Taylor et al. consider the utility of whole-genome sequencing for diagnosis of genetic disorders in routine clinical practice as part of the WGS500 project to sequence the whole genomes of 500 patients. The authors examine whole-genome sequencing data from 217 individuals (including 156 independent cases or families) with a range of genetic disorders for which previous genetic screening had not identified any pathogenic variants. They demonstrate that whole-genome sequencing now allows the identification of at least one variant with a high level of evidence of pathogenicity in 21% of cases (33/156), with higher rates seen for Mendelian disorders (34%; 23/68) or family trios (57%; 8/14). The authors consider analysis strategies that improve the accuracy of variant calling and detection rates, and they review challenges in sequence interpretation and in establishing the pathogenicity of variants.
References
Taylor, J. C. et al. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nat. Genet. http://dx.doi.org/10.1038/ng.3304 (2015)
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Bahcall, O. Clinical whole-genome sequencing. Nat Rev Genet 16, 377 (2015). https://doi.org/10.1038/nrg3973
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DOI: https://doi.org/10.1038/nrg3973