Genome editing for quantitative traits in livestock

牲畜数量性状的基因组编辑

• 批准号: BB/N015339/1
• 负责人: Christopher Whitelaw
• 金额: $ 90.65万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN015339%2F1
• 关键词: Genome; editing; quantitative; traits; livestock

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.

该项目将开发新的实验室技术和新的育种方法，通过基因组编辑来加强牲畜育种计划。基因组编辑用于增加育种群中携带有益基因组变体的动物数量。这使得有可能保存有价值的基因组变异，否则这些变异将丢失，因为它们往往与必须繁殖出来的有害变异一起遗传。尽管动物育种家试图改善的性状都受到数千个基因组变异的控制，我们已经证明，理论上可以产生33%的通过编辑少至5个变异体来改善家畜育种计划中的遗传增益。该项目的目的是通过开发对同一个体和育种进行多次编辑的技术，使这种理论可能性成为现实。该项目包括两个方面的工作，一个是开发基因组编辑方法，另一个是开发育种方法。编辑方法将分三个阶段开发。1.我们将开发工具来进行多次编辑，而不会以任何方式改变基因组的功能。如果编辑不改变基因功能，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编辑，这些编辑应该改善育种并在培养中的细胞上进行测试。3.当这些工具在培养的细胞上工作时，我们将用它们编辑单细胞胚胎，并生产活的编辑过的猪。我们需要育种方法来设计最有用的编辑集，并在育种计划中最有效地部署它们。这些方法将以计算机程序的形式发展，以支持下列三项业务。分析一个庞大的数据集，包含325000头猪的基因组序列以及有关其谱系和育种性状的信息，以决定最有效的编辑和最有用的个体编辑。2.一种选择哪种猪进行育种的策略，可以防止有价值的基因因近亲繁殖而丢失。管理育种计划的策略，以便生成测试当前编辑有效性所需的数据，并确定未来最佳潜在编辑。我们的工业合作伙伴PIC拥有一个育种计划，每年为超过1亿头屠宰猪生成遗传数据。该项目将有助于使这些猪更健康，使它们以更低的投入和更低的环境影响生产更好的肉。育种方法和软件将提供给其他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数量性状的遗传基础，如身高和健康。

项目成果

A high resolution atlas of gene expression in the domestic sheep (Ovis aries).

• DOI: 10.1371/journal.pgen.1006997
• 发表时间: 2017-09
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Clark EL;Bush SJ;McCulloch MEB;Farquhar IL;Young R;Lefevre L;Pridans C;Tsang HG;Wu C;Afrasiabi C;Watson M;Whitelaw CB;Freeman TC;Summers KM;Archibald AL;Hume DA
• 通讯作者: Hume DA

Optimal cross selection for long-term genetic gain in two-part programs with rapid recurrent genomic selection.

• DOI: 10.1007/s00122-018-3125-3
• 发表时间: 2018-09
• 期刊: TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik
• 作者: Gorjanc G;Gaynor RC;Hickey JM
• 通讯作者: Hickey JM

Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function.

• DOI: 10.1371/journal.ppat.1006206
• 发表时间: 2017-02
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Burkard C;Lillico SG;Reid E;Jackson B;Mileham AJ;Ait-Ali T;Whitelaw CB;Archibald AL
• 通讯作者: Archibald AL

AlphaMate: a program for optimizing selection, maintenance of diversity and mate allocation in breeding programs.

• DOI: 10.1093/bioinformatics/bty375
• 发表时间: 2018-10-01
• 期刊: Bioinformatics (Oxford, England)
• 作者: Gorjanc G;Hickey JM
• 通讯作者: Hickey JM

A strategy to exploit surrogate sire technology in livestock breeding programs

在牲畜育种计划中利用代孕父系技术的策略

• DOI: 10.1101/199893
• 发表时间: 2017
• 作者: Gottardo P