Journal
HUMAN MUTATION
Volume 34, Issue 10, Pages 1439-1448Publisher
WILEY
DOI: 10.1002/humu.22387
Keywords
copy number variation; whole exome sequencing; clinical
Categories
Funding
- European Union TECHGENE Project [Health-F5-2009-223143]
- GEUVADIS Project [Health-F7-2010-261123]
- European Research Council [DENOVO 281964]
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Copy number variation (CNV) is a common source of genetic variation that has been implicated in many genomic disorders. This has resulted in the widespread application of genomic microarrays as a first-tier diagnostic tool for CNV detection. More recently, whole-exome sequencing (WES) has been proven successful for the detection of clinically relevant point mutations and small insertion-deletions exome wide. We evaluate the utility of short-read WES (SOLiD 5500xl) to detect clinically relevant CNVs in DNA from 10 patients with intellectual disability and compare these results to data from two independent high-resolution microarrays. Eleven of the 12 clinically relevant CNVs were detected via read-depth analysis of WES data; a heterozygous single-exon deletion remained undetected by all algorithms evaluated. Although the detection power of WES for small CNVs currently does not match that of high-resolution microarray platforms, we show that the majority (88%) of rare coding CNVs containing three or more exons are successfully identified by WES. These results show that the CNV detection resolution of WES is comparable to that of medium-resolution genomic microarrays commonly used as clinical assays. The combined detection of point mutations, indels, and CNVs makes WES a very attractive first-tier diagnostic test for genetically heterogeneous disorders. (C) 2013 Wiley Periodicals, Inc.
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