Breeding Informatics Group, Department of Animal Sciences, Georg-August University, Margarethe von Wrangell-Weg 7, 37075 Göttingen, Germany.
Center for Integrated Breeding Research (CiBreed), Albrecht-Thaer-Weg 3, Georg-August University, 37075 Göttingen, Germany.
Int J Mol Sci. 2021 Jan 8;22(2):562. doi: 10.3390/ijms22020562.
African Animal Trypanosomiasis (AAT) is transmitted by the tsetse fly which carries pathogenic trypanosomes in its saliva, thus causing debilitating infection to livestock health. As the disease advances, a multistage progression process is observed based on the progressive clinical signs displayed in the host's body. Investigation of genes expressed with regular monotonic patterns (known as Monotonically Expressed Genes (MEGs)) and of their master regulators can provide important clue for the understanding of the molecular mechanisms underlying the AAT disease. For this purpose, we analysed MEGs for three tissues (liver, spleen and lymph node) of two cattle breeds, namely trypanosusceptible Boran and trypanotolerant N'Dama. Our analysis revealed cattle breed-specific master regulators which are highly related to distinguish the genetic programs in both cattle breeds. Especially the master regulators and found in this study, seem to influence the immune responses strongly, thereby susceptibility and trypanotolerance of Boran and N'Dama respectively. Furthermore, our pathway analysis also bolsters the crucial roles of these master regulators. Taken together, our findings provide novel insights into breed-specific master regulators which orchestrate the regulatory cascades influencing the level of trypanotolerance in cattle breeds and thus could be promising drug targets for future therapeutic interventions.
非洲动物锥虫病（AAT）由携带唾液中致病锥虫的采采蝇传播，从而对牲畜健康造成严重感染。随着疾病的发展，根据宿主体内显示的渐进性临床症状，观察到多阶段进展过程。研究具有规则单调模式表达的基因（称为单调表达基因（MEGs））及其主调控因子，可以为理解 AAT 疾病的分子机制提供重要线索。为此，我们分析了两种牛品种（易感染锥虫的博兰牛和抗锥虫的恩德马牛）的三种组织（肝脏、脾脏和淋巴结）中的 MEGs。我们的分析揭示了与区分两种牛品种的遗传程序高度相关的牛品种特异性主调控因子。特别是在这项研究中发现的调控因子和 ，似乎强烈影响免疫反应，从而分别影响博兰牛和恩德马牛的易感性和抗锥虫性。此外，我们的途径分析也支持了这些主调控因子的关键作用。总之，我们的研究结果为调控影响牛品种抗锥虫性水平的调控级联的品种特异性主调控因子提供了新的见解，这些主调控因子可能成为未来治疗干预的有希望的药物靶点。
