Compositions and methods for viral resistance genes

Information

  • Patent Application
  • 20050244815
  • Publication Number
    20050244815
  • Date Filed
    December 15, 2004
    20 years ago
  • Date Published
    November 03, 2005
    19 years ago
Abstract
The present invention is directed to methods and compositions for identifying viral resistance genes and for identifying individuals having resistant or susceptible genotypes. Once identified as either resistant or susceptible, appropriate actions, such as vaccination, can be undertaken by the individuals. In particular, methods and compositions for identifying genes associated with resistance or susceptibility for flaviviruses are disclosed.
Description
TECHNICAL FIELD

This invention is directed to compositions and methods for viral resistance genes. In particular, the invention is directed to compositions and methods for identifying viral resistance genes and for identifying individuals having the resistance genes.


BACKGROUND OF THE INVENTION

Viruses cause some of the most debilitating illnesses known in animals, including humans, and plants. Vaccination procedures have provided relief from some of the more deadly viruses, such as smallpox, measles, influenza and poliovirus. However, many viruses still cause much human and animal suffering, loss of work days, and sometimes death.


Not all individuals infected with a virus respond identically to the virus. Such individual variation in response to viral pathogens has been seen in both animals and humans. For example, when Australian rabbit populations were controlled by the introduction of a viral pathogen, 99% of the rabbits were killed, but 1% survived. In humans who were accidentally inoculated with hepatitis B virus, only a small percentage developed clinical hepatitis and only a small percentage of those individuals developed severe disease.


Such variation in response to infection, in the extent of the disease state and the ultimate outcome is presumed to be due to multiple factors. Some of these factors include genetic makeup, nutritional status, age, and immune competency. For particular viral pathogens, some of the factors have been suggested as being important, but there are no tests or assays that would enable one to predict an individual's response to exposure to the pathogen.


What is needed are compositions and methods for determining, prior to exposure to the viral pathogen how ill the individual will become if infected. Additionally, such methods could be used for determining which individuals should be vaccinated.


SUMMARY OF THE INVENTION

The present invention comprises compositions and methods for identifying viral resistance/susceptibility genes and for identifying individuals having such viral resistance/susceptibility genes. In particular, compositions and methods for identifying flavivirus resistance/susceptibility genes are provided. Additionally, methods for testing body samples to determine the presence or absence of genes associated with viral resistance/susceptibility are provided.


Inbred mouse strains exhibit significant differences in their susceptibility to viruses in the genus Flavivirus, which includes human pathogens such as yellow fever, Dengue, and West Nile virus. A single gene, designated Flv, confers this differential susceptibility and maps to a region of mouse chromosome 5. A positional cloning strategy was used to identify twenty-two genes from the Flv interval including ten members of the 2′-5′ oligoadenylate synthetase gene family. One 2′-5′ oligoadenylate synthetase gene, Oas1b, was identified as Flv by correlation between genotype and phenotype in nine mouse strains. Susceptible mouse strains produce a protein lacking 30% of the C-terminal sequence as compared to the resistant counterpart due to the presence of a premature stop-codon. The Oas 1b gene differs from all of the other murine Oas genes by a unique four amino acid deletion in the P-loop located within a conserved domain thought to be involved in RNA binding. Expression of the resistant allele of Oas1b in susceptible embryofibroblasts resulted in partial inhibition of the replication of a flavivirus, but not of an alpha togavirus.


There are three types of Oas genes in mammals. The large three unit-containing Oas 3 gene, the two unit-containing Oas 2 gene and the single unit Oas 1 gene. Many mammals also contain single-unit Oas-like genes. The single unit Oas 1 genes have duplicated in mice; there are 8 mouse Oas1 genes. Only one of these, Oas1b, confers flavivirus resistance/susceptibility. In the human genome there is only a single OAS1 gene, but this gene produces multiple isoforms.


The present invention comprises the finding that resistance to infection by flaviviruses has been associated with variations in human OAS genes, particularly OAS1. If an G (G-allele) is present at nt position 12,349 (numbered beginning from the Atg-start codon in the genomic DNA), the p46 and p48 isoforms are produced. If a G to A transversion (A-allele) at nt position 12,349 is present, the p40, p48 and p52 isoforms are produced. The 346 N-terminal amino acids of these four proteins are identical but their C-terminal regions differ due to alternative splicing.


Data showed that the frequency of the A-allele in ethnic Russian populations who are known to be highly resistant to disease caused by the flavivirus, tick borne encephalitis virus, was significantly increased (up to 99%) as compared with the frequency in a group of patients with tick borne encephalitis virus-induced disease (59%). The GG homozygous individuals exhibited the most severe disease symptoms. No GG-homologous individuals were detected in the native Siberian populations. In contrast, the frequencies of the A-allele and the G-allele were similar in groups of healthy Russians and Russians infected with hepatitis C virus (a distantly related member of the flavivirus family from a different genus). Mutations in the human Oas2 and or Oas3 genes may also be relevant to virus resistance/susceptibility.


Methods for determining the individual genotypes have been developed. To determine the presence of the A and G alleles, samples of genetic material from individuals are obtained and the DNA is characterized for the presence or absence of the susceptibility/resistance polymorphism.




FIGURES


FIG. 1 shows the physical and transcript maps of the mouse Flv interval.



FIG. 2A and B show the structures of the mouse Oas 1b gene and protein.



FIG. 3 is a Northern blot showing the constitutive expression of mouse Oas1b in different mouse tissues.



FIG. 4A is a graph and FIG. 4B is a table showing the effect of low level expression of the resistant Oas1b protein in susceptible C3H/He cells on the growth of a flavivirus, West Nile virus, and an alpha togavirus, Sindbis.



FIG. 5 is an un-rooted neighbor-joining, distance-based phylogenic tree of murine, rat and human Oas sequences.



FIG. 6A-H show multiple alignments of the protein sequences of the murine, rat and human 2′-5′ oligoadenylate synthetases.



FIG. 7 shows the relationship of the human OAS gene family members and the murine Oas gene family members. A comparison of the orthologous 2′-5′ oligoadenylate synthetase genes located on Homo sapiens autosome 12 (HSA12) and Mus musculus autosome 5 (MMA5) are shown. There are eight murine Oas 1 genes (from “a” through “h”) orthologous to a single human OAS1 gene.



FIG. 8 shows the position of a G to A transversion [indicated by r and located at nucleotide position 12,349 (numbered beginning from the ATG-start codon)] in human OAS1 genomic DNA and the amino acids present at the beginning and end of the C-terminal parts of the OAS1 isoforms, p40, p46, p52 and p48, that are generated depending on whether a G or A is present at nucleotide position 12,349.



FIG. 9 is a photograph of ethidium bromide stained PCR DNAs electrophoresed on a 2% agarose gel. The fragment patterns detected for humans with the different genotypes that determine viral resistance/susceptibility are shown. Lane 1—100 bp DNA ladder; Lane 2—AA homozygous DNA digested with Alu I; Lane 3—AG heterozygous DNA digested with Alu I; Lane 4—GG homozygous DNA digested with Alu I; Lane 5—undigested PCR product.




DETAILED DESCRIPTION

The present invention is directed to compositions and methods for determining gene variations that confer resistance/susceptibility to viral pathogens and for determining the presence or absence of such genes in the genotypes of individuals. The determination of the viral resistance genotype of an individual is important in assessing the individual's response to a known viral pathogen, assessing the population's response to a viral pathogen and may be important in predicting the response of both the individual and the population's response to viral pathogens that enter the environment at a later time.


Global connections and travel are some of the causes of entry of viral pathogens into new geographic areas. For example, mobile populations and growing food imports make it more likely that diseases will continue to spread well beyond the borders where the diseases originated. For example, in the U.S., West Nile virus first appeared in New York in 1999 and has spread southward, northward and westward. Thousands of people have been infected. About 10% of these have developed moderate to severe clinical symptoms and several hundreds of people have died. Countless birds, horses and other animals have been infected and many have died. The virus is predicted to spread throughout the continental United States and to all regions of the Americas.


West Nile virus belongs to a family of disease-causing viruses known as flaviviruses, which are spread by insects, usually mosquitoes but also by ticks. The currently identified flaviviruses include, but are not limited to, tick-borne virus such as mammalian tick-borne virus groups including Gadgets Gully virus, Kadam virus, Kyasanur Forest disease virus, Langat virus, Omsk hemorrhagic fever virus, Powassan virus, Royal Farm virus, Karshi virus, tick-borne encephalitis virus, subtypes European, Far Eastern, and Siberian, Louping ill virus, subtypes, Irish, British, Spanish, and Turkish, Seabird tick-borne virus group including Meaban virus, Saumarez Reef virus, Tyuleniy virus and also include mosquito-borne viruses such as the Aroa virus group including Aroa virus, Bussuquara virus, Iguape virus, Naranjal virus, the Dengue virus group including Dengue virus, Dengue virus type 1, Dengue virus type 2, Dengue virus type 3, Dengue virus type 4, Kedougou virus, and the Japanese encephalitis virus group including Cacipacore virus, Koutango virus, Japanese encephalitis virus, Alfuy virus, St. Louis encephalitis virus, Usutu virus, West Nile virus, Kunjin virus, Yaounde virus, the Kokobera virus group including Kokobera virus, Stratford virus, the Ntaya virus group including Bagaza virus, Ilheus virus, Rocio virus, Israel turkey meningoencephalomyelitis virus, Ntaya virus, Tembusu virus, the Spondweni virus group including Zika virus, Spondweni virus, the Yellow fever virus group including Banzi virus, Bouboui virus, Edge Hill virus, Jugra virus, Saboya virus, Potiskum virus, Sepik virus, Uganda S virus, Wesselsbron virus, Yellow fever virus and also include viruses with no known arthropod vector such as the Entebbe bat virus group including Entebbe bat virus, Sokoluk virus, Yokose virus, the Modoc virus group including Apoi virus, Cowbone Ridge Virus, Jutiapa virus, Modoc virus, Sal Vieja virus, San Perlita virus, the Rio Bravo virus group including Bukalasa bat virus, Carey Island virus, Dakar bat virus, Montana myotis leukoencephalitis virus, Phnom Penh bat virus, Batu Cave virus and Rio Bravo virus. Viruses that may also be included in this group include Tamana bat virus and cell fusing agent virus.


Flaviviruses that are important human pathogens include yellow fever virus, Japanese encephalitis virus, dengue virus, tick borne encephalitis virus and Saint Louis encephalitis virus. Most human infections are asymptomatic or mild, causing fever, headache and body aches, often accompanied by a skin rash and swollen lymph glands. If the virus crosses the blood-brain barrier, life-threatening encephalitis or meningitis is often the result. Polio-like paralysis and Parkinson's disease-like symptoms can also result from West Nile virus infection. West Nile is most often transmitted by insect vectors, although transmission can also occur through transfusion, transplantation and from mother to child during birth or during breast feeding.


West Nile virus primarily cycles between mosquitoes and birds. Other animals, such as humans or horses, are incidental hosts to which the virus is transmitted during the mosquito's blood meal. Many bird species are infected with West Nile virus, with crows, bluejays and sparrows being some of the most susceptible species. An increase in dead birds is often the first clue that West Nile is invading an area or that the virus is found there is large numbers.


Currently, there are no drugs to treat West Nile virus and no vaccines are available to prevent infection. This lack of treatment and vaccines is the case for many flaviviruses and other viral pathogens. While vaccines are often a goal for medical treatment, vaccines are not without some risk to the individuals being vaccinated. With the compositions and methods of the present invention, the genotypes of individuals in an infected area can be easily determined and this information used to decide what medical intervention may be necessary. If the population is comprised primarily of individuals who are resistant to infection, mass vaccination would be a waste of resources. Additionally, there may be a subset of the population that is highly susceptible and vaccination may cause harm in these individuals. Further, these highly susceptible individuals could take preventive measures, such as reducing exposure to conditions where insects are feeding, and thus avoid illness.


The methods and compositions of the present invention are useful for identifying individuals who are at risk of developing disease, and also for identifying individuals who are resistant to disease. Such individuals comprise mice, and also other species, including, but not limited to humans, horses, cattle, sheep, pigs, wild birds and chickens. It is very expensive to vaccinate farm animals yearly and if the genotypes of the animals are known, only the susceptible animals need be vaccinated. Wild bird populations could be restocked with resistant individuals.


Innate resistance to flavivirus-induced morbidity and mortality was first demonstrated in mice in the 1920's (1) and showed monogenic autosomal dominant inheritance (2). The alleles that determined resistance and susceptibility were designated Flvr and Flvs, respectively (3). Resistant mice are susceptible to infections with other types of viruses, but are resistant to all flaviviruses (4). The disease resistance conferred by the Flvr allele has been demonstrated with a number of different flaiviviruses. Mosquito-borne flaiviruses tested include West Nile virus, dengue, St Louis encephalitis, yellow fever virus, Japanese encephalitis, Banzi, Ilheus, Murray Valley encephalitis, Kunjin, Alfuy and Kokobera. The tick-borne flaviviruses tested include louping ill and Russian Spring Summer encephalitis viruses. Flavivirus resistant and susceptible mouse strains were shown to be equally susceptible to viruses from other families, such as an arenavirus, three bunyaviruses, a picornavirus, two rhabdoviruses, seven alpha togaviruses, and two herpes viruses.


Resistant mice can be infected by flaviviruses, but the virus titers in their tissues are lower by 1,000- to 10,000-times than those in the tissues of susceptible animals and the spread of the infection in resistant mice is slower (5-6). Cell cultures derived from many different tissues of resistant mice also produce lower yields of virus; peak titers from resistant cultures are 100- to 1,000-times lower than from susceptible cultures (7-9). Previous studies indicate that the Flv gene product acts intracellularly on flavivirus replication.


The flavivirus resistant allele was demonstrated in wild Mus musculus domesticus populations in both the U.S. and Australia and flavivirus genetic resistance was also reported in other Mus species (11-13). Most commonly used inbred laboratory mouse strains were derived from a small number of progenitors and the majority of them have a homozygous flavivirus susceptible genotype. Only the Det, BSVR, BRVR, CASA/Rk, CAST/Ei, MOLD/Rk and PRI inbred strains have the resistant allele (10). The characteristics of a resistant-like allele (designated Flvr-like) in CASA/Rk and CAST/Ei strains were similar to those of the PRI Flvr allele. The MOLD/Rk animals carry an allele designated minor resistance Flvmr, which can protect carriers from disease after infection with the attenuated 17D strain of yellow fever virus, but not from the virulent Murray Valley encephalitis virus (11).


The resistant allele from donor PRI mice was introduced onto the susceptible C3H/He background to produce the congenic inbred C3H.PRI-Flvr (formerly C3H.RV) strain by a standard backcross protocol followed by brother-sister matings with selection at each generation for the resistance phenotype (13). These congenic strains also carry different alleles of the Ric gene, which controls susceptibility to Rickettsia tsutsugamushi and is located on mouse chromosome 5 (14). These data suggested linkage between the Flv and the Ric loci and the congenic strains were subsequently used to map the Flv locus on mouse chromosome 5 by linkage with the Ric and rd loci (15). Subsequently, twelve microsatellite markers from mouse chromosome 5 were genotyped relative to the Flv gene in 1325 backcross animals. Two of the microsatellite markers, D5Mit408, and D5Mit242, exhibited map distances with the Flv locus of 0.30 and 0.15 centiMorgans (cM), respectively, while one additional marker, D5Mit159, showed no recombination with Flv, indicating linkage of <0.15 cM (16).


To isolate the Flv gene a positional cloning strategy was used. The loci located near the D5Mit159 marker were first identified and then their sequences were compared in cells from congenic resistant and susceptible mice. The Flv gene was identified as mouse 2′-5′ oligoadenylate synthetase 1B (Oas1b) by these methods.


Abbreviations used herein include BAC, bacterial artificial chromosome: Flv, flavivirus resistance gene; Oas, 2′-5′ oligoadenylate synthetase; ORF, open reading frame; WNV, West Nile virus


Data depositions, and sequences disclosed herein by specific incorporation, include mouse sequences, AF217002 (SEQ ID 1), AF217003 (SEQ ID 2), AF261233 (SEQ ID 3), AF319547 (SEQ ID 4), AF328926 (SEQ ID 5), AF328927 (SEQ ID 6), AF418004 (SEQ ID 7), AF418005 (SEQ ID 8), AF418006 (SEQ ID 9), AF4188007 (SEQ ID 10), AF88008 (SEQ ID 11), AF418009 (SEQ ID 12), AF418010 (SEQ ID 13), AF453830 (SEQ ID 14), AF459815 (SEQ ID 15), AF459816 (SEQ ID 16), AF478457 (SEQ ID 17), AF480417 (SEQ ID 18), AF481733 (SEQ ID 19), AF481734 (SEQ ID 20), AY055829 (SEQ ID 21), AY055830 (SEQ ID 22), AY055831 (SEQ ID 23), AY057107 (SEQ ID 24), AY196696 (SEQ ID 25), AY196697 (SEQ ID 26), AY196698 (SEQ ID 27), AY196699 (SEQ ID 28), AY196700 (SEQ ID 29), AY221507, (SEQ ID 30), AY196701 (SEQ ID 31), AY227756 (SEQ ID 32), AY230746 (SEQ ID 34), AY237116 (SEQ ID 33), bovine sequence AY243505 (SEQ ID 36), AY250706 (SEQ ID 35), equine sequence AY321355 (SEQ ID 37) Human genomic OAS1 sequence (SEQ ID 38) (derived from the GenBank sequence AC00455 (Homo sapiens 12q24.1 PAC RPCI1-71H24), positions 120325-133280, presented here as the reverse complement of the GenBank sequence):

aaccaacagcagtccaagctcagtcagcagaagagataaaagcaaacaggtctgggaggcagttctgttgccactctctctcctgtcaatgatggatctcagaaataccccagccaaatctctggacaagttcattgaagactatctcttgccagacacgtgtttccgcatgcaaatcaaccatgccattgacatcatctgtgggttcctgaaggaaaggtgcttccgaggtagctcctaccctgtgtgtgtgtccaaggtggtaaaggtgagtccaggcctgcctggccaggggaggggtggctgaatgtgcaagagttgagattgagaatgagagagagagagagagagaagcaaaaacctagaacccagggtgcaaatgtgagtacagagagctgagatcttctgggatggtggtttcttatttatccacacagcatgttaaaatagattctggggtgaaatcctacatccctattattaacaagtgaccctcccccctacttcccgctgaagtttatgaaccactgtcctgggcgatgcccatttcagaaatagggaactgaatcccagctctggtaaacagtttgctaattcgtggccaggctaggggctcaccatttctgcagtgaagaatcatatgttttgaaagcaaatagcacctgctggctgcaagaccttgagcaagtcacttaactactctgtgttccaatttcctcagccataatccccaatactgttgcagtcttgccagtgcaccttaatgtagcagcttctcactgaattagtacccaaggttctttgtcctgcatccaagaaaattaaggaacatggacacaaacgtgagcttggagcaaaagttcagtaagcaaaagaagaaagctgtctccactgtggagagggaagtctgagtggattgccagattgcagctgaatgcaaaaaacttttataagaaaccactctcctccctgtaactgtttgagaaactttttatcagtaaagctgtgcaacttcccttaccttatgcagctgtgggtatatctctaggcaagcataaagcgctgcttctcttgtatgtataactgtggatttgttttaggtaagtcccactccctgcgccagtttcaggcaggccgctcctccagggcccagccttgaccatttacctaactgatttttcctctactttccctcaatacctcatagggccgtgtagattaagtaaaatagtaagtgtgaaccacccagcataagctagtcctgggcatcgtaaaggacaatgggaaaagaacacagatcctggaagaaggcccccaggtttgaattgtatttgccacctactagctgggtgatggggctgatatattatctcactgagcatccattttcccatctgtaaaatgggaactaatgataatggcatccaaatcatagcatcattgtgagcattataggagtttaagacatgcaatgccttcagaacagtggctagtgctccataatgttagtgattgctcctgtcattttatttagggaggtttgcctcactaagcatcaattattatttttgtcgtctttttcagggtggctcctcaggcaagggcaccaccctcagaggccgatctgacgctgacctggttgtcttcctcagtcctctcaccacttttcaggatcagttaaatcgccggggagagttcatccaggaaattaggagacagctggaagcctgtcaaagagagagagcattttccgtgaagtttgaggtccaggctccacgctggggcaacccccgtgcgctcagcttcgtactgagttcgctccagctcggggagggggtggagttcgatgtgctgcctgcctttgatgccctgggtgagagctcccagcttctttttctccctcttcccatttctgagcagaaatctcccacagtttgagagctttttgccccaacagggcatctctctaaagcagggtgggaggagatcttaggatctgtcccggggcaagaatgaatacggtcatgatctatcacaggagagacattaaacagcaaattggcataatgtggggacaaagacatttcttacagaacatctgcaaggcttactggttctgtttaaggcaaaatgtgtgaattttatctttctaaaatcaggcagcaaagatgtggcttaaagttcatgttactctcatctttgtcccaacatgagatctcatcaaacgtatgcagcacgttgggagatagatatttataatttgcaggaacatttggacaggaagtgtaacctctcagaggctcccttgccacatcaggagaattggtaaaaccacactacctgtatcatatcattattttaagtgataaatgatcatctacattcagctctgatgagtaataggtgttcaaaaataggaacttccagccaagtgtggtggctcatgcttgtaattccaacacttttggaggctgaggcaggagggtcgcttgagcccaggagttcaagaccagcctgggcagcaaagtgaaacctcatctctactaaaaattttaaaacattagccaagtgtggtggtacatgcctgtggtcgcagttattcaggacgctgagactgaacgatcacatgaggccagccaaggattcgaggtgtcagtgagccacgaatgtaccactgcactccatcctaggcacagagcaagagcaagaccctgtctcaatcaatcagtcaatcagtcaaaactatgaatttcccagctgtatatgaaggcacctcaaaacaccacagtgaactcacagagggacacggaatagtttagattttaattttttgagggaaatgcgatgacatctgtcacacaccgcacaaacggctactattaaactgaacttactgattagtggctactaattaatagttggtcattaagcagtaattagtgattaattatcaagtaattaggacttaattaaaggaactgtcacagtttcctttagtcctagggcagccatgaaaaaaaaaatgctgactctccaaagacaccagggtatgagaaagttttggattctctcctttgtgccatctcctgtgttgggggctgaagtacaatggttgtaaaagacaagagggagaaggctggtcacagtggctcacgcctgtaatctcagcactttgggaggccaaagtggggggatcacttgaagtcaggaattcaagaccagcctggccaacatggtgaaatctcacatctactaaaaatacaaaaattagctgggcgtggtggtgtgtgcctgtaatcacagctactcgggaggctgaggcaggagaattgcttgaacccaggagatggaggttgcaargagccaagatcatgccattgcactccagcctgggcaacagagtgagactccatctcgaaaaaaagaaaaaagaaaagaatataaggagtgattaaaaaagaaaagaaaagaaaactaagtagggtgaaacaatagatagccatgggggttagggagcttttttagacagggtcgtgagggagggtccctgagcctgagtggcgagaaggagtgagccttggggagatctggaggttctgggaagaggaatggcaagtgcagaggccctgaagcagcaatgaccatggcacatttgaggaagagagaaaaagtcagagaagtagaaagtgggcaaaggaagcaagacaggaggtgaggtgggagaggttccagagaccagatcacaccagacatcattggccaccataagatctttgggttttaaaattccagatgttatgggatgcaggaagcagcatgatcagcagcattctctaggtgccaggttgagaacaggctgtgggggaacctgtaaagaggttgctgccatagttccggcgagtgacggtggtggcttggatggggtgatggcagtggagagggcaggagggaggatcaggaatggacctcaagacttcccagccctgggtctgctgcacttttcaatcaaaccccatggccagggagattgtcccctcagagtgactgaaggaaattcagagaagagctgacacctaagttgtagattttgcccgaacaggtcagttgactggcggctataaacctaacccccaaatctatgtcaagctcatcgaggagtgcaccgacctgcagaaagagggcgagttctccacctgcttcacagaactacagagagacttcctgaagcagcgccccaccaagctcaagagcctcatccgcctagtcaagcactggtaccaaaatgtatggccctcccaccaggcctggtgggtcctgtctcgactgggagcagaggaggggtggggggaggagagaaagaagggagtgaagggaagaggagggggagtggtggagggaaatagagggatggaaaaaggagagaaaggaaaaagaggtggagagaggagcctgcaacagaagggagaatgaaagggaaggaagagagaaaggaagggattttggtgttctgttcactgctgtatccccagaacttaaaacagagcctggtgcataataggtgtaaataactgttgaataaatgaatcaatgctacatacacacacgcacgcacacacacacagagagagagtcaaccacactcttcagaaggtggataagttaaaacaagagtttcaaacaaatatatgttcagatgccctttcctcccacttactggctggctggccttaagtaagcaacttaacctttctgttctttctgctttcttatctgcaacgagtagcatgccatagctagagtaacacggcatatagttggtcctgataaatgtagcatattttagccaccataggagtacacataataaaagctaacatgtagtatgtgcttagcttatctatgttttgtggatgtgatacaattttctgttcacttttaaatgccctgcatcttagtcaattttaacagtgattctgtaagttagataaggttaggcattattattaaatccattttacaccaagagaaacttgggtcaaaaagagaaactcctgggtcacatggctcattcggccaataagtagcagaagtaaaatttgaatttggctgggcgcggtagctcacaccagtaatcccagcactttgggaagccaaggcaggtagattgcttgagcccaggagttcaagactagcctgagcaacatggcaaaacctcgtctctacaaaataaactaaaaatttagccaggtgtgatggtgagcacctgtagccccagctactgggtaggctgaggtgggaggatcgcttgagcctgggaggaggaggttgcagtaagtcaggattgcactactgccctccagcctgtgagacagagcaagatcttctctcaaacaaacaaacaaacaaacaaacaaaaactcgaatttgggtctattgacttaagagtttgcctgataataataggcattcaatgtatatttcttgaatgaacgaatgaatgaaaataatcaggaataaactttccaatttaaaagtaacacctctaggtaaaaaaaagacaatcatttagttgccagacttctaagtgtttgctgttctatgaattgtaatcatggagcctgagcattgtagaatttacaaaagcagttcctgacaaaagcagcactgcccccagggacatattgaaaattaatgagggtgtttttggtaaccatggtgatgggaggacatgggtgctacttatatttagtggaaagaagacaagaatgctagttattgtacaatgatcaagagagtcctgcacagccaagaattgtctttttctttctttcttgatgctgttctcctttaaaacaagacaagattaacaataatttaactccactaaccaccatcatcaccacctccaacttatatgctacatttcttgtatatttcaagtctgtttatattttcaagtgcctcgaagtattattgttttatagccaaatgtttagttaatctgctcacagatttaccactttcttcactattcattctgtcttacacctctaacattccatctggggtaattttcctaaatgatcatgcatcctttgggatttcttttgatgatggtctattggtagtaaactctctcagttattgtttgtctgaaaatgtcatgcttttgccttcattgttgaagggtgcttttgctgggtggtcatttcagtatattgaatatatcattccatcttccagtgtcatcattaaaaagtcagttgccagtctaactgcagctcttttataagtaacctgtcttattcttctggctgcatgtaaaagttttctctttgtctttgattttgtttagcttcaatctgctgtgtcttaatgatgggttcctattgtttgtcctgattgggattccgttaagattcctgaatctgtgggtagatatctttaatcagttttgaaacttctcagccattcttctaaaatattgattctccttcattctctcctcaccttctagaattccaattaaatgtatgttagaccctgctctatctttcatatctctatactctcttctgtgtttttcatccttttgtctatttttccatgctttattctgaatagttccttctaatctaccttccaattaactaattttctctttagctatatctaatttgctgtaattaattacagttgccatttttatcctaaaatttctatttcatatttttgtatctgccatggtacttcttatggcttttaattccctgctaactatttaaagttcttattttatcctgtgaatatgatattcctagttattttatttttaatttttattatttgttaatcttatgttttatttacacttcttttctgtgacatgagcacacacagattcatgtgtatacatatatggctctgatacctctcctttcctgtcctcattcaaaccactgatcacagagagaggactatttttttttatttttaatttttctatttcaataggtttttgggggaacaggtggtgtttggttacatgaataagttctttagtggtgattttggtgcacccatcacccaaacagtgtacattgtacccaatgtgtaatcttttaacccttgccacaccccaccctttccccgcagtccgcaaagtcccatgtatcattcttatgcctttgcttcctcatagcttagctcccacatatgagtgagaacatacaatgtttggttttccattcctgagttatttaattaaaataatagtatccaattccatccaggttgctgtgaatgccattattttgttcctttttatggttgagtagtattccatggtgtgtttgtgtgtgtataacatttttctttatccactcattgattgatgggcatttggctggttccatatttttgcaattgcaaattgtgctgttataaacatgtgtgtgcaagtatcttttttgtataatgacttcttttcctctgggtagatacctagtagtgggattgctggatcaaatggtagatctacttttagttctataaggaatctccacactgttttccatagtggttgtatgagtttacattcccaccaatggtgtaaaagtgttcccttttcaccacatccacaccaacatctattattgtttgattttttattatgaccattcttgcaggagtgaggtggtatcacattgtggttttgatttgcatttccctgataattagggatgttgagcatttttccatatgcttgttggtatttgttttttttttttttttttcattattatactttaagttttagggtacatgtgcacaatgtgcaggttagttacatatgtatacatgtgccatgctggtgtgctgcacccattaacccgtcatttagcattaggtatatctcctaatgctatccctccccaattccccccaccccgcttgttggtatttgtatatcttcatttgagaattctctgttcatgtccttagcccactttttgatgagattttttttttcttgctgattcgtttgagttctttgtagattctggatattagttggatgtatagattgtgaagattttctcccattctgtgggttgtctgttaactctgctaattatttcttttgctttgcagaagctttttagtttaattaagtcccatctatttatctttgtttttgttgcatttgcttttgggttcttggtcatgaagtctttgcctaagccaatgtgtaggagggtttttccaatattatcttctagaatctttatggtttcaggtcttagatttaagtatttgatcgattttgagttgaattttgtataaggggagagagaaggattcagtttcattcttctacatgcaacttgccaattatcctaggaccatttgttgaatagggtgtcctttccccattttatgtttttgtttggtttgtcaaagatcagttggctgtaagtgtttggctttatttctgggttatctattctgttccatttgtctacgtgactatttttataccagtaccatgttgttttggtgactatggccttacagtatagtttgaagtctgataatgtaatgcctccagatttgttctttttacttagtcttgctttggctatgtgagctcttttttggtgccatatgaattttaggattgttttttctagttctgtgaagaatgatggtggtattttgatgggaattgcattgaatttgtagattgtttttgggagtatggtcattttcacaatattgattctacccattcatgagcatgggatgtgtttccatttgtttgtgtcatctatgattttctttcagcaatgttttgtagttttccttgtagagttcctagttattttaaagtctgtgttcggtctttcagcatttaaagtttgtaggtttattactatttctcttctttctgttggtcataactcttagtgttttgtttccttgtgtgcctggttacatatgtgctggtcattgtatttgaaaattatgtgtgaaataatttgaggttttggattatgtatattcctccagaaagaatttcatttgcttctgtgcatttcttaggaacattacaagtccttcttctcagttaattttcgtagtatctttatcagataggtgctattacaaccactcacttagcagatgaaaatcatgaggctctgagagtctaagtcatctacttagaattggacaatggtgaagccaggattcaaacccacatcaataagaatccagcgctcttaacaaggggccagtacacttttttaaaaaataaaaggctagatagtaaatattttagactttgtggactgcacagcctctgttgcaactactcaaccctgcctttgtagcatgaatgcagtcataaactatacataaatgaatgagcctggattcgttccaaggaaactttataaaaacaggtggcaggctggatttggcccatgagaagtgtagtttacacaaaagttgagcaaaccaatttttttctgattgtttttcctcttctcagtgtaagaagaagcttgggaagctgccacctcagtatgccctggagctcctgacggtctatgcttgggagcgagggagcatgaaaacacatttcaacacagcccagggatttcggacggtcttggaattagtcataaactaccagcaactctgcatctactggacaaagtattatgactttaaaaaccccattattgaaaagtacctgagaaggcagctcacgaaacccaggtatgctatccccacatggcttagctcccctatgtaaatgaacacctggatacaggtacagtgccttggaaatggaggaggtgggagggctccccacttagtgagaatctcctgttgcccatcattgtactgggcattttactactgccatctgttttaaacacctacctccaaccctgtgaggcaggcactatgccaattattttacaggtgagtaaactgaggttctgagaggtaaggagcttgtccaacccttaacagaaaatgagtaaaatagctgcagtttgaactgaaataagaacagcagcaacaacaatgatagtaattgctcccaggtattgaaagcttgttgtaagactaacacatgctaatataatagtaaaaattattagcaatattactgatatgtatgttatgttctagtcgctgtgctgagcatttcatataactgggctttttctatcctcacagcatagcctttgagataggtatgtggaactattcccattttacagataagaatcctgaggcttagagagttcaagtgacctacccaagggcacatcactgataaagggcagaggtgggattcaaacccacatctgtcaggtgcaagtgcaaggctccttctcctcatgctcactgcctgctggggaatagggcactggggacataccccagggagcccttcctcatgttctgagtcccagttcatcccatgctgctattttgctctcccaggagcatctggactccctagacagagccccagcttctcacctgtccctctctaaatgctgctctgcaggcctgtgatcctggacccggcggaccctacaggaaacttgggtggtggagacccaaagggttggaggcagctggcacaagaggctgaggcctggctgaattacccatgctttaagaattgggatgggtccccagtgagctcctggattctgctggtgagacctcctgcttcctccctgccattcatccctgcccctctccatgaagcttgagacatatagctggagaccattctttccaaagaacttacctcttgccaaaggccatttatattcatatagtgacaggctgtgctccatattttacagtcattuggtcacaatcgagggtttctggaattttcacatcccttgtccagaattcattcccctaagagtaataataaataatctctaacaccatttattgactgtctgcttcgggctcaggttctgtcctaagccctttaatatgcactctctcattaaatagtcacaacaatcccatgaggcatttttaaaaattttttattattttagattcagagggcacatgtgccatttgttacacagctatattgtgtaatggtggggtttgggcctctattgatcctgtcgcccaaatagtgaacagagtacccaaaaagaattttttcaacctttgcctttctcccttcctcctccctgttggagtccctagtgtctattgttcccatctttagcagatgttaagtatttgattttctgtttctgggttaattcacttcggataatggcctccagctgcaaccatgatttcattctttcttatggctgcataatactccatggtgtagatataccacactttctttatccagttcacactgatgggcacttaagttgattccatgactttgctattgtgaatcgtactgcgataaacatacgagtgccggtgtcttttgatagaatgatttctttacctttgggtagataccgagtagtgggattgctgggttgaatggacattctacttttagttatttgaaaagtcccatgaggcatgttttctatcattcccatcttacagatgagacaaaggctcagagaggtgaggtcacttgctcaaggacatcagctaacaagtggtggaaatggaattcaagctcagtggactctaaagccagtgctcatgtcactgtgctaaacagcctgccttgtcacatccccacctctcatctgaccaatgggagactctgagcagctgagtgacttgggttgtcacacagctaaacaggggcaaaggacccagtcttggatctttccacctccaagcaggaatctgtctgattccaggggattgatgatgttgcagatggctaggaagcagactccaggatggaatttagtatgcaggatgttctgggggagagccactggaaccagcactcagggaaaggggggaagaaaggataggaaggaagcatgaaagagaatagggagaagtgaacagggatgcagagcgaatgccagtttcagccaactccaaggacagccctggagctggaatggcctttagagctgccccatggtgacagaggtggccaggcttctatacccctacgtggatcactcactgtgcttgggcaccttgggaaagggcatggctttgagcaaaaggctctctgcagctgaggcaacccctaaaagggctgacggctgaagtctgtctgctgaccactgtcccagcagctggggcttgttagtccttcctcaaagggggatccagatggcatgtcacagtgtctaccgtaaatgctcactgaatccagctgcaatgcaggaagactccctgatgtgatcatgtgtctcaccctttcaggctgaaagcaacagtgcagacgatgagaccgacgatcccaggaggtatcagaaatatggttacattggaacacatgagtaccctcatttctctcatagacccagcacactccaggcagcatccaccccacaggcagaagaggactggacctgcaccatcctctgaatgccagtgcatcttgggggaaagggctccagtgttatctggaccagttccttcattttcaggtgggactcttgatccagagaggacaaagctcctcagtgagctggtgtataatccaggacagaacccaggtctcctgactcctggccttctatgccctctatcctatcatagataacattctccacagcctcacttcattccacctattctctgaaaatattccctgagagagaacagagagatttagataagagaatgaaattccagccttgactttcttctgtgcacctgatgggagggtaatgtctaatgtattatcaataacaataaaaataaagcaaataccattta


The sequence of the OAS1 PCR fragment for the G-allele (the G nucleotide is indicated in upper case): (SEQ ID 39)

cagatggcatgtcacagtgtctaccgtaaatgctcactgaatccagctgcaatgcaggaagactccctgatgtgatcatgtgtctcaccctttcaGgctgaaagcaacagtgcagacgatgagaccgacgatcccaggaggtatcagaaatatggttacattggaacacatgagtaccctcatttctctcatagacccagcacactccaggcagcatccaccccacaggcagaagaggactggacctgcaccatcctctgaatgccagtgcatcttgggggaaagggctccagtgttatctggaccagttccttcattttcaggtgggactcttgatccagagaggacaaagctcctcagtgagctggtgtataatccaggacagaacccaggtctcctgactcctggccttctatgccctctatcctatcatagataacattctccacagcctcacttcattccacctattctctgaaaatattccctgagagagaacagagagatttagataagagaatgaaattccagccttgactttcttctgtgcacctgatgggagggtaatgtctaatgtattatcaataacaataaaaataaagcaaataccatttattgggtgtttattaacttcaaggcacagagccaagaagtacagatgcatatctaggggtattgtgtgtgtatatacattgattcaacaagaaatatttattgagcacttactatgtgccaagcatagctctgg


The sequence of the OAS1 PCR fragment for the A-allele (the A nucleotide is indicated in upper case): (SEQ ID 40)

cagatggcatgtcacagtgtctaccgtaaatgctcactgaatccagctgcaatgcaggaagactccctgatgtgatcatgtgtctcaccctttcaAgctgaaagcaacagtgcagacgatgagaccgacgatcccaggaggtatcagaaatatggttacattggaacacatgagtaccctcatttctctcatagacccagcacactccaggcagcatccaccccacaggcagaagaggactggacctgcaccatcctctgaatgccagtgcatcttgggggaaagggctccagtgttatctggaccagttccttcattttcaggtgggactcttgatccagagaggacaaagctcctcagtgagctggtgtataatccaggacagaacccaggtctcctgactcctggccttctatgccctctatcctatcatagataacattctccacagcctcacttcattccacctattctctgaaaatattccctgagagagaacagagagatttagataagagaatgaaattccagccttgactttcttctgtgcacctgatgggagggtaatgtctaatgtattatcaataacaataaaaataaagcaaataccatttattgggtgtttattaacttcaaggcacagagccaagaagtacagatgcatatctaggggtattgtgtgtgtatatacattgattcaacaagaaatatttattgagcacttactatgtgccaagcatagctctgg



FIG. 1 shows physical and transcript maps of the Flv interval. Genes are represented by their accepted abbreviations or the GenBank accession numbers of their transcripts. The arrows represent the direction of gene transcription. The centromere is oriented toward the left of the figure. The Oas1b gene is indicated in bold. The flanking microsatellite markers are shown inside vertical rectangles, the D5Mit159 marker is shown inside a horizontal rectangle. The horizontal bars beneath the genes represent the BAC clones listed by the library name.


