June 01, 2014

A molecular basis for classic blond hair (Guenther et al. 2014)

Nature Genetics (2014) doi:10.1038/ng.2991

A molecular basis for classic blond hair color in Europeans

Catherine A Guenther et al.

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 unknown1. Here we dissect a regulatory region of the KITLG gene (encoding KIT ligand) that is significantly associated with common blond hair color in northern Europeans2. 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 human KITLG enhancer 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.



Krefter said...

When they say classic blonde hair do they mean bright yellow? A very small percentage of Europeans have derived alleles in rs12821256, much smaller than what their overall light hair percentages are.


Kurti said...

why no samples from the Caucasus, Iran or Mesopotamia ?

Ryan said...

Any idea on how well they controlled for admixture in the North American samples?

Nathan J. Bowen said...

looks like T on the + strand is the ancestral state.

54markl said...

Colored hair and eye genes probably come ultimately from the Neanderthals.