Use of haploid embryonic cells to generate offspring with predetermined genomes

在自然选择中，差异适应度依赖于减数分裂期间的染色体洗牌，从而产生遗传上不同的单倍体配子。然而，减数分裂引起的遗传变异对动物养殖业来说是一个经济负担，因为后代往往不能从父母那里继承最理想的基因。虽然基因组标记目前被用于在出生时甚至更早的时候识别优秀的后代，但动物或胚胎经常因为没有从父母那里继承最好的基因而被淘汰。该项目旨在通过确定受精前父系配子的基因组价值来消除牛育种计划中的减数分裂不确定性。精子来源的单倍体细胞将被制造出来并进行分析，以识别那些携带优越基因组的细胞以产生后代。项目建议分为4个阶段：(1)通过使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)从雄激素胚胎中获得单倍体胚体和干细胞系；(3)从单倍体胚胎细胞中提取DNA，进行生物信息学分析，以鉴定和选择携带优越基因组的细胞；(4)将单倍体雄激素胚胎细胞注入卵母细胞，重建二倍体受精卵，获得具有预定父系基因组的胚胎及其后代。该提案得到了SEMEX的财政和科学支持，SEMEX是加拿大和国际上牛遗传学的主要工业参与者。预先确定遗传优势父母后代基因组的能力将为SEMEX提供一个独特的技术平台，将其纳入其选择计划，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的研究团队之间的最先进的科学技术交流有望为加拿大高需求领域的HQP培训做出重大贡献。

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.