Barton, PJ

Bhalshankar, J

Buchan, R

Chow, K

Cook, SA

John, S

Lim, J

Lim, JQ

Lim, SQ

Lio, PM

Miao, K

Pua, CJ

Schafer, S

Soh, BY

Tan, P

Walsh, R

Ware, JS

Whiffin, N

Journal of Cardiovascular Translational Research

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

Spiral - Imperial College Digital Repository

Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes

Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes

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Spiral - Imperial College Digital Repository