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Cell Stem Cell. 2016 Jun 2;18(6):749-54. doi: 10.1016/j.stem.2016.04.001. Epub 2016 May 19.

Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes.

Author information

1
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
2
Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
3
Center for Women's Reproductive Care, College of Physicians and Surgeons, Columbia University, New York, NY 10019, USA; Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
4
Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: mh29@cumc.columbia.edu.
5
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA; Naomi Berrie Diabetes Center, Columbia University, Department of Pediatrics, New York, NY 10032, USA. Electronic address: d.egli@nyscf.org.

Abstract

Replacement of mitochondria through nuclear transfer between oocytes of two different women has emerged recently as a strategy for preventing inheritance of mtDNA diseases. Although experiments in human oocytes have shown effective replacement, the consequences of small amounts of mtDNA carryover have not been studied sufficiently. Using human mitochondrial replacement stem cell lines, we show that, even though the low levels of heteroplasmy introduced into human oocytes by mitochondrial carryover during nuclear transfer often vanish, they can sometimes instead result in mtDNA genotypic drift and reversion to the original genotype. Comparison of cells with identical oocyte-derived nuclear DNA but different mtDNA shows that either mtDNA genotype is compatible with the nucleus and that drift is independent of mitochondrial function. Thus, although functional replacement of the mitochondrial genome is possible, even low levels of heteroplasmy can affect the stability of the mtDNA genotype and compromise the efficacy of mitochondrial replacement.

PMID:
27212703
DOI:
10.1016/j.stem.2016.04.001
[Indexed for MEDLINE]
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