Data from: Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus

Milk is composed of a complex mixture of lipids, proteins, carbohydrates and various vitamins and minerals as a source of nutrition for young mammals. The composition of milk varies between individuals, with lipid composition in particular being highly heritable. Recent reports have highlighted a region of bovine chromosome 27 harbouring variants affecting milk fat percentage and fatty acid content. We aimed to further investigate this locus in two independent cattle populations, consisting of a Holstein-Friesian x Jersey crossbreed pedigree of 711 F2 cows, and a collection of 32,530 mixed ancestry Bos taurus cows. Bayesian genome-wide association mapping using markers imputed from the Illumina BovineHD chip revealed a large quantitative trait locus (QTL) for milk fat percentage on chromosome 27, present in both populations. We also investigated a range of other milk composition phenotypes, and report additional associations at this locus for fat yield, protein percentage and yield, lactose percentage and yield, milk volume, and the proportions of numerous milk fatty acids. We then used mammary RNA sequence data from 212 lactating cows to assess the transcript abundance of genes located in the milk fat percentage QTL interval. This analysis revealed a strong eQTL for AGPAT6, demonstrating that high milk fat percentage genotype is also additively associated with increased expression of the AGPAT6 gene. Finally, we used whole genome sequence data from six F1 sires to target a panel of novel AGPAT6 locus variants for genotyping in the F2 crossbreed population. Association analysis of 58 of these variants revealed highly significant association for polymorphisms mapping to the 5′UTR exons and intron 1 of AGPAT6. Taken together, these data suggest that variants affecting the expression of AGPAT6 are causally involved in differential milk fat synthesis, with pleiotropic consequences for a diverse range of other milk components.

乳汁是由脂质、蛋白质、碳水化合物以及各类维生素和矿物质组成的复杂混合物，是幼年哺乳动物的营养来源。乳汁的组成存在个体差异，其中脂质组成的遗传力尤为显著。近期研究指出，牛27号染色体上存在一段区域，其携带的变异会影响乳脂率与脂肪酸含量。本研究旨在对两个独立肉牛群体中的该基因座开展进一步探究：其一为包含711头F2代奶牛的荷斯坦-弗里生牛（Holstein-Friesian）与泽西牛（Jersey）杂交系谱群体，其二为32530头混合血统的普通牛（Bos taurus）群体。基于Illumina牛高密度基因芯片（Illumina BovineHD chip）推算得到的标记进行贝叶斯全基因组关联分析，结果在两个群体中均检测到27号染色体上存在一个影响乳脂率的大型数量性状基因座（quantitative trait locus, QTL）。本研究同时对一系列其他乳汁组成表型展开探究，并报道了该基因座与脂肪产量、蛋白质率及产量、乳糖率及产量、乳体积以及多种乳脂肪酸比例存在额外关联。随后，本研究利用212头泌乳奶牛的乳腺RNA测序数据，对乳脂率QTL区间内的基因的转录本丰度进行评估。该分析鉴定出一个针对AGPAT6的强效应表达数量性状基因座（expression Quantitative Trait Locus, eQTL），证明高乳脂率基因型与AGPAT6基因的表达量上调存在加性关联。最后，本研究利用6头F1代种公牛的全基因组测序数据，筛选出一批全新的AGPAT6基因座变异位点，用于F2杂交群体的基因分型。对其中58个变异位点的关联分析显示，定位至AGPAT6的5'UTR外显子及内含子1区域的多态性位点与该性状存在极显著关联。综上，上述数据表明，影响AGPAT6基因表达的变异位点在乳汁脂肪合成差异中发挥因果性作用，并对多种其他乳汁成分产生多效性影响。