Matching Mitochondrial DNA Haplotypes for Circumventing Tissue-Specific Segregation Bias

• Main Authors: Jianxin Pan, Li Wang, Charles Lu, Yanming Zhu, Zhunyuan Min, Xi Dong, Hongying Sha
• Format: Article
• Language: English
• Published: Elsevier 2019-03-01
• Series: iScience
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004219300689

Summary: Mitochondrial DNA (mtDNA) segregation associated with donor-recipient mtDNA mismatch in mitochondria replacement therapy leads to unknown risks. Here, to explore whether matching mtDNA haplotypes contributes to ameliorating segregation, we reproduced various degrees of heteroplasmic mice with three single nucleotide polymorphisms to monitor segregation severity. “Segregation” presented in tissues of heteroplasmic mice containing low-level donor mtDNA heteroplasmy, and disappeared as donor mtDNA heteroplasmy levels ascended. Meanwhile, we found that distribution of donor mtDNA among the blastomeres of preimplantation embryos from the heteroplasmic mice shared the same tendency as that in adult tissues. Statistical analysis showed that no selective replication of donor mtDNA occurred during lifespan. Tracking donor mtDNA distribution showed that uneven distribution of donor mtDNA among embryonic blastomeres gradually became even as donor mtDNA heteroplasmy increased, indicating that the “segregation” in tissues was inherited from the uneven distribution. Our finding suggested that donor-recipient mtDNA matching could circumvent segregation in mitochondria replacement therapy. : Biological Sciences; Developmental Genetics; Genetics Subject Areas: Biological Sciences, Developmental Genetics, Genetics