cccgcggcag ggcggggacc aacagagggc cntcggggat
420aggggagcgc cgccccgccn tcccggggaa ggacacattg cttgttagca ggaagccagc
480cagacccgga ggaggccgct ccagcgttgg tgttgccggt ccggggctag cctgatccgg
540gcagggtgag ttgagacgat cgggtgagct tgggccgggg acgccagcgt cttcagtcct
600ggggattgtc ccaggagggc aaggagcttg gaggagggag gccgcacagc taggggagtc
660aggtctgagt cccgagtgtg ctctaaagcc ggggcggtga gagtggcggc ccgcccgggg
720ccgcgcagcg ngcagtctcc cccgcgtggg aagtggtaac ttaacgcaca gccacaggat
780tcccggcctt tagctgctgg agggagggtg gcttctcccg gaggagtctg ttgtgaaact
840cggttggagg gcaccgtggg tgcgggcaag ggagagatgg ggtcgccctg aagaagtggg
900gggctggagt agaaagtgga ctttgtgcaa acctcacccc agagtagtta gttaccaagg
960ctggtttttt tttttttttt tttttgctca gacacaagga aaatttgact caatgttaaa
1020atatgtaatt tggcaggaaa acttttttcc tagcctcctt gctaatatag ttggaacagg
1080gggctcccaa gaggtataga gtcccccatt ttacaaaatg tggttcagtg ggactgtggc
1140ccacccagtc gtgtatccat ggaagagtgg cttttatgga gaagttcatt ttccttaacc
1200ttaaaaactg taaaggatct tgtgcttgag aatattgttg gccagcttta tagtcttcat
1260ttataaaact atttagacta gagtgttata gattataggt cttcaagttt ccagtcacca
1320gtccttggct ttttagtatg gaaatcacca gtaatggcaa tataacatcc ctgcttctgt
1380ttcttagaag gctaaattac agtgtgttca aactccgtgt cattgcaaca ggttaaacta
1440actttatacg taggacatca gggtattgac attctcatcc taaagtcagt ttgtctgttt
1500ccagaggagg aactgaagca gtggttcttt aagtaactga ctcagggctt tcctgcctgg
1560cgcgcctgcc aggcatagtg tagcattgta ctgcatcttc tttgaccagt ttccccaggt
1620gaagagcctg
163033883DNARattus norvegicusmisc_feature1- 883n = g, a, c or t(u)
33aaaaattgta aggagttggg ggnatccccc ataattnaaa nagggaacaa nccntaaagg
60gagggnnggg aanggccaan attggnttaa aaanagtang tttggttgat ccanacacaa
120ggaatttgtt anaattttnn taatggaaat ngggcacttc aattgggang ataaaacccc
180aggaagtgat accngggtta tcaagtnaaa cntgattctt ggngnngagg gaaaggatat
240tgaatttgag tgagtgcagg tgaagtgaga cttgggagna caggtcatgc ccacccaagg
300gaggagcaag ggntgggcag tgtaggtggt gnggtggtcc ttcctggggt gggcggggag
360acagatgaga acgttattgg aggacaggca caagtgttac tgaaatgcaa atccctgtag
420atntggaaaa gttctggntt caggcttgat gcttgggccg gcaactgtgn actttccctg
480tacgttcagc ccccccaccc ttacggaagt tntcgtcact gagantagtg gctaatcaga
540gtcttcaatg gacctgccaa tcagaaagga aggcgggctt ttccgggtgc ntaggtgtag
600gattcgctca gtagttaagc agtcttaact ggttntggct gctgtgctct ctgtcctgcc
660gttggattnt ntgaggcatg ttcaggcaag ctccaaagtt gcgacatggt gagcacaggg
720gcaggggggg cgggcggacg ggcaggggac tgagcagtgg gagctggtgt ggtgggtctt
780tcccggggct gagttggaat ccgcggctac ccgtgaggtc ttagccactc actagaccca
840gcggcagttt ctgaataact ttccttgtag gggctgcaac tct
88334913DNARattus norvegicusmisc_feature1- 913n = g, a, c or t(u)
34ttccccccna gaaaaatatt tttngggacc canaaaaaan ggtcccnggn cctgttttct
60tccncccgna aanaacttcc ntttccntgg ggggntttaa naaaagaana tttcattggn
120ggttttntcc naggggggga gaccccnttn nccgcgggcc tttcgnaatt ttttggtcca
180ccngtnaaag attttcccat ggcgcaccat gtacgggttg cgaggngtat taggcggnaa
240cggtttttna gtgggcctaa tacggnanat aggaggacga tttgtnttgg tttgtngagc
300cagtaccttn gnaaagagtt gtagttttga tccggcaacc aaccacngtt gtagcgnggt
360tttttgttga agcagcanta acgcgcagaa aaaaggatnt caggagatcc tttgattttt
420cttcgggttc ngacgttatg ttgtgtggat tgtgagcgga taacaatttc acacagattc
480cgatngtagt ccaatttgtt aaagacagga tatntttccc ttcaaagaaa acagaaaaat
540acagaaacgt taattttcaa atctcnaatc tttcnttctc tcttcnntca ttcattcntt
600cnttctttct tctttctttc tntctttctn nagaggaggc atgctagggt aacagtagct
660cattttaaaa tctggcacct ggaattaatt tagggacaaa acacctttat gcaaaaaaaa
720gtttatgttt ttccatggaa cacagtaaaa tcaaaattaa aagaatataa caaaggcttt
780ggtgatttgg taggattttt tttttcctgg aggggaaaac agatgacttg gaaagtgtta
840ggaacatatc aagccccagg gaaagaaaaa cgtttgattg gtattaatta aaacactgct
900aatatattct aat
91335320DNARattus norvegicusmisc_feature1- 320n = g, a, c or t(u)
35tatgcaccca tgacacaaga tcacagaagt acaggcctgg accatggcag agtatacact
60ggttgggtaa atgaagagga gagacagagt gggaagtcgg cttagtggat atggacttca
120aatttgatga acaagcaatt caaatgagta tcgtgggctt gactggtatg aagacccgtt
180tgcaaagcag tgntcataag agagaaaaga gagagagaga gagagagaga gagagagaga
240gagaaagaga gagagtgtgt gttgttgttg ttgttgttgt tgtttattgg tttataacaa
300gatntacntt tggtaacttt
32036389DNARattus norvegicusmisc_feature1- 389n = g, a, c or t(u)
36gggggggngc naaaagggtc tttcttttna naaaaatcnn gganggaggc cncnanacgg
60ctnttanann tnttcngggt gtncctcncc gntgtgggga atganatntc gntctcgaca
120tcaggggatt ggagattntc tgngctcncc nctcacnacc cagaagaagc gcacagagan
180cagagtanca catcatacac acctnttcag ctacagagcg antnctctan aaggggactc
240ggggganaac acaaccctcc tcctcttctg actgngagng ccgcntgtag gntctgtcta
300cccancaagn cttgtgcagn ntgngaacct ctctntgggg tagagtgtgt tgngggagca
360gggcgtantg ttccaggnct agnctttca
38937882DNARattus norvegicusmisc_feature1- 882n = g, a, c or t(u)
37agnaacgcgg ncggnggnnc tcncccngcg gagcnggncc ncccccnngn ncccagaana
60gnagcgctcg gngannnccc acgngnagac nnnggctgcc ccncgngncc anggcnttnn
120nccnnccccc cgnatccggn ncnccccccc ctccctnggg gngcgggggt cccngngccg
180nggngatacc nggcganncn ttgtgccccc gcnngggggg naggaccccc ggcaccggcc
240cngacccana ncagnngctt ngtggggggc ccccccgcca nagaacgaat tncgccnccg
300gccgcggcca tcggaacncn cctagcagng cgtcntgcta ggcnggnnna cgggnatccg
360caancccncc cttngtaccg ggacagccgn gggnccgtat gggctgngcg ntnggccgta
420gccanntncc tttngaaang acncggnagc tnttcatccg cctcacaaac cncngggncn
480gngggggctn tntcntgngc cgcccgccgc gtgngcgcan aaaaaaaaaa aanncggccn
540tccncccctc ttttggccng ggtnccccgc ncaccccgtg ccgagtnccn nnccccccac
600aacctcacac cgatcccngt gggttcccnn ngggagtcgc ncgngcnnag cnggnttctc
660cccatnncgc gnngcttnag cgngccnnnn cacngtttgt nngngnntgc ctccccttcn
720tccttgaggc aaaagcccgn acngtntctg tggaccacnn tgctgaggng ctgggcgccn
780cgntctctct ctctctcnct ctctctctct ctctatctct ctttctctct ctggggcccc
840tcccttgntg nngccanaag nnngcnnacc cgtaaagtaa gt
88238975DNARattus norvegicusmisc_feature1- 975n = g, a, c or t(u)
38aatttngnca ataanggccc ttcccctgag tgngggganc ncncntgttc anaaggtacg
60tttagcgngg ttctcnagtt natggtaacc nagtacttaa ttggcncnct tgataaatgc
120tngatcctna naatttcaac aaccgcagga ccatttttga acttggcggn ngtttaccct
180tnatgnnctt tccnnaaaat ggcttccttt gncatcnaat agtgntgccc ctaacccctn
240ggttccggag gatgcatnng tggntgtgng tttgnccttg agcatgcngt tccgtnacgg
300gancaagntt ntcaatgttc cntcacncca tacttnggct tggggtacaa nttgtatatc
360ttcgggatta tatnagttta tgtctgnttt tcataaaatc acttgtggat ttggctttaa
420ngttaggaca acttnccaca gtttcttgga tctccntcaa catgttaacg ccattttgtt
480cttgtatact aaagtgacat gtcnttntng acactaacaa tcacaaatta ggagtaccaa
540tcaactttga gaaaatttaa aagatgcccc atctcttgta tcagcaagta ttcagccagg
600atttaattct ttatgtaaaa attagcaagc atttctatnt cattcacgtg caaattttct
660ttgattgtta attaagattg aagtgatatg tatggcccaa ataagtctca ctttaaaaaa
720tatttcttta tgaattatta tccatgaatg tttgatctgt atagctattt tatataagta
780tatgcaagga ttgctaaaac aatttttgag tgaaaaaaga tcctaggtag aaaatgttta
840agactaccta taccgtcatt aaaaactcct caccagcatt tactatggtt ggactttcag
900agatctcaat caactctttc ccacccagtc tactgaaagn ttccacctgt agcggcccaa
960gcaaactgag atntt
97539850DNARattus norvegicusmisc_feature1- 850n = g, a, c or t(u)
39ggggaaaccc acggtnaagg gnngganaac naggtanctn tttctccggg ttccaanaat
60ngaangcctt ccngagggcc ngaaaancat tncttcngga gccgttcaag ccagnaggtg
120ggtttcaaac aatgcttaag ttgtggggag aacnagncag tccgttccng acccngttta
180tcntaaagga gacggnggtt aaaggttagg gggttngaca gtcctgctgg tgttcaagga
240ggaggagaca agttgncatc caggngngca ggaanacctg ttaaattcct gaccnaccgg
300atgnttggag agcnaaggcg gattcttccg gcagtggcca gatttcaacc caggtcccgc
360ccngcttttc ttggttaggc aagcaggcct tagtccgnga ggacgcccct tggtggccag
420ggtatcacgg cccccctngg gtttccattt gcagtttgta ttggaccatg gatcactgct
480tccttntgcc ggaagttcca gattccaaac tgtgngantc ccatntgcaa ctcccatgtt
540tgccgntggg actttttnta atatcntggt acccgcttcc catttcccca cccccntgnt
600cccttcggga ggaatcaccg cccagtgtgt cacttcctgt aggnacttcc aaggntagat
660gagtgagtgg caggcctcac nttggcccag ttantcagtg cccacagagt agcttttttg
720agacgntagt aaggtcttag gggaaggaat gtagtcgatc cttctccttg gtggccctca
780gcactgtgag tagaccccac acatcagggc tgtgtcgtta ggatctctgg gagggttgaa
840agtttcgagg
85040889DNARattus norvegicusmisc_feature1- 889n = g, a, c or t(u)
40ggggtttcca aaaatttggg gntttggana aaccttcggg gaataaaaca acngnnnaaa
60attaaggggg gccgggggaa aaaggagatt nattaaancn ccacccgaat tnaaacnccc
120nccgggaccg naaccgtttt tggccnaaan ncgagaagtg ccttccnggc aaagtagggg
180accaaaggtn gggggagaga attggggttt gtncagngtt ccggttcnac ggaaggagcc
240ggttgttggg attgtttcca aggagngngt ttgngaccgg agcacctcng gggngaccat
300ggggnttgcc tgttagagac cngcgngatg ttttgggttc gnattcgggg agggatttcg
360ggggcctcag acnggggagg agtcccntgc gttcccnatg ggaccggttg tcgggcgggt
420gcagtttcgc tgctgtcctt tggcaatgng cntgggnatt ngtgggcaga ngagattccc
480cngcccccgc natttccccn gttccagttc ntaggnacca gaggttttcc gcagtgtgat
540tcagggagnt agantntagc gtctgtnttn tntgcgtttt ccccttcatg attctcagtt
600attttttagg agaaaaggtg cgtggaaaca gagcgtccct gttccgtgct gtttctcnta
660gcccaaaata cagatttaat tctgaagcca tcgaccccca tatccacttc ccgccctctc
720ataaacgtgt aatatggctt gctttttcct tgtaacgttt catccaacca tagtggtagc
780ggccacctgg catcttgagg tgggttgcga atgagtgaat gaatgagtga gtgaatgaat
840gaatgaatga atgaatgaag caagcttcag ggagattttc agagaagtg
88941929DNARattus norvegicusmisc_feature1- 929n = g, a, c or t(u)
41aatgcccntn aggggnnttt ccccgnattt naaaatgggn tncnngnttc caaagtttcc
60taaaaatttn cantttccgt ttttaccngg tttatggttt ncagcctact cctgttcgan
120ttccaaatcg gtttaantgg ncccnccgaa ncnttntttn tttggcagaa ggtgaanttc
180nttggggccc ttgtttaagg gttttnagcc ttaaattgnt tgntnagnnt ctccntaatt
240agttcattcc tttgaccatc ttttgnccct ccatcttgta aacanttaag tctattgcat
300tccactttnc tntcagttnc cgtttnaccc tcctnagcag aacccgnttc tcagctntgg
360atggttccaa anggtttccc aacctatgct caataccaca ggcagcttgc aggagggaga
420antggtatgt atttaacagc attttgaccc aaacttttag gagcagagag gactttaccc
480aggacaggaa ggcaaaagac ttgaatctta aacaaaggat taagaacagg atgtcatctg
540tgagcctgtc acagtgggtt tgcagagcag gagaacacag acaggattag ctataaagtt
600gttacattag ttattntatt ggagcataca atacttaaat agttctaggg caagagaaat
660gaacagaaat gaccttataa gagccagagc tgtagccaca gctttctttg tgcttagttt
720gctagttcac tctttccagg gcagtctggt ggattacacc aaattgctta gaaaatgcta
780gctctactgt ccctgtctat tgtcagcttt gcaatgtgca tagtgacagg agttgcctgg
840gaagcttggg gcttatgttt tgcagatcca ttgtaattaa aaaagaattg taaggagatg
900gaggcacggg gtgagggtga gggtgagtg
92942943DNARattus norvegicusmisc_feature1- 943n = g, a, c or t(u)
42ttggaaaccc caacctggaa aangngtntt nccgggaaat tcaacctgcg ggcnaatggt
60gtaaaagggc ctaccttggc ttngaaggga atntcctgaa ggnnnaatcc caannttgtg
120natcccaatt aaggntnaac nggtttaatt tgtnntccnc ntaccnaccn ggtttnccgt
180tatactaaag ggctaacaat taaatgctca naagggaccc ccaatcctng gcnagaactt
240gggttaaggn ttccattagg atttgccatc ctntaccgtg atcctgaaca tntnttgaac
300tgntttgcca aggaacngaa ggttttncct naagntagca cacagcagng accaaggatt
360ggaacccagc nagtgcttgg aggtaaaaga tcacttccnt ntcccttagt caggancntt
420agggagtgga ggcatcaccc acacattccc cagtttgnac gtaggtttca gccagcaanc
480cgtccactaa agctgcctcc aattcaaact ggattgagtg acaagtggct tgggtgtctc
540tcaaagattt ataggtggca atggccactc ctctgtgtaa ttaccctnta tgcacgtctt
600tttnttctct cccactccat cccccacccc tctttgtttc ttcntccntt cctntccctc
660ctgttgactt tttctctccc tgcaaacagt tccaggcacc gnttagcatn tgccactctg
720gctntagaaa gctttgcttc ccctctgctc cctggctggc tggaactcag cctccggtgt
780gggcagactg gctcatcctc tgtgtttctc tgagtgtgga ctgctgcctt ccacacagac
840tctctgaagt caaggagccg caccagcact tcagttgtgg gccataatca agncangact
900gaaagttgcc acctgtagng gccgcaagca aactgagatn ttg
94343867DNARattus norvegicusmisc_feature1- 867n = g, a, c or t(u)
43aggaaaccnt tttaaaaaaa aggggggggg gggggggggn ntagnggcaa aaaagatgan
60accctcaagn cggggggggt taaanaagga atcggattcg ggctttgnac aaataaagga
120gttttgngng nattttcccc ntggtcgttt tntgnacgat ccacggttga ccgacgacgn
180acggaccgac aaccaanacg taaaggggaa ttgtggaggg gttggaagtt tagatgcccc
240gacccaggac gtgcggccan cttccggaga cccacctttc ttgtnggccg ggnccggcgg
300cagcgnagcc atttccaccg gatccctata gcnggccagc ctagcaggcn gaacaccagc
360gggaagttga ntnggacctc ggagagcgcc cgcccttccg gcggaagtnc taattccaaa
420gcggcccgcg gcngagtttc ccatacaggt tggttccgtc tcggagtgac gtggcttgaa
480ggacggtctt cgcgcgagaa gagtaccctg cctttcaggt gcgggagtta cntcagcctg
540ctgcacaccc ggctgtgcgc antcttctgg tgtggccggg acggttcacc cagaggagtc
600tctgtagttc ggagcaagat gtcggttaaa tctggcagga aaatgccttc tatgctcatn
660tatatattcc tgcttccctc agcttgcttt cgacttagta aggtaacatt tcagagcggt
720gcacttagta ctttttggca ctgtgctgta taaatataaa tgttccacac ttaacatctt
780agatgttata tctaaagata tgcatcttta aacttcgaaa gcgcataccc taaaatttca
840tatttttgca tacattggtc agctgtg
86744303DNARattus norvegicusmisc_feature1- 303n = g, a, c or t(u)
44ggaaatgatt agtccaagaa atatttgagc agaagggagt tagggttttc aaattaggaa
60agtggaatcc acagagttcc cttgacagag aatataaaaa ggactctggg gtgtcagaat
120ggtgggcatt aacctgatct tccacttgag ggtaagggaa atgattagtc caagaaatat
180ttgagcagaa gggagttagg gttttcaaat taggaaagtg gaatccacag agttcccttg
240acagagaata taaaaaggac tctggggtgt cagaatggtg ggcattaacc tgatcttcca
300ctt
30345840DNARattus norvegicusmisc_feature1- 840n = g, a, c or t(u)
45aaaccggnng aanaaaaaan gaaanngang gcnnnaaaaa agttnngaca gaaaaaactt
60tnggaaaaaa gganggggan aaggcaggng nccnactnaa aanggncttt tcnaagngng
