Objective/Rationale:
Recent genome-wide association studies comparing the DNA of thousands of healthy people with the DNA of Parkinson’s patients showed regions of the human genome that differed slightly. The objective of this project is to focus on these small regions of the human genome that influence susceptibility to Parkinson’s disease (PD) and identify how they contribute to Parkinson’s disease. Many of these regions do not encode proteins and instead they may encode long non-coding RNAs—complex molecules, produced from a DNA blueprint, that appear to regulate genes encoding proteins.
Project Description:
The regions of the genome contributing to Parkinson’s disease are very likely to be producing RNA and this project undertakes to identify these RNAs, which, in turn, will indicate at least some of the basis for the genetic contribution to the disease. RNA will be extracted from the post-mortem brains of Parkinson’s patients and healthy controls and a new technique called RNA CaptureSeq (developed by the Mattick lab) will be used to identify and quantify the RNA transcripts from the regions of interest at a depth never before achieved. Intensive bioinformatic analysis will identify the transcripts that correlate most strongly with the disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The identification of PD-related RNA transcripts have the potential to provide critically needed biomarkers for idiopathic PD, to achieve pre-symptomatic detection of PD, to screen for people at risk, and to monitor both disease progression and therapeutic effectiveness.
Anticipated Outcome:
We anticipate that we will identify RNA transcripts that correlate with PD. The identification of PD informative transcripts may act as critically needed Parkinson’s biomarkers.