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

牛奶胆固醇含量的遗传学：牛奶胆固醇分子决定因素和生物标志物的鉴定

• 批准号: 453002-2013
• 负责人: Zhao, Xin
• 金额: $ 5.22万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=554959
• 关键词: genetics; bovine; milk; cholesterol; content

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.

乳制品行业在加拿大农业部门中排名第三，仅2010年一年就产生了约55亿美元的农场净收入和137亿美元的销售额。近来，人们的健康意识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素，包括生物活性脂质（一些不饱和脂肪酸）和具有良好健康益处的肽。胆固醇（CH）是乳脂中的主要固醇，乳脂是每日膳食CH摄入量的第二大贡献者，仅次于鸡蛋。许多人体研究表明，低密度脂蛋白中CH的血液浓度增加与心血管疾病（CVD）风险增加有关，高密度脂蛋白中CH的血液浓度增加与改善人体健康有关。 在西方，人类死亡在很大程度上仍然是由CVD引起的。牛奶中的CH含量在品种和物种之间存在很大差异，并受到包括遗传在内的多种因素的影响。人类的候选基因和全基因组研究已经将许多基因组区域、基因和基因变体（例如SNP）与CH表型相关联。据我们所知，还没有对奶牛进行过这样的研究。鉴于CH的定量性质，全基因组方法对于决定性地快速确定与牛奶CH有关的基因和致病变体以纳入育种计划是必要的。随着越来越多的健康意识和对健康促进产品的需求，必须适当考虑这方面，以保持可持续的牛奶需求和贸易。 本研究的主要目的是：（1）利用Illumina 50 K SNP芯片进行全基因组关联分析，确定与牛奶CH含量相关的数量性状基因座（QTL）和SNP位点;（2）通过精细定位方法，确定解释最显著QTL峰值遗传方差的因果突变或数量性状核苷酸（QTN）;（3）通过进一步的畜群和功能性研究确定了QTN，以用于乳CH含量的育种计划;（4）确定乳CH与乳脂肪酸之间的关系。