120anagagntgg naatnagnaa naggacattc ttnnaacctc cnanggnggn nggaannaat
180ngggattgag cngccaccat tagggangaa gttngaattn nggggcccgn gngagttaaa
240angattcccn ggttttttaa aacagagaat acctncaggn acagatnaac ccgagattgg
300ttccctngaa aattnnngan aaagataaan gtaggagcat tcaaagtagn anggtaaaan
360taatgggaga catagacacc aaaaaaagcc agttcagtgg gccccgaagg ngcattaagg
420gaggaccagg aaacggcagc anagccacng gcagccgcct gccccnacac cagtnattcc
480cgcacntaga tccaggcgnt gggggcgggg cggggcgcgc ntgngcagng aagntnngcg
540gcaacaantt tgcntagacc ggntggaacc ggttagaacc ggccgcgccg gaccggccgc
600ccgttccgga ttntgcgttc acaaagggag gcgggactca cgacntgngt atcnttgngg
660tcccaacccc ggcccccnac cccnaccccc nttgtccctg tggcattcgc gttctttccg
720ccgtctccct cgcgggccgn ttntctgcgc ctggtgatcc tttcgccatg gtcctntgga
780gaaagaaaaa atctttaatt tnctagggac gtccttttcc tgtagtcgta attgtagaaa
84046893DNARattus norvegicusmisc_feature1- 893n = g, a, c or t(u)
46gagaaggann aggnggggng agngaagana gaggagggaa gaaangaagg tggaganaag
60tggannaaaa agagggagan ggagggagaa ntaaaganag ganaagagng gggaggaggg
120gnagnatagg agaggaaaga aagganggan agaagagaaa agaanganga gagaaaggaa
180agaggaaaga aagaggggag aagaggaaga aanagaggag gggangagag ggaggataag
240agaggaaaga gggaganagg nttgaaaagg gaaagagaag gagaaaggna gnaggngngg
300aagagaggna agggagaggg gganaanggt aagggggnaa agaangagaa gtatnggggg
360aaaggaggag angaaagaag aaagaganga ggaggagagg gagagtgagg aataaagggg
420agggaaaagg angagaaaga gagagaggga gagggaagaa nagagaagga tagnggggtg
480gagaaggaga aaggagagaa ggagaaggng agaggagaan tgaagaagga gggagtaaga
540aaggantgag naggaaagga ganagagagg tagagagaaa anaaagaggg aaanggaggg
600gaggagggng nanaaggaat agagggngga aanangagag aggggaaang gggaaggaaa
660ggaggaaaaa aagnagagaa gaagagnaat gggaaggang nagtagnaaa agaaaagnag
720aggggagagg gggangangg ggganacggg ggggaanaga aaaagtgaag gaggcccccc
780nacccccccc ccccacacac acacacagcc ttttcgccgg cggaagtgca ggttggtcca
840ggagcctgtg gtcaatccag tcagtagtgg gcgaggtgta acatctgtgt ccg
89347789DNARattus norvegicusmisc_feature1- 789n = g, a, c or t(u)
47taaaananng gnngannanc tnnaaaaaan tntcttngga attnncagga nggaggntaa
60tngggcgggc ancatcaatg gtanaaattt gggggggnng annaaaatca tnaanncaac
120cgtttccana gncaaccatt ctgggngncc caaggttnga ngagntccgn tcaaggngaa
180accttttcaa gaccaattaa ctaggggatn agaggcgggn tggttnntga ggggcgggct
240gctgagaaga ttcgttgggg gacccaggag tgaaggtttt tnacctgtgt ntntcgggaa
300ggtcggatnt attatantcc tgctgttgga ggagttcggt ggttcaaggg ccggacccgg
360agcgtttact ttttnttgnc cgcagccaat ttgttntgct tggtttcttc ngaatcccgg
420ggcggggagg gggaagcggg gggcccaatc accacgatcc cggcagccac cgcgaaattg
480ttccggcagn tacgantctt caacaagagc cagagaaggc gggtgcagag nttcattagg
540acgntcggaa acccggcgtg acttactttn tccaagccca ttggttgatg agaatgatga
600ctgacaggga ggcgtggtca cgctgtcgcg ggcgggagcg acgggtggag ttaacgacga
660aagctgcgcg cgcagccatg acccctcaca gccacntatc ggagggaggg gcgggacagc
720tttagcttgg tgcgtgcgca gccggacgtg aggcagttgg tggtcttcca tcgtcgattt
780ctggttacc
78948872DNARattus norvegicusmisc_feature1- 872n = g, a, c or t(u)
48gggggnggct tttttnggag gcatanatng gggnnngtcc ggnaaacccc attggtcggc
60cggggaagga aaanggggct ctnaaaatan gttantggga tggngcctta agggggggcc
120catgngccag gaangcagat tcaaaaatgt tccaagtgga aaaccanggt tggnanaggc
180cctccnggnc gtnaaggagg agaggagaga tggagtttca ggtgtgtttc ccacccagtg
240ttcccaggga acacaaaacg gataggtcac cntcaatgna caaggaatta aaagcttggg
300tgtatnggga ggcctgcttc caaagccacc agaaaatccg gagagccggn ggatcntacn
360cacccagagg ttcataggga gggcantatt aggggtgtgc ccttgtgaga ggaagtgtgg
420cacngtgggg ctgggtttga gatntcagat gntcaagcca ggcccattnt ntctctctca
480gtntctctcg gtctctttct cngtctctnt tcagtctntt cagtctctct cagactctct
540ctctctctct ctctctctnt ctctctctct ctctctctct ctctcccngc tgcnttcaga
600tatagacgta gaantctcnt ntatccagca ccatgtctgc ntgcatgctg ccattnttcc
660caccangacg ataataggct aaacttntga actctaagcc agcctcaatt aaatttntan
720gagtcaaacc agcctcaatt aaatgttttc atttctatga gtcacagtgg tcatggcatt
780tctttacagc aatagaaacc ctaactaaga cttgccgaaa cctcaaccac aacttcagcc
840ctcagaagcc caagagggaa aagaccttga at
87249785DNARattus norvegicusmisc_feature1- 785n = g, a, c or t(u)
49tcgtaanttt tnatccaccn gtanangatn ttccatgcca ccatgtacgg ttacgaggng
60tatagcgtgn acngttttgg agtgngctaa aaggaaatgg agacntattg tnttggtttt
120gtgacccata acttcggaaa ggttgtgttt tatccggcaa caaccacngt gtagcggtgt
180tttttgtttg cagcagcaga taacgcgcag aaaaaggatn tcaggagatc ctttgatttt
240ttnttcgggt tctgacgntc atgttgtgtg gaattgtgag cggataacaa tttcacacag
300aattcaaagg agaggagcca atatagaggg ggaaaaaaaa agaaggggaa agcattagtt
360taaaaagttg agagaacaaa gtatgttttg cttggatggg caaccaaaga agcntgccag
420gaatggtcgg taaaaggtgt aagagtcatg aaacgtcttc tgtccaaccg ttaccggaaa
480catgcaagga atttcttaga ctggccagga ttggattgtg ggaaaggtct cttcaagcnt
540ccccttggct tttatggcaa gaaaatagtg cggactatag agagcgtcgt tctcaaagct
600tgtccccaat agcagaaaag cattgtccta aattccttaa aaggcaccgt gaaataaata
660ttacgaggac acgatggcac aagaaggagc tttcaactct gccaccagaa cagttatact
720tcatagtaac catgttgccc tgttcaatga caaggcacgc tctccagcag aaagggaaaa
780ggagc
78550889DNARattus norvegicusmisc_feature1- 889n = g, a, c or t(u)
50nttnnaaagc ganccggccn gggnggtttg gncggcgctt tatacnaagn cgngccaatn
60ggctttgggn gggntttcat anggnnntgn tttacccaat tcagtttttt attggtnttt
120natgggcgca gggatagngn gttcnggntt cccacangaa tttgatttnt ggaatcacaa
180gtnaccagtn gccgnaatca cgagtttgcc gctttntttc ctaccttana ttcataatan
240gaatgagtan ttttttttta ttgagnaang ttttnacagg tttagtaaac atgaggacag
300aggttttaag ttgangatta ggaaggagag ttccggggga cagaatgtgt gtattntcag
360tcagtgcact acccggaaga gttgcagtca ggttgaggaa gggagcggat ttcctggagg
420ttttaaccaa cagagagaaa aagcatttac tactgattaa gcacacaatc tctggattca
480gagaagggtg tttaccttta tataaaatgt ctcctaactg cgtgactgtg tgactttgtt
540gaagtcaact gagcactgac tgtgttgtgt gcaacatggt aagaggacca actttnttct
600taaattttat ttattattta tgtcacgtgn acacttgttg cttttgtttt tgttctaatt
660ttatctgcat atatgtctgc ataccacgtg catttctgat gcntacagat gccagaaaag
720gacaccgagt ttcccctggg antggagtta tagatggtta taagtctctg agtaggtact
780gggaagtgaa cttcagtttc ctctggaagg gcagaaagcg cttttcaaat gctgggccat
840gtatttcagc ccctacttaa tttataattt tattttagag gatgtgctc
88951947DNARattus norvegicusmisc_feature1- 947n = g, a, c or t(u)
51anaaaaatng agaagangag accccagaga agaagnanga gaganaacag agaagaagag
60agnaagggng anaaantaga gaaaggaaaa gntcttaaag aggcnanaaa ntancnatnn
120aaggagaaga nggaaggnta acataggagn caagaatana aaganaaaaa gaggtagaga
180anncagagaa cgagaaaaga tgaaanaaag antanaangg aagaaagang nccagnanaa
240anaaggcaga aanaagatgn cgtaaaanaa gagagaagat aggnaaaata gaggagaagg
300ccnaacagga ngggaagagc agcgaattnn agataaaacc ggagganagn nagagaaggn
360agagntngnn aaggcaaaga cagnanngag nacggtacnt gccccagaag gnngaagaan
420gncnagangg tgagggnngg cacngnccnt tccccttagg aggncgcccg cccagagatc
480aggtttcnag gncaccgagt tggatacnag attatncacc naggcaggaa angantatng
540caaaangatt cggggngggg tcacggggtg agaaataaan tcannaaana gaggacgngg
600aggagggngg gaaactctng acagaaatng caagcangaa gccagccnca cccaagcccc
660nacngaagca gcngagangt tgcanggcgg naggtccaaa tcancgnagt catggagnga
720gcttcgggng ggcccnganc cantgaggaa gggcaggaaa ccatatcnag ccgagccnng
780nganggntgc cctganacac ccggagaggt aatttttatt tnacgggaag cgtccagnca
840agttcgtggg ccggaagaga cggtacttta gtatacancg ctnntgctnc gagttgtnng
900nccttntnat gnnagatctc acaaangaag ctnanaagta gatatgt
94752860DNARattus norvegicusmisc_feature1- 860n = g, a, c or t(u)
52aagggaattt ttaccccggt tnccttttgn cnggggggna aaaaaannaa aaaataattt
60tttaaaatta aaggggnggg angtttttcc ggttctattn ngccnattcg gggttacact
120tttatccanc ntttgntttt ttanccggcc gggttaaaaa tgggggggga ttagttcggg
180taggngttnc cnacagcaca gccctgtttn tcttcgttcc ngaaaaaaaa aaattttgct
240ggtntcacaa ttttnttaaa caggatttnc ttcaaccatg gattaataca tttccggtgc
300agnttgcccg gtttgttttt tggntggata gggatgccag caggattcag ggatgcccat
360tgtgnttagt ntctggccct ttaggagagc tttgggctaa ttatgtgacc gattttaaga
420agtggtgttg ttgtggttcc agggactcac ggatcagcct ttattttata aggacactgt
480ggaggagaga cagaggctga gctgcattct gatgtcattt gtgctgctgt ggaagttaaa
540gaaaagctgc agaagtcagc aaaacagatg aataccaaga agggcagtgt gagtacagga
600atggagagaa aagtcagagt ccagctttgg ttaactccct aggatcagac anttctgcgt
660aaggacgggt ctacagttta acagaccaca gagcaangtc aaacagcaaa gtggtttcat
720ggcaggcagg aaatggaaca tttaactgga aacactgaac ccacccatgg caaacttagc
780aatgaagctg ggtgtggtgg cacatgcctt taattccaac actcagggga cagatntaat
840gagtttgagg ctagactggt
86053191DNARattus norvegicusmisc_feature1- 191n = g, a, c or t(u)
53aggtctgacc acttggaagc ttgccctgan tcatagatga gccactgtct tcttcccctc
60aattcctcag gatggggaac agccattggg cttttagtag aggagggaca ggcccttttg
120cagcaacagt tctcccctga atgttggatc tccacctata cacatggggt acttagcctt
180atggatgccc c
19154988DNARattus norvegicusmisc_feature1- 988n = g, a, c or t(u)
54ttnttggnna cgggtntccg nantatgaan ccnttcccgg ggtttttaaa aancccngga
60tattcgggga tttgggtttt nnacggcctt tttttnagag gccaaatncc cntntnaang
120ccttttatcc ttccntttnt gccccncttc naattaggaa gcntggtttg nccgantntt
180aaggttttta gtcntccttc gttnntnttt cccttntttt ttccctnaag ttataaagcn
240ggtatntggt ttgccaggnt tctnttgtac ccgtcatngc gggttncggn ttacccaggn
300tttgttcctn ggccggtncc ttccaatttt ggantntccn ggtcnggngt ccnattncct
360tgnaacngtt ccacacntna tgacaattaa ttgtttcctg tgtaatttgt ccccggactt
420ntggattctt gngancaggg cctntgtttc atggaagcaa actcccttaa ntatttacca
480ggttgattga ttaagaaagt antcatgntt gggaaaccca cntgttttnt tcccaggatg
540gaancccagg attttggaac tgcagaggct tcagggtctg ggaagcggag gcaggcaaag
600aatggagtgc actgtccttt tgcaatatgg ggtttgcctg cctgctggct cctctcntgc
660tntctcagat ggtgactgag gctacttcag caggactagg aataatcatg tccaggtggc
720tgcccttccg agcagaaagg gacagacgtg gggcgatgaa gttgctatcg tttttttttt
780tttctgcaca gactgcaaag tgtgcagagg gagggaggct gtgcaaaaaa aaaaaaaaaa
840aaaaaaaaaa aaaaaaccga ggacgcagaa gttagactgc tgacccattt ggtgcatgtg
900tgcccatgga gggaggggac cttctcaaaa gggttcacgc agcangcatt gaaagtnccc
960cacntgtagg gncgcaagca actgagat
98855665DNARattus norvegicusmisc_feature1- 665n = g, a, c or t(u)
55gaaaaagatt caggaanctt atttttntcg gttcgacttc agtnggggaa tgggcggana
60catttcacac ggatttgtaa anacngtnac ngaaacttgg nggttcgtag atccactttt
120ttnagacctg agagtagttt ttaaaatatt tnaattaaag gtttcctgca cccacttttt
180tttttatccc taacttttca tccagtatgg tttttcaata tcacanttta atctaggact
240ccttgcttaa agcaattaca agttaaatta aaagtaagag atggctnata gctctcatta
300ctgggatgca ggtgtgaaac aagtgatttg tgtagaagct ggcaggatgg gtataaacaa
360gaacacgtgc ccagaggatg tattgaaagt tggatttaag tctctgagta gtttatgcta
420ggcggtagca ttgaacaaga tgaantctct gntcatagag gtagaaactn cccagattct
480gaggaagtgt gagggagagc attagatgtt actgttgggg atttgggaag gccaggaaac
540gttactccat gcccaaggag ggtaggagaa aggtttgggc ttagctttga ggacggaggg
600aactggtggg tggatatgag gatggttatg ctaaaagcag agtggttttc aactattgtt
660cttct
66556857DNARattus norvegicusmisc_feature1- 857n = g, a, c or t(u)
56aaaaaaagaa aggaaagggg agananaaaa annangngan aaaanagana ganagaggna
60agaggaagng agggngaaaa gagaggagan aaanaagagg aaggagaann gaggaaaang
120aaaggaacaa aaganaagng anggaagana aagggagaaa aaanaagagg gagaaangga
180ggagggaaan agagaanaga gggggagaga anncagagaa nagaanngag aaaaggngga
240gacnaanana gagggaagaa aagngaggag aagagagggg agaanaaant tgaagaagaa
300gaagangaga agangagnag aggaaganga ggggaagaag aagaggngga ggagaagaag
360aggagaggag gaggaaggag aaggaggagg aagagaagga ggaggaagag gagaggagaa
420ggaggaggat actanggagg ttgtttcaat aaaagagngg gatntaagat taananaagn
480aataatgccg gtttntatct gttcgggggg ggtccttgtt ctccaaacac aganntgggc
540cagtttntca aaattnaant gngaagattt cttggntnga gagcagntca gattnantng
600nattnttttc tagttttnaa cacaancttt gtgntaacaa agagnganga ttcnaggana
660actcgntttt ntttgggagg agactttgtt cctttcnatg aagatgcagg acgnggaaga
720cgcagggtgt gaacaggaca cagnnacgct tnngtntntg tcngcntcag cngcgtggga
780atgagtcaga gcagcacggg gaggtgcctg gatntaagct ttctggtagg gagaacagag
840tgcaggcngc ggcccag
85757902DNARattus norvegicusmisc_feature1- 902n = g, a, c or t(u)
57aaagggggng ggaagaanga aaagggnaaa cnttngtttg gaagccnnca nnaaagnaan
60gncgaattta anaagggggt agggaaaaaa aaaacanaat attccntcct tagccatnaa
120ccgaacttcc ngcaaggaaa aaaaatttgg ngggngtaaa gggcaccncn tcccacaaaa
180ttttgntaan tttgggcgca aattcangca ggntttngtt ggaaaggngn ananaccaaa
240gggatttngg ggatttnaaa atcngngttt nnggcaggnn atccngaagt tngaatcgga
300cgncnaccct ttatttnagc agttatttan gggaacatgg gagggnacca tttcaaacca
360nggatcgggc cnggagtntg agtgttcagc ccacngcctt cnaacantac cgggataagt
420ttttccctgn gccagagacc catccangtt ccagcaaaag gntggtcatc tngggcnagc
480tccnngagtc atcnngggtt tctcccagcc nggggccaat ggtcgaaggc aggttntttt
540tgtctccagc ttgttcccna ccgngggagc ctgtcaaggc tgcacagnac cagantagtg
600gtcatntcng gctagctccn ttagctccnt gtccagggga cttcctggca ctggattagt
660ggnggactca ggcttgcttt tttttcagga gaggttagat tactaatcat tcagatgttc
720ataagtcaga acactgagca aagcaatagn ttctcctcca cntactgant cacacgtgca
780caacagccac acccgcaatg cttntaggag caggtccagn gnacttttgt tttaactatt
840tntggctctt tattaatcag cacataaata cgcttcgttt ctcctttttc aatatgnatg
900tg
90258852DNARattus norvegicusmisc_feature1- 852n = g, a, c or t(u)
58acagaggggg ggggggngtg gaattttngg naggangttn tnggaaggcc nctaaaaaag
60aaatgttccc agaccaaaag ggggggggna gtnnaattca nggatcctna ngaggnggaa
120atttttnnnn tattnaggat caggataaat angaaaangg gnanattttn nnnangnggg
180tttttttttt tttttttttt tttttnngng gnnnnannan annnnnaaat ggcgncgggc
