Amyotrophic lateral sclerosis: an emerging era of collaborative gene discovery.
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS.
Gwinn
Katrina
K
National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America. GwinnK@ninds.nih.gov
Corriveau
Roderick A
RA
Mitsumoto
Hiroshi
H
Bednarz
Kate
K
Brown
Robert H
RH
Cudkowicz
Merit
M
Gordon
Paul H
PH
Hardy
John
J
Kasarskis
Edward J
EJ
Kaufmann
Petra
P
Miller
Robert
R
Sorenson
Eric
E
Tandan
Rup
R
Traynor
Bryan J
BJ
Nash
Josefina
J
Sherman
Alex
A
Mailman
Matthew D
MD
Ostell
James
J
Bruijn
Lucie
L
Cwik
Valerie
V
Rich
Stephen S
SS
Singleton
Andrew
A
Refolo
Larry
L
Andrews
Jaime
J
Zhang
Ran
R
Conwit
Robin
R
Keller
Margaret A
MA
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D016472:Motor Neuron Disease / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide