Researchers at the Translational Genomics Research Institute (TGen) identified 51 genetic abnormalities in people with sporadic amyotrophic lateral sclerosis (ALS).
TGen researchers identified the differences by screening DNA samples from 386 patients with sporadic ALS and 542 without. Associations of SNPs with the disease were confirmed in two independent replication populations: replication series 1, with 766 patients with the disease and 750 neurologically normal controls; and replication series 2, with 135 case patients and 275 controls.
The scientists found 10 loci that were significantly associated with the disease in all three series and 41 loci that were significant in two of the three series. The most significant SNP was found near the gene FLJ10986, which expresses a protein found in the spinal cord and cerebrospinal fluid.
The investigators also identified genes likely to play a role in cell function that controls nerve adhesion. The findings indicate these genes produce a sort of molecular glue that attaches motor neurons to muscle, according to Dietrich Stephan, Ph.D., TGen director of neurogenomics and the study’s principal investigator. It appears that in ALS the nerve is able to peel off the muscle and, when that happens repeatedly, the nerves die.
Study results were published online in the August 1 issue of the New England Journal of Medicine.