Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH Wageningen, the Netherlands; Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.
Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH Wageningen, the Netherlands.
J Dairy Sci. 2017 Nov;100(11):9125-9135. doi: 10.3168/jds.2017-12965. Epub 2017 Aug 31.
The aim of this study was to fine-map a genomic region associated with milk fatty acids (FA) on Bos taurus autosome (BTA) 17. This genomic region has been discovered with 50,000 (50k) single nucleotide polymorphisms (SNP) imputed to 777,000 (777k) SNP. In this study, high-density genotypes were imputed to whole-genome sequences level to identify candidate gene(s) associated with milk FA composition on BTA17. Phenotypes and genotypes were available for 1,640 cows sampled in winter, and for 1,581 cows sampled in summer. Phenotypes consisted of gas chromatography measurements in winter and in summer milk samples of 6 individual FA and the indicator of de novo synthesis, C6:0-C14:0. Genotypes consisted of imputed 777k SNP, and 89 sequenced ancestors of the population of genotyped cows. In addition, 450 whole-genome sequences from the 1,000 Bull Genome Consortium were available. Using 495 Holstein-Friesian sequences as a reference population, the 777k SNP genotypes of the cows were imputed to sequence level. We then applied single-variant analyses with an animal model, and identified thousands of significant associations with C6:0, C8:0, C10:0, C12:0, C14:0, and C6:0-C14:0. For C8:0 in summer milk samples, the genomic region located between 29 and 34 Mbp on BTA17 revealed a total of 646 significant associations. The most significant associations [-log(P-value) = 7.82] were 8 SNP in perfect linkage disequilibrium. After fitting one of these 8 SNP as a fixed effect in the model, and re-running the single-variant analyses, no further significant associations were found for any of the 6 FA or C6:0-C14:0. These findings suggest that one polymorphism underlying this QTL on BTA17 influences multiple de novo synthesized milk FA. Thirteen genes in the QTL region were identified and analyzed carefully. Six out of the 8 SNP that showed the strongest associations were located in the La ribonucleoprotein domain family, member 1B (LARP1B) gene, and we suggest LARP1B as a primary candidate gene. Another gene of interest for this QTL region might be PKL4. None of these suggested candidate genes have previously been associated with milk fat synthesis or milk FA composition.
本研究旨在对牛 17 号染色体上与乳脂脂肪酸（FA）相关的基因组区域进行精细定位。该基因组区域已经发现了 50000 个（50k）单核苷酸多态性（SNP），并被内插至 777000 个（777k）SNP。在这项研究中，高分辨率基因型被内插至全基因组序列水平，以鉴定与 BTA17 上乳脂 FA 组成相关的候选基因。表型和基因型可用于冬季和夏季采集的 1640 头奶牛和 1581 头奶牛。表型包括冬季和夏季牛奶样本中 6 种个体 FA 和从头合成指标 C6:0-C14:0 的气相色谱测量。基因型包括内插的 777k SNP 和该基因型奶牛群体的 89 个测序祖先。此外，还提供了 1000 头公牛基因组联盟的 450 个全基因组序列。利用 495 头荷斯坦-弗里生牛序列作为参考群体，将奶牛的 777k SNP 基因型内插至序列水平。然后，我们应用动物模型进行单变异分析，鉴定出数千个与 C6:0、C8:0、C10:0、C12:0、C14:0 和 C6:0-C14:0 显著相关的位点。对于夏季牛奶样本中的 C8:0，位于 BTA17 29 到 34 Mbp 之间的基因组区域共发现 646 个显著关联。最显著的关联[-log(P 值) = 7.82]是 8 个处于完全连锁不平衡的 SNP。在模型中拟合这 8 个 SNP 中的一个作为固定效应，并重新运行单变量分析后，发现 6 种 FA 或 C6:0-C14:0 中没有进一步显著的关联。这些发现表明，BTA17 上该 QTL 下的一个多态性影响多种从头合成的乳脂 FA。在 QTL 区域鉴定并仔细分析了 13 个基因。表现出最强关联的 8 个 SNP 中有 6 个位于 La 核糖核蛋白家族成员 1B（LARP1B）基因中，我们建议 LARP1B 作为主要候选基因。该 QTL 区域的另一个候选基因可能是 PKL4。这些候选基因中没有一个以前与乳脂合成或乳脂 FA 组成有关。
