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dc.contributor.authorBi, Chongwei
dc.contributor.authorWang, Lin
dc.contributor.authorFan, Yong
dc.contributor.authorRamos Mandujano, Gerardo
dc.contributor.authorYuan, Baolei
dc.contributor.authorZhou, Xuan
dc.contributor.authorWang, Jincheng
dc.contributor.authorShao, Yanjiao
dc.contributor.authorZhang, Pu-Yao
dc.contributor.authorHuang, Yanyi
dc.contributor.authorYu, Yang
dc.contributor.authorIzpisua Belmonte, Juan Carlos
dc.contributor.authorLi, Mo
dc.date.accessioned2020-12-31T11:59:32Z
dc.date.available2020-12-31T11:59:32Z
dc.date.issued2020-12-29
dc.identifier.citationBi, C., Wang, L., Fan, Y., Ramos-Mandujano, G., Yuan, B., Zhou, X., … Li, M. (2020). Single-cell Individual Complete mtDNA Sequencing Uncovers Hidden Mitochondrial Heterogeneity in Human and Mouse Oocytes. doi:10.1101/2020.12.28.424537
dc.identifier.doi10.1101/2020.12.28.424537
dc.identifier.urihttp://hdl.handle.net/10754/666791
dc.description.abstractThe ontogeny and dynamics of mtDNA heteroplasmy remain unclear due to limitations of current mtDNA sequencing methods. We developed individual Mitochondrial Genome sequencing (iMiGseq) of full-length mtDNA for ultra-sensitive variant detection, complete haplotyping, and unbiased evaluation of heteroplasmy levels, all at the individual mtDNA molecule level. iMiGseq uncovers unappreciated levels of heteroplasmic variants in single healthy human oocytes well below the current 1% detection limit, of which numerous variants are detrimental and could contribute to late-onset mitochondrial disease and cancer. Extreme mtDNA heterogeneity among oocytes of the same mouse female, and a strong selection against deleterious mutations in human oocytes are observed. iMiGseq could comprehensively characterize and haplotype single-nucleotide and structural variants of mtDNA and their genetic linkage in NARP/Leigh syndrome patient-derived cells. Therefore, iMiGseq could not only elucidate the mitochondrial etiology of diseases, but also help diagnose and prevent mitochondrial diseases with unprecedented precision.
dc.description.sponsorshipWe thank members of the Li laboratory, Khaled Alsayegh, Samhan Alsolami for helpful discussions; Jinna Xu and Marie Krenz Y. Sicat for administrative support. We thank Chenyang Geng at the BIOPIC core facility at Peking university for technical assistance in PacBio sequencing. We thank Professor Jasmeen Merzaban’s lab and KAUST Animal Research Core Laboratory for sharing mouse strains. The research of the Li laboratory was supported byKAUST Office of Sponsored Research (OSR), under award number BAS/1/1080-01. The work was supported by a KAUST Competitive Research Grant (award number URF/1/3412-01-01) given to ML, YH and JCIB; the National Key R&D Program of China (2016YFC1000601) and the National Natural Science Funds (81571400, 81771580 and 81971381), MMAAP foundation to YY; and the National Key Research and Development Program of China (2019YFA0110804, 2018YFC1003203), and the National Natural Science Foundation of China (81871162) to YF
dc.publisherCold Spring Harbor Laboratory
dc.relation.urlhttp://biorxiv.org/lookup/doi/10.1101/2020.12.28.424537
dc.rightsArchived with thanks to Cold Spring Harbor Laboratory
dc.titleSingle-cell Individual Complete mtDNA Sequencing Uncovers Hidden Mitochondrial Heterogeneity in Human and Mouse Oocytes
dc.typePreprint
dc.contributor.departmentBioscience Program
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBiological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
dc.eprint.versionPre-print
dc.contributor.institutionpresent address: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
dc.contributor.institutionDepartment of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, 510150 Guangzhou, China.
dc.contributor.institutionBeijing Advanced Innovation Center for Genomics (ICG), Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, College of Chemistry, College of Engineering, PekingTsinghua Center for Life Sciences, Peking University, Beijing, China.
dc.contributor.institutionGene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.
dc.contributor.institutionCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
dc.contributor.institutionInstitute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen, China.
dc.contributor.institutionStem Cell Research Center, Peking University Third Hospital, Beijing 100191, China.
kaust.personBi, Chongwei
kaust.personWang, Lin
kaust.personRamos Mandujano, Gerardo
kaust.personYuan, Baolei
kaust.personZhou, Xuan
kaust.personLi, Mo
kaust.grant.numberBAS/1/1080-01
kaust.grant.numberURF/1/3412-01-01)
refterms.dateFOA2020-12-31T12:00:11Z
kaust.acknowledged.supportUnitCompetitive Research
kaust.acknowledged.supportUnitKAUST Office of Sponsored Research (OSR)


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