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On the frequency of copy number variants

Authors :
Iuliana Ionita-Laza
Nan M. Laird
Benjamin A. Raby
Scott T. Weiss
Christoph Lange
Source :
Bioinformatics. 24:2350-2355
Publication Year :
2008
Publisher :
Oxford University Press (OUP), 2008.

Abstract

Motivation: Estimating the frequency distribution of copy number variants (CNVs) is an important aspect of the effort to characterize this new type of genetic variation. Currently, most studies report a strong skew toward low-frequency CNVs. In this article, our goal is to investigate the frequencies of CNVs. We employ a two-step procedure for the CNV frequency estimation process. We use family information a posteriori to select only the most reliable CNV regions, i.e. those showing high rates of Mendelian transmission. Results: Our results suggest that the current skew toward low-frequency CNVs may not be representative of the true frequency distribution, but may be due, among other reasons, to the non-negligible false negative rates that characterize CNV detection methods. Moreover, false positives are also likely, as low-frequency CNVs are hard to detect with small sample sizes and technologies that are not ideally suited for their detection. Without appropriate validation methods, such as incorporation of biologically relevant information (for example, in our case, the transmission of heritable CNVs from parents to offspring), it is difficult to assess the validity of specific CNVs, and even harder to obtain reliable frequency estimates. Availability: Software implementing the methods described in this article is available for download at the following address: http://www.isites.harvard.edu/icb/icb.do?keyword=k36162 Contact: iionita@hsph.harvard.edu Supplementary informantion: Supplementary data are available at Bioinformatics online.

Details

ISSN :
13674811 and 13674803
Volume :
24
Database :
OpenAIRE
Journal :
Bioinformatics
Accession number :
edsair.doi.dedup.....7bd322148dd88d8f9e0a4b9983aa7694
Full Text :
https://doi.org/10.1093/bioinformatics/btn421