| Lameness conditions in cattle cause significant welfare and economic concerns. The incidence of lameness is high with estimates of 30 to 70 percent of individuals in a herd being lame at any one time, making lameness the third most common reason for culling. Due to the costs associated with premature culling and treatment, reduced reproductive fertility, and decreased milk production, lameness conditions cause an economic loss. There are also welfare concerns associated with the pain caused by lesions. Two of the most common lameness disorders are digital dermatitis and sole ulcers. The etiology and pathogenesis of these two conditions differ greatly. Digital dermatitis is likely due to a treponema bacterial infection, whereas sole ulcers are a non-infectious condition that result from physical wear in conjunction with predisposing factors such as concurrent laminitis. Heritability estimates for digital dermatitis and sole ulcers have recently been determined to be 0.4 and 0.3, respectively, signifying both conditions are moderately heritable and indicating the prevalence of digital dermatitis and sole ulcers could be reduced via a genetic selection program. In order to determine loci associated with each condition, genome wide association studies were conducted using cases and controls for digital dermatitis and sole ulcers. Using diagnostic hoof trimming records, and digital dermatitis and sole ulcer sire EBVs from two commercial dairy farms in California, blood samples were taken from 150 selected cows. DNA extracted from each cow was genotyped with the Illumina RTM BovineHD BeadChip (>777,000 SNP markers) and genome wide association studies and haplotype analyses were performed.;Significant associations (Bonferroni-corrected threshold Pgenome ≤ 0.05; -log 10 ≥ 1.3) were noted on chromosomes 3, 8, and 29 for digital dermatitis and a significant haplotype (chi2 -log10 P ≥ 7.00, 95% CI) was noted on chromosome 29. Genome wide significance was reached on chromosomes 3 and 5 for sole ulcers though significant haplotypes were seen on chromosomes 17, 23, 24, 25, 28, and 29 in the sole ulcer analysis, with the three most significant haplotypes being located on chromosomes 17, 25, and 28. Candidate genes were identified in regions upstream and downstream from the significant SNPs. One candidate gene, TIRAP, associated with the significant association on chromosome 29 seemed to be particularly promising for digital dermatitis due to its role in Toll-like receptor 2/1 heterodimer signaling, a component of the innate immune system. We hypothesized treponema (the probable agent of digital dermatitis infections) recognition may occur through the TIRAP gene. The TIRAP gene was sequenced in three digital dermatitis cases and three digital dermatitis controls, but no significant variations were noted in the sequences from any cow. Although the TIRAP gene did not appear to be associated with digital dermatitis, many other genomic regions showed associations indicating that other candidate genes may be identified for both sole ulcers and digital dermatitis. Future work will focus on exploring the other significant genomic associations to identify potential genes involved in the disease pathology for both conditions. |
