An international research team, which took part in Project MinE's global gene sequencing effort, and which was funded by The ALS Association through ALS Ice Bucket Challenge donations, says they have identified a new ALS gene, NEK1, which now ranks among the most common genes that contribute to the disease. Their study (“Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis research”), published in Nature Genetics, will provide scientists with another potential target for therapy development.
This was the largest-ever study of familial (inherited) ALS, involved contributions from over 80 researchers in 11 countries, and was led by John Landers, Ph.D., of University of Massachusetts Medical School and Jan Veldink, Ph.D., of University Medical Center Utrecht.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which leads to total paralysis and death, usually within two to five years of diagnosis. While 10% of ALS is familial, meaning it's genetic, the other 90% of ALS cases are considered sporadic, or without a family history. However, it's very likely that genetics contribute, directly or indirectly, to a much larger percentage of ALS cases.
“The discovery of NEK1 highlights the value of 'big data' in ALS research,” said Lucie Bruijn, Ph.D., chief scientist for the ALS Association. “The sophisticated gene analysis that led to this finding was only possible because of the large number of ALS samples available. The ALS Ice Bucket Challenge enabled The ALS Association to invest in Project MinE's work to create large biorepositories of ALS biosamples that are designed to allow exactly this kind of research and to produce exactly this kind of result.”
NEK1 was discovered through a genome-wide search for ALS risk genes in over 1,000 ALS families, and was independently found through different means in an isolated population in The Netherlands. Further analysis in over 13,000 sporadic ALS individuals compared to controls again revealed an overrepresentation of variants in the same gene. The variations discovered in the gene sequence are predicted to lead to gene loss of function.
NEK1 is known to have multiple roles in neurons, including maintenance of the cytoskeleton that gives the neuron its shape and promotes transport within the neuron. In addition, NEK1 has roles in regulating the membrane of the mitochondrion, which supplies energy to neurons and in repairing DNA. Disruption of each of these cellular functions through other means has been linked to increased risk of ALS.