Next generation diagnostics in inherited arrhythmia syndromes

Ware, James S., John, Shibu, Roberts, Angharad M., Buchan, Rachel, Gong, Sungsam, Peters, Nicholas S., Robinson, David O., Lucassen, Anneke, Behr, Elijah R. and Cook, Stuart A. (2012) Next generation diagnostics in inherited arrhythmia syndromes Journal of Cardiovascular Translational Research, 6, (1), pp. 94-103. (doi:10.1007/s12265-012-9401-8). (PMID:22956155).


Full text not available from this repository.


Next-generation sequencing (NGS) provides an unprecedented opportunity to assess genetic variation underlying human disease. Here, we compared two NGS approaches for diagnostic sequencing in inherited arrhythmia syndromes. We compared PCR-based target enrichment and long-read sequencing (PCR-LR) with in-solution hybridization-based enrichment and short-read sequencing (Hyb-SR). The PCR-LR assay comprehensively assessed five long-QT genes routinely sequenced in diagnostic laboratories and "hot spots" in RYR2. The Hyb-SR assay targeted 49 genes, including those in the PCR-LR assay. The sensitivity for detection of control variants did not differ between approaches. In both assays, the major limitation was upstream target capture, particular in regions of extreme GC content. These initial experiences with NGS cardiovascular diagnostics achieved up to 89 % sensitivity at a fraction of current costs. In the next iteration of these assays we anticipate sensitivity above 97 % for all LQT genes. NGS assays will soon replace conventional sequencing for LQT diagnostics and molecular pathology

Item Type: Article
Digital Object Identifier (DOI): doi:10.1007/s12265-012-9401-8
ISSNs: 1937-5387 (print)
Organisations: Cancer Sciences, Human Development & Health
ePrint ID: 342782
Date :
Date Event
7 September 2012Accepted/In Press
February 2013Published
Date Deposited: 13 Sep 2012 11:47
Last Modified: 17 Apr 2017 16:38
Further Information:Google Scholar

Actions (login required)

View Item View Item