Twenty-two candidate genes for the Flv gene which controls resistance or susceptibility to flavivirus disease were identified. Full-length cDNAs were amplified by RT-PCR from congenic flavivirus resistant (C3H.PRI-Flvr) and susceptible (C3H/He) mouse strains for each gene identified in the Flv region using the primers listed in Table 2, sequenced and compared. The sequences of the majority of the genes in the two mouse strains were either identical or very similar (with only a few silent substitutions). In contrast, two genes, Na+/Ca2+-exchanger and Oas1b, were polymorphic and differed by several missense mutations. The Na+/Ca2+-exchanger cDNA from the C3H.PRI-Flvr and C3H/He mouse strains differed by five non-synonymous substitutions (data not shown). cDNAs for this gene were subsequently sequenced from two additional susceptible (BALB/c and C57BL/6) and one additional resistant (BRVR) mouse strains. A random distribution of substitutions in the Na+/Ca2+-exchanger cDNAs were observed between the five mouse strains studied.


A total of 31 substitutions in Oas1b cDNA were found between the congenic C3H.PRI-Flvr and C3H/He mouse strains. Most of these substitutions were silent, but the C820T transversion, in the susceptible C3H/He strain resulted in a premature stop-codon. The C3H/He Oas1b gene product therefore lacked 30% of its C-terminal sequence as compared to the C3H.PRI-Flvr product (FIG. 2A). Two additional non-synonymous mutations resulted in a threonine to alanine substitution at position 65 and an arginine to glutamine substitution at position 190 in the susceptible C3H/He gene product.



FIG. 2 illustrates the structures of the Oas 1b gene and protein. A. Domain architecture of Oas1b proteins. The N-terminal domain (˜30 aa) (shown in gray) and the C-terminal domain (shown in black) are specific to the Oas protein family (generated with the ProDom tool). The nucleotidyltransferase domain (Pfam 01909) is shown in white. The CFK tetramerization motif is indicated by an asterisk. (1) Products of the Flvr and Flvr-like alleles. (2), Product of the Flvmr allele. (3), Product of the Flvs allele. Positions of amino acid substitutions between the Flvmr and the Flvr proteins are shown as vertical bars. B. Exon-intron structure of the mouse Oas1b gene. Exons are shown as open boxes. The positions of the start (ATG) and stop (TAG) codons, the substitution (CGA/TGA) that results in a premature stop codon and the two potential polyadenylation sites are indicated by vertical lines.


Comparison of Oas1b genomic (AC015535) and cDNA (AF328926) sequences revealed six exons. Based on the results of the 5′ RACE experiments, the size of the first exon was determined to be 243 bp in length and included 64 bp of the 5′ non-coding region (NCR). The lengths of the second, third, fourth and fifth exons were 277, 185, 233 and 154 bp, respectively. The fourth exon of Oas1b in the susceptible strain contained a premature stop-codon (FIG. 2B). All exon-intron boundaries contained conventional splicing sites. In the resistant strain, the sixth exon included the last 102 bp of the ORF and the 3′ NCR, which contained two potential polyadenylation signals separated by about 2 kb.


The individual exons of the Oas1b genes from eight additional mouse strains were next amplified from genomic DNA and sequenced. The Oas 1b gene encodes an identical full-length protein in all resistant strains (BRVR, C3H.PRI-Flvr, CASA/Rk, and CAST/Ei), whereas the homologous gene from all susceptible strains (129/SvJ, BALB/c, C3H/He, C57BL/6, and CBA/J) encodes an identical truncated protein. The flavivirus susceptibility phenotype correlated with the Oas1b genotype in all nine mouse strains studied.


The Oas1b protein contains three domains (FIG. 2A). The N- and the C-terminal domains are unique to the 2′-5′ oligoadenylate synthetase family, whereas the central domain has a distinct nucleotidyltransferase fold. Several motifs were previously detected in murine 2′-5′ oligoadenylate synthetases (FIG. 6). FIG. 6 shows alignment of the protein sequences of the murine, rat and human 2′-5′ oligoadenylate synthetases. Conserved positions within known functional motifs are colored according to the physico-chemical properties of amino acid residues: hydrophobic residues are highlighted in yellow, charged residues are shown in a white or red background and small residues are shown in a white or blue background. The domain structure is shown above the alignment and corresponds to that shown in FIG. 2A. An N-terminal LxxxP motif is required for 2′-5′ oligoadenylate synthetase activity (30), whereas the P-loop motif is responsible for dsRNA binding (31). It has also been shown that a DAD Mg2+ binding motif is required for normal functioning of the murine 2′-5′ oligoadenylate synthetase (32). Although the LxxxP and DAD motifs were conserved in the products of both the resistant and susceptible alleles of the Oas1b gene, the P-loop motif contained a four amino acid deletion that was not found in the other murine 2′-5′ oligoadenylate synthetases (FIG. 6). A C-terminal CFK motif appears to be critical for tetramerization of the small form of mouse 2′-5′ oligoadenylate synthetase (33). The truncated susceptible Oas1b protein does not contain the CFK motif and so could not form the tetramer structure required for 2′-5′ oligoadenylate synthetase activity.


Although the Oas1b cDNA sequence from the MOLD/Rk strain (intermediate Flv phenotype) also encodes a full-length protein, it differs from the proteins of the other resistant strains by 14 amino acid substitutions, F26L, S45F, G63C, T65A, S83Y, C103Y, F110C, H118Q, P176L, S183L, I184T, T322A, G347A and M350T, distributed randomly across the protein (FIG. 2A). The MOLD/Rk Oas1b protein sequence contains alanine at position 65 similar to the proteins encoded by the susceptible strains. The MOLD/Rk Oas1b sequence differs by two substitutions, L26F and R206H, from the recently released sequence, AAH12877, derived from the CZECH II mouse strain, which has an unknown Flv phenotype. Both MOLD/Rk and CZECH II contain the same four amino acid deletion in the P-loop motif found in all Oas1b proteins.


Investigations of the constitutive expression of the Oas1b gene in different mouse tissues were conducted. Although alpha/beta-interferon treatment up-regulated the transcription of the murine Oas1b gene (data not shown), constitutive expression of this locus was detected by Northern blotting in all 14 murine tissues tested. Two transcripts of the expected sizes, 2 kb and 4 kb (FIG. 3), were identified using a labeled cDNA probe derived from the 3′ NCR of Oas1b (cDNA positions 1384-1691 bp). The highest levels of constitutive expression were detected in lung and spleen (FIG. 3), thymus, placenta and uterus (data not shown).



FIG. 3 shows the constitutive expression of mouse Oas1b in different mouse tissues. A labeled Oas1b probe derived from the 3′ NCR of Oas1b was used to probe a BALB/c Northern blot (Stratagene) containing poly-A+ RNA (2 μg/lane) extracted from: 1, heart; 2, kidney; 3, liver; 4, lung; 5, skeletal muscle; or 6, spleen.


The effect of expression of C3H.PRI-FLVr proteins in C3H/He cells on flavivirus replication was investigated. Since the Flvr allele is dominant, its expression in susceptible cells was expected to have a dominant negative effect on flavivirus replication. C3H/He cells were transfected with the mammalian expression vector pEF6/V5-His-TOPO containing either the Oas1b or the Na+/Ca2+-exchanger cDNA from C3H.PRI-Flvr. Stable cell lines were established by selection and cloning of transfected cells. The growth of the flavivirus, WNV, in susceptible C3H/He cell lines expressing either the Na+/Ca2+-exchanger or the Oas1b protein from resistant C3H.PRI-Flvr was compared to that in untransfected C3H/He and C3H.PRI-Flvr cells. No differences were observed either in the yields of WNV or in the time of appearance of cytopathic effect (CPE) between cell lines expressing the Na+/Ca2+-exchanger protein and untransfected C3H/He cells (data not shown). However, in C3H/He cell lines expressing a low level of the resistant Oas1b protein, viral titers were lower than those observed in untransfected cells, but not as low as in untransfected C3H.PRI-Flvr cells (FIG. 4A).



FIG. 4 shows the effect of the low level expression of the resistant Oas1b protein in C3H/He cells on the growth of a flavivirus, West Nile virus, and an alpha togavirus, Sindbis. A. Virus growth curves. Cells were infected with either West Nile or Sindbis virus at a MOI of 0.5. Samples of culture fluid were taken at the indicated times and titered by plaque assay on BHK cells. RU, untransfected resistant C3H.PRI-Flvr cells; SU, untransfected susceptible C3H/He cells; ST, susceptible C3H/He cells stably transfected with Oas1b cDNA from resistant C3H.PRI-Flvr cells. B. Time course of the development of cytopathic effect (CPE) after infection of SU, RU and ST cells with West Nile virus. −, no obvious CPE; +, rounding or detachment of about 25% of the cells in the monolayer; ++, rounding or detachment of about 50% of the cells in the monolayer; +++, rounding or detachment of about 75% of the cells in the monolayer; ++++, complete destruction of the monolayer.


The appearance of CPE in C3H.PRI-Flvr cells after WNV infection was significantly delayed as compared to that in C3H/He cells. The appearance of CPE was also delayed in C3H/He cells expressing the resistant Oas1b (FIG. 4B). In contrast, the growth and the time of appearance of CPE of an alpha togavirus, Sindbis, were similar in the three types of cells. The recombinant Oas1b protein contained both C-terminal 6×His and V5 tags which may have interfered with the activity of the 2′-5′ oligoadenylate synthetase by reducing the efficiency of tetramer formation. Surprisingly, cell lines expressing intermediate levels (8×) of resistant Oas1b protein showed lower levels of WNV suppression, while those expressing high levels (20×) of the protein showed no suppression (data not shown). The reasons for a negative correlation between suppression of WNV replication and the level of resistant protein expressed are currently not understood. Experiments to produce and test knock-in mice are underway.


The N-terminal 346 amino acids of OAS1 represent one functional unit, while OAS2 and OAS3 contain two and three functional units, respectively (19, 34-36). The murine Oas sequences obtained previously by different laboratories were named without knowledge of the entire gene family and designated by different symbols. A proposed simplified nomenclature for the murine Oas gene family is shown in Table 1. The single functional unit sequences were designated Oas1a through Oas1h, whereas the two- and three-unit sequences were designated Oas2 and Oas3, respectively (FIG. 1 and Table 1).


The 2′-5′ oligoadenylate synthetase-like genes, OASL and Oasl2 have recently been cloned from humans (36-37) and mice (38), respectively. A Celera database search revealed an additional murine gene, Oasl1, which was located close to Oasl2 and was about 6 Mb upstream the Oas2 locus. All of the human and mouse 2′-5′ oligoadenylate synthetase-like genes contained C-terminal ubiquitin-like domains. Although the Oas-like 1 (Oasl1) gene was mapped outside of the Flv interval, the cDNA of this gene was cloned and sequenced so that the comparative analysis of 2′-5′ oligoadenylate synthetase motifs included all of the known family members.


Available protein sequences for murine, rat and human 2′-5′ oligoadenylate synthetases were aligned and a phylogenetic tree was constructed (FIG. 5). The known rat proteins, AAC19135 and CAA79317, are encoded by two genes orthologous to murine Oas1b and Oas1a, respectively. Six additional rat Oas1 sequences have now been seqenced and are attached. All rodent Oas1 sequences cluster with the single human ortholog, OAS1. This clustering was fully supported by bootstrap analysis. The existence of eight apparent Oas1 paralogs in mice likely resulted from a series of gene duplication events. The one-to-many orthologous relationship between human and murine genes is unique to Oas1 and was not observed for other members of the Oas family (FIG. 5). FIG. 5 shows unrooted neighbor-joining, distance-based phylogenic tree of murine, rat and human Oas sequences. Human genes are designated by capital letters, while only the first letter is capitalized for the mouse genes. The sequences of the Oas2 and OAS2 proteins were divided into N- and C-terminal domains according to (19). The sequences of Oas3 and OAS3 proteins were divided into N-terminal (N), middle (M) and C-terminal (C) domains. The indicated bootstrap values were obtained with 1000 pseudoreplicates. The Oas1 cluster is shown on a gray background. The bar indicates the number of substitutions per site.


Twenty-two loci, including thirteen novel genes [a Ca2+-channel gene (AF217002), an unknown mRNA (AF217003), an ATP-dependent helicase (AF319547), a serine dehydratase (AF328927), a Na+/Ca2+ exchanger (AF217002), the Oas1b (AF328926), the Oas1d (AY055829), the Oas1e (AY055830 and AY055831), the Oas1f (AF481733), the Oas1g (AF480417), the Oas2 (AF418010), the Oas3 (AF453830), and the Oasl1 (AY057107)] were detected in a region of mouse chromosome 5 during positional cloning of the Flv gene. The D5Mit159 microsatellite sequence used for the initial BAC library screening was detected in the second intron of the Ca2+-channel gene (AF217002). By correlation of a polymorphism in the Oas1b gene with the susceptibility phenotypes of nine strains of flavivirus resistant and susceptible mice, the Flv gene was identified as Oas1b, a member of the 2′-5′ oligoadenylate synthetase gene family. 2′-5′ oligoadenylate synthetases bind dsRNA or particular secondary structures within single-stranded RNA (ssRNA) and catalyze the synthesis of 2′-5′ oligoadenylates (2-5A) from ATP (39). A major function of 2-5A is to bind and activate a latent endoribonuclease, RNase L, responsible for the degradation of viral and cellular ssRNAs (40). 2′-5′ oligoadenylate synthetases are also involved in other cellular processes such as apoptosis, cell growth and differentiation, regulation of gene expression, DNA replication and RNA splicing (19).


Data obtained with the three types of human 2′-5′ oligoadenylate synthetases, OAS1, OAS2, and OAS3 indicate that OAS3 functions as a monomer, while OAS2 and OAS1 are enzymatically active only as a homodimer and a homotetramer, respectively (19). The Oas1b genes from resistant mice encode full-length proteins, while those from susceptible mice encode C-terminally truncated proteins. Since the C-terminal region of the single-unit proteins is required for tetramerization, which is crucial for 2′-5′ oligoadenylate synthetase activity, it is likely that the Oas1b proteins produced by susceptible mice are not active. The OAS1, OAS2 and OAS3 genes are differentially induced by interferons alpha, beta and gamma in various tissues (19). Although the expression of the mouse Oas 1b gene was up-regulated after incubation with alpha/beta-interferon, it was found to be constitutively expressed at low levels in both resistant and susceptible cells (data not shown). These results are consistent with the previous observation that flavivirus resistance was not diminished in resistant mice after injection of anti-alpha/beta interferon antibody (41).


The effect of the Flv gene product is virus-specific, since it suppresses the replication of the members of the genus Flavivirus, but has no effect on the replication of other types of viruses. The functions of 2′-5′A and the latent endoribonuclease, RNase L are both non-specific. The Oas1b proteins from both resistant and susceptible mice differ from other 2′-5′ oligoadenylate synthetases by one unique change, a four amino acid deletion within the P-loop motif. The P-loop region is involved in RNA recognition and binding and may allow the Oas1b protein to specifically recognize and bind a specific conserved RNA structure unique to flavivirus RNAs. In support of this hypothesis, Urosevic and co-authors (42) reported that the OR156 strain of Murray Valley encephalitis virus, which had a 62-nucleotide deletion in its 3′non-coding region (43), replicated more efficiently in resistant mice than did strains of this flavivirus with full-length RNAs. Results from previous sucrose gradient analyses (10) and recent RNase protection experiments (data not shown) indicate that the levels of genomic flavivirus RNA, but not anti-genomic RNA, are preferentially reduced in flavivirus infected resistant cells as compared to susceptible cells. Also, more flavivirus dsRNA and less viral ssRNA were detected in the brains of resistant mice as compared to those of susceptible animals (44). Since genomic RNA is found free in the cytoplasm, it would be more susceptible to digestion by RNase L than would anti-genomic RNA, which is only present in double-stranded replication intermediate RNA structures. Since the Oas1b proteins from both resistant and susceptible mice have the same four amino acid deletion in the P-loop motif, both proteins would be expected to bind specifically to flavivirus RNAs, but RNA binding would only activate the full-length resistant Oas1b protein. It is currently not known whether the 2′-5′ oligoadenylate synthetase activity alone is sufficient to confer the flavivirus resistant phenotype or whether as yet uncharacterized activities of the Oas1b protein also contribute. Even though the Flvmr proteins also had the same deletion in the P-loop motif, the additional amino acid substitutions in these proteins were apparently responsible for the reduced level of resistance observed in this strain. This suggests that additional regions of the Oas1b may also be functionally important for susceptibility. Functional studies with a recombinant Oas1b protein are currently underway to address these questions. The advantage provided to mice and possibly to other rodents by the large number of Oas1 genes is currently not understood. Some of the mouse Oas1 gene products are not active synthetases, including Oas 1b. Preliminary data suggest that an inactive synthetase such as Oas1b can enhance the enzymatic activity of an active synthetase. One mechanism by which this could occur would be via the formation of heterotetramers. The formation of different heterotetramers could regulate activity levels. The Oas1 gene products may also interact with other cell proteins to accomplish additional as yet unknown functions.


Prior to the current invention, inherited flavivirus resistance appeared to be restricted to Mus species. Rats have multiple Oas1 genes and an Oas1b ortholog (AF068268), but resistance to flaviviruses has not yet been studied in rats. Humans have only a single OAS1 gene, but this gene produces multiple isoforms via alternative splicing (FIG. 7).


Human OAS proteins, OAS1, OAS2, OAS3 and OAS-like, are 2′,5′-oligoadenylate synthetases. The members of this family of interferon-induced proteins function in the antiviral action pathways of interferon but also have functions in gene regulation, apoptosis and development. When activated by double-stranded RNA, these proteins polymerize ATP into 2′,5′-linked oligomers with the general formula pppA(2′p5′A)n. This mixture of oligonucleotides is known as 2-5A and currently it is believed that 2-5A binds and activates a latent endoribonuclease responsible for the degradation of viral and cellular RNAs.


Resistance to infection by flaviviruses has been associated with variations in human OAS genes, particularly OAS1. The current invention also contemplates that mutations in other OAS genes may also be important for virus resistance/susceptibility.


When the G is present (G-allele) in the human OAS1 gene at nt position 12,349 (numbered beginning from the ATG-start codon in the genomic DNA) (FIG. 8; Celera SNP accession number hCV2567433) the OAS1 transcripts encoding the p46 and p48 isoforms are produced as a result of alternative splicing events. The conventional splicing acceptor “ag” at the end of intron 5 is utilized for processing of the p46 mRNA. Utilization of a different splice acceptor located 96 nucleotides downstream from the conventional intron 5 acceptor results in the production of the p48 mRNA.


When an A is present (A-allele) at OAS1 nucleotide position 12,349, the splice acceptor site is mutated to a non-functional “aa” and the p40 mRNA is produced by read-through into intron 5 (FIG. 8). An additional splice acceptor (aG, where G is the +1 nucleotide located at the beginning of the conventional exon 6) can alternatively be utilized to produce p52 mRNA designated hCT31628 in the Celera human transcript database. The p48 transcript can also be produced by individuals with the A-allele. The 346 N-terminal amino acids of the p40, p46, p48, and p52 are identical but their C-terminal regions differ due to alternative splicing. Each of the isoforms has a unique C-terminus translated from different ORFs. Stop-codons for the ORFs encoded by p46, p48 and p52 transcripts are located in exon 6 at positions +163/+165, +303/+305, and +341/+343, respectively. The stop-cod the p40 transcript is located at position +54/+57 in intron 5.


Data from a study of human populations indicated that the different alleles of the OAS1 gene are important for determining viral resistance/susceptibility. The frequency of the A-allele in ethnic Russian populations who are known to be highly resistant to disease caused by the flavivirus, tick borne encephalitis virus, was significantly increased (up to 99%) as compared with the frequency in a group of non-ethnic patients with tick borne encephalitis virus-induced disease (59%). The GG homozygous individuals exhibited the most severe disease symptoms. No GG-homologous individuals were detected in the native Siberian populations. In contrast, the frequencies of the A-allele and the G-allele were similar in groups of healthy Russians and Russians infected with hepatitis C virus (a distantly related member of the flavivirus family from a different genus. The data is summarized in Table 1.

TABLE 1Human Viral Resistance GenotypesFrequencies and numbers of genotypesFrequencies of allelesPopulationNAAAGGGAGRussians1340.69(93)0.28(37)0.03 (4)0.83/0.71*0.17/0.29*Altains300.70(21)0.30(9)0.00 (0)0.850.15Chukchi1140.85(97)0.15(17)0.00 (0)0.930.07Tuvinians420.98(41)0.02(1)0.00 (0)0.990.01TBE220.36(8)0.45(10)0.19 (4)0.590.41patients
*Data from two genotypings.


Linkage with additional polymorphisms located in exon 6 has been observed (Table 2).

TABLE 2Linkage disequilibrium of A/G mutations in the intron 5 acceptorsite (hCV2567433) with additional SNPs in exon 6 of the OAS1.hCV2567433rs3177979rs1051042hCV2567429hCV2567429 + 1ntAAAACCAAAGGGGGGGGGGG


The G-allele linked mutations in exon 6 would cause the following amino acids changes: 352A and 361R in p46 and 397G in p48. The A-allele linked mutations in exon 6 would cause the following amino acid changes: 397K/R in p48 and 361R and 429K in p52. Some or all of these additional changes may also be functionally relevant. Data also shows that mutations in other human OAS genes may be relevant in determining viral resistance/susceptibility (Table 3).

TABLE 3Frequencies of genotypes and alleles in OAS2 and OAS3 SNPs.OAS2 SNP rs15895OAS3 SNPs rs2285932GenotypesAllelesGenotypesAllelesPopulationNAAAGGGAGCCCTTTCTAltaians300.000.430.570.130.870.700.300.000.850.15TBE patients180.120.440.440.330.670.330.440.230.560.44


The methods of the present invention comprise the identification of resistant genotypes. By sequencing a human resistance/susceptibility gene, such as the OAS1 gene, specific sequences were identified that were cleaved by a specific restriction endonuclease. A method for identifying the genotype of an individual comprises cleaving a nucleic acid sample from an individual with one or more specific endonucleases that are known to differentiate between viral resistant genotypes. The pattern is observed after separating the cleaved nucleic acid segments by electrophoresis on a gel and used to determine the genotype of the source of the nucleic acid sample.


About 20 ng of human genomic DNA was amplified by PCR for each sample using the HO1-F forward primer (5′ CAGATGGCATGTCACAGTGTCTAC 3′) and the HO1-R reverse primer (5′ CCAGAGCTATGCTTGGCACATAGT 3′) in a total volume of 25 microliters. After amplification, 5 microliters of restriction mix containing 3 microliters of 10× restriction buffer, 10 units of Alu I endonuclease, and 1 microliter of distilled water were added directly to each PCR tube and incubated for 1 hour at 37° C. Restriction reactions were resolved on 2% agarose gels, stained with ethidium bromide and the gels were photographed under UV light. Other visualization or measurement methods are contemplated by the present invention. There are four AluI-recognition sites in the PCR product derived from the G-allele. AluI digestion of this product generates two large restriction fragments of 378 bp and 306 bp as well as three short (invisible) restriction fragments of 46 bp, 12 bp, and 8 bp, respectively. In PCR DNA containing the A-allele, an additional AluI restriction site is present which would divide the 306 bp fragment into a large 255 bp fragment and a short (invisible) 51 bp fragment. Therefore, the AluI restriction pattern of the G-allelic variant contains a unique visible fragment of 306 bp, while that of the A-allelic variant contains a unique visible fragment of 255 bp on the agarose gel (FIG. 9). There are no isoschizomers for AluI. There are currently no additional known restriction enzymes specific for the sequence around the mutation. Additional techniques that could be used for genotyping of this mutation are: 1). Direct sequencing of region containing the mutation; 2). A SNP assay using single nucleotide extension by Real Time PCR; 3). Microchip hybridization. The methods are well known to those skilled in the art.


Compositions of the present invention comprise endonucleases, solutions and buffers necessary for cleaving of DNA samples. Additionally, reference DNA samples of resistant and susceptible genes are included. Preferred compositions are found in kits for testing the genotypes of individuals. Other compositions included in the present invention comprise constructs and vectors comprising the relevant sequences, cell lines derived from individuals that have different alleles, which affect their virus resistance/susceptible phenotype, which could be used for comparing the efficacy of candidate antiviral agents or strategies under different host-virus conditions. Additionally, the present invention comprises compositions comprising cell lines transformed by the relevant sequences comprising the resistant or susceptible variants.


The present invention comprises methods and compositions for determining viral resistance/susceptibility by indentifying the genotype of the human or animal. Alleles of the OAS genes are one set of indentifiable genes that determine viral resistance/susceptibility. Identifying these alleles in a human or animal, either alone or in combination with other genes, determines the resistance/susceptibility to viral infection, particularly flavivirus infection. For example, seven single nucleotide polymorphisms (SNPs) were genotyped within the human locus encoding interferon-inducible double stranded RNA dependent protein kinase (PRKR). Two of these SNPs, rs4648174 and rs2287350, showed complete linkage disequilibrium (always segregated together) in 122 Russian DNA samples tested. However, in 44 DNA samples from TBEV-induced disease patients, the genotype distribution of these two SNPs in 20 patients with febrile disease (fever) differed significantly (χ2=12.4; P=0.002) from that in 24 patients with severe disease (meningitis, encephalitis and/or poliomyelitis). These data suggest that variation in additional innate immune system genes, such as PRKR, could also be associated with the severity of flavivirus-induced disease in humans. The present invention comprises methods and compositions for identifying OAS alleles and other genes for determining the extent of flavivirus infection, severity of viral disease, and susceptible/resistant populations, among other aspects of viral disease.


Methods of the present invention are not limited to the viruses described herein, but include methods for determining the genotype of individuals for a resistant or susceptible response to any virus for which an interferon response is made by the body. Preferred methods comprise determining the genotype of an individual, particularly for OAS alleles, including OAS1, OAS2, OAS3 and OAS-like alleles, using selective endonuclease characterization of the individual's DNA.


Sequences Disclosed Herein:

(SEQ ID 1)LOCUS AF217002 2742 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus calcium channel mRNA, complete cds.ACCESSION AF217002translation=“MAVSLDDDVPLILTLDEAESAPLPPSNSLGQEQLPSKNGGSHSIHNSQVPSLVSGADSPPSSPTGHNWEMNYQEAAIYLQEGQNNDKFFTHPKDARALAAYLFVHNHFFYMMELLTALLLLLLSLCESPAVPVLKLHTYVHATLELFALMVVVFELCMKLRWLGFHTFVRHKRTMVKTSVLVVQFIEAIVVLVRQTSHVRVTRALRCIFLVDCRYCGGVRRNLRQIFQSLPPFMDILLLLLFFMIIFAILGFYLFSTNPSDPYFSTLENSIVNLFVLLTTANFPDVMMPSYSRNPWSCVFFIVYLSIELYFIMNLLLAVVFDTFNDIEKHKFKSLLLHKRTAIQHAYGLLASQRRPAGISYRQFEGLMRFYKPRMSARERFLTFKALNQSNTPLLSLKDFYDIYEVAALQWKAKRNRQHWFDELPRTAFLIFKGINILVNSKAFQYFMYLVVAVNGVWILVETFMLKGGNFTSKHVPWSYLVFLTIYGVELFMKVAGLGPVEYLSSGWNLFDFSVTAFAFLGLLALTLNMEPFYFIVVLRPLQLLRLFKLKKRYRNVLDTMFELLPRMASLGLTLLTFYYSFAIVGMEFFNGRLTPNCCNTSTVADAYRFINHTVGNKTKVEEGYYYLNNFDNILNSFVTLFELTVVNNWYIIMEGVTSQTSHWSRLYFMTFYIVTMVVMTIIVAFILEAFVFRMNYSRKSQDSEVDSGIVIEKEMSKEELMAVLELYREERGTSSDVTRLLDTLSQMEKYQQNSMVFLGRRSRTKSDLSLKMYQEEIQEWYEEHAREQEQQKLRGSVPGPAAQQPPGSRQRSQTVT”BASE COUNT 568a 819c 727g 628tORIGIN1aaggctggcg cagctgccgc tgtggcagcg gtgaggcggc ggtggcggct gctgaggctc61cgcgctgggg atattggcgg cggcaactgc gggctgagct acgctgtgca gacccagtgc121acagtgcggg atcccgggac ggcgcgtacc ttagaagatg cctctgatgg aacaggctct181gggaagcttc cccggccccg tggctttgaa caggagctca agccggaggc agtttaaagc241cctggccgtt gtatcctgag gaccgcaggt caggagaaga tggctgtaag tttagatgac301gatgtgccgc tcatcctgac cttggacgag gctgagagtg ctccgctgcc tccttcgaac361agcctgggcc aagagcagct gcccagcaaa aatgggggca gccacagcat ccacaactcc421caggtcccca gtctggtctc cggagcggac agccccccct ccagtcccac cggacacaac481tgggagatga attatcaaga ggcggcaatc tacctccagg aaggtcagaa caacgacaag541ttcttcaccc accccaagga tgccagagcg ctggcggcct acctcttcgt ccacaaccac601ttcttctaca tgatggagct gctcacggcc ctgctcctgc tgctgctgtc gctgtgcgag661tcccccgctg tccccgtgct caagctgcac acttacgtcc acgccacgct ggaactcttt721gccctcatgg tggtggtatt tgaactctgc atgaaattgc ggtggctggg cttccacacg781ttcgtccggc acaaacgtac catggtcaag acgtccgtcc tcgtggtgca gttcatcgag841gccattgtgg tgctggttcg gcagacgtcc cacgtgcggg tgacccgggc actacgctgc901attttcctgg tggactgtcg ctactgtggc ggtgtacggc gcaacctgcg gcagatcttc961cagtctctcc cacccttcat ggacatcctc ctgttgctgc tcttctttat gatcatcttt1021gccatcctcg gtttctactt attctccaca aatccttccg acccctactt cagcaccctg1081gagaacagca tcgtcaacct gttcgttctc ctgaccacag ccaactttcc agatgtcatg1141atgccctcct actcccggaa cccctggtcc tgcgtcttct tcattgtata cctctccatt1201gagctgtact tcatcatgaa cctgctcctg gccgtggtgt tcgacacctt caacgacatt1261gaaaagcaca agttcaagtc tttgctgctg cacaaacgga ccgccatcca gcatgcctac1321ggcctgcttg ccagccaacg gaggccggct ggcatctcct acaggcagtt cgaaggctta1381atgcgcttct acaagccccg gatgagtgca agggaacgct tcctgacttt caaggccttg1441aaccagagca acacgcctct gctcagcctg aaggacttct atgatattta cgaagtcgct1501gctctgcagt ggaaggcaaa gagaaacaga cagcattggt ttgatgagct cccccggaca1561gccttcctca tcttcaaagg gattaacatc cttgtgaatt ccaaggcctt ccagtatttc1621atgtacttgg tggtggctgt caacggtgtc tggatcctgg tggagacatt catgttgaaa1681ggtgggaatt tcacctcaaa gcatgtgccc tggagttacc tcgtgtttct taccatctat1741ggagttgaac tgttcatgaa ggtggctggc ctgggccctg tggagtacct gtcctctgga1801tggaacctgt tcgatttctc ggtcacggca ttcgccttcc tgggactgct cgcactgacg1861ctcaacatgg aacccttcta tttcattgtg gtcctgcgtc cccttcagct gctgaggtta1921tttaaactga agaaacgcta ccgcaacgtg ttggacacca tgtttgagct gctgccgcgg1981atggccagcc ttggcctcac gctgctcacc ttctactatt ccttcgccat cgtgggcatg2041gagttcttca acgggcggct gacccccaac tgctgcaaca ccagcacagt ggccgacgcc2101taccggttca tcaaccacac tgtgggcaat aagaccaagg tagaggaagg ctactactat2161ctcaacaact ttgacaacat cctcaacagc ttcgtgacct tgtttgagct caccgttgtc2221aacaattggt acatcatcat ggaaggcgtc acctcgcaga cgtcccactg gagccgcctg2281tacttcatga ccttttacat agtgaccatg gtggtgatga ccattatcgt ggccttcatc2341ctggaggcct tcgtcttccg catgaactac agccgcaaga gccaggactc ggaagtggac2401agtggcatcg tcatcgagaa ggaaatgtcc aaggaggagc ttatggccgt cctggagctt2461tatcgtgagg agcgaggcac ctcctctgac gtgacccggc tgctggacac cctctctcag2521atggagaaat accagcaaaa ttccatggtg tttctgggac ggcgatcgag aaccaaaagt2581gacctgagtc tgaagatgta ccaggaggag atccaggagt ggtacgagga gcatgcccgg2641gaacaggagc agcagaagct caggggcagc gtgcccggcc ctgcagccca gcagccccct2701ggcagtcgcc agcgctccca gactgtcacc tagctgggtt tc//(SEQ ID 2)LOCUS AF217003 3569 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus unknown mRNA.ACCESSION AF217003/translation=“MAAPVDGSSGGWAARALRRALALTSLTTLALLASLTGLLLSGPAGALPTLGPGWQRQNPDPPVSRTRSLLLDAASGQLRLEDGFHPDAVAWANLTNAIRETGWAYLDLSTNGRYNDSLQAYAAGVVEASVSEELIYMHWMNTVVNYCGPFEYEVGYCEKLKNFLEANLEWMQREMELNPDSPYWHQVRLTLLQLKGLEDSYEGRLTFPTGRFTIKPLGFLLLQISGDLEDLEPALNKTNTKPSLGSGSCSALIKLLPGGHDLLVAHNTWNSYQNMLRIIKKYRLQFREGPQEEYPLVAGNNLVFSSYPGTIFSGDDFYILGSGLVTLETTIGNKNPALWKYVQPQGCVLEWIRNVVANRLALDGATWADVFKRFNSGTYNSQWMIVDYKAFLPNGPSPGSRVLTILEQIPGMVVVADKTAELYKTTYWASYNIPYFETVFNASGLQALVAQYGDWFSYTKNPRAKIFQRDQSLVEDMDAMVRLMRYNDFLHDPLSLCEACNPKPNAENAISARSDLNPANGSYPFQALHQRAHGGIDVKVTSFTLAKYMSMLAASGPTWDQCPPFQWSKSPFHSMLHMGQPDLWMFSPIRVPWD”BASECOUNT 675a 1133c 945g 816tORIGIN1acctgccctc gcgatggcgg cccccgtgga tgggagctcc ggcggctggg cggcccgggc61gctacggcgg gcactggcgc tgacctccct gaccacactg gccttgctgg cctcgctgac121cgggctgttg ctgagcggcc cggcgggcgc tctccctacc ctggggcccg gctggcagcg181ccaaaatccg gacccgccgg tctcccgcac ccgctcgctg ctgctggacg ccgcgtcggg241ccagctgcgc ctggaggatg gcttccaccc cgacgcggtg gcctgggcca acctcaccaa301cgccatccgc gagaccgggt gggcctatct ggacctgagc acaaatggca ggtacaatga361cagcctgcag gcctatgcag ctggtgtggt ggaggcctct gtgtctgagg agctcatcta421catgcactgg atgaacacgg tggtcaacta ctgcggcccc ttcgaatacg aagtcggcta481ctgtgagaag cttaagaact tcctggaggc caacctggag tggatgcaga gggaaatgga541gcttaacccg gactctccgt actggcacca ggtgcggctg accctcctgc agctgaaagg601cctggaggac agctatgaag gccgtttaac cttcccaact gggaggttca ccatcaaacc661cttggggttc ctcctgctgc agatctctgg agacctggaa gacctagagc cagccctgaa721taagaccaac accaagcctt ccctgggctc cggttcatgc tctgccctca tcaagctgct781gcctggcggg catgacctcc rggtggcgca caacacgtgg aactcctacc agaacatgtt841acgcatcatc aagaagtaca ggctgcagtt ccgggagggg ccgcaagagg agtaccccct901ggttgctggc aacaacttgg ttttctcgtc ctacccgggc accatcttct ccggagatga961cttctacatc ctgggcagtg gcctggtcac cctggagacc accattggca acaagaaccc1021agccctgtgg aagtacgtgc agccccaggg ctgtgtgctg gagtggatac gaaatgtcgt1081ggccaaccgc ctggcctrgg acggggccac ctgggcagac gtcttcaagc ggttcaacag1141cggcacgtac aatagccagt ggatgattgt ggactacaag gcattcctcc ccaacggacc1201cagccctgga agccgggtgc tcactatcct agaacagatc ccgggcatgg tggtggtggc1261tgacaagact gcagagctct acaaaacgac ctactgggct agctacaaca tcccgtactt1321tgagactgta ttcaacgcta gtgggctgca ggccctggtg gcccagtatg gagattggtt1381ctcttacact aagaaccctc gagccaagat cttccagagg gaccagtcac tggtggagga1441catggacgcc atggtccggc tcatgaggta caatgatttc ctccatgacc ctctgtcatt1501gtgtgaagcc tgcaacccaa agcctaatgc ggagaatgcc atctctgccc gctctgacct1561caaccccgcc aatggctcct acccatttca ggccctgcat cagcgcgccc atggtggcat1621tgatgtgaag gtgaccagct ttaccctggc caagtacatg agcatgctgg cggccagtgg1681ccccacgtgg gaccagtgtc ctccgttcca gtggagcaaa tcgccattcc acagcatgct1741gcacatgggc cagcccgacc tctggatgtt ctcacccatc agggtgccat gggactgaga1801gagagtccgc ctccgcctag ctgccttcat tttgtgtggc cagtgggtca tacacctgcc1861gtccacccct cgggcttctg tcttcactag actctggtcc tagcggcttc cttcgcaagg1921acacaaccca gtgggctcag agttgcctct gtccctgagc cctctgcccc ttcatggctc1981atcctccctg tccctgtcac cagcaggctg gggcttatgc ttggctgtgg gcctggtggg2041atccggggca cacattctcc tagtgctggt ccctcagcat atgtgtgaac tgacagggga2101cattatggtt gtcactgctg gcctgtgggc ccatcgcctc agaaggcagc cctgtgccct2161tctgggcagc tcttctaagt gcaggagctt gagaacaaaa ccaaagtttc tggctgcttg2221tagctggagg gccttgagtc ttctttcagc aggaggaatg gaccgtcacc ccacacttct2281acccctactc ccagccaagc ctgcccctgg cctcctggta ggtgtctctg gctgtgtgct2341ccggtcagcg aagcccaggc tgtgcttctg ttaaacaagc cttgtggggc ggcaccacac2401cctgtctgtc catggctgtc tccttccatc tgtcctttct ctagtccacg tacctactgt2461tcacctgcat caccagcccc ctgcccgtcc atcccctctc ctgtccaccc taccgtcttt2521tcactcagtc agcggtccac acacctaccc gtccacttgc ctgccttttc atctgaacgt2581cctcacctct cacccaccca tccacctgcc cgtccgtcag tctgtccacc cagaactgca2641catccctttt cattttggtt ttgctctgta actcagtgtg gccttgaact tgaatgcctt2701gtggtccaca gtcatcctct ggttattgta tctgctggcc gccttcaccc tcacatgctg2761ggtttccatg tacaggccgc cgtgccttga ttctgctttt catcagccca ctcatctctc2821tgtccattta tccctgttag tccttctgct cagcatctgt ctcaagtgct gtattctggg2881tcctagcctg gcccaacctg ctgaccacta agaccctaaa tcctagaccc agagacccac2941atgaaaccaa gtcccctgtg tggggcccag agagctcaca gcctgtgaac cagaggccct3001aagatgtgtg ggtagcttta cccgagccag tccgggcctg ccatgtgttc tgagtttcgt3061tggtagtcag gggttggttt cctgtcaggt tcactccacc ttccctgctc tgcagatgcc3121tgcacggggt tggttttcca gacaccaggg tggggccgct ggtgtctcag gatggccttg3181tcctgtccct aaggacttca tattagcatg tggtggcctt gcctgtgcat ctcccagctg3241ctttgtgacc ccaccctaga tccctgtgtg gcttagctct ggtcctctct cctgacttac3301ggatgtgtgg gttccaccag tcaatccact gggagaccca agaccccaga ggggagcacc3361actcctttga gagccaggga cgatgtggct gggtgtaaag ggagactgaa caaggcaagg3421aagctaacgc ctgtctgccc ggcactcaga agatgaggca ggaggatctc cagtttgaga3481ccagcctggg ctgcacatag accctcatgt caagaacaaa caaagctcaa aagatctttg3541ctctataaat atatatttat tttttattt//(SEQ ID 3)LOCUS AF261233 2868 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus sodium/calcium exchanger protein mRNA, complete cds.ACCESSION AF261233/translation=“MASRWLALLWAPVFLCVALLLETASGTGDPSTKAHGHIQFSAGSVNQTAMADCRAVCGLNTSDRCDFVRRNPDCRSEAGYLDYLEGIFCYFPPNLLPLAITLYVFWLLYLFLILGVTAAKFFCPNLSAISTNLKLSHNVAGVTFLAFGNGAPDIFSALVAFSDPRTAGLAIGALFGAGVLVTTVVAGGITILHPFMAASRPFLRDIAFYMVAVFLTFTALYLGRITLAWALGYLGLYVFYVVTVIICTWVYQRQRSRSLVHSISETPELLSESEEDQMSSNTNSYDYGDEYRPLLLGQETTVQILIQALNPLDYRKWRTQSISWRVLKVVKLPVEFLLLLTVPVVDPDKDDRNWKRPLNCLQLVISPLVLVLTLQSGVYGLYEIGGLLPVWAVVVIVGTALASVTFFATSNREPPRLHWLFAFLGFLTSALWINAAATEVVNILRSLGVILRLSNTVLGLTLLAWGNSIGDAFSDFTLARQGYPRMAFSACFGGIIFNILVGVGLGCLLQIIRNHVVEVKLEPDGLLVWVLASALGLSLIFSLVSVPLQCFQLSKAYGLCLLLFYVCFLVVVLLTEFGVIHLKKA”BASE COUNT 505a 800c 829g 734tORIGIN1ctccgggcca ggactctagg ggcggaaggt tgtggcgctg gccatccggc tagaggaaga61ctccgaggtc gcggatccag gccccgcccg aggcactaga gcagccagcc cgtgagcaga121gagggctctg gtcaggcctc aaggggccca tggcaagcag atggctggct ctgctctggg181ctcctgtctt cctctgtgtg gctctgttac tggagacggc gtctgggacc ggagacccat241ccacaaaagc ccatggacac atccagtttt cagctggaag tgtcaaccag actgccatgg301cggattgccg agccgtgtgt ggcctgaaca catctgatcg ctgtgacttt gtcaggagga361atccggactg ccgcagcgag gcgggctacc tggactacct tgagggcatc ttctgctact421tcccccccaa cctcctccct ctggccatca ccctctacgt tttctggctg ctttacctct481ttctgatcct gggagtcacc gcggccaagt tcttctgccc taacctgtca gccatctcca541ctaacctcaa actctcccac aacgtggcag gtgtcacctt cctggccttt ggaaatggcg601ctccagacat cttcagtgct ttagtggctt tcrcagaccc acgtactgcc ggcctggcca661tcggggctct gtttggtgca ggggtgctgg tcaccactgt ggtggctgga ggcatcacca721tcctgcatcc cttcatggct gcctccaggc ccttcctcag ggacatcgct ttctacatgg781tggctgtgtt cctaaccttc actgcactct atcttggcag gatcacgctg gcgtgggcgc841tgggttacct gggcctctac gtgttctacg tggtcacggt catcatctgc acttgggtct901accaacggca gcgaagcagg tctctggtcc actccatatc ggagacacca gagttgctgt961ctgagtcaga ggaggaccag atgtcttcca acaccaacag ctatgactat ggagatgagt1021accggcctct gttgctgggt caggagacca ctgtccagat cctgatccaa gccctgaatc1081ccttggacta caggaagtgg agaactcagt cgatatcctg gagggtcctg aaggtagtca1141agttacctgt ggagttcttg ttgctgctca cagtaccggt tgtggaccct gacaaggacg1201atcggaattg gaaacggcca ctcaactgtc tgcagctggt catcagcccc ctggtcctgg1261tcctgaccct gcagtcgggg gtctatggcc tctatgagat tggcggtctc cttcctgtct1321gggctgtggt ggtgatcgtg ggcacagcgc tggcttcagt gaccttcttt gccacgtcta1381acagagaacc ccctagactg cactggctct ttgctttcct gggtttcctg accagtgccc1441tgtggatcaa tgcagccgcc acagaggtgg tgaacatctt acggtccctg ggtgtgatcc1501tccgcctgag caacaccgtc ctagggctga ccctcctggc ctggggaaac agcattggag1561atgccttctc agatttcacg ctggcccgcc aaggataccc tcggatggcc ttctccgcct1621gtttcggggg catcatcttc aacatcctgg ttggtgtggg gctgggctgc ttgctgcaga1681tcatcaggaa ccacgttgtg gaggtgaagc tggagccaga cggattactg gtgtgggtgc1741tggccagtgc cctgggcctc agcttgatct tctccctggt ctccgtgccg cttcagtgtt1801tccagctcag caaggcttac ggcctctgcc tcctcctctt ctacgtctgt ttccttgttg1861tggtcctgct cacagagttt ggggtgattc acctgaagaa ggcgtgactg aagctgcttg1921gcctagaggt gtgggggcga ttctgctagc ctcctgaggg ggaggtgtgg ggagggggac1981cctctgtggt ccccgtggat ctcctgagaa gatagtcact ggcagagctc tgcagggtga2041gaaggtcctg actgccggca cctaacagcc ttagtgtggg gatctggagg ctggctttgc2101tggggacaat cccgggtagg aatgatggga tctaaatgac accggaggct ctggggggag2161ggcagccttt cagtcagccc ccatgcctgc tgggctctgg gcagccctgc agttccctct2221ctggctcttc cactctctgt ggggtcctgc gtacctacag ggtggcctga aaacagactc2281cacacgtgga aacaagactg ggtttctcag cttccgtgtc aagtcagcca gaggaaagag2341gtcgagttga cagcagcagg cactgccctt cctagttggt ggctgccatg ttggactgtg2401gatctaaaac acttctagag ctttgtggtc caaactctgg ctctcccgtc tgcaaaacag2461gagccagcat gggctctgtg cctacctcaa ggggagctgg gggttggggg gactgaccct2521ccccagggag gtcttacaag tagtgtgacc agtcttttgt ttgtttggtt ggttggttgt2581tttttggaga cagggtttct ctgtgtagcc ctggctgtcc tggaactcac tctgtagacc2641aggctggcct tgaactcaga aatctgcctg cctttgcctc ccaagtgctg ggactaaagg2701tgtgtgccac cactgtccag cttgtgacca gccttttaaa agtgccactc actccctgac2761tgccttcagc tgtaattaag agacttgact gttggggttt ttttttgttt gtttgttttt2821tgtttttgtt ttttgttgtt tccaaaaata aaagatgagt tatttcac//(SEQ ID 4)LOCUS AF319547 3324 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus ATP-dependent RNA-helicase (Ddx) mRNA,Ddx-RV allele, complete cds.ACCESSION AF319547/translation=“MAAGRRVGPGPPSRPTMAPWKKKRLRKRRTGASQGRDSDSDDGEFEIQAEDDARARKLGPGRALPSFPTSECVSDVEPDTREMVRAQNKKKKKSGGFQSMGLSYPVFKGIMKKGYKVPTPIQRKTIPVILDGKDVVAMARTGSGKTACFLLPMFERLKARSAQTGARALILSPTRELALQTMKFTKELGKFTGLKTALILGGDKMEDQFAALHENPDIIIATPGRLVHVAVEMNLKLQSVEYVVFDEADRLFEMGFAEQLQEIIGRLPGGHQTVLFSATLPKLLVEFARAGLTEPVLIRLDVDSKLNEQLKTSFLLVREDTKAAVLLYLLQNVVRPQDQTVVFVATKHHAEYLTELLMGQGVSCAHIYSALDQTARKINLAKFTHNKCSTLIVTDLAARGLDIPLLDNVINYSFPAKGKLFLHRVGRVARAGRSGTAYSLVAPDEVPYLLDLHLFLGRSVTLARPCEEPSVADAVGRDGVLGRVPQSVVDDEDSSLQTAMGASLDLQGLHRVANNAQQQYVRSRPAPSPESIKRAKELDLAELGLHPLFSSCFEEGELQRLRLVDSIKNYRTRTTIFEINASSKDPSSQMMRAKRQRDRKAVASFQQRRQERQEGPADPAPQRELPQEEEEEMVETVEGVFTEVVGQKRPRPGPSQGAKRRRMETRQRDQEFYVPYRPKDFDSERGLSVSGAGGAFEQQVAGAVLDLMGDEAQNMSRGQQQLKWDRKKKRFVGQSGQEDKKKIKTESGRFISSSYKRDLYQKWKQKQKIDDRDSEEEGPSNQRGPGPRRGGKRGRSQGTSQPRASSVPAGRMRSELKTKEQILKQRRQAQKQRFLQRGGLKQLSARNRRRAQELRQGAFGRGAPSRKGKMRKRM”polyA signal 3303 . . . 3308/gene=“Ddx”BASE COUNT 725a 973c 1023g 603tORIGIN1agttaccaca tctctcacag cttggcattc gcgcagttag taggtccctt aagcatctat61cacggttcag ttgacacatt ccgcccccac cagttggtat gtccctcagg cctcgcctct121gcccggctgg tacaccactt aggccccgcc cccgttctgt tggttcctcc ttctggcttc181gcccattgat aaagccatgt tgacgctccg cccctgcgaa gttggttggt ttcctcaggc241ccggccccgc cctacgggtg aaacctggat tctcgacgcc gctcttgcgt ctcacaggct301ccgcccccgc gcagtcgacg cgtcccttag gccccgccct cttccgggtc taagagcccg361gcccgcatgg ctgctggcag acgtgtggga cctggcccgc cgtcgcgtcc caccatggcg421ccgtggaaga agaagaggct gcggaaacgc cgaactgggg cttcccaagg ccgcgacagc481gactcggatg acggcgagtt cgagatccag gcggaggatg acgcccgggc gaggaagctg541ggccctggca gagccttgcc ctcatttcct acctcagagt gcgtatcaga tgtggagccc601gacactcggg agatggtgcg agcccagaac aagaaaaaga agaagtctgg aggcttccag661tccatgggcc tgagttaccc tgtgttcaag gggatcatga aaaagggcta caaggtgccg721acgcccatcc agaggaagac catccccgtg atcttggatg gcaaggatgt ggtggccatg781gcccggacag gcagtggcaa gacggcctgc ttcctcctcc cgatgtttga gcggctgaag841gcacgcagtg cacagacggg ggctcgagcc ctcatcctct cacccacccg ggagctggcc901ctgcagacca tgaagttcac taaagagcta ggcaagttca ccggcctcaa gactgccttg961atcctgggtg gagacaaaat ggaagaccag tttgcagccc tgcacgagaa ccctgacata1021atcattgcca cccctgggcg tctggtgcat gtggctgtgg agatgaactt gaagctgcag1081agtgtggagt atgtggtgtt cgatgaagca gacaggctct ttgaaatggg ctttgctgag1141cagctacagg agatcatagg ccgccttcct gggggccacc agacggtgct gttctcagct1201acactgccca agctgctggt ggaatttgca cgggcaggcc tcacagagcc cgtgctcatc1261cgcctggacg tagactccaa gctcaatgag cagctcaaga cctccttcct ccttgtgcgc1321gaagacacca aggctgccgt gctcctctac ctgctgcaga atgtcgttcg gccccaggac1381cagactgtgg tgtttgtagc cacaaagcac catgcggagt acctcacaga gttgctgatg1441ggccagggtg tgagttgcgc ccacatctat agtgccttgg accagacggc ccgcaagatc1501aacttggcca agttcacaca caacaaatgt tccaccctca tcgtgactga cctggccgcc1561cggggcctgg acatcccact gctggacaac gtcatcaact acagcttccc tgccaagggc1621aagctcttcc tgcaccgagt gggccgtgtg gcccgagcag gccgaagtgg cacagcctat1681tctttggtgg ccccagacga ggtcccctac ctgcttgacc tacacctgtt cctgggccgc1741tctgtcaccc tggcccgtcc ttgtgaggag ccttcagtgg cagatgcggt tggcagggac1801ggagtgctgg gtcgcgtgcc ccagagtgta gtggatgatg aggacagcag cctgcagact1861gccatggggg catccctgga tcttcagggc ctgcaccgcg tggccaacaa cgctcagcag1921cagtatgtgc gctcacggcc agcgccctcg cctgagtcca tcaagagagc caaggagctg1981gacctggcag agctgggctt gcacccactc ttcagctcat gctttgagga gggagagctc2041caacgcctga ggctggtgga cagcatcaag aactatcgca cgcgcacaac catctttgag2101atcaatgcct ccagcaagga cccaagcagc caaatgatgc gtgccaagcg gcagagggac2161cggaaagctg ttgccagttt ccagcagcgg cgccaggaaa ggcaggaagg cccagctgac2221ccagcccccc agagggagct gcctcaggag gaggaggagg agatggttga gactgtagag2281ggtgtcttca cagaagtcgt gggccagaaa cggccaaggc cgggacccag ccaaggagcc2341aagaggcgga ggatggagac ccgtcagcga gaccaggagt tttatgtccc ctaccggccc2401aaggatttcg acagtgagcg ggggctgagt gtcagtgggg ctggaggggc ctttgagcag2461caggtggctg gtgcagtcct ggacctgatg ggggatgaag cacagaacat gagccggggg2521cagcagcagc tcaagtggga ccggaagaag aagcggtttg tggggcagtc aggccaagaa2581gacaagaaaa agatcaagac agagagcggc cggtttatca gcagctctta caagcgggat2641ctctaccaga agtggaagca gaagcagaaa attgatgacc gggactccga ggaagaaggg2701ccatccaacc agcgaggccc tgggccccgc agaggtggaa agcgaggtcg tagtcaaggc2761acatcccagc cccgagcttc cagtgtaccc gcaggccgca tgcgctcgga actcaagacc2821aaggagcaaa tcctcaagca gcgccggcaa gctcagaagc agcgcttcct gcagcgaggg2881ggcctgaagc agctttcagc acgcaaccga cgccgagccc aggagctgcg ccagggcgcc2941tttggccggg gtgctccctc caggaagggc aagatgagga aaaggatgtg aggagccaga3001cgcagccctg gggcttcctg gtagccccgg gtgtggacgt cagggactat gtccatgtgc3061tgttggaaga tccttccaca ggcgctgctc tgtgaggagt agtgccatat ggccacagag3121caacagctgc ttttgactgg gacattgggt gacctctgaa aggatgcata ggagtctagc3181tatgcaaagc aggcagaccc aagtcctgac cctgcaagtc acagcggctt ctggttccac3241accttcagga ttcagagtca gggccgtgtg gatgcctctg acccagcatt gagttttaat3301gtaataaact ttactgcctc tagt//(SEQ ID 5)LOCUS AF328926 1858 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ oligoadenylate synthetase1B (Oas1b) mRNA, complete cds.ACCESSION AF328926/translation=“MEQDLRSIPASKLDKFIENHLPDTSFCADLREVIDALCALLKDRSFRGPVRRMRASKGVKGKGTTLKGRSDADLVVFLNNLTSFEDQLNQQGVLIKEIKKQLCEVQHERRCGVKFEVHSLRSPNSRALSFKLSAPDLLKEVKFDVLPAYDLLDHLNILKKPNQQFYANLISGRTPPGKEGKLSICFMGLRKYFLNCRPTKLKRLIRLVTHWYQLCKEKLGDPLPPQYALELLTVYAWEYGSRVTKFNTAQGFRTVLELVTKYKQLRIYWTVYYDFRHQEVSEYLHQQLKKDRPVILDPADPTRNIAGLNPKDWRRLAGEAATWLQYPCFKYRDGSPVCSWEVPTEVGVPMKYLFCRIFWLLFWSLFHFIFGKTSSG”BASE COUNT 430a 475c 501g 452tORIGIN1ctgcttcagc gagcctagga gacacaggac ctgctggctg cagaggtatt agctggacct61aggatggagc aggatctgag gagcatcccg gcctcgaagc ttgataagtt catagagaac121catctcccgg acaccagctt ctgtgctgac ctcagagaag tcatagatgc cctgtgtgct181ctcctgaagg acagatcctt ccggggcccc gtccgccgaa tgagggcctc taaaggggtc241aagggcaaag gcaccacact caagggcagg tcagacgctg acctggtggt gttccttaac301aatctcacca gctttgagga tcagttaaac caacagggag tgttgattaa ggaaattaag361aaacagctgt gcgaggttca gcatgagaga cgttgtggag tgaagtttga ggtccacagt421ttaaggagtc ccaactcccg ggctctgagc ttcaagctga gcgcccccga cctgctgaag481gaggtgaagt ttgatgtgct gccagcctat gatttactgg atcatcttaa catcctcaag541aagcctaacc aacaattcta cgccaatctc atcagtgggc gtaccccgcc ggggaaggag601ggcaagttat cgatctgctt tatggggctt cggaagtact tcctgaactg tcgcccaacc661aagctgaagc gcctcatccg cctggtcacg cactggtacc aactgtgtaa ggagaagctg721ggggacccgc tgcccccaca gtatgccctg gagctgctca cagtctatgc ctgggagtat781gggagtcgag taactaaatt caacacagcc cagggcttcc gaaccgtctt ggaactggtc841accaagtaca aacagcttcg aatctactgg acagtgtatt atgactttcg acatcaagag901gtctctgaat acctgcacca acagctcaaa aaagacaggc ctgtgatctt ggaccccgct961gacccaacaa ggaacatagc tggtttgaac ccaaaggact ggcggcgtct agcaggagag1021gctgccacct ggctgcaata cccatgcttt aagtacaggg acggttcccc agtgtgctcc1081tgggaggtgc cgacggaggt tggagtgcca atgaagtatc tcttttgtcg tattttctgg1141ttattgtttt ggtctttgtt tcatttcatc tttgggaaga cttcatctgg atagcccaga1201gtgtcttgga tattgccatc ctcctgcctt agcgctggca tgactgcagc gtaggcctgt1261tatgctctgc ctcccctcca tcctcaagtg gacaagaact gggcatgtgt tttcctgtga1321gcccagtggg acctgtccag gaggctccag agtcaggggc atgtcctgct ctgctacagg1381gccttgaccc agagaagaca ggaaggtgcc caaagcccaa gagagggagg gtccaacctg1441tgatcagact ccaggcttct gtcccctgtc ctcaacccct gcacagacag cctttctcac1501agcatgcttt atctgtcttg tcccccaaca gtgttctctg ggagacaaga gattcagaag1561gagaatatga tggtttgtat atggttggcc cagggaatgg cactgttagg agatgtggcc1621atgttggaat gggtgtggcc ttgtgggtgt gggctttctc ttgtcttagc tgcctggaag1681tcagtatgct gctagcagcc ttcaaatgaa gatgtagaac tctcagctcc tcctgcacca1741tgcctgcctg gacgttgcca tgctcttgcc ttggtgataa tggactgaac ttctgaacct1801gtaagccaac cccaattaaa tgttgttttt ataaaaattg ccttggtcat ggtgtctg//(SEQ ID 6)LOCUS AF328927 1482 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus serine dehydratase (Sds) mRNA, complete cds.ACCESSION AF328927/translation=“MEGALAERVGAEPFHRVTPLLESWALSQVAGMPVFLKYENVQIAGSFKIRGIGHFCQQMAKRGCRHLVCSSGGNAGIAAAYSARKLGIPVTIVLPEGTSVQVVRRLEGEGAEVQLTGKVWDEANVKAQELATRDGWVNVSPFDHPLIWEGHASLVRELKESLGTPPGAVVLAVGGGGLLAGVTAGLLEVGWQHVPIVAMETRGAHSFNSALQAGRPVTLPDITSVAKSLGAKTVAARTLECAKECEVLSEVVEDREAVSAVQRFLDDERMLVEPACGAALAAIYSGILWRLQAEGRLSSALASVVVIVCGGNNISSQQLQELKTSWAALKISGTPPKFLDTWWVIKGPRFQWSCPLPSR”polyA signal 1451 . . . 1456/gene=“Sds”BASE COUNT 296a 396c 487g 303tORIGIN1gaagaccttg acagaaaacc tcacacccca agggcacatg cagaagaggc cttcctgatt61ctgtctcacg tggcttcgtt cttagatgag cccaggtcgt tcatgagcca tgagctgcgt121aaggaagaca gagaggattg aataccccca cgggttcatc ttggtcattt tttgttgtga181gttctcacca ggaccccaga atcaggagct gtccctttaa caaggaggag gggccaggcc241ctggtagccg gaagctgatc tggtagccag tgcgtccagg ttggtcctgg ctgggctgtc301cttcaggaag gtggtcagcg cgctgctgga atggaggggg ccttggcaga acgcgtcggg361gcggagcctt tccacagggt cacgcccctg ctggagagct gggcgctgtc tcaggtggca421ggcatgccgg tcttcctcaa atatgagaat gtgcagatag ctggctcctt taagattcgg481ggcatcggac atttctgcca gcagatggcc aagaggggat gcagacatct ggtgtgctcc541tcagggggca atgcgggcat tgcggctgca tactcggctc gtaagctggg catccccgtc601accatcgtgc tcccagaggg cacctccgtg caggtggtga ggcggctcga gggggaaggg661gccgaggtcc agctgactgg gaaagtctgg gatgaagcca atgtaaaagc acaagaactg721gccacaaggg atggctgggt gaacgtctcc ccgtttgacc atccccttat atgggaaggc781catgccagcc tagtgcggga gctgaaggag tcactaggga cccctccagg tgccgtggtg841ctggccgtgg ggggcggagg gctcctggca ggtgtgactg ctggcctgct ggaggtgggc901tggcagcatg tgcccatcgt tgccatggag acccgcgggg cgcacagttt caattcggcc961ttgcaggcag gcaggccggt caccctgcca gacatcacca gtgtagccaa gagcctcgga1021gccaagacgg tggctgcacg gaccttggag tgtgcaaagg agtgtgaggt cctctctgag1081gtggtagaag accgggaggc tgtcagcgct gtgcagaggt tcctggacga tgagcgcatg1141ctggtggaac ctgcctgcgg tgccgccctg gccgccatct actcgggcat cctgtggagg1201cttcaggctg agggccgcct gagttctgcc ctagcttccg ttgtggtcat cgtgtgcggt1261ggcaacaaca ttagtagcca acagcttcag gagctgaaaa ccagctgggc tgcattgaaa1321atctcaggaa ctcccccaaa gttcctggac acctggtggg tcatcaaggg acctcggttc1381cagtggtcct gccctcttcc ttccaggtag ccctcctggg ttgctctcag tggctccctg1441ctgtccagtg aataaacctg actgagctga aaaaaaaaaa aa//(SEQ ID 7)LOCUS AF418004 1837 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus C3H/He 2′-5′ oligoadenylate synthetase1B (Oas1b) mRNA, complete cds.ACCESSION AF418004/translation=“MEQDLRSIPASKLDKFIENHLPDTSFCADLREVIDALCALLKDRSFRGPVRRMRASKGVKGKGTALKGRSDADLVVFLNNLTSFEDQLNQQGVLIKEIKKQLCEVQHERRCGVKFEVHSLRSPNSRALSFKLSAPDLLKEVKFDVLPAYDLLDHLNILKKPNQQFYANLISGRTPPGKEGKLSICFMGLQKYFLNCRPTKLKRLIRLVTHWYQLCKEKLGDPLPPQYALELLTVYAWEYGSRVTKFNTAQGF”BASE COUNT 428a 476c 491g 442tORIGIN1ctgcttcagc cagcctagga gacacaggac ctgctggctg cagaggtaaa agctggacct61aggatggagc aggatctgag gagcatcccg gcctcgaagc ttgataagtt catagagaac121catctcccgg acaccagctt ctgtgctgac ctcagagaag tcatagatgc cctgtgtgct181ctcctgaagg acagatcctt ccggggcccc gtccgccgaa tgagggcctc taaaggggtc241aagggcaaag gcaccgcgct caagggcagg tcagacgctg acctggtggt gttccttaac301aatctcacca gctttgagga tcagttaaac caacagggag tgttgattaa ggaaattaag361aaacagctgt gcgaggttca gcatgagaga cgttgtggag tgaagtttga ggtccacagt421ttaaggagtc ccaactcccg ggctctgagc ttcaagctga gcgcccccga cctgctgaag481gaggtgaagt ttgatgtgct gccagcctat gatttactgg atcatcttaa catcctcaag541aagcctaacc aacaattcta cgccaatctc atcagtgggc gtaccccgcc ggggaaggag601ggcaagttat cgatctgctt tatggggctt cagaagtact tcctgaactg tcgcccaacc661aagctgaagc gcctcatccg cctggtcacg cactggtacc aactgtgtaa ggagaagctg721ggggacccgc tgcccccaca gtatgccctg gagctgctca cagtctatgc ctgggagtat781gggagtcgag taactaaatt caacacagcc cagggcttct gaaccgtctt ggaactggtc841accaagtaca aacagcttca aatctactgg acagtgtatt atgactttcg acatcaagag901gtctctgaat acctgcacca acagctcaaa aaagacaggc ctgtgatctt ggaccccact961gacccaacaa ggaacatagc cggtttgaac ccaaaggact ggaggcgtct agcaggagag1021gctgccgcct ggctgcaata cccatgcttt aagtacaggg acggttcctc agtgtgctcc1081tgggaggtgc cgacggaggt tgcagtgcca acgaagtatc tcttttgtcg tattttctgg1141ttattgtttt ggtctttgtt tcatttcatc tttgggaaga cttcatctgg atagcccaga1201gtgtcttgga tattgccatc ctcctgcctt agcgctggca tgactgcagc gtaggcctgt1261tatgccctgc ctcccttcca tcctcaagtg gacaagaact gggcatgtgt tttcctgtga1321gcccagtggg acctgtccag gatgctccag agtcagacgc atgtcctgct ctgctgcagg1381gccttgaccc agagaagaca ggaaggtgcc caaagcccaa gagagggagg gtccaacctg1441tgatcagact ccaggcttct gtcccctgcc ctcaacccct gcacagacag cctttctcac1501agcctgcttt atctgccttg tcccccaaca gtgttctctg ggagacaaga gattcagaag1561gagaatatta tggtttgtat atggttggcc cagggaatgg cactgttagg aggtgtggcc1621atgttggagt gggtgtggcc ttgtgggtgt gggctttctc ttgtcttagc tgcctggaag1681tcagtattct gctagcagcc ttcagatgaa gatgtagaac tctcagctcc tcctgcacca1741tgcctgcctg gacgttgcca tgctcttgcc ttggttataa tggactgaac gtctgaacct1801gtaagccaac cccaattaaa tgttgttttt ataaaaa//(SEQ ID 8)LOCUS AF418005 1837 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus BRVR 2′-5′ oligoadenylate synthetase1B (Oas1b) mRNA, complete cds.ACCESSION AF418005/translation=“MEQDLRSIPASKLDKFIENHLPDTSFCADLREVIDALCALLKDRSFRGPVRRMRASKGVKGKGTTLKGRSDADLVVFLNNLTSFEDQLNQQGVLIKEIKKQLCEVQHERRCGVKFEVHSLRSPNSRALSFKLSAPDLLKEVKFDVLPAYDLLDHLNILKKPNQQFYANLISGRTPPGKEGKLSICFMGLRKYFLNCRPTKLKRLIRLVTHWYQLCKEKLGDPLPPQYALELLTVYAWEYGSRVTKFNTAQGFRTVLELVTKYKQLRIYWTVYYDFRHQEVSEYLHQQLKKDRPVILDPADPTRNIAGLNPKDWRRLAGEAATWLQYPCFKYRDGSPVCSWEVPTEVGVPMKYLFCRIFWLLFWSLFHFIFGKTSSG”BASE COUNT 431a 472c 493g 441tORIGIN1ctgcttcagc cagcctagga gacacaggac ctgctggctg cagaggtaaa agctggacct61aggatggagc