Characterization & exploitation of copy number variation in Atlantic salmon

大西洋鲑鱼水产养殖业每年为英国经济带来超过10亿英镑的价值，代表着一个迅速扩张的全球行业，在确保可持续增长方面面临着重大挑战。目前有一个重大的机会来开发基因工具，使其能够培育和生产具有良好特性的三文鱼，包括对疾病和寄生虫的高抵抗力，以及将环境可持续的饲料转化为快速生长和有营养价值的肉类的能力。这项研究的目的是描述大西洋鲑鱼遗传变异中一个未知的方面，称为拷贝数变异(CNV)，并在水产养殖中利用这一知识，重点是改善鱼类的生长和品质特征。CNV是染色体DNA的复制或缺失区域，是区分动物物种中个体的主要基因组变异形式之一。它们广泛地与功能基因有关，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的生物变异联系在一起。然而，尽管人们认识到CNV的重要性，但CNV从未被研究或应用于养殖的鳍鱼物种。这是一个重要的未开发资源，考虑到利用CNV作为有价值的水产养殖特征的标记可能获得的巨大潜在收益。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CNV，包括鱼在鱼片产量(可食用肉类的百分比)、肉裂口(生产过程中对肉类的损害)和肉类质地(可食用肉类的硬度)方面表现出很大的差异。这些特征与水产养殖业的盈利能力密切相关，影响到生产链的许多部分，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CNV，确定那些影响蛋白质编码基因的CNV。我们将使用独立的技术来彻底验证CNV，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来将CNV的特征面板与从更大的鲑鱼群体中获得的特征数据相关联。这里的目标是找出具有较高经济价值的肉质性状的特异性CNV标记。该项目将由阿伯丁大学(UoA)牵头，BBSRC支持的公司Xelect Ltd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，以及对不断增长的性状变异数据库的访问。Xelect的主要业务是开发用于三文鱼行业的遗传标记：该公司目前向世界各地的三文鱼卵生产商发放标记许可证。因此，该项目很可能导致CNV标记在全球范围内的开发和许可，包括已经提到的这些特征，以及未来可能出现的许多其他特征。UOA将受益于对大西洋鲑鱼基因组理解的重大进步，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还可能受益于与Xelect达成的一项合同协议，该协议将分享CNV标志许可所产生的部分财务特许权使用费。最后，由于CNV在鱼类中的特性通常很差，该项目将为CNV检测和开发的可行性提供概念验证，可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.