Tuesday, June 24, 2008

EDAR again   posted by p-ter @ 6/24/2008 09:00:00 PM

There have been a number of posts on this site regarding EDAR--in summary, a non-synonymous SNP has swept up to high frequency in East Asian populations via positive selection, and appears to account for some variation in hair form. The evidence for function in hair form comes largely from an association study on hair thickness. Now add a mouse model to the evidence:
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.
On the right is a wild-type mouse, contrasted with the "Asian" mouse. The mechanism by which this works is kind of intriguing--apparently the substitution in EDAR leads to increased signaling via NFkB, but it's an open question (both in this case and more generally) how the modification of the activity of a transcription factor leads to phenotypic changes at the level of an organism.