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Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes (Jun 2016)

cell
Title:
Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes
Journal:
Cell Stem Cell. 2016 Jun 2;18(6):749-54
Author(s):
Yamada M1, Emmanuele V2, Sanchez-Quintero MJ2, Sun B1, Lallos G1, Paull D1, Zimmer M1, Pagett S1, Prosser RW3, Sauer MV3, Hirano M4, Egli D5
Author(s) affiliation:
1The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
2Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
3Center 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.
4Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: This email address is being protected from spambots. You need JavaScript enabled to view it..
5The 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: This email address is being protected from spambots. You need JavaScript enabled to view it..
 

 

Short description:
*Cryopreservation allows coordinated nuclear transfer in human oocytes
*Stem cell lines and derivatives show low-level carryover of transferred mtDNA
*Recipient mtDNA is functionally compatible with donor nuclear DNA
*Genetic drift can lead to restoration of the original donor mitochondrial genotype
Link to the journal
 

 

Abstract taken from PubMed

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.

Copyright © 2016 Elsevier Inc. All rights reserved.
Link to the paper on PubMed
 




 

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