PgmNr W4154: Transcriptomic Analysis of C. elegans transgenic animals overexpressing human alpha-synuclein (A53T): Comparison to genes regulated in human Parkinson’s Disease brain tissues.

Authors:
C. Wang 1 ; J. Peltonen 2 ; L. Heikkinen 3 ; G. Wong 1


Institutes
1) University of Macau, Macau, MO; 2) University of Eastern Finland, Kuopio, Finland; 3) University of Jyväskylä, Finland.


Keyword: Transcription

Abstract:

Parkinson’s Disease is a devastating neurodegenerative disorder characterized by loss of dopaminergic neurons in the substania nigra pars compacta. We modeled this disease by constructing a transgenic C. elegans strain overexpressing human alpha-synuclein gene with mutation A53T in dopaminergic and other neurons using a pan neuronal promoter. We isolated total RNA and performed RNA-seq transcriptomic analysis on young adult animals and compared the gene expression changes to controls. We observed 1793 genes up- and 92 down-regulated using a Bowtie-Cufflinks-Cuffdiff workflow. Gene set enrichment analysis using David 6.7 indicated that up-regulated annotation clusters included phosphatase activity (46 genes, p<10-20), PapD-like (31 genes, p<10-23), DUF856 (7 genes, p<10-7) and down-regulated included (serine/threonine protein kinase (4 genes, p<0.02). Comparing the list of regulated genes from C. elegans to the top 11 genes related to human Parkinson’s disease confirmed an overlap of 4 genes: DGKQ/GAK, diacylgycerol kinase (dgk-1), MAPT, microtubule-associated protein tau (ptl-1), SYT11/RAB25, synaptotagmin-11 (snt-1), and STK39, SPS1-related proline-alanine-rich protein (gck-3). Taken together, our results suggests that C. elegans could be a useful model to identify gene expression changes in human Parkinson’s disease and ultimately to understand the pathophysiology of this disease.



Wormbase Genetic Index
1. dgk-1
2. ptl-1
3. snt-1
4. gck-3