Abstract
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: (i) The integrated haplotype score (iHS), (ii) the standardized log ratio of integrated site specific extended haplotype homozygosity between populations (Rsb), and (iii) the composite likelihood ratio (CLR) method to discover selective sweeps in the Sheko genome. We identify 99 genomic regions harboring 364 signature genes in Sheko. Out of the signature genes, 15 genes are selected based on their biological importance described in the literature. 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.
Highlights
Trypanosomiasis is a disease caused by uni-cellular protozoan parasites which affects the health of humans and livestock
We have identified the candidate causative genes, pathways, and master regulators associated with the adaptation of the Sheko breed to its natural environmental pressure
Most of the identified candidate signature genes, overrepresented pathways, and master regulator molecules were involved in immune tolerance, neurological dysfunction, and anemia
Summary
Trypanosomiasis is a disease caused by uni-cellular protozoan parasites which affects the health of humans and livestock. Trypanosomiasis is considered as an environmental pressure which plays a major role to create selection signatures in the genome and which is leading to breed formation (Kristjanson et al, 1999; Abebe, 2005; Yaro et al, 2016). These signs or traces of selection in the genome could be detected by using a “bottom-up” or a “from genotype to phenotype” approach (McGuire and McGuire, 2008). Combining methods for the detection of selection signature regions has been suggested as a means of increasing the power of the study compared to single analysis (e.g. Ma et al, 2015; Vatsiou et al, 2016)
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