aggatctgag gagcatcccg gcctcgaagc ttgataagtt catagagaac121catctcccgg acaccagctt ctgtgctgac ctcagagaag tcatagatgc cctgtgtgct181ctcctgaagg acagatcctt ccggggcccc gtccgccgaa tgagggcctc taaaggggtc241aagggcaaag gcaccacact caagggcagg tcagacgctg acctggtggt gttccttaac301aatctcacca gctttgagga tcagttaaac caacagggag tgttgattaa ggaaattaag361aaacagctgt gcgaggttca gcatgagaga cgttgtggag tgaagtttga ggtccacagt421ttaaggagtc ccaactcccg ggctctgagc ttcaagctga gcgcccccga cctgctgaag481gaggtgaagt ttgatgtgct gccagcctat gatttactgg atcatcttaa catcctcaag541aagcctaacc aacaattcta cgccaatctc atcagtgggc gtaccccgcc ggggaaggag601ggcaagttat cgatctgctt tatggggctt cggaagtact tcctgaactg tcgcccaacc661aagctgaagc gcctcatccg cctggtcacg cactggtacc aactgtgtaa ggagaagctg721ggggacccgc tgcccccaca gtatgccctg gagctgctca cagtctatgc ctgggagtat781gggagtcgag taactaaatt caacacagcc cagggcttcc gaaccgtctt ggaactggtc841accaagtaca aacagcttcg aatctactgg acagtgtatt atgactttcg acatcaagag901gtctctgaat acctgcacca acagctcaaa aaagacaggc ctgtgatctt ggaccccgct961gacccaacaa ggaacatagc tggtttgaac ccaaaggact ggcggcgtct ageaggagag1021gctgccacct ggctgcaata cccatgcttt aagtacaggg acggttcccc agtgtgctcc1081tgggaggtgc cgacggaggt tggagtgcca atgaagtatc tcttttgtcg tattttctgg1141ttattgtttt ggtctttgtt tcatttcatc tttgggaaga cttcatctgg atagcccaga1201gtgtcttgga tattgccatc ctcctgcctt agcgctggca tgactgcagc gtaggcctgt1261tatgctctgc ctcccctcca tcctcaagtg gacaagaact gggcatgtgt tttcctgtga1321gcccagtggg acctgtccag gaggctccag agtcaggggc atgtcctgct ctgctacagg1381gccttgaccc agagaagaca ggaaggtgcc caaagcccaa gagagggagg gtccaacctg1441tgatcagact ccaggcttct gtcccctgtc ctcaacccct gcacagacag cctttctcac1501agcatgcttt atctgtcttg tcccccaaca gtgttctctg ggagacaaga gattcagaag1561gagaatatga tggtttgtat atggttggcc cagggaatgg cactgttagg agatgtggcc1621atgttggaat gggtgtggcc ttgtgggtgt gggctttctc ttgtcttagc tgcctggaag1681tcagtatgct gctagcagcc ttcaaatgaa gatgtagaac tctcagctcc tcctgcacca1741tgcctgcctg gacgttgcca tgctcttgcc ttggtgataa tggactgaac ttctgaacct1801gtaagccaac cccaattaaa tgttgttttt ataaaaa//(SEQ ID 9)LOCUS AF418006 1837 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus MOLD/Rk 2′-5′ oligoadenylate synthetase1B (Oas1b) mRNA, complete cds.ACCESSION AF418006translation=“MEQDLRSIPASKLDKFIENHLPDTSLCADLREVIDALCALLKDRFFRGPVRRMRASKGVKGKCTALKGRSDADLVVFLNNLTYFEDQLNQQGVLIKEIKKQLYEVQHERRFGVKFEVQSLRSPNSRALSFKLSAPDLLKEVKFDVLPAYDLLDHLNILKKPNQQFYANLISGRTPLGKEGKLLTCFMGLRKYFLNCRPTKLKRLIRLVTHWYQLCKEKLGDPLPPQYALELLTVYAWEYGSRVTKFNTAQGFRTVLELVTKYKQLRIYWTVYYDFRHQEVSEYLHQQLKKDRPVILDPADPTRNIAGLNPKDWRRLAGEAAAWLQYPCFKYRDCSPVCSWEVPTEVAVPTKYLFCRIFWLLFWSLFHFIFGKTSSG”BASE COUNT 425a 470c 491g 451tORIGIN1ctgcttcagc cagcctagga gacacaggac ctgctggctg cagaggtaaa agctggacct61aggatggagc aggatctgag gagcatcccg gcctcgaagc ttgataagtt catagagaat121catctcccgg acaccagctt gtgtgctgac ctcagagaag tcatagatgc cctgtgtgct181ctcctgaagg acagattctt ccggggcccc gtccgccgaa tgagggcctc taagggggtc241aagggcaaat gcaccgcgct caagggcagg tcagacgctg acctggtggt gttccttaac301aatctcacct actttgagga tcaattaaac caacagggag tgttgattaa ggaaattaag361aaacagctgt acgaggttca gcatgagaga cgttttggag tcaagtttga ggtccagagt421ttaaggagtc ccaactcccg ggctctgagc ttcaagctga gcgcccccga cctgctgaag481gaggtgaagt ttgacgtgct gccagcctat gatttactgg atcatcttaa catcctcaag541aagcctaacc aacaattcta cgccaatctc atcagtgggc gtaccccgct ggggaaggag601ggcaagttat tgacctgctt tatggggctt cggaagtact tcctgaactg tcgcccaacc661aagctgaagc gcctcatccg cctggtcacg cactggtacc aactgtgtaa ggagaagctg721ggggacccgc tgcccccaca gtatgccctg gagctgctca cagtctatgc ctgggagtat781gggagtcgag taactaaatt caacacagcc cagggcttcc gaaccgtctt ggaactggtt841accaagtaca aacagcttcg aatctactgg acagtgtatt atgactttcg acatcaagag901gtctctgaat acctgcacca acagctcaaa aaagacaggc ctgtgatctt ggaccccgct961gatccaacaa ggaatatagc tggtttgaac ccaaaggact ggcggcgtct agcaggagag1021gctgccgcct ggctgcaata cccatgcttt aagtacaggg acggttcccc agtgtgctcc1081tgggaggtgc cgacggaggt tgcagtgcca acgaagtatc tcttttgtcg tattttctgg1141ttattgtttt ggtctttgtt tcatttcatc tttgggaaga cttcatctgg atagcccaga1201gtgtcttgga tattgccatc ctcctgcctt agcgctggca tgactgcagt gtaggcctgt1261tatgccctgc ctcccctcca tcctcaagtg gacaagaact gggcatgtgt tttcctgtga1321gcccagtggg acctgtccag gatgctccag agtcagacgc atgtcctgct ctgctgcagg1381gccttgaccc agagaagaca ggaaggtgcc caaagcccaa gagagggagg ttccaacctg1441tgatcagact ccaggcttct gtcccctgcc ctcaacccct gcacagacag cctttctcac1501agcctgcttt atctgtcttg tcccccaaca gtgttctctg ggagacaaga gattcagaag1561gagaatatga tggtttgtat atggttggcc cagggaatgg cactgttagg aggtgtggcc1621atgttggagt gggtgtggcc ttgtgtgtgt gggctttctc ttgtcttagc tgcctggaag1681tcagtatgct gctagcagcc ttcagatgaa gatgtagaac tctcagctcc tcctgcacca1741tgcctgcctg gacgttgcca tgctcttgcc ttggtgataa tggactgaac ttctgaacct1801gtaagccaac tccaattaaa tgttgttttt ataaaaa//(SEQ ID 10)LOCUS AF418007 1587 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus MOLC/Rk 2′-5′ oligoadenylate synthetase1B (Oas1b) mRNA, complete cds.ACCESSION AF418007/translation=“MEQDLRSIPASKLDKFIENHLPDTSFCADLREVIDALCALLKDRFFRGPVRRMRASKGVKGKCTALKGRSDADLVVFLNNLTYFEDQLNQQGVLIKEIKKQLYEVQHERRFGVKFEVQSLRSPNSRALSFKLSAPDLLKEVKFDVLPAYDLLDHLNILKKPNQQFYANLISGRTPPGKEGKLLICFMGLRKYFLNCRPTKLKRLIRLVTHWYQLCKEKLGDPLPPQYALELLTVYAWESGSRDCEFNTAQGFRTVLELVTKYKRLRIYWTVYYDFRKTKVSEYLHKLLQKDRPVILDPADPTRNIAGLNPKDWRRLAGEAAAWLQYPCFKYRDGSPVCSWEVPTEVAVPTKYLFCRIFWLLFWSLFHFIFGKTSSG”BASECOUNT 372a 414c 428g 373tORIGIN1ctgcttcagc cagcctagga gacacaggac ctgctggctg cagaggtaaa agctggacct61aggatggagc aggatctgag gagcatcccg gcctcgaagc ttgataagtt catagagaat121catctcccgg acaccagctt ctgtgctgac ctcagagaag tcatagatgc cctgtgtgct181ctcctgaagg acagattctt ccggggcccc gtccgccgaa tgagggcctc taagggggtc241aagggcaaat gcaccgcgct caagggcagg tcagacgctg acctggtggt gttccttaac301aatctcacct actttgagga tcaattaaac caacagggag tgttgattaa ggaaattaag361aaacagctgt acgaggttca gcatgagaga cgttttggag tcaagtttga ggtccagagt421ttaaggagtc ccaactcccg ggctctgagc ttcaagctga gcgcccccga cctgctgaag481gaggtgaagt ttgacgtgct gccagcctat gatttactgg atcatcttaa catcctcaag541aagcctaacc aacaatttta cgccaatctc atcagtgggc gtaccccgcc ggggaaggag601ggcaagttat tgatctgctt tatggggctt cggaagtact tcctgaactg tcgcccaacc661aagctgaagc gcctcatccg cctggtcacg cactggtacc aactgtgtaa ggagaagctg721ggggacccgc tgcccccaca gtacgccctg gagctgctca cagtgtacgc ctgggaaagt781gggagtcgag actgtgaatt caacacagcc cagggcttcc gaactgtctt ggaactggtc841accaagtaca agcggcttcg aatctactgg acagtgtatt atgactttag aaagacgaag901gtctctgaat acctgcacaa actgctccaa aaagacaggc ctgtgatctt ggaccccgct961gatccaacaa ggaatatagc tggtttgaac ccaaaggact ggcggcgtct agcaggagag1021gctgccgcct ggctgcaata cccatgcttt aagtacaggg acggttcccc agtgtgctcc1081tgggaggtgc cgacggaggt tgcagtgcca acgaagtatc tcttttgtcg tattttctgg1141ttattgtttt ggtctttgtt tcatttcatc tttgggaaga cttcatctgg atagcccaga1201gtgtcttgga tattgccatc ctcctgcctt agcgctggca tgactgcagt gtaggcctgt1261tatgccctgc ctcccctcca tcctcaagtg gacaagaact gggcatgtgt tttcctgtga1321gcccagtggg acctgtccag gatgctccag agtcagacgc atgtcctgct ctgctgcagg1381gccttgaccc agagaagaca ggaaggtgcc caaagcccaa gagagggagg ttccaacctg1441tgatcagact ccaggcttct gtcccctgcc ctcaacccct gcacagacag cctttctcac1501agcctgcttt atctgtcttg tcccccaaca gtgttctctg ggagacaaga gattcagaag1561gagaatatga tggtttgtat atggttg//(SEQ ID 11)LOCUS AF418008 1587 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus MOLF/Ei 2′-5′ oligoadenylate synthetase1B (Oas1b) mRNA, complete cds.ACCESSION AF418008translation=“MEQDLRSIPASKLDKFIENHLPDTSFCADLREVIDALCALLKDRFFRGPVRRMRASKGVKGKCTALKGRSDADLVVFLNNLTYFEDQLNQQGVLIKEIKKQLYEVQHERRFGVKFEVQSLRSPNSRALSFKLSAPDLLKEVKFDVLPAYDLLDHLSILKKPNRQLYANLISGRTPPGKDPKLSICFMGLRKYFLNCRPTKLKRLIRLVTQWYQLCKEKLGDPLPPQYALELLTVYAWESGSRDCEFNTAQGFRTVLELVTKYKRLRIYWTVYYDFRKTKVSEYLHKLLQKDRPVILDPADPTRNIAGLNPKDWRRLAGEAAAWLQYPCFKYRDGSPVCSWEVPTEVAVPTKYLFCRIFWLLFWSLFHFIFGKTSSG”BASE COUNT 372a 417c 427g 371tORIGIN1ctgcttcagc cagcctagga gacacaggac ctgctggctg cagaggtaaa agctggacct61aggatggagc aggatctgag gagcatcccg gcctcgaagc ttgataagtt catagagaat121catctcccgg acaccagctt ctgtgctgac ctcagagaag tcatagatgc cctgtgtgct181ctcctgaagg acagattctt ccggggcccc gtccgccgaa tgagggcctc taagggggtc241aagggcaaat gcaccgcgct caagggcagg tcagacgctg acctggtggt gttccttaac301aatctcacct actttgagga tcaattaaac caacagggag tgttgattaa ggaaattaag361aaacagctgt acgaggttca gcatgagaga cgttttggag tcaagtttga ggtccagagt421ttaaggagtc ccaactcccg ggctctgagc ttcaagctga gcgcccccga cctgctgaag481gaggtgaagt ttgacgtgct gccagcctat gatttactgg atcatcttag catcctcaag541aagcctaacc gacaattata cgccaatctc atcagtgggc gtaccccgcc ggggaaggac601cccaagttat cgatctgctt tatggggctt cggaagtact tcctgaactg tcgcccaacc661aagctgaagc gcctcatccg cctggtcacg caatggtacc aactgtgtaa ggagaagctg721ggggacccgc tgcccccaca gtacgccctg gagctgctca cagtgtacgc ctgggaaagt781gggagtcgag actgtgaatt caacacagcc cagggcttcc gaactgtctt ggaactggtc841accaagtaca agcggcttcg aatctactgg acagtgtatt atgactttag aaagacgaag901gtctctgaat acctgcacaa actgctccaa aaagacaggc ctgtgatctt ggaccccgct961gatccaacaa ggaatatagc tggtttgaac ccaaaggact ggcggcgtct agcaggagag1021gctgccgcct ggctgcaata cccatgcttt aagtacaggg acggttcccc agtgtgctcc1081tgggaggtgc cgacggaggt tgcagtgcca acgaagtatc tcttttgtcg tattttctgg1141ttattgtttt ggtctttgtt tcatttcatc tttgggaaga cttcatctgg atageccaga1201gtgtcttgga tattgccatc ctcctgcctt agcgctggca tgactgcagt gtaggcctgt1261tatgccctgc ctcccctcca tcctcaagtg gacaagaact gggcatgtgt tttcctgtga1321gcccagtggg acctgtccag gatgctccag agtcagacgc atgtcctgct ctgctgcagg1381gccttgaccc agagaagaca ggaaggtgcc caaagcccaa gagagggagg ttccaacctg1441tgatcagact ccaggcttct gtcccctgcc ctcaacccct gcacagacag cctttctcac1501agcctgcttt atctgtcttg tcccccaaca gtgttctctg ggagacaaga gattcagaag1561gagaatatga tggtttgtat atggttg//(SEQ ID 12)LOCUS AF418009 1587 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus MOLG/Dn 2′-5′ oligoadenylate synthetase1B (Oas1b) mRNA, complete cds.ACCESSION AF418009translation=“MEQDLRSIPASKLDKFIENHLPDTSFCADLREVIDALCALLKDRFFRGPVRRMRASKGVKGKCTALKGRSDADLVVFLNNLTYFEDQLNQQGVLIKEIKKQLYEVQHERRFGVKFEVQSLRSPNSRALSFKLSAPDLLKEVKFDVLPAYDLLDHLNILKKPNQQFYANLISGRTPPGKEGKLSICFMGLRKYFLNCRPTKLKRLIRLVTHWYQLCKEKLGDPLPPQYALELLTVYAWESGSRDCEFNTAQGFRTVLELVTKYKRLRIYWTVYYDFRKTKVSEYLHKLLQKDRPVILDPADPTRNIAGLNPKDWRRLAGEAAAWLQYPCFKYRDGSPVCSWEVPTEVAVPTKYLFCRIFWLLFWSLFHFIFGKTSSG”BASE COUNT 372a 415c 428g 372tORIGIN1ctgcttcagc cagcctagga gacacaggac ctgctggctg cagaggtaaa agctggacct61aggatggagc aggatctgag gagcatcccg gcctcgaagc ttgataagtt catagagaat121catctcccgg acaccagctt ctgtgctgac ctcagagaag tcatagatgc cctgtgtgct181ctcctgaagg acagattctt ccggggcccc gtccgccgaa tgagggcctc taagggggtc241aagggcaaat gcaccgcgct caagggcagg tcagacgctg acctggtggt gttccttaac301aatctcacct actttgagga tcaattaaac caacagggag tgttgattaa ggaaattaag361aaacagctgt acgaggttca gcatgagaga cgttttggag tcaagtttga ggtccagagt421ttaaggagtc ccaactcccg ggctctgagc ttcaagctga gcgcccccga cctgctgaag481gaggtgaagt ttgacgtgct gccagcctat gatttactgg atcatcttaa catcctcaag541aagcctaacc aacaatttta cgccaatctc atcagtgggc gtaccccgcc ggggaaggag601ggcaagttat cgatctgctt tatggggctt cggaagtact tcctgaactg tcgcccaacc661aagctgaagc gcctcatccg cctggtcacg cactggtacc aactgtgtaa ggagaagctg721ggggacccgc tgcccccaca gtacgccctg gagctgctca cagtgtacgc ctgggaaagt781gggagtcgag actgtgaatt caacacagcc cagggcttcc gaactgtctt ggaactggtc841accaagtaca agcggcttcg aatctactgg acagtgtatt atgactttag aaagacgaag901gtctctgaat acctgcacaa actgctccaa aaagacaggc ctgtgatctt ggaccccgct961gatccaacaa ggaatatagc tggtttgaac ccaaaggact ggcggcgtct agcaggagag1021gctgccgcct ggctgcaata cccatgcttt aagtacaggg acggttcccc agtgtgctcc1081tgggaggtgc cgacggaggt tgcagtgcca acgaagtatc tcttttgtcg tattttctgg1141ttattgtttt ggtctttgtt tcatttcatc tttgggaaga cttcatctgg atagcccaga1201gtgtcttgga tattgccatc ctcctgcctt agcgctggca tgactgcagt gtaggcctgt1261tatgccctgc ctcccctcca tcctcaagtg gacaagaact gggcatgtgt tttcctgtga1321gcccagtggg acctgtccag gatgctccag agtcagacgc atgtcctgct ctgctgcagg1381gccttgaccc agagaagaca ggaaggtgcc caaagcccaa gagagggagg ttccaacctg1441tgatcagact ccaggcttct gtcccctgcc ctcaacccct gcacagacag cctttctcac1501agcctgcttt atctgtcttg tcccccaaca gtgttctctg ggagacaaga gattcagaag1561gagaatatga tggtttgtat atggttg//(SEQ ID 13)LOCUS AF418010 3897 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ oligoadenylate synthetase2 (Oas2) mRNA, complete cds.ACCESSION AF418010/translation=“MGNWLTGNWSSDRSSGYSSGWSPGGSSGVPSGPVHKLEKSIQANLTPNENCLKQIAVSSVPSQKLEGYIQENLKPNRESLKQIDQAVDAIWDLLRSQIPVKEVAKGGSYGRETALRGCSDGTLVLFMDCFQQFQDQIKYQDAYLDVIELWLKIHEKKSVKHEHALVVQVSVPGQRILLQLLPVFNPLRSNENPSSCVYVDLKKSMDQVRASPGEFSDCFTTLQQRFFKKYPRRLKDLILLVKHWYEQCQEKWKTPPPQPLLYALELLTVYAWEQGCQAEDFDMAQGVRTVLRLIQRPTELCVYWTVNYNFEDETVRNILLHQLRSQRPVILDPTDPTNNVGKDDGFWELLTEEAMAWLYSPSLNTESPAPYWDVLPMPLFVTPSHLLNKFIKDFLQPNKLFLKQIKEAVDIICSFLKNVCFLNSDTKVLKTVKGGSTAKGTALKRGSDADIVVFLSSLESYDSLKTNRSQFVQEIQKQLEEFVQAQEWEVTFEISKWKAPRVLSFTLKSKTLNESVEFDVLPAYDALGQLRSDFTLRPEAYKDLIELCASQDIKEGEFSICFTELQRNFIQTRPTKLKSLLRLIKHWYKQYERKMKPKASLPPKYALELLTVYAWEQGSGTDDFDIAEGFRTVLDLVIKYRQLCIFWTVNYNFEEEYMRKFLLTQIQKKRPVILDPADPTGDVGGGDRWCWHLLAEEAKEWLSSPCFQVEQKGLVQPWKVPVPRDLKTSDMVGVFTTGGILWQDQGFLSFV”polyA signal 3878 . . . 3883/gene=“Oas2”BASE COUNT 978a 1030c 940g 948t 1 othersORIGIN1gaccagctag caacgatggg aaactggctg actggaaact ggtcatctga caggtcatct61ggctattcat ctggctggtc acctggtggg tcttcagggg tgccctccgg gccagtgcac121aagttagaaa agtctatcca ggcaaacctc acacccaacg aaaactgtct gaagcagatt181gcggtgtcct cggtgccatc gcagaagcta gaagggtata tccaggaaaa cctcaaacct241aacagagaat ctctgaagca gatagaccag gccgtggatg ccatctggga cctgctgcgc301agtcagatcc ctgtgaagga agtggctaag ggtggctcct atggccggga aacagcccta361agaggctgct ccgatggtac ccttgttctc ttcatggact gcttccaaca gttccaggat421cagataaaat accaagatgc ataccttgac gtcattgaac tgtggctgaa aatccatgag481aagaagtcag taaagcatga acatgccctt gtagtacaag tgtctgtacc agggcagaga541atactcctgc aattacttcc agtcttcaat cctctacgct ccaatgagaa tcccagctcc601tgtgtctatg tggatctcaa aaaatccatg gatcaagtaa gagcctcacc aggggagttc661tcagactgct tcaccacact gcagcagcgg tttttcaaga aatatccccg aagactgaag721gatttgatcc tattggtcaa gcactggtat gaacagtgcc aggagaagtg gaaaacaccc781ccacctcagc cattgctgta cgcactggaa ctgctcactg tgtatgcctg ggaacagggc841tgccaagctg aagacttcga catggcacaa ggcgtcagga ccgtgctgcg acttatccag901cggccgacag agctgtgtgt ctactggaca gtcaattaca actttgagga tgagacagtc961cggaacatcc ttctgcacca gctcaggtcc caaagaccag tcatcttgga tccaactgac1021ccaaccaata atgtgggcaa agatgatggg ttctgggagc tactgacaga ggaagctatg1081gcctggctgt actctcccag cctgaatact gagtcacctg caccatattg ggatgttctg1141cccatgccac ttttcgtcac tccaagccac ttactgaaca agttcatcaa ggactttctc1201cagcccaaca agctcttcct aaagcagatc aaggaagctg ttgacattat atgttccttc1261cttaaaaatg tctgcttctt gaattctgac accaaagtcc tgaagaccgt caagggagga1321tccactgcca aaggcacagc tctgaagcgg ggatcagatg ctgacattgt tgtgttcctc1381tcctcgctgg agagttacga ctctctaaaa accaaccgct cccagttcgt ccaggagatc1441cagaagcagt tagaagaatt cgtgcaggcg caggagtggg aggtgacgtt tgagatttca1501aaatggaagg ctcccagagt gctgagtttt accttgaaat ccaagactct caatgaaagt1561gtcgagttcg atgtccttcc cgcctatgat gcactaggtc aactgcggtc tgacttcacc1621ctcaggcccg aagcctacaa ggatctcatt gagctgtgtg catcacagga catcaaagaa1681ggagagtttt ctatctgttt tactgagctg cagagaaact tcattcaaac ccggcccacc1741aaactgaaga gtctactccg cctgatcaag cactggtaca aacagtatga aaggaagatg1801aagccaaaag catctttacc cccaaagtac gccctggagc tgctcaccgt gtatgcctgg1861gagcagggca gtggcacaga tgactttgac attgctgaag gcttccggac cgtcctggac1921ctggttataa aataccggca gctctgcatc ttctggacag tcaattacaa ctttgaagag1981gaatacatgc ggaagttcct actgacccag atccagaaaa agaggcctgt aatcctggat2041ccagcagatc ccacaggcga tgtgggagga ggtgaccgct ggtgctggca tcttctagct2101gaagaagcga aggagtggct gtcctcccct tgtttccaag tggagcaaaa aggcctggta2161cagccttgga aagtgccagt acctagagat ctaaagacaa gtgacatggt gggagtgttc2221actacaggag ggatcttgtg gcaggaccag ggctttttgt catttgtcta ggtaatgcag2281acccccggaa gctgtggagg tcagatctac cccactgtgg gtggagttac taagtaggag2341tccattcagc tctggaagac gcttctggag tgatctggca aagactcaga ctgtgttaga2401aaagggagcc tggttcagtc ctctctggca ggctcgcacc tctattcttc cttcttggaa2461tcaagacatg ggattatcct tcctcctccc ccagggtctc acagcacagg ccctgctctg2521tgtgagtgac ctccttcaga gacacttgcc ccatgcagct cgatgggttc tggttttgtc2581tgtattctgt gcagttattt tcctgcctcc tgctctgtta gtctctagtc agcagctcca2641gactcaccct gtgtcactaa ggttaaggcc ctccctagcc cttcagcatt gtcaatccca2701actagccctc ggagtcttcc attgtgcgtc tttgcctgtc tctttccctg tccctgtgga2761tacagagatg taccatccat ccagcagcta gccaactccc ctccctccac ctctgctgtt2821aaaacccttt ctcttgggga aatgtaaaca atatctacct ctcttaatgt cccaggacaa2881actaagctgc atttctccct tccctgagaa gccaaagctt ccctgattga gcttrgctgc2941tcacaggaga ggggttacag gcctttgaag ctggccacac tagaagatct gcacccagct3001agatgggtgc agatggcttc cctggggctg cataaagaga acccctcccc tcatctttcc3061tcctgtatcc tctagcccct ctcagagatc ctgtgcaatc agggcagaat agcatgcagc3121tggttgaaac cacttgctaa ataactcagg tgagggtccc ataaccttcc cagcccacct3181cccttccaag agtgaagata acagtcaaca agcccagctg tgatgttcat tgataagcag3241gctctggtgg actcctaaag atggtgccag tgtggctcag tgaatagccc tgcataacat3301tttacacaca ccaaatgctg gttgatatct cttgctggct gcccagggag ccttcacccc3361agggctttaa ctgcacagag acatgaggtc taagcccttc gcatccccaa gtaaggctga3421gccttttttc tgcctgtgct tgctctgatg cattgaggat catgcctggc cactgtgcaa3481cttttaagca gagccgtgca acatcccagg gagttgactt ctatgtaaac accttcatcc3541atttctgatg tatgctttga ggtggctcag gctgggctag cccagcccag acagaaatcc3601taggcatgtg attagaggat cagaaccctt ctggcccttc ttcaggggag agatggggct3661gaaggtgggg ttcaaatctc atgccgagtg atggaacccg acatccctag gtgctaaggc3721cccaccaaat tctctggata aggaagttcc aggaatcttt actgataaac atcccaatgt3781atcaacaagg tagactctga cctccatggg acagaagatc ctgggtcagt cccctccctg3841gggactctgc agttggctgt tcatttatat gcttcataat aaatggtttc tttgtgt//(SEQ ID 14)LOCUS AF453830 4708 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ oligoadenylate synthetase3 (Oas3) mRNA, complete cds.ACCESSION AF453830/translation=“MDLFHTPAGALDKLVAHNLHPAPEFTAAVRGALGSLNITLQQHRARGSQRPRVIRIAKGGAYARGTALRGGTDVELVIFLDCFQSFGDQKTCHSETLGAMRMLLESWGGHPGPGLTFEFSQSKASRILQFRLASADGEHWIDVSLVPAFDVLGQPRSGVKPTPNVYSSLLSSHCQAGEYSACFTEPRKNEVNTRPAKLKNLILLVKHWYHQVQTQAVRATLPPSYALELLTIFAWEQGCGKDSFSLAQGLRTVLALIQHSKYLCIFWTENYGFEDPAVGEFLRRQLKRPRPVILDPADPTWDVGNGTAWRWDVLAQEAESSFSQQCFKQASGVLVQPWEGPGLPRAGILDLGHPIYQGPNQALEDNKGHLAVQSKERSQKPSNSAPGFPEAATKIPAMPNPSANKTRKIRKKAAHPKTVQEAALDSISSHVRITQSTASSHMPPDRSSISTAGSRMSPDLSQIPSKDLDCFIQDHLRPSPQFQQQVKQAIDAILCCLREKSVYKVLRVSKGGSFGRGTDLRGSCDVELVIFYKTLGDFKGQKPHQAEILRDMQAQLRHWCQNPVPGLSLQFIEQKPNALQLQLASTDLSNRVDLSVLPAFDAVGPLKSGTKPQPQVYSSLLSSGCQAGEHAACFAELRRNFINTCPPKLKSLMLLVKHWYRQVVTRYKGGEAAGDAPPPAYALELLTIFAWEQGCGEQKFSLAEGLRTILRLIQQHQSLCIYWTVNYSVQDPTIRAHLLCQLRKARPLVLDPADPTWNVGQGDWKLLAQEAAALGSQVCLQSGDGTLVPPWDVTPALLHQTLAEDLDKFISEFLQPNRHFLTQVKRAVDTICSFLKENCFRNSTIKVLKVVKGGSSAKGTALQGRSDADLVVFLSCFRQFSEQGSHRAEIISEIQAQLEACQQTHSFDVKFEVSKRKNPRVLSFTLTSQTLLDQSVDFDVLPAFDALGQLRSGSRPDPRVYTDLIHSCSNAGEFSTCFTELQRDFITSRPTKLKSLIRLVKYWYQQCNKTIKGKGSLPPQHGLELLTVYAWEQGGQNPQFNMAEGFRTVLELIVQYRQLCVYWTINYSAEDKTIGDFLKMQLRKPRPVILDPADPTGNLGHNARWDLLAKEATVYASALCCVDRDGNPIKPWPVKAAV”polyA signal 4690 . . . 4695/gene=“Oas 3”BASE COUNT 1031a 1322c 1248g 1107tORIGIN1gaaactctac tgagagtacc ggtcaacatg gacctgttcc acacgccagc cggagctctg61gataagctgg tggcccacaa cctgcaccca gcccctgagt tcacagcagc cgtacggggt121gctctggggt cgctaaacat caccctacag cagcacagag cccgagggtc acagagacca181agagtgataa ggattgccaa gggaggagcc tatgcccggg gcacagctct cagaggtggc241accgatgtcg aactcgtcat cttcctcgac tgcttccaga gctttggtga ccagaagacc301tgtcactcag agaccctggg tgccatgcga atgttgctgg agtcctgggg gggccacccc361gggcctggcc tgacttttga gttttctcag tcaaaggcgt ccaggatctt acagtttcgt421ctggcatcgg cagacggaga acactggata gatgttagcc tggtgcctgc ctttgatgtc481ctaggacagc cccgctctgg agtcaagccg acacccaacg tgtactcctc cctccttagc541agccactgcc aggccgggga gtactcagcc tgcttcactg agccccgaaa gaactttgtg601aacactcgcc cagccaagct taagaactta atcctgctgg tcaaacactg gtaccaccag661gtgcagacac aggccgtgag ggccacactg ccccccagct acgccctaga gctgcttacc721atctttgcct gggagcaggg ctgtgggaag gacagcttca gcctggccca agggctccgg781accgtcctgg ccttgatcca acacagcaag tacctctgca ttttctggac ggaaaactat841ggcttcgagg accctgcagt tggagagttc ttgcgaaggc agcttaagag acccaggccc901gtgatcctgg atccagctga tccaacgtgg gacgtgggca acgggacagc ctggcgctgg961gatgtgctgg cccaggaggc tgagtccagc tttagccagc agtgcttcaa gcaggcctca1021ggagtccttg tgcagccttg ggaggggccg ggcctgccac gggctgggat cttggatttg1081ggccacccaa tctatcaagg gcctaaccag gcccttgaag acaacaaagg ccaccttgct1141gttcagtcaa aggaaaggag ccaaaaacct tccaattcag ctccaggatt tccagaagca1201gccaccaaga tccctgctat gcccaaccca agtgccaata aaacccgcaa gatccgcaag1261aaagcagctc acccaaagac tgtccaggaa gcagcattgg atagtatctc aagtcatgtt1321cggatcaccc agagcacagc atcctcacac atgcctcctg accgctctag catctccacc1381gctgggtcac ggatgagccc agatctgtca cagatcccca gcaaggatct agactgcttc1441atccaggacc accttaggcc gagtccccag ttccagcagc aggtgaagca ggccatcgac1501gccatcttgt gctgcctccg ggagaagagt gtatacaaag tcttgagggt cagcaagggc1561ggctctttcg gccgtggcac agacctcagg ggcagctgcg atgtggaact tgtcatcttt1621tataaaaccc tcggggactt caagggccag aagcctcacc aggcagagat cctgcgtgac1681atgcaggccc agctacgaca ctggtgtcag aaccccgtgc ctggactgag cctccagttt1741attgaacaga agcccaacgc tctgcaactc cagctggcgt ccaccgacct cagcaaccgg1801gtggacctca gtgtgctgcc tgcttttgat gctgtggggc cgctgaagtc cggcaccaaa1861cctcagcccc aggtgtactc ctcgctcctc agcagcggct gccaggctgg ggagcacgca1921gcctgcttcg cagagcttcg aaggaacttc ataaacactt gccctcccaa acttaagagc1981ctgatgctac tggtcaaaca ctggtaccgc caggttgtca ctcgatataa aggaggagag2041gcggcaggtg atgctccgcc cccagcctac gccctggagc tcctgaccat ctttgcctgg2101gaacaaggct gtggagagca aaagttcagc ctggctgaag gcctgcggac catcctgagg2161ctgatccaac agcaccagtc gctttgtatc tactggacgg tcaactacag tgtgcaggac2221ccgaccatca gagcacatct tctctgccag cttcggaaag ccaggcctct agtcctggac2281cctgcagatc ccacctggaa cgtgggccag ggcgactgga agctattagc tcaggaggca2341gctgcccttg ggtcacaagt ctgccttcag agtggggatg ggactctggt gccaccctgg2401gatgtgacgc cagccctcct tcaccagacc ctagctgagg acctggacaa attcatcagt2461gaattcctcc agcccaaccg ccacttcctg actcaagtga agagagccgt ggacaccata2521tgttccttcc tgaaagaaaa ctgcttccgg aactctacca tcaaggtgct caaggtggtc2581aagggtgggt cttctgccaa aggcacggct ctacaaggac gctcagatgc cgacctggtg2641gtgtttctca gctgcttccg ccagttctct gagcaaggca gccatcgggc agagatcatc2701tcggagatcc aggctcagct ggaggcgtgt cagcagacgc acagcttcga tgtcaagttt2761gaggtctcca agaggaagaa cccccgagtg ctcagcttca cgctgacatc ccagacgctg2821ctggaccaaa gcgtggactt tgacgtcctg ccagcctttg atgctctcgg ccagctgagg2881tccggctctc ggcctgatcc ccgggtctac acagacctca tccacagctg cagtaatgca2941ggagagttct ctacctgctt cacagagctg cagagggact tcattacctc ccgtcccacc3001aaactcaaga gcctgatccg gctggtgaaa tactggtacc aacagtgtaa caagaccatc3061aaggggaagg gttccttgcc tccccagcac gggctggagc tcctaactgt gtacgcctgg3121gagcaaggtg gccagaatcc ccagttcaac atggcggagg gcttccgcac tgttctggag3181ctgattgtcc agtaccggca gctctgcgtc tattggacca tcaactacag cgcagaagac3241aagaccatcg gtgacttcct gaagatgcag cttcggaagc ccaggcctgt catcctggac3301ccagctgacc cgacaggcaa cctgggccac aacgctcgct gggatctgct tgccaaggag3361gctaccgtgt acgcatctgc cctgtgctgc gtggacaggg atggcaatcc catcaagcca3421tggccggtaa aggccgctgt gtgaagtcta gagagatcag tggtcaccat tgatagaaag3481tgacaccagc cctcagcaag tgatactcag agtatctgag tgtgtgtgtg tgtgtgttgt3541atttatctgt atgtgtgtat ttgtggtatg tctgtgtgcc tatatgaggg tgtgtctatg3601tgcgtgtctg tgtatctgtg ggtatctata tgtgtctgta tatatgtatg tgtgtgtgtg3661tgtgtgtgtg tattcatgta tgtgtgtctg tttgtgtata gtgtgtctat aggtgactct3721gtgtgtctgt gtatctgtga gtatctatat gtgtctgtct gtatgtaaat gtgtgtatgt3781atgtgtgttc atatgtctgt gtgtgtgtct atatctgtgt atctttgggt atctatatgt3841gtctatctat atgtaaatgt atgtatgtac ttatgttcat gtgtatctgt gtgaatgtct3901gtgtgtttat gtgtagtgta tctgtaagtg tatctgtatg tctatagatg tattatgtct3961ttgtgtgtcg acatgtctgt gtgtatgtat gtttgtatgt gtatgttata tatgtatata4021tgcatgtatg tgcttcctca caccatctcc cttctgccca cctgcccacc catagccctc4081cctttcttcc cactgtttac ccacctggtg gggcttcatt gacctcaacc atgatcatcc4141cggtgtccct gactcccaca ctagacaccc taggaaccag acatctctag atcttctagt4201ctgctgttca tctaccatgg gctctgcccc aacttccaca gccccaccca ggagtgcctc4261agccctgcca agaagccata ctcctccctg gcatctctct gccccttgag cctgtgtata4321tccctctgcc tacagagacc caccagctga ggtccaacta tgttcctgta ctggctggtt4381ttgtgtgtca acttgacata ggctggagtt atcagagaaa ggagcttcag ttggggaaat4441gcctccatga gatccagctg tggggcattt tctcagttgg tgatcaaaga ggagggccca4501ttgtgggtgg tgccatccct gggctggtag tcttgagttc tataagagat caagctgagc4561aagccagggg aagcaagcca ataagaaaca tccctccatg gcctctgcat cagctcctgc4621ttcctgacct gtttgagttc cagttctgac ttcctttagt gatgaacagc aatgtggaag4681tgtaagctga ataaaccctt tcctcccc//(SEQ ID 15)LOCUS AF459815 1914 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ olygoadenylate synthetase1c (Oas1c) mRNA, Oas1c-RV allele, complete cds.ACCESSION AF459815/translation=“MENGLCSIQARELDEFICDYLFPDTTFLTELRADIDSISAFLKERCFQGAAHPVRVSRVVMGGSYDEHTALKGKSEAKMVLFFNNLTSFEEQLKRRGEFVEEIQKHLCQLQQEKPFKVKFEVQSSEEPNSRSLSFKLSSPELQQEVEFDVQPAYDVLYELRNNTYAEPQFYNKVYAQLIHECTTLEKEGDFSICFTDLHQNFMRYRAPKLWNLIRLVKHWYQLCKEKLREPLPPQYALELLTVYVWEHSNKNQEKVTTAKNFRTFLELVAYYKNLRIYWTWYYDFRHQEVCAYLCRQLKKARPLILDPADPTRNVAGSDLQAWDLLAKEAQTWMQSSCFRNCDMSFVPTWDLSPERQECAFQ”BASE COUNT 495a 486c 489g 444tORIGIN1aaacactcct ggcctcagga tggagaatgg tctctgcagc atccaagcca gggagctgga61cgagttcata tgtgattacc tctttcctga caccaccttc cttactgagc tcagagcaga121catcgactcc ataagtgctt tcctgaagga gagatgcttc caaggtgccg cccatcctgt181gagggtctcc agggttgtga tgggcggctc ctatgatgaa cacactgcac tcaagggcaa241gtcagaggcc aaaatggtgt tgttctttaa caatctcacc agctttgagg agcagttaaa301gcgacgggga gagttcgttg aggaaattca gaaacacctg tgtcagctgc agcaagagaa361accatttaaa gtgaagtttg aagtgcagag ctcagaggag cccaactcca ggtctctgag421cttcaagctg agctcccccg agctccagca ggaggtggaa tttgatgtgc agccagccta481tgatgtccta tatgaactga gaaacaacac gtatgctgaa ccccaattct acaacaaagt541ctacgcccaa ctcatccatg agtgcaccac cctggagaag gagggcgatt tctccatctg601cttcaccgac ctccatcaga acttcatgag gtatcgtgcg cccaagctct ggaacctcat661ccgtctggtc aagcactggt atcaactgtg taaggagaag ctgagggagc cgctgccccc721acagtacgcc ctggagctgc tcactgtcta tgtatgggaa cattcgaata aaaatcaaga781aaaagtaacc acagccaaga acttccggac cttcttagaa ctggtcgcct attacaagaa841tcttcgaatc tactggacat ggtattatga cttccgacat caagaggtct gtgcctacct901gtgcagacag ctcaaaaaag ccaggcctct gatcctggat ccagcagacc caacaaggaa961cgtggctggt tcagacttac aggcatggga cctgctggca aaggaggctc agacctggat1021gcagtcctct tgctttagaa actgtgatat gtcctttgtg cccacctggg atttgtcgcc1081agagagacaa gaatgtgcct tccagtgagc agtgcagcgc ttgctctgaa ggctccagag1141tcaggggcat accttcctct gctgcaagac cttgacctag agaggacagg atggtgctaa1201aggctccagt gaggggcatc cagcctgtga tcagactcca ggcttctgat ccctgactgc1261ccatggatag