Use of haploid embryonic cells to generate offspring with predetermined genomes

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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.