Abstract
Background Trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to this parasite. However, no genes controlling these differences were mapped.MethodsWe studied the genetic control of survival after T. b. brucei infection using recombinant congenic (RC) strains, which have a high mapping power. Each RC strain of BALB/c-c-STS/A (CcS/Dem) series contains a different random subset of 12.5% genes from the parental “donor” strain STS/A and 87.5% genes from the “background” strain BALB/c. Although BALB/c and STS/A mice are similarly susceptible to T. b. brucei, the RC strain CcS-11 is more susceptible than either of them. We analyzed genetics of survival in T. b. brucei-infected F2 hybrids between BALB/c and CcS-11. CcS-11 strain carries STS-derived segments on eight chromosomes. They were genotyped in the F2 hybrid mice and their linkage with survival was tested by analysis of variance.ResultsWe mapped four Tbbr (Trypanosoma brucei brucei response) loci that influence survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have effects on survival independent of inter-genic interactions (main effects). Tbbr3 (chromosome 7) influences survival in interaction with Tbbr4 (chromosome 19). Tbbr2 is located on a segment 2.15 Mb short that contains only 26 genes.ConclusionThis study presents the first identification of chromosomal loci controlling susceptibility to T. b. brucei infection. While mapping in F2 hybrids of inbred strains usually has a precision of 40–80 Mb, in RC strains we mapped Tbbr2 to a 2.15 Mb segment containing only 26 genes, which will enable an effective search for the candidate gene. Definition of susceptibility genes will improve the understanding of pathways and genetic diversity underlying the disease and may result in new strategies to overcome the active subversion of the immune system by T. b. brucei.
Highlights
Sleeping sickness (African trypanosomiasis) continues to pose a major threat to 60 million people in 36 countries in sub-Saharan Africa
The third species, T. b. brucei infects a wide range of mammals, but is unable to infect humans because it lacks the SRA protein that prevents lysis induced by Apolipoprotein L1, which is present in normal human serum [2,3]
T. b. equiperdum and T. b. evansi, which are derived from T. b. brucei, are adapted to transmission without development in tsetse fly, allowing these parasites to spread outside the African tsetse belt [4]
Summary
Sleeping sickness (African trypanosomiasis) continues to pose a major threat to 60 million people in 36 countries in sub-Saharan Africa. The estimated number of new cases is currently between 50 000 and 70 000 per year (WHO 2006 – African trypanosomiasis - http://www.who.int/mediacentre/factsheets/fs259/en/). The disease is caused by infection with the tsetse fly-transmitted [1] protozoan haemoflagellate Trypanosoma brucei, which has three major sub-species: T. b. Rhodesiense cause sleeping sickness in humans and can infect animals; domestic and wild animals are an important parasite reservoir (WHO 2006 http://www.who.int/mediacentre/factsheets/fs259/en/). Brucei, are adapted to transmission without development in tsetse fly, allowing these parasites to spread outside the African tsetse belt [4]. Mouse strains differ greatly in susceptibility to this parasite.
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