Genomic Applications in Inherited Genetic Disorders

Next-generation sequencing (NGS) technology is revolutionizing clinical diagnostics for inherited disorders. The paradigm shift driven by NGS is rooted in its fundamental advances over Sanger sequencing, primarily its ultrahigh throughput and significantly lower cost per base of sequence. These enhanced capabilities have enabled clinical laboratories to go from testing single genes to simultaneously sequencing tens, hundreds, and thousands of genes, even the whole human genome. This dramatic leap in capabilities has come with dramatic success stories, but is also accompanied by numerous new challenges that will face the field for years to come. While clinical application of NGS is still a nascent field, it has been quickly adopted by academic and commercial laboratories which are expanding the applications of this technology at a rapid pace. Indeed, it is clear that NGS based genetic tests are applicable to inherited disorders in all stages of life, from preconception screening to diagnosis of fetal, infant, young child, and adult onset disorders. This chapter presents a brief description of NGS panels, exome and whole-genome tests for germ-line variations and discusses their current clinical applications.