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

• Published in: Journal of human genetics 2022-02, Vol.67 (2), p.107-114
• Main Authors: Chen, Songchang, Zhang, Qian, Chu, Liming, Chang, Chunxin, Chen, Yiyao, Bao, Zhongwei, Peng, Weihua, Zhang, Lanlan, Li, Shuyuan, Liu, Chao, Zhu, Huanhuan, Yu, Feng, Chen, Xiaoyan, Jiang, Lili, Lu, Daru, Jiang, Zhengwen, Jin, Li, Xu, Chenming
• Format: Article
• Language: English
• Subjects: Cell Cycle Proteins - genetics; Chromosomes, Human, Y - genetics; Copy number; DNA Copy Number Variations - genetics; Gene loci; Genetic factors; Genetic Loci - genetics; Humans; In Situ Hybridization, Fluorescence - methods; Infertility; Infertility, Male - diagnosis; Infertility, Male - genetics; Karyotyping - methods; Male; Multiplex Polymerase Chain Reaction; Nuclear Proteins - genetics; Oligospermia - diagnosis; Oligospermia - genetics; Reproducibility of Results; Retrospective Studies; RNA-Binding Proteins - genetics; Sensitivity and Specificity; Sex Chromosome Aberrations; Sex chromosomes; Sperm Count; Y chromosomes
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-021-00973-3

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) (