Applying genomics to establish mechanisms of disease resistance against a virus impacting on a globally farmed fish, the Common Carp (Cyprinus carpio)

随着全球人口的不断增长，对粮食的需求也在迅速增加。野生鱼类种群受到不可持续的过度开发，导致种群数量大幅下降，我们越来越依赖水产养殖(养鱼)来满足我们的全球需求。水产养殖提供了50%以上的捕捞水生生物供消费(超过7000万吨)，是数十亿人动物蛋白的重要来源。预计到2030年，水产养殖业的贡献率将上升到60%以上。然而，由于高种群密度、低种群遗传多样性以及与国际贸易相关的病原体传播增加，进一步的强化将增加疾病风险。传统上，农业中的疾病是通过杀虫剂/抗生素或疫苗来管理的。然而，这些只为疾病预防提供了一种短期和不可持续的解决方案，因为病原体/媒介可能会对药物产生抗药性，导致再次出现传染病。水产养殖的安全至关重要，因此必须开发新的疾病控制方法来确保全球食品安全。切割边缘DNA研究为帮助管理水产养殖中的疾病提供了一种途径。DNA为活细胞如何运作和相互作用提供了蓝图，DNA变异导致了我们观察到的生命的多样性，控制了关键的生物学特征，如外表、行为和疾病易感性。我的研究建议的目的是确定一种重要的水产养殖鱼种鲤鱼(鲤鱼)对致命的锦鲤疱疹病毒(KHV)具有抵抗力或易感的个体之间的DNA差异。重要的是，这是第一个描述鲤鱼和KHV全球DNA变异的项目，这是理解和管理疾病的重要组成部分。了解寄主防御系统和DNA中赋予抗病能力的可变基因组成分，可能会为水产养殖面临的问题提供部分解决方案，使农民能够创造出对当地病原体具有抵抗力的多样化种群。在BBSRC的研究中开发的分析工具可以应用于鲤鱼的其他新出现的传染病，这项研究可以作为其他水产养殖物种的蓝图。鲤鱼是全球第三大养殖鱼，每年价值数十亿英镑。除了作为数百万人的蛋白质来源的全球重要性外，它还在英国和欧洲被种植用于钓鱼和观赏品系(锦鲤)。仅在英国，鲤鱼渔业每年的产值就超过20亿英镑。KHV在全球范围内的快速传播给鲤鱼养殖业造成了巨大的经济损失。尽管鲤鱼的全球价值及其对病毒爆发的脆弱性，但基因知情的选择性育种是不存在的。这是该行业扩张的一个主要限制，令人惊讶的是，鉴于联合国粮食及农业组织(FAO)关于加强了解和控制鲤鱼疾病的强烈建议(2004年)，以及基因组技术现在可以应用于此类问题。通过测试来自世界各地的个体促进抗药性的基因变异，并了解病毒多样性的地理模式，鲤鱼可以由农民人工选择，以生产对当地致命病毒株感染具有强大抵抗力的鱼。纯粹集中在单一宿主和病毒菌株的受控实验室感染试验上的研究，将产生与现实世界水产养殖几乎没有相关性的结果，因为现实世界中包括许多宿主和病原体菌株。因此，我将开创一项全球计划，在鲤鱼水产养殖中进行免疫基因组学知情选择性育种，这将有助于促进这种重要鱼种的食品安全。

With a growing global population, the demand for food is increasing rapidly. Wild fish stocks have been subjected to unsustainable over exploitation, resulting in major population declines, and we are increasingly reliant on aquaculture (the farming of fish) to meet our global needs. Aquaculture provides over 50% of the supply of harvested aquatic organisms for consumption (over 70 million tons), and is an important source of animal protein for billions of people. The contribution of aquaculture is predicted to rise to over 60% by 2030. However, further intensification will increase the risk of disease due to high stocking densities, low genetic diversity in brood-stocks, and increased pathogen dispersal associated with international trade. Traditionally, disease in farming is managed by pesticides/antibiotics or vaccines. These however offer only a short term and unsustainable solution to disease prevention as pathogens/vectors can evolve resistance to medications, resulting in re-emerging infectious diseases. The security of aquaculture is of paramount importance and so new disease control methods must be developed to ensure global food security.Cutting edge DNA research offers an approach to help manage disease in aquaculture. DNA provides the blueprint for how living cells function and interact, and DNA variation results in the diversity of life we observe, controlling key biological characteristics such as appearance, behaviour, and disease susceptibility. The objective of my research proposal is to identify the differences in DNA between individuals of an important aquaculture fish species, the Common Carp (Cyprinus carpio), that are either resistant or susceptible to the deadly Koi Herpesvirus (KHV). Importantly, this is the first project to characterize global DNA variation in carp and KHV, which is an essential component in understanding and managing disease. Understanding host defence systems and the variable genomic components in the DNA that confer disease resistance, may offer part of the solution to the problems facing aquaculture, enabling farmers to create diverse brood-stocks with resistance to local pathogens. The analysis tools developed in this BBSRC fellowship can be applied to other emerging infectious diseases of carp, and the research can be used as a blueprint for other species in aquaculture.Common Carp is the third most farmed fish globally and is worth billions of pounds per annum. Aside from its global importance as a protein source for millions of people, it is also farmed in the UK and Europe for angling and as an ornamental strain (Koi). Alone, the carp fishing industry in the UK is worth over two billion pounds per annum. Huge financial losses have occurred in the carp industry through the rapid global spread of KHV. Despite the global value of carp and its vulnerability to viral outbreaks, genetically informed selective breeding is non-existent. This is a major limitation for the expansion of the industry and surprising given strong recommendations from the Food and Agriculture Organization (FAO) for intensified understanding and control of carp diseases (2004), and the fact that genomic techniques are now available to apply to such problems.By testing individuals from around the world for gene variants that promote resistance, and understanding the geographic patters of viral diversity, carp can be artificially selected by farmers to produce fish that are robust to infection from local strains of deadly viruses. Research focused purely on controlled laboratory infection trials in single host and viral strains, will produce findings that may be of little relevance to real-world aquaculture that comprises many strains of both host and pathogen. As such, I will pioneer a global plan for immuno-genomics informed selective breeding in carp aquaculture, which will contribute to promoting food security in this important species of fish.