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

116 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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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, G. H., Plumb, B. W., Porter, K., Rigby, R. E., ... 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