Next-Generation Sequencing for Gene Panels and Clinical Exomes

Abstract Next-generation sequencing has become deeply integrated into genetic research and clinical practice for the diagnosis of genetic disorders. Its ability to rapidly sequence large amounts of deoxyribonucleic acid (DNA) at high resolution enables the simultaneous analysis of many genes, which is especially useful for atypical or incompletely defined phenotypes or when there is genetic heterogeneity. Genome sequencing analyzes all the sequencable DNA whereas exome sequencing focuses only on the coding regions of genes. In gene panels, specific groups of genes associated with distinct pathologies are targeted. Applications in reproductive medicine include the discovery of causative genes for reproductive disorders and prenatally diagnosed structural fetal anomalies. Gene panels and exome sequencing are already being integrated into preconception, preimplantation, and prenatal genetic screening and diagnosis. This chapter reviews the current experience, benefits, and challenges associated with sequence variant interpretation; its clinical utility; genetic counseling considerations; and ethical and societal issues of fetal genome-wide sequencing.