Location: Animal Disease ResearchTitle: Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple flocks of sheep) Author
Submitted to: Animal Genetics
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/18/2013
Publication Date: 4/1/2014
Citation: White, S.N., Mousel, M.R., Reynolds, J.O., Herrmann-Hoesing, L.M., Knowles Jr, D.P. 2014. Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple flocks of sheep. Animal Genetics. 45(2):297-300. Interpretive Summary: Ovine lentivirus (OvLV), also known as ovine progressive pneumonia or maedi-visna virus, causes pneumonia, "hard bag" mastitis, and body condition wasting in sheep. There is no vaccine or cure, but selective breeding for reduced susceptibility to OvLV is a promising strategy. There is a genetic marker test based on the TMEM154 that has been validated for reducing odds of becoming infected with OvLV, but so far there are no validated genetic markers to improve control of OvLV post-infection. A previous study identified a genomic region strongly associated with such post-infection control, and here we refined this region and identified a specific genetic variant that is consistently associated with post-infection control in multiple flocks of sheep. These flocks included some with natural exposure to OvLV, and one with blood-borne exposure through shared needle use. The breeds represent some of the most common breeds (and crossbred types) used on U.S. range operations. The desirable insertion homozygote genotype had less than half the OvLV proviral concentration compared to other genotypes (P<0.0001). Since previous work has shown a relationship between proviral concentration and severity of pathological lesions from OvLV, this genetic variant also might be associated with reduced disease. Further testing will determine if the variant is useful with other breeds, management conditions, and viral subtypes, and what functional role this region may have in control of OvLV.
Technical Abstract: Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker-assisted selective breeding might improve odds of infection and control of OvLV post-infection. Although variants in TMEM154 have consistent association with odds of infection, no variant in any gene has been associated with host control of OvLV post-infection in multiple animal sets. Proviral concentration is a live-animal diagnostic measure of OvLV control post-infection related to severity of OvLV-induced lesions. A recent genome-wide association study identified a region including four zinc finger genes associated with proviral concentration in one Rambouillet flock. To refine this region, we tested additional variants and identified a small insertion/deletion variant near ZNF389 that showed consistent association with proviral concentration in three animal sets (P < 0.05). These animal sets contained Rambouillet, Polypay and crossbred sheep from multiple locations and management conditions. Strikingly, one flock had exceptionally high prevalence (>87%, including yearlings) and mean proviral concentration (>950 copies/lg), possibly due to needle sharing. The best estimate of proviral concentration by genotype, obtained from all 1310 OvLV-positive animals tested, showed insertion homozygotes had less than half the proviral concentration of other genotypes (P < 0.0001). Future work will test additional breeds, management conditions and viral subtypes, and identify functional properties of the haplotype this deletion variant tracks. To our knowledge, this is the first genetic variant consistently associated with host control of OvLV post-infection in multiple sheep flocks.