DMCA
Review Transmission of Mitochondrial DNA Diseases and Ways to Prevent Them
BibTeX
@MISC{Poulton_reviewtransmission,
author = {Joanna Poulton and Marcos R. Chiaratti and Flávio V. Meirelles and Stephen Kennedy and Dagan Wells},
title = {Review Transmission of Mitochondrial DNA Diseases and Ways to Prevent Them},
year = {}
}
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Abstract
Abstract: Recent reports of strong selection of mitochondrial DNA (mtDNA) during transmission in animal models of mtDNA disease, and of nuclear transfer in both animal models and humans, have important scientific implications. These are directly applicable to the genetic management of mtDNA disease. The risk that a mitochondrial disorder will be transmitted is difficult to estimate due to heteroplasmy—the existence of normal and mutant mtDNA in the same individual, tissue, or cell. In addition, the mtDNA bottleneck during oogenesis frequently results in dramatic and unpredictable intergenerational fluctuations in the proportions of mutant and wild-type mtDNA. Pre-implantation genetic diagnosis (PGD) for mtDNA disease enables embryos produced by in vitro fertilization (IVF) to be screened for mtDNA mutations. Embryos determined to be at low risk (i.e., those having low mutant mtDNA load) can be preferentially transferred to the uterus with the aim of initiating unaffected pregnancies. New evidence that some types of deleterious mtDNA mutations are eliminated within a few generations suggests that women undergoing PGD have a reasonable chance of generating embryos with a lower mutant load than their own. While nuclear transfer may become an alternative approach in future, there might be more difficulties, ethical as well as technical. This Review outlines the implications of recent advances for genetic management of these potentially devastating disorders.
Keyphrases
mtdna disease review transmission mitochondrial dna disease animal model genetic management nuclear transfer new evidence important scientific implication mtdna mutation mutant mtdna wild-type mtdna reasonable chance mitochondrial dna unpredictable intergenerational fluctuation pre-implantation genetic diagnosis vitro fertilization recent advance low mutant mtdna load strong selection mutant load mitochondrial disorder mtdna bottleneck low risk recent report deleterious mtdna mutation alternative approach unaffected pregnancy
