ansfer, iii to assess the poten tial for development of resistance when validating a target for drug development, iv to prioritize targets for develop ment of diagnostics or vaccines, v in the design of con structs for genetic knockout experiments in order to increase the success rate when targeting specific alleles, and vi as genetic markers in association studies or selleck Carfilzomib to further probe the population structure. The genome sequence of the CL Brener clone of T. cruzi was published in 2005, together with those of two other trypanosomatids of medical import ance, Trypanosoma brucei and Leishmania major. However, the genome of T. cruzi was a particular case for a number of reasons, it was obtained from a hybrid TcVI strain composed of two divergent parental haplotypes, and it was sequenced using a whole genome shotgun stra tegy.

This choice of strain and sequencing strategy resulted in high sequence coverage from the two parental haplotypes, which Inhibitors,Modulators,Libraries were derived from ancestral TcII and TcIII strains. Because of the high allelic variation found within this diploid genome, a significant number of contigs were found to be present twice in the assembly. These divergent haplotypes, which were assembled separately in many cases, were the basis of a recent re assembly of the genome. As a consequence, it is now possible to identify the genetic diversity present within this diploid Inhibitors,Modulators,Libraries genome. More recently a number of whole genome sequencing data have become available from Inhibitors,Modulators,Libraries different strains of T. cruzi, the draft genomic sequence of the Sylvio X10 strain, high coverage transcriptomic data, from another TcI strain, as well as 2.

5X WGS shotgun data from the Esmeraldo cl3 strain. To take advantage of the hybrid genome of the CL Brener strain, and of other genome and transcriptome datasets, we designed a bionformatics strategy to obtain information Inhibitors,Modulators,Libraries on the genetic diversity present in these data. As already observed for a significant number of molecular markers, each of the alleles identified in the majority of the polymorphic heterozygous site in strains from hybrid lineages TcV and TCVI can be observed in homozygosity in strains from either of the two proposed parental lineages. Therefore by uncovering the diversity within the CL Brener and Sylvio X10 genomes, we expect to reveal a significant fraction of the diversity that can be observed between extant TcI, TcII, TcIII, and TcVI Cilengitide strains.

In this work we present an initial compilation of a genome wide map of genetic diversity in T. cruzi, and its functional analysis, selleck kinase inhibitor focussed mostly on protein coding regions of the genome. Results Sequence clustering, alignment and identification of polymorphic sites To identify genetic variation in T. cruzi we took advantage of available sequence data in public databanks, including the genome sequence of the CL Brener and Sylvio X10 strains, expressed sequence tags and other sequences submitted by independent authors to these databanks. Our strategy to map this diversity relied on t