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Natural Genetic Variation Screen in Drosophila Identifies Wnt Signaling, Mitochondrial Metabolism, and Redox Homeostasis Genes as Modifiers of Apoptosis.

Rebecca A S Palu | Elaine Ong | Kaitlyn Stevens | Shani Chung | Katie G Owings | Alan G Goodman | Clement Y Chow
G3 (Bethesda, Md.) | 2019

Apoptosis is the primary cause of degeneration in a number of neuronal, muscular, and metabolic disorders. These diseases are subject to a great deal of phenotypic heterogeneity in patient populations, primarily due to differences in genetic variation between individuals. This creates a barrier to effective diagnosis and treatment. Understanding how genetic variation influences apoptosis could lead to the development of new therapeutics and better personalized treatment approaches. In this study, we examine the impact of the natural genetic variation in the Drosophila Genetic Reference Panel (DGRP) on two models of apoptosis-induced retinal degeneration: overexpression of p53 or reaper (rpr). We identify a number of known apoptotic, neural, and developmental genes as candidate modifiers of degeneration. We also use Gene Set Enrichment Analysis (GSEA) to identify pathways that harbor genetic variation that impact these apoptosis models, including Wnt signaling, mitochondrial metabolism, and redox homeostasis. Finally, we demonstrate that many of these candidates have a functional effect on apoptosis and degeneration. These studies provide a number of avenues for modifying genes and pathways of apoptosis-related disease.

Pubmed ID: 31570502

Research resources used in this publication

Antibodies used in this publication

None found

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R21 AI128103
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM124780
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007464
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK110966

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FlyMine (tool)

RRID:SCR_002694

An integrated database of genomic, expression and protein data for Drosophila, Anopheles, C. elegans and other organisms. You can run flexible queries, export results and analyze lists of data. FlyMine presents data in categories, with each providing information on a particular type of data (for example Gene Expression or Protein Interactions). Template queries, as well as the QueryBuilder itself, allow you to perform searches that span data from more than one category. Advanced users can use a flexible query interface to construct their own data mining queries across the multiple integrated data sources, to modify existing template queries or to create your own template queries. Access our FlyMine data via our Application Programming Interface (API). We provide client libraries in the following languages: Perl, Python, Ruby and & Java API

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Cytoscape (tool)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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GeneMANIA (tool)

RRID:SCR_005709

Data analysis service to predict the function of your favorite genes and gene sets. Indexing 1,421 association networks containing 266,984,699 interactions mapped to 155,238 genes from 7 organisms. GeneMANIA interaction networks are available for download in plain text format. GeneMANIA finds other genes that are related to a set of input genes, using a very large set of functional association data. Association data include protein and genetic interactions, pathways, co-expression, co-localization and protein domain similarity. You can use GeneMANIA to find new members of a pathway or complex, find additional genes you may have missed in your screen or find new genes with a specific function, such as protein kinases. Your question is defined by the set of genes you input. If members of your gene list make up a protein complex, GeneMANIA will return more potential members of the protein complex. If you enter a gene list, GeneMANIA will return connections between your genes, within the selected datasets. GeneMANIA suggests annotations for genes based on Gene Ontology term enrichment of highly interacting genes with the gene of interest. GeneMANIA is also a gene recommendation system. GeneMANIA is also accessible via a Cytoscape plugin, designed for power users. Platform: Online tool, Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

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FlyBase (tool)

RRID:SCR_006549

Database of Drosophila genetic and genomic information with information about stock collections and fly genetic tools. Gene Ontology (GO) terms are used to describe three attributes of wild-type gene products: their molecular function, the biological processes in which they play a role, and their subcellular location. Additionally, FlyBase accepts data submissions. FlyBase can be searched for genes, alleles, aberrations and other genetic objects, phenotypes, sequences, stocks, images and movies, controlled terms, and Drosophila researchers using the tools available from the "Tools" drop-down menu in the Navigation bar.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMJ23517}attP40 (organism)

RRID:BDSC_61934

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMJ23517}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03867}attP2 (organism)

RRID:BDSC_55682

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03867}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00978}attP2 (organism)

RRID:BDSC_34012

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00978}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05706}attP40 (organism)

RRID:BDSC_64671

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05706}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC04255}attP40 (organism)

RRID:BDSC_55961

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC04255}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC04883}attP40 (organism)

RRID:BDSC_57566

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC04883}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05771}attP40 (organism)

RRID:BDSC_64898

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05771}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05818}attP40 (organism)

RRID:BDSC_64944

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05818}attP40 from BDSC.

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y[1] v[1]; P{y[+t7.7]=CaryP}attP40 (organism)

RRID:BDSC_36304

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7]=CaryP}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC04877}attP40 (organism)

RRID:BDSC_57560

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC04877}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01307}attP2 (organism)

RRID:BDSC_34320

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01307}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03574}attP40 (organism)

RRID:BDSC_53345

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03574}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00763}attP2/TM3, Sb[1] (organism)

RRID:BDSC_32967

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMC02374}attP2 (organism)

RRID:BDSC_44483

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00046}attP2 (organism)

RRID:BDSC_33645

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00046}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01914}attP2 (organism)

RRID:BDSC_38998

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01914}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7]=CaryP}attP2 (organism)

RRID:BDSC_36303

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7]=CaryP}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05160}attP40 (organism)

RRID:BDSC_62153

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05160}attP40 from BDSC.

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