A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep
A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep
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DOI：
10.1038/ng1810
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发表时间：
2006-07-01
期刊：
影响因子：
30.8
通讯作者：
Georges, Michel
中科院分区：
文献类型：
--
作者：
Clop, Alex;Marcq, Fabienne;Georges, Michel
特克塞尔羊是著名的特殊肉质。为了确定这一经济上重要的特征背后的基因，我们在罗曼诺夫×特克塞尔F2种群中进行了全基因组扫描。我们将一个对肌肉质量有重要影响的数量性状位点定位到2号染色体上，随后将其精细定位到包含肌肉生长抑制素（GDF8）基因的染色体间隔上。我们在此证明Texel绵羊的GDF8等位基因的特征在于在3'UTR中的G到A的转变，其产生了在骨骼肌中高度表达的microRNA（miRNAs）mir1和mir206的靶位点。这会导致肌肉生长抑制素基因的翻译抑制，从而导致特克塞尔羊的肌肉肥大。对人类和小鼠SNP数据库的分析表明，产生或破坏推定的miRNA靶位点的突变是丰富的，并且可能是表型变异的重要效应子。
Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation.