Multiple Breed Validation of Five QTL Affecting Mastitis Resistance

Mastitis is a major animal welfare problem and the most costly disease in dairy cattle worldwide. Within the EU FP7 Quantomics project, we aimed at validating quantitative trait loci affecting mastitis resistance at the molecular level. Eight chromosome regions with major effects on resistance to mastitis were identified by GWAS using high-density SNP array in the Finnish Ayrshire and Brown Swiss breeds. These targeted regions were analyzed for polymorphisms from 20X whole-genome sequences of 38 ancestral bulls of the two populations. A set of 384 SNPs were selected based on their ranking from the estimated effect: creating stop gain/loss, affecting splice site or RNA structure (RNAsnp), predicted disruptiveness (SIFT), occurring in miRNA or miRNA target site, or in UTR or ncSNP overlapping with a GERP element. Their effects on mastitis traits were estimated in new validation samples from Finnish Ayrshire (SCC, clinical mastitis, udder conformation) and Valdostana (SCC, milk bacteriological results). Furthermore, association analysis across the regions was performed with a linear mixed model using imputed sequence for 845 Danish Red sires with nine mastitis phenotypes. Associations in five regions (on BTA3, BTA6, BTA8, BTA19, and BTA27) agreed across the breeds, but no identical associated SNPs were detected. Higher power (imputation to bigger population samples) will be needed to confirm results. On BTA6 the results indicate several QTL within a 5 Mb region. The results provide a basis for functional studies of promising candidates. The information can also be used for prior weighting of genomic segments in genomic selection.