Objective/Rationale:
The recent discovery of a hidden universe of regulatory, non-coding transcripts and previously unknown variants of protein-coding transcripts is challenging conventional thinking about gene-RNA-protein interactions and disease processes.
Project Description:
To begin to systematically identify all splice variants and non-coding transcripts associated with the onset of PD pathology (and without confounding by dopamine replacement medications), we will interrogate the RNA content of vulnerable nigral dopamine neurons of 15 cases with incidental Lewy body disease and 15 matched controls using massively parallel deep sequencing combined with ab initio transcript reconstruction.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This study will enhance our understanding of early stages of the disease process, begin a search for viable targets for splicing repair and may enable future non-coding RNA therapeutics.
Anticipated Outcome:
We will provide the as of yet highest resolution catalog of coding splice variants and the first ever look at the “dark universe” of non-coding RNAs in the human dopamine neuron. These insights will set the foundation for a 10x more detailed understanding of sporadic PD than previously possible and prioritize novel targets for replication.