Accurate and reliable high-throughput detection of copy number variation in the human genome

Heike Fiegler, Richard Redon, Dan Andrews, Carol Scott, Robert Andrews, Carol Carder, Richard Clark, Oliver Dovey, Peter Ellis, Lars Feuk, Lisa French, Paul Hunt, Dimitrios Kalaitzopoulos, James Larkin, Lyndal Montgomery, George H. Perry, Bob W. Plumb, Keith Porter, Rachel E. Rigby, Diane RiglerArmand Valsesia, Cordelia Langford, Sean J. Humphray, Stephen W. Scherer, Charles Lee, Matthew E. Hurles, Nigel P. Carter

Research output: Contribution to journalArticle

115 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1566-1574
Number of pages9
JournalGenome research
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2006

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Human Genome
Clone Cells
Oligonucleotide Array Sequence Analysis
Chromosomes
Population

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Fiegler, H., Redon, R., Andrews, D., Scott, C., Andrews, R., Carder, C., ... Carter, N. P. (2006). Accurate and reliable high-throughput detection of copy number variation in the human genome. Genome research, 16(12), 1566-1574. https://doi.org/10.1101/gr.5630906
Fiegler, Heike ; Redon, Richard ; Andrews, Dan ; Scott, Carol ; Andrews, Robert ; Carder, Carol ; Clark, Richard ; Dovey, Oliver ; Ellis, Peter ; Feuk, Lars ; French, Lisa ; Hunt, Paul ; Kalaitzopoulos, Dimitrios ; Larkin, James ; Montgomery, Lyndal ; Perry, George H. ; Plumb, Bob W. ; Porter, Keith ; Rigby, Rachel E. ; Rigler, Diane ; Valsesia, Armand ; Langford, Cordelia ; Humphray, Sean J. ; Scherer, Stephen W. ; Lee, Charles ; Hurles, Matthew E. ; Carter, Nigel P. / Accurate and reliable high-throughput detection of copy number variation in the human genome. In: Genome research. 2006 ; Vol. 16, No. 12. pp. 1566-1574.
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Fiegler, H, Redon, R, Andrews, D, Scott, C, Andrews, R, Carder, C, Clark, R, Dovey, O, Ellis, P, Feuk, L, French, L, Hunt, P, Kalaitzopoulos, D, Larkin, J, Montgomery, L, Perry, GH, Plumb, BW, Porter, K, Rigby, RE, Rigler, D, Valsesia, A, Langford, C, Humphray, SJ, Scherer, SW, Lee, C, Hurles, ME & Carter, NP 2006, 'Accurate and reliable high-throughput detection of copy number variation in the human genome', Genome research, vol. 16, no. 12, pp. 1566-1574. https://doi.org/10.1101/gr.5630906

Accurate and reliable high-throughput detection of copy number variation in the human genome. / Fiegler, Heike; Redon, Richard; Andrews, Dan; Scott, Carol; Andrews, Robert; Carder, Carol; Clark, Richard; Dovey, Oliver; Ellis, Peter; Feuk, Lars; French, Lisa; Hunt, Paul; Kalaitzopoulos, Dimitrios; Larkin, James; Montgomery, Lyndal; Perry, George H.; Plumb, Bob W.; Porter, Keith; Rigby, Rachel E.; Rigler, Diane; Valsesia, Armand; Langford, Cordelia; Humphray, Sean J.; Scherer, Stephen W.; Lee, Charles; Hurles, Matthew E.; Carter, Nigel P.

In: Genome research, Vol. 16, No. 12, 01.12.2006, p. 1566-1574.

Research output: Contribution to journalArticle

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AU - Fiegler, Heike

AU - Redon, Richard

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AU - Andrews, Robert

AU - Carder, Carol

AU - Clark, Richard

AU - Dovey, Oliver

AU - Ellis, Peter

AU - Feuk, Lars

AU - French, Lisa

AU - Hunt, Paul

AU - Kalaitzopoulos, Dimitrios

AU - Larkin, James

AU - Montgomery, Lyndal

AU - Perry, George H.

AU - Plumb, Bob W.

AU - Porter, Keith

AU - Rigby, Rachel E.

AU - Rigler, Diane

AU - Valsesia, Armand

AU - Langford, Cordelia

AU - Humphray, Sean J.

AU - Scherer, Stephen W.

AU - Lee, Charles

AU - Hurles, Matthew E.

AU - Carter, Nigel P.

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N2 - 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.

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Fiegler H, Redon R, Andrews D, Scott C, Andrews R, Carder C et al. Accurate and reliable high-throughput detection of copy number variation in the human genome. Genome research. 2006 Dec 1;16(12):1566-1574. https://doi.org/10.1101/gr.5630906