Accession Number : ADA570146

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

Descriptive Note : Journal article


Personal Author(s) : White, Stephen N ; Mousel, Michelle R ; Herrmann-Hoesing, Lynn M ; Reynolds, James O ; Leymaster, Kreg A ; Neibergs, Holly L ; Lewis, Gregory S ; Knowles, Donald P

Full Text :

Report Date : 17 Oct 2012

Pagination or Media Count : 12

Abstract : 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 and/or control of OvLV infection. Methodology/Principal 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 DPPA2/DPPA4 (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), C19orf42/TMEM38A (P = 0.047), and DLGAP1 (P = 0.092). Conclusions/Significance: 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


Subject Categories : Animal Husbandry and Veterinary Medicine
      Genetic Engineering and Molecular Biology

Distribution Statement : APPROVED FOR PUBLIC RELEASE