Nucleotide diversity and population differentiation of the melanocortin 1 receptor gene, MC1R.
BACKGROUND
The 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.


RESULTS
Allele frequency data were compiled on 55 single nucleotide polymorphisms from seven geographically distinct human populations (n = 2306 individuals). MC1R nucleotide diversity, pi, was much higher (10.1 x 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.


CONCLUSIONS
This study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R.
Savage
Sharon A
SA
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, USA. savagesh@mail.nih.gov
Gerstenblith
Meg R
MR
Goldstein
Alisa M
AM
Mirabello
Lisa
L
Fargnoli
Maria Concetta
MC
Peris
Ketty
K
Landi
Maria Teresa
MT
D000483:Alleles; D001483:Base Sequence; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008545:Melanoma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012641:Selection, Genetic; D012878:Skin Neoplasms / Q000235:genetics; D012880:Skin Pigmentation / Q000235:genetics*
D044102:Receptor, Melanocortin, Type 1