Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry

Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry

Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signa...

Full description

Saved in:
Bibliographic Details
Published in:BMC evolutionary biology Vol. 13; no. 1; p. 150
Main Authors: Hider, Jessica L, Gittelman, Rachel M, Shah, Tapan, Edwards, Melissa, Rosenbloom, Arnold, Akey, Joshua M, Parra, Esteban J
Format: Journal Article
Language:English
Published: England BioMed Central Ltd 12-07-2013
BioMed Central
Subjects:
Analysis
Asian Continental Ancestry Group - ethnology
Asian Continental Ancestry Group - genetics
China - ethnology
Evolution
Genes
Genetic aspects
Genetic research
Genetic Variation
Genetics, Population
Haplotypes
Humans
Japan - ethnology
Mutation
Phenotype
Polymorphism, Single Nucleotide
Proteins - genetics
Selection, Genetic
Skin color
Skin Pigmentation - genetics
Studies
East Asia
Europe
Africa
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1) Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima's D, Fay and Wu's H and Fu and Li's D* and F*), 2) Tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb) and 3) Tests based on genetic differentiation between populations (LSBL). Based on the results obtained from a genome wide analysis of 25 kb windows, we constructed an empirical distribution for each statistic across all windows, and identified pigmentation genes that are outliers in the distribution. Our tests identified twenty genes that are relevant for pigmentation biology. Of these, eight genes (ATRN, EDAR, KLHL7, MITF, OCA2, TH, TMEM33 and TRPM1,) were extreme outliers (top 0.1% of the empirical distribution) for at least one statistic, and twelve genes (ADAM17, BNC2, CTSD, DCT, EGFR, LYST, MC1R, MLPH, OPRM1, PDIA6, PMEL (SILV) and TYRP1) were in the top 1% of the empirical distribution for at least one statistic. Additionally, eight of these genes (BNC2, EGFR, LYST, MC1R, OCA2, OPRM1, PMEL (SILV) and TYRP1) have been associated with pigmentary traits in association studies. We identified a number of putative pigmentation genes showing extremely unusual patterns of genetic variation in East Asia. Most of these genes are outliers for different tests and/or different populations, and have already been described in previous scans for positive selection, providing strong support to the hypothesis that recent selective sweeps left a signature in these regions. However, it will be necessary to carry out association and functional studies to demonstrate the implication of these genes in normal pigmentation variation.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1471-2148
1471-2148
DOI:10.1186/1471-2148-13-150