Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle
Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle
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DOI：
10.1101/gr.3806705
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发表时间：
2005-07-01
期刊：
影响因子：
7
通讯作者：
Ron, M
中科院分区：
文献类型：
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作者：
Cohen-Zinder, M;Seroussi, E;Ron, M
我们先前将位于6号染色体上影响乳脂和蛋白质浓度的一个数量性状基因座（QTL）定位在一个以微卫星BM143为中心的4厘摩置信区间内。我们对该区域的基因和序列变异进行了特征分析，并确定了在IBSP、SPP1、PKD2和ABCG2基因中跨越5个多态性位点的常见单倍型，这是针对该QTL为杂合子的两头公牛而言。从分娩到泌乳期，牛乳腺中SPP1和ABCG2的表达量增加。对这两头公牛的SPP1以及ABCG2和PKD2的所有编码外显子进行了测序。在ABCG2转运蛋白中能够编码将酪氨酸 - 581替换为丝氨酸（Y581S）的单核苷酸变化是唯一与以色列和美国荷斯坦群体中该QTL的所有3头杂合子和15头纯合子公牛的分离状态相对应的多态性。等位基因替换对335头以色列公牛的遗传评估的固定效应为产奶量 - 341千克、脂肪含量 + 0.16%以及蛋白质含量 + 0.13%（F值 = 200）。在也包含Y581S的模型中，没有其他多态性对脂肪和蛋白质浓度产生显著影响。等位基因替换对670头母牛（两头杂合子公牛的女儿）的遗传评估的效应为产奶量 - 226千克、脂肪含量0.09%以及蛋白质含量0.08%（F值 = 394），对581S纯合子具有部分显性。因此，我们提出ABCG2中的Y581S是该QTL的致因位点。
We previously localized a quantitative trait locus (QTL) on chromosome 6 affecting milk fat and protein concentration to a 4-cM confidence interval, centered on the microsatellite BM143. We characterized the genes and sequence variation in this region and identified common haplotypes spanning five polymorphic sites in the genes IBSP, SPP1, PKD2, and ABCG2 for two sires heterozygous for this QTL. Expression of SPP1 and ABCG2 in the bovine mammary gland increased from parturition through lactation. SPPI and all the coding exons of ABCG2 and PKD2 were sequenced for these two sires. The single nucleotide change capable of encoding a substitution of tyrosine-581 to serine (Y581S) in the ABCG2 transporter was the only polymorphism corresponding to the segregation status of all 3 heterozygous and 15 homozygous sires for the QTL in the Israeli and U.S. Holstein populations. The allele Substitution fixed effects on the genetic evaluations of 335 Israeli sires were -341 kg milk, +0.16% fat, and +0.13% protein (F-value = 200). No other polymorphism gave significant effect for fat and protein concentration in models that also included Y581S. The allele substitution effects on the genetic evaluations of 670 cows, daughters of two heterozygous sires, were -226 kg milk, 0.09% fat, and 0.08% protein (F-value = 394), with partial dominance towards the 581S homozygotes. We therefore propose that Y581S in ABCG2 is the causative site for this QTL.