Abstract
BackgroundThe melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles. Some MC1R variants have been associated with skin cancer risk.ResultsAllele frequency data were compiled on 55 single nucleotide polymorphisms from seven geographically distinct human populations (n = 2306 individuals). MC1R nucleotide diversity, π, was much higher (10.1 × 10-4) than in other genes for all subjects. A large degree of population differentiation, determined by FST, was also present, particularly between Asia and all other populations, due to the p.R163Q (c.488 G>A) polymorphism. The least amount of differentiation was between the United States, Northern Europe, and Southern Europe. Tajima's D statistic suggested the presence of positive selection in individuals from Europe.ConclusionThis study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R.
Highlights
The melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles
It has been suggested that as humans migrated out of Africa to climates with more limited exposure to sunlight, relaxation of functional constraints in pigmentation genes, including MC1R, or selection for functionally relevant variants that led to lighter skin pigmentation occurred[24]
In most regions of the genome, there is a higher degree of genetic variation in individuals of African descent than in other populations, most likely due to evolutionary history [31,32]
Summary
The melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles. The melanocortin 1 receptor gene (MC1R, MIM#155555), a member of the G protein-coupled receptors superfamily, is the major contributor to normal pigment variation in humans. It is a small, highly polymorphic gene consisting of one exon with 951 coding nucleotides on chromosome 16q24.3. Numerous studies have demonstrated associations between specific MC1R variants and red hair, light skin, poor tanning ability and heavy freckling [4-9]. A recent genome-wide association scan confirmed the role of MC1R SNPs in hair, eye, and skin pigmentation[3]. Several MC1R variants are associated with increased risk of malignant melanoma in a variety of populations [14-22] The effect of MC1R polymorphisms in melanoma risk appears to extend (page number not for citation purposes) http://www.biomedcentral.com/1471-2156/9/31 beyond its effect on pigmentation in most of these investigations, and to be linked to melanomas harboring mutations in the BRAF oncogene[23]
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