It wouldn’t be the Symposium without a new gene discovery.
Although technology has allowed incredible advances in the gene-hunting field, this is countered by the fact that as more and more familial amyotrophic lateral sclerosis (FALS) genes are found, it makes the search for the remaining unknown genes harder This is in part due to the fact that the undiscovered genes are likely to be increasingly rare (so even more rigorous detective work is needed) but the challenge is compounded by the fact that there are fewer and fewer samples with an unknown cause available each time a new gene is found.
Dr Brad Smith (King’s College London) unveiled the latest collaborative effort, involving over 50 researchers across 9 countries. The researchers took an approach called Exome Sequencing, which analyses the 1% of the genetic code where most mutations are likely to be found, to look for genes in several hundred FALS cases where the genetic cause was still unknown. They then compared their findings with those from 60,000 individuals in publicly available databases.
After this major piece of number crunching they were left with a long list of possible FALS genes, which is forming the basis of further follow-up studies. Dr Smith was reporting on one of these, which appears to account for 1-2% of FALS. Variants of the gene also appeared in a similar proportion of sporadic ALS, suggesting that in some cases it may act more as a risk factor rather than a single driver of disease. This is substantiated by the fact that it is associated with a relatively late onset ALS.
It is still not clear how the mutated protein causes motor neuron damage, but Dr Smith showed preliminary studies in cell cultures that indicated that the mutants appear to be involved in two processes linked to motor neuron degeneration in ALS.
To paraphrase a quote associated with Cape Canaveral, just east of this meeting, ‘another small step’ has been made. Hopefully it will help lead the scientific community closer to making that ‘giant leap’.