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Segmental aneuploidies with 1 Mb resolution in human preimplantation blastocysts

  • Pingyuan Xie
    Affiliations
    Hunan Normal University School of Medicine, Changsha, Hunan, China

    National Engineering and Research Center of Human Stem Cells, Changsha, China

    Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, Hunan, China
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  • Ping Liu
    Affiliations
    BGI-Shenzhen, Shenzhen, China
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  • Shuoping Zhang
    Affiliations
    Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China

    Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
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  • Dehua Cheng
    Affiliations
    Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
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  • Dayang Chen
    Affiliations
    BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China
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  • Yue-Qiu Tan
    Affiliations
    National Engineering and Research Center of Human Stem Cells, Changsha, China

    Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, Hunan, China

    Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China

    Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
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  • Liang Hu
    Affiliations
    National Engineering and Research Center of Human Stem Cells, Changsha, China

    Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, Hunan, China

    Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China

    Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
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  • Yong Qiu
    Affiliations
    BGI-Shenzhen, Shenzhen, China
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  • Shuang Zhou
    Affiliations
    National Engineering and Research Center of Human Stem Cells, Changsha, China

    Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, Hunan, China
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  • Qi Ou-Yang
    Affiliations
    National Engineering and Research Center of Human Stem Cells, Changsha, China

    Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, Hunan, China

    Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
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  • Keli Luo
    Affiliations
    National Engineering and Research Center of Human Stem Cells, Changsha, China

    Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China

    Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
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  • Guangxiu Lu
    Affiliations
    National Engineering and Research Center of Human Stem Cells, Changsha, China

    Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, Hunan, China

    Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China

    Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
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  • Shaohong Zhang
    Affiliations
    BGI-Shenzhen, Shenzhen, China
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  • Fei Gong
    Affiliations
    National Engineering and Research Center of Human Stem Cells, Changsha, China

    Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China

    Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
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  • Ge Lin
    Correspondence
    Correspondence and requests for materials should be addressed to Ge Lin, Department of Genetics, Reproductive and Genetic Hospital of CITIC-Xiangya, 567 TongZipo Road, Yuelu District, Changsha 410078, China
    Affiliations
    Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China

    Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
    Search for articles by this author
Published:September 15, 2022DOI:https://doi.org/10.1016/j.gim.2022.08.008

      Abstract

      Purpose

      This study aimed to investigate the spectrum and characteristics of segmental aneuploidies (SAs) of <10 megabase (Mb) length in human preimplantation blastocysts.

      Methods

      Preimplantation genetic testing for aneuploidy was performed in 15,411 blastocysts from 5171 patients using a validated 1 Mb resolution platform. The characteristics and spectrum of SAs, including the incidence, sizes, type, inheritance pattern, clinical significance, and embryo distribution, were studied.

      Results

      In total, 6.4% of the 15,411 blastocysts carried SAs of >10 Mb, 4.9% of embryos had SAs ranging between 1 to 10 Mb, and 84.3% of 1 to 10 Mb SAs were <5 Mb in size. Inheritance pattern analysis indicated that approximately 63.8% of 1 to 10 Mb SAs were inherited and were predominantly 1 to 3 Mb in size. Furthermore, 18.4% of inherited SAs and 51.9% de novo 1 to 10 Mb SAs were pathogenic or likely pathogenic (P/LP). Different from whole-chromosome aneuploidies, reanalysis indicated that 50% of the de novo 1 to 10 Mb SAs and 70% of the >10 Mb SAs arose from mitotic errors.

      Conclusion

      Based on the established platform, 1 to 10 Mb SAs are common in blastocysts and include a subset of P/LP SAs. Inheritance pattern analysis and clinical interpretation based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines contributed to determine the P/LP SAs.

      Keywords

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