A molecular basis for classic blond hair color in Europeans.
A molecular basis for classic blond hair color in Europeans.
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DOI：
10.1038/ng.2991
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发表时间：
2014-07
期刊：
影响因子：
30.8
通讯作者：
Kingsley DM
中科院分区：
文献类型：
--
作者：
Guenther CA;Tasic B;Luo L;Bedell MA;Kingsley DM
发色差异是人类表型变异最明显的例子之一。尽管全基因组关联研究（GWAS）已经发现了人类色素变异的多个位点，但致病碱基对的变化在很大程度上仍是未知的。在这里，我们剖析了kitlggene（编码KIT配体）的一个调控区域，该区域与北欧人常见的金发颜色显著相关。功能测试表明，该区域含有一种调控增强子，可在发育中的毛囊中驱动表达。该增强子含有一个共同的SNP (rs12821256)，该SNP改变了淋巴细胞增强因子结合因子1 （LEF1）转录因子的结合位点，降低了培养的人角化细胞中LEF1的反应性和增强子活性。携带人类kitlgenhancer祖先或衍生变体的小鼠在头发色素沉着方面表现出显著差异，证实了一种基本生长因子调节的改变有助于北欧人发现的经典金发表型。
Hair color differences are among the most obvious examples of phenotypic variation in humans. Although genome-wide association studies (GWAS) have implicated multiple loci in human pigment variation, the causative base-pair changes are still largely unknown. Here we dissect a regulatory region of theKITLGgene (encoding KIT ligand) that is significantly associated with common blond hair color in northern Europeans. Functional tests demonstrate that the region contains a regulatory enhancer that drives expression in developing hair follicles. This enhancer contains a common SNP (rs12821256) that alters a binding site for the lymphoid enhancer-binding factor 1 (LEF1) transcription factor, reducing LEF1 responsiveness and enhancer activity in cultured human keratinocytes. Mice carrying ancestral or derived variants of the humanKITLGenhancer exhibit significant differences in hair pigmentation, confirming that altered regulation of an essential growth factor contributes to the classic blond hair phenotype found in northern Europeans.