Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation

Variants of the melanocortin 1 receptor(MC1R) gene are common in individual s with red hair and fair skin, but the relative contribution to these pigme ntary traits in heterozygotes, homozygotes and compound heterozygotes for v ariants at this locus from the multiple alleles present in Caucasian popula tions is unclear. We have investigated 174 individuals from 11 large kindre ds with a preponderance of red hair and an additional 99 unrelated redheads , for MC1R variants and have confirmed that red hair is usually inherited a s a recessive characteristic with the R151C, R160W, D294H, R142H, 86insA an d 537insC alleles at this locus. The V60L variant, which is common in the p opulation may act as a partially penetrant recessive allele, These individu als plus 167 randomly ascertained Caucasians demonstrate that heterozygotes for two alleles, R151C and 537insC, have a significantly elevated risk of red hair, The shade of red hair frequently differs in heterozygotes from th at in homozygotes/compound heterozygotes and there is also evidence for a h eterozygote effect on beard hair colour, skin type and freckling. The data provide evidence for a dosage effect of MC1R variants on hair as well as sk in colour.