Accurate and reliable high-throughput detection of copy number variation in the human genome.
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.
Fiegler
Heike
H
The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
Redon
Richard
R
Andrews
Dan
D
Scott
Carol
C
Andrews
Robert
R
Carder
Carol
C
Clark
Richard
R
Dovey
Oliver
O
Ellis
Peter
P
Feuk
Lars
L
French
Lisa
L
Hunt
Paul
P
Kalaitzopoulos
Dimitrios
D
Larkin
James
J
Montgomery
Lyndal
L
Perry
George H
GH
Plumb
Bob W
BW
Porter
Keith
K
Rigby
Rachel E
RE
Rigler
Diane
D
Valsesia
Armand
A
Langford
Cordelia
C
Humphray
Sean J
SJ
Scherer
Stephen W
SW
Lee
Charles
C
Hurles
Matthew E
ME
Carter
Nigel P
NP
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
D022041:Euchromatin; D004247:DNA