Fujimoto Akihiro, Kimura Ryosuke, Ohashi Jun, Omi Kazuya, Yuliwulandari Rika, Batubara Lilian, Mustofa Mohammad Syamsul, Samakkarn Urai, Settheetham-Ishida Wannapa, Ishida Takafumi, Morishita Yasuyuki, Furusawa Takuro, Nakazawa Minato, Ohtsuka Ryutaro, Tokunaga Katsushi
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo, Japan.
Hum Mol Genet. 2008 Mar 15;17(6):835-43. doi: 10.1093/hmg/ddm355. Epub 2007 Dec 8.
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-kappaB. 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.
头发形态是人类群体中差异最大的特征之一。然而，不同人群之间头发形态差异的遗传背景尚未明确。此外，对于作用于头发形态的进化力量也知之甚少。为了鉴定决定头发形态的基因，利用国际人类基因组单体型图计划（International HapMap project）的数据，评估了170个与头发形态发生相关基因的局部遗传分化水平。在高分化基因中，含有亚洲特异性非同义单核苷酸多态性（1540T/C，370Val/Ala）的外胚层发育不良蛋白A受体（EDAR）被确定为一个强有力的候选基因。基因型与头发形态的关联研究表明，亚洲特异性的1540C等位基因与头发变粗有关。报告基因检测表明，1540T/C影响下游转录因子NF-κB的活性。从1540T/C的地理分布和长程单倍型检测推断，1540C在亚洲人与欧洲人分化之后出现，并且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，并且由于近期的正选择，1540C等位基因在亚洲人群中扩散开来。
