Advances in sequencing technologies for amyotrophic lateral sclerosis research

Amyotrophic lateral sclerosis (ALS) is caused by upper and lower motor neuron loss and has a fairly rapid disease progression, leading to fatality in an average of 2-5 years after symptom onset. Numerous genes have been implicated in this disease; however, many cases remain unexplained. Several technologies are being used to identify regions of interest and investigate candidate genes. Initial approaches to detect ALS genes include, among others, linkage analysis, Sanger sequencing, and genome-wide association studies. More recently, next-generation sequencing methods, such as whole-exome and whole-genome sequencing, have been introduced. While those methods have been particularly useful in discovering new ALS-linked genes, methodological advances are becoming increasingly important, especially given the complex genetics of ALS. Novel sequencing technologies, like long-read sequencing, are beginning to be used to uncover the contribution of repeat expansions and other types of structural variation, which may help explain missing heritability in ALS. In this review, we discuss how popular and/or upcoming methods are being used to discover ALS genes, highlighting emerging long-read sequencing platforms and their role in aiding our understanding of this challenging disease.

Automated summary

ALS is a progressive and fatal disease caused by motor neuron loss. Despite the discovery of numerous ALS-linked genes, there are still cases that cannot be explained. Various technologies have been used to identify regions of interest and investigate candidate genes, including traditional methods like linkage analysis and Sanger sequencing, as well as more recent methods like whole-exome and whole-genome sequencing. The complex genetics of ALS have led to the development of novel sequencing technologies, such as long-read sequencing, which can uncover the contribution of repeat expansions and other types of structural variation. These advancements are crucial for our understanding of ALS and the discovery of new genes associated with the disease.