Genetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition
Genetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition
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DOI：
10.1073/pnas.0308518100
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发表时间：
2004-02-24
影响因子：
11.1
通讯作者：
Georges, M
中科院分区：
文献类型：
--
作者：
Grisart, B;Farnir, F;Georges, M
我们最近使用定位克隆的方法鉴定了牛DGAT1基因中一个非保守的赖氨酸到丙氨酸替代(K232A)，该基因被认为是影响乳脂组成的数量性状基因座(QTL)的起因，该QTL以前被定位在牛14号染色体着丝粒末端。在此，我们产生了证实DGAT1 K232A突变的因果关系的遗传和功能数据。我们构建了包含该QTL的3.8-centimorgan BULGE30-BULGE9区间的高密度单核苷酸多态图谱，表明与乳脂率的关联在DGAT1基因上达到最大。我们提供了K等位基因已经经历了选择性扫描的证据。利用杆状病毒表达系统，我们在Sf9细胞中表达了两个DGAT1等位基因，结果表明，导致活体动物乳脂率增加的K等位基因具有比A等位基因更高的产生甘油三酯的V-max。
We recently used a positional cloning approach to identify a nonconservative lysine to alanine substitution (K232A) in the bovine DGAT1 gene that was proposed to be the causative quantitative trait nucleotide underlying a quantitative trait locus (QTL) affecting milk fat composition, previously mapped to the centromeric end of bovine chromosome 14. We herein generate genetic and functional data that confirm the causality of the DGAT1 K232A mutation. We have constructed a high-density single-nucleotide polymorphism map of the 3.8-centimorgan BULGE30-BULGE9 interval containing the QTL and show that the association with milk fat percentage maximizes at the DGAT1 gene. We provide evidence that the K allele has undergone a selective sweep. By using a baculovirus expression system, we have expressed both DGAT1 alleles in Sf9 cells and show that the K allele, causing an increase in milk fat percentage in the live animal, is characterized by a higher V-max in producing triglycerides than the A allele.