Institute for Genomic Biology, Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Physiol Genomics. 2011 Nov 7;43(21):1185-97. doi: 10.1152/physiolgenomics.00253.2010. Epub 2011 Sep 6.
The goal of this study was to identify candidate genes and DNA polymorphisms for quantitative trait loci (QTL) affecting milk yield (MY), fat yield (FY), and protein yield (PY) previously mapped to bovine chromosome 3 (BTA3). To accomplish this, 373 half-siblings sired by three bulls previously shown to be segregating for lactation trait QTL, and 263 additional sires in the U.S. Dairy Bull DNA Repository (DBDR) were genotyped for 2,500 SNPs within a 16.3 Mbp QTL critical region on BTA3. Targeted resequencing of ∼1.8 Mbp within the QTL critical region of one of the QTL heterozygous sires identified additional polymorphisms useful for association studies. Twenty-three single nucleotide polymorphisms (SNPs) within a fine-mapped region were associated with effects on breeding values for MY, FY, or PY in DBDR sires, of which five SNPs were in strong linkage disequilibrium in the population. This multisite haplotype included SNPs located within exons or promoters of four tightly linked genes: RAP1A, ADORA3, OVGP1, and C3H1orf88. An SNP within RAP1A showed strong evidence of a recent selective sweep based on integrated haplotype score and was also associated with breeding value for PY. Because of its known function in alveolar lumen formation in the mammary gland, RAP1A is thus a strong candidate gene for QTL effects on lactation traits. Our results provide a detailed assessment of a QTL region that will be a useful guide for complex traits analysis in humans and other noninbred species.
本研究旨在鉴定与先前定位到牛 3 号染色体（BTA3）上的乳产量（MY）、脂肪产量（FY）和蛋白质产量（PY）数量性状基因座（QTL）相关的候选基因和 DNA 多态性。为了实现这一目标，对 373 头半同胞进行了基因分型，这些半同胞由 3 头公牛的父本产生，这 3 头公牛之前被证明存在与泌乳性状 QTL 分离的情况，此外还对美国奶牛公牛 DNA 资源库（DBDR）中的 263 头额外的公牛进行了基因分型，共对 BTA3 上一个 16.3 Mb 大小的 QTL 关键区域内的 2500 个 SNP 进行了基因分型。在一个 QTL 杂合子公牛的 QTL 关键区域内对大约 1.8 Mb 进行靶向重测序，鉴定出了另外一些与关联研究有用的多态性。在 DBDR 公牛中，23 个单核苷酸多态性（SNP）位于精细定位区域内，与 MY、FY 或 PY 的育种值效应相关，其中 5 个 SNP 在群体中存在强烈的连锁不平衡。这个多态性包括位于紧密连锁的四个基因的外显子或启动子内的 SNP：RAP1A、ADORA3、OVGP1 和 C3H1orf88。RAP1A 内的一个 SNP 显示出基于综合单体型评分的近期选择清除的有力证据，并且还与 PY 的育种值相关。由于其在乳腺肺泡腔形成中的已知功能，RAP1A 因此是一个与 QTL 对泌乳性状影响相关的强有力的候选基因。我们的研究结果提供了对 QTL 区域的详细评估，这将是人类和其他非近交物种进行复杂性状分析的有用指南。
