Study Rationale:
Mutations in the GBA gene are the most common genetic cause of Parkinson’s disease. This gene has a nearby pseudogene, which is a genetic material that is very similar to the original gene but does not encode a protein. Because of the presence of the pseudogene, it is often difficult to identify mutations in the gene using traditional mutation detection techniques. Furthermore, specific mutations that occur as a result of a recombination between the gene and the pseudogene are often missed by the traditional genetic methods.
Hypothesis:
By using a novel technology called “targeted locus amplification” (TLA) we hypothesize that we will be able to better discriminate between the gene and its pseudogene, and to identify specific recombinations between GBA and its pseudogene.
Study Design:
First, we will design the TLA methods to match the target gene, GBA, and its pseudogene, and examine if it works using random DNA samples. Then, we will examine if the method works by using DNA samples from individuals who are known to have recombination of the GBA gene and its pseudogene, as well as other mutations in GBA, and in controls without mutations.
Impact on Diagnosis/Treatment of Parkinson’s disease:
If our plan will be successful, we will develop a simple and efficient method to identify different forms of GBA mutations and recombinations. This will allow easier diagnosis of patients with Parkinson’s disease due to mutations in this gene. It can be a useful tool for other research groups, and could be especially important for recruitment of patients with GBA mutations to clinical trials, because this method, unlike other methods, will be able to identify all forms of GBA mutations.
Next Steps for Development:
Next steps will include implementation of this method in research and in preparation towards clinical trials.