ccttcctcac aggctgcttc gtctgcctta gcttccaaca gtgttctctg1321ggagtcagac tgtgatggac agagaagaac gcaagctcga cttccatctg tccacctgtt1381gggaggttct gtccaacagt ggctgattgt catcaacaaa ccacagcaag ccatggggga1441gggtgcactc tgagagaagg aacctttaag tacacttgtg tgtctgtgtg tttaaggatg1501tggtgtgtcc atatgcaact agaaaccttg agcacgtgtt acaagctcca catgggccca1561ggtaattgcc agaaaggggt ggacagagca aaaccaaact gttacacgta ttgatgttgg1621gtagcttggg atccttctag atctctgatg caagaaaccc agactagaat ccatggctcc1681tgctgtccat tctcctgtga caaaatttta ggccttcccc atcccacaca gaaactgttc1741tccaaccaca catgaccctg gagccctggg aatctggcca gcgtgcatcg tggtgcactg1801attctgcagc atgcaggctg aggtccacag cagtgtggga aagtaaaact atgtgcaatt1861tgtgaccagt gatgacttga aagcttagct gtctgtgtga gggtgagatt tgaa//(SEQ ID 16)LOCUS AF459816 1911 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ olygoadenylate synthetase1c (Oas1c) mRNA, Oas1c-He allele, complete cds.ACCESSION AF459816/translation=“MENGLCSIQARELDEFICDYLFPDTTFLTELRADIDSISAFLKERCFQGAAHPVRVSRVVMGGSYDEHTALKGKSEAKMVLFFNNLTSFEEQLKRRGEFVEEIQKHLCQLQQEKPFKVKFEVQSSEEPNSRSLSFKLSSPELQQEVEFDVQPAYDVLYELRNNTYAEPQFYNKVYAQLIHECTTLEKEGDFSICFTDLHQNFMRYRAPKLWNLIRLVKHWYQLCKEKAEEPLPPQYALELLTVYVWEHSNKNQEKVTTAKNFRTFLELVAYYKNLRIYWTWYYDFRHQEVCAYLCRQLKKARPLILDPADPTRNVAGSDLQAWDLLAKEAQTWMQSSCFRNCDMSFVPTWDLSPERQECAFQ”BASE COUNT 494a 487c 487g 443tORIGIN1aaacactcct ggcctcagga tggagaatgg tctctgcagc atccaagcca gggagctgga61cgagttcata tgtgattacc tctttcctga caccaccttc cttactgagc tcagagcaga121catcgactcc ataagtgctt tcctgaagga gagatgcttc caaggtgccg cccatcctgt181gagggtctcc agggttgtga tgggcggctc ctatgatgaa cacactgcac tcaagggcaa241gtcagaggcc aaaatggtgt tgttctttaa caatctcacc agctttgagg agcagttaaa301gcgacgggga gagttcgttg aggaaattca gaaacacctg tgtcagctgc agcaagagaa361accatttaaa gtgaagtttg aggtgcagag ctcagaggag cccaactcca ggtctctgag421cttcaagctg agctcccccg agctccagca ggaggtggaa tttgatgtgc agccagccta481tgatgtccta tatgaactga gaaacaacac gtatgctgaa ccccaattct acaacaaagt541ctacgcccaa ctcatccatg agtgcaccac cctggagaag gagggcgatt tctccatctg601cttcaccgac ctccatcaga actttatgag gtatcgtgcg cccaagctct ggaacctcat661ccgtctggtc aagcactggt atcaactgtg taaggagaaa gctgaggagc cgctgccccc721acagtacgcc ctggagctgc tcactgtcta tgtatgggaa cattcgaata aaaatcaaga781aaaagtaacc acagccaaga acttccggac cttcttagaa ctggtcgcct attacaagaa841tcttcgaatc tactggacat ggtattatga cttccgacat caagaggtct gtgcctacct901gtgcagacag ctcaaaaaag ccaggcctct gatcctggat ccagcagacc caacaaggaa961cgtggctggt tcagacttac aggcatggga cctgctggca aaggaggctc agacctggat1021gcagtcctct tgctttagaa actgtgatat gtcctttgtg cccacctggg atttgtcgcc1081agagagacaa gaatgtgcct tccagtgagc agtgcagcgc ttgctctgaa ggctccagag1141tcaggggcat accttcctct gctgcaagac cttgacctag agaggacagg atggcactca1201aggctccagt gaggggcatc cagcctgtga tcagactcca ggcttctgat ccctgactgc1261ccatggatag ccttcctcac aggctgcttc atctgcctta gcttccaaca gtgttctctg1321ggagtcagac tgtgatggac agagaagaac gcaagctcga cttccatctg tccacctgtt1381gggaggttct gtccaacagt ggctgattgt catcaacaaa ccacagcaag ccatggggga1441gggtgcactc tgagagaagg aacctttaag tacacttgtg tgtctgtgtg tttaaggatg1501tggtgtgtcc atatgcaact agaaaccttg agcacgtgtt acaagctcca catgggccca1561ggtaattgcc agaaaggggt ggacagagaa aaaccaaact gttacacgta ttgatgttgg1621gtagcttggg atccttctag atctctgatg caagaaaccc agactagaat ccatggctcc1681tgctgtccat tctcctgtga caaaatttta ggccttcccc atcccacaca gaaactgttc1741tccaaccaca catgaccctg gagccctggg aatctggcca gcgtgcatcg tggtgcactg1801attctgcagc atgcaggctg aggtccacag cagtgtggga aactatgtgc aatttgtgac1861cagtgatgac ttgaaagctt agctgtctgt gtgagggtga gatttgaagc a//(SEQ ID 17)LOCUS AF478457 4380 bp mRNA linear PRI 25-JUN-2002DEFINITION Homo sapiens ATP-dependent RNA helicase mRNA, complete cds.ACCESSION AF478457/translation=“MAADKGPAAGPRSRAAMAQWRKKKGLRKRRGAASQARGSDSEDGEFEIQAEDDARARKLGPGRPLPTFPTSECTSDVEPDTREMVRAQNKKKKKSGGFQSMGLSYPVFKGIMKKGYKVPTPIQRKTIPVILDGKDVVAMARTGSGKTACFLLPMFERLKTHSAQTGARALILSPTRELALQTLKFTKELGKFTGLKTALILGGDRMEDQFAALHENPDIIIATPGRLVHVAVEMSLKLQSVEYVVFDEADRLFEMGFAEQLQEIIARLPGGHQTVLFSATLPKLLVEFARAGLTEPVLIRLDVDTKLNEQLKTSFFLVREDTKAAVLLHLLHNVVRPQDQTVVFVATKHHAEYLTELLTTQRVSCAHIYSALDPTARKINLAKFTLGKCSTLIVTDLAARGLDIPLLDNVINYSFPAKGKLFLHRVGRVARAGRSGTAYSLVAPDEIPYLLDLHLFLGRSLTLARPLKEPSGVAGVDGMLGRVPQSVVDEEDSGLQSTLEASLELRGLARVADNAQQQYVRSRPAPSPESIKRAKEMDLVGLGLHPLFSSRFEEEELQRLRLVDSIKNYRSRATIFEINASSRDLCSQVMRAKRQKDRKAIARFQQGQQGRQEQQEGPVGPAPSRPALQEKQPEKEEEEEAGESVEDIFSEVVGRKRQRSGPNRGAKRRREEARQRDQEFYIPYRPKDFDSERGLSISGEGGAFEQQAAGAVLDLMGDEAQNLTRGRQQLKWDRKKKRFVGQSGQEDKKKIKTESGRYISSSYKRDLYQKWKQKQKIDDRDSDEEGASDRRGPERRGGKRDRGQAGASRPHAPGTPAGRVRPELKTKQQILKQRRRAQKLHFLQRGGLKQLSARNRRRVQELQQGAFGRGARSKKGKMRKRM”polyA signal 4351 . . . 4356BASE COUNT 935a 1293c 1361g 791tORIGIN1ccttctgcgt tcccagcgcg cggcccgaat ggcggccgac aagggcccgg cggctggacc61tcggtcgcga gctgccatgg cccagtggag gaagaagaaa gggctccgga agcgccgagg121cgcggcctcc caggcccgcg gcagcgactc ggaggacggc gagtttgaga tccaggcgga181agatgacgcc cgggcccgga agctgggacc tggaagaccc ctgcccacct tccccacctc241ggaatgcacc tcggatgtgg agccggacac ccgggagatg gtgcgtgccc agaacaagaa301gaagaagaag tctggaggct tccagtccat gggcctgagc tacccggtgt tcaaaggcat361catgaagaag gggtacaagg tgccaacacc catccagagg aagaccatcc cggtgatctt421ggatggcaag gacgtggtgg ccatggcccg gacgggcagt ggcaagacag cctgcttcct481cctcccaatg ttcgagcggc tcaagaccca cagtgcccag accggggccc gcgccctcat541cctctcgccg acccgagagc tggccctgca gaccctgaag ttcactaagg agctaggcaa601gttcactggc ctcaagactg ccctgatcct gggtggagac aggatggaag accagtttgc661agccctgcac gaaaatcccg acataattat tgccacgccc ggacggttgg tgcatgtggc721tgtggaaatg agcctgaagc tgcagagtgt ggaatacgtg gtgttcgatg aagctgaccg781gctttttgaa atgggtttcg cagagcagct gcaggagatc atcgcccgcc tccccggggg841ccaccagacg gtgctgttct ccgccacgct gcccaaactg ctggtggaat ttgcccgggc901tggcctcacg gagcccgtgc tcatccggct tgacgtggat accaagctca acgagcagct961gaagacctcc ttcttcctcg tgcgggagga caccaaggct gccgtgctgc tccacctgct1021gcacaacgtg gtgcggcccc aggaccagac cgtggtgttt gtggccacga agcaccacgc1081cgagtacctc actgagctgc tgacgaccca gcgggtgagc tgcgcccaca tctacagtgc1141cctagacccg acagcccgca agatcaatct cgccaaattc acgcttggca agtgctccac1201tctcattgtg actgacctgg ccgcccgagg cctggacatc ccgctgctgg acaatgtcat1261caactacagc ttccccgcca agggcaaact cttcctgcac cgcgtgggcc gtgtggctcg1321ggctggccga agtggcacag cctactcctt ggtggcccct gatgaaatcc cctacctgct1381ggatctgcac ctgttcctgg gccgctccct caccctcgcc cgacccctca aggagccctc1441aggtgtggcc ggtgtggatg gcatgctggg tcgggtgcca cagagtgtgg tggacgagga1501ggacagtggt ctgcagagca ccctggaggc atcgctggag ctacggggcc tggcccgcgt1561tgctgataac gcccagcagc agtatgtgcg ctcacgcccg gcgccctcgc ctgagtccat1621caagagggcc aaggagatgg accttgtggg gctgggcctg caccccctct tcagctcgcg1681ttttgaggag gaggagctgc agcggctgag gctggtggac agcataaaga actaccgctc1741ccgggcgact atctttgaga tcaacgcctc cagccgagac ctgtgcagcc aggtgatgcg1801cgccaagcgg cagaaggacc gcaaggccat cgcccgcttc cagcagggac agcaggggcg1861gcaggagcag caggagggcc cagtgggccc agccccgagc cgcccagcac tgcaggagaa1921gcagcctgag aaggaggagg aggaggaggc gggagagagt gtggaggaca ttttctcaga1981ggtcgtgggc cggaagcggc agcggtcagg acccaacagg ggagccaaga ggcggaggga2041ggaggcccgg cagcgggacc aggaattcta catcccctac cggcccaagg actttgacag2101cgagcggggc ctgagcatca gcggggaagg gggagccttt gagcagcagg cagctggcgc2161tgtcctggac ttgatggggg atgaagccca gaacctgacg aggggccggc agcagctcaa2221gtgggaccgt aagaagaagc ggtttgtggg acagtcagga caggaagaca agaagaagat2281taagacagag agcggccgct acatcagcag ctcctacaag cgagacctgt atcagaagtg2341gaaacagaaa cagaaaattg atgatcgtga ctcggacgaa gaaggggcat ctgaccggcg2401aggcccagag cgaagaggtg ggaagcgaga ccgtggccaa gcaggtgcat cccggcccca2461cgccccaggc acccctgcag gccgagtccg cccggaactc aagaccaagc agcagatcct2521gaagcagcgg cgccgggccc agaagctgca cttcctgcag cgtggtggcc tcaagcagct2581ctctgcccgc aaccgccgcc gcgtccagga gctgcagcag ggcgccttcg gccggggtgc2641ccgctccaag aagggcaaga tgcggaagag gatgtgagga ccaggaccca gccccgtggc2701tccttgattg gccttagggt gggcatcagc agacgttccc gtgcaccact gtgtgcctgg2761ccctgtgctg ggcactgggg gcactccctg caggagccat catctgtgaa aaggagcact2821gtatggccac agaagggcag cagctgcgtc agcctaagac agagacattt gaacagggcc2881ttgaagggtg tgcaggagtt cgccagcaaa gccaggcagg ccaagacttg agttggcaac2941tcagctgctg ctgcttccat gtgttctggg ttcagaggtc atggctgcac cggtcagagc3001cctgagtgcc tcagggtttg gcaatggaat ttttaatgta ataaatcttt attgagcact3061gctggtggcc aggagtgcgg tctacttggg gaactggaat ggagagaccc aggtactaaa3121atcccagcta acgtggcaga ggagttgcgg gtctcctgag ggtgagttct gctgccttgt3181ccatttagcg atgaggaaag tgaagctcag agcacaaacc aggtgccaga ggcgggagtt3241ggtccccctt cctcccactg gacatggttg cagctgggag tgggctgggg gaggggaaca3301ggatgcccag cccagggggc aaggacacag ctgctcccct ctggctatga agaggttaac3361gcggcccctc cacacctgga ggtcagaacc tggcctgtcc tctgtcttct tgccacccac3421cccctgtttg aggttctgag aaggtcaagg gcagccccag cagctggatt ctcaggctgg3481gcccctcacc tggcagagtc catagtggag ggggccttgg tgatctctca tctagcatgg3541accctgttct gagacctgac aaagagtttt ttttcatgcc ccaaccaccc tggcagggag3601ggcctggtct gatctcattt tagaggcagt tgccccacac atagcccctt gaccttccca3661tcacctcctc atcagggcct gcatttatgg agtgcttgct atgtgcccct catggcaggc3721ccacagcact ctgaacaggc acagccctcc catcttccca atgaggaaac ggattcagga3781agagccactc agtccacacc ccattggaaa tgtgggccct cctatctcag ggtctctcag3841gggttccctc tcccgctgct cacctgtgtc agggctagga ggcaggggct gcaggctcag3901cctgacccag gccggccagc atggcagaga ggtcctgcat gaacagcttc acctgggggg3961gcccagcacg aagtcacatc ccagccccag agtcactgtc cagcccccac ccctcaacac4021gcgggggagg ccgaaaggta gggcggggac tggagatccc ctcattaaaa gaacagtgat4081gatggtggtt cccagaggtg gtgactgaga tcctaaaccg ttctgggttt tgaaagcctc4141aggccaacct tcccaactgc tgcgtgagca gacaccttca cagcttcctc gctgctgtca4201cctgcactat ccaattagta ttttcattta catcaatcag ctttattttc ttgtaactgg4261atcagtcata ttcattggtt tgtgacctac tcttatctcc gtgggtggct ctccttttgt4321tttaattaac ttctttatga atatgaactt aataaatacc atggatccat tgtaaaaact//(SEQ ID 18)LOCUS AF480417 1993 bp mRNA linear ROD 26-JUN-2002DEFINITION Mus musculus 2′-5′ olygoadenylate synthetase1G (Qas1g) mRNA, complete cds.ACCESSION AF480417/translation=“MEHGLRSIPAWTLDKFIEDYLLPDTTFGADVKSAVNVVCDFLKERCFQGAAHPVRVSKVVKGGSSGKGTTLKGRSDADLVVFLNNLTSFEDQLNRRGEFIKEIKKQLYEVQHERRFRVKFEVQSSWWPNARSLSFKLSAPHLHQEVEFDVLPAFDVLGHGSINKKPNPLIYTILIWECTSLGKDGEFSTCFTELQRNFLKQRPTKLKSLIRLVKHWYQLCKEKLGKPLPPQYALELLTVYAWEQGNGCNEFNTAQGFRTVLELVINYQHLRIYWTKYYDFQHKEVSKYLHRQLRKARPVILDPADPTGNVAGGNPEGWRRLAEEADVWLWYPCFMKNDGSRVSSWDVPTVVPVPFEQVEENWTCILL”BASE COUNT 493a 495c 537g 468tORIGIN1gccaggctgg gagacccagg aagctccaga cttagcatgg agcacggact caggagcatc61ccagcctgga cgctggacaa gttcatagag gattacctcc ttcccgacac cacctttggt121gctgatgtca aatcagccgt caatgtcgtg tgtgatttcc tgaaggagag atgcttccaa181ggtgctgccc acccagtgag ggtctccaag gtggtgaagg gtggctcctc aggcaaaggc241accacactca agggcaggtc agacgctgac ctggtggtgt tccttaacaa tctcaccagc301tttgaggatc agttaaaccg acggggagag ttcatcaagg aaattaagaa acagctgtac361gaggttcagc atgagagacg ttttagagtc aagtttgagg tccagagttc atggtggccc421aacgcccggt ctctgagctt caagctgagc gccccccatc tgcatcagga ggtggagttt481gatgtgcttc cagcctttga tgtcctgggt catggtagta tcaataagaa gcctaatccc541ttaatctaca ccatcctcat ctgggaatgt acctccctgg ggaaggatgg cgagttctct601acctgcttca cggagctcca gcggaacttc ctgaagcagc gcccaaccaa gctgaagagt661ctcatccgcc tggtcaaaca ctggtaccaa ctgtgtaagg agaagctggg gaagccactg721cccccacagt atgccctgga gctactcact gtctatgcct gggaacaggg gaatggatgt781aatgagttca acacagccca gggcttccgg accgtcttgg aactggtcat caattatcag841catcttcgaa tctactggac aaagtattat gactttcaac acaaggaggt ctccaaatac901ctgcacagac agctcagaaa agccaggcct gtgatcctgg acccagctga cccgacaggg961aatgtggctg gtgggaaccc agagggctgg aggcggttgg ctgaagaggc tgatgtgtgg1021ctgtggtacc catgttttat gaaaaatgat ggttcccgag tgagctcctg ggatgtgccg1081acggtggttc ctgtaccttt tgagcaggtg gaggagaact ggacatgtat cctgctgtga1141gcacagcagc acctgcccag gagactgctg gtcaggggca tttgctgctc tgctgcaggc1201ccatgaccca gtgagggagg gccccacctg gcatcagact ccgtgcttct gatgcctgcc1261agccatgttt gactcctgtc caatcacagc cagccttcct caacagattc agaaggagag1321gaaagaacac acgcttggtg tccatctgtc cacctgttgg aaggttctgt ctgacaaagt1381ctgatcaaca ataaaccaca gcaggtgccg tcatggtgtg tgaactctga ggagtgggcc1441atacaagaac agtgcaggtg tgtgagcgtg tgtgtgccca tgcacatgcg tgtgtgtctt1501cacggttcaa ctagatgcat ttagtgagca cttactacat atgctacatg attcagatgt1561tcagcagtgg ttagagcaaa gcctaactgc taggcttttt gatgcaagtt ggattgggat1621ccttccaggt ctcttcttac acatacacac aagagaggaa cccttggttt cttctgccca1681tgaccccaag acaagattct agccctgccc tatctgacac agaaacagtt ccctggccac1741acatggacat ggaacactga gactgtggcc tgtgctctca gggtgccctt gagtggctac1801aacatgcagg ctgggggccc ataggtatga tgaaaataaa aggtacctgg aatttttgac1861acatgtaact ttgaaacagg gtcattggta gcaacgatca gctttatcac atttagttaa1921atcacaatga ttgtggtttc ctttctgaga catgaatttg atgtgacaca cgctgtcgtg1981gaactcacag gaa//(SEQ ID 19)LOCUS AF481733 1476 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ olygoadenylate synthetase1F (Oas1f) mRNA, complete cds.ACCESSION AF481733translation=“MVKDLSSTPACELDKFIRDHLLPDSSFHAEARADVDFIGAFLKERCFQGATHPVRVSRVVMGGSYDEHTALKSKSEAKMVVFLNNLTSFEEQLKRRGEFIEEIRKHLCQLQDEKPFKVKFEVQSSEEPNSRSLSFKLSSPELQQEVEFDVQPAYDVLYELRNNKYAELYLYNKIYAQLIHECTTLKKEGEFSICFTDLHQSFLEDRAPKLKNLIRLVKHWYQLCKEKLGKPLPPQYALELLTVYAWESGSRDCEFNTAQGFRTVLELVTKYKWLRIYWTVYYDFRKTKVSEYLHKMLQKVRPVILDPADPTRNVAGTNLLGWGLLAKEAAIWLQSSCFRNCDTCLVGPWGVPVKVEIPQDCVLL”polyA signal 1459 . . . 1464/gene=“Oas1f”BASE COUNT 378a 391c 385g 322tORIGIN1tcagcaaaca cttcctggcc ataaaatggt gaaggatctt agcagcaccc cagcctgtga61gctggacaag ttcatacgtg atcatctcct tcccgattcc agcttccatg ctgaggccag121agcagacgtg gacttcatag gtgctttcct gaaggagaga tgcttccaag gtgccaccca181ccctgtgagg gtctccaggg ttgtgatggg cggctcctac gacgaacaca ctgcactcaa241gagcaagtca gaggctaaaa tggtggtgtt ccttaacaat ctcaccagct tcgaggagca301gttaaagcga cggggagagt tcattgagga aattcggaaa cacctgtgtc agctgcagga361tgagaaacca tttaaagtga agtttgaggt gcagagctca gaggagccca actccaggtc421tctgagcttc aagctgagct cccctgagct ccagcaggag gtggaatttg atgtgcagcc481agcctatgat gtcctgtatg aactgagaaa caacaagtat gctgaactct acttgtacaa541caaaatctac gcccaactca tccatgagtg caccacacta aagaaggagg gcgagttctc601catctgcttc accgacctcc atcagagctt cctggaggat cgtgcaccca agctgaagaa661cctcatccgt ttggtcaagc actggtatca actgtgtaag gagaagctgg ggaagccgct721gcccccacag tatgccctgg agctgctcac agtgtacgcc tgggaaagtg ggagtagaga781ctgcgaattc aacacagccc agggcttccg aactgtcttg gaactggtca ccaagtacaa841gtggcttcga atctactgga cagtgtatta tgactttaga aagacgaagg tctctgaata901cctgcacaaa atgctccaaa aagtcaggcc tgtgatcctg gaccctgctg acccaacaag961gaacgtggct ggtaccaacc tactaggctg ggggctgttg gcaaaagaag ctgccatctg1021gctgcagtcc tcctgcttta ggaactgtga tacgtgcctc gtgggcccct ggggtgtgcc1081ggtgaaggtc gagattccac aggactgtgt ccttctatga gcaccaaagc acctgccagg1141atgctcaaga gtcagggata tgagatcctt gctctgctgc aggcccttga accagagaag1201ggggaaagct gctcacggcc ccaatcaggg agggtccaac ctgtgatcag actccaggct1261tctgacccct gccttctcac ccctgcatcc ggtcctatca cagatagcct tcttcgaagc1321ctgctttatc tgccttatcc accaacagtg tcctccggga gatgagagat tcagaattca1381gaaggggagg caggaactca agcttgactt ccacctgtcc acctgttggg aggttctgtc1441caatgtctga tgcacaataa taaatcacag agagcc//(SEQ ID 20)LOCUS AF481734 13943 bp DNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ olygoadenylate synthetase1b (Flv) gene, Flv-C3H.PRI-Flvr allele, complete cds.ACCESSION AF481734translation=“MEQDLRSIPASKLDKFIENHLPDTSFCADLREVIDALCALLKDRSFRGPVRRMRASKGVKGKGTTLKGRSDADLVVFLNNLTSFEDQLNQQGVLIKEIKKQLCEVQHERRCGVKFEVHSLRSPNSRALSFKLSAPDLLKEVKFDVLPAYDLLDHLNILKKPNQQFYANLISGRTPPGKEGKLSICFMGLRKYFLNCRPTKLKRLIRLVTHWYQLCKEKLGDPLPPQYALELLTVYAWEYGSRVTKFNTAQGFRTVLELVTKYKQLRIYWTVYYDFRHQEVSEYLHQQLKKDRPVILDPADPTRNIAGLNPKDWRRLAGEAATWLQYPCFKYRDGSPVCSWEVPTEVGVPMKYLFCRIFWLLFWSLFHFIFGKTSSG”polyA signal 12974 . . . 12979/gene=“Flv”polyA site 12996/gene=“Flv”BASE COUNT 3434a 3551c 3318g 3640tORIGIN1catccttttt ttttttttcc attcatttct tcatctgttt tagggttttt tccccctcac61actctggagt gaatccagct gtagtgtagc ccaggatgga ccagcctcca ctatccatcc121tcctgcatca gcctctgcct gctgaactgc tagggccacc cacaatgctg tttttcttcc181ctgttttcct gcatgtgaag ggctaatgac ctagaagccc caggcagtct gagtgactcc241ctgcaggagg agatatggtg ctgatgtcag tgtgcagtga ggatcaggga ggccaacggg301gtaagcaccc caccaaaatc caccagcttg gggaagcagg actaggtctg cagaccccca361aaggtcccat ttccacccta atcccctgga gctccctgtg cccggtgagc agtctccact421agcaatggct tccttcctgg agatgcataa aggccaatcc tgctcttgca gaaggccaga481ctctttattt cctcatcgaa gtacatcctg gttaatgctc gggtgtgcac atgtgagtat541acacttgttt gtgtatttgt gtgcatatgt gcacaggcaa gctcaggagt gtatttagtg601tgtgcatgcc ctgtgcgtgt gcatgtgaat gtgtgtgtgt gtgtgtgtgt gtgtgtgttt661gggacctgcc atgtcagttc tcagaattgg aactggaagc acagcccgag ctcttaaact721ctgagccctc tctctgccct ctaaacaaga gatgagaaga tggaggcagg ggttggaggg781catcaaactg ttttgatgag gccttgggta tgtcacccaa aggtgatttt caaccttgcc841agggccctga aagacagctc attttaatag tcactgctga cctgtactgt ccccagcttg901gtggtacggc ctgtacttca cccttgggga tgcccagacc ccaccctcac ccagaccccc961tgcaccacag gggaaaatgt agggtgtgag taggagaggg ggcttctggg aagtctgagc1021tttctgttag aattgtctgt aatcctagac ctgcaagtcc agaggtaaag gaaaaacaaa1081acctggggag gtgctgttct taaaaagaaa aaaaaaaaaa aaaagcagtt ccgcctaaaa1141cgtttgcagg agatggaagc cgagctcagg agccaccagc caccttctgt ggtttcctga1201ttccgtttcc cttcttctac gtgcacagat tgttcctaaa acgtaccgtg taacagcctt1261ttttccagaa gaaatcccga gaaagccagg tcagtttcct tacacattct tccctgggcc1321ggatcttaag aaagctcagg cttggatggg gaggtacctg ttcagaagcc ctaacgccat1381tggctgctcg ggcctggatg atttgcatat ccgcgccctt cccgggaaat ggaaactgaa1441agtcccattt ctgcttcagc gagcctagga gacacaggac ctgctggctg cagaggtatt1501agctggacct aggatggagc aggatctgag gagcatcccg gcctcgaagc ttgataagtt1561catagagaac catctcccgg acaccagctt ctgtgctgac ctcagagaag tcatagatgc1621cctgtgtgct ctcctgaagg acagatcctt ccggggcccc gtccgccgaa tgagggcctc1681taaaggggtc aaggtgagcc ttcctcagcc tgagctggcc gagatgaggt gggacaggac1741tttcagaagc caggctgcaa ccctgatccc tcctcttaat tctgatcaca gctggcgatg1801ggttcttccc cccaagtccc acatctgtat tggagaagga gcctcagcta cagtttatgt1861tccccactcc caggccatgt ccatttcaga gtcggggaaa ctgaggccca gaatggcaaa1921gcagttttct ggaaagtgga ggggcaggtg gtggggcagt ggtaatacaa cctttgcact1981gctgtgtgac ttatggtaac ttaactacct tctccatgtc cagtgttcca cgccccagga2041atgataaggt cacatagact aagtcaaatg tgacacggag gacagaccag gactcgcctg2101ctatgtgact ggattgatgg accctctctg gactcggttc ccgggctgtc tgtcaaatca2161catttcatga cactggtact taactctcag actctgtgaa gggtgcagaa atgaagttgt2221tttcttgttt tcagttgact gtatttctac atttttagtt gtgagtgggg ctctgtatgt2281gttagtgcag gtttggtcag aattgaaaag ggggtgtcag atcccttaga gctgcagtta2341cataggtggc tctgagctgg cctgcttggg tgctgggaac taaactgagg tcatcagcag2401gaacagcagg cagttttagc tactgaccca cctctccatc cggagatgtg acaatttgta2461atgccctctc tcaacagtag ctgatgctta tgtgtgttag tgatgattct aagcatttta2521tttagggagg ctttgttcag catgaattct tctttttatg atatttgttt tacagacttg2581gatcaccttt attgtttttt tcagtttctc tatgatgtta tatgttattc tatatcacac2641aaggccatct tctctttaat gatgtcactt gcgcatattt cctcccagct aacaatgcca2701accatgggac tatggctaca ttctcatata tctgtattaa tttagtcata gtctccttcc2761aatctctact atcctttacc tcccaccaga ccctccccag agattcactc tctgatggta2821tgtcacatgt gtgcagctaa tgtgggcact gcatgagtgc tactgtaccc ttcccaaact2881cttctgtgct tgtttcattt agacctctcc cccactccca tacacagccc ccccccacac2941acacacacac ttgaacacac agagactcca cagatgaaca tggatatttt ccttcacggt3001gtggtttatc ttctgtatca agaggagatc cagcaccctc tattttccta catagattct3061gatgtcactc ttcagggctg actaatattc tcctgcacat ctagcagctt gctccatcca3121tccaaccatc catccatcca tccatccatc tatcaccttg gtgatggact ccagttcagc3181atctggacct cccagcatgg ctctccctgt cctttgtcat tctctttctt gtctttcagg3241gcaaaggcac cacactcaag ggcaggtcag acgctgacct ggtggtgttc cttaacaatc3301tcaccagctt tgaggatcag ttaaaccaac agggagtgtt gattaaggaa attaagaaac3361agctgtgcga ggttcagcat gagagacgtt gtggagtgaa gtttgaggtc cacagtttaa3421ggagtcccaa ctcccgggct ctgagcttca agctgagcgc ccccgacctg ctgaaggagg3481tgaagtttga tgtgctgcca gcctatgatt tactgggtaa ggcagcctgc cagagagcct3541cagctcaccc ttctgcatgc cttcatcctc ccttctagtt ccacctctgt gtgtgtgcac3601atgtgtgttg cgtaggtgtt ctcttgtgtg tgggtgtgat ccggaaccat ggctaactca3661tctcaagagt catccatctt ttttgagacc ttgtctctcc ctggttcaga attcacactt3721gagcctgact ggctgggaag agccccaggg accctcagag tctccccctt ctcagttctg3781agattacaat cctacaccac caacactggc tttttctctg agttctggga ttccgacggg3841ggtcctcatg cttgcgagcc aagcacgtta cagactgagc tatctcccca gcccacacct3901tccatccctg aactgaaaac cattatcatt tgagaaattc aactaaagag aatgtctctt3961taaagctgcg ctggggagga gggattttgg aaatttggta gcggggagac agaatccatc4021ccacagggac attgagcagc ctgctggctc acttagggga gggagtcaca ctagatgctc4081cctcagcata ccagtcctac tcacggctag ctgtgggttt tgtcttctta aacatgagac4141agtgtagact tcactgaaaa taacaaactc gcgaattttc tccctcagag ctgttcagag4201acctggggtg tctgcaggag agtttgcaca ggacgcagat ctcatcggag ctctggcccc4261tcagtaaaac tgcagatgca gacacccaac tcacacatgc acacacattt tataacatta4321cacattaaaa gatcttatct tttgacaaaa atctcaatta ttcaatttta ccaatgaaga4381cttgcaaagc cagatactgt ggtaaaatcc tgctagctca gggaggcaga gaaagcacct4441agctgacctt cctcctgagc cagaatgttc cagaatgcat ccccttctca tgctatctca4501taacctcttt caaatggaat gtccctcccc tctacttcct gtgggtctct ctatccctcc4561ttctgactcc ctcttactct ctgtggttcc ttcttagtaa tcccatgttc gcttctggtc4621agctggttgc ttgctctgcc tcttgatcta tgattggctt tatttaatcc tgtttacaat4681attcaagcag aaagctcctg gattaagggt gtgtgctaag gctgagccac cacacctaaa4741accagttttt tccaataaac aactcaatct cagggttcac agtgtgatca aatatcctgc4801aacaatcttt taccaggcct gatacagcat gcgtcgccaa aattacagat tgtccaactc4861aggaaacact cctgagagca cagtgggatc ttgggggagc ttagagaata cttgaggctt4921tacatttggg ggaagcacag caccccctgt tggccactgt gtgaacttct gctgttaact4981tagtgacaag gccactagcc cttggcttag gagagccgtg gaaacagtcc agagtctcag5041gcagcaggga ctgagagggc cagcctggga gtaggaccag ggcagcctgc tgtgggaagc5101tgcaagaggc ttagaacctt gttcagtgga gggggatcag agtgggtgac cagaaatgat5161ctgtgacagc aggtcccaca gaagcctgtc tgggtcatgg atttcctcag cctcagcagc5221tttccagtgg tgaggggctc taccacagaa ggactgcctg tgggcaacag ccaaagagag5281gatcatagcc acagccctat agaagatgac ataaagcaat gagccctatt gtaactagac5341cctgacacta atctagacta gcccataacc tccatggtca ctgagtgaca ggcttgtcga5401agctccatcc gtgagtgact ttgccctgtg tcagcatcac agtctgatgg tgtggtctgc5461tgcatggcac acatgtgcac acacctaagg cacagcctgc ctagactact caaatgtgca5521cacacaccta tacacacatc tattccatag tctgctgctc ttctactcta taagtgcaca5581ggacacacac acacaaacac acacacaccc taacactgcc atatcttgtt ccatctggac5641aaacaaaacc acatgatatt aacttatcac tacaagaaat cacccaccga aaacacacag5701tggctgggga gacagctcag tggataaggg cgattgctgc tcaagcatga gtacctgagt5761tcaaatcccc aatatccacc taaacttagg aagtgccaca cattgacctg gatacctggt5821cactatgggg gcaaaagaca ggagattctg taagacctgc aggattccag ccaagctcca5881catttacaga cagactctga cgcaaagaaa catactgaca aactataaag aagagacacc5941ttaggtcctc tcctgtctct gaacatatca ggaacactcg ccatgcatac acaatataga6001gcagagactc tgtcagtgtg agacgtgata tgtgaatgca gccgactgct ccacagtgaa6061ctttgacaca tacatgagtg cacaactttg acaagaacta tgcagaagat actggaacca6121gacgtggttg gccattatct gatgatcacg tgtgtgtgac cacagtgtgc tggttcctcc6181cacctctgtc tccaggcctg caagaaagac cctcactaga gcaaactggg agcagggact6241ttgtagtgca cagcatgtgt gcagtcctaa ggagtggtgg ggcagatggg tatatgcgga6301gcgatgcctg ctggggaaaa acgctgcctg ttcgctgaac cccataggct gtgattctgg6361acctggggag actgaggaac ctcagagagg ggctgagctg ttccactgaa tgaaatcttg6421tttacagatc atcttaacat cctcaagaag cctaaccaac aattctacgc caatctcatc6481agtgggcgta ccccgccggg gaaggagggc aagttatcga tctgctttat ggggcttcgg6541aagtacttcc tgaactgtcg cccaaccaag ctgaagcgcc tcatccgcct ggtcacgcac6601tggtaccaac tggtaaggca ttggcctggt cactgtgcgc ttcatctgta cagagtgtag6661acagggggca gagaaaatgt gtactctagt tcggcgtcta ttgaggtaat aactctarca6721catgaccaaa acgctcctgg gaaggaaggg tattcttatg tttacacatc taaggcacac6781tccatcattg agggaagtca gaggaataac tgaagcagag gccatggagg aattctgctc6841accgtttgct gtccatgacg cactcagcgg ccatttctac acagcccaag gccacattcc6901attcatggct ccaaccacag tggtctggtc ccacccacat caatcagtga ttagtaacat6961gcccataaac tacccaagcc agtcagatgg atctgcattt tactgagcaa gatggactcc7021taccagagga ggctagctgg tgtttagtgg acaaaaagta agcagcacaa ttgacccctt7081ttcaacatgg cacacaaaca aaccacagtt gaaccataac ctttcccttc ttgcttgtcc7141ctaagatctc atgtcgctat cacaccatag aacacaactt aggtttaaag tccccaaatt7201aaaaatcaaa cctaaagaaa ctcccaacac ataaaaagac tagtctctca atgctggcct7261catataaaat taaaacacaa gttaaatact ttcttactgc aagagggaag aaccaagtca7321ctgtcacaat ctaattaaaa cacaaccaaa attcaacaga acaaaaggct cagtatctga7381tatctgggac tcatagttct ctgagctttt tgggctctgc catccacagc acacacagca7441ggtctcaggc tcaggccagc tttgttctca cagtgctctg ttcctgacag tcatctcctg7501ctcagggcaa ggccagtatc ttggggtttc cactgccatt gaggctgcac tttcactaat7561ggcttctcct ggcctctcgc agtgccaggc ctcagctgct ctccaaggcc ccttcagtcc7621agcagttctc atgggacttg aaatctggga gacatctctg cagttccagg tgtgattgac7681acttggagat gcagacttgg gacccctgga ctacagctga tagagtccat ggtctgccaa7741agaatgatgt cctgcactca aattgtatgc aaaagcaaag agcgttttta ttctgtggag7801tccagcatgc tgggatctat cattaaccaa gatggagatg cccagatgag atcacaggct7861caatttaaag cacattagtg gaattccatg gaagagtagg tgaccttttt cttgattggt7921tggctctatt ctagggacat tcctgaatca ttactggggg gctagaaact gtcacttggg7981gaagcctgga aactgttgct gactctgttc tttccctagg ccaggtggca gggaagcttc8041tgatggctgg gcagtttctg attggatgct ctaggcctgg ggtttttcca ataaatgact8101tgcctggact tgtacagttc tgagaaacac aaattcaggc ctagtctcct gatatgccag8161tttgaagccc attatggaat caccctggct cagtccactt acacctactc ttgctgacta8221tgaagaaact ctttccaaaa gatttgcacc ccccccccca cacacaccca tggtgcaggt8281ttcttcttta tcagagcaga ttttcagccc caactgatga gaaattactg actcttaatg8341taaacacagc acacaaacag cccagatggg tttttgcttt tctctgaaac ttcactccag8401cctctgtcac ctacctgcct ctcagcactc ctgtcttcca agttcccaca aacagcctgg8461taggctctca gctctcaaca gctctcccac ccaaagttcc ataatccttt ctcaatcctc8521ccaaggagca acatggcagg tcagtcacag cagcgcccct cctccctagg accagtttct8581gtcctagttt gctctgactg ctgtggtaaa gatgctgcaa agtaaattga ggtggaaatg8641gattgtctgg ctcacgttcc tgcatcacac tccatcactg agggaagcag aggcaggaac8701tgaagctgag gccatggagg aactctgcta gctgccggag acccttgggc gatcagtctg8761atttttacaa acaactcagg aacacctgcc cagggcaggc aatgcccaca atgggcgggg8821cccttctaca ctgatcaagg aaatgcccca caggcttgac tccaggccag gctgatggag8881gcattttctc agttgtgggt ccatcttctc cagatgattc tgtgtcactt tggcaaaaag8941aatcaaaatt agcaaaagca gtgagaaaaa caatgtaaaa aaaaaaaaaa agtgggtgga9001ggggaatcag aggggagggg atgagagaga agcaggggtg agtggagatg gggggagatg9061atgctgtagg aggggcaagg agtggggtgg gggatctgag aggagggagg attttccttg9121cctgttctag gtgatttctt ctagtccact ttccaatccg ctaactctct cttcagctgt9181gtctgattca ctgttccatg gcttctgctt catttgtctt tggatttttc tcccattgtt9241ggcaaatcct tcatgtcact tttcatactt tgattttcct gtcttgtcaa gctatgtttt9301taaatgtgtg atttcttatt atatcctgag tgtttttatg tgtatgtgtt tatacctatt9361cttggaaaca