A scan for genetic determinants of human hair morphology:: EDAR is associated with Asian hair thickness
A scan for genetic determinants of human hair morphology:: EDAR is associated with Asian hair thickness
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DOI：
10.1093/hmg/ddm355
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发表时间：
2008-03-15
影响因子：
3.5
通讯作者：
Tokunaga, Katsushi
中科院分区：
文献类型：
--
作者：
Fujimoto, Akihiro;Kimura, Ryosuke;Tokunaga, Katsushi
毛发形态是人类群体中最具差异性的特征之一。然而，种群间毛发形态差异的遗传背景尚未明确。此外，对影响头发形态的进化力量所知甚少。为了鉴定毛发形态决定基因，利用国际HapMap项目的数据，对170个与毛发形态发生相关的基因的局部遗传分化水平进行了评估。在高度分化的基因中，具有亚洲特异性非同义单核苷酸多态性（1540T/C, 370Val/Ala）的外胞浆异常蛋白A受体（ectodysplasin A receptor， EDAR）被认为是强有力的候选基因。基因型与头发形态之间的关联研究表明，亚洲特有的1540C等位基因与头发厚度的增加有关。报告基因分析表明，1540T/C影响下游转录因子NF-kappa b的活性。从1540T/C的地理分布和远程单倍型检验推断，1540C是在亚洲人与欧洲人分化后出现的，其频率在东亚人群中迅速增加。这些发现使我们得出结论，EDAR是亚洲人头发厚度的主要遗传决定因素，1540C等位基因在亚洲人群中传播是由于最近的正选择。
Hair morphology is one of the most differentiated traits among human populations. However, genetic backgrounds of hair morphological differences among populations have not been clarified yet. In addition, little is known about the evolutionary forces that have acted on hair morphology. To identify hair morphology-determining genes, the levels of local genetic differentiation in 170 genes that are related to hair morphogenesis were evaluated by using data from the International HapMap project. Among highly differentiated genes, ectodysplasin A receptor (EDAR) harboring an Asian-specific non-synonymous single nucleotide polymorphism (1540T/C, 370Val/Ala) was identified as a strong candidate. Association studies between genotypes and hair morphology revealed that the Asian-specific 1540C allele is associated with increase in hair thickness. Reporter gene assays suggested that 1540T/C affects the activity of the downstream transcription factor NF-kappa B. It was inferred from geographic distribution of 1540T/C and the long-range haplotype test that 1540C arose after the divergence of Asians from Europeans and its frequency has rapidly increased in East Asian populations. These findings lead us to conclude that EDAR is a major genetic determinant of Asian hair thickness and the 1540C allele spread through Asian populations due to recent positive selection.