Whole Genome Distribution and Ethnic Differentiation of Copy Number Variation in Caucasian and Asian Populations

Jian Li,Christopher J Papasian,Qi Zhou,Yumei Peng,Betty M Drees,Hongyi Deng,Yinping Zhang,Zhixin Zhang,James J Hamilton,Robert R Recker,Han Yan,Jing Cheng,Shawn Levy,Feng Pan,Liang Wang,Yan Guo,Lina He,Tie‐Lin Yang ,Xinyao Zhu ,Hong Wen Deng

doi:10.1371/journal.pone.0007958

Abstract

Although copy number variation (CNV) has recently received much attention as a form of structure variation within the human genome, knowledge is still inadequate on fundamental CNV characteristics such as occurrence rate, genomic distribution and ethnic differentiation. In the present study, we used the Affymetrix GeneChip® Mapping 500K Array to discover and characterize CNVs in the human genome and to study ethnic differences of CNVs between Caucasians and Asians. Three thousand and nineteen CNVs, including 2381 CNVs in autosomes and 638 CNVs in X chromosome, from 985 Caucasian and 692 Asian individuals were identified, with a mean length of 296 kb. Among these CNVs, 190 had frequencies greater than 1% in at least one ethnic group, and 109 showed significant ethnic differences in frequencies (p<0.01). After merging overlapping CNVs, 1135 copy number variation regions (CNVRs), covering approximately 439 Mb (14.3%) of the human genome, were obtained. Our findings of ethnic differentiation of CNVs, along with the newly constructed CNV genomic map, extend our knowledge on the structural variation in the human genome and may furnish a basis for understanding the genomic differentiation of complex traits across ethnic groups.

Highlights

Variation within the human genome can take many different forms
Brief summaries of copy number variation (CNV) and copy number variation regions (CNVRs) characteristics in each ethnic group were shown in Table 1, with detailed summaries being presented in the corresponding supplementary tables
Using the Affymetrix GenechipH 500K array, we have identified a large number of CNVs and CNVRs in US Caucasian and Chinese Han populations

Summary

Introduction

Variation within the human genome can take many different forms. One form of structural variation is copy number variation (CNV), in which a DNA segment, ranging from 1 kb to several megabases, is present at a variable copy number in comparison to a reference genome [1]. It has been difficult to combine results from different studies to produce an accurate description of genomic CNV characteristics such as the total number, genomic position, gene content, and frequency distribution [7]. One approach that can minimize the problems listed above is to use large sample sizes comprised of subjects from comparatively homogeneous ethnic backgrounds for each study population [15]. Recent technologic developments such as the availability of high-density SNP microarrays have been helpful, in terms of providing an efficient and affordable tool for CNV discovery in the human genome

Methods

Results

Conclusion