I was doing some snooping around due some questions about the HERC2 & eye color papers I mentioned yesterday. Guess what? Earlier this month a Danish group published a similar paper, Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. It’s Open Access, so you can read it yourself. The language is a bit more stilted and hurried than the two papers I mentioned yesterday, but the basically independently confirmed the Australian group’s specific finding:
In conclusion, we have identified a conserved regulatory element within intron 86 of the HERC2 gene that is perfectly associated with the brown/blue eye color in studied individuals from Denmark, Turkey and Jordan. This element had an inhibitory effect on the OCA2 promoter activity in cell cultures, and the blue and the brown alleles were shown to bind non-identical subsets of nuclear extracts. In total, all these data strongly support a model where the blue eye color in humans is caused by homozygosity of the rs12913832*G allele.
Instead of just doing comparative analysis they actually tested the hypothesis in cell culture after preforming linkage & association, and seem to have come out with what you’d expect, the SNP on intron 86 of HERC2 regulates transcription at OCA2. Their Ns were a little small compared to the other two groups, but their inclusion of Middle Eastern individuals was interesting. They imply that it’s a common haplotype derived from a single mutational event, presumably recently driven up in frequency by selection. Their conjecture of location and rationale aren’t convincing, I’m sure commenters here could offer many more ingenious models based on historical & geographical particulars (I know the reasons proffered overlap with some of mine, but I’m a dude on a blog). I get the impression they haven’t heard of Haplotter (look at the references). All that being said, at the rate that papers are being pumped out the golden age of pigmentation genetics may not have a very long shelf life (granted, that’s a good thing). By the way, the gene they say has an association with hair color, RABGGTA, has been pegged as being under negative selection.
Update: ScienceDaily has a summary up with a most retarded title.