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Transmission of Mitochondrial DNA Diseases and Ways to Prevent Them
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Transmission of Mitochondrial DNA Diseases and Ways to Prevent Them
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Journal Article
Transmission of Mitochondrial DNA Diseases and Ways to Prevent Them
2010
Overview
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 inter-generational 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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Diseases
/ DNA, Mitochondrial - genetics
/ Embryos
/ Ethics
/ Genetics and Genomics/Disease Models
/ Genetics and Genomics/Gene Therapy
/ Genetics and Genomics/Medical Genetics
/ Humans
/ Methods
/ Mice
/ Mitochondrial Diseases - diagnosis
/ Mitochondrial Diseases - genetics
/ Mitochondrial Diseases - prevention & control
/ Mutation
/ Review