cacgtgtatg tgtaggcatg tgtgtccatt aggatttgag ggcagagtgt9421gagagcaggt tctgagtcac gccccacctt gtgtaatcag tcagggtttc acacgtgaca9481ctccgtgtgc tagattagca gttctggaca gtcatacagc ccgggggagc cccatcttta9541tccccttgaa cagggatgag gagtcagctt cctcaagagc ctgacaacac atagatgctg9601gggatctgac ctccagttct catccctgca tggggaggga ggcgctttac ctctgagccc9661tttatctccc tggccccttc ccagttactt cagagaccac aagcgaactt ctacagtgag9721tactccttat gtcctgcccc accctcactc ctagctgtca ctcatggtgt cctgattcct9781cctgggcctg ttagttacgt gctcagtctg tggagcacac agtgtccatc tcaaccgctc9841agctcttggc tatagcacaa gaaggcatag actgaattca agtgactggg tgtgacagtg9901tgacaataac cctgtcatga catcatcagg tggcagctga attgagcctg tgagaagcag9961ccccacacac aaccaccagg aaccccgttt tttttctcat tgcctttctc ttctcagtgt10021aaggagaagc tgggggaccc gctgccccca cagtatgccc tggagctgct cacagtctat10081gcctgggagt atgggagtcg agtaactaaa ttcaacacag cccagggctt ccgaaccgtc10141ttggaactgg tcaccaagta caaacagctt cgaatctact ggacagtgta ttatgacttt10201cgacatcaag aggtctctga atacctgcac caacagctca aaaaagacag gtagtctgtc10261cccacatgcc tgtgatcccc gtggagtgtc aggctgcact tgtgtttaaa gggggaggtg10321ggagctctgt gtctatgcag catcccctgt actgagcact gtcctgctgt cacctgattg10381acatgaggtc ctacagccct gggaggcagg ggtgggctct cctgtctgca gatgaggaga10441ccaaggctct gacattgtcc caacccaatc agcaaaggaa aggggggggg gacatggagt10501ggggactgag attttccaac agtgacagca tcataaaggc tgtgaggcac caaagacctg10561aggtggacaa attacctgta aataatacag tgctatgtca ccctagggag tgacatgtct10621tcattctgtg ttgtgttcag tttccacacc ctattctttg agcctggctg gtccaacact10681cttcatgtca cagatcagag accctgaggg atctgtccca ggacacacag ctactaaatc10741atgcccaagg atccctccag gcttctatat gctgtggggc agggacaaaa aaaaaatctt10801tgaaaaggag ctctctgctg ggctcctccc ccacccctgt gcagtggttc ctgggtcagt10861tgacagcagc tcgtttccct ctcttcatgt tgctctgcag gcctgtgatc ttggaccccg10921ctgacccaac aaggaacata gctggtttga acccaaagga ctggcggcgt ctagcaggag10981aggctgccac ctggctgcaa tacccatgct ttaagtacag ggacggttcc ccagtgtgct11041cctgggaggt gccggtgaga acgtgtcacc atcatcttca ttccacaccc cccccccttc11101tcttcatcta cctggagaat cttcccacac agatgtggtc tccgcactcc tgtggaggcc11161attggctctc cttattccac agccatctta gcgctattca cagatttcat ggactcacag11221gatggctcag tgggtaaagg tgcttgctgc caacacagat gacctgggtt tcatcccagg11281atctcctatg gtagaaggag agaatcaaat ccccaaagtt atcctctgac cttcatctct11341gctgttacac acagggacat gagtgtgtgc atacacacac atacacatac acacacacat11401gtcactacac ccacccaccc acctatccac aggttgcccc caaccaccac cacatagaca11461gacacacaca aaaatacaca aacacagagg ttgcccacac ccattcacac aaagacacac11521acacagacac acacacacag acacacctac acacacacac accatcatca tcatcatcat11581catcatcatc cacaaataga taacacacat acatagactt ggagacctga agccactggc11641tcggggacac tcagatagag tgaagaacgg ctgggacccc gtggactctg aagcccctgt11701caggtccatg aagcagcctg tcttccctgt ctctatcatg tggccaatgg gactcagctg11761ggctctatca cagcacagag gcacagaggg acctgcactt ggacctttct cctcctgggg11821cagggcctgc ctgatgctag ggacccagtg atgccatgtg tgccctccag atggcgttta11881gcatggctgt agtaatgctg gaaccatacc ccagggcaga atgggagttt gatgggtgtg11941gggatggtga tttgggaggt gggaggggcg agtcagactg cagtggcctt tagagctgtc12001cctctggcta tgcccactct caattgatgg atctgtcagt ggatgagagg ggacaagtgg12061gaggcatggc ttcagggaag agctgtatat atcctcaagg gcctaggccc tgtttagcct12121actgttgacc ttctcagcag cctgaccaag gggcccaggt ggcctgtcac agaactcatc12181ttcagggctc agttgcatcc ccttcccagt aagaatgtag gctcctgaca tgatcgtgtt12241ttctattaca gacggaggtt ggagtgccaa tgaagtatct cttttgtcgt attttctggt12301tattgttttg gtctttgttt catttcatct ttgggaagac ttcatctgga tagcccagag12361tgtcttggat attgccatcc tcctgcctta gcgctggcat gactgcagcg taggcctgtt12421atgctctgcc tcccctccat cctcaagtgg acaagaactg ggcatgtgtt ttcctgtgag12481cccagtggga cctgtccagg aggctccaga gtcaggggca tgtcctgctc tgctacaggg12541ccttgaccca gagaagacag gaaggtgccc aaagcccaag agagggaggg tccaacctgt12601gatcagactc caggcttctg tcccctgtcc tcaacccctg cacagacagc ctttctcaca12661gcatgcttta tctgtcttgt cccccaacag tgttctctgg gagacaagag attcagaagg12721agaatatgat ggtttgtata tggttggccc agggaatggc actgttagga gatgtggcca12781tgttggaatg ggtgtggcct tgtgggtgtg ggctttctct tgtcttagct gcctggaagt12841cagtatgctg ctagcagcct tcaaatgaag atgtagaact ctcagctcct cctgcaccat12901gcctgcctgg acgttgccat gctcttgcct tggtgataat ggactgaact tctgaacctg12961taagccaacc ccaattaaat gttgttttta taaaaattgc cttggtcatg gtgtctgttc13021acagcagtaa aaccctaaga cagggaggga ggaactcaag cttgaattgc atatgttcgc13081acgtcgggag gttctgtata tcaataacaa caaaccacag caagccatga gtgtgtgtgt13141atgtgtgtgg gtgtgggtct ctctttgtgt ctgtacctgt gtgtgtataa ggatgtgtgt13201gtgtatctct gtgtctgcat ttgtgtataa gaatgtgtgt gtatctgtgc atgtgtgtgt13261atgtggaatt gtgtgtgttt gtatctctct gtgtctgcat gtgtgtgtag gagggtgtat13321gtgtgtgcat ctgtgtatgt atatgtgttt gtctttctgt gtgtgtgtct ctgtgtgtgt13381gtgtctgcag attcatggtc aagtagctgc acttattaca ttctccatgt gggtcccagc13441accaagtcct cagtggtgga cagagcagaa ccaaactgat acaacttttg atgtcaggta13501gcctgggatc cttccaggtc tcttcttgca cataaacttg agacaggaat tcttagttcc13561ttctgtgttc ccaagcaaca ataatttctc ttgggaacaa ccccctttta gctatcttaa13621agcacatagt gtcttttcct ggtctgtttt gttttgctct ctctttctgg cttagagtca13681gatgaccgtt tgatctgaga tagagatttg aggagactaa acaggctgct taggttggga13741gaggagggtc ataatccaac tccagagcca gctttataat aatgctgaac agcataaaat13801aatgcttcag tgttattcat gcccaaaaga cagcatagct gagtacctgc aaaatggact13861caaggactgc agggagtgac tagagcaaac agagatcaaa ggacactcaa agatctgaga13921tttagcagga cttaaacatc agg//(SEQ ID 21)LOCUS AY055829 1695 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ olygoadenylate synthetase1D (Oas1d) mRNA, complete cds.ACCESSION AY055829translation=“MARELFRTPIWRLDKFIEDQLLPDTTFLTELRADIDSISAFLMERCFQGAAHPVRVSRVVMGGCYNEYTVLKGRSEANMVVFLINLTSFEDQFNGQVVFIEEIWRHLLQLQQEKLCKLKFEVQSPKEPNSRFLSFKLSCPERQHELEFDVQPAYDALYEVRHFKPFDSSNYNKVYAQLTHECTTLEKEGEFSICFTDLHQSFLRYRAPKLWNLIRLVKHWYQLCKEKLRGPLPPQYALELLTVYVWEYGIHENPGLHTAQCFRTVLELVTKYKRLRSTFFTNHDMSIVEAWEVMPERQECVFL”BASE COUNT 438a 432c 432g 393tORIGIN1gcagtcagca aacactcctg gcctcaggat ggcgagggaa ctcttcagaa ccccaatctg61gaggctggat aagttcatag aggatcaact ccttcctgac accaccttcc ttactgagct121cagagcagac atcgactcca taagtgcttt cctgatggag agatgcttcc agggtgccgc181ccatcctgtg agggtctcca gggttgtgat gggtggctgc tacaatgaat acactgtgct241caagggcagg tctgaggcca acatggtggt gttccttatc aatctcacaa gctttgagga301tcagttcaac ggacaggtag tgttcattga ggaaatttgg agacacctac tccagttgca361gcaagagaaa ctatgtaaac tcaagtttga ggtccagagc ccaaaggagc ccaactccag421gtttctgagc ttcaagctga gctgccccga gcgccagcat gagttggaat ttgatgtgca481gccagcctat gatgccctgt atgaagtaag acacttcaag ccctttgact ccagtaacta541caacaaagtc tacgcccaac tcacccatga gtgcaccaca ctggagaagg agggcgagtt601ctccatctgc ttcaccgacc tccatcagag cttcctgagg tatcgtgcgc ccaagctctg661gaacctcatc cgtttggtca agcactggta tcaactgtgt aaggagaagc tgagggggcc721gctgcctcca cagtacgccc tggagctgct cacagtctac gtctgggaat acgggatcca781cgaaaaccct ggactccata cagcccagtg cttccgcact gtcttagaac ttgtcaccaa841gtacaaacgg cttcgaatct actggacatg gtgttatgac tttcaacacg agatctctga901ctacctgcag ggacagatca aaaaagccag gcctctgatc ctggatccag cagacccaac961aaggaatgtg gctggttcag acttacaggc atgggacctg ctggcaaagg aggctcagat1021ctggatagat tcgactttct ttacgaacca tgatatgtcc attgtggaag cctgggaagt1081gatgccagag agacaagaat gtgtcttcct gtgagcaccc ccagcatctg cctaggagac1141tccagagtca ggggcatgtc ctcctcttct gtaagacctt gacctagaga ggacagacag1201gatggcactc aaggctccag cgaggggcat ccaacctgtg atcagactcc aggcttctga1261tccctgcctg cccatggaca gccttcctca caggctgctt cgtctgcctt agcttccaac1321agtgttctct gggagtcaga ctgtgatgga cagagaagaa cgcaagctcg acttccatct1381gttcacctgt tgggaggtta tgtccaatag tggctgatca tcatcaacaa accacagcaa1441gccatgaggg ggggtgcact ctgagggagg agtcctcaga ccacacagaa acttttcagc1501agtgcatgtg gccctggagc cctgggaatc tggccagtgt tcatcaaggt gcactgtttc1561tgcaacatgc aggctgggtt tatggtagtg caggaaaata aaattgcatg cattttaaaa1621tttatgattt taaaacttag gggtgtgtgt gtatgagatt tgaagcacta aattaaagca1681aaacgcattg aatta//(SEQ ID 22)LOCUS AY055830 1336 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ olygoadenylate synthetase1E, 45kD isoform (Oas1e) mRNA, complete cds; alternatively spliced.ACCESSION AY055830/translation=“MARELFRTPIWRLDNFIEDQLLPDTTFLTELRADIDSISAFLKERCFQGATHPMRVSRVVMGGSYDEHNALKGRSEANMVVFFNDLTSFEDQLKWQQVFIEEIRKHLLQLQQEKPCKLKFEVQSSEEPNTRSLTFKLCSPERQQEVEFDVQPAYDALYEGGYCKSFESINYNKVYAQLIHECTTLEKEGEFSICFTDLHQSFLRYRAPKLWNLIRLVKHWYQLCKEKLRGPLPPQYALELLTVYVWEFGVQDSFGLHAAQCFRTVLELVTKYKCLLIYWTWFYDFRPEISDYLHGQIKKARPLILDPADPTRNVAGSDLQAWDLLAKEAQTWIHSNFFRNCDMSLVNGWEVSLPTVFSGSQAVMDREERKLDFHLSTCWEVLSNSG”BASE COUNT 335a 342c 349g 310tORIGIN1tcaggatggc gagggaactc ttcagaaccc caatctggag gctggataac ttcatagagg61atcaactcct tcctgacacc accttcctta ctgagctcag agcagacatc gactccataa121gtgctttcct gaaggagaga tgcttccaag gtgccaccca ccctatgagg gtctccaggg181ttgtgatggg aggctcctat gatgaacaca atgcactcaa gggaaggtca gaggccaaca241tggtggtgtt ctttaatgat ctcaccagct ttgaggacca gttaaagtgg cagcaagtgt301tcattgaaga aattcggaaa cacctgctcc agttgcagca agagaagcca tgtaaactca361agtttgaggt gcagagctca gaggagccca acaccaggtc tctgaccttc aagctgtgct421cccccgagcg ccagcaggag gtggaatttg atgtgcagcc agcctatgat gctctgtatg481aagggggata ctgcaagtcc tttgaatcca ttaactacaa caaagtctac gcccaactca541tccatgagtg caccaccctg gagaaggagg gcgagttctc catctgcttc accgaccttc601atcagagctt cctgaggtat cgtgcgccca agctctggaa cctcatccgt ctggtcaagc661actggtatca actgtgtaag gagaagctga ggggaccgct gcctccacag tatgccctgg721agctgctcac agtctacgtc tgggaatttg gggtccaaga cagctttgga ctccatgcag781cccagtgctt ccgaacggtc ttagaactgg tcaccaagta caaatgcctt ctaatctact841ggacatggtt ttatgacttt cgacctgaga tctctgacta cctgcacgga cagatcaaaa901aagccaggcc tctgatcctg gatccggcag acccaacaag gaacgtggct ggttcagact961tacaggcatg ggacctgctg gcaaaggagg ctcagacctg gatacattca aattttttta1021ggaactgtga tatgtccctt gtgaatggct gggaagtgtc gcttccaaca gtgttctctg1081ggagtcaggc tgtgatggac agagaagaac gcaagctcga cttccatctg tccacctgtt1141gggaggttct gtccaatagt ggctgatcgt catcatcaaa tcacagcaag ccatggggga1201gggtgcactc tgagggagtc ctcagaccac acagaaactt ttcagcagtg catgtggccc1261tggcaccctg ggaatctggc cagtgttcat caaggtgcac tgtttctaca acatgcaggc1321cgggtttatg gcagtt//(SEQ ID 23)LOCUS AY055831 1559 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-5′ olygoadenylate synthetase1E, 42kD isoform (Oas1e) mRNA, complete cds; alternatively spliced.ACCESSION AY055831translation=“MARELFRTPIWRLDNFIEDQLLPDTTFLTELRADIDSISAFLKERCFQGATHPMRVSRVVMGGSYDEHNALKGRSEANMVVFFNDLTSFEDQLKWQQVFIEEIRKHLLQLQQEKPCKLKFEVQSSEEPNTRSLTFKLCSPERQQEVEFDVQPAYDALYEGGYCKSFESINYNKVYAQLIHECTTLEKEGEFSICFTDLHQSFLRYRAPKLWNLIRLVKHWYQLCKEKLRGPLPPQYALELLTVYVWEFGVQDSFGLHAAQCFRTVLELVTKYKCLLIYWTWFYDFRPEISDYLHGQIKKARPLILDPADPTRNVAGSDLQAWDLLAKEAQTWIHSNFFRNCDMSLVNGWEVSPEKQ”BASE COUNT 385a 403c 405g 366tORIGIN1tcaggatggc gagggaactc ttcagaaccc caatctggag gctggataac ttcatagagg61atcaactcct tcctgacacc accttcctta ctgagctcag agcagacatc gactccataa121gtgctttcct gaaggagaga tgcttccaag gtgccaccca ccctatgagg gtctccaggg181ttgtgatggg aggctcctat gatgaacaca atgcactcaa gggaaggtca gaggccaaca241tggtggtgtt ctttaatgat ctcaccagct ttgaggacca gttaaagtgg cagcaagtgt301tcattgaaga aattcggaaa cacctgctcc agttgcagca agagaagcca tgtaaactca361agtttgaggt gcagagctca gaggagccca acaccaggtc tctgaccttc aagctgtgct421cccccgagcg ccagcaggag gtggaatttg atgtgcagcc agcctatgat gctctgtatg481aagggggata ctgcaagtcc tttgaatcca ttaactacaa caaagtctac gcccaactca541tccatgagtg caccaccctg gagaaggagg gcgagttctc catctgcttc accgaccttc601atcagagctt cctgaggtat cgtgcgccca agctctggaa cctcatccgt ctggtcaagc661actggtatca actgtgtaag gagaagctga ggggaccgct gcctccacag tatgccctgg721agctgctcac agtctacgtc tgggaatttg gggtccaaga cagctttgga ctccatgcag781cccagtgctt ccgaacggtc ttagaactgg tcaccaagta caaatgcctt ctaatctact841ggacatggtt ttatgacttt cgacctgaga tctctgacta cctgcacgga cagatcaaaa901aagccaggcc tctgatcctg gatccggcag acccaacaag gaacgtggct ggttcagact961tacaggcatg ggacctgctg gcaaaggagg ctcagacctg gatacattca aattttttta1021ggaactgtga tatgtccctt gtgaatggct gggaagtgtc gccagagaaa caataatgtg1081tcttccagtg agcagtgtag cacttgccta gaaggctcca gagtcaggat catgtgctcc1141tccgctgtaa gactttgacc tagagaggac aggatggtgc tcatgtctcc agcgaggggt1201atccaacctg tgattagact ccaggcttct gatccctgcc tgcccatgga tagccttcct1261cacaggctgc ttcatctgcc ttagcttcca acagtgttct ctgggagtca ggctgtgatg1321gacagagaag aacgcaagct cgacttccat ctgtccacct gttgggaggt tctgtccaat1381agtggctgat cgtcatcatc aaatcacagc aagccatggg ggagggtgca ctctgaggga1441gtcctcagac cacacagaaa cttttcagca gtgcatgtgg ccctggcacc ctgggaatct1501ggccagtgtt catcaaggtg cactgtttct acaacatgca ggccgggttt atggcagtt//(SEQ ID 24)LOCUS AY057107 2041 bp mRNA linear ROD 25-JUN-2002DEFINITION Mus musculus 2′-′ olygoadenylate synthetase-like1 (Oas11) mRNA, complete cds.ACCESSION AY057107/translation=“MAVAQELYGFPASKLDSFVAQWLQPTREWKEEVLETVQTVEQFLRQENFREDRGPARDVRVLKVLKVGCFGNGTVLRSTTDVELVVFLSCFHSFQEEAKHHQAVLRLIQKRMYYCQELMDLGLSNLSVTNRVPSSLIFTIQTRETWETITVTVVPAYRALGPSCPSSEVYANLIKANGYPGNFSPSFSELQRNFVKHRPTKLKSLLRLVKHWYQQYVRDKCPRANLPPLYALELLTVYAWEAGTREDANFRLDEGLATVMELLQDHELLCIYWTKHYTLQHPVIEACVRRQLRGQRPIILDPADPTNNVAEGYRWDIVAQRANQCLKQDCCYDNRDSPVPSWRVKRAPDIQVTVQEWGHSDLTFWVNPYEPIKKLKEKIQLSQGYLGLQRLSFQEPGGERQLIRSHCTLAYYGIFCDTHICLLDTISPEIQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVILSKTTEGAAPFVPS”polyA signal 2013 . . . 2018/gene=“Oas11”BASE COUNT 469a 591c 551g 430tORIGIN1gtgtagccat ggcagtcgcc caggagctgt acggcttccc ggcctccaag ctggactcct61ttgtggctca gtggctgcag ccaaccagag agtggaaaga agaggtcctg gagaccgtgc121agacagtgga gcagttcctg aggcaggaga atttccgtga agatcgtggc ccggctcggg181atgtgcgcgt gctcaaggta ctcaaggtag gctgctttgg gaatggcacc gtgctcagga241gcactacaga cgtggagctg gtcgtgttcc tgagctgttt ccacagcttc caggaagaag301ccaagcacca tcaggctgtc ctgagactga tacagaaaag gatgtactac tgccaggagc361tgatggacct tgggctcagt aacctgagtg tgactaacag agtacccagt agtctcatct421tcacgatcca gaccagggag acctgggaga ccatcactgt caccgttgtg cccgcctaca481gagccctggg cccttcctgt cccagctccg aggtctacgc aaatctgatc aaggctaatg541ggtacccagg aaatttctct ccatccttca gcgagctgca gcgaaacttc gtgaagcatc601ggccgacgaa gctgaagagc ctccttcggt tggtcaaaca ctggtaccag cagtatgtga661gagacaagtg cccccgggcc aacctgcccc ctctctatgc cctggagctg ctcactgtct721atgcctggga agcgggcacc cgggaggatg ccaacttcag gctggatgaa ggcctcgcca781cggtgatgga gctgctccag gatcatgagc tcctctgtat ctactggacc aagcactaca841cgctgcagca cccggtcatc gaggcctgtg tcaggagaca gctcagggga caaaggccta901tcatcctgga cccagcagac cccaccaaca atgtggcaga aggctacaga tgggacatag961tggctcagcg ggccaaccag tgtctgaaac aggactgttg ctatgacaac agggacagcc1021ccgtccccag ctggagggtg aagagagcac ccgatatcca ggtgaccgtg caggagtggg1081ggcactcgga tttaaccttc tgggtgaacc cttatgaacc cataaagaaa ctgaaagaga1141aaatccaact gagccagggc tacttgggcc tgcagcgtct gtcctttcag gagcccggcg1201gagaacgtca gctcatcaga agccattgca cgctcgccta ctacggaatc ttctgcgaca1261cccacatctg cctgctggac accatctccc ctgagatcca ggtctttgtg aaaaacccgg1321atggcaggag ccacgcctat gcgatccacc cgcttgatta tgtcctgaac ctgaagcagc1381agatagaaga caggcagggc cttcgatgcc aggagcagcg cctggagttc cagggccaca1441tcctggagga ctggtttgac tttaaatcct atggcatcca agacagtgtc acagtcatcc1501tgtccaagac gacggagggg gcagctccat ttgtgcccag ctagcttcct ctgtcggtgg1561ctctgcctgt tttattgtct catcctagac tcagcctagt tgcctctcct tcccgtcctc1621tgcccggatg gtccacgtct tcagtacctt gccagcaggg agtcagaggg ggtgtgagaa1681gtcgtgtaca gccagacact cttgtgtgac aatggaattc tgcagtcccc tgggaagtca1741tgccaggacc tctgccttcc tcgtggcctc actgtcaaga ctgtgtcagt gaatagctgg1801cctcacagac tattctcaca tgttcagaga aagccaaacc atcttcctaa ccaattacag1861ggaccctgct tgaggttgtc ccacctccaa attcttccca gtgacctcca tcagggcggc1921tctgaagcct tcccctgtgt ccccaaccac ttctgcctgc cttcgactat ccaaggcaag1981gtaggagggg atcaagttcc tttcaaatgg agaataaaaa agccattgtt tcttcccaga2041t//(SEQ ID 25)LOCUS AY196696 1442 bp mRNA linear ROD 20-MAY-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase1A mRNA, complete cds.ACCESSION AY196696translation=“MEKDLKSTPASELDKFIQDHLLPDTTFRDEVRADIDFICTFLKEKCFHGAALKVSKVVKGGSSGKGTTLQGKSDADLVVFLNNLTSFEDQLKRRGEVIEKIRKHLCQLQQEKQFKLKFEFQTPEQANSRSLSFKLSSPQLQHVVKFDVLPAYDVLGHVNINSKPNAQIYASLIRKCTDLNKEGAFSTCFTELQRNFLKRRPTKLKSLIRLVKHWYQLCKEKLGDSLPPQYALELLTVHAWERGNGLTEFNTAQGFRTVLELVTKYQQLRIYWTMYYDFQHLDVSKYLYRQLKKPRPVILDPADPTGNVAGGNQEGWRRLASEARLWLQCPCFMNRDGSPVSSWEVQTEVPVCF”BASE COUNT 366a 380c 387g 309tORIGIN1gctatggata taagggcagc caactccaga ggcaaggctg cagtcagcaa acatttgtgg61cctcaggatg gagaaggatc tcaagagtac tccagcctcg gagctggaca agttcataca121ggatcacctt cttcctgaca ccacattccg tgatgaggtt agagcagaca ttgacttcat181atgtactttc ctgaaggaga aatgcttcca cggtgccgcc ttgaaggtct ctaaggttgt241gaagggtggc tcctcaggca aaggaaccac gctacagggc aagtcagatg cagacctggt301ggtgttcctt aacaatctca ccagctttga ggatcagtta aagcgacggg gagaggtcat361tgagaaaatt cggaaacacc tgtgccagtt gcagcaagag aaacagttta aactgaagtt421tgagttccag accccagagc aggccaactc caggtctctg agcttcaagc tgagctcgcc481ccagctccag catgtggtga agtttgatgt gctaccagcc tatgatgtcc tgggtcatgt541taacatcaac agcaagccta acgcccaaat ctatgccagt ctcatcagga agtgcaccga601cctgaataaa gagggcgcgt tttctacctg cttcacggag ctccagagga acttcctgaa661gcggcgccca accaagctga agagtctcat ccgcctggtc aagcactggt accaactgtg721taaggagaag ctgggggatt cgctgccccc acagtatgcc ctggagctgc tcacggtcca781tgcctgggaa cgtggaaatg gacttactga gttcaacaca gctcagggct tccggacagt841cttggaactg gtcacaaagt accagcagct tcgaatctac tggactatgt attatgactt901tcaacaccta gatgtctcca aatacctata cagacagctc aaaaaaccca ggcctgtgat961cctggaccct gctgacccaa cagggaacgt ggctggtggg aaccaagaag gctggcggcg1021gttggcctca gaggcgaggc tgtggctgca gtgcccatgt tttatgaaca gggatggttc1081cccagtgagc tcctgggaag tgcagacgga ggttcctgta tgtttctagc aggtggatga1141ggcctggtca tgcatcctgc tgtgaaccca gcagcaccag cccaggaggc tccggagtca1201ggggcacgtg ctgctctgct gcaggacctt gacacagtga gggagggccc cactcgggat1261cacagtccat gcttctgatg cccgcccgcc atgtttgaat actgtccaat cacagatagc1321cttcctcaac agattcagaa ggggcggaaa gaactcaagc ttgacttcca tctgaccgtc1381cacctgttgg gaggttctgt ccaaccatgt ctgtcaacaa caataaagta caccaggtgc1441ca//(SEQ ID 26)LOCUS AY196697 1680 bp mRNA linear ROD 20-MAY-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase1D mRNA, complete cds.ACCESSION AY196697translation=“MGHGLSSISASELDKFIEVYLLPNTSFGADVKLAINVVCDFLKERCFRGAAHPVRVSKVVKGGSSGKGTTLKGKSDADLVVFLNNLTSFEDQLNRRGEFIKEIKKQLYEVQRERHFGVKFEVQSSWWPNPRALSFKLSAPHLQQEVEFDVLPAYDVLGHVSIYSMPDPQIYASLIRKCMYLGKEGEFSTCFTELQRNFLKRRPTKLKSLIRLVKYWYHLCKEKLGKPLPPQYALELLTVYAWERGNGFVDFETAQGFRAVLELIIKYQELRIYWTTYYNFQHQEVSNYLHTQLTRIRPVILDPADPTGNIAGSNPEGWRRLAGEAAAWLRYPCFKYKDGSPVCPWDVPMEVDVPYQEDHFFRNFCLFFLFLFLFIFWRVSCV”BASE COUNT 410a 438c 441g 391tORIGIN1aggctgcaga agcaaatgct ccggaccaat catggggcac ggactcagca gtatctcagc61ctcggagctg gacaagttca tagaggttta cctccttcca aacaccagct ttggtgctga121cgtcaaatta gcgatcaatg tcgtgtgtga tttcctgaag gagagatgct tccgaggtgc181tgcccaccca gtgagggtct ccaaggtggt gaagggtggc tcctcaggca aaggcaccac241actcaagggc aagtcagacg ctgacctggt ggtgttcctt aacaatctca ccagctttga301ggatcagtta aacagacggg gagagttcat caaggaaatt aagaaacagc tgtatgaggt361tcaacgtgaa agacattttg gagtgaagtt tgaggtccag agttcatggt ggcccaaccc421ccgggctctg agcttcaagc tgagtgcacc acacctccaa caggaggtgg agtttgatgt481gcttccagcc tatgatgtcc taggtcatgt aagcatctac agcatgcctg acccccaaat541ctatgccagt ctcatcagga agtgcatgta cctggggaag gagggcgagt tctctacctg601cttcacggag ctccagagga acttcctgaa gcggcgccca accaagctga agagtctcat661ccgcctggtc aagtactggt accatctgtg taaggagaag ctggggaagc cgctgccccc721acagtacgcc ctggagctgc tcacggtcta tgcctgggag cgtggaaatg gatttgtcga781ttttgagaca gcccagggct tccgggcagt cttggaactg atcataaagt accaggagct841tagaatctac tggacaacct attataactt tcagcaccaa gaggtctcca actacctgca901cacacagctc acaagaatca ggcctgtgat cctggacccg gctgacccaa caggaaacat961tgctggttcg aacccagagg gctggaggcg actagcagga gaggctgctg cctggctgcg1021gtacccatgc tttaagtaca aggacggttc cccagtgtgt ccctgggatg tgccgatgga1081ggttgacgtg ccgtaccagg aggatcactt ttttcgtaat ttttgtctat tttttttgtt1141tttgttcctt ttcatatttt ggagggtttc ttgtgtatag tgcaggctct cgtgtatatc1201gtcatcctcc tgcctcggtg ctggcatgac tgcagagtcc gcctgatgtg ccctggattc1261cctccatcct caagtggaca agactgtgca tctgtcgtcc tgtgagccca gcaggacctg1321cccaggaggc tccagagtca gtcatggctt tctgtgctgc aggcccttga cccagagagg1381gaaggaaggt tcccaagacc ccagtgaggg agggtccaac ctgtgatcag actctggtct1441tctgacccct gccttcctac tcctgcatcc tgtcccatca cagacagccc tcctcacagc1501ctgcttcatc tgccttgtcc tccaacagtg ctctcttggg agacaagaga ttcagaaggg1561gaggcaggaa ctcgagcttg acttccacct gtccacctgt tgggagttct gtccaatgtg1621tgaccaacga caataaacca tagcaagcaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa//(SEQ ID 27)LOCUS AY196698 1712 bp mRNA linear ROD 20-MAY-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase1C mRNA, complete cds.ACCESSION AY196698translation=“MSRRLARTPIWRLDRFIEDHLLPDTTFLTEVRADIDSICAFLTERCFQGATHPVRVSRIVKGGWFNKYTMLKGRSEATLVVFLNNLTCFEDQLKRREEFTEEIWKHLCQLQQEKQFKLNFEVQSTEQPDSRTLSIKLSSPQLQQEVEFDVQPAYDVLYELRDKDDFNPDNYREIYARLIRESTTLEMEGEFSVCFTDLHQNFLKYRAPKLWNIIRLVKHWYQLCKKRLKYPLPPQYALELLTVYAWERGLEDRPALHTGHCFRSVLDLITEYKKLRIYWTWCYEFKKETFDYLSRQIKKDRPVILDPADPTRNVAGSNIQSWHVLAKEAAVWARSSFFRNSDMTFVNGWKVSAQKQECVYQ”BASE COUNT 458a 427c 452g 375tORIGIN1gcagtcagca cacattcctg acctcaggat gtcgaggcga ctcgccagaa ccccaatctg61gaggctggac agattcatag aggatcacct ccttcctgac accaccttcc ttactgaggt121cagagcagac attgactcta tatgtgcttt cctgactgag agatgcttcc aaggtgccac181ccaccctgtg agggtctcta ggattgtgaa gggtggctgg ttcaataaat acaccatgct241taagggaagg tcagaggcca ccctggtggt gttccttaac aatctcacct gctttgagga301tcagttaaag cgacgagaag agttcactga ggaaatttgg aaacacctgt gccagttgca361gcaagagaaa cagtttaaac tgaattttga ggtccagagc acagaacagc ccgactccag421gactctgagc atcaagctga gctcgcccca gctccagcag gaggtggagt ttgatgtgca481gccagcctat gatgtcctgt atgagctaag agacaaggac gactttaacc cggataacta541cagggaaatc tatgcccgcc ttatccgtga gagcaccacc ctggagatgg agggcgagtt601ctccgtctgc ttcacggacc ttcatcagaa cttcctgaag tatcgtgcac ccaagctgtg661gaatatcatc cgtctggtca agcactggta tcaactgtgt aagaagaggc tgaagtatcc721gctgccccca cagtacgccc tggagctgct cacggtctat gcctgggagc gtgggctgga781agaccgccct gcactacata caggccactg tttccgaagt gtcttagatc tgatcacaga841gtacaagaag cttcgaatct actggacatg gtgctatgaa ttcaaaaaag agacctttga901ctatctgagc agacagataa aaaaagacag gcccgtgatc ctggaccctg ctgacccaac961aaggaacgtg gctggttcaa acatccaatc ctggcacgtg ctggcaaaag aagctgcggt1021ctgggcgcgg tcgtctttct ttaggaacag tgatatgacc tttgtcaatg gctggaaagt1081gtcggcacag aaacaagaat gtgtctacca gtgagcacca cagcccttgc ccaggaggct1141tctgaagtca gggccatatg ctcttctgct gcaagacctt gtcctgaaga gaacagtttg1201gcgcaccagg gtccagtgag gggcatccaa cctgtgatca gactccaggc ttctattccg1261tcctgcccat gggacagcct tcctcacagc ctgcttcacc tgccttatcc cccacagtgt1321tctttgggag tcagactccg aaggaaagag aagagctcaa acgtggcttc tgtctgtcca1381cctgtgggga ggctctgtcc acaaacatgt ctgatcatga acaatcgacc acagcaatcc1441ctgagggagt gtgcactcgg aggggtgagt cctcagccca cataggaacg gctcagcaga1501ggagcgtggc ccgggaacgc tggggatctg gccagtgtgc atcgaggtgc actgttgggc1561aaagtgtgag ctggggttac ggcagtgcag ggaaataaaa ttgtatgcac tttaaaactt1621aggaccttaa aacttagatg tgtgtgcgtg tgaggatgag atttgaagcc ctgaattaaa1681gtaaaatgca aaaaaaaaaa aaaaaaaaaa aa//(SEQ ID 28)LOCUS AY196699 1518 bp mRNA linear ROD 20-MAY-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase1E mRNA, complete cds.ACCESSION AY196699translation=“MPWKLANTPIWRLDRFIQDHLLPDTTFLTEVRADIDFICAFLTERCFQGATHPVRVSRIVMGGCYDEYSMLKGRSEATLVVFLNNLTCFEDQLKRREEFIEEIWKHLCQLQQEKQFKLNFEFQTSEQANSRSLSIKLSSPQLQQEVEFDVQPAYDVLYAWRYNKYLDPRIYNKIYASLIRESTNLDKEGEFSVCFTELQQHFLKHPGHKMWNLIRLVKYWYQLWKEKLGDLLPPQYALELLTVHAWELGIENTCELYIARGFRSVLELIIKYRCLLIFWTLCYDFNHNEVSEYLNKQLQKDRPVILDPADPTRNVAGSNLQAWHLLAEEAGAWVQSSFFRNSDMSLVHSWKVPPEKQTCVIL”BASE COUNT 375a 404c 382g 357tORIGIN1tcaggatgcc gtggaaactt gccaataccc ccatctggag gctggacaga ttcatacagg61atcacctcct tcctgacacc accttcctta ctgaggtcag agcagacatt gactttatat121gtgctttcct gactgagaga tgcttccaag gtgccaccca ccctgtgagg gtctctagga181ttgtgatggg cggctgctac gatgaatact ccatgctcaa gggaaggtca gaggccaccc241tggtggtgtt ccttaacaat ctcacctgct ttgaggatca gttaaagcga cgagaagagt301tcattgagga aatttggaaa cacctgtgcc agttgcagca agagaaacag tttaaactga361attttgagtt ccagacctca gagcaggcca actccaggtc tctgagcatc aagctgagct421cgccccagct ccagcaggag gtggagtttg atgtgcagcc agcctatgat gtcctgtatg481cttggagata caacaagtac cttgatccca gaatctacaa caaaatctac gccagcctca541tccgtgagag caccaacctg gataaggagg gcgagttctc cgtctgcttc acagagctcc601aacaacactt cctgaagcat cctggacata agatgtggaa tctcatccgc ctggtcaagt661actggtatca actgtggaag gagaagctgg gggatttgct gcccccacag tacgccctgg721agctgctcac ggtccatgcc tgggaactgg ggattgaaaa cacctgtgag ctatacatag781cccggggctt ccgaagtgtc ttagaactga tcatcaaata tcggtgtctc ctaatcttct841ggacattgtg ttatgacttt aatcacaatg aggtctctga gtacctgaac aaacaactcc901aaaaagacag gcccgtgatc ctggaccctg ctgacccaac aaggaacgtg gctggttcaa961acctccaggc ctggcacctg ctggcagaag aggctggggc ctgggtgcag tcgtctttct1021ttaggaacag cgatatgtcc cttgttcaca gttggaaagt gccgccagag aaacaaacat1081gtgtcatcct gtgagcccag caggacctgc ccaagaggct tcggagtcag ggccatgtgc1141tcttctgctg caagaccttg ccctggagag aacagttcgg tgcaccaggc tccagtaagg1201ggcatccaac ctgtgatcag actccaggct tctgatcccg tcctgccctg cccagggaca1261gccttcctca cagcctgctt cacccgcctt atcccccaca gtgttctctg ggagtcggac1321tctgaaggaa agggacaaac ttaaccttga cttccacctt ttcacctgtt gtgaagctca1381gtccaacaat gtctgattat ctatgataag ccacagcaag ccattgcggg ggggtgtgca1441ctctgaggga tggggcctta gaagtacgtg tatgactttt catgctctac tagaaacatt1501gagtacttgt tgcaagct//(SEQ ID 29)LOCUS AY196700 1619 bp mRNA linear ROD 20-MAY-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase1F mRNA, complete cds.ACCESSION AY196700/translation=“MVNLSSTPACELDRFIKDHLPADTSFHAELRADIDFICAFLKERCFQGAAHPVRVSRVVMGEHTMLKGRSEANLVVFLNDLPSFEDQLNLQGEFIEEIRKRLCQLQQEKTLQVKLEVQSSEQPSSKSLSFTLSSPQLQQEVEFDVQPAYDVLFALRNNHKPDPQIYTKTYAYLISVCTTLKKEGEFSTCFMELRQNFLKHREPKLKSLIRLVKHWYQLCKEKLGKPLPPQYALELLTVYAWESGSRDCEFNTAQGFRTVLELVTKYQWLRIYWTLYYDFRNKKVSDYLHKQLKKTRPVILDPADPTRNVAGSNPLCWRLLAKEAASWLQCPCFRTCDMSLVHSWEVLTKVEFPQECVLL”BASE COUNT 409a 462c 388g 359t 1 othersORIGIN1ggctgcagtc agcaaacact cccggcctta aaatggtgaa cctcagcagc accccagcct61gtgagctgga caggttcata aaggatcacc tccctgctga caccagcttc catgctgagc121tcagagcaga cattgacttc atatgtgctt tcctgaagga gagatgcttc caaggtgccg181ctcaccctgt gagggtctcc agggttgtga tgggcgaaca caccatgctt aagggtaggt241cagaagccaa cctagtggtg ttccttaacg atctccccag ctttgaggat cagttgaatc301tacagggaga gttcattgag gaaattcgga aacgactgtg tcagctgcag caagagaaaa361cgttacaagt gaagcttgag gtccagagct cagagcagcc cagctccaag tctctgagct421tcacgctgag ctcgccccag ctccagcagg aggtggagtt tgatgtgcag ccagcctatg481atgtcctgtt tgccctaaga aacaaccaca agcccgaccc ccaaatctac accaaaacct541acgcctacct catcagtgtg tgcaccactc tgaagaagga gggcgagttc tccacctgct601tcatggagct ccggcaaaac ttcctgaagc atcgggaacc caagctgaag agcctcatcc661gtctggtcaa gcactggtat caactgtgta aggagaagct ggggaagccg ctgcccccac721agtacgccct ggagctgctc acggtctatg cctgggaaag tgggagtaga gactgtgaat781tcaacacagc ccagggcttc cgaaccgtct tggaactggt caccaagtat cagtggcttc841gaatctactg gacattgtat tatgacttta gaaacaagaa ggtctctgat tacctacaca901aacagctcaa aaaaaccagg cctgtgatcc tggacccggc tgacccgaca agaaatgtgg961ctggttcaaa ccccctctgc tggcgactgt tggcaaaaga agctgctagc tggctgcagt1021gcccatgctt taggacctgt gatatgtccc tcgtgcactc ctgggaagtg ctgacaaagg1081tcgagtttcc acaggaatgt gtccttctat gagcaccaaa gcacctgccc aggatgctca1141agagtcaggg gcatgacctc tgctgcaggc ccttgaccta gagaggagag gaagctcccc1201aaaaccccaa caagggaggg tccaacctgt gatcagactc tggtcttctg acccctgcct1261tcctactcct gcatcctgtc ccatcacaga cagccctcct cacagcctgc ttcatctgcc1321ttgtcctcca acagtgctct cttgggagac aagagattca gaaggggagg caggaactcg1381agcttgactt ccacctgtcc acctgttggg agttctgtcc aatgtgtgac caacgacaat1441aaaccatagc aagccatgag gatatgtgaa cattctgaag gatgtgtgtt ctcctccctc1501tccctctccc cttccctacc taccctgtcc tgcctcacat acgttttctt acctctacnt1561gcatatgaca tgatagtata tttaagtgat cccaaaagtt ccaccagaga actactaaa//(SEQ ID 30)LOCUS AY221507 1469 bp mRNA linear ROD 02-JUN-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase1G (Oas1g) mRNA, complete cds.ACCESSION AY221507translation=“MEQELRSTPSWKLDKFIEVYLLPNTSFRDDVKSAINVLCDFLKERCFRDTVHPVRVSKVVKGGSSGKGTTLKGKSDADLVVFLNNFTSFEDQLNRRGEFIKEIKKQLYEVQREKHFRVKFEVQSSWWPNPRALSFKLSAPHLQQEVEFDVLPAYDVLGHVSLYSNPDPKIYTILISECISLGKEGEFSTCFTELQRNFLKQRPTKLKSLIRLVKHWYQLCKEKLGKPLPPQYALELLTVYAWERGNGITEFNTAQGFRTILELVTKYQQLRIYWTKYYDFQHPDVSKYLHRQLRKSRPVILDPADPTGNVAGGNQEGWRRLASEARLWLQYPCFMNRGGSPVSSWEVPTEVPVPSEQVDEAWSCILL”polyA_signal 1428 . . . 