For example, it has been widely shown that the major lineages of T. cruzi exhibit significant differences in pathogenic potential. Trypanosoma cruzi I, generally less pathogenic for humans, has a lower acute infectious profile and progression, a more extensive chronic profile, and invades and causes pathology in different organs. Comparison of at least one T. cruzi I isolate (e.g., Silvio ×10) with the other isolates will provide an opportunity to discover the genetic basis of these phenomena. Another outstanding question
relates to the genetic basis for a variety of phenotypes (cell cycle, host range, vector selection, pathogenic and clinical manifestations, etc.) of the major groups of pathogenic Dabrafenib in vivo trypanosomatids. Again, considering T. cruzi as an example, isolates of the six lineages of T. cruzi are quite divergent in many respects. Although superficially similar, their preferred hosts and vectors, method of invasion, effects on the invaded cells, levels of parasitemia, mechanisms of pathogenesis and clinical outcomes are quite different. Whereas it is quite well documented that the
differences among T. cruzi isolates are genetically programmed, it is not yet established that genes or gene networks confer these different phenotypes. The genome of www.selleckchem.com/products/Gefitinib.html trypanosomes is transcribed into long polycistronic primary transcripts (mostly by RNA polymerase II) and pre-mRNAs are processed into mature individual mRNAs through coupled trans-splicing and polyadenylation events (8). It has therefore been widely considered that trypanosomes heavily rely on post-transcriptional regulation and RNA turn-over rather than transcription initiation to regulate gene expression (28). Nonetheless, several genome-wide gene expression profiling studies have been carried out to interrogate the
differences in the distinct developmental life cycle stages in trypanosomatids. Many of the studies have revealed considerable numbers of regulated genes during trypanosome development (29–35), although some analyses noted limited and inflexible transcriptome responses across the life cycle stages (36–38). Results from multiple microarray studies were recently integrated bioinformatically selleck inhibitor and co-expression clusters were used to predict putative gene functions and potential regulatory networks (38). In addition, DNA microarrays coupled with chromatin immunoprecipitation (ChIP-chip) have allowed the identification of the origins of polycistronic transcription initiation through histone acetylation profiling (39). The application of NGS technologies to transcriptome profiling (40,41) has prompted the use of alternative and more powerful approaches for analysing gene expression in trypanosomatids.