title: Accurate and reliable high-throughput detection of copy number variation in the human genome.
abstract: This study describes a new tool for accurate and reliable high-throughput detection of copy number variation in the human genome. We have constructed a large-insert clone DNA microarray covering the entire human genome in tiling path resolution that we have used to identify copy number variation in human populations. Crucial to this study has been the development of a robust array platform and analytic process for the automated identification of copy number variants (CNVs). The array consists of 26,574 clones covering 93.7% of euchromatic regions. Clones were selected primarily from the published "Golden Path," and mapping was confirmed by fingerprinting and BAC-end sequencing. Array performance was extensively tested by a series of validation assays. These included determining the hybridization characteristics of each individual clone on the array by chromosome-specific add-in experiments. Estimation of data reproducibility and false-positive/negative rates was carried out using self-self hybridizations, replicate experiments, and independent validations of CNVs. Based on these studies, we developed a variance-based automatic copy number detection analysis process (CNVfinder) and have demonstrated its robustness by comparison with the SW-ARRAY method.
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
authors.forename: Heike
authors.initials: H
authors.lastname: Fiegler
authors.forename: Richard
authors.initials: R
authors.lastname: Redon
authors.forename: Dan
authors.initials: D
authors.lastname: Andrews
authors.forename: Carol
authors.initials: C
authors.lastname: Scott
authors.forename: Robert
authors.initials: R
authors.lastname: Andrews
authors.forename: Carol
authors.initials: C
authors.lastname: Carder
authors.forename: Richard
authors.initials: R
authors.lastname: Clark
authors.forename: Oliver
authors.initials: O
authors.lastname: Dovey
authors.forename: Peter
authors.initials: P
authors.lastname: Ellis
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
authors.forename: Lisa
authors.initials: L
authors.lastname: French
authors.forename: Paul
authors.initials: P
authors.lastname: Hunt
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kalaitzopoulos
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.forename: Lyndal
authors.initials: L
authors.lastname: Montgomery
authors.forename: George H
authors.initials: GH
authors.lastname: Perry
authors.forename: Bob W
authors.initials: BW
authors.lastname: Plumb
authors.forename: Keith
authors.initials: K
authors.lastname: Porter
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Rigby
authors.forename: Diane
authors.initials: D
authors.lastname: Rigler
authors.forename: Armand
authors.initials: A
authors.lastname: Valsesia
authors.forename: Cordelia
authors.initials: C
authors.lastname: Langford
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Humphray
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
mesh_terms: D000465:Algorithms; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D016172:DNA Fingerprinting; D022041:Euchromatin / Q000737:chemistry; D005188:False Negative Reactions; D005189:False Positive Reactions; D018628:Gene Dosage; D020869:Gene Expression Profiling; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results
chemical_list: D022041:Euchromatin; D004247:DNA