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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Animal Health Genomics » Research » Publications at this Location » Publication #360658
Research Project: Genomic Intervention Strategies to Prevent and/or Treat Respiratory Diseases of Ruminants

Location: Animal Health Genomics

Title: Association of TMEM154 variants with visna/maedi virus infection in Turkish sheep

Author
item YAMAN, YALCIN - KOYUNCULUK ARASTIRMA ENSTITÜSÜ MÜDÜRLÜGÜ
item KELES, MURAT - KOYUNCULUK ARASTIRMA ENSTITÜSÜ MÜDÜRLÜGÜ
item AYMAZ, RAMAZAN - KOYUNCULUK ARASTIRMA ENSTITÜSÜ MÜDÜRLÜGÜ
item SEVIM, SEMIH - KOYUNCULUK ARASTIRMA ENSTITÜSÜ MÜDÜRLÜGÜ
item SEZENLER, TAMER - KOYUNCULUK ARASTIRMA ENSTITÜSÜ MÜDÜRLÜGÜ
item ONALDI, TANER - KOYUNCULUK ARASTIRMA ENSTITÜSÜ MÜDÜRLÜGÜ
item KAPTAN, CUNEYT - KOYUNCULUK ARASTIRMA ENSTITÜSÜ MÜDÜRLÜGÜ
item BASKURT, ATILLA - KOYUNCULUK ARASTIRMA ENSTITÜSÜ MÜDÜRLÜGÜ
item KONCAGUL, SEYRANI - ANKARA UNIVERSITY OF TURKEY
item ONER, YASEMIN - ULUDAG UNIVERSITY
item OZTURK, EGEMEN ERDEM - HARRAN UNIVERSITY
item IRIADAM, MEHMET - HARRAN UNIVERSITY
item UN, CEMAL - EGE UNIVERSITY
item Heaton, Michael - Mike

Submitted to: Small Ruminant Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/7/2019
Publication Date: 6/21/2019
Citation: Yaman, Y., Keles, M., Aymaz, R., Sevim, S., Sezenler, T., Onaldi, A.T., Kaptan, C., Baskurt, A., Koncagul, S., Oner, Y., Ozturk, E., Iriadam, M., Un, C., Heaton, M.P. 2019. Association of TMEM154 variants with visna/maedi virus infection in Turkish sheep. Small Ruminant Research. 177:61-67. https://doi.org/10.1016/j.smallrumres.2019.06.006.
DOI: https://doi.org/10.1016/j.smallrumres.2019.06.006

Interpretive Summary: Visna/maedi is a lentiviral disease that targets the immune system and causes persistent untreatable infections affecting millions of sheep worldwide. Two common signs of the disease, wasting (visna) and struggling to breathe (maedi), are eventually fatal. In North America, the equivalent disease is called ovine progressive pneumonia. Previously, an ovine gene with large allelic effects (TMEM154) has been associated with disease susceptibility in North American sheep and is being successfully used in selective breeding. In the present study, we evaluated the effect of TMEM154 in flocks of Turkish sheep from around the country. Results reported in North America were validated in Turkish sheep and suggest that breeding for TMEM154 may reduce infection and offer some protection for both commercial and rare native breeds.

Technical Abstract: Visna/maedi (VM) is a multisystemic disease of sheep characterized by persistent lentiviral infection, slow progression and eventually death. The VM virus (VMV) affects sheep throughout the world and is the focus of national eradication campaigns. A major host gene associated with infection has been identified in North American sheep (TMEM154); however, its effect is unknown in Turkish sheep. Our aim was to determine VMV seroprevalence in naturally infected Turkish sheep, characterize their TMEM154 alleles, and test for association with infection. A 2017 serological census was taken of 2266 ewes from 11 flocks, at six locations, comprising seven native and four composite Turkish breeds. VMV serum antibodies were measured with an enzyme linked immunosorbent assay. Eight of 11 flocks were infected with VMV (2 to 83% seroprevalence). TMEM154 variants were typed by sequencing exon 2 from all 287 seropositive ewes and a subset of their seronegative flockmates (1059 total). TMEM154 sequencing revealed five of 12 known haplotypes encoding missense mutations, and one previously unreported variant (G38R) in Kivircik sheep. VMV seroprevalence in ewes with highly-susceptible TMEM154 haplotypes (full length E35 variants) was higher than the overall flock seroprevalence and independent of breed type. Genetic association was tested in 76 matched case-control pairs from 751 comingled ewes from a research flock. Pairwise analyses showed the risk of infection was 3-fold greater for ewes with one or two copies of highly-susceptible TMEM154 haplotypes compared to those with combinations of K35 and deletion variants (CI95 1.3–8.7, p-value 0.009). Allelic combinations of TMEM154 K35 and deletion variants had an apparent protective effect against VMV strains in Turkish sheep. The low frequencies of K35 and deletion alleles in native Turkish breeds suggests selective breeding may help reduce the seroprevalence in affected flocks and decrease the risk of outbreaks in VMV-free flocks.