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The chromosomal characteristics of spontaneous abortion and its potential associated copy number variants and genes

  • Genetics
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Abstract

Purpose

This study aimed to investigate the correlation between chromosomal abnormalities in spontaneous abortion with clinical features and seek copy number variations (CNVs) and genes that might be connected to spontaneous abortion.

Methods

Over 7 years, we used CNV-seq and STR analysis to study POCs, comparing chromosomal abnormalities with clinical features and identifying critical CNVs and genes associated with spontaneous abortion.

Results

Total chromosomal variants in the POCs were identified in 66.8% (2169/3247) of all cases, which included 45.2% (1467/3247) numerical abnormalities and 21.6% (702/3247) copy number variants (CNVs). Chromosome number abnormalities, especially aneuploidy abnormalities, were more pronounced in the group of mothers aged ≥ 35 years, the early miscarriage group, and the chorionic villi group. We further analyzed 212 pathogenic and likely pathogenic CNVs in 146 POCs as well as identified 8 statistically significant SORs through comparison with both a healthy population and a group of non-spontaneously aborted fetuses. Our analysis suggests that these CNVs may play a crucial role in spontaneous abortion. Furthermore, by utilizing the RVIS score and MGI database, we identified 86 genes associated with spontaneous abortion, with particular emphasis on PARP6, ISLR, ULK3, FGFRL1, TBC1D14, SCRIB, and PLEC.

Conclusion

We found variability in chromosomal abnormalities across clinical features, identifying eight crucial copy number variations (CNVs) and multiple key genes that may be linked to spontaneous abortion. This research enhances the comprehension of genetic factors contributing to spontaneous abortion.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful to Berry Genomics Corporation (Beijing, China), for their expert technical assistance and data analysis (Yuanyuan Zhu, Yang Bai, Xiang Wang, Berry Genomics Corporation, Beijing 102200, China). We thank Shanghai NewCore Biotechnology Co., Ltd. (https://www.bioinformatics.com.cn, last accessed on 20 Feb 2024) for providing data analysis and visualization support.

Funding

This work was supported in part by grants from the National Natural Science Foundation of China (Grant No. 81200354); the National Science and Technology Major Project of China (2017ZX09304022); and the National Key Research and Development Program of China (2018YFC1002900).

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Authors and Affiliations

  1. Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan, 430030, Hubei, China

    Yu Qin, Koksear Touch, Yanan Sun, Shunran Zhang, Jianli Wu, Yuanyuan Wu, Ling Feng, Suhua Chen & Juan Xiao

  2. Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Menghan Sha

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  1. Yu Qin
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  2. Koksear Touch
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  3. Menghan Sha
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  4. Yanan Sun
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  8. Ling Feng
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  10. Juan Xiao
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Contributions

S.C. and J.X. participated in and designed the study. Y.Q., K.T., M.S., Y.S., S.Z., J.W., Y.W., and L.F. collected medical records and interpreted data. Y.Q. completed data organization and functional enrichment analysis as well as drafted the manuscript. K.T. completed further data analysis and processing. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Suhua Chen or Juan Xiao.

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The studies involving human participants were reviewed and approved by the guidance of the Ethics Committee of Tongji Hospital, Huazhong University of Science and Technology (TJ-IRB202303141). The patients provided their written informed consent to participate in this study.

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The authors declare no competing interests.

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Qin, Y., Touch, K., Sha, M. et al. The chromosomal characteristics of spontaneous abortion and its potential associated copy number variants and genes. J Assist Reprod Genet 41, 1285–1296 (2024). https://doi.org/10.1007/s10815-024-03119-4

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