Dissecting structural and functional genomic factors underlying the resistance of Atlantic salmon fry to infectious pancreatic necrosis

感染性胰腺坏死（IPN）是目前影响英国鲑鱼养殖业的最严重的病毒性疾病。IPN是由感染性胰腺坏死病毒（IPNV）引起的，它会导致受感染鲑鱼的胰腺、肠道和肝脏受损。据估计，IPN给英国水产养殖业造成的年度经济损失为5-10百万英镑。存活的鲑鱼可以成为感染的携带者，然后将疾病传播给其他易感鱼类，使养殖和野生鱼类的IPN持续存在。大西洋鲑鱼在其整个生命周期中对IPNV感染的易感性各不相同。新孵化的鲑鱼，即鱼苗，生活在淡水中。它们特别容易受到IPN的影响，在孵化场流行的典型特征是突然大规模死亡。随后，在小鲑鱼的生命周期阶段，鲑鱼改变了它们的生理机能，准备从淡水转向海水。鲑鱼幼崽（更具体地说，幼崽）在海水转移后的2 - 10周内易患IPN。某些家族表现出对IPN的遗传抗性，我们以前已经表明，可以使用遗传标记来识别耐药和易感的鲑鱼幼崽。然而，与IPN耐药性有关的一些问题仍未得到解答。特别是，虽然有证据表明这些遗传影响在鲑鱼生命周期的不同阶段是一致的，即在小鲑鱼和鱼苗中是一致的，但这并不是决定性的。此外，还不知道哪些特定的基因和分子途径是对IPN的遗传抗性的基础。为了回答这些问题，我们有三个主要目标。首先，我们将确认和描述鲑鱼鱼苗对IPN的遗传抗性，并确定影响抗性的特定基因组区域。其次，我们将确定感染后，哪些鲑鱼基因在基因抗性和易感鱼之间的作用不同。这将使我们深入了解哪些生物机制导致了抗性的遗传差异。第三，我们将汇集所有结果，以确定可能导致遗传抗性的特定基因。这项研究的结果将通过提供遗传标记测试来在鲑鱼生命周期的早期识别抗IPN的鱼，从而加强鲑鱼育种计划，从而降低成本并减少患病鱼的数量。对确定IPN耐药性的关键基因的进一步了解也可能有助于合理制定针对IPNV感染的控制措施，包括疫苗接种，并提供敏感的诊断测试。该项目将由罗斯林研究所和斯特林大学水产养殖研究所的研究人员承担，并将利用韦茅斯环境、渔业和水产养殖科学中心的设施和专业知识。这些英国研究人员将与加拿大的大西洋鲑鱼基因组研究项目（GRASP）合作，提供世界领先的鲑鱼基因组资源。创新的鲑鱼养殖公司Landcatch Natural Selection的参与，确保了研究结果的直接商业应用有一条明确的路线。该项目与BBSRC支持的旨在分析免疫功能和疾病机制的研究相关，并且符合与传染病控制相关的优先事项，包括宿主抗感染的遗传学。

Infectious pancreatic necrosis (IPN) is currently the most serious viral disease affecting the UK salmon farming industry. IPN is caused by infectious pancreatic necrosis virus (IPNV) which results in damage to the pancreas, intestine and liver of infected salmon. The annual economic loss to the UK aquaculture industry from IPN is estimated to be £5-10 million. Surviving salmon can become carriers of infection and then spread the disease to other susceptible fish, perpetuating IPN in both farmed and wild fish populations. Atlantic salmon vary in susceptibility to IPNV infection as they proceed through their life cycle. Newly-hatched salmon, i.e. fry, live in freshwater. They are particularly susceptible to IPN, and epidemics in hatcheries are typified by sudden large-scale mortalities. Subsequently, at the smolt life cycle stage, salmon alter their physiology in readiness for the move from freshwater to seawater. Salmon smolts (more specifically post-smolts) are susceptible to IPN during a period lasting from 2 - 10 weeks after seawater transfer. Certain families show genetic resistance to IPN, and we have previously shown that it is possible to identify resistant and susceptible salmon smolts using genetic markers. However, a number of questions relating to IPN resistance remain unanswered. In particular, whilst there is evidence that these genetic effects are consistent across different stages of the salmon life-cycle, i.e. consistent in smolts and fry, it is not conclusive. Furthermore, it is not known which specific genes and molecular pathways underlie genetic resistance to IPN. In an attempt to answer these questions we have three major objectives. First, we will confirm and describe genetic resistance to IPN in salmon fry and identify specific genomic regions affecting resistance. Second, we will determine which salmon genes work differently between genetically resistant and susceptible fish following infection. This will give insight into which biological mechanisms lead to genetic differences in resistance. Third, we will bring together all of the results to identify specific genes that may be responsible for the genetic resistance. The results of the study will strengthen salmon breeding programmes by providing genetic marker tests to identify IPN resistant fish early in the salmon life-cycle, thus reducing costs and reducing the number of diseased fish. The improved knowledge of the crucial genes defining IPN resistance may also contribute to the rational development of control measures against IPNV infections, including vaccination, and provide sensitive diagnostic tests. This project will be undertaken by researchers based at the Roslin Institute and the Institute of Aquaculture at Stirling University, and will also utilise the facilities and expertise of the Centre for Environment, Fisheries and Aquaculture Science, Weymouth. These UK researchers will collaborate with the Genomic Research on Atlantic Salmon Project (GRASP) in Canada, providing access to world-leading salmon genomics resources. The involvement of the innovative salmon breeding company Landcatch Natural Selection ensures that a clear route exists for the immediate commercial application of the results. This project is relevant to research supported by the BBSRC aimed at the analysis of the mechanisms of immune function and disease, and fits the priority relating to the control of infectious diseases, including the genetics of host resistance to infection.