June 2, 2014

A genetic actor for blond hair in Eurasia

Interesting find on hair color genetic determination, which must be understood nonetheless as only one factor among several in this aspect.

Catherine A. Guenther et al., A molecular basis for classic blond hair color in Europeans. Nature Genetics 2014. Pay per viewLINK [doi:10.1038/ng.2991]


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.

The study, quite technical, is mostly about mice (a close relative of primates and hence humans) in which a SNP in the same non-coding upstream position relative to the Kitl gene (equivalent to the human KITLG) causes white hair coloration. In the case of some humans it seems to work almost exactly the same way, causing blond coloration of hair, a change already apparent in the mouse embryos.

Figure 1: A distant regulatory region upstream of the KITLG gene controls hair pigmentation in humans and mice.
(b) Frequency distribution of rs12821256 in different populations. The G allele associated with blond hair (yellow) is most prevalent in northern Europe. Green color represents the frequency of the ancestral A allele.

The distribution of the rs12821256-G allele is consistent with the presence of blond hair, including a small slice in SE Asia, where blond hair is known to happen even if rarely. 

However looking particularly at West Eurasia there is still a lot of unexplained blond hair: this allele is most common in England, which is not such an outstanding region for blond hair pigmentation, with highest phenotype frequencies concentrated around the Baltic instead. Basque blondes (which are quite a few) are absolutely unexplained by this particular allele, for example. 

So there must be necessarily other SNPs involved in blond hair formation. One of them was discovered in 2012 among Australasians but it is not found in the mainland apparently. The rest are still unknown.


  1. I wonder if those yellow slices in North America are strictly from European admixture or not. The whole blonde Inuit reports being the alternative I guess.

  2. 23andme actually tests this SNP. But it says the alleles are T and C instead of A and G like the paper says. I think the C allele at 23andme may be the same as the G allele in the paper

    1. Double helix' issues. G binds with C, so same thing, I believe.


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