13TSB_AgriFood: Optimising the delivery of superior genetics through advanced genomic selection of embryos

该提案是TSB资助的两个现有项目的自然但重要的延伸，涉及两个合作的学术机构(即TS/101069[“应用先进育种技术来扩增和传播牛基因以提高生产效率和可持续性”，涉及诺丁汉大学]和TS/J003182/1[猪体外受精和遗传学：与商业合作伙伴（如Paragon/XLVets、Cogent breeding Ltd和Illumina Inc）一起开发先进的育种技术，这些技术将允许销售经过完整基因组评估（包括性别鉴定）的胚胎，以便在发育的最早阶段估计后代的育种价值，以获得具有商业重要性的性状。该项目将应用先进的育种技术来生产（体内和体外）植入前的牛胚胎，并使用单核苷酸多态性芯片（SNP芯片）对其进行活组织检查，以询问其基因组组成。目前，对奶牛和肉牛进行基因筛选是可能的，但对选择的反应受到等待小牛妊娠的阻碍，因为要对小牛进行基因组选择。然而，通过提前选择时间和减少不合适性别的不需要的小牛的“浪费”，对牛胚胎的筛选将优化优良基因的传递和扩增。因此，该项目将把先进的胚胎育种技术与最先进的基因组筛选（即所谓的植入前遗传学诊断）和核作图（将亲代DNA信息与后代基因组信息相结合，以提供更多的遗传细节）结合起来。它将制定以下策略：(i)使用性别精液进行最佳牛胚胎培养，（ii）胚胎活检以便提取少量卵裂球进行基因组分析，（iii）从多位移扩增产品中提取SNP基因型数据的核定位，（iv）加强冻融胚胎的妊娠建立。通过对小牛进行基因组分析，可以证实新技术可以更有效地向繁殖群传递优良基因的原理。重要的是，该项目旨在开发和使用一种独特的、高度市场化的产品（即基因评估的性别胚胎），以低成本、高福利和生物安全的方式向全球市场提供优越的基因。这将为英国的相关商业公司带来巨大的经济利益，并为英国畜牧业的乳制品和牛肉部门带来巨大的经济利益；并确保英国保持在技术创新的前沿，保持其相对于目前位于欧洲、北美和南美的大型育种公司的竞争优势。

This proposal is a natural but significant extension of two existing TSB funded projects involving the two collaboratingacademic institutions (i.e. TS/101069 ['Applying advanced breeding technologies to amplify and distribute bovine geneticsto Increase production efficiency and sustainability', involving the University of Nottingham], and TS/J003182/1 [Pig IVF andgenetics: a route to global sustainability, involving the University of Kent]) to develop advanced breeding technologies incattle with commercial partners (i.e. Paragon/XLVets, Cogent Breeding Ltd and Illumina Inc) that will allow the marketing ofembryos that have undergone a complete genomic evaluation (including sexing) in order to estimate the breeding value ofprogeny for traits of commercial importance at the earliest possible stage of development.This project will apply advanced breeding technologies to produce (both in-vivo and in-vitro) pre-implantation bovineembryos from which biopsies will be taken to interrogate their genomic makeup using single nucleotide polymorphismarrays (SNP chips). It is currently possible to screen dairy and beef cattle genomically, but responses to selection areimpeded by waiting for the gestation of the calf on which genomic selection is performed. The screening of bovineembryos, however, would optimise the delivery and amplification of superior genetics by advancing the time of selectionand reducing "wastage" of unwanted calves of inappropriate sex. This project will, therefore, combine advanced embryobreeding technologies with state-of-the-art genomic screening (so called pre-implantation genetic diagnosis), andkaryomapping (combining parental DNA information with the offspring's genomic information to provide more geneticdetail). It will develop strategies for: (i) optimal bovine embryo culture using sexed semen, (ii) embryo biopsy in order toextract a small number of blastomeres for genomic analysis, (iii) karyomapping SNP genotype data from MultipleDisplacement Amplification products and (iv) ehnancing pregnancy establishment of frozen-thawed embryos. Proof ofprinciple that the new technologies can be used to deliver superior genetics more efficiently to the breeding herd will beconfirmed by conducting genomic analyses of calves.Importantly, this project is geared towards the development and use of a unique and highly marketable product (i.e.genetically evaluated sexed embryos) that will deliver superior genetics to the global market at low cost, and in a highwelfare and bio-secure manner. This will have huge economic benefits for the UK based commercial companies concerned, and for both the dairy and beef sectors of the UK cattle industry; and ensure that the UK remains at the cutting edge of technical innovation retaining its competitive advantage over larger breeding companies currently situated inEurope, North and South America.