Genetic Variation in Regulatory Regions of Human Pigmentation Genes

We are interested in identifying the genes and polymorphisms that contribute to normal variation in human eye, hair, and skin color.  Much of our understanding of human pigmentation comes from studies of mutations resulting in oculocutaneous albinism (OCA).  Many polymorphisms in genes associated with OCA are likely to affect gene function, and are expected to have similar effects on pigmentary phenotypes.  To investigate this hypothesis, we have surveyed a collection of human genomic DNA samples from individuals of diverse continental ancestries for single nucleotide polymorphisms (SNPs) in evolutionarily conserved regions of 6 candidate genes:  TYR, TYRP1, MATP, MC1R, OCA2, and SLC24A5.

We resequenced a total of 70 amplicons (420-650 bp each) in 230 individuals and identified 44 to 100 polymorphisms for each gene.  Frequencies of these polymorphisms range from 0.4% to 48.6%.  The genetic variants identified will be used for a large-scale association study based on 1000 DNA samples collected from subjects at the University of Arizona.  To control for the effects of population substructure, I used Ancestry Informative Markers (AIMs) to measure the extent of admixture present in each group.  We will evaluate which of these SNPs might contribute to phenotypic pigmentary variation.  The results will provide a genetic architectural glimpse of one of the most visible characteristics that contributes to human diversity.