Identifying the genetic architecture of pigmentary traits in populations of diverse ancestry

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The remarkable variation in skin, hair and iris pigmentation observed in human populations is due to differences in the amount, type and distribution of melanin, which is synthesized by specialized cells known as melanocytes. The detailed picture of the genes involved in these traits remains far from complete. In particular, very few studies have focused on the genetics of pigmentation in non-European populations, in spite of the fact that quantitative studies of skin, hair and iris color in these populations show that there is substantial diversity in these traits. ******In this project, I propose to identify genetic markers responsible for normal variation in skin, hair and iris colour, as well as iris structure, in a large sample of individuals of diverse ancestry (3,000 individuals of East Asian, European and South Asian ancestry, 1,000 per group). Detailed quantitative measures of skin and hair pigmentation (using reflectance spectroscopy), and iris colour and structure (using high-resolution photography), will be obtained for each individual, and a microarray will be used to characterize more than 1.7 million genetic markers throughout the genome. This will make it possible to evaluate the association of the genetic markers with pigmentary traits and iris structure. ******Pigmentation is a particularly fascinating phenotype to study in human populations, because in many respects it is an atypical trait. Numerous genetic studies have indicated that the average proportion of genetic variation due to differences between major continental groups is just 10-15% of the total genetic variation. In contrast, pigmentary traits show large differences between continental populations. The reasons for this discrepancy can be traced back primarily to the strong influence of natural selection, which has shaped the distribution of pigmentation according to a clear latitudinal gradient. The proposed systematic study of pigmentary phenotypes in populations of diverse ancestry is important from evolutionary, genetic, and anthropological points of view; it will clarify the connection between the molecular variation and the phenotypic diversity observed in our species, while providing insights on how diverse factors (particularly natural selection) have shaped the evolution of pigmentation and pigmentation genes. The research is also relevant from a biomedical perspective, given that many variants associated with common pigmentation variation are also associated with skin cancer risk. Finally, this project will explore the genetic architecture of iris structure (e.g., contraction furrows, Fuchs' crypts, nevi, and Wolfflin nodules). These traits show substantial variation in human populations, but very few studies have been devoted to the identification of the genetic factors underlying this variation.