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IDENTIFICATION OF GENETIC VARIATION AND TRANSCRIPTIONAL PERTURBATIONS IMPLICATED IN PARKINSON’S DISEASE
Abstract
Aims
This study aims to systematically characterize and functionally annotate the candidate structural variants (SVs) causal for Parkinson's disease (PD) using dopaminergic neuronal (DN) cell cultures derived from healthy controls and idiopathic (iPD) patients iPSC lines.
Methods
For this purpose, we generated long-read DNA and RNA sequencing data from 10 DN cell lines with ONT-PromethION. Long-read DNA sequencing data was used for SV detection. Long-read RNA-seq data was used for isoform expression and splicing analysis. Resolved perturbations in the transcriptome were associated to the presence of SVs in the coding and non-coding regions.
Results
We developed a conceptual approach for SV prioritization on genomic and transcriptomic levels and applied it to obtain a list of candidate genetic risk factors for the iPD samples in our cohort.
Conclusions
Our results expand the knowledge about the PD risk variants and their biological functions as well as shed light on the underlying mechanism of pathogenesis, which could suggest novel therapeutic targets for PD.