Use of haploid embryonic cells to generate offspring with predetermined genomes

使用单倍体胚胎细胞产生具有预定基因组的后代

• 批准号: 487107-2015
• 负责人: Smith, Lawrence
• 金额: $ 14.57万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=619121
• 关键词: Use; haploid; embryonic; cells; generate

In natural selection, differential fitness relies on the chromosomal shuffling during meiosis that enables the production of haploid gametes that are genetically different. However, meiotic-induced genetic variability can be an economic burden to the animal breeding industry since offspring often do not inherit the most desirable genes from their parents. Although genomic markers are currently being used to identify superior offspring at birth or even sooner, animals or embryos are frequently culled for not inheriting the best genes from their parents. This project is aimed at eliminating meiotic uncertainty from cattle breeding programs by determining the genomic value of paternal gametes before fertilization. Sperm-derived haploid cells will be produced and analyzed to identify those carrying a superior genome to generate offspring. The project proposal is divided into 4 phases: (1) deriving sperm-derived (androgenetic) haploid embryos by fertilizing enucleated oocytes, followed by culture; (2) production of haploid embryonic outgrowths and stem cell lines from androgenetic embryos; (3) recovering DNA from haploid embryonic cells with the purpose of performing bioinformatics analysis to identify and select those carrying a superior genome; (4) reconstruction of diploid zygotes by the injection of haploid androgenetic embryonic cells into oocytes to obtain embryos and their consequent offspring with predetermined paternal genomes. The proposal is financially and scientifically supported by SEMEX, a major industrial player in cattle genetics in Canada and internationally. The ability to predetermine the genome of offspring derived from genetically superior parents will provide SEMEX with a unique technical platform to incorporate into their selection programs and provide a considerable competitive advantage worldwide. Moreover, state-of-the-art scientific and technical exchanges between two graduate students and SEMEX's research team is expected to contribute significantly to training of HQP in areas in high demand for Canada.

在自然选择中，差异适合度依赖于减数分裂过程中的染色体洗牌，这使得遗传上不同的单倍体配子的产生成为可能。然而，减数分裂引起的遗传变异可能会给动物养殖业带来经济负担，因为后代往往不会从父母那里继承最可取的基因。尽管基因组标记目前被用来在出生时甚至更早识别出更好的后代，但动物或胚胎经常因为没有继承父母最好的基因而被淘汰。该项目旨在通过在受精前确定父本配子的基因组价值来消除牛育种项目中减数分裂的不确定性。将产生精子来源的单倍体细胞并进行分析，以识别那些携带优势基因组的细胞以产生后代。该项目建议分为4个阶段：(1)通过去核卵母细胞受精获得精子来源的单倍体胚胎，然后进行培养；(2)从雄性发育胚胎中产生单倍体胚胎突起和干细胞系；(3)从单倍体胚胎细胞中提取DNA，以便进行生物信息学分析，以识别和选择携带优势基因组的细胞；(4)通过将单倍体雄性发育胚胎细胞注射到卵母细胞中重建二倍体受精卵，以获得胚胎及其具有预先确定的父系基因组的后代。这项提议得到了加拿大和国际上牛遗传学的主要行业参与者Semex的资金和科学支持。预先确定来自遗传优势父母的后代基因组的能力将为Semex提供一个独特的技术平台，将其纳入他们的选择计划，并在全球范围内提供相当大的竞争优势。此外，两名研究生和Semex研究团队之间最先进的科学和技术交流预计将为加拿大需求较高地区的HQP培训做出重大贡献。