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.
Journal of human genetics. 2021 Aug 31 [Epub ahead of print]
Songchang Chen, Qian Zhang, Liming Chu, Chunxin Chang, Yiyao Chen, Zhongwei Bao, Weihua Peng, Lanlan Zhang, Shuyuan Li, Chao Liu, Huanhuan Zhu, Feng Yu, Xiaoyan Chen, Lili Jiang, Daru Lu, Zhengwen Jiang, Li Jin, Chenming Xu
Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China., The First Hospital Affiliated to Army Medical University, Chongqing, China., Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China., The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Genesky Diagnostics (Suzhou) Inc., Suzhou, Jiangsu, China. ., The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. ., Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China. .