Tuesday, August 13, 2013

Fwd: Detection of clinically relevant copy number variants with whole exome sequencing

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Detection of clinically relevant copy number variants with whole exome sequencing: "

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 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.

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(Via human mutation.)