Searching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.

<h4>Background</h4>The symptoms of numerous diseases result from genetic mutations that disrupt the homeostasis maintained by the appropriate integration of signaling gene activities. The relationships between signaling genes suggest avenues through which homeostasis can be restored and...

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Autores principales:	Anna Y Lee, Richard Perreault, Sharon Harel, Elodie L Boulier, Matthew Suderman, Michael Hallett, Sarah Jenna
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cfafbc64268f4960ac6a62ee18e8b454
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spelling	oai:doaj.org-article:cfafbc64268f4960ac6a62ee18e8b4542021-12-02T20:21:41ZSearching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.1932-620310.1371/journal.pone.0010624https://doaj.org/article/cfafbc64268f4960ac6a62ee18e8b4542010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20498707/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The symptoms of numerous diseases result from genetic mutations that disrupt the homeostasis maintained by the appropriate integration of signaling gene activities. The relationships between signaling genes suggest avenues through which homeostasis can be restored and disease symptoms subsequently reduced. Specifically, disease symptoms caused by loss-of-function mutations in a particular gene may be reduced by concomitant perturbations in genes with antagonistic activities.<h4>Methodology/principal findings</h4>Here we use network-neighborhood analyses to predict genetic interactions in Caenorhabditis elegans towards mapping antagonisms and synergisms between genes in an animal model. Most of the predicted interactions are novel, and the experimental validation establishes that our approach provides a gain in accuracy compared to previous efforts. In particular, we identified genetic interactors of gdi-1, the orthologue of GDI1, a gene associated with mental retardation in human. Interestingly, some gdi-1 interactors have human orthologues with known neurological functions, and upon validation of the interactions in mammalian systems, these orthologues would be potential therapeutic targets for GDI1-associated neurological disorders. We also observed the conservation of a gdi-1 interaction between different cellular systems in C. elegans, suggesting the involvement of GDI1 in human muscle degeneration.<h4>Conclusions/significance</h4>We developed a novel predictor of genetic interactions that may have the ability to significantly streamline the identification of therapeutic targets for monogenic disorders involving genes conserved between human and C. elegans.Anna Y LeeRichard PerreaultSharon HarelElodie L BoulierMatthew SudermanMichael HallettSarah JennaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 5, p e10624 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Y Lee Richard Perreault Sharon Harel Elodie L Boulier Matthew Suderman Michael Hallett Sarah Jenna Searching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.
description	<h4>Background</h4>The symptoms of numerous diseases result from genetic mutations that disrupt the homeostasis maintained by the appropriate integration of signaling gene activities. The relationships between signaling genes suggest avenues through which homeostasis can be restored and disease symptoms subsequently reduced. Specifically, disease symptoms caused by loss-of-function mutations in a particular gene may be reduced by concomitant perturbations in genes with antagonistic activities.<h4>Methodology/principal findings</h4>Here we use network-neighborhood analyses to predict genetic interactions in Caenorhabditis elegans towards mapping antagonisms and synergisms between genes in an animal model. Most of the predicted interactions are novel, and the experimental validation establishes that our approach provides a gain in accuracy compared to previous efforts. In particular, we identified genetic interactors of gdi-1, the orthologue of GDI1, a gene associated with mental retardation in human. Interestingly, some gdi-1 interactors have human orthologues with known neurological functions, and upon validation of the interactions in mammalian systems, these orthologues would be potential therapeutic targets for GDI1-associated neurological disorders. We also observed the conservation of a gdi-1 interaction between different cellular systems in C. elegans, suggesting the involvement of GDI1 in human muscle degeneration.<h4>Conclusions/significance</h4>We developed a novel predictor of genetic interactions that may have the ability to significantly streamline the identification of therapeutic targets for monogenic disorders involving genes conserved between human and C. elegans.
format	article
author	Anna Y Lee Richard Perreault Sharon Harel Elodie L Boulier Matthew Suderman Michael Hallett Sarah Jenna
author_facet	Anna Y Lee Richard Perreault Sharon Harel Elodie L Boulier Matthew Suderman Michael Hallett Sarah Jenna
author_sort	Anna Y Lee
title	Searching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.
title_short	Searching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.
title_full	Searching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.
title_fullStr	Searching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.
title_full_unstemmed	Searching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.
title_sort	searching for signaling balance through the identification of genetic interactors of the rab guanine-nucleotide dissociation inhibitor gdi-1.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/cfafbc64268f4960ac6a62ee18e8b454
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Searching for signaling balance through the identification of genetic interactors of the Rab guanine-nucleotide dissociation inhibitor gdi-1.

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