1433/gene=“Oas1g”BASE COUNT 385a 388c 392g 304tORIGIN1gttccaagtt caaccaggct gcgagacaca ggacctgcag gctgcagagg caaaagctcc61ggaggtcatg gagcaggaac tcaggagcac cccgtcctgg aagctggaca agttcataga121ggtttaccrc cttccaaaca ccagcttccg tgatgatgtc aaatcagcta tcaatgtcct181gtgtgatttc ctgaaggaga gatgcttccg agatactgtc cacccagtga gggtctccaa241ggtggtgaag ggcggctcct caggcaaagg caccacactc aagggcaagt cagacgctga301cctggtggtg ttccttaaca atttcaccag ctttgaggat cagttaaaca gacggggaga361gttcatcaag gaaattaaga aacagctgta tgaggttcag cgtgaaaaac attttagagt421gaagtttgag gtccagagtt catggtggcc caacccccgg gctctgagct tcaagctgag481tgcaccacac ctccaacagg aggtggagtt tgatgtgctt ccagcctatg atgtcctagg541tcatgttagc ctctacagca atcctgatcc caagatctac accatcctca tctccgaatg601tatctccctg gggaaggagg gcgagttctc tacctgcttc acggagctcc agaggaactt661cctgaagcag cgcccaacca agctgaagag tctcatccgc ctggtcaagc actggtacca721actgtgtaag gagaagctgg ggaagccgct gcccccacag tacgccctgg agctgctcac781ggtctatgcc tgggaacgtg gaaatggaat tactgagttc aacacagctc agggcttccg841gacaatcttg gaactggtca caaagtacca gcagcttcga atctactgga caaagtatta901tgactttcaa cacccagatg tctccaaata cctacacaga cagctcagaa aatccaggcc961tgtgatcctg gaccctgctg acccaacagg gaacgtggct ggtgggaacc aagaaggctg1021gcggcggttg gcctcagagg cgaggctgtg gctgcagtac ccatgtttta tgaacagggg1081tggttcccca gtgagctcct gggaagtgcc gacagaggtt cctgtgcctt cagagcaggt1141ggatgaggcc tggtcatgca tcctgctgtg aacccagcag caccagccca ggaggctccg1201gagtcagggg cacgtgctgc tttgctgcag gaccttgaca cagtgaggga gggccccact1261cgggatcaca gtccatgctt ttgatgcccg cccgccatgt ttgaatactg tccaatcaca1321gacagccttc ctcaacagat tcagaagggg cggaaagaac tcaagcttga cttccatctg1381accgtccacc tgttgggagg ttctgtccaa ccatgtctgt caacaacaat aaagtacagc1441aggtgccaaa aaaaaaaaaa aaaaaaaaa//(SEQ ID 31)LOCUS AY196701 1701 bp mRNA linear ROD 20-MAY-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase1H mRNA, complete cds.ACCESSION AY196701translation=“MEKDLKSTPAWKLDKFIQNHLLADTTFVTEAKADIEFLCDFLTERCFQDASHPVRVSRIVMGGCYDEYSMLKGRSEATLVVFFNNLTRFEDQLKRREELIEEIWKHLCQLQHEKQFKLKFEVQSSEQDNYSSLSIKLSSPQLQQEVEFDVQPAYDVLYELKEKLELDCEFYNKIYARLIRECITLRKEGEFSVCFMELQQKFLWNRPEDLRNLLVLVKHWYQLCKEKLGDSLPPQYALELLTVHAWENEIPAKYGAQTARGFQSVLELIIKYTCLRVYWTFYYDILHQDVSSYLHKQLRKERPVILDPADPTRNVAGLNIDGWCELAKEAEAWLKYPCFRHIDETFVGSWEVPPEKQGGVFL”BASE COUNT 440a 421c 460g 380tORIGIN1gcagtcagca aacattcctg gcctcaggat ggagaaggat ctcaagagta ctccagcttg61gaagctggac aagttcatac agaatcacct ccttgctgac accaccttcg ttactgaggc121caaggcagac atagagttcc tatgtgattt cctgactgag agatgcttcc aagatgcctc181ccaccctgtg agggtctcta ggattgtgat gggcggctgc tatgatgaat actccatgct241caagggaagg tcagaggcca ccctggtggt gttctttaac aatctcacca gatttgagga301tcagttaaag cgacgggaag agctcattga agaaatttgg aaacacctgt gccagttgca361gcacgagaaa cagtttaaac tgaagtttga ggtccagagc tcagagcagg acaactacag421ctctctgagc atcaagctga gctcgcccca gctccagcag gaggtggagt ttgatgtgca481gccagcctat gatgtcctgt atgaactgaa agaaaaactg gagcttgact gtgagttcta541caacaaaatc tatgcccggc tcatccgtga gtgcatcacc ctgaggaagg agggcgagtt601ctccgtctgc ttcatggagc tccagcaaaa gttcctgtgg aatcgtccag aagacctgag661gaatctcctc gtactggtca agcactggta tcaactgtgt aaggagaagc tgggggattc721gctgccccca cagtacgccc tggagctgct cacggtccat gcctgggaaa acgaaattcc781agccaaatat ggagcacaga cagctcgggg tttccagagt gtcttagaac tgatcattaa841gtacacctgt cttcgagtct actggacatt ttattacgac attctacacc aggatgtctc901cagctacctg cacaaacagc tccgtaaaga aaggcctgtg atcctggacc ctgctgaccc961aacaaggaac gtggctggtt tgaacataga tggctggtgt gagctggcaa aagaggcaga1021agcctggctg aagtacccgt gctttaggca catcgatgag acctttgtgg gctcctggga1081agtgccgcca gagaaacaag gaggtgtctt cctgtgagca ccacagccct tgcccaggag1141gctctggagt caggggcatt cactcctctg ctgcaagacc ttgtcctgca gagaacagtt1201tggtacacca ggctccagtg aggggcatcc aacctgtgat cagactctag gcttctgatc1261ccgtcctgcc catgggacag ccttcctcac agcctgcttc acctgcctta tcctccacag1321tgctctctgg gagtcagact ccgaaggaaa gagaagagct caaacttggc ttctgtctgt1381ccacctgtgg ggaggctctg tccacaaaca tgtctgatca tgaacaattg accacagcaa1441tccctgaggg agtgtgcact cggaggggtg agtcctcagc ccacatagga acggctcagc1501agaggagcgt ggcccggaac gctggggatc tggccagtgt gcatcaaggt gcactgttgg1561gcaaagtgtg agctggggtt acggcagtgc agggaaataa gattatgtac actttaaaac1621ttaggacctt aaaacgtatg tgtgtgcatg tgaggatgag atttgaagcc ctgaattaaa1681gtaaaatgca aaggactaaa c//(SEQ ID 32)LOCUS AY227756 1980 bp mRNA linear ROD 06-JUN-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase-like1 protein (Oas11) mRNA, complete cds.ACCESSION AY227756/translation=“MAVAQELYSFPASKLDSFVAQWLQPTREWKEEVLETVQTVEQFLRQENFRGERGPAQDVRVLKVLKVGCFGNGTVLRSTTDVELVVFLSCFHSFQEEAKHHQAVLRLIQKRMSYCRDLLDLGLSNLSVIEEVPSSLIFTIQTRETWEPITVTIVPAFRALGPSCPNSAEVYVNLIKANGYPGNFSPSFSELQRSFVKHRPTKLKSLLRLVKHWYQQYVRDKCPRANLPPLYALELLTVYAWEAGTQEDSNFRLDEGLATVMELLQDHELLCIYWTKYYTLQHPVIERFVRRQLKGERPIILDPADPTHNVAQGYRWDIVAQRASQCLKQDCCYDDRDAPVPSWTVKRAPYIQVTVQQWGHPDLILWVNPYEPIKKLKEKIRLSRGYSGLQRLSFQEPGGQRQLIRSQCSLAYYGIFCDTQICLLDTISPEIQVFVKNPDGGSHAYALHPLDFVLSLKQQIEDRQGLQSQEQQLEFQGRVLEDWFDFKSYGIQDSITIILSRKREGKAPSAPS”polyA_signal 1953 . . . 1958/gene=“Oasl1”BASE COUNT 477a 586c 510g 407tORIGIN1gcgcagacat ggcagtagcc caggagcttt acagcttccc agcctccaag ctggactcct61ttgtggctca gtggctgcag ccaaccagag aatggaagga ggaggtcctg gagacggtgc121agacagtgga gcagttcctg aggcaggaga acttccgtgg agaacgtggc ccggcccagg181atgtacgagt gctcaaggta ctcaaggtag gctgctttgg gaatggcaca gtactcagga241gtaccacaga cgtggagctg gtggtgttcc tgagctgttt ccacagcttc caggaagagg301ccaaacacca ccaggctgtt ctgagactga tacagaaaag gatgtcttac tgccgggacc361tgctggatct cgggctcagt aacctgagtg tgattgaaga agtgcccagt agtctcatct421tcactatcca gaccagggag acctgggagc ccatcactgt caccatcgtg cccgccttca481gagccctggg accttcctgt cccaactccg ccgaggtcta tgtgaatctg atcaaggcta541acggctaccc cggaaatttc tctccttcct tcagcgagct acagaggagc ttcgtgaagc601ataggccgac taagctgaag agcctcctac ggttggtcaa acactggtac cagcagtacg661tgagagacaa gtgcccccgg gccaacctgc cccccctcta tgccctggag ctgctaactg721tctacgcgtg ggaagcaggt acgcaggagg attcgaactt caggctggat gaaggtctcg781ccactgtcat ggagttgctc caggatcatg aactcctgtg catctactgg accaagtact841acaccctgca acacccagtc attgagcgct tcgtcaggag acagctcaaa ggagaaaggc901ccattatcct ggacccagca gaccccaccc acaacgtggc gcaaggctac aggtgggata961tagttgctca gcgcgccagc cagtgtctga aacaggactg ttgctatgac gacagggacg1021cccccgtccc cagctggact gtgaagagag caccatatat ccaggtgacc gtgcagcagt1081ggggtcaccc ggatttaatc ctctgggtga acccttatga acccataaag aagctgaaag1141agaaaatccg actgagccgg ggctactccg gcctgcagcg cctgtccttt caggagcccg1201gcggccaacg gcagctcatc agaagccaat gctcgcttgc ctactacgga atcttctgcg1261acactcagat ctgcctgctg gacaccatct cccccgagat ccaggtcttt gtgaaaaacc1321cggatggtgg aagccacgcc tacgccatcc acccacttga cttcgtcctg agcctgaagc1381agcagatcga agataggcag ggccttcaaa gccaggagca gcagctggag ttccagggcc1441gcgtcctgga agactggttt gactttaaat cctatggcat ccaagatagt atcacgatca1501tcctatccag gaagagggag gggaaagccc catctgcgcc cagctagctt cctctgcctc1561ttttgctatc tcatcctaaa gtcagcctag tcacccctcc ttccggtcct cagccgggat1621gatcccagca gggagccaga agggaatact gccagacgct cttgtgtgac aatgaaactc1681tgcagtcacc tgtgaaatca caccaggacc tctacgctct caagactggg tcagtgaatg1741gccgtcccac aaataaacta ttctcgcttg ttcttgggaa gccaaacgat cttcctaacc1801aatcaaatgg accctgcttc aggttgttcc cccacacaca ccagcaacct ccatcaggtt1861ggatctgaag ccttcccctg tgctcccaac cacttctgcc tgcctcagcc tatccaaggc1921aaggtagggt atcaagttcc tttcaaatgg agaataaaca acctttgttt cctcccagat//(SEQ ID 33)LOCUS AY237116 1750 bp mRNA linear ROD 12-JUN-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase2-like protein (Oas12) mRNA, complete cds.ACCESSION AY237116/translation=“MDTLPDLYGTVGDSLDYFLEHSLQPQRDWKEEGKDAWERIERFFREKCFCDELLLDQEVRVLKVVKGGSSGKGTALNHRSDQDMILFLSCFSSFKQQARDRKAVIDFIKSKLIHCRKSLAYNITVRQHKEGKRTPRSLTLEIQSRKSNDIICMDILPAYNALGSFSRDCKPEPEIYENLIRCKGYPGDFSPSFAELQRHFVKSRPVKLKNLLRLVKFWHLKYLRHKYRRAVLPSKYALELLTIYAWEMGTDSSDNFNLDEGFVAVMELLRDYQDICIYWTKYYDFQNEVVRNFLKEQLKGDRPIILDPADPTNNLGRRGKWELVAKEATYCLLQLCCVTADRWNVQVSIAHYLRGARDVQVTVKQTGREEWILLTNPHSPIRKLKAKIKKRMNLCGELRISFQEPGGERQPLSGRKTLSDYGIFSKVNIRVMETFPPEIQVFVRYPGGQNKPFAIDPDATILSLWEKIEEDGGPCTEDWVLLFEGEELDDDDNLAELQIKDCDTIQLSRVS”BASE COUNT 485a 415c 468g 382tORIGIN1ttctcccagc attgctgagc agaagcacag aagattcaat ccagaggaca ggctgatcca61gcagagatgg atacattacc cgacctgtat gggaccgttg gggacagtct agactacttc121ctggaacaca gccttcagcc ccaaagggac tggaaagagg aaggaaagga tgcctgggag181agaattgaga ggttctttcg ggaaaagtgc ttctgtgatg agctgctcct ggaccaagaa241gtcagggtgc ttaaagtggt aaagggaggc tcctcaggaa aggggacggc gctgaaccac301agatctgacc aggacatgat tctgttcctg agctgttttt ccagtttcaa acagcaggca361agagaccgga aggccgtcat agacttcatt aagagcaagc tgattcattg taggaaaagc421ctggcctaca acatcactgt ccgtcaacac aaagaaggca aaaggacccc tcgctccctg481accctagaga tccagtccag gaagagcaat gacataattt gcatggatat tctccctgct541tacaatgcct tgggatcctt ttccagagac tgcaaaccag aacctgaaat ctacgagaat601ctgataaggt gtaagggcta ccctggcgac ttctcgccaa gtttcgcaga gttacagaga661cattttgtga aaagtcgccc ggttaaactg aaaaacctcc tacggttggt gaagttctgg721cacctgaagt acctgaggca taaatataga agagcagtgt tgccctcaaa atatgcactg781gagttgctga ccatctatgc ttgggagatg ggtacagaca gcagtgataa tttcaatctg841gatgaagggt ttgtagccgt catggagctc ctcagggact accaagacat ctgcatctac901tggaccaagt actatgattt ccaaaatgag gtcgtcagga acttcctgaa ggaacagctt961aagggcgacc ggcctatcat tctagaccca gctgacccca ccaacaacct aggaagaaga1021ggaaaatggg aactggtggc caaagaagct acttactgcc tgctacagtt gtgttgtgtg1081actgcagacc gctggaatgt tcaggtatct atcgcgcact acctccgagg agcgagggac1141gttcaggtga cagtgaaaca aacaggaagg gaagagtgga ttctcttgac aaacccccac1201agccccatca ggaagttgaa ggcaaagatc aagaagagaa tgaacctctg tggggagctg1261cgtatctcct tccaggagcc gggaggggag aggcagccgc tgagtggccg gaaaaccctg1321tcggattatg gaattttctc taaggtgaac atccgggtga tggagacctt tcctcctgag1381atccaggtct ttgtgaggta tcccggtggc cagaacaagc cttttgccat cgaccctgat1441gctaccatct taagcctgtg ggagaaaatt gaggaagatg gaggcccatg tacggaggat1501tgggtactac tgtttgaggg tgaggagctg gacgatgatg acaaccttgc agagcttcag1561atcaaggact gtgacaccat ccagctcagc agggtctcct agtctgcctc cccacatcac1621ccctttactc tgacatattc ctcctgtagc ttaaacatca tcatatccgg ttggggattt1681ggctcagtgg tagagcgctt gcctagcaac cgcaaggccc tgggttcggt ccccagctcc1741gaaaaaaaaa//(SEQ ID 34)LOCUS AY230746 2311 bp mRNA linear ROD 05-JUN-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase2 (Oas2) mRNA, complete cds.ACCESSION AY230746/translation=“MGNWMPGWSSSGSLGVPPMPVQKLEKSVQVNLEPDEKCLSQTEVSSVPSQKLEEYIQANLKPDEESLKQIDQAVDAISDLLCSEVMIDVLKVVKGGSYGRKTVLRDCSDGTLVLFTGLFKQFQDQKKYQDKLLDLIEQRLKSHEKYKKSVKRKLSLLEVQVSIPGQSILLQLLPTFNPLCISENPSAQVYQNLKRSMDQVKASPGEFSDCFTTLQQRFFEKYPGRLKDLILLVKHWYKQLQDKWIIPSPPPLLYALELLTVYAWEQGCQTKDFDITQGIRTVLQLISQPTNLCVYWLDNYNFEDETVRNNLLHQLNSPRPVILDPTDPTNNVGKDDRFWQLLAEEAQEWLNSLRLNKPHKPCWDVLPMPFFITPSHCLDKFIKDFLQPDKVFLNQIKRAVDIICSFLKETCFQNSDIKVLKIIKGGSTAKGTALQQRSDADIIVFLSSLDSYDSLETERSQYVQEIRKQLEACQKAFNLGVKFDISKWMAPRVLSFTLESKSLKQSVEFDVLPAYDALGQLRSDYTSRLKAYKKLIELYASQDSLKGGEFSVCFTELQRDFIETRPTKLKGLIRLIKHWYKQCERKMKPKASLPPKYALELLTVYAWEHGSGTDGFDTAEGFRTVLDLVIRYRQLCVFWTVNYNFEEDHMRKFLLTQIQKKRPVILDPADPTGDVGGGDRWCWHLLAKEAKEWLSSSCFQVEPKSPVQPWKVPVVQTPGSCGAQIYPVVGGVY”BASE COUNT 649a 573c 566g 523tORIGIN1agtgctctgc ctctgtcatt cacaagccca gctagcaact atgggaaact ggatgcctgg61ctggtcatcc agtgggtctt tgggggtgcc ccccatgcca gtgcagaagc tagaaaagtc121tgtccaggta aaccttgaac cagatgaaaa atgtctgagt cagaccgagg tgtcctctgt181accatcccag aagctagaag aatatatcca ggcaaacctc aaacccgatg aagaatctct241gaagcagata gaccaggctg tggatgccat ctctgacctg ctgtgcagtg aggtgatgat301cgatgtgctg aaagtggtta agggtggctc ctatggtcgg aaaacagtcc taagagactg361ctccgatggt acacttgttc tcttcaccgg tctcttcaaa cagttccaag accagaagaa421ataccaagat aagctccttg acttgattga acaacggctg aaaagccatg agaaatacaa481gaagtcagta aaacgtaaac ttagcctcct tgaagtacaa gtgtctatac cagggcagag541tatactcttg cagttgcttc caaccttcaa tcctctgtgc atcagtgaga atcccagcgc601ccaggtctat cagaatctca aaagatccat ggatcaagta aaagcatcac ctggggaatt661ctcagactgc ttcaccacac tgcagcagag gtttttcgag aaatatcccg ggagactgaa721ggatttgatt ctattggtca agcactggta taaacagttg caggataagt ggataatacc781ctcacctccg ccattgctat atgcactgga gctgcttact gtgtatgcct gggaacaggg841ctgccagact aaagactttg acatcacgca aggtatcagg actgtgctgc aactcatcag901tcagccgaca aacctgtgtg tctactggtt agacaattac aactttgagg atgagacagt961ccggaacaac cttctgcacc agctcaactc cccaagaccg gtcatcttgg atccaaccga1021cccaaccaac aatgtgggca aagatgacag gttctggcag ctactggcag aagaggctca1081ggagtggctg aactctctca gactgaataa gccacacaaa ccatgttggg atgttctgcc1141catgccattt ttcatcaccc caagccactg cctggacaag ttcatcaaag acttcctcca1201acctgacaag gtcttcctaa accaaatcaa aagagctgtt gacattatct gttcattctt1261aaaagagacc tgcttccaga attctgacat caaagtcctg aagatcatca agggaggatc1321cactgccaaa ggcacagctc tgcagcagag atcagatgct gacatcatag tgttcctcag1381ctcactggat agttatgact ccctagaaac tgaacgctcc cagtacgtcc aggagatccg1441aaagcagtta gaagcctgcc agaaggcctt taatttaggg gtgaagtttg atatttccaa1501atggatggcc cccagggtgc tgagttttac cctggaatcc aagagtctca agcaaagtgt1561ggagttcgat gtccttcccg cctatgatgc actaggtcag ctgcggtctg actacacctc1621caggctcaaa gcctacaaga agctcattga gctgtatgcc tcacaggaca gcctcaaagg1681aggggagttt tcagtctgtt ttacagagct acagagagac ttcattgaaa ccaggcccac1741caaactcaag ggtctgatcc gcctgatcaa gcactggtac aaacagtgtg aaaggaagat1801gaagccaaaa gcatctttgc ctccaaagta cgcactggag ctgctcaccg tgtatgcgtg1861ggagcatggc agtggcacag atggcttcga cactgctgaa ggcttccgga ccgtcctgga1921cttggtcata agataccggc agctctgcgt cttctggaca gtcaattaca actttgagga1981ggatcacatg aggaagttcc tactgaccca gatccagaaa aagaggcctg tgatcctgga2041tccagcagat cccacaggtg atgtgggagg aggtgaccgc tggtgttggc atcttctagc2101caaagaagca aaggagtggc tgtcctcctc ctgtttccaa gtggagccaa aaagccccgt2161gcagccgtgg aaagtaccag tagtacagac tccaggaagc tgtggagctc agatctaccc2221tgtggtgggt ggggtgtact aagagagtgc attcagctct ggagggaaaa tgctggaaga2281agcttctaga gacatctggc aaagactctg c//(SEQ ID 35)LOCUS AY250706 4015 bp mRNA linear ROD 06-MAR-2003DEFINITION Rattus norvegicus 2′-5′ oligoadenylate synthetase3 mRNA, complete cds.ACCESSION AY250706/translation=“MDLYHTPAGALDKLVAHSLHPAPEFTAAVRRALGSLDNVLRKNGAGGLQRPRVIRIIKGGAHARGTALRGGTDVELVIFLDCLRSFGDQKTCHTEILGAIQALLESWGCNPGPGLTFEFSGPKASGILQFRLASVDQENWIDVSLVPAFDALGQLHSEVKPTPNVYSSLLSSHCQAGEHSACFTELRKNFVNIRPVKLKNLILLVKHWYRQVQTQVVRATLPPSYALELLTIFAWEQGCRKDAFSLAQGLRTVLALIQRNKHLCIFWTENYGFEDPAVGEFLRRQLKRPRPVILDPADPTWDLGNGTAWCWDVLAKEAEYSFNQQCFKEASGALVQPWEGPGLPCAGILDLGHPIQQGAKHALEDNNGHLAVQPMKESLQPSNPARGLPETATKISAMPDPTVTETHKSLKKSVHPKTVSETVVNPSSHVWITQSTASSNTPPGHSSMSTAGSQMGPDLSQIPSKELDSFIQDHLRPSSQFQQQVRQAIDTILCCLREKCVDKVLRVSKGGSFGRGTDLRGKCDVELVIFYKTLGDFKGQNSHQTEILCDMQAQLQRWCQNPAPGLSLQFIEQKSNALHLQLVPTNLSNRVDLSVLPAFDAVGPLKSGAKPLPETYSSLLSSGCQAGEHAACFAELRRNFLNTRPAKLRSLMLLVKHWYRQVAAREEGGETAGAALPPAYALELLTVFAWEQGCGEQKFSMAEGLRTVLRLVQQHQSLCIYWTVNYSVQDPAIRAHLLRQLRKARPLILDPADPTWNMDQGNWKLLAQEAAALESQVCLQSRDGNLVPPWDVMPALLHQTPAQNLDKFICEFLQPDRHFLTQVKRAVDTICSFLKENCFRNSTIKVLKVVKGGSSAKGTALQGRSDADLVVFLSCFRQFSEQGSHRAEIIAEIQAQLEACQQKQRFDVKFEISKRKNPRVLSFTLTSKTLLGQSVDFDVLPAFDALGQLKSGSRPDPRVYTDLIQSYSNAGEFSTCFTELQRDFISSRPTKLKSLIRLVKHWYQQCNKTVKGKGSLPPQHGLELLTVYAWERGSQNPQFNMAEGFRTVLELIGQYRQLCVYWTINYGAEDETIGDFLKMQLQKPRPVILDPADPTGNLGHNARWDLLAKEAAAYTSALCCMDKDGNPIKPWPVKAAV”BASE COUNT 887a 1086c 1119g 923tORIGIN1gaaactctcc tgagggcatg ggtcaacatg gacctgtacc acacgccagc cggagctctg61gacaagctgg tggcccacag cctgcaccca gcccctgagt tcacagcggc tgtgcggcgt121gctctggggt ccctggacaa cgtcctaagg aagaacggag ccggagggtt acagagacca181agggtgataa ggatcatcaa gggaggagcc catgctcgag gcacagctct cagaggtggc241actgatgtcg aactcgtcat cttcctcgac tgcctccgga gctttggcga ccagaagacc301tgtcacacag agatcctggg cgccatacaa gcattgctgg agtcctgggg gtgcaaccct361gggcctggcc tgacttttga gttttctggg ccaaaggcgt ctggcatctt acagtttcgc421ctggcatcgg tggaccaaga aaactggata gatgttagcc tggtgcctgc cttcgatgcc481ctaggacagc tccactctga agtcaagcca acacccaatg tgtactcctc cctcctcagc541agccactgcc aggctgggga acactcagcc tgcttcacag agctccggaa gaactttgtg601aatatccgcc cagtcaaact taagaactta atcctgctgg tcaaacactg gtaccgccag661gtgcagacac aggttgtgag agccacactg ccccctagct acgcgctgga gctgctcacc721atctttgcct gggagcaggg ctgtaggaag gatgccttca gcctggccca agggctccgg781actgtcctgg ccttgatcca acgcaacaag catctctgca ttttctggac ggaaaactac841ggcttcgaag accctgcagt tggggagttc ttgcgaaggc agcttaagag acccaggccc901gtgatcctgg atccagctga cccaacatgg gacttgggca atgggacagc ctggtgctgg961gatgtgcttg ccaaggaggc tgaatacagc tttaaccagc agtgcttcaa ggaggcctca1021ggagcccttg tgcaaccttg ggaggggccg ggccttccat gtgctgggat cttggatttg1081ggtcacccta tccaacaagg agctaagcat gcccttgaag acaacaatgg ccaccttgct1141gttcagccaa tgaaagagag cctacaacca tcaaatccag cccgaggact cccagaaaca1201gccaccaaga tctccgctat gccagaccca acggtcactg aaacccacaa gagcctcaaa1261aaatcagtgc acccaaagac tgtcagtgaa acagtggtga atccctcaag tcatgtttgg1321atcacccaga gtacagcatc ctcaaacacg cctccgggcc actctagtat gtccaccgct1381gggtcacaga tgggcccaga tctgtcacag atccccagca aggagctgga ctccttcatc1441caggaccace tcaggccgag ttcccagttc cagcagcagg tgaggcaggc catcgacacc1501atcctgtgct gcctccggga gaagtgtgta gacaaagtct tgagagtcag caagggtggc1561tcttttggcc gtggcacaga cctcaggggc aaatgtgatg tggagcttgt catcttttat1621aaaactctcg gggacttcaa gggccagaac tcacaccaga cagagatcct gtgtgacatg1681caggcccagc tgcagcgctg gtgtcagaac ccagcacctg gactgagcct ccagtttatt1741gaacagaagt ccaatgctct gcatcttcag ctggtgccca ccaacctcag caaccgggta1801gacctcagtg tgctgcccgc ttttgatgca gtggggccgc tgaagtccgg cgccaaacct1861ctacccgaga cgtactcctc cctcctcagc agcggctgcc aggctgggga gcatgcagcc1921tgcttcgcag agctccgaag gaacttcata aacactcgcc ctgccaaact taggagcctg1981atgctactgg tcaaacactg gtaccgccag gttgccgctc gatttgaagg aggagagaca2041gcaggtgctg ctctgccccc agcctatgcc ctggagctcc tgacagtctt tgcctgggaa2101caaggctgcg gagaacaaaa gtttagcatg gctgaaggcc tgcggactgt cctgaggctg2161gtccagcagc accagtcact ctgtatctac tggacagtca actacagtgt gcaggaccca2221gccatcagag cacaccttct ccgccagctt cggaaagcca ggcctctaat cctagaccct2281gcagatccca cctggaacat ggaccagggc aactggaagt tgctggctca ggaggcggct2341gccctggagt cacaagtctg ccttcagagt agggatggga atctggtgcc accatgggat2401gttatgccag ccctccttca ccagaccccg gctcagaacc tggacaagtt catctgtgaa2461ttcctccagc ctgaccgcca tttcctgact caggtgaaga gagcagtgga caccatatgt2521tccttcctga aagaaaactg cttccggaat tctaccatca aggtgctcaa ggtggtcaag2581ggtgggtctt ctgccaaagg cactgctcta caagggcgct cggatgctga cctggtggtg2641ttcctcagct gcttccgcca gttctctgaa caaggcagcc atcgggcaga gatcatcgcg2701gagatccagg ctcagctgga ggcgtgtcag cagaagcaga ggttcgatgt caagtttgag2761atctccaaga ggaagaaccc ccgagttctc agcttcacgc tgacatccaa gacgctgcta2821ggccagagcg tggacttcga tgtgctgcca gccttcgatg ctcttggtca gctgaagtcc2881ggctctcggc cagatccccg ggtctacacg gacctcatcc agagctacag taatgcagga2941gagttctcta cctgcttcac ggagctgcag cgggacttca ttagctcccg tcccaccaaa3001ctcaagagtc tgatccgtct ggtgaaacac tggtaccaac agtgtaacaa gacagtcaag3061gggaagggtt ccttgccccc ccagcacggg ctggagctcc tgactgtgta cgcctgggag3121cgaggcagcc agaaccccca gttcaacatg gcggagggct tccgcacagt tctggagctg3181attggccagt accgtcagct gtgcgtctat tggaccatca actacggtgc agaagacgag3241accatcggag acttcctgaa gatgcagctt cagaagccca ggcctgtcat cctggaccca3301gctgacccga caggcaacct aggccacaat gcccgctggg acctgcttgc caaggaggct3361gcagcataca catctgccct gtgctgcatg gacaaggacg gcaaccccat caagccatgg3421ccagtaaagg ccgctgtgtg aagtccagaa agatcaaaaa gtgacaccag ccctcagcaa3481gggatactca gaatatctgg ccagatgtgt gtgtgtgtgt gtgtgtgtgt gtgttgtgta3541ttgtgtttat ctatatatgt ttctgtgctg tgtctgtgtg tctctgtagg tggtgtgtgt3601ctgtgtaccc acaggtgtct acatgtgtct gtatatatgt aagagtgtgt gtatgtatgt3661atgttcacgt gtctctgtgt gtgtgcatct gtgtgtttgt atgtagtgtg tctataggtg3721tatccttatg agtgtgtgtg tttgtggtgg agtgtgtgtg tgtctgtgta tctgtgggtg3781tctatatgtg tctgagtgtg tgtgattatt tgtgtgttta tgtgtctgtg tatttgtgtg3841tagtgagttt ataggtgcat ctgtgtgtct atatgtatat gtgtgtctat gtgtgtctat3901ggtgtgtgtc cgtgtatctg tgggtgtcta tgtgtgtctg tatgtacgtg tgtgtgtgtg3961tgacttgctt tgtccaaatg attgtatgta tgtatgtgtg ctcatgtggc tctgt//(SEQ ID 36)LOCUS AY243505 1682 bp mRNA linear MAM 13-JUN-2003DEFINITION Bos taurus 2′-5′-oligoadenylate synthetase1 (OAS1) mRNA, complete cds.ACCESSION AY243505VERSION AY243505/translation=“MELRNTPAGSLDKFIEDHLLPDEEFRMQVKEAIDIICTFLKERCFRCAPHRVRVSKVVKGGSSGKGTTLRGRSDADLVVFLTNLTSFQEQLERRGEFIEEIRRQLEACQREETFEVKFEVQKRQWENPRALSFVLRSPKLNQAVEFDVLPAFDALGQLTKGYRPDSRVYVRLIQECKYLKREGEFSPCFTELQRDFLKNRPTKLKSLIRLVKHWYQLCKEQLGKPLPPQYALELLTVYAWEQGCNKTGFITAQGFQTVLKLVLKYQKLCIYWEKNYNSENPIIEEYLTKQLAKPRPVILDPADPTGNVAGKDANSWERLAQAALVWLDYPCFKKWDGSPVGSWDVSPQEHSDLMFQAYDFRQHCRPSPGIQFHGGASPQVEENWTCTIL”BASE COUNT 436a 431c 431g 384tORIGIN1gcacgagcac agattcaggc agcagctctg ccgcctctgg ctctccagtc cccagcaccg61tgatggagct cagaaatacc ccggccgggt ctctagacaa gttcatcgaa gaccacctcc121tgccagacga ggagttccgc atgcaggtca aagaagccat cgacatcatc tgcactttcc181tgaaggagag gtgtttccga tgtgcccctc acagagttcg ggtgtccaaa gttgtgaagg241gcggctcctc aggcaaaggc acgaccctca ggggacgatc agatgctgac ctcgtcgtct301tcctcaccaa tctcacaagt tttcaggaac agcttgagcg ccgaggagaa ttcatcgaag361aaatcaggag acagctggaa gcctgtcaaa gagaggaaac atttgaagtg aagtttgagg421tccagaaacg gcaatgggag aatccccgcg ctctcagctt tgtgctgagg tcccccaagc481tcaaccaggc ggtggagttc gatgtcctgc ccgcctttga tgccctaggt cagttgacca541aaggttacag acctgactct agagtctatg tccggctcat ccaagagtgc aagtacctga601agagagaagg cgagttctcc ccctgcttca cggagctgca gcgagacttc ctgaagaatc661gtccaaccaa gctgaagagc ctcatccgcc tggtgaagca ctggtaccaa ctgtgtaagg721agcagcttgg aaagccattg cccccacaat atgctctgga gcttctgacg gtctatgcct781gggagcaagg atgcaataaa acaggattca tcacagctca gggatttcag actgtcttga841aattagtcct aaagtatcag aagctttgca tctactggga aaagaactat aactctgaaa901accctattat tgaagaatat ctgacgaagc aacttgcaaa acccaggcct gtgattctgg961acccggcgga ccctacagga aatgttgctg gtaaagacgc aaatagctgg gagcggcttg1021cacaagcggc tttggtctgg ctggattacc cgtgctttaa gaaatgggat gggtctcccg1081tgggctcctg ggatgtgtcg ccccaagaac acagtgacct gatgttccag gcctatgatt1141ttagacagca ctgtagaccc tctccaggaa tccagttcca cggaggagcc tctccccagg1201tggaagagaa ctggacatgt accatcctct gaatgccaga gtatcttgga ggcaaggtct1261ccagagccgt ctgggccagc cctcttcact tctagggata gggggcttgg atccaaagac1321agctgtgaat tgatgtcaga cctgggacca gaatccaggt ctcctgaccc ccagccttcc1381tgctattctg tgctgtcttt tctttcatag acaatgctcc ccattggagc ctgacaatag1441cctctctgag ccaccaggag agactcaggc aaaagagtgg aatcccagcc ttgactttct1501tctgtgaacc tgaggggaaa ggtgatggtc caatttattg tcaataataa caaaaatagt1561agcaaatgcc atttgttggg tgttaattag cttcaaggta cagcgccaag aagtatacct1621gcatattatg tgtgtgtgtg catattcatt gattcaacta aagatattaa ttgggcacct1681gc//(SEQ ID 37)LOCUS AY321355 1601 bp mRNA linear MAM 11-JUN-2003DEFINITION Equus caballus 2′-5′ oligoadenylate synthetase1A (Oas1a) mRNA, complete cds.ACCESSION AY321355/translation=“MELQKTPARNLDKFIEDYLLPDTRFRRQVREAIDIICSFLKERCFRGAVPPVRVSKVVKGGSSGKGTTLRGRSDADLVVFLDYLTSFREQFERRAEFIKEIRRQLEACQREKRFDVEFEVQGQQWARPRALSFVLTSPQLNEGVEFDVLPAFDVLGQVTTSYRPDPDIYVLLIKECQSLGKEGEFSPCFTELQRAFLRQRPTKLKSLIRLVKHWYQKCKDKLGKPLPAQYALELLTVYAWEQGSRQTEFNTAQGFRTVLELVLKYQQLCIYWTKYYNFDDPVIGQYLKRQLKKPRPVILDPADPTGNVGGGDPRSWPRLAQEARAWLSYPCFKNWDGSPVGSWDVGPEEDSEDDTLTWAERAYYQCDHGRRPEFPQTGSTPQRASAPDAEENWTCTIL”polyA_signal 1576 . . . 1581/gene=“Oas1a”BASE COUNT 372a 452c 450g 327tORIGIN1agtttctggg agccagtccc acgagcacca gctcctctgt ccccacccgg gcgtcacgat61ggagctccaa aagaccccag ccaggaatct ggacaagttc attgaagact atctcttgcc121agacacacgg ttccgcaggc aggtccgaga agccatcgac attatctgca gtttcctgaa181ggagaggtgt ttccgaggtg ccgttccccc tgtgcgggtg tccaaagtgg tgaagggtgg241ctcctcaggc aaaggcacga ccctcagagg ccgatccgat gctgacctcg tcgtcttcct301tgactacctc acgagtttcc gggagcagtt tgagcgccga gcagagttca tcaaggagat361tcggaggcag ctggaagcct gtcaaagaga gaagaggttt gacgtggagt tcgaggtcca421ggggcagcag tgggcgaggc cccgcgcgct cagcttcgtg ctcacgtcgc cccagctcaa481tgagggggtg gaatttgatg tcctgcctgc ctttgatgtc ctaggtcagg tgactacatc541gtacagacct gaccctgaca tatatgtcct actcatcaaa gaatgccagt ccctggggaa601ggagggagag ttctccccct gcttcacgga gctgcagcga gccttcctga ggcagcggcc661aaccaagctc aagagcctca tccgcctggt caagcactgg taccaaaagt gcaaggataa721acttgggaaa ccactgccag cacagtacgc cctggagctc ctgacagtct atgcttggga781acagggaagc agacaaacag aattcaacac agctcaggga tttcggactg tcttggaact841agtcctgaag taccagcagc tttgcatcta ctggacaaag tattacaact ttgatgaccc901tgttattgga caatacctga aaaggcagct caagaaaccc aggcctgtga ttctggaccc961ggctgacccc acaggaaacg ttggtggtgg agacccacgc agctggcctc ggctggcaca1021ggaggcgaga gcctggctga gttacccgtg ctttaagaat tgggacgggt ctccagtggg1081ctcctgggac gtggggcctg aagaagacag cgaggacgac actttgacct gggctgagcg1141cgcatattac cagtgcgacc acggacggcg ccctgaattc ccgcagaccg gcagcacgcc1201ccagagggca tccgctcccg acgcggaaga gaactggacc tgcaccatcc tctgatcgcc1261ggcgcagcgt ggaggagagg actccagagt cgggggggcc agccccctca tttcctgggc1321gggatcttat cggctgtgac ttggcatcag tcctaggacc agaatccggg tctcctgacc1381cctcttcctg ctgttcccct ctttctcgcc ctccctaggt agcgctgccc gcagcctcat1441cccgccacag cctgttttct gacaatattc tctgagaggc aacagttgag gtttagacaa1501aagagtggaa actcagcctt gactttcttc tgtgtgcctg gtgagaaggt tatggtccaa1561tttattatca ataacaataa aaataatagc agataaaaaa a


