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养殖的可持续生产，也阻碍了世界上大多数水产养殖物种的可持续生产。通过选择性育种以生产抗性种群为目标是一个长期目标，并将有助于在种群水平上控制疾病。在先进的基因组学工具和技术的支持下，利用遗传标记数据来识别育种计划中的抗性亲本鱼，可以加速抗病基因的改进。此外，大的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优秀模型。该项目重点关注智利大西洋鲑鱼的两种最具问题的疾病（海虱和鲑鱼立克次体综合征；SRS），将利用这些基因组工具：(i)发现影响养殖鲑鱼宿主对传染病反应的基因和功能变异；（ii）在育种计划中改进基因组工具的使用，通过基因组预测提高种群水平的抗病能力，并减少疫情的负面影响。现在有大量的基因组工具箱可供大西洋鲑鱼使用（例如，先进的参考基因组组装和高密度遗传标记阵列），这为定位宿主对病原体反应的特定基因和致病基因组变异提供了前所未有的资源。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，并使用以下补充方法定位对每种疾病的抗性的功能变体：(i)高功率全基因组关联分析；（ii）最耐药个体(R)和易感个体(S)的RNA-Seq（基因表达）比较；（iii）结合功能注释对R和S个体的池进行全基因组重测序。除了提高宿主对病原体反应的基本生物学知识外，这些结果至少在两个重要领域具有潜在的商业意义。首先，鉴定出的基因及其编码蛋白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异纳入选择性育种计划。这些结果和技术将改善智利水产养殖业的疾病控制，并为通过在世界范围内的其他养殖水生物种中进行选择性育种来解决传染病问题提供一个范例。

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.