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

Mitsutoshi Yamada, Valentina Emmanuele, Maria J. Sanchez-Quintero, Bruce Sun, Gregory Lallos, Daniel Paull, Matthew Zimmer, Shardonay Pagett, Robert W. Prosser, Mark V. Sauer, Michio Hirano, Dieter Egli

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)749-754
Number of pages6
JournalCell stem cell
Volume18
Issue number6
DOIs
Publication statusPublished - 2016 Jun 2

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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