RGD Reference Report - Convergence of miRNA expression profiling, alpha-synuclein interacton and GWAS in Parkinson's disease. - Rat Genome Database

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Convergence of miRNA expression profiling, alpha-synuclein interacton and GWAS in Parkinson's disease.

Authors: Martins, M  Rosa, A  Guedes, LC  Fonseca, BV  Gotovac, K  Violante, S  Mestre, T  Coelho, M  Rosa, MM  Martin, ER  Vance, JM  Outeiro, TF  Wang, L  Borovecki, F  Ferreira, JJ  Oliveira, SA 
Citation: Martins M, etal., PLoS One. 2011;6(10):e25443. doi: 10.1371/journal.pone.0025443. Epub 2011 Oct 7.
RGD ID: 10755479
Pubmed: PMID:22003392   (View Abstract at PubMed)
PMCID: PMC3189215   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0025443   (Journal Full-text)

miRNAs were recently implicated in the pathogenesis of numerous diseases, including neurological disorders such as Parkinson's disease (PD). miRNAs are abundant in the nervous system, essential for efficient brain function and play important roles in neuronal patterning and cell specification. To further investigate their involvement in the etiology of PD, we conducted miRNA expression profiling in peripheral blood mononuclear cells (PBMCs) of 19 patients and 13 controls using microarrays. We found 18 miRNAs differentially expressed, and pathway analysis of 662 predicted target genes of 11 of these miRNAs revealed an over-representation in pathways previously linked to PD as well as novel pathways. To narrow down the genes for further investigations, we undertook a parallel approach using chromatin immunoprecipitation-sequencing (ChIP-seq) analysis to uncover genome-wide interactions of alpha-synuclein, a molecule with a central role in both monogenic and idiopathic PD. Convergence of ChIP-seq and miRNomics data highlighted the glycosphingolipid biosynthesis and the ubiquitin proteasome system as key players in PD. We then tested the association of target genes belonging to these pathways with PD risk, and identified nine SNPs in USP37 consistently associated with PD susceptibility in three genome-wide association studies (GWAS) datasets (0.46



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Objects Annotated

Genes (Rattus norvegicus)
Mir19b1  (microRNA 19b-1)
Mir29b1  (microRNA 29b-1)
Mir301a  (microRNA 301a)

Genes (Mus musculus)
Mir19b-1  (microRNA 19b-1)
Mir29b-1  (microRNA 29b-1)

Genes (Homo sapiens)
MIR19B1  (microRNA 19b-1)
MIR29B1  (microRNA 29b-1)
MIR301A  (microRNA 301a)


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