What we have learned from the next-generation sequencing: Contributions to the genetic diagnoses and understanding of pathomechanisms of neurodegenerative diseases

Abstract

Since its first availability in 2009, the next-generation sequencing (NGS) has been proved to be a powerful tool in identifying disease-associated variants in many neurological diseases, such as spinocerebellar ataxias, Charcot-Marie-Tooth disease, hereditary spastic paraplegia, and amyotrophic lateral sclerosis. Whole exome sequencing and whole genome sequencing are efficient for identifying variants in novel or unexpected genes responsible for inherited diseases, whereas targeted sequencing is useful in detecting variants in previously known disease-associated genes. The trove of genetic data yielded by NGS has made a significant impact on the clinical diagnoses while contributing hugely on the discovery of molecular pathomechanisms underlying these diseases. Nonetheless, elucidation of the pathogenic roles of the variants identified by NGS is challenging. Establishment of consensus guidelines and development of public genomic/phenotypic databases are thus vital to facilitate data sharing and validation.

Keywords: Neurodegenerative diseases; neurogenetics; next generation sequencing; targeted sequencing; whole exome sequencing.