February 26, 2008

Axon Guidance Genes Implicated in ALS

Investigators at the Mayo Clinic in Rochester, Minn., and the University of Miami have applied a new approach to studying genetic variants that may play a role in ALS and say genes involved in “axon guidance” are significantly different in people with ALS.

Axon guidance refers to the process by which the brain and spinal cord are “wired” during fetal development and the process by which brain wiring is maintained and repaired throughout life.

Two previous analyses, called “whole-genome association” studies, compared all the DNA of a group of people with ALS to all the DNA of a group of people without ALS. The first study, which was MDA-supported and conducted by the Translational Genomics Research Institute in Phoenix, found some 50 variants that might contribute to ALS, including one that was particularly significant. (The function of the gene in which this variant was found has not yet been identified.)

The second study, conducted by the National Institutes of Health, found no significant DNA differences between the ALS-affected and unaffected groups.

In this new analysis, Demetrius Maraganore at the Mayo Clinic and colleagues, who published their findings in the January issue of PLoS One, hypothesized that genes involved in axon guidance might have ALS-associated variant DNA sequences.

When they looked at 128 genes already identified as being in the axon-guidance pathway and compared them as a group in the ALS-affected and unaffected study participants, they found a significant difference in the two types of participants.

MDA is talking with the Mayo Clinic group about pursuing this line of research.