Aetiopathogenesis and genomic architecture of resistance to claw horn disruption lesions in dairy cattle

The project will (i) determine and evaluate factors affecting the development of claw horn disruption lesions (CHDL) in dairy cattle; (ii) identify genomic markers (SNPs) and regions associated with animal resistance to CHDL development; (iii) identify and characterise causal genes and regulatory regions underlying pathways and networks associated with CHDL; (iv) develop and evaluate breeding tools and strategies for enhanced animal resistance to CHDL while at the same time improving other important dairy cattle traits. The study will involve 3,000 pedigree Holstein cows. Animals will be repeatedly examined by a qualified veterinarian for CHDL. In addition, mobility and foot conformation scores, digital cushion thickness, body condition score, claw temperature and backfat thickness will be recorded along with environmental temperature and animal activity and resting patterns. Blood levels of hormones, immuno-modulating cytokines, non-esterified fatty acids and beta-hydroxybutyric acid will also be measured. Statistical analysis of all these data, using mixed models, will reveal the impact of foot structure and anatomy, periparturient hormonal profile and inflammatory status, fat mobilisation and metabolic stress, and environmental and management conditions on CHDL. Interactions among factors will be also assessed. All animals will have genome-wide genotypes generated to identify SNPs and genomic regions associated with CHDL. Additive and dominance effects of significant SNPs and genomic heritabilities will be derived. Whole-genome sequencing and RNA-sequencing results on a subset of animals with extreme phenotypes and genotypes will be combined with pathways analyses and functional interpretation to reveal the underlying molecular mechanisms of CHDL development. All results will inform simulation studies to assess breeding strategies and tools (including a trait-specific SNP array) to enable breeding for resistance to CHDL development.