Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes.

Autor: Pua CJ; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore., Bhalshankar J; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore., Miao K; Division of Cardiovascular & Metabolic Disorders, Duke-National University of Singapore, 169857, Singapore, Singapore., Walsh R; NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, SW3 6NP, UK.; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK., John S; NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, SW3 6NP, UK.; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK., Lim SQ; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore., Chow K; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore., Buchan R; NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, SW3 6NP, UK.; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK., Soh BY; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore., Lio PM; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore., Lim J; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore., Schafer S; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore., Lim JQ; Division of Medical Sciences, National Cancer Centre Singapore, 169610, Singapore, Singapore., Tan P; Division of Cancer and Stem Cell Biology, Duke-National University of Singapore, 169857, Singapore, Singapore.; SingHealth/Duke-NUS Precision Medicine Institute, National Heart Centre Singapore, 168752, Singapore, Singapore., Whiffin N; NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, SW3 6NP, UK.; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK., Barton PJ; NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, SW3 6NP, UK.; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK., Ware JS; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK.; MRC Clinical Sciences Centre, Imperial College London, London, W12 0NN, UK., Cook SA; National Heart Research Institute Singapore, National Heart Centre Singapore, 168752, Singapore, Singapore. stuart.cook@singhealth.com.sg.; Division of Cardiovascular & Metabolic Disorders, Duke-National University of Singapore, 169857, Singapore, Singapore. stuart.cook@singhealth.com.sg.; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, UK. stuart.cook@singhealth.com.sg.; MRC Clinical Sciences Centre, Imperial College London, London, W12 0NN, UK. stuart.cook@singhealth.com.sg.
Jazyk: angličtina
Zdroj: Journal of cardiovascular translational research [J Cardiovasc Transl Res] 2016 Feb; Vol. 9 (1), pp. 3-11. Date of Electronic Publication: 2016 Feb 17.
DOI: 10.1007/s12265-016-9673-5
Abstrakt: 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 ).
Databáze: MEDLINE
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