Whole-exome and whole-genome sequencing in the molecular diagnostic laboratory

Next-generation sequencing (NGS) continues to push the boundaries of genomic medicine and transform clinical genome sequencing. With the introduction of NGS assays, whole-exome sequencing (WES) and whole-genome sequencing (WGS) are paving the way to interrogate many or all genes simultaneously as well as previously inaccessible portions of the genome. WES and WGS have integrated rapidly into molecular diagnostics with their clinical deployment being supported by increased automation that is tailored to both sample processing and sequencing as well as its downstream interpretation. With these advances comes an increasing need for high-quality bioinformatics that allows for careful variant interpretation, particularly as we begin to consider the relevance of noncoding variants to clinical diagnostic evaluations. This chapter takes a broad look at the scope of WES/WGS and its important role in molecular diagnostics.