Global variation in copy number in the human genome

Abstract

Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies. Where to next after sequencing the human genome? We want to know how human genomes differ from each other. Last year the International HapMap Project published a map of single nucleotide changes, and now an international consortium has mapped even larger areas of differences, called copy number variants (CNVs). Each CNV involves at least 1,000 base-pair differences between individuals, and they have been linked to both benign and disease-causing changes in the genome. The new map is based on analysis of DNA from 270 individuals. Over 1,400 CNVs were found, covering 12% of the genome. This makes them far more prevalent than was thought, and suggests that unless analysed for directly, these differences could be missed by present strategies used to identify genes mutated in genetic diseases. Last year the first map of single nucleotide changes was published; now an international consortium has mapped even larger areas of differences, called copy number variants. These variants are at least 1,000-base-pair differences between individual people, and have been linked to both benign and disease-causing changes in the human genome.