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Journal of Cardiovascular Translational Research

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Open Access 01-02-2016 | Original Article

Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes

Authors: Chee Jian Pua, Jaydutt Bhalshankar, Kui Miao, Roddy Walsh, Shibu John, Shi Qi Lim, Kingsley Chow, Rachel Buchan, Bee Yong Soh, Pei Min Lio, Jaclyn Lim, Sebastian Schafer, Jing Quan Lim, Patrick Tan, Nicola Whiffin, Paul J. Barton, James S. Ware, Stuart A. Cook

Published in: Journal of Cardiovascular Translational Research | Issue 1/2016

Abstract

Inherited cardiac conditions (ICCs) are characterised by marked genetic and allelic heterogeneity and require extensive sequencing for genetic characterisation. We iteratively optimised a targeted gene capture panel for ICCs that includes disease-causing, putatively pathogenic, research and phenocopy genes (n = 174 genes). We achieved high coverage of the target region on both MiSeq (>99.8 % at ≥20× read depth, n = 12) and NextSeq (>99.9 % at ≥20×, n = 48) platforms with 100 % sensitivity and precision for single nucleotide variants and indels across the protein-coding target on the MiSeq. In the final assay, 40 out of 43 established ICC genes informative in clinical practice achieved complete coverage (100 % at ≥20×). By comparison, whole exome sequencing (WES; ∼80×), deep WES (∼500×) and whole genome sequencing (WGS; ∼70×) had poorer performance (88.1, 99.2 and 99.3 % respectively at ≥20×) across the ICC target. The assay described here delivers highly accurate and affordable sequencing of ICC genes, complemented by accessible cloud-based computation and informatics. See Editorial in this issue (DOI: 10.1007/s12265-015-9667-8).

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Title: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes
Authors: Chee Jian Pua
Jaydutt Bhalshankar
Kui Miao
Roddy Walsh
Shibu John
Shi Qi Lim
Kingsley Chow
Rachel Buchan
Bee Yong Soh
Pei Min Lio
Jaclyn Lim
Sebastian Schafer
Jing Quan Lim
Patrick Tan
Nicola Whiffin
Paul J. Barton
James S. Ware
Stuart A. Cook
Publication date: 01-02-2016
Publisher: Springer US
Published in: Journal of Cardiovascular Translational Research / Issue 1/2016
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-016-9673-5

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