The genetics of bovine milk cholesterol content: Identification of molecular determinants and biomarkers of milk cholesterol

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The dairy industry ranks third in the Canadian agricultural sector generating about $5.5 billion in net farm receipts and sales of $13.7 billion in year 2010 alone. Recently, health conscious people have driven changes in the demand for milk and milk components resulting in the restructuring of major global milk markets. Milk/dairy products supply high quality nutrients in the diets of Canadians, including bioactive lipids (some unsaturated fatty acids) and peptides with well documented health benefits. Cholesterol (CH) is the major sterol in milk fat and milk fat is the second contributor to daily dietary CH intake after eggs. Numerous human studies have linked increased blood concentrations of CH in low density lipoprotein to increase risk of cardiovascular diseases (CVD) and increased blood concentrations of CH in high density lipoprotein to improved human health. Human mortality in the West is still caused to a large extent by CVD. Milk CH content is highly variable between breeds and species and is influenced by several factors including genetics. Candidate gene and genome wide studies in humans have associated many genomic regions, genes and gene variants (e.g. SNPs) with CH phenotypes. To the best of our knowledge, no such studies have been done with dairy cows. Given the quantitative nature of CH, genome wide approaches are necessary to decisively and quickly determine genes and causal variants implicated in milk CH for inclusion in breeding programs. With an increasingly health conscious population and demand for health promoting products, it is imperative that this aspect be given due consideration in order to maintain sustainable milk demand and trade. The objectives of the proposed research are: (1) Determine quantitative trait loci (QTL) and SNPs associated with milk CH content through a genome wide association study using Illumina 50K SNP chip; (2) Identify causal mutations or quantitative trait nucleotide (s) (QTN) explaining heritable variance of most significant QTL peaks through a fine mapping approach; (3) Validate identified QTN in further herds and by functional studies for use in breeding programs for milk CH content; (4) Determine the relationship between milk CH and milk fatty acids.