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Evaluation of genetic risk of apparently balanced chromosomal rearrangement carriers by breakpoint characterization

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To report genetic characteristics and associated risk of chromosomal breaks due to chromosomal rearrangements in large samples.

Methods

MicroSeq, a technique that combines chromosome microdissection and next-generation sequencing, was used to identify chromosomal breakpoints. Long-range PCR and Sanger sequencing were used to precisely characterize 100 breakpoints in 50 ABCR carriers.

Results

In addition to the recurrent regions of balanced rearrangement breaks in 8q24.13, 11q11.23, and 22q11.21 that had been documented, we have discovered a 10-Mb region of 12q24.13-q24.3 that could potentially be a sparse region of balanced rearrangement breaks. We found that 898 breakpoints caused gene disruption and a total of 188 breakpoints interrupted genes recorded in OMIM. The percentage of breakpoints that disrupted autosomal dominant genes recorded in OMIM was 25.53% (48/188). Fifty-four of the precisely characterized breakpoints had 1–8-bp microhomologous sequences.

Conclusion

Our findings provide a reference for the evaluation of the pathogenicity of mutations in related genes that cause protein truncation in clinical practice. According to the characteristics of breakpoints, non-homologous end joining and microhomology-mediated break-induced replication may be the main mechanism for ABCRs formation.

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Acknowledgements

We thank the patients and family members for their participation. Thanks to the National Natural Science Foundation of China for the strong support to this project.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81873478).

Author information

Author notes

  1. Yanqin Xiao and Dehua Cheng contributed equally to this work.

Authors and Affiliations

  1. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410008, Hunan, China

    Yanqin Xiao, Keli Luo, Yueqiu Tan, Ge Lin & Liang Hu

  2. Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410023, Hunan, China

    Dehua Cheng, Keli Luo, Yueqiu Tan, Ge Lin & Liang Hu

  3. National Engineering and Research Center of Human Stem Cells, Changsha, 410023, Hunan, China

    Mengge Li, Ge Lin & Liang Hu

  4. Hunan Guangxiu Hospital, Changsha, 410023, Hunan, China

    Mengge Li

  5. Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, 410008, Hunan, China

    Ge Lin & Liang Hu

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  1. Yanqin Xiao
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Contributions

Conceptualization: DC, YT, LH, GL; methodology: DC, GL, YT, LH; formal analysis and investigation: DC, YX, KL, ML; writing—original draft preparation: DC, YX; writing—review and editing: YX, LH; visualization: YX; funding acquisition: LH; resources: YT, GL, LH; supervision: LH.

Corresponding author

Correspondence to Liang Hu.

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Ethics approval and consent to participate

This study was approved by Reproductive and Genetic Hospital of CITIC Xiangya Ethics Committee and informed consent was obtained from the patients. The ethical approval number is LL-SC-2016-002.

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All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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The authors declare no competing interests.

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Xiao, Y., Cheng, D., Luo, K. et al. Evaluation of genetic risk of apparently balanced chromosomal rearrangement carriers by breakpoint characterization. J Assist Reprod Genet 41, 147–159 (2024). https://doi.org/10.1007/s10815-023-02986-7

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  • DOI: https://doi.org/10.1007/s10815-023-02986-7

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