Molecular Human Reproduction, Vol. 9, No. 10, 631-638,
October 2003
© 2003 European Society of Human Reproduction and Embryology
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Prospect of preimplantation genetic diagnosis for heritable mitochondrial DNA diseases
Submitted on April 1, 2003; resubmitted on June 11, 2003. accepted on June 18, 2003
1 Department of Obstetrics and Gynecology, Royal Victoria Hospital, Montreal, H3A 1A1, Quebec, 2 Department of Experimental Medicine, McGill University, Montreal, H3A 1A1, Quebec, 3 Montreal Neurological Institute, Montreal, H3A 2B4, Quebec, 4 Department of Human Genetics, McGill University, Montreal, Quebec, Canada and 5 The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507-1627, USA
6 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, McGill University, Montreal, H3A 1A1, Quebec, Canada. e-mail: asangla.ao{at}muhc.mcgill.ca
To perform preimplantation genetic diagnosis for women carrying heteroplasmic mitochondrial DNA (mtDNA) mutations, it is necessary to ensure that the proportion of mutant mtDNA diagnosed in the biopsied cell gives an accurate indication of the mutant load in the remaining embryo. A heteroplasmic mouse model, carrying NZB and BALB mtDNA genotypes, was used to study the relative proportions of each mtDNA genotype in the ooplasm and first polar body of mature oocytes, and between blastomeres of early cleavage stage embryos. The levels of heteroplasmy varied widely in the gametes compared with the maternal genotype. However, the distribution of the two mtDNA genotypes was virtually identical between the ooplasm and polar body of a mature oocyte, and also between the blastomeres of each 2-, 4- and 6–8-cell embryo. Therefore, the level of heteroplasmy diagnosed from the polar body of an unfertilized oocyte or from a single blastomere of an embryo is representative of the level in the embryo as a whole. Reliable results were obtained from both polar bodies and blastomeres, but the efficiency of diagnosis was greater with blastomeres. We conclude that preimplantation genetic diagnosis is feasible for mtDNA diseases, although it should be approached with caution, as it is possible that transmission of some pathogenic mutations could behave in a different manner.
Key words: heteroplasmy/mitochondrial DNA/mtDNA diseases/mouse model/preimplantation genetic diagnosis
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