240atggntaatg gggaanttgg gganaattac agagatttnt ttttcccatg ggnttccagg
300atgaattcag ntaccaacca ggttggtacc agcattttaa cattcgagtt agacatcaat
360ggttaggtcg ggagtgagag gttcggggcc ngacatatat tcntggtgaa cccagtgcac
420cttntggttt ntacaaggag cttgaggtag tcgcccacca gtagctgtca ggcaggtggc
480ttaagttcag aaccgnttcg tggaacccga gaagcagaaa aagacataag ttntgcngct
540tcanaatcca ctcntgaata cananatctc ggccaaagaa gcacagccag tctttccgtt
600nacangaggc cgggagcaac aantccacag ccagcccaag ganatacaaa ggacttgggt
660cagttctgna ccagttggag tcagagatgg ggccctcaaa gtcccagcag tgaagggcat
720ggtctccagc nnacagtgga acctttaaga ggtggggact tgtaggagga gttagataat
780tggggtgtgc ctttgtcccc nacntcgttc tttccctctt tatggccttg atgtggacaa
840gattgtttct gc
85259884DNARattus norvegicusmisc_feature1- 884n = g, a, c or t(u)
59aaaaaaaatt ntttttccna ggnaaataac ccgngcttaa ccgggcgggg gagatcaatt
60ntttgtngtt gtttcctcng aggcggagng tcaaaanaga acacnnctgg naaacccccc
120ttaaaanaca aaaatttgan ggggnnggng ngttacaaaa agacaggatg ttttccgagt
180cggattcaat cccaccacaa catggggttc acaccatngt aaggaatcgn tgcctttttg
240ggggtatcct agggggtana nttccaaata nngataanaa tttttttaaa aatttaattg
300tanatattta ttanataatt taataaataa tatttggana nantnatgtt ctngcgcctt
360gnggactggt agttttttnt ccnnattnna actttcccag nactnggtag cctatgtgnt
420tatgcaaccc nttagaagct gccttcanta ttnaactcat actgtttctc gataatcngg
480ggagtagctc cagttngcta tgaagctgcg gaaaggtagg cggacatccc aggcttagac
540agagttcagg ttatttggaa ctttnnaaca gaagtgtgtt cntgcacggc agcaagacna
600tntgggtccc gtagttccgg tcgccaggag tagtgtattg cttaggacca ttctgggtgg
660aatgcatctg gtgggtctta aannatgtca ggcagggcct ggcaccaggg tctggcggga
720agcctcacat accgttntaa tgacttcatc tgcttagaat ttgtggggaa acgatgcaga
780aaaatctaac cagggatgtt tctgggccag tcatgttggg gatgcctcag tcatgtaaaa
840ttgagctccc cctggagcac accttaaaac atcttctgtt taat
88460955DNARattus norvegicusmisc_feature1- 955n = g, a, c or t(u)
60cccntggaaa accnaanana atangnnnan anaaanactc cncccattga gggaacnttt
60tagggnttcc nnntttcccc gganccgcca aatgngacac caaaanngac cgnantcttt
120ggnngttgct tctcttggan cgcnttttgt tcgaccgggg tgactaaggn catgtngggg
180acgantaatt gtttccgggg gcngntcggc accttccnan gngngngngg tttggttctg
240gaagnccgaa nnggcatgtn ttaagatttg ccnatccatt tagggttcgt tcaacgcctt
300atctttngag tttntggagt ttgggtgggg aggggagatt tagtggagga gtaaattttt
360agtagggaga gagggaaggg agatagaccc ggagacagag aagggaggga ggaagggagg
420gattatcctg taggatgtga gcccagacnt gtctgtggtn tctttccatg acacaagaga
480ctttntgctt gtccctagaa tgcttcattt tntagtgtct caaacttaaa gggctagtgt
540aaagttagac tgtgaacann tngtaaacac aggtgacagg aatgtntgtc agctgggccc
600nttatatgcc acggcagagt ggtacgtgat gcccccacat gttatgtgga agttntcatg
660cagggcttca gaacacagta gatggagatt gtgaaaatct gttgttnact taagagactg
720gccccaagga tccatgtgat gntacttctg ttgcttgtgc tttaaaatct tatgtgatgt
780tttgcagact ccnttcggga ccccagcaca cagctgagag tctgccctgc tggcactgct
840gcctgtctgc tgaaggggaa cccaggcatt tgatgttggc cggcccaagg aggggctgaa
900gctantgagc aaggacagtg atagacccac acagnagttt gcaagtaaat gagnc
955611107DNARattus norvegicusmisc_feature1- 1107n = g, a, c or t(u)
61caaannncaa nggtncnncn ggnccattgg ggggggttaa naatggaggg gnttngggtt
60ttaaannttc ccccnggntt caaggaaatg gggcttttga ttggcaagga aggaatgggg
120nttcccntga ancctcctga ggggccaaan attggggggg gttnacaccc ccggggaaac
180ccttcttgac cccnagaaan gcngtttagn ttcccnccca tgggntccct taccctgggn
240tttttttgna cagccnagca gccctggttt tccttgtttc cttgggcncc gaaaatttga
300atccagtgca ttccaccatt gagccngcag aggttgatng gcaggaangg tttaaccctt
360ngaccaggag tgacaaattt ngngggacnc cccagtgnga gctcacaaca ngtngacatt
420gaggcnccaa aggattgttg aggggatgga ttgtgtcgca gtctggttgc ctttatagtg
480ccagcatcgt tgagccccgc ccagggagtg ttggcacgcc caaaccccna cccagcgctt
540gaggcaaggc aaacacactt cccagcccct taanttncna cgcctttgtt gcttggacgt
600cccggantgg gagcaggatg aaggatttta gtgcaggaga agaccagtgc aagccggaga
660catngagttc cctntaattc ggtgttcagt ttgccnttnt ggcacgtgac tcgtaactct
720ggtatgtgtg ctgaaccntc taccagccag agatcagtgt ccttaaagtt cgaatcagtg
780tgagggggac tgggaacaat actgatgctg ttgccctcta gtggcaaggt caactccaag
840cgagagggga agcagtcagt ctaccgcatc ctctaagata gtggttctcg acctctctaa
900tactgcggat taatacattc ttcatgttgt ggtgacgctc caaccataaa gtgattttcg
960ttgctgcttc ataactatat ttttgctact gttatgaatc gtgacataaa tactgtgttt
1020tcagatggtc tcaggcaatt cctgtgaaag gggtctccca caggtttgaa agtntcccac
1080ctgtaggtgg gccaagctaa atgagat
11076292DNARattus norvegicusmisc_feature1- 92n = g, a, c or t(u)
62atggggcatc ttgtaacagg aggcctggat tgagtactgt aactgagntc ttgaaagact
60ttacctgtag gtttggncng cttgaaagag at
9263209DNARattus norvegicusmisc_feature1- 209n = g, a, c or t(u)
63aattccagcc catcctgaga cacacagtga ccctgtctca caaaaccagg gaaaagccag
60gtgcggagtc tcacgccttt aatctcagtc tccggaaaca gaggcagngg gatctctgtg
120agttcccagg cgaganttct ttgtacaggg nnccctctga anncncctga aagatttcac
180ctgtaggttg ggccnagctt aaaagagat
2096497DNARattus norvegicus 64acagagaaac agtgtttccg ttccttaaaa cgttgctcta
tcttgaataa caagcttatt 60acatgcgaat cgtattggga acctactgaa ttccgat
97651047DNARattus norvegicusmisc_feature1- 1047n
= g, a, c or t(u) 65caaggtgaat tccanttggn gtttnnaaat ngtttttnaa
aaanaaattt tntttggnna 60ttgccttnaa ngtttgggnc ctgaattcaa aattccaant
tacccaaaat ttcatgttcc 120atccanaatt naattccgga aatttacaat aatttgaatt
ntagttttcc caattntaat 180ntcagtagtt tgnntttgtg tgccccnatt ntaanatcag
acccgtccaa tcacccaatt 240gntttttnaa attgaatngt tttcccntgt accttccttg
caangttgct ttaaattnga 300atttcagaat ccccattgaa aagaatccgg gnnaaagcaa
caccnttaag gaccccagga 360aaccagaaat tngnagaaan ttggacgnag gganttnaca
ttnttnccgc canaggatgn 420ttgggntaaa aaccgcgttt gcgcaaggct cntgtgttgg
cctcttttcc gccgggggcg 480ctgtggataa tctctgggtc agtcgaaccg ttttaccatc
catttcgtta ctccgagaga 540ctggcgcncn gcgggttcct ccaagatggc ggcgcagagg
aggagcttgc tccagagtgt 600gaggaaaccg acccgctctc tgggctggga gggttgggag
ctcgggtgtg tcntcgggtg 660cagaagctgt tgtctttaga tggcagagtg cggacccctc
gccccagagg ccntagggtg 720cttgcagcgc gcgcaagacc ctttccagtc tagagcctcg
cctagttctg cgcgtgcgcg 780ccacagagcc gggcctctga gggtcaaggg cgccggggtc
ctgcggaatg ggagcgtcct 840caagccggaa agggacatgg cgccgccgag cgggccatcc
ggagggcgga cacgactaat 900aataaatcgc ccccccgccc ccgcttgtgt aaggcgcgct
gtatctctgg cattgtgtgg 960accgcctcac attcataagc ttcgtcagca gcagtagaga
atggcttgaa agacnttnac 1020ctgtaggttt ggcnagcttt aaaagat
1047661063DNARattus norvegicusmisc_feature1- 1063n
= g, a, c or t(u) 66catnggagtt cccaatggnt tccntnaann ggttntnttc
aggttgggca ncntttagga 60attgaaaatn ttnnttggga ttcccctaga atttgatccc
attngggaaa ttttttattt 120ccngaacagt ccantnttaa aattgggcct nttgggatta
acggattcca aggttgcaac 180anattggcaa gtttnnggac aggaggtttc aantggntaa
agtggataaa tngtgaattt 240tggagangga attgacttgg ttgggggcca aaantaggta
gcattttgcc cggagggttg 300attgcattct gttttgtgta aanatgaagn tacttgacag
ctttgagata agaaggagac 360ntaatttgct aaacatttta agtgttctat tctgccggag
ttttggagag ggtatatgcc 420ggtcaggaag ggagccagaa gccagtaaca ttgcaagtat
ttcaacatgg aaagctttag 480gttatctctt gtgcatctta tgctcggnta atgatgtaan
ccaattgtaa ttctgggcac 540agctttccca tgtgtctttg gaacagtctg ggtttgtggt
tntaaaacaa catttgtatn 600tagttggagg cttatctaag gagcttctta gcatttgggt
tgtaatttat tttagtattg 660tttcagctac ccattgctac atagtaaatg tacaaaaatt
tagtggatta aaataatgat 720gtttggtttg ctcacgaatc tttcatgttg gctgaagttg
ccatttctgc ttctctctgc 780tgaacttggc atcaactgag agggttggaa tcatctgaag
atggggttag ccacacctcg 840cagttgatat tggctgtcag ttggaacctc agctggggtc
agcatgcata agtaagcatg 900tgtcactttt ccaggtttct gtcttacagc atggtggctt
ggttctgaag ggccatcact 960ctaatggtgg ctgggttccc agcgagaacc agtgganccc
aaggatagct tttggtgact 1020gaaagacttt aacctgtagg ttggggccna gctanaaaga
gat 106367815DNARattus norvegicusmisc_feature1- 815n
= g, a, c or t(u) 67cccccccccc aaaccttcct tccaaaccct tnggggtggg
gaaaacattg ggcaangggg 60caaattnana ccccttggaa tngttngccn ggnaaagttn
cngttcccca aaagccaaag 120ggggggggtt tccaaanatt ccnggggttt tttnnggggg
taaagggntt naaaggtnaa 180aaaatgttcc cggngccccc anacttccaa aggttttccc
ttnnaaaatt ccnggccttc 240cgggggnccn tntgtncccc ccnttccccn aaatnncntt
nngaaaaggg ttnaanantg 300ttnaaaancc cnaangttaa angggnnnat nnaaanggtt
tccctnncnn ggggngggna 360aaaaggtttc gcgcgganac cnntgatgcc caggttcagt
ttccccggag cttggggcca 420gacccgcggc gcgccntggg tgtggcggga gcgcgcgggc
ttgcgcccgg acggcttctc 480cccgcccccg actcccctcc gcggcggcgg gagtaggttc
ttccggctcc ggtctgaggc 540ggtgcctggc accttctgac caggatccgc gggtccccgt
gctgtggtcc cgggaggcac 600gcggggcctg cctgctatag cgggtttgca gggcgagcct
ccctggagcg gtagggtcgg 660tttgggtgtt gcacgctcgg tttgacgttt taatccggag
gagttgtggg gttcctcgaa 720tctcaaactg ccttcttccc ttttgagact tgaaaatacc
cgaagcctgc cttgtactga 780aagacnttac ctgtaggttt ggcagcttaa aagat
815681034DNARattus norvegicusmisc_feature1- 1034n
= g, a, c or t(u) 68aaaaaanagg tttccccngg angtccctng gggntcnttt
tnngancntn cgttangggg 60ncctncncct tttccccttg ggggaggggg ntttttaaag
cnannnntng gtttcnnntn 120gggttaagtn tttncccaaa agttggtttt tnnaaaaanc
ccctttnncc cggacgtttn 180ccttnncngg anaatatntt ttgggccaaa ccngttagnc
gggatttccc aattgcgncn 240cccttgnaaa cgggttnccg gggggngtnt tnaggggttg
aacngggttt taaangtgcc 300aaaacgggta aattggaggc attttngnaa tggcttttgt
tnaaccnntc ccttgggaaa 360gggttgtagt tttnaacggg naaacaaacc ccgtngtagc
gggtgttttt tntttnccaa 420gcgccggnta agccncggaa aaaaaggatn ccnggagacc
ttgnattttn nnnggggttt 480nacgcnatnt tttttggaat tttgggggga taanaatttt
nnaccngaat ttttngnggc 540cncncnnngg gnnaaaaatc tnannannat tnggntattg
aacatttctt ccntgcatat 600ttatngangt atgacccttt aaacaattaa gtacttggct
tcagtgggag agaaagtgct 660tagcctcaaa aagacttgaa gtgcccaggg tgtgtgtgtg
tgtgtgtgtg tgtgtgtgtg 720tatgtgtgtg tgtgtgtgtt tgtgtgtgtg taacccagag
gggtgcccac ttgctcaaaa 780gagaaggggc agaggaatat gagggaagga ttgtgggagg
gagtgaccag tagggaaaca 840gtgagtgtga tgtaaagtga ataagtaaaa aaattaaatt
aaattaaaag taaataaagt 900gtctacaaag tcaattactc ctttcccttc ctccaccctt
tcttctaata ttaggcaaaa 960acaaacncaa aaacanaaac aancaaactg aaagactnta
acctgtaggt tggncagctt 1020gaaagagatn tttc
103469186DNARattus norvegicusmisc_feature1- 186n =
g, a, c or t(u) 69agaccacctg ggtggaaact cctattctta caccaagctg cctctgtatc
cacagatacc 60aagaagtagc caccgttgtt ttacttaact catggtccac ggggtgagct
gaggtctcct 120tcctgagcaa gatggaaatt ttacttggtc tgttaactag cgtgcattga
atggangaca 180tatgat
186701028DNARattus norvegicusmisc_feature1- 1028n = g, a, c
or t(u) 70aaagggaacn ttttaagcnt ttnnaattnn gttnccnaan aaggatttgc
atttaccacc 60cttaaattta ggnatttttg aatnatttca acccnttgca ggcagtttgt
nccatgttnt 120gggaaagttt taacaggatg gttatttnga caaaacaggt tttttcagac
catttgtgna 180ntatcttgaa atttcccagt ttttnaattn tattntaang atattntagt
tnnaattnna 240tgacttcaat ttgtatanac aggttcttaa caaacagtgt gtaactgagt
accttgcccc 300agcatttaag gttacacaca tcatacgaac actgaagaaa atgtctgntc
tttaattttc 360cccttttctc tgtgtaattt ccttcaggac tcctttgtcc tgagtggtca
ggcccttgat 420aagatggttn atcttatttc tgtttgccca tgtgttgtaa tcntgcctga
cagttcttgc 480ttaatgcaga aaccaagcaa aggttcagtt tgtactggcn tccctttnta
gttatctgac 540agggatcagt tttcaagctg tagccgtggt cctcagagag acctctgccc
atatacagca 600gcagtctttc tcatcccagc cctgggagtt ctagcaaaga tttgactttc
tgagttgttc 660agggtcagag accatgtatc aagcctcggc tctatttctt gagtaaaatg
ggcatctggc 720acatctactt agatgcagaa atagtcagaa tgaagtgaag atgtaggagg
agtcgtgtgg 780agaaataggc tctctgaaag gaggcttctt cttcacttta taagctgtag
tgtcatccct 840tcccaagtgg ctctgaaact gtgttagaag acatggcctc cccagagctt
ggggaaacct 900taaataaggc tgctgctcag atgtcagcac attttacgct ttactggaag
acttctgctt 960cctcttccta tttctccaaa tncanntgaa agacttgtac ctgtaggttt
gggccagctg 1020aaaagatc
1028711034DNARattus norvegicusmisc_feature1- 1034n = g, a, c
or t(u) 71aaaaaanagg tttccccngg angtccctng gggntcnttt tnngancntn
cgttangggg 60ncctncncct tttccccttg ggggaggggg ntttttaaag cnannnntng
gtttcnnntn 120gggttaagtn tttncccaaa agttggtttt tnnaaaaanc ccctttnncc
cggacgtttn 180ccttnncngg anaatatntt ttgggccaaa ccngttagnc gggatttccc
aattgcgncn 240cccttgnaaa cgggttnccg gggggngtnt tnaggggttg aacngggttt
taaangtgcc 300aaaacgggta aattggaggc attttngnaa tggcttttgt tnaaccnntc
ccttgggaaa 360gggttgtagt tttnaacggg naaacaaacc ccgtngtagc gggtgttttt
tntttnccaa 420gcgccggnta agccncggaa aaaaaggatn ccnggagacc ttgnattttn
nnnggggttt 480nacgcnatnt tttttggaat tttgggggga taanaatttt nnaccngaat
ttttngnggc 540cncncnnngg gnnaaaaatc tnannannat tnggntattg aacatttctt
ccntgcatat 600ttatngangt atgacccttt aaacaattaa gtacttggct tcagtgggag
agaaagtgct 660tagcctcaaa aagacttgaa gtgcccaggg tgtgtgtgtg tgtgtgtgtg
tgtgtgtgtg 720tatgtgtgtg tgtgtgtgtt tgtgtgtgtg taacccagag gggtgcccac
ttgctcaaaa 780gagaaggggc agaggaatat gagggaagga ttgtgggagg gagtgaccag
tagggaaaca 840gtgagtgtga tgtaaagtga ataagtaaaa aaattaaatt aaattaaaag
taaataaagt 900gtctacaaag tcaattactc ctttcccttc ctccaccctt tcttctaata
ttaggcaaaa 960acaaacncaa aaacanaaac aancaaactg aaagactnta acctgtaggt
tggncagctt 1020gaaagagatn tttc
103472824DNARattus norvegicusmisc_feature1- 824n = g, a, c or
t(u) 72gggggntttt cnnanntanc aaaaantngn tntancanng antnnttgag ntgttgaagn
60aangnggaaa angttttgaa atcantgtaa tgaggttcca aaaattgagc aggaaattgg
120atgntgtcag gagaaacccn ttcagtnttg tgcaattggt tcgccagcag ttaggaccgn
180ttccccatca cttgtgccag cggacatcca gntattgagc cntgnatcat ttatggnaca
240aattaggaac acacaacaga gatccgcttt ntgactgcca tgttcgccaa actcaattgg
