Fine-mapping sequence mutations with a major effect on oligosaccharide content in bovine milk

Human milk contains abundant oligosaccharides (OS) which are believed to have strong health benefits for neonates. OS are a minor component of bovine milk and little is known about how the production of OS is regulated in the bovine mammary gland. We have measured the abundance of 12 major OS in milk of 360 cows, which had high density SNP marker genotypes. Most of the OS were found to be highly heritable (h(2) between 50 and 84%). A genome-wide association study allowed us to fine-map several QTL and identify candidate genes with major effects on five OS. Among them, a putative causal mutation close to the ABO gene on Chromosome 11 accounted for approximately 80% of genetic variance for two OS, N-acetylgalactosaminyllactose and lacto-N-neotetraose. This mutation lies very close to a variant associated with the expression levels of ABO. A third QTL mapped close to ST3GAL6 on Chromosome 1 explaining 33% of genetic variation of an abundant OS, 3′-sialyllactose. The presence of major gene effects suggests that targeted marker-assisted selection would lead to a significant increase in the level of these OS in milk. This is the first attempt to map candidate genes and causal mutations for bovine milk OS.