African Animal Trypanosomiasis (AAT) is a neglected tropical disease and spreads by the vector tsetse fly, which carries the infectious Trypanosoma sp. in their saliva. Particularly, this parasitic disease affects the health of livestock, thereby imposing economic constraints on farmers, costing billions of dollars every year, especially in sub-Saharan African countries. Mainly considering the AAT disease as a multistage progression process, we previously performed upstream analysis to identify transcription factors (TFs), their co-operations, over-represented pathways and master regulators. However, downstream analysis, including effectors, corresponding gene expression profiles and their association with the regulatory SNPs (rSNPs), has not yet been established. Therefore, in this study, we aim to investigate the complex interplay of rSNPs, corresponding gene expression and downstream effectors with regard to the AAT disease progression based on two cattle breeds: trypanosusceptible Boran and trypanotolerant N\'Dama. Our findings provide mechanistic insights into the effectors involved in the regulation of several signal transduction pathways, thereby differentiating the molecular mechanism with regard to the immune responses of the cattle breeds. The effectors and their associated genes (especially MAPKAPK5, CSK, DOK2, RAC1 and DNMT1) could be promising drug candidates as they orchestrate various downstream regulatory cascades in both cattle breeds.

African Animal Trypanosomiasis (AAT) is a disease caused by pathogenic trypanosomes which affects millions of livestock every year causing huge economic losses in agricultural production especially in sub-Saharan Africa. The disease is spread by the tsetse fly which carries the parasite in its saliva. During the disease progression, the cattle are prominently subjected to anaemia, weight loss, intermittent fever, chills, neuronal degeneration, congestive heart failure, and finally death. According to their different genetic programs governing the level of tolerance to AAT, cattle breeds are classified as either resistant or susceptible. In this study, we focus on the cattle breeds N\'Dama and Boran which are known to be resistant and susceptible to trypanosomiasis, respectively. Despite the rich literature on both breeds, the gene regulatory mechanisms of the underlying biological processes for their resistance and susceptibility have not been extensively studied. To address the limited knowledge about the tissue-specific transcription factor (TF) cooperations associated with trypanosomiasis, we investigated gene expression data from these cattle breeds computationally. Consequently, we identified significant cooperative TF pairs (especially D B P - P P A R A and D B P - T H A P 1 in N\'Dama and D B P - P A X 8 in Boran liver tissue) which could help understand the underlying AAT tolerance/susceptibility mechanism in both cattle breeds.

Immune response to infections has been shown to be mediated by genetic diversity in pattern recognition receptors, leading to disease tolerance or susceptibility. We elucidated naturally occurring variations within the bovine CD14 gene promoter in trypanosome-tolerant (N\'Dama) and susceptible (White Fulani) cattle, with genomic and computational approaches. Blood samples were collected from White Fulani and N\'Dama cattle, genomic DNA extracted and the entire promoter region of the CD14 gene amplified by PCR. We sequenced this region and performed in silico computation to identify SNP variants, transcription factor binding sites, as well as micro RNAs in the region. CD14 promoter sequences were compared with the reference bovine genome from the Ensembl database to identify various SNPs. Furthermore, we validated three selected N\'Dama specific SNPs using custom Taqman SNP genotyping assay for genetic diversity. In all, we identified a total of 54 and 41 SNPs at the CD14 promoter for N\'Dama and White Fulani respectively, including 13 unique SNPs present in N\'Dama only. The significantly higher SNP density at the CD14 gene promoter region in N\'Dama may be responsible for disease tolerance, possibly an evolutionary adaptation. Our genotype analysis of the three loci selected for validation show that mutant alleles (A/A, C/C, and A/A) were adaptation profiles within disease tolerant N\'Dama. A similar observation was made for our haplotype analysis revealing that haplotypes H1 (ACA) and H2 (ACG) were significant combinations within the population. The SNP effect prediction revealed 101 and 89 new transcription factor binding sites in N\'Dama and White Fulani, respectively. We conclude that disease tolerant N\'Dama possessing higher SNP density at the CD14 gene promoter and the preponderance of mutant alleles potentially confirms the significance of this promoter in immune response, which is lacking in susceptible White Fulani. We, therefore, recommend further in vitro and in vivo study of this observation in infected animals, as the next step for understanding genetic diversity relating to varying disease phenotypes in both breeds.

