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Question continued: Ie. is it possible right now? Does the current technology allows us to, hypothetically swap an “unwanted” chromosome (one that contain a dominant genes for a disease, for example) with a “clean” chromosome? I want to focus on just the swapping. Does the chromosome have to come from the same person that produce the gamete? What about replace a X chromosome of an otherwise Y sperm?

Tirumalai Kamala’s answer:

  • Technology exists today to swap out all chromosomes from one egg (oocyte) to another.
  • Proof of concept resulted in healthy infant rhesus macaque babies.
  • Chromosome swap method of all chromosomes between oocytes from different donors is thus feasible.
  • Don’t know if single/specifically chosen chromosome swap is as yet feasible.
  • Don’t know if sperm chromosome swaps have been done or are feasible.

Mammalian egg development 101

  • Egg development, oogenesis, results in a single, haploid egg following two meiotic divisions.
  • The 1st meiotic division starts in the fetal ovary, with division arresting at prophase I of the 1st meiotic cell cycle.
  • Oocytes resume division at puberty, become mature and arrest cell division again at metaphase II (MII) of the 2nd meiotic cell cycle.
  • Sperm entry at fertilization completes oocyte meiosis with separation of chromosomes into the 2nd polar body.

Successful chromosome swap of rhesus macaque MII phase mature oocyte chromosome

  • Scientists’ early attempts (Cohen, Jacques, et al. “Ooplasmic transfer in mature human oocytes.” Molecular Human Reproduction 4.3 (1998): 269-280. Page on oxfordjournals.org; Tanaka, Atsushi, et al. “Metaphase II karyoplast transfer from human in-vitro matured oocytes to enuclueated mature oocytes.” Reproductive biomedicine online 19.4 (2009): 514-520. Page on rbmojournal.com) to swap chromosomes in MII oocytes largely failed due to
    • Low fertilization rates
    • Anomalies
    • Poor embryo development
  • A team led by scientists at the Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA (Tachibana, Masahito, et al. “Mitochondrial gene replacement in primate offspring and embryonic stem cells.” Nature 461.7262 (2009): 367-372. Page on fbae.org) successfully swapped out rhesus macacque MII stage oocyte chromosomes derived from separate rhesus macaques.
  • They developed new methods that overcame previous technical challenges.
  • Genetic analyses confirmed infant macaques had nuclear DNA of the donor egg who donated nuclear material while their mitochondrial DNA was of the cytoplast egg donor’s.
  • The authors’ online video (Tachibana, Masahito, Michelle Sparman, and Shoukhrat Mitalipov. “Chromosome transfer in mature oocytes.” Fertility and sterility 97.5 (2012): e16): Chromosomal Transfer in Mature Oocytes – Fertility Sterility Discussion
    • Explains the therapeutic implications of their oocyte chromosome swap.
    • Explains the step-by-step procedure.
  • Three healthy infants resulted from implanted oocytes containing swapped chromosomes.

Another group (Paull, Daniel, et al. “Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants.” Nature 493.7434 (2013): 632-637) successfully applied a similar approach and generated stem cells from two swapped unfertilized human eggs. In vitro tissue culture work of course. Ethical issues preclude anything else.