Autor: |
Duong My Phung, Jinwoo Lee, SangKyoon Hong, Young Eun Kim, Jeehee Yoon, Yun Joong Kim |
Jazyk: |
angličtina |
Rok vydání: |
2020 |
Předmět: |
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Zdroj: |
Frontiers in Neuroscience, Vol 14 (2020) |
Druh dokumentu: |
article |
ISSN: |
1662-453X |
DOI: |
10.3389/fnins.2020.596105 |
Popis: |
BackgroundStudies regarding differentially expressed genes (DEGs) in Parkinson’s disease (PD) have focused on common upstream regulators or dysregulated pathways or ontologies; however, the relationships between DEGs and disease-related or cell type-enriched genes have not been systematically studied. Meta-analysis of DEGs (meta-DEGs) are expected to overcome the limitations, such as replication failure and small sample size of previous studies.PurposeMeta-DEGs were performed to investigate dysregulated genes enriched with neurodegenerative disorder causative or risk genes in a phenotype-specific manner.MethodsSix microarray datasets from PD patients and controls, for which substantia nigra sample transcriptome data were available, were downloaded from the NINDS data repository. Meta-DEGs were performed using two methods, combining p-values and combing effect size, and common DEGs were used for secondary analyses. Gene sets of cell type-enriched or disease-related genes for PD, Alzheimer’s disease (AD), and hereditary progressive ataxia were constructed by curation of public databases and/or published literatures.ResultsOur meta-analyses revealed 449 downregulated and 137 upregulated genes. Overrepresentation analyses with cell type-enriched genes were significant in neuron-enriched genes but not in astrocyte- or microglia-enriched genes. Meta-DEGs were significantly enriched in causative genes for hereditary disorders accompanying parkinsonism but not in genes associated with AD or hereditary progressive ataxia. Enrichment of PD-related genes was highly significant in downregulated DEGs but insignificant in upregulated genes.ConclusionDownregulated meta-DEGs were associated with PD-related genes, but not with other neurodegenerative disorder genes. These results highlight disease phenotype-specific changes in dysregulated genes in PD. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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