Presentation Abstract

Title: P10.31 - Pigmentation gene MC1R shows strong genetic patterning in Eurasia
Keywords: MC1R; Eurasia; variation
Authors: E. C. Royrvik1, K. K. Nicodemus1, N. Y. Yuldasheva2,3, S. Wells4, R. M. Ruzibakiev3, W. F. Bodmer1;
1Cancer and Immunogenetics, Department of Clinical Pharmacology, University of Oxford, Oxford, UK, Oxford, United Kingdom, 2Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom, 3Institute of Immunology, Academy of Sciences, Tashkent, Uzbekistan, 4The Genographic Project, National Geographic Society, Washington, DC, United States.
Abstract Body: The population genetics of the Central Asian heartland is of great interest, both in and of itself and because prehistoric populations ancestral to those of Europe and East Asia are thought to have passed through this region. However, Central Asia has not been as extensively studied as the eastern and western parts of the continent. Of particular interest in this geographical context is the MC1R gene due to its importance in skin pigmentation. We present a comprehensive analysis of allele/haplotype frequencies from five functional SNPs (rs1805005, rs2228479, rs1805007, rs1805008, and rs885479) in MC1R throughout Eurasia, including from 12,151 individuals from 141 regional populations, focussing on novel genotype data from 38 Central Asian populations.
We performed analyses of allelic differentiation (FST) and direct statistical tests of allele/haplotype frequency differences using Fisher’s exact test. These revealed several significant differences between populations for all SNPs, and a striking pattern of highly significant differences between even some Central Asian populations (e.g. p=2.38x10-23 for Iranians from Samarkand and neighbouring Kyrgyz).
Our results confirm divergent trends in eastern and western Eurasia, with strong minor allele frequency gradients, perhaps reflecting selection of different variants in MC1R, such as are seen in other pigmentation genes. Data from the mitochondrial genome and Y chromosome are included to provide a framework for interpretation. Finally, as Central Asia consists of a patchwork of linguistic areas with related language groups frequently being geographically distant from one another, we investigate whether any subordinate genetic patterning is associated with linguistic rather than geographic affiliation.