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.

乳是由脂质、蛋白质、碳水化合物以及多种维生素和矿物质组成的复杂混合物，作为幼年哺乳动物的营养来源。不同个体的乳汁成分存在显著差异，其中脂质组成的遗传力尤为突出。近期研究表明，牛27号染色体上存在一段区域，其携带的变异可影响乳脂百分比与脂肪酸含量。本研究旨在针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代杂交母牛的荷斯坦-弗里生牛（Holstein-Friesian）与泽西牛（Jersey）杂交家系群体，其二为32530头混合血统普通牛（Bos taurus）的集合群体。利用基于Illumina牛高密度基因芯片（Illumina BovineHD chip）进行基因型填充得到的标记开展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百分比的大型数量性状位点（quantitative trait locus, QTL）。此外，我们还对一系列其他乳成分表型进行了研究，并报道了该基因座在乳脂产量、蛋白质百分比与产量、乳糖百分比与产量、乳体积以及多种乳脂肪酸比例方面的额外关联。随后，我们使用来自212头泌乳母牛的乳腺RNA测序数据，对该乳脂百分比QTL区间内的基因转录本丰度进行了评估。该分析揭示了AGPAT6基因存在一个强烈的表达数量性状位点（expression quantitative trait locus, eQTL），表明高乳脂百分比基因型也与AGPAT6基因的表达量上调存在加性关联。最后，我们利用6头F1代公牛的全基因组测序数据，为F2代杂交群体设计了一组针对AGPAT6基因座变异的新型基因分型标记。对其中58个变异的关联分析显示，定位至AGPAT6基因5'UTR外显子及内含子1的多态性与乳脂百分比呈现极显著关联。综上，这些数据表明，影响AGPAT6基因表达的变异在乳汁脂肪合成差异中发挥着因果作用，并对多种其他乳成分产生多效性影响。