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. 2021 Apr;38(4):941-948.
doi: 10.1007/s10815-020-02031-x. Epub 2021 Jan 16.

Y chromosome structural variation in infertile men detected by targeted next-generation sequencing

Xiangyin Liu  1 , Han Zhang  1 , Xinyue Zhang  1 , Hongguo Zhang  1 , Yuting Jiang  1 , Ruizhi Liu  1 , Jia Fei  2 , Ying Wang  2 , Yang Yu  3
Affiliations

Y chromosome structural variation in infertile men detected by targeted next-generation sequencing

Xiangyin Liu et al. J Assist Reprod Genet. 2021 Apr.

Abstract

Purpose: To provide a validated method to identify copy number variation (CNV) in regions of the Y chromosome of infertile men by next-generation sequencing (NGS).

Methods: Semen analysis was used to determine the quality of semen and diagnose infertility. Deletion of the azoospermia factor (AZF) region in the Y chromosome was detected by a routine sequence-tagged-site PCR (STS-PCR) method. We then used the NGS method to detect CNV in the AZF region, including deletions and duplications.

Results: A total of 326 samples from male infertility patients, family members, and sperm donors were studied between January 2011 and May 2017. AZF microdeletions were detected in 120 patients by STS-PCR, and these results were consistent with the results from NGS. In addition, of the 160 patients and male family members who had no microdeletions detected by STS-PCR, 51 cases were found to exhibit Y chromosome structural variations by the NGS method (31.88%, 51/160). No microdeletions were found in 46 donors by STS-PCR, but the NGS method revealed 11 of these donors (23.91%, 11/46) carried structural variations, which were mainly in the AZFc region, including partial deletions and duplications.

Conclusion: The established NGS method can replace the conventional STS-PCR method to detect Y chromosome microdeletions. The NGS method can detect CNV, such as partial deletion or duplication, and provide details of the abnormal range and size of variations.

Keywords: Copy number variation (CNV); Male infertility; Next generation sequencing (NGS); Spermatogenic failure; Y chromosome microdeletion.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flowchart on detection of Y chromosome microdeletion with STS-PCR and NGS method
Fig. 2
Fig. 2
Results of sY1191 and sY1291 by STS-PCR method. Note: ① represent detection of marker sY1191; ② represent detection of marker sY1291. JX009 and Y053 are cases with b1/b3 deletion. Y108 is a case of gr/gr deletion. Y046 is a case of b2/b3 deletion
Fig. 3
Fig. 3
The pattern graph of normal male NGS method results
See this image and copyright information in PMC

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