1a.Objectives (from AD-416):
Risk-based management systems for the control of zoonotic parasites in swine.
1b.Approach (from AD-416):
Will determine genetic and antigenic variation among toxoplasma isolates from food animals.
Toxoplasma gondii is a widespread parasitic infection that can cause severe disease in immunocompromised patients. Our studies seek to define the factors that contribute to the severity of disease caused by this parasite. By understanding the virulence determinants of the parasite that enable it to cause harm, it may be possible to develop new therapeutic approaches to combat human infection. Towards this goal, some 150 distinct genotypes recognized by the intersection of three typing methods have been defined, based on initial analysis of more than 1,000 strains. Comparison of restriction fragment length polymorphisms (RFLP) and intron-based datasets provides robust support for 14 major haplogroups of T. gondii as revealed by various methods (including network reconstruction, Bayesian statistical assignment, and principle component analyses). Microsatellite analysis is being used to further divide these groups and population genetic analyses are being used to estimate gene flow between them. One example of the value of this approach is that we recently characterized a new clonal lineage from North America from a group of isolates that had previously been defined only by RFLP markers. This new group is common in wild animals, shows intermediate virulence in rodent models, and can also cause disease in humans. A genetic cross between North American type II, which contains the monomorphic version of chromosome 1a (Chr1a*), and type X, which is from South America and contains a highly divergent chromosomal allele, was performed successfully. Analysis of the progeny of this cross is not yet complete, however, we can make the following initial conclusions:. 1)there is no evidence of meiotic drive or segregation distortion associated with this chromosome,. 2)both monomorphic and divergent versions of this chromosome propagate in the cat, and give rise to viable progeny,. 3)there is no evidence for an influence on mating type, and. 4)there is no evidence of large scale rearrangement or insertion or deletion between monomorphic and divergent versions of this chromosome. Collectively, these results indicate that the abundance of the Chrla* variant in nature likely resulted from a selective advantage, although the basis of this phenotype remains to be defined.