Direct Phenotyping and Principal Component Analysis of Type Traits Implicate Novel QTL in Bovine Mastitis through Genome-Wide Association

SIMPLE SUMMARY: It is well established that the physical conformation of a cow’s udder and teats may influence her susceptibility to mastitis, an inflammatory condition of the udder, which has 25% prevalence in the United States. Our aim was to improve the biological understanding of the genetics underlying mastitis by intensively characterizing cows for udder and teat conformation, including the novel traits of teat width and end shape, and directly associating those phenotypes with high-density genotypes for those exact same cows. We also generated a composite measure that accounts for multiple high-mastitis-risk udder and teat conformations in a single index for risk phenotypes. Using this approach, we identified novel genetic markers associated with udder and teat conformation, which may be good candidates for inclusion in national genetic evaluations for selection of mastitis-resistant cows. Mastitis is the costliest disease facing US dairy producers, and integrating genetic information regarding disease susceptibility into breeding programs may be an efficient way to mitigate economic loss, support the judicious use of antimicrobials, and improve animal welfare. ABSTRACT: Our objectives were to robustly characterize a cohort of Holstein cows for udder and teat type traits and perform high-density genome-wide association studies for those traits within the same group of animals, thereby improving the accuracy of the phenotypic measurements and genomic association study. Additionally, we sought to identify a novel udder and teat trait composite risk index to determine loci with potential pleiotropic effects related to mastitis. This approach was aimed at improving the biological understanding of the genetic factors influencing mastitis. Cows (N = 471) were genotyped on the Illumina BovineHD777k beadchip and scored for front and rear teat length, width, end shape, and placement; fore udder attachment; udder cleft; udder depth; rear udder height; and rear udder width. We used principal component analysis to create a single composite measure describing type traits previously linked to high odds of developing mastitis within our cohort of cows. Genome-wide associations were performed, and 28 genomic regions were significantly associated (Bonferroni-corrected p < 0.05). Interrogation of these genomic regions revealed a number of biologically plausible genes whicht may contribute to the development of mastitis and whose functions range from regulating cell proliferation to immune system signaling, including ZNF683, DHX9, CUX1, TNNT1, and SPRY1. Genetic investigation of the risk composite trait implicated a novel locus and candidate genes that have potentially pleiotropic effects related to mastitis.