title: Paired-end mapping reveals extensive structural variation in the human genome.
abstract: Structural variation of the genome involves kilobase- to megabase-sized deletions, duplications, insertions, inversions, and complex combinations of rearrangements. We introduce high-throughput and massive paired-end mapping (PEM), a large-scale genome-sequencing method to identify structural variants (SVs) approximately 3 kilobases (kb) or larger that combines the rescue and capture of paired ends of 3-kb fragments, massive 454 sequencing, and a computational approach to map DNA reads onto a reference genome. PEM was used to map SVs in an African and in a putatively European individual and identified shared and divergent SVs relative to the reference genome. Overall, we fine-mapped more than 1000 SVs and documented that the number of SVs among humans is much larger than initially hypothesized; many of the SVs potentially affect gene function. The breakpoint junction sequences of more than 200 SVs were determined with a novel pooling strategy and computational analysis. Our analysis provided insights into the mechanisms of SV formation in humans.
authors: Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA.
authors: Jan O
authors: JO
authors: Korbel
authors: Alexander Eckehart
authors: AE
authors: Urban
authors: Jason P
authors: JP
authors: Affourtit
authors: Brian
authors: B
authors: Godwin
authors: Fabian
authors: F
authors: Grubert
authors: Jan Fredrik
authors: JF
authors: Simons
authors: Philip M
authors: PM
authors: Kim
authors: Dean
authors: D
authors: Palejev
authors: Nicholas J
authors: NJ
authors: Carriero
authors: Lei
authors: L
authors: Du
authors: Bruce E
authors: BE
authors: Taillon
authors: Zhoutao
authors: Z
authors: Chen
authors: Andrea
authors: A
authors: Tanzer
authors: A C Eugenia
authors: AC
authors: Saunders
authors: Jianxiang
authors: J
authors: Chi
authors: Fengtang
authors: F
authors: Yang
authors: Nigel P
authors: NP
authors: Carter
authors: Matthew E
authors: ME
authors: Hurles
authors: Sherman M
authors: SM
authors: Weissman
authors: Timothy T
authors: TT
authors: Harkins
authors: Mark B
authors: MB
authors: Gerstein
authors: Michael
authors: M
authors: Egholm
authors: Michael
authors: M
authors: Snyder
mesh_terms: D007446:Chromosome Inversion; D002874:Chromosome Mapping; D019295:Computational Biology; D005260:Female; D050939:Gene Fusion; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D016254:Mutagenesis, Insertional; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D018626:Retroelements; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D018626:Retroelements