title: Characterization of missing human genome sequences and copy-number polymorphic insertions.
abstract: The extent of human genomic structural variation suggests that there must be portions of the genome yet to be discovered, annotated and characterized at the sequence level. We present a resource and analysis of 2,363 new insertion sequences corresponding to 720 genomic loci. We found that a substantial fraction of these sequences are either missing, fragmented or misassigned when compared to recent de novo sequence assemblies from short-read next-generation sequence data. We determined that 18-37% of these new insertions are copy-number polymorphic, including loci that show extensive population stratification among Europeans, Asians and Africans. Complete sequencing of 156 of these insertions identified new exons and conserved noncoding sequences not yet represented in the reference genome. We developed a method to accurately genotype these new insertions by mapping next-generation sequencing datasets to the breakpoint, thereby providing a means to characterize copy-number status for regions previously inaccessible to single-nucleotide polymorphism microarrays.
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Kidd
authors.forename: Nick
authors.initials: N
authors.lastname: Sampas
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonacci
authors.forename: Tina
authors.initials: T
authors.lastname: Graves
authors.forename: Robert
authors.initials: R
authors.lastname: Fulton
authors.forename: Hillary S
authors.initials: HS
authors.lastname: Hayden
authors.forename: Can
authors.initials: C
authors.lastname: Alkan
authors.forename: Maika
authors.initials: M
authors.lastname: Malig
authors.forename: Mario
authors.initials: M
authors.lastname: Ventura
authors.forename: Giuliana
authors.initials: G
authors.lastname: Giannuzzi
authors.forename: Joelle
authors.initials: J
authors.lastname: Kallicki
authors.forename: Paige
authors.initials: P
authors.lastname: Anderson
authors.forename: Anya
authors.initials: A
authors.lastname: Tsalenko
authors.forename: N Alice
authors.initials: NA
authors.lastname: Yamada
authors.forename: Peter
authors.initials: P
authors.lastname: Tsang
authors.forename: Rajinder
authors.initials: R
authors.lastname: Kaul
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.forename: Laurakay
authors.initials: L
authors.lastname: Bruhn
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
mesh_terms: D020451:Contig Mapping / Q000379:methods*; D004251:DNA Transposable Elements / Q000235:genetics; D005787:Gene Frequency; D015894:Genome, Human; D056914:Genomic Structural Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004251:DNA Transposable Elements