300gggaagtaat cctccagacc gttccgtttg cacgtntagg aagccacagt gaaaacacaa
360aattcgtgga ggcgactcta accaggaagc ctaatcccnt agattcccgg gacactgggg
420caggcgtcct aaaaacagct ttgtggggct tcagtcctcc gtgcggttcc agtccgggtc
480ttggggatcg ccctcgcggg gaatgtccgg gactccggtc ggtatctttt tggcctggga
540atttccagcg tgtggaaaaa gtccacaaac ttagtcctca ctgcccgcct cgcctcctcc
600ggcccttctc ggtgcccacg caccccccga tcgaacccga ggatgagcat agggtgtatt
660ttaggcgtgc tgggcttccc cgcccccctc tgcccactta gctggcaaga agaaagccag
720cactataaag gaggccaggg ccaaggactg gcctcctctt gctcacgagg tcagacgcga
780gctctgaaag acttcacctg taggtttggc aagctgaaga gatc
82473774DNARattus norvegicusmisc_feature1- 774n = g, a, c or t(u)
73gagggganna ncancaggac caancngata agggggtcaa caacntgngt tccncccntt
60gagngggaaa tgagcacgng gcantccaac cgntcaaggt cccgnttcgg acggtcacac
120antaggttnt catntggatt gccngngttc cngttggcat ccgggaaaan tgagactgtg
180tcggtaccag agntaggatg gccntccttc ccngccccgg ccttnttggc gccttgcgat
240ccttcccgaa ccggcccntg gcgtctccgc cttnggcact tgcacatntg gcggcccagg
300atggcgcttc cgggatggcg ccagcgcgcg tacgtcatca cggagcgtcc atgtgttcct
360tctgtccaag cgcntaggag cctgcgcgta ctcccagcaa ggaagatgta ggaccaaaat
420gtagaagcac ttaacatgaa cgtcaaaacg atgaccaatc acagggcgat atatgcgcat
480gcgcaatgtt ccaatcatgg ctcataagca atccggaagt ggccaattaa atatactatt
540tactaatcca gggttacaca gtgaaaccct gtctcgaaaa ataaacacag ggctggagag
600atggctcact gattaagaac actgactgct cttccagaag tcttgagttc aattccgagc
660aagcacatgg tggctcacaa ccatctgtaa cagattctgg tttatgtnga gacaactaca
720gtgtactcgt attgaaagnt ncccacctgt aggttnggca agctaaanga gatc
77474248DNARattus norvegicusmisc_feature1- 248n = g, a, c or t(u)
74tgacacttca tggaaactga gaccgggagc ttccaccaga aggcactgcc cagtggagaa
60aaccgacttc tttttgttgt tgttctgatg ttttgttttt gagataaagg tctcactgtg
120tagctcaggc tggttttgaa atcaggatcc tgaccctcag gaatgttaaa gtgcctaaaa
180gtggngacaa attattttac gtgcctttga aagacttcac ctgtaggttn ggcnagctag
240aagagatc
24875833DNARattus norvegicusmisc_feature1- 833n = g, a, c or t(u)
75aanggggtta tnntggagan atnctaagnt cccaaagcaa nttaggattg ctnccnnnng
60aattnttaag cntttgcatt aagtantaat gccaaaatga ccccaanata tngntccttg
120antgtnntaa aaangaggat cttcnttgnc catanacgcc ntatatgaaa gcaactgaac
180aagatttaaa attggacagg tcacaancgg gcgtgtgcct ttaatcccag cactcgntgg
240ctgatagaag cagatgcatn tatgtgggtt tgaggacagn tngnttnacg tagagagttc
300ntatatcagt agggctttgt agagaccnta tctcaaaaaa caaaagcaaa acaacagaga
360aaaaatcaat tgaccatgtc ccaattacct ttatttatct gtaacctatc cttagttata
420ctcgtaatct ttttctctct tcagtttgcg tacgggacag cagacctact cacaacccaa
480gctntaaatg atgagcgtac tcagccaggg agcttcaccc cacttaaccc cataagatgg
540cggcagcgcc tcttcaccca ctcagggctg aagcacgcat cacgtgatgc gctccagctc
600tcgccgcggt ggctgacggg aggtggagat agaacgaggg tgtcggccat tttgtgtctg
660tttcctgccg gacgtggtgg tggcggttgg ttccgagaac tgtgcgagtc tcttctctct
720tttttttttt ttgtttttcg ttttcccccc agcttctttt cgcctctntt ctgcatagtc
780tgtagtgcgc agttgaaaga ttccacctgt aggttgggca agctaaaaga gat
83376880DNARattus norvegicusmisc_feature1- 880n = g, a, c or t(u)
76aanatggntt ggttntaaag gttaaaattg gggcaaaatt tttccgcccg ggtccttaaa
60ccggattaac tccaaggcca aaattccgag ggggaatcaa caacaaggac ccaaccggat
120taaggcgggt tcaaacaaac ttggatttcc ngccctttgg ggcgggggaa atgggcacgg
180gngcattcca agcngntcaa ggttccggct tgcggacggt taacacaant aggtttctca
240tctagattgg ccngcgttgc ggttgagcat ccgggaaaat tgagattgtg tcggtaccag
300aggtaggatg ggccttcctt cccngccccg gcttcctggc gccttgcnat ccttcccgaa
360ccggcccttg ggtctccggc cttgggcact tgcacatctg gcggccagga tgcgcttccg
420ggatggcgcc agcgcgcgta cgtcatcacg gagcgtccat gtgttcnttc tgtccaagcg
480cttaggagcc tgcgcgtact cccagcaagg aagatgtagg accaaaatgt agaagcactt
540aacatgaacg tcaaaacgat gaccaatcac agggcgatat atgcgcatgc gcaatgttcc
600aatcatggct cataagcaat ccggaagtgg ccaattaaat atactattta ctaatccagg
660gttacacagt gaaaccctgt ctcgaaaaat aaacacaggg ctggagagat ggctcactga
720ttaagaacac tgactgctct tccagaagtc ttgagttcaa ttccgagcaa gcacatggtg
780gctcacaacc atctgtaaca gattctggtt tatctggnnt cnactacagt gtannggcat
840tgaaagatnn tacctgtagg ttggncagct aaaaaggatc
88077864DNARattus norvegicusmisc_feature1- 864n = g, a, c or t(u)
77aattttaant tgttggnata anggcttgnc catatccttc ctnttgtttg ccctaagtaa
60cagccaattg ggggagaant tttntgtcag tatcatattt ttcgttaggg aacggaggcn
120caggaantga tccntntggg ttacagtcat tttagcatag gntgacagtt ggngaccaan
180tnatcttgcc gtgttggaag gagaggggan taaggntgaa gctcttgagt ccnttgangc
240ccttggaatc gggaantccc ttaaaccaac cccttttgcc gttgaattgc accaaccaga
300ttcttccagt ctgcttgagg angacaggac ttcattgctn tggagagggg caggagggtt
360gggagttgac ntnacagggc tcagggattc ttttagaagg gtccaggttc atggcttccc
420ccccccccag ccaggtcaga cactaaagtg tcttaagccc ctccatactt gccgctcccc
480cacnttggat gaagccggcc attaggcagg gaccgtctct gggagaggcc aagccctctg
540gctcacttgt ggatttcctt taagcaagac ttcctctctg cttccaggac tcctgtcaaa
600caagagggtc cctggcttag agtttgggag ctgcaggcag aacagacatt ccccgatgac
660tcacaagcct ggaactctgt gggccagcag gaatggggat ggctttctgg tcagtcaggg
720tcaactggga cactcactct gagacaggga ggcaagggag aaacaggtca gaggtagaga
780gagctcagtc ccagggactc acgttgaggt ccctaaggtg cgctagggag aggnttttac
840attcggttng gcaagctaaa agag
86478874DNARattus norvegicusmisc_feature1- 874n = g, a, c or t(u)
78gaggttggac cacaaggagn ttggnggaaa atnnaaaagt caacctatca gggtgtcttt
60tagtttggaa cagaggcttg ggcagaaata tgggcaagta ttaggaaagt acaaggggaa
120atgttgtcaa cgcgnttgtt ttcccagttg ttgnactgat cccnccagga tgttttccca
180cntatgntat ggaaccntct ctttcaggaa gccattntna ncntatggnt tgcaacccct
240ttggggtcgc aacagcaggt attaacatta ggattcataa cgntagcaaa atnacagtta
300tggagtagca atgaaataac tctatgnttg ggagggtcac cacaacanga gggacggtat
360cacaggnttt tagcattagg aaggttgagg accttatttc agagtgtcnt gacaatcntt
420cntgggacca cttgacttna tctggagccc tttccctcac gctcntactc cttaccatct
480ctgcacagct ctntgaggct tagagcggtc tttcttcata gctttccntt ttccttcagg
540tatgcagtca catcttgctt tagaccccag ggacattccg tgtctgactc actgcacaaa
600atagtttccc acatatgagt cctcaaccgc cccacatcac gagacggaca agaccggaga
660cgccatacat tctgtatttg ccctccttcc tcatttaaat aggaatttgt tgctgtttaa
720tttttcatta tttgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg
780tgcgcgcgca cgttaatatg ccgctcagaa tagtctaaaa ctgctgggct tgaaagacnt
840ncacctgtag gtttgggcna gctaaaagag tatc
87479886DNARattus norvegicusmisc_feature1- 886n = g, a, c or t(u)
79atttttnaat tgcagcaatc ctcctgcctt ttttcttggt tgttaantca caggatnttt
60gcacacttga ggttgaantt gcagcaatcc tcctgctttt gtttnttggg cgcttggatt
120atagtatgtg cataacactt gagcagtaac tgttttcttc aatctcattt atctcagaag
180ttccccttgn tgattcagac gttattaatt aggcaaacca atgttgattg tcattaccca
240tgagttgctt ggcttgtgag atgcatactg tgtgttcgtg aggcacntac tgtgaggcat
300gtgcccgtga ggttcatggc tgtgaggtgt gtgcccgtga ggttcatggc tttctngacc
360acngggagta tgaaggagag gaatcctacg tttgatgcca gccagggtta tacagcaaga
420tcccgtctca aaacaaaatg aagaagtaga gagattagtg ttaataagca actgaggcct
480tgaagggctg aggtcaggcg gtgccctggt gcacacacag aagcgtgcca gtgacgtcag
540acagactcag ccctgtgtca gacaggccgg agggtgactg gccatgtggc gtgattggac
600acattcccaa aaaaggaact cgatggaaga ggctcctcnt gctccagaca gggcggtggt
660tatgtgactt gtgcgagatt agtctcatac cctattgcta gcctgtgcct ggtaccacgg
720acatggtaca atccagggag gagccgtaag cactacaggg gagccatcct gaatcccagc
780aagtccaact tctgtttttt cttccttccc cgcaacatta ggaatgactt ctaagagngc
840tgttgaaaga ctttcacctg taggttgggc aagcttaaaa gaggat
88680865DNARattus norvegicusmisc_feature1- 865n = g, a, c or t(u)
80tggaggtaaa agtcacaagn ttttcaaggg tttgagatga cagttcaacg tgagnattng
60acaaggattg attcttgtnn acaggaaagn tccccatccc accaananac accgtgttca
120ggcccantgc tcagagctcc gggcgccagc gaagggcaaa cggccactga ttggaaagnt
180gcagtttaaa gacatgtccc aggaactggt anccttgtgt gactggactt agccttgcaa
240ntctgtctga agcataacnt gntgctgtct ntgggcgagc atttatgtgc cccacttgag
300acccatctca ggacacgcag gacacggtcc agtggagctt tccctccaga gagaggtgtt
360agggnccatc agtgagcttc caaggacagg ggaccagaac ggtgaaaaca aaccagggct
420gtgaaggaga gcagggcggg ggggggggga gggggggcgc tctntagaat agattgaacc
480tgcagagctg cttgctacct gaagttgtca cccttttacc cacccacntc atctgtctct
540gcttgaccat ctcagcaagt gtcacctcgc tgccaggaca caagtttcct aaagcttatt
600tcagtgtcag ccgctgggga gacacattca gggcatgggc gtcccccagc cctcggggag
660aatgtgggag gtggcgatgt gggagggatt cgagagaaga gaatgcttaa gaaccatcca
720gggaacctgt gcgtttgaag gtctgagtta cacacaggct gctcaggaag gagctagagc
780tccaaatagg agctgtgatc aggctgtgtg tgtgtgcctg gtgaaagact ttnacctgta
840ggtttgggcn agcttgaaaa gtatc
86581859DNARattus norvegicusmisc_feature1- 859n = g, a, c or t(u)
81cangagcant ntgaancagg catttntgga agggctccng agaaaacacg tggaattnct
60tgtctctggg actttagtnc cagcnaggan gatncagtga gggaacacac cgggcttttg
120ttgtgcacgg gaggccaggc tcancnncct tgggagnttg acatccagca ggctatanac
180agtgatccag gggacatgta cacatgggga actgnccagg cagagaaaga caagagaaaa
240tctcaaanga tgaagacaga gangagtaat atggccagaa ngatacagtg cctcntgcat
300aacccttgag tttaatttcc agggtcaact gtattttgaa agtataaatg aaagttcctg
360aagtaataaa tttataggat gttagtatca cactgttcag aatagctcaa aaaatcctgc
420cntgtcctct taagtatgtg aatcatcttt tactgcaacg tgtccacaat gtatatacta
480catacccaaa agtcctcact gttatcccaa ttagtaggct ggctgccaat agttgtccat
540acagagtgcc tgctgctgtg gccatccnta ctgtagtaaa cagtcatcca aagctcagga
600gtgaggctat tgtagaaatg cacttcctgg gggccctact gtcagtgagc acctgagaga
660gaaagggaca caggcccaag gtgggaggcc ttagataaag gcccatcatg ctcaggaaag
720gatttntaca gatctcttag ggaagttaca atcaaattca tacctcacag cagagctcag
780gagaagaatc cataaagnnt gaagacatgc ttgtngtgnc tgaaggacnn tacntgtagn
840tngggccngc tgaaatttt
859821021DNARattus norvegicusmisc_feature1- 1021n = g, a, c or t(u)
82caatngncaa aggtttggaa cccgngaaat ttnaaaagtt tgcgngantg gttgacnttc
60cnggtgtnaa nggtttcccc gttcngattg nagggatcnc ttttatccct tttttnagnt
120tttttttgag nggaattttg ggttcnaant gngttaccct taagtaaccc cattttgcan
180ggcatggaaa atacctaaan tgggatngaa agttcanatn gaggtcagga anggntggaa
240cagggtngac cggttngacc gttggacctt tgaganccat cagatntttc ccaggttncc
300ccaaggactt gaaatgaccn tgtnccttat ttnaantacc caatcagttg gtttctcgct
360tctgttcgcg cgtttttgtt cccggagttc aataaaggag cccacaaccc ntcantnggg
420cgccagtcct ccgattgact gagtcgcccg ggtacccgtg tatccaataa accntcttgc
480agttgcatcc gacttgtggt cttcgctgtt ccttgggagg gtctcctctg agtgattgac
540tacccgtcag cgggggtctt tcaaactgca gttctcaagt aagctcaacc atccgagggt
600cattctcaaa gccaagtcaa acttgggagc cctcactcct ggtggtcttt caaaagaccg
660tgcattggat agtcagagac tctgcaggag cggattaagt ccaggcctgt ctccctgctt
720tctgcctggg ttctaaagtc aagaaggcca gatggctcag atagttgaga cagtggctta
780gctgattctc tggggatgca tttggtctgc ccaggaaacc ctggagagtt ttctacccaa
840gatactaaag ttcaaacggc agcgcctgtc ggcagactca gcctatacaa agctggcctg
900tatctgatgg gattntaagt ccctgggcag acccgggttt gtgggcctga agcttgagtt
960ncaggagact tagtgggcca tgggattctt ttaggatccc gatatggnca aacttaaact
1020g
1021831013DNARattus norvegicusmisc_feature1- 1013n = g, a, c or t(u)
83ttttgagttt tctcngcccg nttgtgncng aaanncagcg ggggtntntc actgtgnntc
60tcacatgtnc tcacacanat cngggggacn ctcacancnn catctcacnt ntgnganctc
120acactcgtgt gggntctttc aaaacantgt ncnntggata cncagacact cnncnagngn
180ggtntatctn cacnngtgtc tcngngnttt nngcnngnnn tcnaanctca aaagcgncat
240nnggcacata tntntgacac ngnggtatat nngnctctcn ggnganacat ttgntncgca
300caaaaanccn tggagatttn tctacncaat annctanttt tcacaggnga gcncntgtnn
360anacncncac cntanacaan tnnggnntgt ntcagaggng attttanctc nntggncana
420cccgnttntg tgnnccaaan tnttgttttc caagacatat agtggnacat gnnactctnc
480gatntccgat gagnananat gtgntcngac ntttacagcg natacacngt ggngcanntn
540tcacagatat gtgtntatnt cnnacanaca aatntgcnng actcctctcg tgtataaatc
600aatanacggg ngggttaaca tnnggccncn gttgnncagt natancgnga aacacactcn
660caagggctnc aanttttnca nctatacacn cncncccgan gggncngngc acaaatgtgc
720nccgaaattt tatncgccnc naacactctn aaattnntcc cgggacccta gatatatttn
780tccncattna aaatttgcac attntttncc anttgcangg gnantcgggg gttcacccnc
840cncnttggga aggggnntnt tnaacccggg ttcnaantta taggggggtt tanatcnccc
900cattttttna aaaagngttt accntgggcc ccntnttttn cnaaaaaatt tgnccccgnt
960ttancnccgg ggttggggaa cncgaatttc ttngggngcc cccctnagnn ttt
1013841002DNARattus norvegicusmisc_feature1- 1002n = g, a, c or t(u)
84aaananttna cacggattcc ttttcctcaa aaccaatggg ggaataaatg atgtngtagg
60gttccccngt aatggatact aggttgaact tccangggga antattattt caataaggtt
120ttagaggtcc cacttgtnat caggttattc tgttgctttg ggtcaagcaa acagccnatc
180aggattgtga ttattngant aacccattta cctnacagcn gggaggaaan ccaangggag
240gcttgaggaa acggcttgtg ggttcataaa ctctttgaat cataccttgg gtgattcaaa
300tgctttttac taggctctcc tttcatagta cctctcttgt ggacaaggac ccagtccttt
360gaaaagcatt gaaaactcaa accataccac tatcagtttc agctttaata taaattagct
420ttctaagttc agctgaccac nttttcactg gaccttcact gatctcacag ggaagatata
480ttttcaacaa ttacaaagac atttctgggt tggactatgc attcctttgg gccagattct
540acatcctttt tttatgccag aattttttag cgttcctgta agattgtcag tttcccctag
600gaaatccata aagctttaaa tgccttctaa atagccaata ttttaatgag aaatgtagtc
660actgatatct ctttgtattt aaaggttatt ttgaggggag ttgcttggtt ggttggttgg
720ttggttggtt ggttggttag ttggttggtt ttggctttgg ttttctgtcc catggtaata
780tgatacttat gtcatagatt agttaactca aatggtcttt tcaggtggca gtctggaaaa
840caactaactt ggggggaaaa aggctgctcc atgttctata aaagctgtac atgtgatttt
900ctctgcttta ccttttatac tcatttattn tgttatttgt gtatgaaagc cttccgtatg
960aaagaccntt acctgtaggt ttggggngct agaaaagatc tc
