Abstract
African bovine trypanosomiasis caused by Trypanosoma sp., is a major constraint on cattle productivity in sub-Saharan Africa. Some African Bos taurus breeds are highly tolerant of infection, but the potentially more productive Bos indicus zebu breeds are much more susceptible. Zebu cattle are well adapted for plowing and haulage, and increasing their tolerance of trypanosomiasis could have a major impact on crop cultivation as well as dairy and beef production. We used three strategies to obtain short lists of candidate genes within QTL that were previously shown to regulate response to infection. We analyzed the transcriptomes of trypanotolerant N'Dama and susceptible Boran cattle after infection with Trypanosoma congolense. We sequenced EST libraries from these two breeds to identify polymorphisms that might underlie previously identified quantitative trait loci (QTL), and we assessed QTL regions and candidate loci for evidence of selective sweeps. The scan of the EST sequences identified a previously undescribed polymorphism in ARHGAP15 in the Bta2 trypanotolerance QTL. The polymorphism affects gene function in vitro and could contribute to the observed differences in expression of the MAPK pathway in vivo. The expression data showed that TLR and MAPK pathways responded to infection, and the former contained TICAM1, which is within a QTL on Bta7. Genetic analyses showed that selective sweeps had occurred at TICAM1 and ARHGAP15 loci in African taurine cattle, making them strong candidates for the genes underlying the QTL. Candidate QTL genes were identified in other QTL by their expression profile and the pathways in which they participate.
Highlights
African bovine trypanosomiasis caused by Trypanosoma sp., is a major constraint on cattle productivity in sub-Saharan Africa
We screened an EST library for nonsynonymous SNP in genes within the quantitative trait loci (QTL); second, we used gene expression data from spleen, liver, and lymph nodes at nine time points to identify pathways that responded to infection and genes within those pathways that were in QTL; third, we undertook a genetic screen of 17 loci to discover evidence of selection; and fourth, we screened two QTL using published SNP data from the bovine HapMap for signatures of selection
To determine whether the ARHGAP15282H→P polymorphism might cause a difference in the rate of GTP hydrolysis by RAC1, the two alleles were expressed in vitro, and the rate of GTP hydrolysis was measured by following the change in absorbance at 360 nm caused by an increase in γPi abundance (Fig. 1)
Summary
African bovine trypanosomiasis caused by Trypanosoma sp., is a major constraint on cattle productivity in sub-Saharan Africa. We sequenced EST libraries from these two breeds to identify polymorphisms that might underlie previously identified quantitative trait loci (QTL), and we assessed QTL regions and candidate loci for evidence of selective sweeps. Genetic analyses showed that selective sweeps had occurred at TICAM1 and ARHGAP15 loci in African taurine cattle, making them strong candidates for the genes underlying the QTL. Ten major quantitative trait loci (QTL) that control trypanotolerance in cattle have been genetically mapped by our group using an F2 cross between Boran (zebu) and N’Dama cattle [6]. In the present study we have used transcriptome analyses to identify pathways that are responding to infection in the liver, spleen, and precrural lymph nodes We have combined these data with three different genetic analyses to identify mutations and signatures of selective sweeps in genes in those pathways that might. Anemia is the most prominent and consistent clinical sign of infection and is the main indicator for treatment rather than parasitemia, which is highly variable, in indicine cattle
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