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Comprehensive copy number analysis of Y chromosome-linked loci for detection of structural variations and diagnosis of male infertility

Journal of Human Genetics volume 67, pages 107–114 (2022)Cite this article

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Abstract

Infertility affects about 15% of heterosexual couples and male factors account for ~45–50% of clinical cases. Genetic factors play an important role in male infertility and thus we try to develop a cost-effective method for screening the genetic factors in male infertility. In our retrospective proof-of-concept study, we employed the high-throughput ligation-dependent probe amplification (HLPA) to examine the copy number by 115 genomic loci covering the Y chromosome, and 5 loci covering the X chromosome-specific region. We identified 8 sex chromosome aneuploid people from the low sperm concentration (LSC) group, and Y chromosome-specific microdeletion/duplications in 211 samples from the LSC group, and in 212 samples from the control group. 35 samples showed complete loss of AZFc (BPY2 to CDY1B deletion), which was not observed in controls. Nevertheless, a partial loss of AZFc (BPY2 to BPY2B deletion) was detected at comparable frequencies in both groups (68/211 vs. 108/212, respectively). And we further found structural variations in 28.6 and 26.9% samples from infertility and fertility groups. Moreover, we found that there were lower copy numbers for heterochromatic sequences in men with LSC. Especially, we reported that ultra-low relative copy number (RCN) (<0.5) type and low RCN (0.5 to <0.75) type in Yq12 were more often in the LSC group for the first time. Our results not only shed light on the potential role of low RCN in Yq12 in male infertility but also showed that HLPA can be a powerful and cost-effective tool for clinical screening in male infertility.

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All data generated or analyzed during this study are included in this published article and Supplementary information files.

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Acknowledgements

This study was sponsored by the National Natural Science Foundation of China (81771638, 81901495, 81971344), Shanghai Sailing Program (18YF1424800), the National Key R&D Program of China (2018YFC1004901), the Shanghai Municipal Commission of Science and Technology Program (15411964000), the Shanghai “Rising Stars of Medical Talent” Youth Development Program Clinical Laboratory Practitioners Program (201972) and the National Key Research and Development Program of China (2016YFC0905103). The funding bodies did not contribute to the design of the study or collection, analysis, and interpretation of data and writing the manuscript.

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Author notes

  1. These authors contributed equally: Songchang Chen, Qian Zhang, Liming Chu

Authors and Affiliations

  1. Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China

    Songchang Chen, Daru Lu & Chenming Xu

  2. The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Songchang Chen, Chunxin Chang, Yiyao Chen, Lanlan Zhang, Shuyuan Li, Li Jin & Chenming Xu

  3. Shanghai Key Laboratory of Embryo Orignal Diseases, Shanghai, China

    Songchang Chen, Chunxin Chang, Yiyao Chen, Lanlan Zhang, Shuyuan Li, Li Jin & Chenming Xu

  4. The First Hospital Affiliated to Army Medical University, Chongqing, China

    Qian Zhang, Zhongwei Bao & Weihua Peng

  5. Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China

    Liming Chu, Chao Liu, Huanhuan Zhu, Feng Yu, Xiaoyan Chen, Lili Jiang & Zhengwen Jiang

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  1. Songchang Chen
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Contributions

SCC, QZ, LMC, DL, ZWJ, LJ, and CMX participated in study design, data analysis, and manuscript drafting. SCC, QZ, LMC, CXC, YYC, ZWB, WHP, LLZ, SYL, CL, HHZ, FY, XYC, LLJ participated in sample preparation, experiment performing, data collection, interpretation of results.

Corresponding authors

Correspondence to Zhengwen Jiang, Li Jin or Chenming Xu.

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Competing interests

LMC, CL, HHZ, FY, XYC, LLJ, and ZWJ are members of Genesky Diagnostics (Suzhou) Inc.

Ethics approval and consent to participate

This study was approved by the ethics committee of the International Peace Maternity & Child Health Hospital in Shanghai and the ethics committee of Southwest Hospital in Chongqing. All subjects provided informed consent before participating in the study.

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Chen, S., Zhang, Q., Chu, L. et al. Comprehensive copy number analysis of Y chromosome-linked loci for detection of structural variations and diagnosis of male infertility. J Hum Genet 67, 107–114 (2022). https://doi.org/10.1038/s10038-021-00973-3

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