title: Mapping and sequencing of structural variation from eight human genomes.
abstract: Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.
authors.affiliation: Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Kidd
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cooper
authors.forename: William F
authors.initials: WF
authors.lastname: Donahue
authors.forename: Hillary S
authors.initials: HS
authors.lastname: Hayden
authors.forename: Nick
authors.initials: N
authors.lastname: Sampas
authors.forename: Tina
authors.initials: T
authors.lastname: Graves
authors.forename: Nancy
authors.initials: N
authors.lastname: Hansen
authors.forename: Brian
authors.initials: B
authors.lastname: Teague
authors.forename: Can
authors.initials: C
authors.lastname: Alkan
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonacci
authors.forename: Eric
authors.initials: E
authors.lastname: Haugen
authors.forename: Troy
authors.initials: T
authors.lastname: Zerr
authors.forename: N Alice
authors.initials: NA
authors.lastname: Yamada
authors.forename: Peter
authors.initials: P
authors.lastname: Tsang
authors.forename: Tera L
authors.initials: TL
authors.lastname: Newman
authors.forename: Eray
authors.initials: E
authors.lastname: Tüzün
authors.forename: Ze
authors.initials: Z
authors.lastname: Cheng
authors.forename: Heather M
authors.initials: HM
authors.lastname: Ebling
authors.forename: Nadeem
authors.initials: N
authors.lastname: Tusneem
authors.forename: Robert
authors.initials: R
authors.lastname: David
authors.forename: Will
authors.initials: W
authors.lastname: Gillett
authors.forename: Karen A
authors.initials: KA
authors.lastname: Phelps
authors.forename: Molly
authors.initials: M
authors.lastname: Weaver
authors.forename: David
authors.initials: D
authors.lastname: Saranga
authors.forename: Adrianne
authors.initials: A
authors.lastname: Brand
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
authors.forename: Erik
authors.initials: E
authors.lastname: Gustafson
authors.forename: Kevin
authors.initials: K
authors.lastname: McKernan
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Maika
authors.initials: M
authors.lastname: Malig
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Smith
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Korn
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarroll
authors.forename: David A
authors.initials: DA
authors.lastname: Altshuler
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Peiffer
authors.forename: Michael
authors.initials: M
authors.lastname: Dorschner
authors.forename: John
authors.initials: J
authors.lastname: Stamatoyannopoulos
authors.forename: David
authors.initials: D
authors.lastname: Schwartz
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.forename: Laurakay
authors.initials: L
authors.lastname: Bruhn
authors.forename: Maynard V
authors.initials: MV
authors.lastname: Olson
authors.forename: Rajinder
authors.initials: R
authors.lastname: Kaul
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Smith
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
mesh_terms: D007446:Chromosome Inversion / Q000235:genetics; D022041:Euchromatin / Q000235:genetics; D017353:Gene Deletion; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D005843:Geography; D006239:Haplotypes; D006801:Humans; D016254:Mutagenesis, Insertional / Q000235:genetics; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044469:Racial Groups / Q000235:genetics; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
chemical_list: D022041:Euchromatin