g experi ment sellckchem we decided to focus our analysis of genetic diver sity on the subset of high quality SNPs that are also located in regions of good sequence neighborhood. This subset was therefore used throughout the study. Because the candidate allelic copies of each reference coding sequence are now aligned in our dataset, we use the words gene and alignment interchangeably to refer to the genomic loci represented by these sequences. A first genome wide look at the genetic diversity of T. cruzi In the subset of high quality SNPs, we first looked at the types of changes observed at the DNA level, transitions and transversions. Theoretically, there are twice the number of possible transversions than transitions. How ever, because of the nature of the molecular mechanisms involved in the generation of these mutations transitions are found more frequently than transversions.

And T. cruzi was not exception. As observed previously for rRNA genes we observed an excess of transi tions over transversions. When analyzing the subset of high quality SNPs at the codon level, SNPs were more frequently observed at the Inhibitors,Modulators,Libraries 3rd codon position, followed by the 1st codon position and the 2nd. Functional characterization of polymorphic sites, Inhibitors,Modulators,Libraries nonsense SNPs Using the set of high quality SNPs we observed 76,452 silent SNPs, 99,552 non synonymous SNPs and 161 non sense Inhibitors,Modulators,Libraries SNPs those introducing or removing stop codons in proteins. After manual inspection of alignments containing nonsense SNPs, to filter out cases that could be explained by genome assembly problems, we ended up with 113 alignments with clear nonsense polymorphisms, many of which correspond to hypothetical proteins.

These nonsense polymorphisms were produced by changes affecting different positions of the codon. Interestingly, we also observed a bias in the codon position affected by these nonsense SNPs. Even though, theoretically, we would expect nonsense SNPs in the 1st base of a codon in 9 out of 23 nonsense SNPs, we observed a significantly Inhibitors,Modulators,Libraries higher number of nonsense SNPs arising from mutation of the 1st base of a codon or as generating a read through codon. The comparison of nonsense mutations in the available data suggest that in 3 cases the ancestral state of the codon was most prob ably a STOP that was changed into a read through codon in one strain lineage only.

In other cases the situation might be similar, although the corresponding CDS was missing from one of the strains. In contrast, in 44 cases the nonsense mutation was only observed once, and can therefore correspond to the alternative case, in which the ances tral codon was replaced by a premature stop, therefore Brefeldin_A generating a truncated http://www.selleckchem.com/products/mek162.html protein product. Analysis of the these cases, revealed that the majority of them contained the nonsense SNP in the final 10% of the corresponding coding sequence, near the 3 end of the other allele, and therefore may not be asso ciated with large functional changes. However, in a few cases the identified nonsense SN