High throughput exome coverage of clinically relevant cardiac genes

• DOI: 10.1186/s12920-014-0067-8
• Publication Date: 2014-12-10T15:59:44Z
• Authors: Dorin Manase; Lisa CA D’Alessandro; Ashok Kumar Manic...; Saeed Al Turki; Matthew E Hurles; Seema Mital
• Keywords: Exome; Human genetics; Ensembl; Candidate gene; Medical genetics

Given the growing use of whole-exome sequencing (WES) for clinical diagnostics complex human disorders, we evaluated coverage clinically relevant cardiac genes on WES and factors influencing uniformity depth exonic regions.Two hundred thirteen DNA samples were exome sequenced via Illumina HiSeq using different versions Agilent SureSelect capture kit. 50 further analyzed including 31 from American College Medical Genetics (ACMG) list reporting incidental findings 19 associated with congenital heart disease which testing is available. Gene coordinates obtained two databases, CCDS Known compared. Read each region was extracted exomes used to assess variability between kits individual genes, overall coverage. GC content, gene size, inter-sample also tested as potential contributors in coverage.All (designed based Consensus coding sequence) included only 55% known genomic regions genes. Although newer kit showed improvement 99%, 64% captured even kits. There considerable 10 6 ACMG had less than optimal 30X. Within gene, 32 majority their bases covered at an interquartile range ≥30X. Heterogeneity modestly size significantly content.Despite across higher depths, 50% are targeted non-uniform. This may contribute a bias greater attribution causation mutations well-represented well-covered Improvements technology needed before widespread application.