Duplications in 19p13.3 are associated with male infertility
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GENETICS
Duplications in 19p13.3 are associated with male infertility Vertika Singh 1 & Renu Bala 1 & Arijit Chakraborty 1 & Singh Rajender 2 & Sameer Trivedi 3 & Kiran Singh 1 Received: 23 May 2019 / Accepted: 24 July 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Purpose To identify genomic imbalances and candidate loci in idiopathic male infertility. Methods 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. Results 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. Conclusion 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. Keywords Copy number variations . Genomic imbalances . Cytogenetic microarray . Infertility . Spermatogenesis
Introduction Infertility refers to the inability of a couple to attain pregnancy after 1 year of regular intercourse without any contraception (WHO) [1]. It affects around 10–15% of all couples and approximately 50% of all infertility cases are attributed to “male Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10815-019-01547-1) contains supplementary material, which is available to authorized users. * Kiran Singh [email protected]; [email protected] 1
Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi 221005, India
2
Division of Endocrinology, Central Drug Research Institute, Lucknow, India
3
Department of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India
factor.” Human male infertility is a complex multifactorial disorder, commonly identified by dis
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