Application of next generation sequencing to molecular diagnosis of inherited diseases

Abstract

Recent development of high throughput, massively parallel sequencing (MPS or next generation sequencing, NGS) technology has revolutionized the molecular diagnosis of human genetic disease. The ability to generate enormous amount of sequence data in a short time at an affordable cost makes this approach ideal for a wide range of applications from sequencing a group of candidate genes, all coding regions (known as exome sequencing) to the entire human genome. The technology brings about an unprecedented application to the identification of the molecular basis of hard-to-diagnose genetic disorders. This chapter reviews the up-to-date published application of next generation sequencing in clinical molecular diagnostic laboratories. We also emphasize the various target gene enrichment methods and their advantages and shortcomings. Obstacles to compliance with regulatory authorities like CLIA/CAP in clinical settings are also briefly discussed.