Characterizing dopaminergic neuron vulnerability using Genome-wide analysis

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 (DGRP). Here we identify the top associated genes containing SNPs 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.

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Genome-wide analysis reveals novel regulators of growth in Drosophila melanogaster

10.1101/017855 ◽

2015 ◽

Author(s):

Sibylle Chantal Vonesch ◽

David Lamparter ◽

Trudy FC Mackay ◽

Sven Bergmann ◽

Ernst Hafen

Keyword(s):

Drosophila Melanogaster ◽

Phenotypic Diversity ◽

Genome Wide Association ◽

Genome Wide Analysis ◽

Epistasis Analysis ◽

Genome Wide ◽

Genetic And Environmental Factors ◽

Developmental Traits ◽

Drosophila Genetic Reference Panel ◽

Growth Pathway

Organismal size depends on the interplay between genetic and environmental factors. Genome-wide association (GWA) analyses in humans have implied many genes in the control of height but suffer from the inability to control the environment. Genetic analyses in Drosophila have identified conserved signaling pathways controlling size; however, how these pathways control phenotypic diversity is unclear. We performed GWA of size traits using the Drosophila Genetic Reference Panel of inbred, sequenced lines. We find that the top associated variants differ between traits and sexes; do not map to canonical growth pathway genes, but can be linked to these by epistasis analysis; and are enriched for genes and putative enhancers. Performing GWA on well-studied developmental traits under controlled conditions expands our understanding of developmental processes underlying phenotypic diversity.

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Faculty Opinions recommendation of Genome-wide analysis of Polycomb targets in Drosophila melanogaster.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1032753.374447 ◽

2006 ◽

Author(s):

Juerg Mueller

Keyword(s):

Drosophila Melanogaster ◽

Genome Wide Analysis ◽

Genome Wide

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Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease

Current Neuropharmacology ◽

10.2174/1570159x19666210826130210 ◽

2021 ◽

Vol 19 ◽

Author(s):

Md. Sahab Uddin ◽

Md. Tanvir Kabir ◽

Maroua Jalouli ◽

Md. Ataur Rahman ◽

Philippe Jeandet ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Innate Immune ◽

Misfolded Proteins ◽

Inflammatory Signaling ◽

Genome Wide Analysis ◽

Genome Wide ◽

Immunological Mechanisms ◽

The Brain

: Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.

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Genome-wide analysis of Polycomb targets in Drosophila melanogaster

Nature Genetics ◽

10.1038/ng1817 ◽

2006 ◽

Vol 38 (6) ◽

pp. 700-705 ◽

Cited By ~ 389

Author(s):

Yuri B Schwartz ◽

Tatyana G Kahn ◽

David A Nix ◽

Xiao-Yong Li ◽

Richard Bourgon ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Genome Wide Analysis ◽

Genome Wide

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Genome-wide analysis of promoter architecture in Drosophila melanogaster

Genome Research ◽

10.1101/gr.112466.110 ◽

2010 ◽

Vol 21 (2) ◽

pp. 182-192 ◽

Cited By ~ 151

Author(s):

R. A. Hoskins ◽

J. M. Landolin ◽

J. B. Brown ◽

J. E. Sandler ◽

H. Takahashi ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Genome Wide Analysis ◽

Promoter Architecture ◽

Genome Wide

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Erratum: Corrigendum: Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster

Nature Communications ◽

10.1038/ncomms8296 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 4

Author(s):

Adam J. Dobson ◽

John M. Chaston ◽

Peter D. Newell ◽

Leanne Donahue ◽

Sara L. Hermann ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Genetic Determinants ◽

Genome Wide Analysis ◽

Genome Wide ◽

Host Genetic

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Genome-wide analysis of Sox genes in Drosophila melanogaster

Mechanisms of Development ◽

10.1016/s0925-4773(01)00529-9 ◽

2001 ◽

Vol 109 (2) ◽

pp. 371-375 ◽

Cited By ~ 50

Author(s):

Frédéric Crémazy ◽

Philippe Berta ◽

Franck Girard

Keyword(s):

Drosophila Melanogaster ◽

Genome Wide Analysis ◽

Genome Wide ◽

Sox Genes

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Structural variants and selective sweep foci contribute to insecticide resistance in the Drosophila melanogaster genetic reference panel

10.1101/301937 ◽

2018 ◽

Cited By ~ 1

Author(s):

Paul Battlay ◽

Llewellyn Green ◽

Pontus B. Leblanc ◽

Joshua M. Schmidt ◽

Alexandre Fournier-Level ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Transposable Element ◽

Selective Sweep ◽

Association Studies ◽

Transcript Abundance ◽

Reference Panel ◽

Drosophila Genome ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Number Variation

AbstractPatterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweep loci to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome wide association studies map ‘survival-on-malathion’ to two of the largest sweeps in the D. melanogaster genome; Ace and Cyp6g1. Malathion survivorship also correlates with lines which have high levels of Cyp12d1 and Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a selective sweep driven by insecticide use, the derived state seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility.

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