1002851031DNARattus norvegicusmisc_feature1- 1037n = g, a, c or t(u)
85caacnnccat nttttggaat ttgnggggta aaatttaaac cgattcnttt tccncaaacc
60caantggggg atatnnatgt atgtngtagg gtcccccngt aatggaatat ttaggttgaa
120cttacaaggg aaatattatt ttcacaatgg tttagaggtt ccactgtnac aagtattctg
180ttgctttggn ccangtcaaa cagcccatca ggatggtgat attagaatta accatttatc
240caacagccag gagaaancca aagggagctt gagaaacggc tgtgggttca taaaactctt
300tgaatcatac cttggtgatt caaatgcttt ttattaggct ctccttcata gtacctctct
360tgtggacaaa gaccccagtc ctttgaaagc attgaaactc aaaccatacc actatcagtt
420tcagctttaa tataaattag ctttctaagt tcagctgacc accttttcac tggaccttca
480ctgatctcac agggaagata tattttcaac aattacaaag acatttctgg gttggactat
540gcattccttt gggccagatt ctacatcctt tttttatgcc agaatttttt agcgttcctg
600taagattgtc agtttcccct aggaaatcca taaagcttta aatgccttct aaatagccaa
660tattttaatg agaaatgtag tcactgatat ctctttgtat ttaaaggtta ttttgagggg
720agttgcttgg ttggttggtt ggttggttgg ttggttggtt agttggttgg ttttggcttt
780ggttttctgt cccatggtaa tatgatactt atgtcataga ttagttaact caaatggtct
840tttcaggtgg cagtctggaa aacaactaac ttggggggaa aaaggctgct ccatgttcta
900taaaagctgt acatgtgatt ttctctgctt taccttttat actcatttat tttgttattt
960gtgtatgaaa gcccttcncc tatgaaagac nttcactgta ggtttgggcn gctagaaagn
1020gatcnnnaaa a
1031861039DNARattus norvegicusmisc_feature1- 1039n = g, a, c or t(u)
86aanttttgng agtntttgga atnnaacngc ggttccttat gntggnnaan aaaccnctnc
60nanaccccaa taccttggat nttttaanat gcncctgggt aagcnaantt gaattatttt
120ccntgggata anaagtggaa tcattgacag ttttgtggtc cttttnncat ccccatgngg
180tttnatgact aggcacttta tttcatggac aaaccagtgt tgtccctcnt ggggactgag
240tgggattaaa aaaaccttcc aaaaatgtgt aatntgatca aacccattga gacaatcagt
300gnggagtatt agcaaattaa actgacttgt tcacttntga aaantgatgt ctgatttcgg
360aagaatccca gtgcctcggg acatgaaagg gagatgtaac cttgagttca tggttaggag
420ggaattcata gagacagttg gtaaaaatct gagtgaggtt gagaggttgg aggaccacat
480tgtgtatttg ctcatcntgt gagggagaga ctttgtactc tgctctgaga aggcagaact
540gttaggcaga cacttagaga atatatgtca tggcaaaaga catccaccca acaagtcttc
600agtaacaaag cactaaacag aaaggggttg aagagactgg tcagtggctg agagctttta
660ttgctcttac agaggactcg gcatgcntag cagctcacaa cagcntgtga cttcaacact
720atgcctctgg cctcaggaga cacctgtgta ctcccaccca gacacatata cttaaaaata
780aaagaaatct tttaaacatt gagcaaatgt aatcaggtac taacattgaa tatatctggg
840gccaggaatt attctggttt attgcctttt tcggaagcct aatatcacac atagagaaat
900aggcagcaca ggcctaacag cccataatgt gtgctattct atcaatagtg ccaagtattg
960acatggacta ttcaaaaggc ccaaaagtta aatggcccag aagtncaaca taaagncggg
1020cnagctaaaa gagatcntc
1039871058DNARattus norvegicusmisc_feature1- 1058n = g, a, c or t(u)
87aaaagctttt tttcagnttg gccaattttt aacccattaa anattgttnt ttggaatcng
60catttggtna ngttattgnc gaggaaggta ntaagggant ttttcccaaa ttncaaccat
120tnttggccag ttgggatttt gattgantgg gaacccccca ggntttaata agcctttgga
180tttgttcaca ggggattaac aaantccttt gnttaatggg gattgaattt gggaaattgn
240ttccntaatt ttccaggacc aatgcacant ggantattag aactgatgta acagagtgat
300atgggaccaa gtaggaacaa gggtgcaggt ttgccgaggc aggtaattgn tggtcttgtc
360attgtcataa ctttcttgaa agttttagga cttggacgga cagaagacat gatcattagt
420atacttgatg acaagtggag atgaaaggac aaaaattgtg cacatcaaga ggagaattta
480acattgggtt ttcttgcatt agctatccac tcttgccctc accctcccac ccccttaatc
540ccagttacct tgacgattga ggtcattttc tctgaacaca ttctcttctt ggatgttaaa
600gtgccatttg acactgtgtt tagggacact gcttaggccg gggtggggga attgccacag
660aagcttgacc ttagaaggtt gagactctgg aagcctgaga gagatgagat ctgtcaaaga
720aacgcttagc gttggtatgg gatgcgtagg aggctgtact cttgttctct agatgctatc
780acgggtgatg taggagaaat gatctcactc agcccaagat cattcccttc caaatgtgct
840catcccatca gcaagcaaga cctgtactga agccagcagg ggcgtggtac agagtccggc
900attttttgca tgccatgctg gtttgatgtt tgaactctaa aggtggagac tgttgggggc
960agcagggcag acagtcttct gatgatttct ctgccttcaa actgaggtnn actcttgaaa
1020gattncacct gtaggtnggg caagctaaaa gagaggcc
1058881043DNARattus norvegicusmisc_feature1- 1043n = g, a, c or t(u)
88attttccatt gcgcnccatt gaacggnttt gcgnggggtn ttaggggtnn aanggatttt
60nagtgtgccn aanaaggtac attgaaggcn ttntttggat ttggntttgt aaanccattc
120ccttngaaaa ngagttgtag tnttaancgg caaacaacca ccggttgtag cgtggttttt
180tgttgcaagc ngcggttagg gcggaaaaaa ggatntaagg agatcctttn ncttttcttg
240ggggtctgac gnntcatgtt gtgtggaatt ntgagcggtt acaatttcac acngattttt
300tatgcaaatc cacttgccaa gttggnataa ctgacttatt ttaccgggaa ntctccatgt
360atcttctttg gacacttacc cttacagagc ccaggatgaa ttttgaccaa gccaagtatt
420cacacagccc aatgtgacat gttaccacaa attggngatt ttccttcagt acactcaaat
480gacacaagct ttttctcgat gtctttcttg tcattcacta ccaggatgaa attaatttta
540tcttctgagg angcaatata cgatccaccc aggaaaattc actttagatc ttcgttctca
600tttcttggca aacagaattt gagctgaatt tctcttagaa aaatctgtcn ttcagaaact
660taaattcttg ctgttccata acagaagtca gcaagtgact caccctccag atacaggtat
720attacctcca ctcccatcca cagagactta attctagtca gcttcatgat agtgagcctt
780catccgtaag gagctgtatg gtatgggaag gggatacaga cagggccagg ggtgttttta
840aacggtaacc cagggaccac atccattaaa aacactggac tgtttgtgag agtgtatatt
900cctgagcatt gcctatccct taaggtacta caaaatttgg gagtgaggct cagcaaacta
960ttttaacatg cctctccacc aacnactcaa gattcccgtg nacagttgaa agtttncacc
1020aaaggtgggc aagctaaaga gat
104389454DNARattus norvegicusmisc_feature1- 454n = g, a, c or t(u)
89aattcatccc tcatttgccc tgctagtgaa aactatttca gacctgaaga caacatcctt
60gaaaacttct ctggagaatg tgcagagatc accatggcaa cctgtcccgg gccctgcctg
120gcagggctcc aaggcacaca aataacgcca ctggaatgtg gtgcagggct ccgggtgggg
180tgactagaaa agctgccaat tttccatgaa aaccaccggt gagaagcctc agcctcagga
240aggtgtcagt agagagggct gggttctctc tagcaccaag ggacaggctg tgcgcaagca
300tgcgcagaag cacactcacc ggcctccttt ggggcagggc tgcctgaaat gaaccggctt
360cagttttgtg cagctcaagg gcacaaggnt agtgcccttt ncttggncnt gaggcactnn
420taaatgtagg ttgggcgcgc taanaaagat ccnt
45490873DNARattus norvegicusmisc_feature1- 873n = g, a, c or t(u)
90gttgttattc aatcatccac atttgtaaaa acacacttcg ggtcctcctt gtgtcnggca
60gtaccatcca ttgagtttca ggaagcagaa gttttaaaag ctnccagcan cntttaaatc
120cacagctcaa gttgttgaac accttgggaa actaccactt attcacccag aggagagttg
180attcaagtag ttagtaccnt tntgcatcag aanccaccag ntactgccgg tgagagtcgg
240taatnccang aactcatcca tgcaggcaaa tttaaggaca cacggcttga cacagagatg
300gttanatcgg ctgtgacagt tctttagtgg gagacttttg ctttctgaat ccacagggct
360tactttcttt ctttttcttt ttaagacaag ctctcatttt catcttgaga aaatgtctga
420tcaagccacc aactgaaaac ctgccattat aaacgaggga tttcacaatg ctcattccaa
480aatctgcggc tattcatttc tggaagtgac tcactgagga aggacggctg ttgggggtgg
540gagggagaga tcatttttag gagaccgcct gctctctgag aactgagcag aaaccccaga
600gtggctagca cgtgtgtgca gcgaccccag ctcagctctc tgagtcaccc cctcccccag
660atgacacgcc atgaccagtc tcctcgtgaa agccacttgg tggacaaaaa gccctttggg
720ctgtgcaccc agcctcacat ctgcctctct gggggctatt ttcacataaa tcaggaggga
780ggcagcagca gttgcccacc tgttttngac tccgattgct tggggantga aggactttnt
840naatgtaggt ttgggncngc tnaaaagatc cnt
87391876DNARattus norvegicusmisc_feature1- 876n = g, a, c or t(u)
91gttgttattc aatcaattct gttgctttgg nccangtcaa acagcccatc cgggatgtga
60ntatnggaac taacccattt atcctacagc caggaggaaa cccaanggga ggctgaggaa
120acggctgtgg nttcataaaa ctctttgaat cataccttgg gtgattcaaa tgctttttac
180taggctctcc ttcatagtac ctctctgtgg acaaagaccc agtccctttg aaaagcattg
240aaactcaaac cataccacta tcagtttcag ctttaatata aattagcttt ctaagttcag
300ctgaccacct tttcactgga ccttcactna tctcacaggg aagatatatt ttcaacaatt
360acaaagacat ttctgggttg gactatgcat tcctttggcc agattctaca tccttttttt
420atgccagaat tttttagcgt tcctgtaaga ttgtcagttt cccctaggaa atccataaag
480ctttaaatgc cttctaaata gccaatattt taatgagaaa tgtagtcact gatatctctt
540tgtatttaaa ggttattttg aggggagttg cttggttggt tggttggttg gttggttggt
600tggttagttg gttggttttg gctttggttt tctgtcccat ggtaatatga tacttatgtc
660atagattagt taactcaaat ggtcttttca ggtggcagtc ttgaaaacaa ctaacttggg
720gggaaaaagg ctgctccatg ttctataaaa gctgtacatg tgattttctc tgctttacct
780tttatactca tttattttgt tatttntgta tgaaagccct tccgtcctga aagaccttta
840cctgtaggtt tggnccgttn aaaagatcnc tgggcc
87692459DNARattus norvegicusmisc_feature1- 459n = g, a, c or t(u)
92aattcagaag gatctcagaa attgaaagca tgtgcaaaga taaagatttg gggtagtagn
60agtggtcaaa agggacaagg taataatggt aatatgcttt tgtgtatgtg ttcttttaga
120gttatgttaa aatctagaga agcaaagtcg attctcatag atgcttttag tctttggacc
180ctgactagag acagtttaca ccctagacaa gagagagaat ggggttgagt aaaacagtcc
240tcccgaactc tccacagatg ctttggcaaa agaaggaaat gagcttaaac tttttggagc
300tctcctggga acagaaggag gtgggagacg tcttgcctcc ttgctggctc ctattggaga
360agtgcttatt tctggttntg ggttttttag gtngnttgtc tgggttcctn gggncctgag
420ggcacttnna aatgtaggtn tggcgcgcta aaaangatc
459933133DNARattus norvegicusmisc_feature1- 3133n = g, a, c or t(u)
93acccacacnc cnancnacac ccacacacca anccacaccc acacaccaaa ccacacccac
60acaccaaacc acacccacac accaaaccac acccacacac caaaccacac ccacacaccc
120gagtgtggtg tgtcctcctc actgagtgtc agccagccct ttcctctact tcaggtaaag
180gtttctccac tgcctcactg tgtccctgtc acatgggcac aaagccatct cagcagtcct
240tctcaaggac gtgggtgcca ggtttggaag ctggaatgcc tacatctaaa atcttggcca
300tgacttgtga caacttacat atacatagac atatatacat atacagctta catagacgca
360gagcctcaga ctcctctgaa gaacgggttg attctgtgct ctgcagagat gctgggagag
420tgtataaaaa ggtcaagaaa gcaggcttag aaagaagggc aactctacct agtgtctcct
480tacaattttg ttttacgtcc tcttctgccc acagagccct taagacactc cctactttct
540gcatcattcc tggtgtcttg taggaacaag ttagtgaatg atcactctgt aaacacatac
600ctacaggtcc tccttacctt gggctctgga acacccggtg aagtctgtgg gtaggagggt
660ctggctgagg ttgagtgtat caagtaatca actggcagta ccctntgggg agtggcctgt
720ggtttcctgc tcccctcttt gggtgagaaa tcctagggtg gtgggagcca aggcttaggc
780aaaggttcag gcacagcagg gtgtgggagg gagtgagact atagtagagg tgagtggaag
840gtatggattc gaagactttc ggattaaaaa aaaagcaaaa aaaaaaaaaa aaaaaaaacc
900aaaaaccaaa acaaaacaaa aaaccaaaaa acaaaacggt ccaaccagtg agatgtggct
960tgctctgagt tgctaattat gcagggctta gatctcaaaa acagtctgtg ctctggggcc
1020actgctgaca tccaagtcag gcccagaagc tcttggtctt catctttcct ttccctctca
1080ggctgcttga agctgattga ggtattcctt gcttgttcag ccggttcntg atggtctccn
1140tgttcntccc agttctctcc atgtttcttt tgctttgaag tacaaaggaa tacagttgca
1200ggggttacat ggcactcccn tattcacttt tagggttacc acaaaagctt gtgattcttt
1260ccctcnttag gactgagctt ctacccccgc acacaggcct aactttggtt tccccaccca
1320taatggggca cccaccccca ccnccgcccc accccacccc aagaaaaaga aaaaagaaaa
1380agaaagaaat gaaacggcca gctggctctt acccactttg ggcagcaggt gtttcctccc
1440tagcttccct tttgcatctc atacttgttg cttgcacacc ctcacccctc tcttgctgcc
1500tttttcaaat taatagcctg caacttccct tgcatataga gaatggttcc caggttctta
1560ctgggattag tgaacgctct ttttgttgag gaaatgcttt taacaccacc aagtgctgta
1620cccctcaaag ttggtgaagc tctagattca ntgggctgta caagggacac ttgggaaaaa
1680tttgaacagg acaagcctga gggtgtgagt ggggttggct catctacaca ggagctgcga
1740ntgagaggga aagggccccc aaacatcttt gctaccactg ccttcttaag tttggggact
1800tggaaatccc gttgtttaga tcttgaccgt aatcaggagt cagcgtagag gaggccccgg
1860aaggagggcc cagcgcggat tcgcccgcgg cagggcgggg accaacagag ggccntcggg
1920gataggggag cgccgccccg ccntcccggg gaaggacaca ttgcttgtta gcaggaagcc
1980agccagaccc ggaggaggcc gctccagcgt tggtgttgcc ggtccggggc tagcctgatc
2040cgggcagggt gagttgagac gatcgggtga gcttgggccg gggacgccag cgtcttcagt
2100cctggggatt gtcccaggag ggcaaggagc ttggaggagg gaggccgcac agctagggga
2160gtcaggtctg agtcccgagt gtgctctaaa gccggggcgg tgagagtggc ggcccgcccg
2220gggccgcgca gcgngcagtc tcccccgcgt gggaagtggt aacttaacgc acagccacag
2280gattcccggc ctttagctgc tggagggagg gtggcttctc ccggaggagt ctgttgtgaa
2340actcggttgg agggcaccgt gggtgcgggc aagggagaga tggggtcgcc ctgaagaagt
2400ggggggctgg agtagaaagt ggactttgtg caaacctcac cccagagtag ttagttacca
2460aggctggttt tttttttttt ttttttttgc tcagacacaa ggaaaatttg actcaatgtt
2520aaaatatgta atttggcagg aaaacttttt tcctagcctc cttgctaata tagttggaac
2580agggggctcc caagaggtat agagtccccc attttacaaa atgtggttca gtgggactgt
2640ggcccaccca gtcgtgtatc catggaagag tggcttttat ggagaagttc attttcctta
2700accttaaaaa ctgtaaagga tcttgtgctt gagaatattg ttggccagct ttatagtctt
2760catttataaa actatttaga ctagagtgtt atagattata ggtcttcaag tttccagtca
2820ccagtccttg gctttttagt atggaaatca ccagtaatgg caatataaca tccctgcttc
2880tgtttcttag aaggctaaat tacagtgtgt tcaaactccg tgtcattgca acaggttaaa
2940ctaactttat acgtaggaca tcagggtatt gacattctca tcctaaagtc agtttgtctg
3000tttccagagg aggaactgaa gcagtggttc tttaagtaac tgactcaggg ctttcctgcc
3060tggcgcgcct gccaggcata gtgtagcatt gtactgcatc ttctttgacc agtttcccca
3120ggtgaagagc ctg
3133942161DNARattus norvegicusmisc_feature1- 2161n = g, a, c or t(u)
94ctggaagctc ccttctcccc tgtactctac tctgcaaatc cctgcaggtg gacactgaga
60gaagccacac acacctgttt ttgttttcca tctctgaggg atctgccatc tactgtacat
120gcagtttctg aaaacatttg tttggcggtt ttctatttgt ttactaagtt agttcagttt
180tcatcagtgg cacaaactag aagtcattca tatgagtaaa atttgttaaa acgtcttcat
240aaagttttca gtttgcgagg agcatacaag gaaagggtcg cttaagtgga aagggagcag
300gctctgtggc tttctcattc taacccttgt ttgttcctgt gaggtgtgga gccctgctct
360gctgctgtct ggacagagca gagatccttg cagcagccac agctctttac tgcagatgtg
420ttctgggggc ctggttctga ctccttcagc tcctggtagt gccctgcgtg ataataacag
480cctcctgctc ccagctccag acagctcgtc tttctgttgc agcagcactg tgaacaccag
540agtgattctg agcttagatt caagatgacc tcacacttat gggaatcctg tgcgtggacg
600tgttgcttsc tgtttttact gcccavgatc ttccagctga atgccagagt gttgagtgtg
