DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content

Lactose provides an easily-digested energy source for neonate mammals, and is the primary carbohydrate in milk. Lactose is also a key component of many human food products, though compared to analyses of other milk components, the genetic control of lactose has been little studied. Here we present the first GWAS of milk lactose concentration and yield, investigated in a population of 12,000 taurine dairy cattle. We detail 27 QTL spanning these traits, and subsequently validate the effects of 26 of these loci in a separate population of 18,000 cows. We next present data implicating causative genes and variants for these QTL. Fine mapping of these regions using imputed, whole genome sequence-resolution genotypes reveals protein-coding candidate causative variants affecting the ABCG2, DGAT1, STAT5B, KCNH4, NPFFR2 and RNF214 genes. Eleven of the remaining QTL appear to be driven by regulatory effects, suggested by the presence of co-locating, co-segregating eQTL discovered using mammary RNA...

乳糖（Lactose）是新生哺乳动物易于消化利用的能量来源，同时也是牛乳中的核心碳水化合物组分。乳糖亦是诸多人类食品的关键成分，但相较于其他乳成分的相关研究，针对乳糖的遗传调控机制迄今仍鲜有系统性探索。本研究针对12000头乳用普通奶牛群体，开展了首个针对牛乳乳糖浓度与乳糖产量的全基因组关联分析（Genome-Wide Association Study, GWAS）。我们共鉴定得到覆盖这两类性状的27个数量性状位点（Quantitative Trait Locus, QTL），随后在包含18000头奶牛的独立验证群体中，证实了其中26个位点的遗传效应。本研究进一步挖掘了这些QTL的潜在因果基因与致病变异：利用插补获得的全基因组序列分辨率基因型对这些位点区域进行精细定位后，发现了可影响ABCG2、DGAT1、STAT5B、KCNH4、NPFFR2及RNF214基因的蛋白编码类候选致病变异。剩余11个QTL则似乎由调控效应介导，这一推论得到了共定位且共分离的表达数量性状位点（expression Quantitative Trait Locus, eQTL）的支持——此类eQTL可通过乳腺组织RNA测序数据鉴定得到。