Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form - PubMed (original) (raw)

. 2008 Dec;29(12):1405-11.

doi: 10.1002/humu.20795.

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Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form

Chunyan Mou et al. Hum Mutat. 2008 Dec.

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Abstract

Hair morphology differs dramatically between human populations: people of East Asian ancestry typically have a coarse hair texture, with individual fibers being straight, of large diameter, and cylindrical when compared to hair of European or African origin. Ectodysplasin-A receptor (EDAR) is a cell surface receptor of the tumor necrosis factor receptor (TNFR) family involved in the development of hair follicles, teeth, and sweat glands. Analyses of genome-wide polymorphism data from multiple human populations suggest that EDAR experienced strong positive selection in East Asians. It is likely that a nonsynonymous SNP in EDAR, rs3827760, was the direct target of selection as the derived p.Val370Ala variant is seen at high frequencies in populations of East Asian and Native American origin but is essentially absent from European and African populations. Here we demonstrate that the derived EDAR370A common in East Asia has a more potent signaling output than the ancestral EDAR370 V in vitro. We show that elevation of Edar activity in transgenic mice converts their hair phenotype to the typical East Asian morphology. The coat texture becomes coarse, with straightening and thickening of individual hairs and conversion of fiber cross-sectional profile to a circular form. These thick hair fibers are produced by enlarged hair follicles, which in turn develop from enlarged embryonic organ primordia. This work shows that the multiple differences in hair form between East Asian and other human populations can be explained by the simplest of genetic alterations.

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