660cccarcctgg ggtarcccag cttgctccac caccctctgt ggatactcca cccagtctgc
720tgttaccagg cactggccca gtgaaaatct aaaggtttta ttgtttagta gaaaattaaa
780acacttacta cagtttgaat gtgttgcaca ttatggtttg aggccaaagg aaggtaggca
840gaaggaaaac aggaggcaag gaggggaaga aagctggaga gtctggctgg agggcgatgc
900cctcctggtt ctgaaagagc cacacccctc tgctgccagt tacaggccga tctgctgctt
960agcaccaccc tgatgtgctc cagcatctcc cgttccagcg tggtttctgg tcgraccttt
1020attccacggt tacttgaggg gtgtgtgtgc gtgcgtgtgt gtgtgtgtgt gtgtgtgtgt
1080gtgtgtgtgt gtgtacatgt ctgtgtcccc atgccacagc acttgtggag gtcagaggac
1140aaaggacact aaattgcttc tccctttcca tcacgtgggt ccctcaagct tggatcttga
1200aaacgttact tctagtgtaa ttgtcctaaa agttcacgtg gactttaagt ctcttgttta
1260aagtctgtag gcagttctgt tcccgcagca cagttcctca caaagccctc tgatggctga
1320ttctttgctc ttggangcac aaggctgtgc cgtgcttaag acaggctgca cagcttarga
1380cttgcactga gggcgttctc gcctggttgg ctcarcatct ggagtatatt ggtcatggcg
1440agtcagggct cagctctcgg tatttatctt tcagtgcatt gatgtatttg cccttacaga
1500cactgtacct gaattattta acactgtaat gctagtgcct gatactgaat tcatgactat
1560aagttcanar ctgcaracac agccttaggt gttaaacagt atatttttaa gagcttcaag
1620tgcacagaac agtaggggtg cagttttgac cccctaggtc tggactttga ggttgcatct
1680catgaatgca gctctgagct gggggcgcca tactctacat tgtaaagtaa tgcacctcct
1740aactacctgc catggtagca agctccagcc acctgaaaag cagccagccc tcttggggca
1800gcactgcatg aggaagcctg aaccccagca aaggagcatt gggctgctat gtctgttctg
1860ctacagcgac aaatcccagt gtgcacttgc caacagctgg aggcatgcca tagccagggt
1920ttcagcatgg ctgcccttgg agagaggcgt gcgctgtgtg tgtgtgtgtg tgtgtgtgtg
1980tgtgtgtgtg tgtgtgtgtg tgttagaata agcaactact gacaaattca rgarcataaa
2040cattatggaa atttttttgt gtatgtcatc attttaattt taaaagatgc cttattttct
2100cctcttggaa ctaaagagat tatatttcac tttataaaga aaaaaaaaaa aaaaaaaaaa
2160a
216195824DNARattus norvegicusmisc_feature1- 824n = g, a, c or t(u)
95gggggntttt cnnanntanc aaaaantngn tntancanng antnnttgag ntgttgaagn
60aangnggaaa angttttgaa atcantgtaa tgaggttcca aaaattgagc aggaaattgg
120atgntgtcag gagaaacccn ttcagtnttg tgcaattggt tcgccagcag ttaggaccgn
180ttccccatca cttgtgccag cggacatcca gntattgagc cntgnatcat ttatggnaca
240aattaggaac acacaacaga gatccgcttt ntgactgcca tgttcgccaa actcaattgg
300gggaagtaat cctccagacc gttccgtttg cacgtntagg aagccacagt gaaaacacaa
360aattcgtgga ggcgactcta accaggaagc ctaatcccnt agattcccgg gacactgggg
420caggcgtcct aaaaacagct ttgtggggct tcagtcctcc gtgcggttcc agtccgggtc
480ttggggatcg ccctcgcggg gaatgtccgg gactccggtc ggtatctttt tggcctggga
540atttccagcg tgtggaaaaa gtccacaaac ttagtcctca ctgcccgcct cgcctcctcc
600ggcccttctc ggtgcccacg caccccccga tcgaacccga ggatgagcat agggtgtatt
660ttaggcgtgc tgggcttccc cgcccccctc tgcccactta gctggcaaga agaaagccag
720cactataaag gaggccaggg ccaaggactg gcctcctctt gctcacgagg tcagacgcga
780gctctgaaag acttcacctg taggtttggc aagctgaaga gatc
82496774DNARattus norvegicusmisc_feature1- 774n = g, a, c or t(u)
96gagggganna ncancaggac caancngata agggggtcaa caacntgngt tccncccntt
60gagngggaaa tgagcacgng gcantccaac cgntcaaggt cccgnttcgg acggtcacac
120antaggttnt catntggatt gccngngttc cngttggcat ccgggaaaan tgagactgtg
180tcggtaccag agntaggatg gccntccttc ccngccccgg ccttnttggc gccttgcgat
240ccttcccgaa ccggcccntg gcgtctccgc cttnggcact tgcacatntg gcggcccagg
300atggcgcttc cgggatggcg ccagcgcgcg tacgtcatca cggagcgtcc atgtgttcct
360tctgtccaag cgcntaggag cctgcgcgta ctcccagcaa ggaagatgta ggaccaaaat
420gtagaagcac ttaacatgaa cgtcaaaacg atgaccaatc acagggcgat atatgcgcat
480gcgcaatgtt ccaatcatgg ctcataagca atccggaagt ggccaattaa atatactatt
540tactaatcca gggttacaca gtgaaaccct gtctcgaaaa ataaacacag ggctggagag
600atggctcact gattaagaac actgactgct cttccagaag tcttgagttc aattccgagc
660aagcacatgg tggctcacaa ccatctgtaa cagattctgg tttatgtnga gacaactaca
720gtgtactcgt attgaaagnt ncccacctgt aggttnggca agctaaanga gatc
77497248DNARattus norvegicusmisc_feature1- 248n = g, a, c or t(u)
97tgacacttca tggaaactga gaccgggagc ttccaccaga aggcactgcc cagtggagaa
60aaccgacttc tttttgttgt tgttctgatg ttttgttttt gagataaagg tctcactgtg
120tagctcaggc tggttttgaa atcaggatcc tgaccctcag gaatgttaaa gtgcctaaaa
180gtggngacaa attattttac gtgcctttga aagacttcac ctgtaggttn ggcnagctag
240aagagatc
24898880DNARattus norvegicusmisc_feature1- 880n = g, a, c or t(u)
98aanatggntt ggttntaaag gttaaaattg gggcaaaatt tttccgcccg ggtccttaaa
60ccggattaac tccaaggcca aaattccgag ggggaatcaa caacaaggac ccaaccggat
120taaggcgggt tcaaacaaac ttggatttcc ngccctttgg ggcgggggaa atgggcacgg
180gngcattcca agcngntcaa ggttccggct tgcggacggt taacacaant aggtttctca
240tctagattgg ccngcgttgc ggttgagcat ccgggaaaat tgagattgtg tcggtaccag
300aggtaggatg ggccttcctt cccngccccg gcttcctggc gccttgcnat ccttcccgaa
360ccggcccttg ggtctccggc cttgggcact tgcacatctg gcggccagga tgcgcttccg
420ggatggcgcc agcgcgcgta cgtcatcacg gagcgtccat gtgttcnttc tgtccaagcg
480cttaggagcc tgcgcgtact cccagcaagg aagatgtagg accaaaatgt agaagcactt
540aacatgaacg tcaaaacgat gaccaatcac agggcgatat atgcgcatgc gcaatgttcc
600aatcatggct cataagcaat ccggaagtgg ccaattaaat atactattta ctaatccagg
660gttacacagt gaaaccctgt ctcgaaaaat aaacacaggg ctggagagat ggctcactga
720ttaagaacac tgactgctct tccagaagtc ttgagttcaa ttccgagcaa gcacatggtg
780gctcacaacc atctgtaaca gattctggtt tatctggnnt cnactacagt gtannggcat
840tgaaagatnn tacctgtagg ttggncagct aaaaaggatc
88099864DNARattus norvegicusmisc_feature1- 864n = g, a, c or t(u)
99aattttaant tgttggnata anggcttgnc catatccttc ctnttgtttg ccctaagtaa
60cagccaattg ggggagaant tttntgtcag tatcatattt ttcgttaggg aacggaggcn
120caggaantga tccntntggg ttacagtcat tttagcatag gntgacagtt ggngaccaan
180tnatcttgcc gtgttggaag gagaggggan taaggntgaa gctcttgagt ccnttgangc
240ccttggaatc gggaantccc ttaaaccaac cccttttgcc gttgaattgc accaaccaga
300ttcttccagt ctgcttgagg angacaggac ttcattgctn tggagagggg caggagggtt
360gggagttgac ntnacagggc tcagggattc ttttagaagg gtccaggttc atggcttccc
420ccccccccag ccaggtcaga cactaaagtg tcttaagccc ctccatactt gccgctcccc
480cacnttggat gaagccggcc attaggcagg gaccgtctct gggagaggcc aagccctctg
540gctcacttgt ggatttcctt taagcaagac ttcctctctg cttccaggac tcctgtcaaa
600caagagggtc cctggcttag agtttgggag ctgcaggcag aacagacatt ccccgatgac
660tcacaagcct ggaactctgt gggccagcag gaatggggat ggctttctgg tcagtcaggg
720tcaactggga cactcactct gagacaggga ggcaagggag aaacaggtca gaggtagaga
780gagctcagtc ccagggactc acgttgaggt ccctaaggtg cgctagggag aggnttttac
840attcggttng gcaagctaaa agag
864100874DNARattus norvegicusmisc_feature1- 874n = g, a, c or t(u)
100gaggttggac cacaaggagn ttggnggaaa atnnaaaagt caacctatca gggtgtcttt
60tagtttggaa cagaggcttg ggcagaaata tgggcaagta ttaggaaagt acaaggggaa
120atgttgtcaa cgcgnttgtt ttcccagttg ttgnactgat cccnccagga tgttttccca
180cntatgntat ggaaccntct ctttcaggaa gccattntna ncntatggnt tgcaacccct
240ttggggtcgc aacagcaggt attaacatta ggattcataa cgntagcaaa atnacagtta
300tggagtagca atgaaataac tctatgnttg ggagggtcac cacaacanga gggacggtat
360cacaggnttt tagcattagg aaggttgagg accttatttc agagtgtcnt gacaatcntt
420cntgggacca cttgacttna tctggagccc tttccctcac gctcntactc cttaccatct
480ctgcacagct ctntgaggct tagagcggtc tttcttcata gctttccntt ttccttcagg
540tatgcagtca catcttgctt tagaccccag ggacattccg tgtctgactc actgcacaaa
600atagtttccc acatatgagt cctcaaccgc cccacatcac gagacggaca agaccggaga
660cgccatacat tctgtatttg ccctccttcc tcatttaaat aggaatttgt tgctgtttaa
720tttttcatta tttgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg
780tgcgcgcgca cgttaatatg ccgctcagaa tagtctaaaa ctgctgggct tgaaagacnt
840ncacctgtag gtttgggcna gctaaaagag tatc
874101886DNARattus norvegicusmisc_feature1- 886n = g, a, c or t(u)
101atttttnaat tgcagcaatc ctcctgcctt ttttcttggt tgttaantca caggatnttt
60gcacacttga ggttgaantt gcagcaatcc tcctgctttt gtttnttggg cgcttggatt
120atagtatgtg cataacactt gagcagtaac tgttttcttc aatctcattt atctcagaag
180ttccccttgn tgattcagac gttattaatt aggcaaacca atgttgattg tcattaccca
240tgagttgctt ggcttgtgag atgcatactg tgtgttcgtg aggcacntac tgtgaggcat
300gtgcccgtga ggttcatggc tgtgaggtgt gtgcccgtga ggttcatggc tttctngacc
360acngggagta tgaaggagag gaatcctacg tttgatgcca gccagggtta tacagcaaga
420tcccgtctca aaacaaaatg aagaagtaga gagattagtg ttaataagca actgaggcct
480tgaagggctg aggtcaggcg gtgccctggt gcacacacag aagcgtgcca gtgacgtcag
540acagactcag ccctgtgtca gacaggccgg agggtgactg gccatgtggc gtgattggac
600acattcccaa aaaaggaact cgatggaaga ggctcctcnt gctccagaca gggcggtggt
660tatgtgactt gtgcgagatt agtctcatac cctattgcta gcctgtgcct ggtaccacgg
720acatggtaca atccagggag gagccgtaag cactacaggg gagccatcct gaatcccagc
780aagtccaact tctgtttttt cttccttccc cgcaacatta ggaatgactt ctaagagngc
840tgttgaaaga ctttcacctg taggttgggc aagcttaaaa gaggat
886102865DNARattus norvegicusmisc_feature1- 865n = g, a, c or t(u)
102tggaggtaaa agtcacaagn ttttcaaggg tttgagatga cagttcaacg tgagnattng
60acaaggattg attcttgtnn acaggaaagn tccccatccc accaananac accgtgttca
120ggcccantgc tcagagctcc gggcgccagc gaagggcaaa cggccactga ttggaaagnt
180gcagtttaaa gacatgtccc aggaactggt anccttgtgt gactggactt agccttgcaa
240ntctgtctga agcataacnt gntgctgtct ntgggcgagc atttatgtgc cccacttgag
300acccatctca ggacacgcag gacacggtcc agtggagctt tccctccaga gagaggtgtt
360agggnccatc agtgagcttc caaggacagg ggaccagaac ggtgaaaaca aaccagggct
420gtgaaggaga gcagggcggg ggggggggga gggggggcgc tctntagaat agattgaacc
480tgcagagctg cttgctacct gaagttgtca cccttttacc cacccacntc atctgtctct
540gcttgaccat ctcagcaagt gtcacctcgc tgccaggaca caagtttcct aaagcttatt
600tcagtgtcag ccgctgggga gacacattca gggcatgggc gtcccccagc cctcggggag
660aatgtgggag gtggcgatgt gggagggatt cgagagaaga gaatgcttaa gaaccatcca
720gggaacctgt gcgtttgaag gtctgagtta cacacaggct gctcaggaag gagctagagc
780tccaaatagg agctgtgatc aggctgtgtg tgtgtgcctg gtgaaagact ttnacctgta
840ggtttgggcn agcttgaaaa gtatc
865103859DNARattus norvegicusmisc_feature1- 859n = g, a, c or t(u)
103cangagcant ntgaancagg catttntgga agggctccng agaaaacacg tggaattnct
60tgtctctggg actttagtnc cagcnaggan gatncagtga gggaacacac cgggcttttg
120ttgtgcacgg gaggccaggc tcancnncct tgggagnttg acatccagca ggctatanac
180agtgatccag gggacatgta cacatgggga actgnccagg cagagaaaga caagagaaaa
240tctcaaanga tgaagacaga gangagtaat atggccagaa ngatacagtg cctcntgcat
300aacccttgag tttaatttcc agggtcaact gtattttgaa agtataaatg aaagttcctg
360aagtaataaa tttataggat gttagtatca cactgttcag aatagctcaa aaaatcctgc
420cntgtcctct taagtatgtg aatcatcttt tactgcaacg tgtccacaat gtatatacta
480catacccaaa agtcctcact gttatcccaa ttagtaggct ggctgccaat agttgtccat
540acagagtgcc tgctgctgtg gccatccnta ctgtagtaaa cagtcatcca aagctcagga
600gtgaggctat tgtagaaatg cacttcctgg gggccctact gtcagtgagc acctgagaga
660gaaagggaca caggcccaag gtgggaggcc ttagataaag gcccatcatg ctcaggaaag
720gatttntaca gatctcttag ggaagttaca atcaaattca tacctcacag cagagctcag
780gagaagaatc cataaagnnt gaagacatgc ttgtngtgnc tgaaggacnn tacntgtagn
840tngggccngc tgaaatttt
859104883DNARattus norvegicusmisc_feature1- 883n = g, a, c or t(u)
104ggggggnnaa naatttccca aaaanngnng gncccntttt ttatccagtt tnnggttgaa
60natctcnccc cggtttnaaa acccncaatg gggaaaaagg tacancngat tntttatngg
120tttgggcgga gggggaaatt tttttggttt ttttntttnn gggatttttg aaaaaaaaan
180gaanttttta ggtttcccnn angtaattta tttcaatgga ccatttttgg ggttctccct
240tttgtaanan gttaaaaana aggganttcc aannttnctt ttcagtttcc agtttcacct
300tcngtagcag acccagtttt cattttgagn tggtnccnaa aaggnttccc aactatgttc
360aataccacag gcagcctgca ggagggagaa tgggtatgta tttaacagca tttgaccaaa
420ttataagagc agagaggagc tttaccaggg acaggaaggc aaaagagctg aatnttaaac
480aaaagaataa gaacaggatn tcatctgtga gctgtcacag tgggtttgca gagcaggaga
540acacagacag gattagctat aaagttgtta cattagttat tntattggag catacaatac
600ttaaatagtt ctagggcaag agaaatgaac agaaatgacc ttataagagc cagagctgta
660gccacagctt tctttgtgct tagtttgnta gttcantctt tccagggcag tctggtggat
720nacaccaaat tgctttagaa aatgctagnt ctactgtccc tgtctattgt cagctttgca
780atgtgcatag tgacaggagt tgcctgggag cttggggctt atgttttgca gatccattgt
840aattaaaaaa gaattgtaag gagatggagg cacggggtga ggg
883105987DNARattus norvegicusmisc_feature1- 987n = g, a, c or t(u)
105canntttccc ntanccgaaa ntttnttttt ggcccaaccn gtaagacgga ttttttncaa
60ttgcggancc aatggaaccg gtttgccggg nngtnttttg gggtgaacgg tttnttaant
120ggngccaaan aaggttnatt ggaggncnta tttgaattgg tntgtaaanc ntttncttgg
180aaaaggnttg tagcnttaan ccggcaacaa accaccggtt gtacggtgtt tttttgttgc
240agccgcagnt tangggcaga aaaagaattc aggagatcct taancttttt nttcgggntc
300tgacgctcat gttgtgtgga tttntgagcg gttacanttt nacacggaat tctattcact
360ggcatgactc acttccccgg gttcatgagt cagcagtgag ttatctaggt atgtgttttg
420tgttgcaaat tcccatatat agaatatggt cccggggacc atagaaagtt gagcagttgg
480gcaaaattct tccccaggag gtgtgttcaa gagaagaggt tcagcccttg aaagagcttc
540cgtttctatc ntcacaaaca tcntgaaaaa taggctaaat gttattctgt gaagagtcat
600tactggtttt actgatggtg gaagttctca gactgtctag aaaggtaatt ttaaaacgta
660agaaaattag acccctgtcc ccagatctgt tggtgttgag aaatctgtag aaacttgagc
720aggaggaagt acaagaaagt atgtagctat tgtaatccct ttcaggaagg atgtgtttaa
780agctctattg ttagggcctt tcgcttgcac tgtgaagtaa ttttttactt tttataagct
840taaaggatgg cttaataaga cgtcttagaa atgtccacat tatattggat caacaaacgc
900caaagcatca gtttgcgtca ggggccacgg ggcatgggga ctaacggttc attcttttgg
960aatctggatg cctaggtgca gtagggc
9871061031DNARattus norvegicusmisc_feature1- 1031n = g, a, c or t(u)
106agtcctgccc ccntgggaag ggtaaccttg acctaacccc cnaataantt ncccttagga
60ttgcttggca tggnttttac gcgtaaccct antaaaactt tgangaaant tccttccctt
120tgattctagc aatgnaccgg cattttgcca atcnattcng ctgnantaat tatgaagttc
