Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes.
J Cardiovasc Transl Res
; 9(1): 3-11, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26888179
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; â¼ 80×), deep WES (â¼ 500×) and whole genome sequencing (WGS; â¼ 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 ).
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Análise Mutacional de DNA
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Polimorfismo de Nucleotídeo Único
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Sequenciamento de Nucleotídeos em Larga Escala
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Cardiopatias
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Mutação
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Limite:
Humans
País/Região como assunto:
Asia
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Europa
Idioma:
En
Revista:
J Cardiovasc Transl Res
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Singapura