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

奶制品行业在加拿大农业部门中排名第三，仅2010年一年就创造了约55亿美元的农场净收入和137亿美元的销售额。最近，具有健康意识的人推动了对牛奶和牛奶成分需求的变化，导致全球主要牛奶市场的重组。牛奶/乳制品在加拿大人的饮食中提供高质量的营养物质，包括生物活性脂肪(一些不饱和脂肪酸)和多肽，这些都有充分证据证明对健康有好处。胆固醇(CH)是乳脂中的主要类固醇，乳脂是仅次于鸡蛋的每日膳食CH摄入量的第二大贡献因素。大量的人体研究表明，低密度脂蛋白中CH的血液浓度增加会增加心血管疾病(CVD)的风险，而高密度脂蛋白中CH的血液浓度增加会改善人类健康。在西方，人类死亡在很大程度上仍然是由心血管疾病造成的。牛奶中的胆固醇含量在品种和物种之间差异很大，并受到包括遗传在内的几个因素的影响。人类候选基因和基因组范围的研究已经将许多基因组区域、基因和基因变体(如SNPs)与CH表型联系在一起。就我们所知，还没有对奶牛进行过这样的研究。鉴于CH的数量性质，全基因组方法是必要的，以果断和快速地确定与牛奶CH有关的基因和因果变异，并将其纳入育种计划。随着健康意识日益增强的人口和对健康促进产品的需求，必须适当考虑这一方面，以维持可持续的牛奶需求和贸易。拟议研究的目标是：(1)通过使用Illumina 50K SNP芯片进行全基因组关联研究，确定与牛奶CH含量相关的数量性状座位(QTL)和SNPs；(2)通过精细定位方法，识别解释最显著QTL峰值的可遗传变异的因果突变或数量性状核苷酸(S)(QTN)；(3)在进一步的牛群中验证已识别的QTN，并通过功能研究将其用于牛奶CH含量育种计划；(4)确定牛奶CH与牛奶脂肪酸之间的关系。

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.