Project description:This SuperSeries is composed of the following subset Series: GSE11437: Expression QTL mapping of Toxoplasma gondii genes, Bradyzoite array GSE11514: Expression QTL mapping of Toxoplasma gondii genes, Tachyzoite array Keywords: SuperSeries Refer to individual Series
Project description:This SuperSeries is composed of the following subset Series: GSE26558: Expression Quantitative Trait Locus (eQTL) Mapping of Stage-specific Gene Expression in Progeny from a type I X III Genetic Cross of Toxoplasma gondii GSE26607: Genomic hybridizations for the parents and progeny of the Toxoplasma gondii I X III genetic cross Refer to individual Series
Project description:Toxoplasma gondii is a ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America. To test the hypothesis that strain divergence might be driven by differences between mammalian and avian response to infection, we examine in vitro strain-dependent host responses in a representative avian host, the chicken. To identify parasite drivers of strain-dependent host response, QTL mapping was used; analysis revealed a locus on Toxoplasma chromosome VIIb. To determine whether this was the parasite gene ROP16, array analysis was performed on chicken embryonic fibroblasts infected with Type I parasites and ROP16-KO parasites (of a Type I background).
Project description:Toxoplasma gondii is an intracellular parasite with a significant impact on human health, especially in cases where individuals are immunocompromised (e.g., due to HIV/AIDS). In Europe and North America only a few clonal genotypes appear to be responsible for the vast majority of Toxoplasma infections, and these clonotypes have been intensely studied to identify strain-specific phenotypes that may play a role in the manifestation of more severe disease. To identify and genetically map strain-specific differences in gene expression, we have carried out expression quantitative trait locus (eQTL) analysis on Toxoplasma gene expression phenotypes using spotted cDNA microarrays. This led to the identification of 16 Toxoplasma genes that had significant and mappable strain-specific variation in hybridization intensity. While the analysis should identify both cis and trans-mapping hybridization profiles, we only identified loci with strain-specific hybridization differences that are most likely due to differences in the locus itself (i.e., cis-mapping). Interestingly, a larger number of these cis-mapping genes than would be expected by chance encode either confirmed or predicted secreted proteins, many of which are known to localize to the specialized secretory organelles characteristic of members of the phylum Apicomplexa. For 6 of the cis-mapping loci we determined if the strain-specific hybridization differences were due to true transcriptional differences or rather strain-specific differences in hybridization efficiency because of extreme polymorphism and/or deletion, and we found examples of both scenarios. Keywords: eQTL mapping; virulence; Toxoplasma gondii 17 F1 progeny from a cross between a type II parent (PDS) and a type III parent (CTG) were used in RNA hybridizations to identify cis and trans-mapping loci regulating gene expression
Project description:Toxoplasma gondii is an intracellular parasite with a significant impact on human health, especially in cases where individuals are immunocompromised (e.g., due to HIV/AIDS). In Europe and North America only a few clonal genotypes appear to be responsible for the vast majority of Toxoplasma infections, and these clonotypes have been intensely studied to identify strain-specific phenotypes that may play a role in the manifestation of more severe disease. To identify and genetically map strain-specific differences in gene expression, we have carried out expression quantitative trait locus (eQTL) analysis on Toxoplasma gene expression phenotypes using spotted cDNA microarrays. This led to the identification of 16 Toxoplasma genes that had significant and mappable strain-specific variation in hybridization intensity. While the analysis should identify both cis and trans-mapping hybridization profiles, we only identified loci with strain-specific hybridization differences that are most likely due to differences in the locus itself (i.e., cis-mapping). Interestingly, a larger number of these cis-mapping genes than would be expected by chance encode either confirmed or predicted secreted proteins, many of which are known to localize to the specialized secretory organelles characteristic of members of the phylum Apicomplexa. For 6 of the cis-mapping loci we determined if the strain-specific hybridization differences were due to true transcriptional differences or rather strain-specific differences in hybridization efficiency because of extreme polymorphism and/or deletion, and we found examples of both scenarios. Keywords: eQTL mapping; virulence; Toxoplasma gondii 19 F1 progeny from a cross between a type II parent (PDS) and a type III parent (CTG) were used in RNA hybridizations to identify cis and trans-mapping loci regulating gene expression
