TY - JOUR
T1 - State of play in amyotrophic lateral sclerosis genetics
AU - Renton, Alan E.
AU - Chiò, Adriano
AU - Traynor, Bryan J.
N1 - Funding Information:
This work was supported in part by the Intramural Research Programs of the US National Institutes of Health, National Institute on Aging (Z01-AG000949-02) and National Institute of Neurological Disorders and Stroke. The work was also supported by the Packard Center for ALS Research at Hopkins (B.J.T.), the ALS Association (B.J.T., A.C.), Microsoft Research (B.J.T.), AriSLA (B.J.T., A.C.), the Italian Health Ministry (Ricerca Sanitaria Finalizzata 2007 to A.C.), Fondazione Vialli e Mauro ONLUS (A.C.), Federazione Italiana Giuoco Calcio (A.C., B.J.T.), Compagnia di San Paolo (A.C.) and the European Community’s Health Seventh Framework Programme under grant agreement 259867 (A.C.).
Funding Information:
By their very nature, GWAS of outbred populations require several thousand case and control samples to have sufficient power to identify risk loci. The Coriell ALS DNA Repository (http://www.coriell.org/), funded by the ALS Association, the Muscular Dystrophy Association and the National Institute of Neurological Disorders and Stroke, distributes well-phenotyped biological samples from ~2,000 case and ~6,000 population control subjects84. The availability of this resource has invigorated the field by lowering the barriers for laboratories to engaging in genetic research.
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84893649256
U2 - 10.1038/nn.3584
DO - 10.1038/nn.3584
M3 - Review article
AN - SCOPUS:84893649256
SN - 1097-6256
VL - 17
SP - 17
EP - 23
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 1
ER -