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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 #381301
Research Project: Genomic Intervention Strategies to Prevent and/or Treat Respiratory Diseases of Ruminants

Location: Animal Health Genomics

Title: Association of TLR2 haplotypes encoding Q650 with reduced susceptibility to ovine Johne’s disease in Turkish sheep

Author
item YAMAN, YALÇIN - Koyunculuk Arastirma Enstitüsü Müdürlügü
item AYMAZ, RAMAZAN - Koyunculuk Arastirma Enstitüsü Müdürlügü
item KELES, MURAT - Koyunculuk Arastirma Enstitüsü Müdürlügü
item BAY, VEYSEL - Koyunculuk Arastirma Enstitüsü Müdürlügü
item ÜN, CEMAL - Ege University
item Heaton, Michael - Mike

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/18/2021
Publication Date: 3/29/2021
Citation: Yaman, Y., Aymaz, R., Keles, M., Bay, V., Ün, C., Heaton, M.P. 2021. Association of TLR2 haplotypes encoding Q650 with reduced susceptibility to ovine Johne’s disease in Turkish sheep. Scientific Reports. 11. Article 7088. https://doi.org/10.1038/s41598-021-86605-4.
DOI: https://doi.org/10.1038/s41598-021-86605-4

Interpretive Summary: Johne’s disease is a contagious bacterial disease in ruminants caused by an infectious intracellular bacterium. It affects cattle, sheep, goats, and wild ruminants world-wide, causing a progressive chronic inflammation of the gut, resulting in significant production loss. The most common route of disease transmission is oral-fecal, and infections are life-long with no effective treatments or vaccines. Control strategies for Johne’s disease consist of testing for infected animals and removing them from production. However, disease control is hampered by hidden inactive infections with long incubation periods and wild-life reservoirs. If available, selective breeding strategies for reduced Johne's disease susceptibility would be welcome tools in disease eradication efforts. Here we report the discovery of gene variants associated with reduced susceptibility to ovine Johne’s disease in Turkish sheep. Ewes with one or two copies of the variants had a 6.6-fold reduced risk for Johne's infections in the study population. This suggests that selection for the gene variants in Turkish sheep may be useful for reducing Johne's disease prevalence. Moreover, it raises the possibility that similar variants in other breeds or species may affect susceptibility to infections causing Johne’s disease.

Technical Abstract: Ovine Johne’s disease (OJD) is caused by Mycobacterium avium subsp. paratuberculosis (MAP) and carries a potential zoonotic risk for humans. Selective breeding strategies for reduced OJD susceptibility would be welcome tools in disease eradication efforts, if available. The Toll-like receptor 2 gene (TLR2) plays an important signaling role in immune response to MAP, and missense variants are associated with mycobacterial infections in mammals. Our aim was to identify and evaluate ovine TLR2 missense variants for association with OJD in Turkish sheep. Eleven TLR2 missense variants and 17 haplotype configurations were identified in genomic sequences of 221 sheep from 61 globally-distributed breeds. The five most frequent haplotypes were tested for OJD association in 102 matched pairs of infected and uninfected ewes identified in 2257 Turkish sheep. Ewes with one or two copies of TLR2 haplotypes encoding glutamine (Q) at position 650 (Q650) in the Tir domain were 6.6-fold more likely to be uninfected compared to ewes with arginine (R650) at that position (CI95 = 2.6 to 16.9, p-value = 3.7x10-6). The protective TLR2 Q650 allele was present in at least 25% of breeds tested and thus may facilitate selective breeding for sheep with reduced susceptibility to OJD.