Genetic and expression analysis of cattle identifies candidate genes in pathways responding to Trypanosoma congolense infection

• DOI: 10.1073/pnas.1013486108
• Publication Date: 2011-05-19T04:44:34Z
• Authors: Harry Noyes; Andy Brass; Isaiah Obara; Susan Anderson; Alan L. Archibald; Dan G. Bradley; Paul Fisher; Abigail Freeman; John Gibson; Michael Gicheru; Laurence Hall; Olivier Hanotte; Helen Hulme; Declan McKeever; Caitriona Murray; Sung Jung Oh; Catriona Tate; Ken Smith; Miika Tapio; John Wambugu; Diana J. Williams; Morris Agaba; Stephen J. Kemp
• Keywords: 570; trypanosomosis; Genotype; Trypanosoma congolense; Immunology; Molecular Sequence Data; Quantitative Trait Loci; Ko; bovine trypanosomiasis; 630; Afrikka; Nagana; 03 medical and health sciences; /dk/atira/pure/subjectarea/asjc/1000; Genetics; Animals; Tissue Distribution; geeniekspressio; nagana; Cloning, Molecular; General; Alleles; Expressed Sequence Tags; 2. Zero hunger; 0303 health sciences; geenit; Polymorphism, Genetic; kestävä maatalous; Models, Genetic; Trypanosomosis; Gene Expression Profiling; Trypanosomiasis, Bovine; Sustainable agriculture; positional cloning; sustainable agriculture; kloonaus; Gene Expression Regulation; Positional cloning; Mutation; Genes & Society; Cattle

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.