Project description:Toxoplasma gondii is an intracellular parasite with a significant impact on human health, especially in cases where individuals are immunocompromised (e.g., due to HIV/AIDS). In Europe and North America only a few clonal genotypes appear to be responsible for the vast majority of Toxoplasma infections, and these clonotypes have been intensely studied to identify strain-specific phenotypes that may play a role in the manifestation of more severe disease. To identify and genetically map strain-specific differences in gene expression, we have carried out expression quantitative trait locus (eQTL) analysis on Toxoplasma gene expression phenotypes using spotted cDNA microarrays. This led to the identification of 16 Toxoplasma genes that had significant and mappable strain-specific variation in hybridization intensity. While the analysis should identify both cis and trans-mapping hybridization profiles, we only identified loci with strain-specific hybridization differences that are most likely due to differences in the locus itself (i.e., cis-mapping). Interestingly, a larger number of these cis-mapping genes than would be expected by chance encode either confirmed or predicted secreted proteins, many of which are known to localize to the specialized secretory organelles characteristic of members of the phylum Apicomplexa. For 6 of the cis-mapping loci we determined if the strain-specific hybridization differences were due to true transcriptional differences or rather strain-specific differences in hybridization efficiency because of extreme polymorphism and/or deletion, and we found examples of both scenarios. Keywords: eQTL mapping; virulence; Toxoplasma gondii
Project description:Toxoplasma gondii is an intracellular parasite with a significant impact on human health, especially in cases where individuals are immunocompromised (e.g., due to HIV/AIDS). In Europe and North America only a few clonal genotypes appear to be responsible for the vast majority of Toxoplasma infections, and these clonotypes have been intensely studied to identify strain-specific phenotypes that may play a role in the manifestation of more severe disease. To identify and genetically map strain-specific differences in gene expression, we have carried out expression quantitative trait locus (eQTL) analysis on Toxoplasma gene expression phenotypes using spotted cDNA microarrays. This led to the identification of 16 Toxoplasma genes that had significant and mappable strain-specific variation in hybridization intensity. While the analysis should identify both cis and trans-mapping hybridization profiles, we only identified loci with strain-specific hybridization differences that are most likely due to differences in the locus itself (i.e., cis-mapping). Interestingly, a larger number of these cis-mapping genes than would be expected by chance encode either confirmed or predicted secreted proteins, many of which are known to localize to the specialized secretory organelles characteristic of members of the phylum Apicomplexa. For 6 of the cis-mapping loci we determined if the strain-specific hybridization differences were due to true transcriptional differences or rather strain-specific differences in hybridization efficiency because of extreme polymorphism and/or deletion, and we found examples of both scenarios. Keywords: eQTL mapping; virulence; Toxoplasma gondii
Project description:Tymoshenko2015 - Genome scale metabolic model
- ToxoNet1
This model is described in the article:
Metabolic Needs and
Capabilities of Toxoplasma gondii through Combined
Computational and Experimental Analysis.
Tymoshenko S, Oppenheim RD, Agren R,
Nielsen J, Soldati-Favre D, Hatzimanikatis V.
PLoS Comput. Biol. 2015 May; 11(5):
e1004261
Abstract:
Toxoplasma gondii is a human pathogen prevalent worldwide
that poses a challenging and unmet need for novel treatment of
toxoplasmosis. Using a semi-automated reconstruction algorithm,
we reconstructed a genome-scale metabolic model, ToxoNet1. The
reconstruction process and flux-balance analysis of the model
offer a systematic overview of the metabolic capabilities of
this parasite. Using ToxoNet1 we have identified significant
gaps in the current knowledge of Toxoplasma metabolic pathways
and have clarified its minimal nutritional requirements for
replication. By probing the model via metabolic tasks, we have
further defined sets of alternative precursors necessary for
parasite growth. Within a human host cell environment, ToxoNet1
predicts a minimal set of 53 enzyme-coding genes and 76
reactions to be essential for parasite replication.
Double-gene-essentiality analysis identified 20 pairs of genes
for which simultaneous deletion is deleterious. To validate
several predictions of ToxoNet1 we have performed experimental
analyses of cytosolic acetyl-CoA biosynthesis. ATP-citrate
lyase and acetyl-CoA synthase were localised and their
corresponding genes disrupted, establishing that each of these
enzymes is dispensable for the growth of T. gondii, however
together they make a synthetic lethal pair.
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MODEL1504280000.
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