APA
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Walsh, R., Thomson, K., Ware, J., Funke, B., Woodley, J., McGuire, K., … Watkins, H. (2016). Reassessment Of Mendelian Gene Pathogenicity Using 7,855 Cardiomyopathy Cases And 60,706 Reference Samples. Genetics in Medicine.
Chicago/Turabian
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Walsh, R., K. Thomson, J. Ware, B. Funke, Jessica Woodley, K. McGuire, F. Mazzarotto, et al. “Reassessment Of Mendelian Gene Pathogenicity Using 7,855 Cardiomyopathy Cases And 60,706 Reference Samples.” Genetics in Medicine (2016).
MLA
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Walsh, R., et al. “Reassessment Of Mendelian Gene Pathogenicity Using 7,855 Cardiomyopathy Cases And 60,706 Reference Samples.” Genetics in Medicine, 2016.
BibTeX Click to copy
@article{r2016a,
title = {Reassessment Of Mendelian Gene Pathogenicity Using 7,855 Cardiomyopathy Cases And 60,706 Reference Samples},
year = {2016},
journal = {Genetics in Medicine},
author = {Walsh, R. and Thomson, K. and Ware, J. and Funke, B. and Woodley, Jessica and McGuire, K. and Mazzarotto, F. and Blair, E. and Seller, A. and Taylor, Jenny C. and Minikel, E. and MacArthur, D. and Farrall, M. and Cook, S. and Watkins, H.}
}
Purpose:The accurate interpretation of variation in Mendelian disease genes has lagged behind data generation as sequencing has become increasingly accessible. Ongoing large sequencing efforts present huge interpretive challenges, but they also provide an invaluable opportunity to characterize the spectrum and importance of rare variation.Methods:We analyzed sequence data from 7,855 clinical cardiomyopathy cases and 60,706 Exome Aggregation Consortium (ExAC) reference samples to obtain a better understanding of genetic variation in a representative autosomal dominant disorder.Results:We found that in some genes previously reported as important causes of a given cardiomyopathy, rare variation is not clinically informative because there is an unacceptably high likelihood of false-positive interpretation. By contrast, in other genes, we find that diagnostic laboratories may be overly conservative when assessing variant pathogenicity.Conclusions:We outline improved analytical approaches that evaluate which genes and variant classes are interpretable and propose that these will increase the clinical utility of testing across a range of Mendelian diseases.Genet Med 19 2, 192–203.