Journal Article

State of play in amyotrophic lateral sclerosis genetics

Chiò, Adriano, Renton, Alan E, Traynor, Bryan J

2014

Overview

In this review, the authors examine how the identification and analysis of genes associated with ALS have begun to provide insight into the onset and pathology of this motor disease. In addition, they discuss some emerging themes that are poised to inform future efforts to identify further gene targets. Considerable progress has been made in unraveling the genetic etiology of amyotrophic lateral sclerosis (ALS), the most common form of adult-onset motor neuron disease and the third most common neurodegenerative disease overall. Here we review genes implicated in the pathogenesis of motor neuron degeneration and how this new information is changing the way we think about this fatal disorder. Specifically, we summarize current literature of the major genes underlying ALS, SOD1 , TARDBP , FUS , OPTN , VCP , UBQLN2 , C9ORF72 and PFN1 , and evaluate the information being gleaned from genome-wide association studies. We also outline emerging themes in ALS research, such as next-generation sequencing approaches to identify de novo mutations, the genetic convergence of familial and sporadic ALS, the proposed oligogenic basis for the disease, and how each new genetic discovery is broadening the phenotype associated with the clinical entity we know as ALS.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 45 / 45/23 / 45/43 / 692/699/375/1917 / Adaptor Proteins, Signal Transducing / Amyotrophic lateral sclerosis / Amyotrophic Lateral Sclerosis - genetics / Analysis / Animal Genetics and Genomics / Autophagy-Related Proteins / Behavioral Sciences / Biological Techniques / Biomedicine / C9orf72 Protein / Care and treatment / Cell Cycle Proteins - genetics / Disease / DNA sequencing / DNA-Binding Proteins - genetics / Etiology / Gene therapy / Genes / Genetic aspects / Genetic Predisposition to Disease / Genetic research / Genetics / Genome-Wide Association Study / Genomes / Health aspects / Humans / Membrane Transport Proteins / Mutation / Mutation - genetics / Neurobiology / Neurosciences / Nucleotide sequencing / Pathogenesis / Pathology / Profilins - genetics / Proteins / Respiratory failure / review-article / RNA-Binding Protein FUS - genetics / Superoxide Dismutase - genetics / Superoxide Dismutase-1 / Transcription Factor TFIIIA - genetics / Ubiquitins - genetics