Analysis of candidate SNPs affecting milk and functional traits in the dual-purpose Italian Simmental cattle

• The candidate gene approach has higher statistical power in moderate size studies than GWAS.
• In Italian Simmental, a cosmopolite dual-purpose breed, improvement of milk traits is of relevance.
• Twelve out of 37 SNPs analyzed were found in association with production and functional traits.
• Results provide association newly detected and already described in Italian Holstein and Brown breeds.

A total of 113 DNA polymorphisms in 32 candidate genes were pre-screened to assess their variability in 32 Italian Simmental bulls. A total of 64 variants successfully genotyped and having a minor allele frequency (MAF) higher than 0.03 were then analyzed in 477 Italian Simmental bulls. Among these 37 had a MAF ≥0.05 and were investigated for association with milk production and functional traits. Daughter yield deviations (DYD) were available for milk, protein and fat yield (MY, PY and FY, respectively), somatic cell count (SCC), udder score (US), feet and legs score (FLS), while for protein percent (PP), calving ease direct effect (CED), fertility (FE) and milkability (MA) associations were computed using (EBVs).Twelve SNPs were significantly associated with at least one trait (P≤0.05). The strongest association (P=0.0009) was found between rs385640152 in the growth hormone receptor gene (GHR) and PP. Also marker rs42714483 in the thyroid hormone responsive gene (THRSP) was associated with PP (P=0.004). Pleiotropic effects were detected only for β-lactoglobulin (LGB or PAEP progestagen-associated endometrial protein) polymorphisms on. SNP rs29004488 in the leptin gene (LEP) and rs41974998 in milk fat globule-epidermal growth factor 8 protein gene (MFGE8) were associated with MY (P=0.043 and P=0.033, respectively). Suggestive associations with functional traits were also detected: rs43347906 in the leptin receptor gene (LEPR) with US (P=0.029), rs29004485 in LEP with FLS (P=0.049), rs41703837 in the v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) with CED (P=0.021) and rs109019599 in the oxidized low density lipoprotein receptor 1 gene (OLR1) with MA (P=0.024). Our results both provide loci newly associated with functional traits and confirm associations already detected in Italian Holstein and Italian Brown breeds.