Article abstract
Nature Genetics 41, 1061 - 1067 (2009)
Published online: 30 August 2009 | doi:10.1038/ng.437
Personalized copy number and segmental duplication maps using next-generation sequencing
Can Alkan1,2, Jeffrey M Kidd1, Tomas Marques-Bonet1,3, Gozde Aksay1, Francesca Antonacci1, Fereydoun Hormozdiari4, Jacob O Kitzman1, Carl Baker1, Maika Malig1, Onur Mutlu5, S Cenk Sahinalp4, Richard A Gibbs6 & Evan E Eichler1,2
Abstract
Despite their importance in gene innovation and phenotypic variation, duplicated regions have remained largely intractable owing to difficulties in accurately resolving their structure, copy number and sequence content. We present an algorithm (mrFAST) to comprehensively map next-generation sequence reads, which allows for the prediction of absolute copy-number variation of duplicated segments and genes. We examine three human genomes and experimentally validate genome-wide copy number differences. We estimate that, on average, 73–87 genes vary in copy number between any two individuals and find that these genic differences overwhelmingly correspond to segmental duplications (odds ratio = 135; P < 2.2 
10-16). Our method can distinguish between different copies of highly identical genes, providing a more accurate assessment of gene content and insight into functional constraint without the limitations of array-based technology.
- Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
- Howard Hughes Medical Institute, Seattle, Washington, USA.
- Institut de Biologia Evolutiva (UPF-CSIC), Barcelona, Catalonia, Spain.
- School of Computing Science, Simon Fraser University, Burnaby, British Columbia, Canada.
- Department of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
- Baylor College of Medicine, Houston, Texas, USA.
Correspondence to: Evan E Eichler1,2 e-mail: eee@gs.washington.edu
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