Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges

Brain Res. 2015 May 14;1607:75-93. doi: 10.1016/j.brainres.2014.10.009. Epub 2014 Oct 12.


The genetic architecture of amyotrophic lateral sclerosis (ALS) is being increasingly understood. In this far-reaching review, we examine what is currently known about ALS genetics and how these genes were initially identified. We also discuss the various types of mutations that might underlie this fatal neurodegenerative condition and outline some of the strategies that might be useful in untangling them. These include expansions of short repeat sequences, common and low-frequency genetic variations, de novo mutations, epigenetic changes, somatic mutations, epistasis, oligogenic and polygenic hypotheses. This article is part of a Special Issue entitled ALS complex pathogenesis.

Keywords: Amyotrophic lateral sclerosis; GWAS; Gene discovery; Genetic heterogeneity; NGS; Somatic mosaicism.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Genetic Predisposition to Disease
  • Genetic Techniques
  • Humans
  • Mutation