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The preimplantation genetic testing for monogenic disorders strategy for blocking the transmission of hereditary cancers through haplotype linkage analysis by karyomap**

  • Genetics
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Abstract

Purpose

Providing feasible preimplantation genetic testing strategies for monogenic disorders (PGT-M) for prevention and control of genetic cancers.

Methods

Inclusion of families with a specific pathogenic mutation or a clear family history of genetic cancers. Identification of the distribution of hereditary cancer-related mutations in families through genetic testing. After a series of assisted reproductive measures such as down-regulation, stimulation, egg retrieval, and in vitro fertilization, a biopsy of trophectoderm cells from a blastocyst was performed for single-cell level whole-genome amplification (WGA). Then, the detection of chromosomal aneuploidies was performed by karyomap**. Construction of a haplotype-based linkage analysis to determine whether the embryo carries the mutation. Meanwhile, we performed CNV testing. Finally, embryos can be selected for transfer, and the results will be verified in 18–22 weeks after pregnancy.

Results

Six couples with a total of 7 cycles were included in our study. Except for cycle 1 of case 5 which did not result in a transferable embryo, the remaining 6 cycles produced transferable embryos and had a successful pregnancy. Four couples have had amniotic fluid tests to confirm that the fetus does not carry the mutation, while 1 couple was not tested due to insufficient pregnancy weeks. And the remaining couples had to induce labor due to fetal megacystis during pregnancy.

Conclusion

Our strategy has been proven to be feasible. It can effectively prevent transmission of hereditary cancer-related mutations to offspring during the prenatal stage.

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Data availability

The data that support the results of this study can be obtained from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank all the participants that took part in the study. This work was supported by the National Natural Science Foundation of China for the National Key R&D Program of China (2019YFA0110900) to Yingpu Sun.

Funding

This work was supported by funding from the National Natural Science Foundation of China for the National Key R&D Program of China (2019YFA0110900) to Y.-P.S.

Author information

Author notes

  1. Chuanju Chen and Hao Shi contributed equally to this work.

Authors and Affiliations

  1. Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Chuanju Chen, Hao Shi, Wenbin Niu, **ao Bao, **gya Yang, Haixia **, Wenyan Song & Yingpu Sun

  2. Henan Key Laboratory of Reproduction and Cenetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Chuanju Chen, Hao Shi, Wenbin Niu, **ao Bao, **gya Yang, Haixia **, Wenyan Song & Yingpu Sun

  3. Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Chuanju Chen, Hao Shi, Wenbin Niu, **ao Bao, **gya Yang, Haixia **, Wenyan Song & Yingpu Sun

  4. Henan Engineering Laboratory of Preimplantation Genetic Diagnosis and Screening, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Chuanju Chen, Hao Shi, Wenbin Niu, **ao Bao, **gya Yang, Haixia **, Wenyan Song & Yingpu Sun

Authors
  1. Chuanju Chen
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Contributions

Chuanju Chen: conceptualization (supporting), data curation (lead), formal analysis (equal), validation (equal), visualization (lead), writing – original draft preparation (lead), writing – review and editing. Hao Shi: conceptualization (lead), formal analysis (equal), investigation (lead), methodology (lead), project administration (lead), supervision, writing – review and editing (lead). Wenbin Niu: formal analysis (equal), resources (equal). **ao Bao: formal analysis (equal), resources (equal). **gya Yang: validation (equal). Haixia **: formal analysis (equal), resources (equal). Wenyan Song: formal analysis (equal), resources (equal). Yingpu Sun: funding acquisition (lead), supervision (lead).

Corresponding author

Correspondence to Yingpu Sun.

Ethics declarations

Ethics approval

Ethical approval to conduct this retrospective study was obtained from the Internal Review Board of The First Affiliated Hospital of Zhengzhou University (Ethic no. 2023-KY-0361).

Conflict of interest

The authors declare no competing interests.

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Supplementary information

ESM 1

SUPPLEMENTAL Figure 1. Family trees of all family were included. (TIF 1252 kb)

High resolution image (PNG 254 kb)

ESM 2

SUPPLEMENTAL TABLE 1. The results of haplotype linkage analysis of case 1 by SNPs within 2M of upstream and downstream of the RET gene. (DOCX 30 kb)

ESM 3

SUPPLEMENTAL TABLE 2. The results of haplotype linkage analysis of case 1 by SNPs within 2M of upstream and downstream of the BRCA1 gene. (DOCX 21 kb)

ESM 4

SUPPLEMENTAL TABLE 3A. The results of haplotype linkage analysis of case 3 by SNPs within 2M of upstream and downstream of the RAD51D gene. SUPPLEMENTAL TABLE 3B. The results of haplotype linkage analysis of case 3 by SNPs within 2M of upstream and downstream of the TP53 gene. (DOCX 39 kb)

ESM 5

SUPPLEMENTAL TABLE 4. The results of haplotype linkage analysis of case 4 by SNPs within 2M of upstream and downstream of the RB1 gene. (DOCX 21 kb)

ESM 6

SUPPLEMENTAL TABLE 5A. The results of haplotype linkage analysis of case 5 by SNPs within 2M of upstream and downstream of the FH gene. SUPPLEMENTAL TABLE 5B. The results of haplotype linkage analysis of case 5 by SNPs within 1M of upstream and downstream of the NPHS1 gene from paternal chromosome. SUPPLEMENTAL TABLE 5C. The results of haplotype linkage analysis of case 5 by SNPs within 1M of upstream and downstream of the NPHS1 gene from maternal chromosome. (DOCX 38 kb)

ESM 7

SUPPMENTAL TABLE 6. The results of haplotype linkage analysis of case 6 by SNPs within 2M of upstream and downstream of the BRCA1 gene. (DOCX 28 kb)

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Chen, C., Shi, H., Niu, W. et al. The preimplantation genetic testing for monogenic disorders strategy for blocking the transmission of hereditary cancers through haplotype linkage analysis by karyomap**. J Assist Reprod Genet 40, 2933–2943 (2023). https://doi.org/10.1007/s10815-023-02939-0

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