This work was supported by Public Health Service Grants: GM54896 from the National Institute of General Medical Sciences and AI45135 from the Institute of Allergy and Infection Diseases, National Institutes of Health.


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EXAMPLES
Example 1

Cell Cultures and Virus Stocks


Cell lines were previously established by SV-40 transformation of embryofibroblasts obtained from congenic C3H.PRI-Flvr and C3H/He (9). Baby hamster kidney (BHK-21/WI2) cells (referred to hereafter as BHK cells) were used for virus plaque assays (8).


The cDNAs corresponding to the ORFs of the C3H.PRI-Flvr alleles of the Oas1b (AF328926) and Na+/Ca2+-exchanger (AF261233) genes were cloned separately into the pEF6/V5-His-TOPO mammalian expression vector (Invitrogen) and these plasmids were transfected into susceptible C3H/He cells using LipofectAMINE 2000 (Life Technologies). Stable integrants were selected using blasticidin S and cells from individual foci were isolated with cloning rings and propagated. Expression of the recombinant proteins, which contained C-terminal 6×His and V5 tags, was analyzed by Western blotting of cell lysates using V5 antibody (Invitrogen). Stable cell lines expressed a low level (1×), an intermediate level (8×) or a high level (20×) of Oas1b protein were obtained.


A stock of West Nile virus (WNV), strain Eg101, was prepared as a 10% (w/v) newborn mouse brain homogenate (titer=2×108 PFU/ml). A stock of Sindbis virus, strain SAAR 339, was prepared as a 10% (w/v) newborn mouse brain homogenate (titer=7×109 PFU/ml). For virus growth experiments, confluent monolayers in T25 flasks were infected with WNV or Sindbis virus at a multiplicity of infection (MOI) of 0.5. Both viruses were titered on BHK cells by plaque assay.


Example 2

Construction of the BAC Contig


A single genomic clone, 171N24, which contained the D5Mit159 marker and was about 40 kb in length, was isolated from a mouse BAC library (Baylor College of Medicine) using a unique probe derived from D5Mit159. The terminal sequence obtained from the T7 promoter side of the 171N24 clone did not match any of the DNA sequences in the GenBank database, but the sequence located next to the SP6 promoter was part of a large interspersed repeat. Additional BAC clones were subsequently isolated from the RPCI-23 C57BL/6 mouse BAC library (Roswell Park Cancer Institute) using a probe designed from the 171N24 clone sequence adjacent to the T7 promoter. Four positive signals were detected and the clones, 244P21, 274O1, 297M4, and 359J23, were purchased and analyzed. The size of the insertion in each clone was estimated from restriction patterns observed after pulse-field gel electrophoresis. The terminal DNA sequences for each of the BAC clones were determined and used to design eight new primer pairs for PCR amplification of fragments from each end of each BAC clone. Each BAC clone DNA was then tested as a template in a PCR with each primer pair and the data obtained was used to align the clones into a single BAC contig of 300 kb.


Two sequences, 297M4T7 and 244P21SP6, which were the most distal in the initial contig were then used to re-screen the library and eight additional BAC clones were isolated. These clones were partially sequenced and aligned into the contig by screening them with other BAC clone terminal sequences. A GenBank search against the 5′ and 3′ BAC insert sequences identified of one additional BAC clone, 39M18 (AC015535).


Physical Map of the Flv Interval


To create a genomic contig, two independent mouse BAC libraries were screened and fourteen BAC clones were isolated. Alignment of these clones provided a BAC contig with an estimated length of more than 700 kb (FIG. 1). Two flanking microsatellite markers, D5Mit408 and D5Mit242, were mapped outside the contig according to the Celera mouse database. The D5Mit159 marker was located in the central part of the contig (FIG. 1).


Example 3

Isolation of Transcription Units from the BAC Contig


Direct cDNA selection, exon trapping and searches of genes annotated in the Celera database (www.celera.com), were used to identify transcripts from the Flv interval. Direct cDNA selection was performed according to the protocol of Lovett (17) using adaptor-ligated double-stranded cDNA prepared from C3H.PRI-Flvr cells. Exon trapping was performed using an Exontrap kit (MoBiTec). The cDNAs obtained after each exon trapping or cDNA selection experiment were tested by hybridization with the different BAC clone DNAs, and those that showed specific hybridization with the initial BAC clone DNA were cloned into a pCR-XL-TOPO vector (Invitrogen) and sequenced.


The length of the mRNA corresponding to a partial cDNA isolated by cDNA selection or exon trapping was estimated by Northern blotting using the method of Sambrook et al. (18). The partial cDNA sequences were extended by RACE using a Marathon cDNA amplification kit (Clontech). The expression patterns of the candidate genes were analyzed using mouse multiple tissue poly-A+ (Stratagene) and total RNA (Seegene) Northern blots hybridized to probes excised with endonucleases from the cDNAs and labeled with the RTS RadPrime kit (Life Technologies).


Partial and full-length cDNA sequences were used to search the Celera mouse genome database to identify additional transcripts from closely linked genes in the Flv region. Primer pairs designed from sequenced cDNAs and from gene sequences obtained from the Celera database were used to amplify cDNAs from the congenic C3H.PRI-Flvr and C3H/He mouse strains. The primer sequences are listed in Table 5 (published as supporting information).


Transcript Map of the Flv Region


Direct cDNA selection and exon trapping techniques as well as searches of the GenBank and Celera mouse databases were used to identify candidate genes. Four novel transcripts, a Ca2+-channel (AF217002), an unknown mRNA (AF217003), an ATP-dependent helicase (AF319547), and a serine dehydratase (AF328927), were identified by direct cDNA selection. Three novel transcripts, a Na+/Ca2+-exchanger (AF261233), the Oas2 (AF418010), and the Oas3 (AF453830), were detected by exon trapping. The partial sequences obtained were extended to full-length cDNAs by 5′ and 3′ RACE techniques. Two previously identified genes, Oas1a and Oas1b (AF328926), were also cloned using the exon trapping technique (FIG. 1).


Although small (42 kDa), medium (70 kDa), and large (105 kDa) forms of 2′-5′ oligoadenylate synthetases had previously been detected in mice using various biochemical techniques (25-26), only the cDNAs of some of the mouse 42 kDa proteins had been previously cloned (27-29). Three DNA sequences of the Oas1a gene were reported in the Mouse Genome Informatics (MGI) database (www.informatics.jax.org) under the accession ID 97429. Two of these sequences, M33863 and X04958, are almost identical to each other and to the Celera transcript, mCT15312, whereas the third sequence, X58077, is similar to the Celera transcript mCT15074, which maps to a different genomic region. We designated this gene Oas1g (see below). The sequence, AF328926, cloned in this study was identical to the previously isolated partial (576 bp) Oas1b sequence, X55982 (28). Two other sequences, M63849 and M63850, deposited in MGI under the accession ID 97430 and also designated Oas1b were similar to each other, but not to X55982 and AF328926 nor to any mouse transcripts, expressed sequence tags (EST) or genomic sequences in neither the NCBI or the Celera databases. However, M63849 and M63850 showed identity with the human OAS1 sequences and it is likely that these two sequences were cloned from a mouse cDNA library contaminated with human clones.


Twelve additional genes were identified in the Flv region by searching the Celera mouse database with sequences from the nine loci detected by cDNA selection and exon trapping. The LIM homeobox 5 (Lhx5), a threonine dehydratase (BC021950), an unknown protein (AK017032), the RAS protein activator-like 1 (Rasal1), the deltex 1 (Dtx1), the Oas1c (AB067528), the rabphilin 3A (Rph3a), and the protein tyrosine phosphatase, non-receptor type 11 (Ptpn11) sequences were available in GenBank. Genomic and cDNA sequences of four novel genes annotated by the Celera database (subsequently named Oas1d, Oas1e, Oas1f, Oas1g, see Table 1) were also identified in the Flv region and their sequences were used to search the NCBI mouse EST database. The EST sequences obtained were used to generate cDNA consensus sequences, as well as to design PCR primers for the amplification of each novel gene from mRNA. One additional gene, Oas1h (AB067530), not annotated in Celera, was subsequently identified using a BLAST search of the NCBI database using the Oas1b sequence as a query. The Oas1h cDNA sequence was used to search the Celera database and this gene was mapped on the Flv interval between Oas1f and Oas1g (FIG. 1).


Example 4

Amplification and Sequencing of the Oas1b Exons from Genomic DNA


Genomic DNAs for eight mouse strains, 129/SvJ, BALB/c, BRVR, C57BL/6, CASA/Rk, CAST/Ei, CBA/J, and MOLD/Rk, were purchased from Jackson laboratory and used for PCR amplification of Oas1b exons. The primers (Table 6, supporting information) used for amplification and direct sequencing were designed from the genomic DNA sequence of the Oas1b gene (AC015535).


Example 5

Phylogenetic and Domain Architecture Analysis of Oas Sequences


Protein sequences of mouse and human 2′-5′ oligoadenylate synthetases 2 and 3 were divided into fragments corresponding to a single functional unit (19). Multiple sequence alignments were constructed using CLUSTAL X (20). Phylogenetic trees were built from multiple alignments using the neighbor-joining method (21). The bootstrapping procedure (22) was applied to the PHYLIP format tree output. Known and putative domains in Oas sequences were revealed by searches against Pfam (23) and ProDom (24) databases.

TABLE 4Mouse 2′-5′ oligoadenylate synthetase genes and their orthologs.GenBankaccession #Mouse(cDNA cloneCeleraOrthologousgenename)transcriptsequencesOas1aX04958,mCT15312rat - Z18877,M33863 (L3),pig - AJ225090,BC013715marmot - AF082498OAS1*-NM_002534,NM_016816Oas1bX55982 (L1),mCT15306rat - AF068268AF328926,OAS1*-NM_002534,AB067529,AF418004-AF418009BC012877,NM_016816Oas1cAB067528,mCT15073OAS1*-NM_002334,AF459815NM_016816Oas1dAB067532,mCT15317OAS1*-NM_002334,AY055829NM_016816Oas1eAB067531,mCT15075OAS1*-NM_002334,AY055830,NM_016816AY055831Oas1fAF481733mCT15304OAS1*-NM_002334,NM_016816Oas1gX58077 (L2),mCT15074OAS1*-NM_002334,BC018470NM_016816Oas1hAB067530noneOAS1*-NM_002334,NM_016816Oas2AB067535,mCT15077OAS2*-NM_002535,AF418010NM_016817Oas3AB067534,mCT15081OAS3*-NM_006187AF453830Oasl1AB067533,mCT18390OASL*-NM_003733AY057107Oasl2AF068835mCT118383unknownmCT18449










TABLE 5










Primers used for PCR amplification



of murine genes from the Flv interval.









Gene
Forward Primer (5′ to 3′)
Reverse Primer (5′ to 3′)













AF217002
AAGGCTGGCGCAGCTGCCGCT
AACCCAGCTAGGTGACAGTCTGG






AF217003
ACCTGCCCTCGCGATGGCGGC
ATCCTCCTGCCTCATCTTCTGAGT





AF261233
ACTAGAGCAGCCAGCCCGTGAGCA
CTGGCTTACAGAGTGAGTTCCAGG





AF319547
TGTTATGTCCCTCAGGTCCTGCTC
AAACTCAATGCTGGGTCAGAGGCA





AK017032
TTACTGGAGGCTGTGAAATCTAGG
TAGGGCGTGGTGGAAGCTGAACA





BC021950
CAGACACAATCTACTCCTCTCGCT
CATTGTCAAGTGTATCCCACCCCA





Dtx1
CTAAGGGATTGAGATCATGTCCCC
GTGCTTGACTCAAGTCCTGGGAAA





Lhx5
GAAGTCTTGGTTGATCCGTAACGG
TGACTTTGGTCCCGAGAAATTGCG





Oas1a
AGACCCAGGAAGCTCCAGACTTAG
GACAGAACCTTCCAACAGGTGGAC





Oas1c
AAACACTCCTGGCCTCAGGATGG
CAGCCCCAGTGCATTGTGATTTAA





Oas1d
GTCAGCAAACACTCCTGGCCTC
GCGTTTTGCTTTAATTTAGTGCTTC





Oas1e
TCAGGATGGCGAGGGAACTCTTCA
AACTGCCATAAACCCGGCCTGCAT





Oas1f
GTCAGCAAACACTTCCTGGCCATA
CAGGTGGAAGTCAAGCTTGAGTTC





Oas1g
AGACCCAGGAAGCTCCAGACTTAG
AGTTCCACGACAGCGTGTGTCACA





Oas1h
GGCTGCAGTCAGCAAACATTCCTG
CGGTCCTCTCTAGGTCAAAGTCTT





Oas2
GACCAGCTAGCAACGATGGGAAAC
ACTGACCCAGGATCTTCTGTCCCA





Oas3
GAAACTCTACTGAGAGTACCGGTC
GGGGAGGAAAGGGTTTATTCAGCT





Ptpn11
AAGACGGGAGGAACATGACATCGC
AGCAGTCTCTCCTTAGCTGAGGAA





Rasal1
TGAACCGGCTGACAGCGTGCTTG
AAGAGCCTGTGTCCGGCTTCGAG





Rph3a
AACCTTCCATGTGGAGTAGTCTGG
GGACCTGAAGATGCTTAAGGTCAG





Sds
TTCCTGATTCTGTCTCACGTGGCT
TTGATGACCCACCAGGTGTCCAGG

















TABLE 6










Primers used for PCR amplification



of the Oas1b exons from genomic DNA.









Exon
Forward Primer (5′ to 3′)
Reverse Primer (5′ to 3′)













First
AATCCTAGACCTGCAAGTCCAGAG
GGTTGCAGCCTGGCTTCTGAAAGT






Second
TGGTGATGGACTCCAGTTCAGCAT
ACTAGAAGGGAGGATGAAGGCATG





Third
GGCTGAGCTGTTCCACTGAATGAA
CTCTGTACAGATGAAGCGCACAGT





Fourth
TGGCTATAGCACAAGAAGGCATAG
TGACATGAAGAGTGTTGGACGACC





Fifth
GGTCAGTTGACAGCAGCTCGTTTC
AATAAGGAGAGCCAATGGCCTCAA





Sixth
CTATTACAGACGGAGGTTGCAG
TGCTACTGTGAACAGACACCATGACC









Claims
  • 1. A method for genotyping flavivirus resistance, comprising, a) restricting a nucleic acid sample of amplified DNA obtained from a subject with at least one endonuclease wherein the endonuclease restricts the DNA at a site so that the DNA fragments obtained differentiate between a flavivirus resistance allele and a flavivirus susceptibility allele; and b) identifying the restricted DNA fragments.
  • 2. The method of claim 1, wherein the nucleic acid sample is obtained from a human.
  • 3. The method of claim 1, wherein the nucleic acid sample is derived from an animal other than humans.
  • 4. The method of claim 1, wherein the at least one endonuclease is Alu1.
  • 5. The method of claim 21, wherein the identifying is by gel electrophoresis.
  • 6. The method of claim 1, wherein the identifying is by differential binding of the fragments to a microarray of known sequences.
  • 7. The method of claim 1, wherein the amplified products comprise nucleic acids encoding SEQ ID No. 39.
  • 8. The method of claim 1, wherein the amplified products comprise nucleic acids comprising SEQ ID No. 40.
  • 9. The method of claim 6, wherein the microarray comprises sequences complementary to SEQ.ID No. 39.
  • 10. The method of claim 6, wherein the microarray comprises sequences complementary to SEQ ID No. 40.
  • 11. A composition, comprising an isolated nucleic acid construct of a human OAS 1 gene sequence comprising SEQ ID No. 39 or SEQ. ID. No. 40.
  • 12. The composition of claim 11, wherein the composition comprises a cell comprising the isolated nucleic acid construct comprising SEQ ID No. 39.
  • 13. The composition of claim 11, wherein the composition comprises a cell comprising the isolated nucleic acid construct comprising SEQ ID No. 40.
  • 34. The composition of claim 11, wherein the nucleic acid construct is capable of expressing a protein.
  • 35. The composition of claim 11, wherein the nucleic acid construct is SEQ ID No. 39.
  • 16. The composition of claim 11, wherein the nucleic acid construct is SEQ. ID. No. 40.
  • 17. A method of testing agents for antiviral activity, comprising a) applying an agent to a cell line expressing a human OAS 1 gene sequence of SEQ ID No. 39 or SEQ. ID No. 40; and b) measuring a change in the cells.
  • 18. The method of claim 17, wherein the gene sequence is SEQ ID No. 39.
  • 19. The method of claim 37, wherein the gene sequence is SEQ ID No. 40.
RELATED APPLICATIONS

This application is a continuation-in-part of PCT/US2003/19300, filed Jun. 19, 2003, which claimed priority to U.S. Provisional Patent Application No. 60/390,046, filed Jun. 19, 2002, each of which is herein incorporated in its entirety.

Provisional Applications (1)
Number Date Country
60390046 Jun 2002 US
Continuation in Parts (1)
Number Date Country
Parent PCT/US03/19300 Jun 2003 US
Child 11012762 Dec 2004 US