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养殖的可持续生产，也阻碍了全世界大多数水产养殖物种的可持续生产。通过选择育种来瞄准抗病种群的生产是一个长期目标，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，利用遗传标记数据在育种计划中识别抗病亲鱼，可以加速抗病的遗传改良。此外，大家庭和大规模疾病挑战实验的实际可行性使鲑鱼成为发现支持宿主对病原体反应的基因和突变的极佳模型。该项目聚焦于智利大西洋鲑鱼中问题最严重的两种疾病(海虱和鲑鱼立克次体综合征；SRS)，将利用这些基因组工具(I)发现影响养殖鲑鱼对传染病的宿主反应的基因和功能变异，(Ii)改进基因组工具在育种计划中的使用，通过基因组预测提高种群水平的抗病能力，并减少暴发的负面影响。现在大西洋鲑鱼有一个重要的基因组工具箱(例如，先进的参考基因组组合和高密度遗传标记阵列)，这为定位支持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，我们将利用先前从两个大规模疾病挑战实验(海虱和SRS挑战)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(I)高功率全基因组关联分析；(Ii)最抗性(R)和易感(S)个体的RNA-Seq(基因表达)比较；(Iii)R池和S个体池的全基因组重测序结合功能注释的互补方法，实现对每种疾病的抗性功能变异的定位。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，已确定的基因及其编码的蛋白是潜在的药物或疫苗靶点。其次，通过提高基因组抗病预测的准确性和成本效益，基因组区域和特定变异体可以被纳入选择育种计划。这些结果和技术将改善智利水产养殖业的疾病控制，并为通过在世界各地选择性繁殖其他养殖水生物种来解决传染病问题提供了一个范例。

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.