Duplications in 19p13.3 are associated with male infertility
To identify genomic imbalances and candidate loci in idiopathic male infertility.
Affymetrix CytoScan 750K Array was used to analyze genomic imbalances and candidate loci in 34 idiopathic infertile cases of different phenotypes (hypo-spermatogenesis, n = 8; maturation arrest, n = 7; and Sertoli cell-only syndrome, n = 13, severe oligozoospermia, n = 6, and 10 normozoospermic fertile men). Ten ethnically matched controls were screened for comparison.
The cytogenetic array analysis detected a genomic gain at the 19p13.3 region in 9 (26.47%) cases, with the highest frequency in patients with Sertoli cell-only syndrome (SCOS) (38%). Its complete absence in the control group suggests its likely pathogenic nature. In addition to Y-classical, micro, and partial deletions, the duplication in 19p13.3 could serve as a unique biomarker for evaluation of infertility risk. The common region across the individuals harboring the duplication identified STK11, ATP5D, MIDN, CIRBP, and EFNA2 genes which make them strong candidates for further investigations. The largest duplicated region identified in this study displayed a major network of 7 genes, viz., CIRBP, FSTL3, GPX4, GAMT, KISS1R, STK11, and PCSK4, associated with reproductive system development and function. The role of chance was ruled out by screening of ethnically matched controls.
The result clearly indicates the significance of 19p13.3 duplication in infertile men with severe testicular phenotypes. The present study underlines the utility and significance of whole genomic analysis in the cases of male infertility which goes undiagnosed due to limitations in the conventional cytogenetic techniques and for identifying genes that are essential for spermatogenesis.
KeywordsCopy number variations Genomic imbalances Cytogenetic microarray Infertility Spermatogenesis
The authors thank the patients for providing blood samples and their consent for genetic analysis. We would like to acknowledge the Interdisciplinary School of Life Sciences (ISLS), Banaras Hindu University for Affymetrix Microarray Facility. The first author thanks CSIR for the Senior Research Fellowship.
The study was funded by the Board of Research in Nuclear Sciences (BRNS), Govt. of India, with sanction number 2013/37B/27/BRNS.
Compliance with ethical standards
This study was approved by the Institutional Human Ethics Committee of the Institute of Science, Banaras Hindu University, Varanasi, approved this study (Approval letter No. Dean/2011-12/119).
Informed consent was obtained from all individual participants included in the study.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee.
Conflict of interest
The authors declare that they have no competing interests.
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