The genetic map and comparative analysis with the physical map of Trypanosoma brucei

Abstract

Trypanosoma brucei is the causative agent of African sleeping sickness in humans and contributes to the debilitating disease ‘Nagana’ in cattle. To date we know little about the genes that determine drug resistance, host specificity, pathogenesis and virulence in these parasites. The availability of the complete genome sequence and the ability of the parasite to undergo genetic exchange have allowed genetic investigations into this parasite and here we report the first genetic map of T.brucei for the genome reference stock TREU 927, comprising of 182 markers and 11 major linkage groups, that correspond to the 11 previously identified chromosomes. The genetic map provides 90% probability of a marker being 11 cM from any given locus. Its comparison to the available physical map has revealed the average physical size of a recombination unit to be 15.6 Kb/cM. The genetic map coupled with the genome sequence and the ability to undertake crosses presents a new approach to identifying genes relevant to the disease and its prevention in this important pathogen through forward genetic analysis and positional cloning.

Population genetics of Trypanosoma brucei gambiense , the agent of sleeping sickness in Western Africa

“…It is thus better to remove this locus from further analyses. The absence of individuals with 3 or 4 alleles at any of the 6 remaining loci, and the constant level of heterozygosity across loci and samples, strongly support (if not prove) the diploid status of T. brucei gambiense, as already supported by genetic cross studies (47). The monophyly of T. brucei gambiense group 1, in particular as compared to T. brucei gambiense group 2, was already demonstrated (21).…”

Hemizygous subtelomeres of an African trypanosome chromosome may account for over 75% of chromosome length

“…However, it is possible that VSG arrays may be found at both telomeres on Tb427-chrIb. The schematic in Figure 6B illustrates our model, showing a striking modular organization for these chromosomes: a diploid "central core" (Melville et al 1998(Melville et al , 2000MacLeod et al 2005) consisting of just 750-850 kb of relatively gene-dense DNA, while the remainder, almost 3 Mb in the case of the larger chrI homolog, consists of highly polymorphic gene families in largely aneuploid segments of the chromosome.…”

Role for Parasite Genetic Diversity in Differential Host Responses toTrypanosoma bruceiInfection

“…In the future, therefore, it will be important to study different host-parasite genotype combinations, as the role of a particular host pathway may depend on both the host and parasite genetic backgrounds. The observed differences in pathology also open up the possibility of identifying the parasite genes that are responsible, for example, by using a forward genetic approach, as has been employed in Toxoplasma gondii (70,78,80), particularly as a genetic map exists for a cross using the strains involved in this study (40,47). The findings also obviously have implications for the use of genetic improvement by selective breeding of cattle for trypanotolerance, as any breeding must take into account the ability of animals to cope with the range of trypanosome virulence that is undoubtedly present in the field.…”