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: IMMUNOGLOBULIN, ANTISERUM, ANTIBODY, OR ANTIBODY FRAGMENT, EXCEPT CONJUGATE OR COMPLEX OF THE SAME WITH NONIMMUNOGLOBULIN MATERIAL
Publication date: 04/09/2009
Patent application number: 20090092594

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 T_m (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 T_m (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 T_m 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

Patent applications by Donald H. Rubin, Nashville, TN US

Patent applications by Edward L. Organ, Nashville, TN US

Patent applications by Raymond N. Dubois, Franklin, TN US

Patent applications in class IMMUNOGLOBULIN, ANTISERUM, ANTIBODY, OR ANTIBODY FRAGMENT, EXCEPT CONJUGATE OR COMPLEX OF THE SAME WITH NONIMMUNOGLOBULIN MATERIAL

Patent applications in all subclasses IMMUNOGLOBULIN, ANTISERUM, ANTIBODY, OR ANTIBODY FRAGMENT, EXCEPT CONJUGATE OR COMPLEX OF THE SAME WITH NONIMMUNOGLOBULIN MATERIAL

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Patent application title: MAMMALIAN GENES INVOLVED IN VIRAL INFECTION AND TUMOR SUPPRESSION

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