Personalized copy number and segmental duplication maps using next-generation sequencing

Can Alkan, Jeffrey M. Kidd, Tomas Marques-Bonet, Gozde Aksay, Francesca Antonacci, Fereydoun Hormozdiari, Jacob O. Kitzman, Carl Baker, Maika Malig, Onur Mutlu, S. Cenk Sahinalp, Richard A. Gibbs, Evan E. Eichler

Research output: Contribution to journalArticlepeer-review

516 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1061-1067
Number of pages7
JournalNature Genetics
Issue number10
StatePublished - Oct 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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