Characterization & exploitation of copy number variation in Atlantic salmon

大西洋鲑鱼养殖业每年对英国经济的价值超过10亿英镑，代表着一个快速扩张的全球产业，面临着确保可持续增长的重大挑战。目前有一个开发遗传工具的重大机会，可以培育和生产具有有利特性的鲑鱼，包括对疾病和寄生虫的高抵抗力，以及将环境可持续的饮食转化为快速生长和营养价值高的肉的能力。这项研究的目的是表征大西洋鲑鱼遗传变异的一个未被研究的方面，即拷贝数变异（CNV），并将这一知识应用于水产养殖，重点是改善肉的生长和品质特征。CNVs是染色体DNA的复制或缺失区域，是动物物种中区分个体的基因组变异的主要形式之一。它们与功能基因广泛相关，许多科学数据将它们与人类和其他物种的一系列疾病或其他重要生物变异联系起来。然而，尽管CNVs具有公认的重要性，但它们从未在养殖鱼类中进行研究或应用。考虑到利用CNVs作为有价值的水产养殖性状标记可能获得的巨大潜在收益，这是一项重大的未开发资源。我们的项目将利用深度DNA测序技术和最新的计算方法来检测来自许多遗传背景的大西洋鲑鱼的CNVs，包括在鱼片产量（可食用肉的百分比）、肉间隙（生产过程中对肉的损害）和肉质地（可食用肉的硬度）方面表现出巨大差异的鱼。这些特征与水产养殖的盈利能力密切相关，影响到生产链的许多环节，最终导致超市货架上的消费者。因此，我们将描述跨越基因组的鲑鱼CNVs，确定那些影响蛋白质编码基因的CNVs。我们将使用独立的技术来彻底验证CNVs，并确定它们对基因表达的影响——这是衡量动物功能重要性的重要指标。我们项目的最后一步将涉及使用统计方法将CNVs的特征面板与从更大的鲑鱼群体中获取的特征数据联系起来。这里的目标是鉴定具有高经济价值的肉性状的特异性CNV标记。该项目将由阿伯丁大学（UoA）与Xelect有限公司（BBSRC支持的公司）作为其工业合作伙伴。Xelect将提供一系列鲑鱼种群，遗传学和性状鉴定方面的专业知识，以及不断增长的性状变异数据库。Xelect的主要业务是开发用于鲑鱼产业的遗传标记：该公司目前向世界各地的鲑鱼卵生产商许可标记。因此，该项目可能会导致全球范围内CNV标记的开发和许可，包括已经提到的性状，以及未来可能出现的许多其他性状。UoA将受益于对大西洋鲑鱼基因组理解的重大进展，这除了具有应用价值外，还与许多其他学术研究背景具有很强的相关性。UoA还可以从与Xelect签订的合同协议中获益，Xelect将分享CNV标记物许可产生的部分财务特许权使用费。最后，由于CNV在鱼类中的特征通常很差，该项目将为CNV检测和开发的可行性提供概念验证，这可以应用于其他具有社会重要性的物种。

Atlantic salmon aquaculture is worth more than 1 billion pounds sterling annually to the UK economy and represents a rapidly expanding global industry facing major challenges to ensure sustainable growth. There is currently a major opportunity to develop genetic tools that allow the breeding and production of salmon with favourable traits, including high resistance to disease and parasites and the capacity to convert environmentally sustainable diets into fast-growing and nutritionally-valuable flesh. The objective of this studentship is to characterize an unstudied aspect of genetic variation in Atlantic salmon called copy number variation (CNV) and to exploit this knowledge in aquaculture, focussing on improved flesh growth and quality characteristics.CNVs are duplicated or deleted regions of chromosomal DNA and one of the main forms of genomic variation distinguishing individuals within animal species. They are widely associated with functional genes and much scientific data links them to a range of diseases or other important biological variation in humans and other species. However, despite their recognised importance, CNVs have never been researched or applied in farmed finfish species. This represents a major untapped resource considering the large potential gains that might be made using CNVs as markers for valuable aquaculture traits. Our project will exploit deep DNA sequencing technology and the latest computational methods to detect CNVs in Atlantic salmon from many genetic backgrounds, including fish showing large variation in fillet yield (the percentage of edible flesh), flesh gaping (damage to the flesh arising during production) and flesh texture (the firmness of edible flesh). These traits are strongly linked to the profitability of aquaculture, impacting many parts of the production chain that ultimately leads to the consumer at the supermarket shelf.Thus, we will characterize salmon CNVs spanning the genome, determining those affecting protein-coding genes. We will use independent technologies to thoroughly validate the CNVs and to establish their effects on gene expression - an important measure of functional importance for the animal. The final step of our project will involve using statistical methods to associate a characterized panel of CNVs with trait data taken from a much larger group of salmon. The objective here will be to identify specific CNV markers for flesh traits which have high economic value. The project will be led by the University of Aberdeen (UoA) with Xelect Ltd - a BBSRC supported company - as its industrial partner. Xelect will provide a range of salmon populations, expertise in genetics and trait identification, plus access to a growing database of trait variation. The main business of Xelect is to develop genetic markers for use in the salmon industry: the company currently licenses markers to salmon egg producers across the world. Therefore, the project is likely to lead to the development and licensing of CNV markers globally, both for the traits mentioned already, and potentially many others in the future. The UoA will benefit from a major advancement in understanding of the Atlantic salmon genome, which, in addition to having applied value, has strong relevance in many other academic research contexts. The UoA may also benefit from a contractual agreement with Xelect to share a portion of financial royalties coming from licensing of CNV markers. Finally, as CNVs are very poorly characterized in fish generally, the project will provide proof-of-concept on the feasibility of CNV detection and exploitation, which can be applied in other species of societal importance.