title: Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly.
abstract: Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise breakpoints, and in contrast to other methods, can resolve complex rearrangements. In total, we identified 277,243 SVs ranging in length from 1-23 kb. Validation using computational and experimental methods suggests that we achieve overall <6% false-positive rate and <10% false-negative rate in genomic regions that can be assembled, which outperforms other methods. Analysis of the SVs in the genomes of 106 individuals sequenced as part of the 1000 Genomes Project suggests that SVs account for a greater fraction of the diversity between individuals than do single-nucleotide polymorphisms (SNPs). These findings demonstrate that whole-genome de novo assembly is a feasible approach to deriving more comprehensive maps of genetic variation.
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Hancheng
authors.initials: H
authors.lastname: Zheng
authors.forename: Ruibang
authors.initials: R
authors.lastname: Luo
authors.forename: Honglong
authors.initials: H
authors.lastname: Wu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhu
authors.forename: Ruiqiang
authors.initials: R
authors.lastname: Li
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Cao
authors.forename: Boxin
authors.initials: B
authors.lastname: Wu
authors.forename: Shujia
authors.initials: S
authors.lastname: Huang
authors.forename: Haojing
authors.initials: H
authors.lastname: Shao
authors.forename: Hanzhou
authors.initials: H
authors.lastname: Ma
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Shuijian
authors.initials: S
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hongli
authors.initials: H
authors.lastname: Du
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.forename: Jingxiang
authors.initials: J
authors.lastname: Li
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Adam J
authors.initials: AJ
authors.lastname: de Smith
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: Lachlan J M
authors.initials: LJ
authors.lastname: Coin
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002874:Chromosome Mapping; D014644:Genetic Variation; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods*