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

塑造牛宿主防御并影响高和低免疫反应表型疾病结果的机制和基因

• 批准号: RGPIN-2017-03932
• 负责人: Mallard, Bonnie
• 金额: $ 2.48万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=685299
• 关键词: Mechanisms; Genes; Shape; Bovine; Host

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.****** ****

这项研究 * 解决了控制牛免疫力的遗传和表观遗传机制，以 * 更好地了解食品生产乳制品物种的抗病性。家畜疾病是现代农业的一个主要问题，影响着动物和人类的健康。免疫系统是由基因调控的细胞和分子组成的，它们具有控制对传染病反应的特殊能力。了解免疫系统内的生物学、遗传学和表观遗传学 * 关系有助于识别 * 具有上级免疫反应（IR）和增强抗病能力的个体。*为此，我们设计了第一个识别具有 * 升高的固有IR的牛的专利系统。凭借我们基于抗体的估计育种值（AMIR）和对1型和2型测试抗原的细胞介导的免疫应答（CMIR）来识别高（H）、低（L）和 * 平均（A）免疫应答者的独特能力，* 我们有一种新的工具来进一步检查基因，分子和途径，* 支持这些不同的表型。事实上，H应答者的疾病约为其他表型的一半，需要较少使用抗生素。由于这些IR性状是可遗传的（h2~25%），因此这些基因可以传递给它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以控制不同病原体的能力。识别具有增强的免疫能力的个体是一种自然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，我们对控制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，本研究的目标是：* 1-更好地了解H、A和L-IR表型牛在关键IR * 基因和分子的 * 性质（质量）和表达（数量）方面的差异。对这些差异的更好理解将导致更好地理解重要食品生产物种的抗病性，以及开发改善动物健康的新工具。* * 2-提高与这些IR表型相关的基因表达的知识，并了解调节其表达的DNA上的表观遗传标记。我们最近的数据显示了关键牛细胞因子的表观遗传调控，我们假设这将扩展到其他基因，并解释这些IR表型之间的一些变异。这种结合了遗传学和生物学的研究，利用具有已知IR表型的个体（基于其育种价值），为研究牛免疫力提供了独特的机会。这种方法允许知识扩展 * 关于决定免疫反应变化的各种因素 *，有助于确保动物的健康和福祉在一个重要的牛奶和肉类生产 * 物种。这些结果预计也与其他生物系统有关。****