Genome, Exome, and Gene Panel Sequencing in a Clinical Setting

As technological progress opens up undreamt of possibilities to analyze the human genome, it is vital to be aware of some basic principles about why and when to consider genetic testing in a patient. This chapter describes different applications of next-generation sequencing (NGS) in genetic diagnostics, and illustrates the approaches with practical examples from the clinic. NGS has considerably increased the number of patients who have received a secure clinical diagnosis based on molecular genomic analyses, even if a patient presents with a very ambiguous phenotype. Methodologically, there exist four main approaches for the identification of the molecular cause of rare genetic diseases: whole-genome sequencing (WGS), whole-exome sequencing (WES), and panel sequencing, all being based on NGS, and single-gene sequencing, based on Sanger sequencing. Panel sequencing has revolutionized human genetic diagnostics, as it offers an effective and affordable opportunity to obtain fast and secure diagnosis for many so-far undiagnosed patients.