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Ever since December, I’ve been reading a lot of research about the genetics of human skin color variation. To date, many genes have been identified in the skin pigmentation biochemical pathway. This suggests that the evolution of human skin color is multifaceted. Some of the genes you may have heard of before are ASIP, MC1R (more info), SLC24A5, TYR, KITL, HERC2, and the OCA gene family. To add a layer of complexity, many different alleles of each gene exist and ultimately affect the functionality of the gene product in the pigmentation pathway. Projects like the HapMap initiative have identified that certain populations have unique distributions and frequencies of skin color alleles.

A new research paper shared by Razib and published in the open access PLoS Genetics journal reports on new human skin color alleles not identified before. The paper is titled, “A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation.” The authors of this paper scanned the genomes of over 10,000 people of European ancestry to find alleles associated with hair and skin color, using the Illumina HumanHap300 array. They were able to identify IRF4 and SLC24A4 as two loci highly associated with hair and skin color.

Within IRF4 and SLC24A4, two SNPs had the most statistically significant associations to pigmentation:

  • The rs12896399 SNP is 15.5 kb upstream of the SLC24A4 gene, and was highly associated with light color. Almost 99% of Africans do not carry this allele, whereas there’s a 60:40 distribution among Europeans.
  • The rs12203592 SNP is found in intron 4 of the IRF4 gene. It was strongly associated with pigmentation. This SNP is associated with a black to blonde or red change in pigmentation of hair. I want to point out that this SNP seems to be found exclusively in 17% of people with European ancestry — or at least that’s what two different tests have shown.

The authors were also able to identify three chromosomal regions adjacent to the previously known pigmentation genes: MC1R, OCA2, and MATP. Further work needs to be done to figure out what IRF and SLC24A4 do in the pigmentation pathway. We already know that SLC24A4 is very similar to SLC24A5 in sequence and is most likely a calcium and sodium antiporter protein. According to the authors, the gene product of IRF4 falls under a member of the interferon regulatory factor family of transcription factors that regulate genes in response to interferons (immune proteins) and other cytokines (signaling proteins). This factoid makes me wonder if IRF4 also regulates the transcription of many known pigmentation genes and also how integrated are immune response and skin coloration (hint: tuberculosis and light skin)?

    Han, J., Kraft, P., Nan, H., Guo, Q., Chen, C., Qureshi, A., Hankinson, S.E., Hu, F.B., Duffy, D.L., Zhao, Z.Z., Martin, N.G., Montgomery, G.W., Hayward, N.K., Thomas, G., Hoover, R.N., Chanock, S., Hunter, D.J., Abecasis, G. (2008). A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation. PLoS Genetics, 4(5), e1000074. DOI: 10.1371/journal.pgen.1000074