Genetic and expression analysis of cattle identifies candidate genes in pathways responding to Trypanosoma congolense infection
Open accessAbstract
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.
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During trypanosome infection, listlessness and emaciation are clinical signs of the infection.
“Furthermore, during trypanosome infection, listlessness and emaciation are some of the clinical signs of the infection (Nantulya, 1986; Steverding, 2008; Noyes et al., 2011).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Noyes et al., 2011
The Discussion and Conclusion (page unavailable) says trypanosome infection causes a generalized response with cachexia, which supports emaciation as a clinical sign. It does not identify listlessness as a sign; a search for listlessness, lethargy, and weakness found no supporting passage in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe E2F network as well as the Cdk1 and Cdk2 related pathways are associated with anemia, the most prominent and consistent clinical sign of trypanosome infection.
“The E2F network as well as the Cdk1 and Cdk2 related pathways are also associated with anemia which is the most prominent and consistent clinical sign of trypanosome infection (Kaminski et al., 2001; Dimova and Dyson, 2005; Noyes et al., 2011, Hu and Sun, 2016).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Noyes et al., 2011
The paper’s introductory section states that anemia is the most prominent and consistent clinical sign of infection. It does not link the E2F network or Cdk1/Cdk2-related pathways to anemia; its pathway table instead identifies other pathways and cell-cycle genes associated with anemia-related QTL. (LLM, conf=0.89)
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Cites
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- Authors
- Noyes, H., Brass, A., Obara, I., Anderson, S., Archibald, A. L., Bradley, D. G., Fisher, P., Freeman, A., Gibson, J., Gicheru, M., Hall, L., Hanotte, O., Hulme, H., McKeever, D., Murray, C., Oh, S. J., Tate, C., Smith, K., Tapio, M., Wambugu, J., Williams, D. J., Agaba, M., & Kemp, S. J.
- Affiliations
- University of Liverpool (GB)
- University of Manchester (GB)
- International Livestock Research Institute (KE)
- Roslin Institute (GB)
- Molecular Population Genetics, Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland;
- Trinity College Dublin (IE)
- Kenyatta University (KE)
- Royal Veterinary College (GB)
- National Institute of Animal Science (KR)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-05-18
- Volume
- 108
- Issue
- 22
- Pages
- 9304-9309
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3107286
- OpenAlex
- W2152476474
- Cited by
- 88
- References
- 1
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 3 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 5 · 2013: 5 · 2012: 2
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- EPubDev Repository (submittedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- CGSPace A Repository of Agricultural Research Outputs (Consultative Group for International Agricultural Research) (submittedVersion, other-oa)
- Kenyatta University Institutional Repository (Kenyatta University) (submittedVersion)
- Jukuri (Natural Resources Institute Finland (Luke)) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- RUNE (Research UNE) (submittedVersion)
- Funders
- Wellcome Trust (GR066764MA)
- Science Foundation Ireland (02/IN.1/B256)
- International Atomic Energy Agency
- International Livestock Research Institute
- Topics
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- Trypanosoma congolense, trypanotolerance, N'Dama cattle, Boran cattle, cattle, candidate genes, quantitative trait loci, TICAM-1, Toll-like receptor signaling, MAPK signaling, selective sweeps, transcriptome, host-pathogen response
- MeSH terms
- Alleles, Animals, Cattle, Cloning, Molecular, Gene Expression Regulation, Genotype, Models, Genetic, Molecular Sequence Data, Mutation, Polymorphism, Genetic, Tissue Distribution, Trypanosoma congolense, Trypanosomiasis, Bovine, Expressed Sequence Tags, Gene Expression Profiling, Quantitative Trait Loci
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