Nucleotide diversity and population differentiation of the Melanocortin 1 Receptor gene, MC1R

Sharon A Savage¹ , Meg R Gerstenblith² , Alisa M Goldstein² , Lisa Mirabello¹ , Maria Concetta Fargnoli³ , Ketty Peris³ and Maria Teresa Landi²

¹Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, USA

²Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, USA

³Department of Dermatology, University of L'Aquila, Via Vetoio – Coppito 2, 67100 L'Aquila, Italy

author email corresponding author email

BMC Genetics 2008, 9:31doi:10.1186/1471-2156-9-31


Published:	10 April 2008

Abstract

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, π, was much higher (10.1 × 10^-4) than in other genes for all subjects. A large degree of population differentiation, determined by F_ST, 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.

Conclusion

This study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R.