180cggtttaanc aatttgaagt ttaacattca tgtatcttca cagtcatgtg tttttgtgta
240tgatgaaacn ccatgctgtc ttgcnccatt tgntcaggan tgagtcattt gtctagcntg
300nccatgctgt atatgctacc natccatcag ttattcatag ccagcttggt tgtngactaa
360caacagtagt ttcacantgc tttgtgttaa agtcaccttc agtttattta atgttggcac
420caaagcacat gntagtgatg tcagcantgc tgatatgcca gggaaaagcc attaggtatt
480cctttatgtg taaaggttga aaattgttga ttgaatgaag ggaaaaatta ttctgctgat
540tgatgttggg aagggcatta gaggatcata ttactagttt ttgactaagc tctgaagttt
600gtacatgaat ttatggatcc tccctgcaat agattcctga tgctctctaa catccatctt
660ctcatatgac atccttctgg ccagatatct agctttattt tctctactct gctgcaccac
720tgcctctgcc tttggggatc agtccccata gaatgggagg aaaacaatgg cctccttaga
780ccatgaatgg ccttctctca gtaccatgaa gaatcgggcc atcttgtcag agggaaattt
840tccttacatc ctcagtcact gtttctgtca ccattataca ttatatgttt gcctaagagt
900gagggtgatt tgtgtagtaa ggaatgtatg tgttgttgtg gtagtttgga tgagaacggc
960tccccaaagc tcatgtattt gaatggntat gaaagacntt cacctgtagg tttggcnagc
1020tagaaagagg a
10311071138DNARattus norvegicusmisc_feature1- 1138n = g, a, c or t(u)
107caancaccnc ncggananga ncccggnnga anngagaccg gncanacacg acgngancag
60cgaagncanc ncgnnnnngg cncgncagag cgnncgancg cgacnanagn acgncgccga
120nangannnaa nccggngnna ncanncagnn gggaaacagc ccagagagat aggacancaa
180acnaganagn acacancgng acgagananc ccgaaagnnn nanacnnana nanaannaag
240agaanagnnc aacnnnnnca nnnngaccng gaanagggnn nnngaacngc nancnnccna
300gnngcgngan cnanacacga cngaagagac gngngcngaa naganacncn gaanngnaac
360aagangnana annngacagg aancacnnag nagggngngg gcaagcgcaa ngnnnganaa
420nnnacaacag aaaaagannc anancanaag ngncgagagn annagaanna gngaaanncg
480nanncgcncc gaagaagaac gnnggacaaa naccgacgna ncnnnnncan ngannaaanc
540gcangnancn gacnaggaac gacngnaagn gcnaagnnac ganngncaga nnanangaaa
600cacgnnnnan acannnaccn ancgcagcgg nncaggaaag nggngcnacn gaggngngcc
660aanaaganaa nngngagann acaaaaaaaa nggnggncan gcagnanaaa accgagnncn
720nnnnnannna gaganagaac gagannnang nncgaannac gcgnacaaga angggaannn
780cgnangacgc nncggaacaa ngaccnnnnn aaanncagnn anccaacnag gnaannnaga
840nnnagngncn ccanngcaag cncncacnaa gaagaagana cccccccccn annangnagn
900aagcnccncc ngngaggnaa cncgagaccc cccngnaggc agcancgcca agngnagcgn
960ncagagnacn nanntaacag accgaaggaa nagccgnaaa acaccaaana cnagacnacn
1020agcnagnccc gcgcacnnng gagnaancna ccnncnaang acnganancg nggnccncgc
1080tnttnngttn aacgcancnn ggggcggccc nngggaaacn cngggggaca aaaggcgg
11381081072DNARattus norvegicusmisc_feature1- 1072n = g, a, c or t(u)
108cccttnaant gggnccccaa ngggnntccc ccccaggggt tccccccccc cctaaanttg
60cctttntaac ccagggntgg nnnnntggaa tttttgaann tggaggntcn nnngnaacat
120tnccgggatt tttgaggagt ttgaatgacc ggaattntac tttttgggtt ccggcnggca
180ccccnntccc ccaaggttna gngagttttg aaggtaaaag tcacaaggtt tttaaagggt
240ttgaggatga cagttcaacg tgaagatntt gacaangatt gatttttgta nacaggaaaa
300gntcccnatc ccaaccaana aaaccgtgtt naggcccaat gttcagagct cngggcncca
360gggaagggca aacgcccaat tgattggaaa gctgcagttt aagacatgtc ccaggaattg
420gtaccttgtg tgattggact tanccttgca actttgtttg angcataact tgntgtgtct
480ttgggggagc atttatgtgc cccacttgag acccatntca ggacacgcag gacacggtcc
540cagtgagctt tccctccaga gagaggtgnt agggtccatc agtgagctnc caaggacagg
600ggaccagaac gttgaaaaca aaccagggtt gtgaaggaga gcagggcggg ggggggggga
660gggggggcgt tctctagaat agattgaacc tgcagagctg cntgctacct gaagttgtca
720cccttttacc cacccacctc atctgtctct gcttgaccat ctcagcaagt gtcacctcgc
780tgccaggaca caagtttcct aaagcttatt tcagtgtcag ccgctgggga gacacattca
840gggcatgggc gtcccccagc cctcggggag aatgtgggag gtggcgatgt gggagggatt
900cgagagaaga gaatgcttaa gaaccatcca gggaacctgt gcgtttgaag gtctgagtta
960cacacaggct gctcagaagg agctagagct cccaaatagg agctgtgatc aggctgtgtg
1020tgtgtgctgg tgaaagactn ccacctgtag gtnggccaag ctaaatgaga tc
10721091094DNARattus norvegicusmisc_feature1- 1094n = g, a, c or t(u)
109ggtttngggt ganatcctcc caatgccnan aanttccctt ttttaagatt ttttttttcc
60gggaaaattn taaaantttt aactggggtg gnaaataata aggntgtttn tggggttggc
120ccaatttttg nantttagga aaagttcttt gggtnaattc cagcnttgat tggaggagca
180attatnttgt tanaanttat ggttgtgggg atgcttgtta aatcttttag atgtttcccc
240ttctgtctcc cttttggaat ggtcttaata ggttgcnaaa attntacntn ttggatcagc
300tttttnatna gatttagccc agtgtgctna ncttgtgaga cccntttnac agganttgct
360tggnccattt gaaacacgta tttatgtcan gattcataac agtngcaaaa atatagttat
420gaagcagcaa gaaaatcact ttatgnttgg aggtcaccac aacatgagga atgtattaan
480cgcagtatta gagagttcga ganccactat cttngaggat gcgttagact gatgtttccc
540ttctcgcttg gagttgacnt tgccantaga gggcaacagc atcagtattg ttcccagtcc
600ccntcacant gattcgaact ttaaggacac tgatctctgg ctggtagagg gttcagcaca
660cataccagag ttacgagtca cgtgccagaa gggcaaactg aacacggaat tagagggaac
720tcgatgtctc cggcttgcac tggtcttctc ttgcactaga atcnttcatc ntgctcccag
780tccgggacgt ccaggcaaca agggcgtgga aagtgagggg gctgggaggt gtgtttgcct
840tgcctcaggc gctgggtggg gttggggcgt gccagcactc cctgggcggg cctcaccgat
900gctggccact ataaggccag ccagactgcg acacagtcca tcccctcgac cactcttttg
960gcgcttcatt gtcgagtgtg gtgagctctc actggggcgt ccctctaaga tctgtccact
1020cctggtttta ggggttaagc ctttcgtgcc cctgaaagtt ncccacctgt agtgggccaa
1080gctaaaatga gatc
10941101107DNARattus norvegicusmisc_feature1- 1107n = g, a, c or t(u)
110atctcattta gcttggccca cctacaggtg gganactttc aaacctgtgg gagacccctt
60tcacaggaat tgcctgagac catctgaaaa cacagtattt atgtcacgat tcataacagt
120agcaaaaata tagttatgaa gcagcaacga aaatcacttt atggttggag cgtcaccaca
180acatgaagaa tgtattaatc cgcagtatta gagaggtcga gaaccactat cttagaggat
240gcggtagact gactgcttcc cctctcgctt ggagttgacc ttgccactag agggcaacag
300catcagtatt gttcccagtc cccctcacac tgattcgaac tttaaggaca ctgatctctg
360gctggtagan ggttcagcac acataccaga gttacgagtc acgtgccana anggcaaact
420gaacaccgaa ttanagggaa ctcnatgtct ccggcttgca ctggtcttct cctgcactaa
480aatccttcat cctgctccca ntccgggacg tccaagcaac aaaggcgtng naanttaagg
540ggctgggaag tgtgtttgcc ttgcctcaag cgctgggtng gggtttgggc gtgccaacac
600tccctgggcg gggctcaacg atgctggcac tataaaggca accagactgc gacacaatcc
660atcccctcaa caatcctttg gngcctcaat gtcnacntgt tgtgagctcn cactggggng
720tcccncnaaa tttgtcactc ctggtcnaag ggttaaaccn ttcctgccna tcaacctctg
780cnggctcaat ggtggaatgc actggattca aattttcggn gcccaaggaa acaaggaaaa
840ccagggctgc tnggctgtnc aaaaaaancc cagggtaagg gancccatgg gngggaanct
900aaacngcntt tctnggggtc aagaagggtt tccccggggg tgtnaacccc ccccaatntt
960tggcccctca ggaggnttca ngggaanccc cattccttcc ttgccaatca aaagccccat
1020ttccttgaan ccngggggaa nntttaaaac ccnaancccc tccattntta acccccccca
1080atggnccngn ngnaccnttg nnntttg
11071111069DNARattus norvegicusmisc_feature1- 1069n = g, a, c or t(u)
111aatttttttt nccggnaaaa ttttnaaant tttaantggg ggggtaanna nnaaggttgt
60ttctgggntt ggcccatttt tgcacattag gganagttnt ttggggtaaa nttccagcng
120ttgattggag gagcaagtga tnttgttana atttatggtt gtgggggatg ntgttaaaat
180cttttaggat tggttcccct tntgtctccc tttttggaca tggntcttan ataggtggnt
240caaaattcta cntnttggaa tcagcntatn tcatcaggat ttagcccagt gtgntnaacc
300tgtggagacc cntttcacag ganttgcttg agaccatttg aaacacagta tttatgtcan
360gattcataac agtagcaaaa atatagttat gaagcagcaa cgaaatcact ttatggttgg
420agcgtcacca caacatgagg aatgtattaa tccgcagtat tagagaggtc gaganccact
480atcttagagg atgcggtaga ctgattgctt cccntcttcg cttggagttg accttgccan
540tagagggcaa cagcatcagt attgttccca gtccccctca cactgattcg aactttaagg
600acactgatct ctggctggta gagggttcag cacacatacc agagttacga gtcacgtgcc
660agaagggcaa actgaacacg gaattagagg gaactcgatg tctccggctt gcactggtct
720tctcttgcac tagaatcctt catcctgctc ccagtccggg acgtccaggc aacaagggcg
780tggaaagtga gggggctggg aggtgtgttt gccttgcctc aggcgctggg tggggttggg
840gcgtgccagc actccctggg cgggcctcac cgatgctggc cactataagg ccagccagac
900tgcgacacag tccatcccct cgaccactct tttggcgctt cattgtcgac gtgtggtgag
960ctctcactgg ggcgtccctc taagatctgt ccactcctgg tntaggggtt aagcctttcg
1020tgccctgaaa gatttncacc tgtaggtggg gcaagctaaa agagangcc
10691121058DNARattus norvegicusmisc_feature1- 1058n = g, a, c or t(u)
112caggttttgg gttttccaag gncccccccc tgggggttac aaaatggcgn nnantcgngg
60tgggaaccng acgggtttaa gntaccgggt ttccccntgg agtccntggg ggttcctntc
120cgaccttcgg ttaccggtac ctgcccnctt tttcctttgg gagggtgggn tttttcatag
180ctcagctgta gtatctcagt tcgtttagtc nttngnccaa gttggtttnt gcaggacccc
240cngtnagccg gaccggtgcc ccttatccgg taatattgtc ttgagtccaa ccngtagaca
300ngattattgc cattggcagc agcaatgtaa caggttngca gagcgaggta tgtaggcggt
360gtacngggtt cttgaagtgg tgccntaant tacggntaca ntngagggac agtatttggt
420atttgcgctn ttgttgaagc cagttacttt nggaaaggag ttgntagttc ttnatccggc
480aaacaancca cngttgntag cggtggtttt tttgtttgca agcagcagat tacgcgcaga
540aaaaaagnat ctcaggaaga tcctttnatc ttttctttcg gggtctgacg ctcatgttgt
600gtggaattgt gagcggataa caatttcaca cagaatttct cttagaaaaa tctgtccttc
660agaaacttaa attctgctgt tccataacag aagtcagcaa gtgactcacc ctccagatac
720aggtatatta cctccactcc catccacaga gacttaattc tagtcagctt catgatagtg
780agccttcatc cgtaaggagc tgtatggtat gggaagggga tacagacagg gccaggggtg
840tttttaaacg gtaacccagg gaccacatcc attaaaaaca ctggactgtt tgtgagagtg
900tatattcctg agcattgcct atcccttaag gtactacaaa atttgggagt gaggctcagc
960aaactatttt aacatgcctc tcccacccaa ctactcaaga ttccccgtgc acagttgaaa
1020gntttnccac ctgnaggtgg ggccaagcta aaagagat
10581131046DNARattus norvegicusmisc_feature1- 1046n = g, a, c or t(u)
113cannaaaann agttccaagg aantggntgc ccngaacaag gacccaaaac ntgnnnnana
60angggggann naanggcana annnatggac gagagtnaan ancgcnangn agaagantna
120aaantcncca nntggngccc caaatnncnc aattgancca aancnntaga ggnncccaag
180acnaatgggc actntganna gancnggcca gaagncaagn gggggannnt catagnnaca
240tggnanaaat aaagntntgt aaacccggan tggcaatnga aaccagcaaa gacccatgaa
300cgtgagngan accagttgga aacaatgaan nnantgggtn antnacagga atgnggtnan
360gacgcnnagt gancccaaan aggcaacncc attgaaagcc ttcnccncca tggaaatact
420gtanntaaaa caaacaaaca aatnacaaaa anaaaaaacc caaagcttaa gtggagtgcc
480cnttccagnt agccaccnnn taagaactgt aaatcgcacc ntcccangcc agatgcaggt
540aaggnaggat tacaggnatn tcggagggct caggagggaa tgggtcncaa nntgagctga
600ggcncnggtg anttncgcta cntcgnaaaa aangagaagt catgtgggac gnatgtgtgt
660aagcacagct cntgtgangt caagtcagca acantatgcc atactctgaa gacagaggnc
720cataatagna ttgttacang atncnngact tttanaaaan caaaatccta aatcctattc
780tccgtgggcc cacacgaaac anccatccat caggatcatc tcacagttgc ctctgannnt
840tngtnttctn ggaancntan gntntcggag ttggggaccg aactcagggc cgtgtgcttg
900ctaggcaagc gctctaccag tgagctaaat ccncaacccc cacagntgcc tcntntgatt
960gnaggtntcn tatcccnttc ttttgtggca agntcttctg ggccccntga aagtgaannc
1020acntaagngg ncgccagcta agnaga
10461141083DNARattus norvegicusmisc_feature1- 1083n = g, a, c or t(u)
114ctcccnggcc ccaaaaattn ttttanaaan tttttttttc gggnaaattt tnaaaatttt
60aagngggggg aannacaaag nnnnttntgg gntggnccaa tggggaaaat taagnnnann
120ttgnntgggg tgaattcccg ccntngnttg gaggaggnaa ttatnttgta gaaatttatg
180gttgtggggg atnttgttaa atcttttgaa tgtgttcccc ttntgtttcc cttttgggac
240atggntctta ataggtggnc aaattttacc ntnttggaat cagcctattt atcaagatta
300gcccagtgtg ctcaaccttg tggaacccct ttaacaggat ttgcttggnc catntgaaac
360acagtattta tgtcaggatt cataacagta gcaaaantat agttatgang cagcaagaaa
420atcactttat ggttggagcg tcaccacaac atgaggaatg tattaatccg cagtattaga
480gaggtcgaga accactatct tagaggatgc ggtagactga ttgcttccct tctcgcttgg
540agttgacctt gccactagag ggcaacagca tcagtattgt tcccagtccc cctcacactg
600attcgaactt taaggacact gatctctggc tggtagaggg ttcagcacac ataccagagt
660tacgagtcac gtgccagaag ggcaaactga acacggaatt agagggaact cgatgtctcc
720ggcttgcact ggtttctctt gcactagaat ccttcatcnt gctcccagtc cgggacgtcc
780aggcaacaag ggcgtggaaa gtgagggggc tgggaggtgt gtttgccttg cctcaggcgc
840tgggtggggt tggggcgtgc cagcactccc tgggcgggcc tcaccgatgc tggccactat
900aaggccagcc agactgcgac acagtccatc ccctcgacca ctcttttggc gcttcattgt
960cgacgtgtgg tgagctctca ctggggcgtc cctctaagat ctgtccactc ctggtttagg
1020ggttaagcct ttngtgcccc tgaaagtttn ncacctgtag gtggggcaag ctanagagat
1080ntt
1083115913DNARattus norvegicusmisc_feature1- 913n = g, a, c or t(u)
115ggggaaaaaa atntgggncc ctttnaaaga aattctggaa anccgccggt ggggnatttt
60taanataggt ggggnccnaa aancttgatt ttcccttttc cctttgantg nntaaagttg
120cnaanttccc tttggacgcc ntttacaaga ttagccngtg tgtaaccttt gggcccttta
180acaggattnc ttggccntnt gaaacacgta tttatgtcag gnttntaccg tngcaaantt
240ngttttgagc agcaacgaaa tcactttatg gttggaggtc accacaactt gaggatgtat
300taatccgcag tattagagag tcgagaacca ntatcttaga ggatcggtag actgatgttt
360cccntttngc ttggagttgn cttnccacta gaggcaacag catcagtatt gttccccagt
420ccccctcaca ttgattcgaa ctttaaggac actgatctct ggcttggtag agggttcagc
480acacatacca gagttacgag tcacgtgcca gaaggcaaac tgaacacgga attagaggga
540actcgatgtc tccggcttgc actggtcttn tcttgcacta gaatcnttca tcntgctccc
600agtccgggac gtccaggcaa caagggcgtg gaaagtgagg gggctgggag gtgtgtttgc
660cttgcctcag gcgctgggtg gggttggggc gtgccagcac tccctgggcg ggcctcaccg
720atgctggcca ctataaggcc agccagactg cgacacagtc catcccctcg ccactctttt
780ggcgcttcat tgtcgacgtg tggtgagctc tcactggggc gtccctctaa gatctgtcca
840ctcctggtct agggnttaag cctttcctgc cctgaaagac cntacntgta ggttngncaa
900gctaaatgag atc
9131161123DNARattus norvegicusmisc_feature1- 1123n = g, a, c or t(u)
116acgcnatntt ggtggaattt ggggggtaaa aattttnaac gaattaggna ncttagggna
60cnaaatccga aatggggaat ngggntaaat ttcgaaccnt ttnggaggnn ntaaatntaa
120aaatgaggnt aattggnttn gaaangcnta tcaggcattc caaattntta aatttccctt
180ggccagagat tggggaaaat tttncccgga ntccagnttt aggttnnttg gaaaaacggn
