Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, China Agricultural University, No. 2 Yuanmingyuan West Road, Haidian District, Beijing, 100193, China.
Beijing Dairy Cattle Center, Beijing, 100192, China.
BMC Genet. 2019 Aug 16;20(1):69. doi: 10.1186/s12863-019-0769-1.
Our initial genome-wide association study (GWAS) identified 20 promising candidate genes for milk fatty acid (FA) traits in a Chinese Holstein population, including PRLR, MOGAT1, MINPP1 and CHUK genes. In this study, we performed whether they had significant genetic effects on milk FA traits in Chinese Holstein.
We re-sequenced the entire exons and 3000 bp of the 5' and 3' flanking regions, and identified 11 single nucleotide polymorphisms (SNPs), containing four in PRLR, two in MOGAT1, two in MINPP1, and three in CHUK. The SNP-based association analyses showed that all the 11 SNPs were significantly associated with at least one milk FA trait (P = 0.0456 ~ < 0.0001), and none of them had association with C11:0, C13:0, C15:0 and C16:0 (P > 0.05). By the linkage disequilibrium (LD) analyses, we found two, one, one, and one haplotype blocks in PRLR, MOGAT1, MINPP1, and CHUK, respectively, and each haplotype block was significantly associated with at least one milk FA trait (P = 0.0456 ~ < 0.0001). Further, g.38949011G > A in PRLR, and g.111599360A > G and g.111601747 T > A in MOGAT1 were predicted to alter the transcription factor binding sites (TFBSs). A missense mutation, g.39115344G > A, could change the PRLR protein structure. The g.20966385C > G of CHUK varied the binding sequences for microRNAs. Therefore, we deduced the five SNPs as the potential functional mutations.
In summary, we first detected the genetic effects of PRLR, MOGAT1, MINPP1 and CHUK genes on milk FA traits, and researched the potential functional mutations. These data provided the basis for further investigation on function validation of the four genes in Chinese Holstein.
我们的全基因组关联研究（GWAS）最初确定了 20 个在中国荷斯坦牛群体中与乳脂肪酸（FA）性状相关的有希望的候选基因，包括 PRLR、MOGAT1、MINPP1 和 CHUK 基因。在这项研究中，我们研究了它们是否对中国荷斯坦牛的乳 FA 性状有显著的遗传效应。
我们重新测序了整个外显子和 5'和 3'侧翼区域的 3000bp，鉴定了 11 个单核苷酸多态性（SNP），包括 PRLR 中的 4 个，MOGAT1 中的 2 个，MINPP1 中的 2 个，CHUK 中的 3 个。基于 SNP 的关联分析表明，这 11 个 SNP 均与至少一个乳 FA 性状显著相关（P=0.0456<0.0001），并且它们均与 C11:0、C13:0、C15:0 和 C16:0 无关（P>0.05）。通过连锁不平衡（LD）分析，我们分别在 PRLR、MOGAT1、MINPP1 和 CHUK 中发现了两个、一个、一个和一个单倍型块，每个单倍型块均与至少一个乳 FA 性状显著相关（P=0.0456<0.0001）。此外，PRLR 中的 g.38949011G>G、MOGAT1 中的 g.111599360A>G 和 g.111601747>T>A 被预测改变了转录因子结合位点（TFBS）。错义突变 g.39115344G>A 可能改变 PRLR 蛋白结构。CHUK 的 g.20966385C>G 改变了 microRNA 的结合序列。因此，我们推断这五个 SNP 为潜在的功能突变。
综上所述，我们首次检测了 PRLR、MOGAT1、MINPP1 和 CHUK 基因对乳 FA 性状的遗传效应，并研究了潜在的功能突变。这些数据为进一步研究这四个基因在中国荷斯坦牛中的功能验证提供了依据。
