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

TitlePersonalized copy number and segmental duplication maps using next-generation sequencing.
Publication TypeJournal Article
Year of Publication2009
AuthorsAlkan, C, Kidd, JM, Marques-Bonet, T, Aksay, G, Antonacci, F, Hormozdiari, F, Kitzman, JO, Baker, C, Malig, M, Mutlu, O, S Sahinalp, C, Gibbs, RA, Eichler, EE
JournalNat Genet
Volume41
Issue10
Pagination1061-7
Date Published2009 Oct
ISSN1546-1718
KeywordsAlgorithms, Chromosome Mapping, DNA, Gene Dosage, Gene Duplication, Genome, Human, Genomic Library, Humans, Polymorphism, Genetic, Sequence Analysis, DNA
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 x 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.

DOI10.1038/ng.437
Alternate JournalNat. Genet.
PubMed ID19718026
PubMed Central IDPMC2875196
Grant ListR01 HG006004 / HG / NHGRI NIH HHS / United States
P01 HG004120-03 / HG / NHGRI NIH HHS / United States
HG004120 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
P01 HG004120 / HG / NHGRI NIH HHS / United States