DNA Sequencing Resolves Misdiagnosed and Rare Genetic Disorders

Abstract

This chapter focuses on the mandatory requirement of DNA sequencing approaches for genetic diagnosis and recurrence prevention of inherited diseases. Sequencing the DNA and coded transcripts has intensely promoted our understanding of functional genomics and the fundamental importance of non-coding genomic sequences in causing heritable diseases, when mutated. Though Sanger sequencing, the first employed approach in identifying genetic mutations has been replaced nowa-days in many laboratories with the highly robust massive parallel sequencing tech-niques, “Sanger” remains vital in countries with limited resources and also of essential importance in validating the results of large scale sequencing technologies. Next generation sequencing (NGS) enabled the parallel sequencing of the whole exome (WES) and whole genome (WGS) regions of human genome and has revolutionized the field of genetic and genomic research in human. WES and WGS have facilitated the identification of the role of previously unrecognized genes in causing neurologic phenotypes, brain structural malformation, and resolved the causal genes in puzzling and misdiagnosed genetic phenotypes. Role of fusion genes and non-coding RNA in causing neurogenetic recessive diseases has been uncovered by the application of NGS platforms, published examples are presented in this chapter. Extensive phenotypic variability that retained patients either as misdiagnosed or undiagnosed cases for years has been correctly diagnosed through NGS research applications.