title: Personalized copy number and segmental duplication maps using next-generation sequencing.
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.
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Can
authors.initials: C
authors.lastname: Alkan
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Kidd
authors.forename: Tomas
authors.initials: T
authors.lastname: Marques-Bonet
authors.forename: Gozde
authors.initials: G
authors.lastname: Aksay
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonacci
authors.forename: Fereydoun
authors.initials: F
authors.lastname: Hormozdiari
authors.forename: Jacob O
authors.initials: JO
authors.lastname: Kitzman
authors.forename: Carl
authors.initials: C
authors.lastname: Baker
authors.forename: Maika
authors.initials: M
authors.lastname: Malig
authors.forename: Onur
authors.initials: O
authors.lastname: Mutlu
authors.forename: S Cenk
authors.initials: SC
authors.lastname: Sahinalp
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
mesh_terms: D000465:Algorithms; D002874:Chromosome Mapping / Q000379:methods*; D004247:DNA / Q000032:analysis* / Q000235:genetics; D018628:Gene Dosage; D020440:Gene Duplication; D015894:Genome, Human; D015698:Genomic Library; D006801:Humans; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004247:DNA