Genome-wide association with footrot in hair and wool sheep

Authors: CINAR, MEHMET - Erciyes University; OLIVEIRA, RYAN - Washington State University; HADFIELD, TRACY - Utah State University; LICHTENWALNER, ANNE - University Of Maine; BRZOZOWSKI, RICHARD - University Of Maine; SETTLEMIRE, THOMAS - Bowdoin College; SCHOENIAN, SUSAN - University Of Maryland; PARKER, CHARLES - Retired ARS Employee; NEIBERGS, HOLLY - Washington State University; COCKETT, NOELLE - Utah State University; White, Stephen

Submitted to: Frontiers in Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2023
Publication Date: 1/15/2024
Citation: Cinar, M.U., Oliveira, R.D., Hadfield, T.S., Lichtenwalner, A.B., Brzozowski, R.J., Settlemire, T.C., Schoenian, S.B., Parker, C., Neibergs, H.L., Cockett, N.E., White, S.N. 2024. Genome-wide association with footrot in hair and wool sheep. Frontiers in Genetics. 14. https://doi.org/10.3389/fgene.2023.1297444.
DOI: https://doi.org/10.3389/fgene.2023.1297444

Interpretive Summary: Ovine footrot is an infectious disease characterized by separation of the hoof from underlying tissue, and this causes severe lameness that negatively impacts animal well-being, growth, and profitability. Economic losses are substantial, and genetic resistance to footrot would be a valuable tool to improve disease management. Prior studies had examined only wool sheep breeds, but hair sheep breeds have been reported to have increased resistance to footrot. Thus, we examined footrot condition scores for 251 U.S. sheep including Katahdin and Blackbelly hair sheep. We identified three genome-wide significant associations, including in or near the GBP6 and TCHH genes. We also identified 33 additional associations with genome-wide suggestive evidence, including a cluster close to the genome-wide significance threshold located near the glutamine transporter gene SLC38A1. These genes suggest genetic susceptibility to footrot may be influenced by genes involved in divergent biological processes such as immune responses to footrot, nutrient availability, and hoof growth and integrity. This is the first genome-wide study to investigate susceptibility to footrot by including hair sheep, and also the first study to identify multiple genome-wide significant associations with ovine footrot. These results provide a foundation for developing genetic tests for marker-assisted selection to improve susceptibility to ovine footrot through additional research.

Technical Abstract: Ovine footrot is an infectious disease with important contributions from Dichelobacter nodosus and Fusobacterium necrophorum. Footrot is characterized by separation of the hoof from underlying tissue, and this causes severe lameness that negatively impacts animal well-being, growth, and profitability. Economic losses result from lost production as well as treatment costs, and they have been estimated at $20 million per year in the UK alone, with global costs certainly much higher. Genetic resistance to footrot would be a valuable tool to improve disease management. Prior studies had examined European wool sheep, but hair sheep have been reported to have increased resistance to footrot. Thus, footrot condition scores were collected from 251 U.S. sheep including Katahdin, Blackbelly, and European-influenced crossbred sheep with direct and imputed genotypes at OvineHD array (>500,000 SNP) density. Genome-wide association was performed with a mixed model accounting for farm and principal components derived from animal genotypes, as well as a random term for the genomic relationship matrix. We identified three genome-wide significant associations, including SNPs in or near GBP6 and TCHH. We also identified 33 additional associated SNPs with genome-wide suggestive evidence, including a cluster of 6 SNPs in a peak near the genome-wide significance threshold located near the glutamine transporter gene SLC38A1. These genes suggest genetic susceptibility to footrot may be influenced by genes involved in divergent biological processes such as immune responses to footrot, nutrient availability, and hoof growth and integrity. This is the first genome-wide study to investigate susceptibility to footrot by including hair sheep and also the first study of any kind to identify multiple genome-wide significant associations with ovine footrot. These results provide a foundation for developing genetic tests for marker-assisted selection to improve susceptibility to ovine footrot, once additional steps like fine mapping and validation are complete.