Technische Universitaet Muenchen, Freising-Weihenstephan, Germany.
PLoS One. 2012;7(7):e40711. doi: 10.1371/journal.pone.0040711. Epub 2012 Jul 11.
Milk composition traits exhibit a complex genetic architecture with a small number of major quantitative trait loci (QTL) explaining a large fraction of the genetic variation and numerous QTL with minor effects. In order to identify QTL for milk fat percentage (FP) in the German Holstein-Friesian (HF) population, a genome-wide association study (GWAS) was performed. The study population consisted of 2327 progeny-tested bulls. Genotypes were available for 44,280 SNPs. Phenotypes in the form of estimated breeding values (EBVs) for FP were used as highly heritable traits. A variance components-based approach was used to account for population stratification. The GWAS identified four major QTL regions explaining 46.18% of the FP EBV variance. Besides two previously known FP QTL on BTA14 (P = 8.91×10-(198)) and BTA20 (P = 7.03×10(-12)) within DGAT1 and GHR, respectively, we uncovered two additional QTL regions on BTA5 (P = 2.00×10(-13)) and BTA27 (P = 9.83×10(-5)) encompassing EPS8 and GPAT4, respectively. EPS8 and GPAT4 are involved in lipid metabolism in mammals. Re-sequencing of EPS8 and GPAT4 revealed 50 polymorphisms. Genotypes for five of them were inferred for the entire study population. Two polymorphisms affecting potential transcription factor binding sites of EPS8 (P = 1.40×10(-12)) and GPAT4 (P = 5.18×10(-5)), respectively, were highly significantly associated with the FP EBV. Our results provide evidence that alteration of regulatory sites is an important aspect of genetic variation of complex traits in cattle.
牛奶成分特征表现出复杂的遗传结构，少数主要数量性状位点 (QTL) 解释了遗传变异的很大一部分，还有许多具有较小影响的 QTL。为了鉴定德国荷斯坦-弗里森牛（HF）群体中牛奶脂肪百分比（FP）的 QTL，进行了全基因组关联研究（GWAS）。研究群体由 2327 头后裔测试公牛组成。可获得 44280 个 SNP 的基因型。FP 的估计育种值（EBV）表型作为高度遗传的性状。使用基于方差分量的方法来解释群体分层。GWAS 鉴定出四个主要的 QTL 区域，解释了 FP EBV 方差的 46.18%。除了先前在 BTA14（P=8.91×10−198）和 BTA20（P=7.03×10−12）上发现的两个已知的 FP QTL，分别位于 DGAT1 和 GHR 内，我们还在 BTA5（P=2.00×10−13）和 BTA27（P=9.83×10−5）上发现了两个额外的 QTL 区域，分别包含 EPS8 和 GPAT4。EPS8 和 GPAT4 参与哺乳动物的脂质代谢。EPS8 和 GPAT4 的重测序揭示了 50 个多态性。对于整个研究群体，推断出其中五个多态性的基因型。影响 EPS8（P=1.40×10−12）和 GPAT4（P=5.18×10−5）潜在转录因子结合位点的两个多态性与 FP EBV 高度显著相关。我们的结果提供了证据，表明调节位点的改变是牛复杂性状遗传变异的一个重要方面。
