UBC Theses and Dissertations

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UBC Theses and Dissertations

Comparative genome analysis in rodent models of Parkinson’s disease and spinocerebellar ataxia type 3 Thatra, Nivretta


The shared hallmarks of neurodegenerative diseases (NDs) – notably, the existence of protein deposits, selective vulnerability of cell types, chronic neuroimmune response, and early dysfunction in brain vasculature – support the idea of studying different transgenic models relevant to NDs in concert rather than separately. Indeed, transgenic models of different NDs, namely Parkinson’s disease (PD) and spinocerebellar ataxia type 3 (SCA3), show comparable behavioral abnormalities and some similarities in cell loss. In this project, we hypothesized the reflection of these previously characterized similarities at the transcriptomic level in transgenic models of PD and SCA3, and that prioritizing overlaps in gene expression across transgenic models might allow the identification of genes that are involved in pathological pathways relevant to more than one ND. I show in an unpublished dataset of rodent transcriptomes from two time points and up to three brain regions that most overlaps in gene expression patterns are specific both to the brain region and time point from which samples are obtained. Overlaps in gene expression are found between transgenic models that study the effects of the same gene, synuclein alpha (Snca). In examining the overlaps of the interpretations of gene expression via cell type proportional estimations and functional analysis, I find commonalities across models suggesting changes in endothelial cells at the earlier time point and oligodendrocytes at the later time point.

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