Abstract
Sex chromosome-related anomalies engender plethora of conditions leading to male infertility. Hypogonadotropic hypogonadism (HH) is a rare but well-known cause of male infertility. Present study was conducted to ascertain possible consensus on the alterations of the Y-linked genes and loci in males representing hypogonadism (H), which in turn culminate in reproductive dysfunction. A total of nineteen 46, XY males, clinically diagnosed with H (11 representative HH adults and eight prepubertal boys suspected of having HH) were included in the study. Sequence-tagged site screening, SRY gene sequencing, fluorescence in situ hybridization mapping (FISH), copy number and relative expression studies by real-time PCR were conducted to uncover the altered status of the Y chromosome in the patients. The result showed random microdeletions within the AZFa (73%)/b (78%) and c(26%) regions. Sequencing of the SRY gene showed nucleotide variations within and outside of the HMG box in four males (21%). FISH uncovered mosaicism for SRY, AMELY, DAZ genes and DYZ1 arrays, structural rearrangement for AMELY (31%) and duplication of DAZ (57%) genes. Copy number variation for seven Y-linked genes (2–8 rounds of duplication), DYZ1 arrays (495–6201copies) and differential expression of SRY, UTY and VCY in the patients’ blood were observed. Present work demonstrates the organizational vulnerability of several Y-linked genes in H males. These results are envisaged to be useful during routine diagnosis of H patients.
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Acknowledgements
We thank Prof. Schempp, Institute of Human Genetics, University of Freiburg, Germany for gifting the clones of DAZ and AMELY genes and Prof. Jamal Ahmad, J.N. Medical College, Aligarh Muslim University, Aligarh, India for providing H patient blood samples. We also thank patients for their consent, thus enabling us to undertake this study. We acknowledge Shri Khem Singh Negi for technical assistance. SA acknowledges Department of Science and Technology (DST), New Delhi, Government of India for the award of J. C. Bose National Fellowship and Alexander Von Humboldt Foundation, Bonn, Germany for equipment donation. This work was supported by the core grant provided by the Department of Biotechnology (DBT), New Delhi, to National Institute of Immunology, New Delhi, India and DBT grant BT/PR11805/MED/12/424/2009 to SA.
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[Pathak D., Yadav S. K., Rawal L. and Ali S. 2015 Mutational landscape of the human Y chromosome-linked genes and loci in patients with hypogonadism. J. Genet. 94, xx–xx]
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PATHAK, D., YADAV, S.K., RAWAL, L. et al. Mutational landscape of the human Y chromosome-linked genes and loci in patients with hypogonadism. J Genet 94, 677–687 (2015). https://doi.org/10.1007/s12041-015-0582-1
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DOI: https://doi.org/10.1007/s12041-015-0582-1