Genome editing for quantitative traits in livestock

该项目将开发新的实验室技术和新的育种方法，以通过基因组编辑来加强牲畜育种计划。基因组编辑被用来增加繁殖群体中携带有益基因组变异的动物的数量。这使得保存有价值的基因组变异成为可能，否则这些变异就会丢失，因为它们往往与必须繁殖的有害变异一起遗传。尽管动物育种者试图改善的性状每个都由数千个基因组变异控制，但我们已经证明，理论上有可能通过编辑只需5个变异就能使家畜育种计划的遗传收益提高33%。该项目的目的是通过开发对同一个体进行多次编辑的技术和决定最佳编辑的育种方法，使这一理论上的可能性成为现实。最适合编辑的动物以及如何最好地管理育种计划。该项目包括两个方面的工作，一个将开发基因组编辑方法，另一个将开发育种方法。编辑方法将分三个阶段开发。1.我们将开发工具，进行不会以任何方式改变基因组功能的多次编辑。如果编辑不改变遗传功能，则测试工具的安全性和有效性将容易得多。当我们可以进行多次编辑时，我们将配置工具来产生应该改进育种的编辑，并在培养中的细胞上测试它们。当这些工具作用于培养中的细胞时，我们将使用它们来编辑单细胞胚胎，并生产出经过编辑的活猪。我们需要育种方法来设计一套最有用的编辑，并将其最有效地应用于育种计划。这些方法将以支持以下三项行动的计算机程序的形式制定。分析一个庞大的数据集，其中包含325000头猪的基因组序列以及关于它们的系谱和繁殖特性的信息，以决定最有效的编辑和最有用的编辑个体。选择要繁殖的猪的策略将防止因近亲繁殖而丢失有价值的基因。一种管理育种计划的策略，以便它生成测试当前编辑的有效性和确定最佳潜在未来编辑所需的数据。我们的工业合作伙伴PIC有一个育种计划，每年在超过1亿头屠宰猪中产生遗传学。该项目将帮助这些猪更健康，并使它们以更低的投入和更低的环境影响生产更好的肉类。育种方法和软件将提供给其他饲养猪和其他牲畜品种的公司。这些结果也将有助于理解人类身高和健康等数量性状的遗传基础。

This project will develop new laboratory techniques and new breeding methods to enhance livestock breeding programmes by genome editing. Genome editing is used to increase the numbers of animals in the breeding herd that carry beneficial genome variants. This makes it possible to conserve valuable genome variants that would otherwise be lost because they tend to be inherited together with harmful variants that must be bred out.Although the traits that animal breeders seek to improve are each controlled by thousands of genome variants, we have shown that it is theoretically possible to produce a 33% improvement in genetic gain in a livestock breeding programme by editing as few as 5 variants.The aim of this project is to make this theoretical possibility a practical reality by developing the techniques to do multiple edits on the same individual and the breeding methods to decide on the best edits, the best animals to edit and how best to manage the breeding programme.The project consists of two strands of work, one will develop the genome editing methods, the other will develop the breeding methods.The editing methods will be developed in three stages. 1. We will develop the tools to make multiple edits that do not change the function of the genome in any way. It will be much easier to test the safety and efficacy of the tools if the edits do not alter genetic function.2. When we can make multiple edits we will configure the tools to produce edits that should improve breeding and test them on cells in culture.3. When the tools work on cells in culture, we will use them to edit single-cell embryos and produce live, edited pigs.We need the breeding methods to design the most useful set of edits and to deploy them most effectively in a breeding programme. The methods will be developed in the form of computer programmes that support the following three operations.1. Analysis of a huge dataset, containing the genome sequences of 325000 pigs together with information about their pedigrees and their breeding traits, in order to decide on the most effective edits and the most useful individuals to edit.2. A strategy for selecting which pigs to breed from that will prevent the loss of valuable genes by inbreeding.3. A strategy for managing the breeding programme so that it generates the data needed to test the effectiveness of current edits and identify the best potential future edits.Our industrial partner, PIC, has a breeding programme that generates the genetics in over 100 million slaughter pigs every year. This project will help make those pigs healthier and make them produce better meat with lower inputs and lower environmental impact. The breeding methods and software will be made available to other companies breeding pigs and other livestock species. The results will also be useful for understanding the genetic basis of quantitative traits, like height and health, in humans.