Background: Animal trypanosomosis is a major cause of economic loss in livestock production in Africa. A suggested control measure is to use breeds with traits of trypanotolerance. The study examines the effect of natural Trypanosoma vivax challenge on haematological parameters in two trypanotolerant cattle [N\'Dama and West African Short Horn (WASH)] herds. Methods:T. vivax-specific primers were used to diagnose T. vivax infection in an N\'Dama herd at Cape Coast in southern Ghana and a WASH herd at Chegbani in northern Ghana from May to July 2011 in a cross-sectional study. Levels of haematological parameters comprising packed cell volume (PCV), haemoglobin (Hb) concentration and total red blood cell (RBC) and white blood cell (WBC) counts; differential WBC counts (neutrophils, lymphocytes, eosinophils, monocytes and basophils); and RBC indices of mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were determined in blood samples and then compared between infected and uninfected cattle. Results: We found that haematological indices for infected and uninfected animals in both breeds were within the normal range. However, the mean PCV values for T. vivax-infected WASH and N\'Dama were lower in infected compared to uninfected animals. The difference was significant ( p< 0.05) in N\'Dama but not in WASH. The RBC indices were higher in infected N\'Dama compared to infected WASH with a significant difference in total RBC ( p < 0.05). Conclusion: We conclude from our findings that despite the presence of infection by T. vivax, N\'Dama and WASH cattle maintained their haematological parameters within acceptable normal ranges, and this underscores the need for routine diagnosis and treatment so that such trypanotolerant cattle do not serve as potential reservoirs of trypanosome parasites.

Many breeding programs have been implemented in developing countries, many of which have been unsuccessful. To better understand the failure of these breeding programs, it is proposed to analyze their adequacy with innovations that are actually adopted by smallholders. The proposed methodology takes account of these innovations, the reasons for their adoption and the objectives of livestock keeping. The N\'Dama cattle-breeding program in Senegal was used as a case study. Surveys were carried out among 54 farmers: 27 breeders who participated in this program, 17 of whom recently resigned, and 27 breeders who have never participated. Feeding was the most frequently cited area of innovation, followed by infrastructure. Genetics, animal health and reproduction held the third rank. Milk production appeared as an important objective of breeders, although the context remains one of strong multifunctionality. Principal component analysis highlighted three categories of breeders according to the innovations they adopted: institutional, modernizing, and integrating innovators. The groups of institutional and modernizing innovators dominate, gathering each 41% of the farmers. In the first category, breeders have organized themselves in an association and use N\'Dama sires, livestock aiming at an insurance objective. In the second category, artificial insemination with exotic breeds and other technical innovations (cowshed, vaccination, urea treatment of straw) are used to improve production of milk and meat. The third group is termed \'integrating innovators,\' since their innovations aim at integrating livestock and crop production. Gathering 18% of the sampled breeders, this group presents intermediate features between the two previous groups, using animals as draught power and for manure production. These results indicate that a process of intensification is at play and that the genetic improvement through the selection of N\'Dama cattle for production criteria does not meet the breeders\' demand. However, the N\'Dama\'s adaptive traits justify its use as part of the breeding strategy of farmers, either in pure-breeding or in crossbreeding. The study thus tends to show the interactive link between genetic improvement and other innovations. It suggests that the success of a breeding program depends on its adequate positioning within the set of innovations adopted by breeders and proposes a method to inform breeding programs accordingly.

Many local livestock breeds in developing countries are being replaced by exotic breeds, leading to a loss of genetic resources. In southern Mali, for the past two decades, a trend towards increasing crossbreeding between the trypanotolerant N\'Dama cattle and the trypano-susceptible Fulani Zebu cattle has been taking place. A survey with 160 farmers owning a cattle herd was carried out in southern Mali to investigate their production objectives, as well as trait and breed preferences and correlated socio-economic determinants in order to understand farmers\' breeding decisions and to identify comparative advantages of three breed groups (N\'Dama, Fulani Zebu and crossbreds) raised in the study area. Data were analyzed using an exploded logit model. The reasons for raising cattle, as well as trait and breed preferences reflected the multiple objectives of the farmers. Draught power and savings were the most important production objectives. Productive traits were ranked highest; farmers reported large body size as the most preferred trait, followed by fertility, draught ability and milk yield. Crossbreds were the favored breed group. Breed preferences were mainly explained by \'resistance to disease\' for N\'Dama cattle and \'high market price\' for Fulani Zebu and crossbred cattle. Production objectives, trait and breed preferences were mainly influenced by farmer group (local farmers and settled transhumants). Local farmers put comparatively more emphasis on livestock functions linked to crop production such as draught power. They had a higher preference for traction ability as a selection trait and preferred N\'Dama over Fulani Zebu cattle. Settled transhumants emphasized milk yield as a selection trait and preferred Fulani Zebu over N\'Dama. The results indicate that the trend towards more crossbreeding will continue putting the N\'Dama breed under high risk of genetic dilution in southern Mali. The N\'Dama cattle remain a valuable breed due to their adaptive traits such as disease and drought tolerance and their good traction ability, fulfilling the diverse objectives of local farmers. Crossbreeding was found to be a promising breeding strategy, which might contribute to the maintenance of the local breed, provided that breeding schemes are thoroughly planned and organized.