Scientists at deCODE genetics and colleagues in Iceland and Holland today report the discovery of variations in the human genome that influence pigmentation of hair, eyes and skin. By studying more than 300,000 SNPs (single-letter variants in the human genome) across the whole genome in close to seven thousand individuals of European origin, the deCODE team discovered several novel SNPs influencing hair, eye, and skin pigmentation, at the same time refining earlier findings influencing these traits.

The findings contribute to an understanding of the molecular basis for and evolution of these most visible of characteristics, and may be useful for teasing out the biology of skin and eye disease as well as for forensic DNA analysis. The paper, entitled “Genetic determinants of hair, eye and skin pigmentation in Europeans,” is published today online in Nature Genetics at will be published in an upcoming print edition of the journal.

It has long been recognized that pigmentation characteristics such as freckles and hair and eye color run in families. However, only few genes have been strongly linked to normal variation of these characteristics. Skin pigmentation in human populations tends to be darkest near the equator and to lighten with increasing latitude. This variation has a generally accepted dual biological function: heavier pigmentation affords protection against ultraviolet radiation in sunlight, protecting against sunburn and skin cancer but also reduces the body’s capacity to synthesize vitamin D. By contrast, there is no clear functional role for hair and eye color. The vast majority of variations in these two traits is confined to populations of European origin, with most populations around the globe with only dark hair and brown eyes.

Most of the novel variants presented in this study demonstrate signs of positive evolutionary selection in people of European origin, and those contributing to lighter pigmentation of the skin appear to have been under the strongest selective pressure. Intriguingly, some variants contribute to variation in just one trait; others to two or three. Among the findings of the deCODE group is a SNP on chromosome 14 in the SLC24A4 gene that is associated with increased likelihood of blond as opposed to brown hair and blue as opposed to green eyes. A SNP on chromosome 6p25 is associated with an increased likelihood of freckles and skin sensitivity to sunlight, as well as to brown hair. A sequence variant near the KITLG gene on chromosome 12 is associated with an increased likelihood of having blond rather than brown hair. One SNP in the tyrosinase gene is associated with freckling, and another associates with the likelihood of having blue as opposed to green eyes, as well as to skin sensitivity to sunlight.

The deCODE team has also provided strong and detailed support for the previously reported association in the MC1R gene with red hair, freckling and skin sensitivity to sun. Similarly, the well known association of variants near the OCA2 gene with eye and hair color, was replicated but also substantially refined. Taken together, the variants described in this report enable prediction of pigmentation traits based upon an individual’s DNA. This study has significantly improved the accuracy of predicting green eyes (SLC24A4, TYR), hair shade (SLC24A4, TYR, KITLG) and freckling (TYR, 6p25). Some of the novel association patterns differ in unexpected ways from previous findings. The variant in SLC24A4 is important for gauging likelihood of blue versus green eyes, but, in contrast to variants in OCA2, has only marginal impact on likelihood of blue versus brown eyes. The completely novel SNP discovered on 6p25 associates with freckles and brown hair, whereas the SNPs in MC1R associate with freckles and red hair. The multitude of genes affecting pigmentation and their varied effects are reflected in the great degree of diversity of pigmentation seen in Europeans.