Mechanisms and Genes that Shape Bovine Host Defence and Impact Disease Outcomes in High and Low Immune Responder Phenotypes

这项研究 阐述了控制牛免疫的遗传和表观遗传机制 更好地了解产粮乳品品种的抗病能力。 家畜疾病是影响现代农业发展的主要问题。 动物和人类健康。免疫系统由遗传基因组成 具有特殊能力控制反应的受调控细胞和分子 传染病。理解生物学、遗传学和表观遗传学 免疫系统内的关系可以帮助识别 具有优越的免疫反应(IR)和增强的抗病能力的个人。 为此，我们设计了第一个识别牛的专利系统 固有IR升高。凭借我们独特的识别高音(H)、低音(L)和 平均(A)免疫应答者，基于它们对1型和2型测试抗原的抗体(AMIR)和细胞介导的免疫反应(CMIR)的估计繁殖值； 我们有了一种新的工具来进一步检查基因、分子和途径 支撑了这些不同的表型。事实上，H应答者的疾病大约有其他表型的一半，需要较少使用抗生素。由于这些IR性状是可遗传的(H2~25%)，这些基因可以遗传给他们的后代，以改善后代。 免疫系统独特地具有改变和适应宿主反应的能力，以控制不同的病原体。识别免疫能力增强的个体，是一种自然地改善一系列先天和适应性防御机制，以及改善整体动物健康的方法。然而，对控制H、L或A免疫反应的基因、遗传途径或表观遗传影响知之甚少，需要进一步研究。 因此，这样做的目标是 研究内容包括： 1-为了更好地了解H、A和L牛的表型如何以及为什么不同 关键信息检索的性质(质)和表达(量) 基因和分子。对这些差异的更好理解将导致 更好地理解重要粮食生产物种的抗病能力 作为改善动物健康的新工具的开发。 2-提高与这些IR表型相关的基因表达的知识，并了解调控其表达的DNA上的表观遗传标记。 我们最近的数据显示了关键的牛细胞因子的表观遗传调节，我们 假设这将延伸到其他基因，并解释一些 这些IR表型之间的差异。 这项结合了遗传学和生物学的研究，利用了已知的 根据它们的育种价值，IR表型提供了独特的 研究牛免疫的机会。这种方法允许知识扩展 关于决定免疫反应性变化的各种因素 在重要的牛奶和肉类生产中帮助确保动物健康和福祉 物种。预计这些结果也将与其他生物系统有关。

This research addresses genetic and epigenetic mechanisms that control bovine immunity to better understand disease resistance of food-producing dairy species. Diseases of livestock are a major problem for modern agriculture affecting animal and human health. The immune system is composed of genetically regulated cells and molecules with specialized ability to control response to infectious disease. Understanding the biological, genetic and epigenetic relationships within the immune system can facilitate identification of individuals with superior immune response (IR) and enhanced disease resistance. To that end, we devised the first patented system identifying cattle with elevated inherent IR. With our unique ability to identify high (H), low (L) and average (A) immune responders based on Estimated Breeding Values of their antibody (AMIR) and cell-mediated immune response (CMIR) to type 1 and 2 test antigens, we have a novel tool to further examine the genes, molecules and pathways that underpin these diverse phenotypes. In fact, H responders have about half of the disease of other phenotypes requiring less use of antibiotics. Since these IR traits are heritable (h2~25%) these genes can be passed on to their offspring to improve future generations. The immune system uniquely has the ability to vary and adapt host responses to control diverse pathogens. Identifying individuals with enhanced immuno-competence, is a method to naturally improve a range of innate and adaptive defense mechanisms, as well as to improve overall animal health. However, little is known about the genes, genetic pathways, or epigenetic influences that control H, L, or A immune responses and require further investigation. Therefore the goals for this research are: 1 - To better understand how and why cattle with H, A and L-IR phenotypes differ in the nature (quality) and expression (quantity) of key IR genes and molecules. Improved understanding of these differences will lead to better comprehension of disease resistance in important food-producing species, as well as development of new tools to improve animal health. 2- To improve knowledge of gene expression associated with these IR phenotypes and learn about the epigenetic marks on the DNA that regulate their expression. Our recent data show epigenetic regulation of key bovine cytokines and we hypothesize this will extend to other genes and account for some of the variation between these IR phenotypes. This combined genetic and biological research, utilizing individuals with known IR phenotypes based on their breeding values, provides a unique opportunity to study bovine immunity. This approach allows knowledge expansion regarding the various factors which dictate variation in immune responsiveness helping to ensure animal health and well-being in an important milk and meat producing species. These results are expected to also relate to other biological systems.