Oral communication, iL9

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Human pigmentation genes and population polymorphism

The physical appearance of skin, hair and eye colour can vary dramatically among geographically isolated human populations. It has long been speculated that this is due to adaptive changes, but the genetic causes for this degree of phenotypic variation have remained largely unknown. It is apparent that a large number of genes impacting melanosome biogenesis or the melanin biosynthetic pathway will influence the diversity seen in human pigmentation. The discovery and characterisation of human pigmentation gene polymorphism within and between human populations, combined with functional studies, have provided a framework to understand normal variation in this physical trait. Major candidate genes include the enzymes encoded by tyrosinase, tyrosinase-related protein-1 and dopachrome tautomerase (TYR, TYRP1 and DCT), the P-protein (OCA2) and the melanocortin-1 receptor (MC1R). Variant alleles of the MC1R gene resulting from a range of amino acid substitutions have been associated with red hair, fair skin, a high degree of freckling as well as increased incidence of melanoma. A single SNP located in a regulatory region upstream of the OCA2 locus that determines blue-brown eye colour inheritance in Europeans. Other population studies have revealed specific polymorphisms within the MATP (SLC45A2) and NCKX5 (SLC24A5) protein coding regions associated with the degree of skin pigmentation. Our studies take advantage of cultures of human primary melanocytes derived from donor skin tissue and selected based on pigmentation genotype and/or phenotype. Direct testing of a range of clonal melanocyte cultures characterised for three causal SNPs within SLC45A2, SLC24A5 and OCA2 have assessed their impact on melanin content and tyrosinase enzyme activity.

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