Abstract
Although copy-number variations (CNVs) in Y-chromosomal azoospermia factor (AZF) regions have been associated with the risk of spermatogenic failure (SF), the precise frequency, genomic basis and clinical consequences of these CNVs remain unclear. Here we performed multiplex ligation-dependent probe amplification (MLPA) analysis of 56 Japanese SF patients and 65 control individuals. We compared the results of MLPA with those of conventional sequence-tagged site PCR analyses. Eleven simple and complex CNVs, including three hitherto unreported variations, were identified by MLPA. Seven of the 11 CNVs were undetectable by conventional analyses. CNVs were widely distributed in AZF regions and shared by ~60% of the patients and ~40% of the controls. Most breakpoints resided within locus-specific repeats. The majority of CNVs, including the most common gr/gr deletion, were identified in the patient and control groups at similar frequencies, whereas simple duplications were observed exclusively in the patient group. The results imply that AZF-linked CNVs are more frequent and heterogeneous than previously reported. Non-allelic homologous recombination likely underlies these CNVs. Our data confirm the functional neutrality of the gr/gr deletion in the Japanese population. We also found a possible association between AZF-linked simple duplications and SF, which needs to be evaluated in future studies.
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Acknowledgements
We are grateful to the participants of this study. The study was supported by the Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology and from the Japan Society for the Promotion of Science and by the Grants from the Ministry of Health, Labor and Welfare (Grant Numbers: H26-062, 082, Tokyo, Japan) from National Center for Child Health and Development (Grant Numbers: 26-11, 26-19, Tokyo, Japan) and from Takeda foundation. The sponsors had no role in study design, in the collection, analysis or interpretation of data, in the writing of the report or in the decision to submit the article for publication.
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Saito, K., Miyado, M., Kobori, Y. et al. Copy-number variations in Y-chromosomal azoospermia factor regions identified by multiplex ligation-dependent probe amplification. J Hum Genet 60, 127–131 (2015). https://doi.org/10.1038/jhg.2014.115
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DOI: https://doi.org/10.1038/jhg.2014.115
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