Global variation in copy number in the human genome

Richard Redon

Shumpei Ishikawa

Karen Fitch

Lars Feuk

Andrew Carson+34 authors

^{The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK}

^{Genome Science, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 Japan}

^{Affymetrix, Inc., Santa Clara, CA, USA}

^{The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, MaRS Centre- East Tower, 101 College Street, Rm. 14-701, Toronto, Ontario, M5G 1L7, Canada}

^{Department of Molecular and Medical Genetics, University of Toronto}

^{Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA 02115}

^{Genes and Disease Program, and Barcelona CeGen Unit, Center for Genomic Regulation, Barcelona, Catalonia, Spain}

^{Dependable and High Performance Computing, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 Japan}

^{Departments of Medical Genetics and Pediatrics, University of Alberta, Edmonton, Canada}

^{Department of Human Genetics, University of Chicago, 920 East 58th Street, Chicago, Illinois, USA}

^{Department of Life and Health Sciences, Pompeu Fabra University, Barcelona, Catalonia, Spain}

^{Japan Science and Technology Agency Kawaguchi, Saitama, 332-0012, Japan}

^{Harvard Medical School, Boston, MA, USA 02115}

Senior Corresponding Authors: Matthew E. Hurles, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK, E-mail: ku.ca.regnas@hem

Stephen W. Scherer, The Centre for Applied Genomics, The Hospital for Sick Children, MaRS Centre- East Tower, 101 College Street, Rm. 14-701, Toronto, Ontario, M5G 1L7, Canada, E-mail: ac.no.sdikkcis.teneg@evets

^{First author equal contribution}

^{Principal Investigator equal contribution}

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. 1,447 copy number variable regions covering 360 megabases (12% of the genome) were identified in these populations; these CNV regions contained hundreds of genes, disease loci, functional elements and segmental duplications. Strikingly, these CNVs 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 dramatic variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.

Abstract

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