240gccccaggga ttgttgcacc nttcccaatn aaggnggttt tccntccaan gcctttnggg
300gnaaacccag ggggggnttn aggggcccaa ttcaggaaaa ggggaccgga ntcgggtccc
360ggaaggnttc ccggngggga atcaacccgg ttcccntccg gaggccgggg gggaccttta
420ggtttcccct tgcaggggta anatcccctt tttcaacccg gggggtttgc ggggnacgcc
480cctttgccct ttcccttccc ttgccnggcc cgttttgccc aattnggccg gtcctaactt
540gttggcgcaa gggacttttg gcagccccgg ccggtttggc ggttggactc caagggggta
600acagggccaa accntttggt tgaaanaagt taacttgcgc ccccagtcan gcgtcagtgg
660gnangtgacc ccgcntttag gagtttgccc cngccnttag gccttgcccc cagaggtcgc
720cccacntact agagtgtcgc ttggcgcgat gacgtangan gacgcaggcg cagtgagtag
780gcgacgttgg gacggccctt ggttgtgtcg ggggcggaac tntgntggct ttgagcgcct
840tcnaaacagt aggttgcttg gggctctgcg gcgtcggaaa taaggcgggg aggagcaaga
900aaacagggat cctccagtcg tgtggaccga cccgagtccc gcaccctttt taaggcctgt
960gttgcggatc cgcgcggcca tcacgcattg catcacggtt ttactgtgtg ggaaacgtag
1020ccgtccatac ctgggtgtag tcagggacct ttatggtggc tgtcacgcag gcgatttgnc
1080aattgaaaga ctttnncctg taggnanggg nagctaaaaa gat
11231171116DNARattus norvegicusmisc_feature1- 1116n = g, a, c or t(u)
117aattttttaa ccncccccnt tttnaagntt gaanttgcan tgcctaggag ccctattttt
60cccccttgna anttttcccc gtaaataagg naatgntgna nttgtattta ncttgcccaa
120aaaaaacnnt gttcttnaat gcaaggtant tgggggttat tattntgaaa ggcaactaat
180tnttaatggt ggattnaaca attttgaagn ggattaaana aaanaaatna ttgntttcca
240ttggnggtgt gggnttaaaa cccttggtnn ccagggttcc antgggttca ggccctttga
300gngggntccc cnttccccgg gaatnggntt gaaccggaaa ttgaacattt tgcacccttt
360tccggnggcc cttaaggatt gcagcnccag ttgcggggaa ggggtaattc cttgcccncc
420gtggaagggg tttcagnttc cttcccaacc cccccccggc cgggagtccg gnggggcggt
480ttntttcacc ttaagggcgg gcgtggantt aaattaagcg ccggggnggg ntcccaagcc
540ntccggcccg gctttggttc cttntgggcg ccgggggcna acggccccng gggctttggg
600cggttntccn nccggccaac cgggncccgt ggttgntggg ttaggccagt gcaccnggag
660ttnccggggg caaccaaatg tccaggactt angctntgca aggagtttgg gataggactc
720ntacaatggt ccctccctcc gtttgccccc gaggcccttt gggagctggt tnatcccaga
780actcagtgag tcactctcat gaagcacggt tggctgcttt ggaatgctgg gcaaccccag
840aacacagtgc tgtactagta cacacacaca cacacacaca cacacacacg ttacacatgc
900tgacacaaac atgaaaatgc agtcaacggc aggcagagat ggatggatgc acattgctgt
960ggaatggtac actttgcacc tcacactctt ccagagggac agtccataca acactcagct
1020tcgcttccca ctataggctt cacatgacca gctcttcagc gtcggaaagg acngtactga
1080aagacttnac ctgtaggnng gncagctaaa aagatc
1116118900DNARattus norvegicusmisc_feature1- 900n = g, a, c or t(u)
118gggngttngc tctcagatgc nagntacnnn tcagggggng tctcacgaga aaanctnatg
60tgtgggggnt antntgtatc ccctnnnctc nctcgaganc ccnnntctcg anattttggn
120gaccnggggc cggggcccag anactcncca ccccatatgg ngaccctnta taagtgtcnn
180ccagggnntg ttttgggnaa aatatancnn anagnggtgt ntntnanatc tcggggggtg
240acagacccnn attttttttt ataaagaccc ggggcatntt ctcngccccn tctcctcngc
300tacangnnac ccacacacag tgtgtctcct ctcagccccc tggcacactt tntntngant
360cngnggggat atgagattcn cnagactggg nccgcnntan tanncncccc cntgtctcct
420ctcatagtgt ngtgtccccc cctcacccnn tnttgnggtn ccctacaccc acacaatnta
480gactctnccc nccntcngct ntgngacnca canctgnaaa tcccgnnncn caaaaagggc
540tgtnctcctc tctnttacng ggnggtcncc cncnnnngac tctnaaangt ccctcncaaa
600agggacnctt ttctatacac ncttantttn cctcctttgt ntngcaaaaa annancctgt
660gttncccccc nctttatnat ntttnttttn ttccccaaac taanctttta ggnntnanct
720tccggggccc caaccccaaa atcccantnt tcttttntnt tggttggggt gtcaaaattc
780ctncccctaa anttttgaac cccctttaat tccccccccc ggntnaaggc ccnacttccc
840tnggntnttt tcnctaaaaa attttttgtn gccctccctg ggaaatcccc ggtattcctc
900119498DNARattus norvegicusmisc_feature1- 498n = g, a, c or t(u)
119atgttgtgtg gaattgtgag cggataacaa tttcacacag aattcagaag gatctcagaa
60attgaaagca tgtgcaaaga taaagatttg gggtagtagt agtggtcaaa agggacaagg
120taataatggt aatatgcttt tgtgtatgtg ttcttttaga gttatgttaa aatctagaga
180agcaaagtcg attctcatag atgcttttag tctttggacc ctgactagag acagtttaca
240ccctagacaa gagagagaat ggggttgagt aaaacagtcc tcccgaactc tccacagatg
300ctttggcaaa agaaggaaat gagcttaaac tttttggagc tctcctggga acagaaggag
360gtgggagacg tcttgcctcc ttgctgctcc tattggagaa gtgcttattt ctggttctgg
420gttttttagg taggntgtct gggtcccttt ggtntgaaag accttacctg taggtttggn
480cgntngaaaa gatcntgg
498120380DNARattus norvegicusmisc_feature1- 380n = g, a, c or t(u)
120aatgggnggt ttccgaaaan aacgcnaaaa aaaaagttag ggaatttggg gaattaagaa
60nccgggaacn tgnaaacatt gaccaanctt gttttaatta ccggtttggg gnaaaagggg
120caaccccaaa ggggaaggga anggaangga aaatnaattn cctttnnaaa aaggagnaaa
180tncgggtang gaaaattccg gtgnggggtt ttcaaaggtc cccccccgnn ggnntaaaaa
240attgaagttn antcnngggg gggaacccaa nagaatataa anaaaccggg gtttcccccn
300gggagttcct tgggggtttn ccggttcgac ccgncgntta ccggaaacct ntcncctttt
360tcccttgggg nagggggggg
380121998DNARattus norvegicusmisc_feature1- 998n = g, a, c or t(u)
121acatgtacac aactgggtcc cagccaagtc aggttccagc tgccagcaga ggcctggagc
60tagcttcgcg tgcactacca ccctgcccaa cctggcactg tgcccattga cttcgggggg
120ccgggggcag gaggtaccca cctccccacc ctcctcttcc ctcctctcag gagcttatct
180atcggtgagc agcaagtagg aaaaggtaag ctgagaaaga gcacttggct ggctacagga
240cctcagcctg aggtgtgaaa caggagactg ggcactgggg aaacagcagc actggctggg
300ccaaagggga gggaggaagg caatgaatgg gcaagcctgt gccttacaga aacagactcc
360cttgggctgg gtgctggaat cctaacccct cagtgatggg ggaactctgc tccagtgagc
420tgaagtatac atgtggggaa ttggggggtg gggtaggggg aaggcaatcc aaaggtcact
480cccctgacct agttggacca cagttaatta aggctcccaa gccctgctga ctcttnacgt
540ctggtttctg gaaagaaggg agttaatcag caaacaattt aagaaaggta taactgtcta
600cccctgcaga ggatcatggg ttncctctct anncttctga gccgtggatc tcagccaaaa
660acaaaaacca aaacaaagaa acaaacgcct atttaaaagg gggttggagt tgggcagggg
720tgaggtngtt agatcatctg agagctccag gacacgcana tagttgaaga ggaaaccaag
780atccaaatgt cttctgacat cacacgggat gcagcagcac accaacatat actttancct
840cnccagagag gaaaacaacc gcctagttaa taagcagagt tgggctgttg gcaaaccgtc
900attccagatc tgaggnaagt tggatggttc gggtgtctat gttnacntaa gacctgtttt
960acaagctnnt atgggcaagg gctttggttc nagnaagg
998122970DNARattus norvegicusmisc_feature1- 970n = g, a, c or t(u)
122ccggtcnccg aaggannttg aaccttcccg gtttttaann aanacccgna tnttcgggat
60tgggttttta acggcttttt ttanaaggcc nagataccct tttnatggcc tttattccct
120tccgttttnt tccccccctt caatttggaa gtttggtttg ccgaanttta agttnttgtc
180ntcctncgtt ntttttttcc nttntttttt cccaaaagta acaanccggt attggtttcc
240aaggntnttn ttgaacccgt aatngcggnt ttccggttaa ccnagggttt gttcctnngc
300cgnttcctcc aatttttgga ntttcccagn tnggggtccn ttntcttgtt nacngttcca
360aacntaattg acanttaatt tttcctgtgt aanttgtccc cgganattnt gggntcttgg
420ngcagggcct tttttcattg gaagcaaccc cntaaatttt taccaggctt gattgtttag
480gaagtaatcc ttgcttngaa nccccacttn ttntttccaa ggntggaaac caggattttg
540gaactgcaga ggcttcaggg tctgggaagc ggagcangca aagantggag tgcactgtcc
600ttttgcaata tggggtttgc ttgcttgctg gctcntntcn tgctntntca gatggtgact
660gaggctactt cagcaggact aggaataatc atgtccaggt ggntgccctt ccgagcagaa
720agggacagac gtggggcgat gaagttgcta tcgttttttt ttttttctgc acagactgca
780aagtgtgcag agggagggag gctgtgcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaac
840cgaggacgca gaagttagac tgctgaccca tttggtgcat gtgtgcccat ggagggaggg
900gaccttctca aaagggttca cgcagcaagc attgaaagnt tccacntgta gngtcgcaag
960caactgagat
970123884DNARattus norvegicusmisc_feature1- 884n = g, a, c or t(u)
123ngggcccccc tcgaggtcga cggtatcgat aagcttgagg gacccacgtg atggaaaggg
60agaagcaatt tagtgtcctn tgtcctctga cctccacaag tgctgtggca tggggacaca
120ggactgtaca cacacacaca cacacacaca cacacacaca cacacacgca cgcacacaca
180cccctcaagt aaccgtggaa taaaggtccg accagaaacc acgctggaac gggagatgct
240ggagcacatc agggtggtgc taagcagcag atcggcctgt aactggcagc agaggggtgt
300ggctctttca gaaccaggag ggcatcgccc ctccagccag actctccagc tttcttcccc
360tccttgcctc ctgttttcct tctgcctacc ttcctttggc ctcaaaccat aatgtgcaac
420acattcaaac tgtagtaagt gttttaattt tctactaaac aataaaacct ttagattttc
480actgggccag tgctggtaac agcagactgg gtggagtatc acagagggtg tggagcaagc
540tggctaccca gggctgggca cactcaacac tctggcattc ngtggaagtt ctgggcagta
600aaaacagaag canacgtcac gcacaggttc catagtgtna ggcatcttaa tctancnaga
660anacctggtg ttnagtntgt nnacaaaann gantgntgna cttggacagn ggtgttttnn
720tcccagggct tccaggantt aggggtatac caggcccann acattgggna aacgtgtgtg
780tnaannnttt cntntnaaac cnccnnggtt gacnactngn nntccntttn aanggnccca
840gttccccttg gggggttngn tntggaaaaa ggctttccgg tttc
884124855DNARattus norvegicusmisc_feature1- 855n = g, a, c or t(u)
124ccccttccgg ggggtttana anggaatnaa tgggtntntn ccaggggggg aaacccttna
60ccgcgngcct ttcggaattt tngtccaccg naaaaaattt nccatgngca ccatgnaagn
120tnacgagggn attnggggtt anagttttgg agtgggccaa nangaacatg gaggaatatt
180tgttttggtt tgngaaccat accttggaaa gattgtattt ttatccgcca acaaccacng
240tggtagggtg tttttttgtt tgcagcagca gataagggca gaaaaaagat ntcagagatc
300ctttgatntt tnttcggggt ngacgttcat gttgngngga ttgggagcgg anaacaattt
360cacacagcaa ggagaggagc caatatagag gggaaaaaaa aagaagggga aagcagttag
420tttaaaaagt tgagagaaca aagtatgttt tgnttggatg ggcaaccaaa gaagcntgcc
480aggaatggtc ggtaaaaggt gtaagagtca tgaaagtntt ctgtccaacc gttaccggaa
540acatgcaagg aatttcttag actggccagg attggattgt gggaaaggtn tnttcaagcn
600tccccttggc ttttatggca agaaaatagt gcggactata gagagcgtcg ttctcaaagc
660tttccccaat agcagaaaag cattgtccta aattccctaa aaggcaccgt gaaataaata
720ttacgggaca cgatggcaca agaaggagct ttcaactctg ccaccagaac agttatactt
780catagtaacc atgttgccct gttcaatgac aaggcacgct ctccagcaga aagggaaaag
840gagctgagtt cgcac
8551251059DNARattus norvegicusmisc_feature1- 1059n = g, a, c or t(u)
125caatttttaa aaaaaagaat ttgggtttaa tccaaaantt gnnncaaaaa ttggttgacc
60ntttnaaccc caaaaccatg nnttgncctt tcccctnacc ngtnatagtg nttgnantgt
120aacccaacaa tcaacggnta tttgttcagg ganttnttgg taccaggcnn ttggttttga
180naanacggta ggtccgggaa gcnttgacgg taagcccngg gganaagggc caacggngat
240cccaaattag gagcttgacg cattgttttc ntttgcntgg aatgncattc ttctcttctc
300cntttatcta gaaaacgntt actcatgctt caaanccacn gttgacttcc ccagcattgn
360ttcncntagc tccttctttg aaacaactga ttgggaaatc aggaggatan gaaaagcttt
420aacaagagct ttcaggggct ttcggagaga actcattctt gtaggacgca ggccatgcaa
480gcatcaggct ctgccttctg gaccccagta tacagacata tgcacaactg cagtggttca
540tacttgtaat cccagtgtta ggaagactta gacttggagc ttgctggtca gactggtaag
600cccagttcag tgagaccctg acttaaaaat gaagttggaa agaaatttgg aaagataatc
660tggtattcat ctctgggctc tatttgcaca ggcacacaca caaatatacc aatataacat
720acacagaaag agaaggggag ggaggaagag agggagggcg gtagagaact tgtgaatgtc
780ttttgatagg ttttttttta agttattgga ttaaaccatc agcagtgtca cattggttaa
840gttaaaaata ataaaatgaa gcaacttatc tttgctgaaa ttcattactc attatgagag
900tttgataaaa aaaaagagga gtctcccaca gttttcctgt ctcatctttt actccagggg
960acggtcacac tattcagtaa gatacctagg ctatctggct cactggactn ggcgtgaaag
1020actnnacctg taggtttgng cgctgaaaag atcttnaac
10591261042DNARattus norvegicusmisc_feature1- 1042n = g, a, c or t(u)
126aaacncnttc tgaancccca aatcctnaga atnttttnaa aatcccccng gggngnagcc
60aaatttaacn nttttttcca agagcatgaa cagngngatt cttggganag ctttngggtt
120ccctttttnt naatcnncat ngagggttct aantgaacct naaggnnatt taacttttna
180tggaacaaac ccgttggtgt gtcccctcct tggaganttg agttggaact taaaaaaaac
240ctttccnaaa aattgtgtaa tctgantcca aacccaaatg aggacaaatc cagtgtagga
300ggnatttagg caaattaaac tgacttggtc aactttctga aaatgatgtc ttgatttcag
360gaaggatccc cagtgcntcg gggacntgaa agggagatgt aacccttgag ctcatggnta
420ggaagggaaa tcttagagac agcttggtaa aatctgagtg aggttgagag gttggaggac
480cacattgtgt atntgctcat ccctgtgagg gagagacttg tactctgctc ttgagaaggc
540agaactgtta ggcagacact tagagaatat atgtcatggc aaangacatc cacccaacaa
600gtcttcagta acaaagcact aaacagaaag gggttgaaga gacttggtca gtggcatgag
660agnttttatt gctcttacag aggactcggc atgcntagca gctcacaaca gcctgtgact
720tcaacactat gcctcttggc ctcaggagac acctgtgtac tcccacccng acacatatac
780ttaaaaataa aagaaatctt ttaaacattg agcaaatgta atcaggtact aacattgaat
840atatctgggg ccaggaatta ttctggttta ttgccttttt cggaagccta atatcacaca
900tagagaaata ggcagcacag gcctaacagc ccatantgtg tgctattcta tcaatagtgc
960caagtattga catggactat tnttaaggcc aaangagagg tcnccagaaa gttatacatg
1020taggttggcg cgctgaaagg at
1042127960DNARattus norvegicusmisc_feature1- 960n = g, a, c or t(u)
127ggcccnnaat naaanggnng gttgaacccc ntnttngaca ngntgcccaa aantacnggn
60aaccattncc naaatttnna agtgtgggat naaggcntgn cccatnatcc tccctnttga
120ntgcncccaa agtaaagncc aanttgaggg ngganntttn ttgaaacgta attaanattt
180ttccgataag gaaacggagg cccgggaant gatccntttg gagttaccag gtcagtttag
240cattaggntg acagttgnga ccaattnatc cttgcccgtt ggttggaagg agaggggant
300aagggttaag ctcntgagtc ccttgaaggc cttggaatcg ggaattccct taaagccaac
360ccctttgccg ttgaactgca ccaaccagat gtctnccagt ttgcttgaag agacgggatt
420cantgntgtg gagaggggca ggagggntgg gaggtgacnt nacagggttc agggattctt
480ttagaagggt ccaggctcat ggcttccccc ccccccagcc aggtcagaca ctaaagtgtc
540ttaagcccct ccatacctgc cgctccccca ccttggatga agccggccat taggcaggga
600ccgtctctgg gagaggccaa gccctctggc tcacttgtgg atttccttta agcaagactt
660cctctctgct tccaggactc ctgtcaaaca agagggtccc tggcttagag tttgggagct
720gcaggcagaa cagacattcc ccgatgactc acaagcctgg aactctgtgg gccagcagga
780atggggatgg ctttctggtc agtcagggtc aactgggaca ctcactctga gacagggagg
840caagggagaa acaggtcaga ggtagagaga gctcagtcca gggactcacg gtgaggtccc
900taaggtgcgt agggagagga tntaacattc ggtttggnna gctagaaaag atctntaaaa
960
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