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Molecular, cell biological and genetic aspects of diseases:
The “three parent child” -Mitochondrial donation for prevention of mitochondrial
disease – methods, technical and ethical concerns
Iita Palosaari, Marika Pätsi
Mitochondrial genome replacement techniques
Mitochondrial replacement techniques (MRT) are designed to prevent the transmission of
mitochondrial DNA (mtDNA) diseases from mother to child.
The transmission of mtDNA mutations that potentially may cause disease has been estimated to be as high as one in every 200 newborns.
MRT could satisfy the desire of women seeking to have a genetically related child without
the risk of passing on mtDNA disease
The goal of MRT is to prevent the transmission of these serious diseases by creating an
embryo with nuclear DNA (nDNA) from the intended mother and mtDNA from a woman
with nonpathogenic mtDNA through modification of either an oocyte (egg) or zygote (fertilized egg).
Picture 1. A) Spindle Transfer involves isolation and transfer of a nuclear genetic material (spindle-chromosomal complex) from an unfertilized oocyte containing mutated mtDNA to the cytoplasm of another enucleated oocyte containing healthy mtDNA. The reconstructed oocyte is then fertilized and transplanted. (B) Pronuclear Transfer takes place
after fertilization, at the one-cell embryo stage containing male and female pronuclei (zygote). Both pronuclei are
isolated and transplanted into a cytoplasm of another enucleated zygote.
Germline therapy or not?
- PNT and MST don’t (shouldn’t) act on nucleus
- mtDNA is not modified; whole mitochondrial genomes replaced
- though these genes will be incorporated to germline and passed on maternallyheritable, irreversible and affects every cell type of the child
- three genetic contributions confused self-image?
- does the person seek for the bio-history, who was the donor?
- issue of consent
Three “parents”, two “mothers”
- only 0.1 % from total DNA from donor
Unnatural? Form of eugenics?
- impact on persons with disabilities; pressure to mutated women to use the techniques?
“Unmatched” nuclear and mitochondria genomes
- takes several generations to see if the procedure has been safe
Importance of giving information and counselling for donors and couples and long-term
follow-up for children
- status of the mitochondrial or sperm donor
Current challenge is to chart a course that translates preclinical and clinical studies into
clinical trials evaluating efficacy and safety
- might be considered unethical to deny germline gene therapies for nuclear DNA diseases
2015 UK approved laws to permit procedure
BUT doesn’t help with mitochondrial diseases connected to genes located in nucleus