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- Title
Characterizing dopaminergic neuron vulnerability using genome-wide analysis.
- Authors
Davis, Jacinta; Da Silva Santos, Claire; Zavala, Narda Caudillo; Gans, Nicholas; Patracuolla, Daniel; Fehrenbach, Monica; Babcock, Daniel T.
- Abstract
Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. To identify genes that are associated with DA neuron loss, we screened through 201 wild-caught populations of Drosophila melanogaster as part of the Drosophila Genetic Reference Panel. Here, we identify the top-associated genes containing single-nucleotide polymorphisms that render DA neurons vulnerable. These genes were further analyzed by using mutant analysis and tissue-specific knockdown for functional validation. We found that this loss of DA neurons caused progressive locomotor dysfunction in mutants and gene knockdown analysis. The identification of genes associated with the progressive loss of DA neurons should help to uncover factors that render these neurons vulnerable in PD, and possibly develop strategies to make these neurons more resilient.
- Subjects
NEURON analysis; DOPAMINE analysis; DRUG therapy for Parkinson's disease; REVERSE transcriptase polymerase chain reaction; DIGITAL image processing; GENETIC mutation; ANALYSIS of variance; IMMUNOHISTOCHEMISTRY; GENETIC polymorphisms; RNA; COMPARATIVE studies; GENE expression; GENOMES; DESCRIPTIVE statistics; POLYMERASE chain reaction; DATA analysis software; NEURODEGENERATION
- Publication
Genetics, 2021, Vol 218, Issue 4, p1
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1093/genetics/iyab081