Interpreting Reports of a 'Genomic Pathway' to Predict Parkinson's
On June 15, Mayo Clinic researchers published a paper in the journal PLoS Genetics reporting that genetic changes within a group of genes that control how brain cells reach out and connect with other brain cells had been linked to as much as a 90-fold increase in the risk of Parkinson's disease for some people. The new paper builds on results of earlier work funded by The Michael J. Fox Foundation.
To gain a clearer understanding of the new findings and their implications both for people living with Parkinson's disease today, and for future research into the genetics behind the disease, the Foundation spoke with SAB members Mark Cookson, PhD, and Andy Singleton, PhD, both of the National Institute on Aging. Also participating was Brian Fiske, PhD, MJFF's associate director of research programs.
Q: What led the researchers to do this work?
Brian Fiske: Let me provide a little background information. A couple of years ago, the Foundation partnered with Mayo Clinic and Perlegen Sciences to perform a scan of the entire human genome for genetic variations, or SNPs (small nucleotide polymorphisms; single-letter changes in the DNA code) that may be associated with Parkinson's disease risk. The results of that study, as well as a second genome-wide study completed by investigators at the National Institutes of Health (including our own Dr. Andy Singleton), did not find any single genetic variation that could explain a large number of the Parkinson's cases in those populations. But although no single genetic changes were found to have much of an impact, the investigators wondered whether many genetic changes in concert might play a bigger role.
Q: So the investigators decided to look for effects of multiple genetic changes together, instead of single changes alone?
Brian Fiske: Yes. Although the whole genome scans didn't find any major single smoking genetic guns, they did find a number of SNPs with smaller, weaker associations to Parkinson's disease that might increase risk only slightly. One of these was a SNP within a gene involved in axon guidance call Sema5a. Axons are the long ‘wires' that brain cells send out to make connections with other brain cells. Genes like Sema5a code for proteins that help guide these axons to the appropriate target cells. Sort of like road signs on the highway telling you to take the next exit.