Expression QTL mapping of Toxoplasma genes reveals multiple mechanisms for strain-specific differences in gene expression

Eukaryot Cell. 2008 Jun 13. [Epub ahead of print]

Expression QTL mapping of Toxoplasma genes reveals multiple mechanisms for strain-specific differences in gene expression

Boyle JP, Saeij JP, Harada SY, Ajioka JW, Boothroyd JC.

Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild Building Room D305, Stanford, CA 94305, USA; Department of Pathology, Cambridge University, Cambridge, CB2 1QP, UK.

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.

PMID: 18552283 [PubMed - as supplied by publisher]