The development of novel quantification assay for mitochondrial DNA heteroplasmy aimed at preimplantation genetic diagnosis of Leigh encephalopathy

Tajima, Hiroto; Sueoka, Kou; Moon, Sung Yung; Nakabayashi, Akira; Sakurai, Takeshi; Murakoshi, Yukitaka; Watanabe, Hiroyoshi; Iwata, Susumu; Hashiba, Tsuyoshi; Kato, Shingo; Goto, Yu Ichi; Yoshimura, Yasunori

doi:10.1007/s10815-007-9114-0

Cited by 26 publications

(18 citation statements)

References 22 publications

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“…A previous study showed that polar bodies are effective for preimplantation genetic diagnosis (PGD) to deduce the proportion of mutated mtDNA in mouse oocytes (20). However, subsequent studies using polar bodies from human oocytes (30) and blastomeres from human embryos (31,32) indicated that blastomeres are more appropriate than are polar bodies for PGD to deduce the proportion of mutated mtDNA. Although this procedure would not completely exclude the mutated mtDNA from the affected mothers, our previous studies (33,34) showed the presence of intermitochondrial complementation to maintain normal respiratory function in the presence of the mutated mtDNA.…”

Section: Discussionmentioning

confidence: 99%

Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA ^Lys gene

Shimizu¹,

Mito²,

Hayashi³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance We generated transmitochondrial mito-mice-tRNA Lys7731 as models for precise examination of the pathogenesis and transmission profiles of mtDNA mutations in the tRNA Lys genes and have obtained important information regarding primary prevention of the diseases caused by the mtDNA mutations. Although nuclear transplantation from oocytes of affected mothers into enucleated oocytes of unrelated women has been suggested, the methodology carries the technical risk of inducing nuclear abnormalities and prompts ethical concerns regarding the production of three-parent babies with normal mtDNA from unrelated oocyte donors. The current study suggests that the selection of oocytes with high proportions of normal mtDNA from affected mothers can be used to avoid these issues and therefore provides insights into mitochondrial genetics and medicine.

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Section: Discussionmentioning

confidence: 99%

Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA ^Lys gene

Shimizu¹,

Mito²,

Hayashi³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…In contrast to the similarity of heteroplasmy levels of blastomeres within an embryo, the heteroplasmy levels among embryos varied considerably. Interestingly, the heteroplasmy levels of individual lymphocytes from a subject with a 44.3% whole blood heteroplasmy proved to be highly variable, ranging from 11% to 70% (Tajima et al 2007).…”

Section: Mitochondrial Dna Geneticsmentioning

confidence: 97%

Mitochondrial DNA Genetics and the Heteroplasmy Conundrum in Evolution and Disease

Wallace

Chalkia

2013

Cold Spring Harbor Perspectives in Biology

557

532

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The unorthodox genetics of the mtDNA is providing new perspectives on the etiology of the common "complex" diseases. The maternally inherited mtDNA codes for essential energy genes, is present in thousands of copies per cell, and has a very high mutation rate. New mtDNA mutations arise among thousands of other mtDNAs. The mechanisms by which these "heteroplasmic" mtDNA mutations come to predominate in the female germline and somatic tissues is poorly understood, but essential for understanding the clinical variability of a range of diseases. Maternal inheritance and heteroplasmy also pose major challengers for the diagnosis and prevention of mtDNA disease. THE GENETIC CHALLENGES OF mtDNA DISEASES

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“…Available data on human preimplantation embryos are limited and suffer from small sample size and technical limitations (Monnot et al, 2011; Steffann et al, 2006; Tajima et al, 2007) emphasizing the need to conduct thorough studies in nonhuman primate models.…”

Section: Introductionmentioning

confidence: 99%

Rapid Mitochondrial DNA Segregation in Primate Preimplantation Embryos Precedes Somatic and Germline Bottleneck

et al. 2012

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SUMMARY The timing and mechanisms of mitochondrial DNA (mtDNA) segregation and transmission in mammals are poorly understood. Genetic bottleneck in female germ cells has been proposed as the main phenomenon responsible for rapid intergenerational segregation of heteroplasmic mtDNA. We demonstrate here that mtDNA segregation occurs during primate preimplantation embryogenesis resulting in partitioning of mtDNA variants between daughter blastomeres. A substantial shift toward homoplasmy occurred in fetuses and embryonic stem cells (ESCs) derived from these heteroplasmic embryos. We also observed a wide range of heteroplasmic mtDNA variants distributed in individual oocytes recovered from these fetuses. Thus, we present here evidence for a previously unknown mtDNA segregation and bottleneck during preimplantation embryo development, suggesting that return to the homoplasmic condition can occur during development of an individual organism from the zygote to birth, without a passage through the germline.

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The development of novel quantification assay for mitochondrial DNA heteroplasmy aimed at preimplantation genetic diagnosis of Leigh encephalopathy

Cited by 26 publications

References 22 publications

Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA ^Lys gene

Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA ^Lys gene

Mitochondrial DNA Genetics and the Heteroplasmy Conundrum in Evolution and Disease

Rapid Mitochondrial DNA Segregation in Primate Preimplantation Embryos Precedes Somatic and Germline Bottleneck

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The development of novel quantification assay for mitochondrial DNA heteroplasmy aimed at preimplantation genetic diagnosis of Leigh encephalopathy

Cited by 26 publications

References 22 publications

Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA Lys gene

Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA Lys gene

Mitochondrial DNA Genetics and the Heteroplasmy Conundrum in Evolution and Disease

Rapid Mitochondrial DNA Segregation in Primate Preimplantation Embryos Precedes Somatic and Germline Bottleneck

Contact Info

Product

Resources

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Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA ^Lys gene

Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA ^Lys gene