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DNA Research Advance Access published online on March 15, 2007
DNA Research, doi:10.1093/dnares/dsm002
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© The Author 2007. Kazusa DNA Research Institute
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Genome-wide Copy Number Profiling on High-density Bacterial Artificial Chromosomes, Single-nucleotide Polymorphisms, and Oligonucleotide Microarrays: A Platform Comparison based on Statistical Power Analysis

Jayne Y. Hehir-Kwa, Michael Egmont-Petersen, Irene M. Janssen, Dominique Smeets, Ad Geurts van Kessel and Joris A. Veltman*

Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Received 25 September 2006 ; revised 16 January 2007

Recently, comparative genomic hybridization onto bacterial artificial chromosome (BAC) arrays (array-based comparative genomic hybridization) has proved to be successful for the detection of submicroscopic DNA copy-number variations in health and disease. Technological improvements to achieve a higher resolution have resulted in the generation of additional microarray platforms encompassing larger numbers of shorter DNA targets (oligonucleotides). Here, we present a novel method to estimate the ability of a microarray to detect genomic copy-number variations of different sizes and types (i.e. deletions or duplications). We applied our method, which is based on statistical power analysis, to four widely used high-density genomic microarray platforms. By doing so, we found that the high-density oligonucleotide platforms are superior to the BAC platform for the genome-wide detection of copy-number variations smaller than 1 Mb. The capacity to reliably detect single copy-number variations below 100 kb, however, appeared to be limited for all platforms tested. In addition, our analysis revealed an unexpected platform-dependent difference in sensitivity to detect a single copy-number loss and a single copy-number gain. These analyses provide a first objective insight into the true capacities and limitations of different genomic microarrays to detect and define DNA copy-number variations.

Key words: array CGH; molecular cytogenetics; microdeletion; copy-number variation; power analysis

* To whom correspondence should be addressed. Tel. +31-24-3614941. Fax. +31-24-3668752, E-mail: j.veltman{at}antrg.umcn.nl

Communicated by Toshihiko Shiroishi


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