Data from: Haplotype-based genome-wide association study identifies loci and candidate genes for milk yield in Holsteins

Since milk yield is a highly important economic trait in dairy cattle, the genome-wide association study (GWAS) is vital to explain the genetic architecture underlying milk yield and to perform marker-assisted selection (MAS). In this study, we adopted a haplotype-based empirical Bayesian GWAS to identify the loci and candidate genes for milk yield. A total of 1 092 Holstein cows were sequenced by using the genotyping by genome reducing and sequencing (GGRS) method. After filtering, 164 312 high-confidence SNPs and 13 476 haplotype blocks were identified to use for GWAS. The results indicated that 17 blocks were significantly associated with milk yield. We further identified the nearest gene of each haplotype block and annotated the genes with milk-associated quantitative trait locus (QTL) intervals and ingenuity pathway analysis (IPA) networks. Our analysis showed that four genes, DLGAP1, AP2B1, ITPR2 and THBS4, have relationships with milk yield, while another three, ARHGEF4, TDRD1 and KIF19, were inferred to have potential relationships. Additionally, a network derived from the IPA containing one inferred (ARHGEF4) and all four confirmed genes likely regulates milk yield. Our findings add to the understanding of identifying the causal genes underlying milk production traits and could guide follow up studies for further confirmation of the associated genes, pathways and biological networks.牛奶产量是奶牛极为重要的经济性状，全基因组关联分析（genome-wide association study, GWAS）对于解析牛奶产量背后的遗传架构、开展标记辅助选择（marker-assisted selection, MAS）均具有关键意义。本研究采用基于单倍型的经验贝叶斯全基因组关联分析，以挖掘牛奶产量相关位点及候选基因。本研究通过基因组简化测序（genotyping by genome reducing and sequencing, GGRS）技术，对1092头荷斯坦奶牛进行了测序。经过质量过滤后，共获得164312个高置信度单核苷酸多态性（single nucleotide polymorphism, SNPs）以及13476个单倍型区块，用于后续全基因组关联分析。分析结果显示，共有17个单倍型区块与牛奶产量显著相关。我们进一步对每个单倍型区块的邻近基因进行了鉴定，并结合牛奶相关数量性状基因座（quantitative trait locus, QTL）区间与Ingenuity通路分析（Ingenuity Pathway Analysis, IPA）网络对基因进行了注释。本研究分析发现，DLGAP1、AP2B1、ITPR2及THBS4这4个基因与牛奶产量存在明确关联；另有ARHGEF4、TDRD1、KIF19这3个基因被推测具有潜在关联。此外，由Ingenuity通路分析构建的网络中，包含1个推测关联基因（ARHGEF4）与全部4个已验证关联基因，该网络可能参与调控牛奶产量。本研究结果深化了对牛奶生产性状因果基因的挖掘认知，可为后续验证关联基因、通路及生物网络的相关研究提供参考。