RCUK-CONICYT: Utilising functional genomic variation for improved disease resistance in Chilean salmon aquaculture

传染病的经济负担阻碍了智利大西洋鲑鱼的可持续养殖生产，以及全球大多数水产养殖物种。通过选择性育种定向生产抗性种群是一个长期目标，将有助于在种群水平上控制疾病。通过先进的基因组学工具和技术，可以使用遗传标记数据来加速抗病性的遗传改良，以在育种计划中识别抗性亲本鱼。此外，大家族和大规模疾病挑战实验的实际可行性使鲑鱼成为发现宿主对病原体反应的基因和突变的极好模型。关注智利最棘手的两种疾病（海虱和鲑鱼立克次氏体综合征; SRS）在大西洋鲑鱼中的应用，该项目将利用这些基因组工具（i）发现影响养殖鲑鱼中宿主对传染病反应的基因和功能变体，以及（ii）改进基因组工具在育种计划中的使用，以通过基因组预测提高种群水平的抗病性，现在有大量的基因组工具箱可用于大西洋鲑鱼（例如先进的参考基因组组装和高密度遗传标记阵列），这提供了前所未有的资源来定位特定基因和支持宿主对病原体的反应的致病基因组变异。在拟议的项目中，我们将利用以前从两个大规模疾病挑战实验（海虱和SRS挑战）中收集的数据和样本。将生成所有动物的全基因组遗传标记数据，并将使用以下互补方法定位对每种疾病具有抗性的功能变体：（i）高功率全基因组关联分析;（ii）RNA-Seq最耐药（R）和最易感（S）个体的（基因表达）比较;（iii）结合功能注释的R个体池和S个体池的全基因组重测序。除了提高宿主对病原体反应的基础生物学知识外，这些结果在至少两个重要领域具有潜在的商业相关性。首先，所鉴定的基因及其编码的蛋白质是潜在的药物或疫苗靶点。其次，通过提高抗病基因组预测的准确性和成本效益，可以将基因组区域和特定变体纳入选择性育种方案。这些结果和技术将改善智利水产养殖业的疾病控制，并为通过选择性育种解决全球其他养殖水生物种的传染病问题提供范例。

The economic burden of infectious disease hinders sustainable farmed Atlantic salmon production in Chile, and most aquaculture species worldwide. Targeting production of resistant stocks by selective breeding is a long term goal, and will contribute to disease control at a population level. Enabled by advanced genomics tools and technology, genetic improvement of disease resistance can be accelerated using genetic marker data to identify resistant parent fish in breeding programs. Further, the large families and the practical feasibility of large scale disease challenge experiments make salmon excellent models to discover genes and mutations underpinning host response to pathogens. Focusing on two of Chile's most problematic diseases (sea lice and Salmon Rickettsial Syndrome; SRS) in Atlantic salmon, this project will harness these genomic tools to (i) discover genes and functional variants affecting host response to infectious disease in farmed salmon and (ii) improve the use of genomic tools in breeding programs to increase population-level disease resistance via genomic prediction, and reduce the negative impact of outbreaks.There is now a substantial genomic toolbox now available for Atlantic salmon (e.g. an advanced reference genome assembly and high density genetic marker arrays), this offers an unprecedented resource to locate specific genes and causative genomic variation underpinning host response to pathogens. In the proposed project, we will utilise data and samples previously collected from two large-scale disease challenge experiments (sea lice and SRS challenges. Genome-wide genetic marker data will be generated for all animals, and locating functional variants for resistance to each of the diseases will be achieved using the complementary approaches of (i) high power genome-wide association analysis; (ii) RNA-Seq (gene expression) comparison of the most resistant (R) and susceptible (S) individuals; (iii) Whole genome resequencing of pools of the R and pools of the S individuals combined with functional annotation. In addition to improving knowledge of the fundamental biology of host response to pathogens, these results have potential commercial relevance in at least two important fields. Firstly, the genes identified and their encoded proteins are potential drug or vaccination targets. Secondly, genomic regions and specific variants can be incorporated into selective breeding schemes, via improvement of the accuracy and cost-efficiency of genomic prediction of disease resistance. These results and techniques will lead to improved control of disease in Chilean aquaculture, and also provide a paradigm for tackling infectious disease problems via selective breeding in other farmed aquatic species worldwide.