title: Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges.
abstract: 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.
authors.affiliation: Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA; Institute of Medical Genetics, Catholic University, Roma, Italy. Electronic address: giuseppe.marangi@rm.unicatt.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marangi
authors.affiliation: Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005821:Genetic Techniques; D006801:Humans; D009154:Mutation
keywords: Amyotrophic lateral sclerosis; GWAS; Gene discovery; Genetic heterogeneity; NGS; Somatic mosaicism