Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition GenesReportar como inadecuado

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Journal of Cardiovascular Translational Research

, Volume 9, Issue 1, pp 3–11

First Online: 17 February 2016Received: 15 October 2015Accepted: 07 January 2016DOI: 10.1007-s12265-016-9673-5

Cite this article as: Pua, C.J., Bhalshankar, J., Miao, K. et al. J. of Cardiovasc. Trans. Res. 2016 9: 3. doi:10.1007-s12265-016-9673-5


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.

KeywordsInherited cardiac conditions Targeted sequencing Whole exome sequencing Whole genome sequencing Genetics Diagnostics Editor-in-Chief Jennifer L. Hall oversaw the review of this article

Chee Jian Pua and Jaydutt Bhalshankar are co-first authors.

Electronic supplementary materialThe online version of this article doi:10.1007-s12265-016-9673-5 contains supplementary material, which is available to authorized users.

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Autor: Chee Jian Pua - Jaydutt Bhalshankar - Kui Miao - Roddy Walsh - Shibu John - Shi Qi Lim - Kingsley Chow - Rachel Buchan -


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