非洲动物锥虫病(AAT)是一种被忽视的热带病,通过矢量采采蝇传播,携带传染性锥虫。在他们的唾液中。特别是,这种寄生虫病影响牲畜的健康,从而对农民施加经济约束,每年花费数十亿美元,特别是在撒哈拉以南非洲国家。主要考虑AAT疾病是一个多阶段的进展过程,我们之前进行了上游分析以鉴定转录因子(TFs),他们的合作,过度代表的途径和主监管者。然而,下游分析,包括效应器,相应的基因表达谱及其与调节性SNPs(rSNPs)的关联,尚未建立。因此,在这项研究中,我们的目标是研究rSNP的复杂相互作用,关于AAT疾病进展的相应基因表达和下游效应子,基于两个牛品种:锥虫易感的Boran和锥虫耐受性N\'Dama。我们的发现提供了对涉及几种信号转导途径调节的效应子的机制见解,从而区分与牛品种免疫反应有关的分子机制。效应子及其相关基因(特别是MAPKAPK5、CSK、DOK2,RAC1和DNMT1)可能是有前途的候选药物,因为它们在两个牛品种中协调了各种下游调控级联反应。
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.