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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01095

Identification of Candidate Signature Genes and Key Regulators Associated with Trypanotolerance in the Sheko Breed

  • 1University of Göttingen, Germany
  • 2International Livestock Research Institute, Ethiopia

African Animal Trypanosomiasis (AAT) is caused by a protozoan parasite that affects the health of livestock. Livestock production in Ethiopia is severely hampered by AAT and various controlling measures were not successful to eradicate the disease. AAT affects the indigenous breeds in varying degrees. However, the Sheko breed shows better trypanotolerance than other breeds. The tolerance attributes of Sheko are believed to be associated with its taurine genetic background but the genetic controls of these tolerance attributes of Sheko are not well understood. In order to investigate the level of taurine background in the genome, we compare the genome of Sheko with that of 11 other African breeds. We find that Sheko has an admixed genome composed of taurine and indicine ancestries. We apply three methods to discover selective sweeps in the Sheko genome. We identify 99 genomic regions harboring 364 signature genes in Sheko using (i) the integrated haplotype score (\textit{iHS}), (ii) the standardized log ratio of integrated site specific extended haplotype homozygosity (EHH) values between populations (\textit{Rsb}) and (iii) the composite likelihood ratio (CLR) method. We find 15 highly significant genes associated with trypanotolerance based on the literature survey. Most of these gene regions show strong selective sweep reflecting a strong selection pressure. We also identify 13 overrepresented pathways and 10 master regulators in Sheko using the TRANSPATH database in the geneXplain platform. Most of the pathways are related with oxidative stress responses indicating a possible selection response against the induction of oxidative stress following trypanosomiasis infection in Sheko. Furthermore, we present for the first time the importance of master regulators involved in trypanotolerance not only for the Sheko breed but also in the context of cattle genomics. Our finding shows that the master regulator Caspase is a key protease which plays a major role for the emergence of adaptive immunity in harmony with the other master regulators. These results suggest that designing and implementing genetic intervention strategies is necessary to improve the performance of susceptible animals. Moreover, the master regulatory analysis suggests potential candidate therapeutic targets for the development of new drugs for trypanosomiasis treatment.

Keywords: Trypanosomiasis, selection signature, candidate signature genes, Master regulators, overrepresented pathways

Received: 03 Jun 2019; Accepted: 11 Oct 2019.

Copyright: © 2019 Schmitt, Mekonnen, Gültas, Effa and Hanotte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Armin O. Schmitt, University of Göttingen, Göttingen, 37073, Lower Saxony, Germany,