Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair

The association between MSHR coding region variation and hair colour inhumans has been examined by genotyping 25 red haired and 62 non-redCaucasians, all of whom were 12 years of age and members of a twin pairstudy. Twelve amino acid substitutions were seen at 11 different sites,nine of these being newly described MSHR variants. The previously reportedVal92Met allele shows no association with hair colour, but the threealleles Arg151Cys, Arg160Trp and Asp294His were associated with red hairand one Val60Leu variant was most frequent in fair/blonde and light brownhair colours. Variant MSHR genotypes are associated with lighter skin typesand red hair (P < 0.001). However, comparison of the MSHR genotypes indizygotic twin pairs discordant for red hair colour indicates that the MSHRgene cannot be solely responsible for the red hair phenotype, since five of13 pairs tested had both haplotypes identical by state (with three of thefive having both identical by descent). Rather, it is likely thatadditional modifier genes exist, making variance in the MSHR gene necessarybut not always sufficient, for red hair production.