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Genome-Wide Association Identifies Multiple Genomic Regions Associated with Susceptibility to and Control of Ovine Lentivirus

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Background Like human immunodeficiency virus HIV, ovine lentivirus OvLV is macrophage-tropic and causes lifelong infection. OvLV infects one quarter of U.S. sheep and induces pneumonia and body condition wasting. There is no vaccine to prevent OvLV infection and no cost-effective treatment for infected animals. However, breed differences in prevalence and proviral concentration have indicated a genetic basis for susceptibility to OvLV. A recent study identified TMEM154 variants in OvLV susceptibility. The objective here was to identify additional loci associated with odds andor control of OvLV infection. MethodologyPrincipal Findings This genome-wide association study GWAS included 964 sheep from Rambouillet Polypay, and Columbia breeds with serological status and proviral concentration phenotypes. Analytic models accounted for breed and age, as well as genotype. This approach identified TMEM154 nominal P 9.261027 empirical P 0.13 provided 12 additional genomic regions associated with odds of infection, and provided 13 regions associated with control of infection all nominal P,161025. Rapid decline of linkage disequilibrium with distance suggested many regions included few genes each. Genes in regions associated with odds of infection included DPPA2DPPA4 empirical P 0.006 and SYTL3 P 0.051. Genes in regions associated with control of infection included a zinc finger cluster ZNF192, ZSCAN16 ZNF389, and ZNF165 P 0.001, C19orf42TMEM38A P 0.047, and DLGAP1 P 0.092. ConclusionsSignificance These associations provide targets for mutation discovery in sheep susceptibility to OvLV. Aside from TMEM154, these genes have not been associated previously with lentiviral infection in any species, to our knowledge. Further, data from other species suggest functional hypotheses for future testing of these genes in OvLV and other lentiviral infections. Specifically, SYTL3 binds and may regulate RAB27A, which is required for enveloped virus

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  • Animal Husbandry and Veterinary Medicine
  • Genetic Engineering and Molecular Biology

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