Extensive copy number variations in admixed Indian population of African ancestry: potential involvement in adaptation.

Ankita Narang,Mitali Mukerji,Anupam Kumar Mondal,Debasis Dash,Rintu Kutum,Pankaj Jha,Dhirendra Kumar

doi:10.1093/gbe/evu250

Abstract

Admixture mapping has been enormously resourceful in identifying genetic variations linked to phenotypes, adaptation, and diseases. In this study through analysis of copy number variable regions (CNVRs), we report extensive restructuring in the genomes of the recently admixed African-Indian population (OG-W-IP) that inhabits a highly saline environment in Western India. The study included subjects from OG-W-IP (OG), five different Indian and three HapMap populations that were genotyped using Affymetrix version 6.0 arrays. Copy number variations (CNVs) detected using Birdsuite were used to define CNVRs. Population structure with respect to CNVRs was delineated using random forest approach. OG genomes have a surprising excess of CNVs in comparison to other studied populations. Individual ancestry proportions computed using STRUCTURE also reveals a unique genetic component in OGs. Population structure analysis with CNV genotypes indicates OG to be distant from both the African and Indian ancestral populations. Interestingly, it shows genetic proximity with respect to CNVs to only one Indian population IE-W-LP4, which also happens to reside in the same geographical region. We also observe a significant enrichment of molecular processes related to ion binding and receptor activity in genes encompassing OG-specific CNVRs. Our results suggest that retention of CNVRs from ancestral natives and de novo acquisition of CNVRs could accelerate the process of adaptation especially in an extreme environment. Additionally, this population would be enormously useful for dissecting genes and delineating the involvement of CNVs in salt adaptation.

Highlights

Copy number variations (CNVs) range in size from 1 kb to several megabases and include deletions, duplications, and large insertions–deletions (Sebat et al 2004; Feuk et al 2006; Redon et al 2006)
As Luhya is represented in HapMap, we used this population as a surrogate for BantuKenyans for CNV analysis
We checked for the concordance of CNV calls using two other softwares—PennCNV and Affymetrix Genotyping Console (GTC)

Summary

Introduction

Copy number variations (CNVs) range in size from 1 kb to several megabases and include deletions, duplications, and large insertions–deletions (indels) (Sebat et al 2004; Feuk et al 2006; Redon et al 2006). CNVs occupy a larger fraction of the human genome in terms of nucleotide sequences when compared with the single-nucleotide polymorphisms (SNPs) (Wain et al 2009). These have been implicated in many human disorders such as autism, schizophrenia, glioblastoma, and in phenotypic diversity (Freeman et al 2006; Beckmann et al 2007; Cooper et al 2007; Cook and Scherer 2008; Conrad et al 2010; Stankiewicz and Lupski 2010). In a genome-wide study on large CNVs across 26 Indian populations, we observed population-specific functional enrichments of processes such as serine proteases and their inhibitors, keratinization, and olfactory receptors (Gautam et al 2012). Its identification and characterization and its correlation with function is extremely challenging (Alkan et al 2011; Gautam et al 2012)

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Results

Conclusion