Changes to the DNA sequence are risk factors for Parkinson’s disease. While we know where many of these changes occur in our DNA, we still do not know how they cause Parkinson’s disease.
We think that changes to DNA found in the glucocerebrosidase (GBA) gene control other genes (e.g., NECAB2 and SYT11), which can predispose a person to develop Parkinson’s disease.
We will use computer programs to identify genes that are controlled by the DNA switches located within the GBA gene. We will repeat this process for every mutation in GBA that has been linked to Parkinson’s disease to create a network of the genes that are affected by these mutations. We will then make pairs of cells that contain a working and broken version of the same DNA switch to see how these switches affect cells and contribute to Parkinson’s disease.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This is an unconventional approach to understand how Parkinson’s disease develops. If successful, we will identify DNA switches within the GBA gene that control other genes and play a role in Parkinson’s disease development. This would provide Parkinson’s researchers with a new framework within which to study the functional impacts of disease-associated genetic variants.
Next Steps for Development:
The better we understand the causes of PD at a genetic, molecular level, the greater our chances of predicting the disease and developing treatments that could mitigate or even reverse this disease. If successful, the results of this study will be translated to move new treatments toward the clinic.