Abstract
Owing to clonal inheritance, haploid status and lack of recombination, structural polymorphism in the human Y chromosome is more prevalent than that in the remaining parts of the genome. We studied structural organization of the AZFc region, assessed microdeletions therein and studied copy number variation (CNV) of several candidate genes in 750 Indian males. FISH mapping of 13 Y-specific BAC/cosmid clones uncovered a hitherto unreported AZFc configuration showing inter-DAZ gene sequence onto the Yp instead of Yq region. Such inter-DAZ gene arrangements were also detected in five German males (European Y). In 40–50% males, partial u3 and one of the green amplicons, g1, g2 or g3 was present on the Yp in addition to Yq, suggesting an alteration in the IR3 region. Among other AZFc candidates, complete TTY3 and partial CDY1 BAC sequences were detected on the proximal 5p and distal 15q regions, respectively, in both the sexes. However, primers deduced from these clones showed male specific amplification of TTY3 and CDY1 exons suggesting (re)organization of their flanking sequences between Y and autosomes. Importantly, ∼5% males showed CNV of various Y-linked genes, and ∼3%, random microdeletions across the AZF region. Present study demonstrates hitherto unreported singular structural organization with respect to DAZ, TTY3 and CDY1 genes highlighting organizational complexities of the human Y chromosome in the global context.
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Abbreviations
- AZF:
-
Azoospermia factor
- BAC:
-
Bacterial artificial chromosome
- BPY:
-
Basic protein on Y
- CDY:
-
Chromodomain protein on Y
- CDYL:
-
Chromodomain protein, Y-like
- CNP:
-
Copy number polymorphism
- CNV:
-
Copy number variations
- CHORI:
-
Children's Hospital Oakland Research Institute
- CSPG4LY:
-
Chondroitin sulfate proteoglycan 4-like, Y-linked pseudogene 1
- Ct:
-
Cycle threshold
- DAZ:
-
Deleted in azoospermia
- DAZLA:
-
Deleted in azoospermia-like
- DDX3Y:
-
Dead (aspartate-glutamate-alanine-aspartate) box polypeptide 3, Y-linked
- FISH:
-
Fluorescence in situ hybridization
- GOLGA2LY:
-
Golgi auto antigen, golgin subfamily a, 2-like, Y-linked
- HERV:
-
Human retro-viral sequences
- MSY:
-
Male specific region on Y chromosome
- NAHR:
-
Non-allelic homologous recombination
- NBR:
-
Natural background radiation
- NIIEBC:
-
National Institute of Immunology Ethical and Biosafety Committees
- NRY:
-
Non-recombining region of the Y
- PCR:
-
Polymerase chain reaction
- PRY:
-
PTPN13-like, Y-linked
- SNV:
-
Single nucleotide variants
- SRY:
-
Sex determining region on Y chromosome
- STS:
-
Sequence tagged sites
- TTY:
-
Testis specific transcripts, Y-linked
- USP9Y:
-
Ubiquitin specific peptidase 9 on Y
- UTY:
-
Ubiquitously transcribed tetra-tricopeptide repeat gene, Y-linked
- VCY:
-
Variable charge, Y-linked
- WCP:
-
Whole chromosome painting
- XKRY:
-
XK, Kell blood group complex subunit-related, Y-linked
- YAC:
-
Yeast artificial chromosome
- ZFX:
-
Zinc finger protein, X-linked
- ZFY:
-
Zinc finger protein, Y-linked
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Acknowledgements
This work was supported by a DBT Grant No. BT/PR8476/AAQ/01/315/2006 to SA and a core grant from the Department of Biotechnology, Govt. of India to the National Institute of Immunology, New Delhi. Senior Research Fellowship from the Council of Scientific and Industrial Research, New Delhi to SP and Equipment donation from the Alexander Von Humboldt Foundation, Bonn, Germany to SA are gratefully acknowledged. We thank Dr. Sangeeta Thatai and Shri Khem Singh Negi for technical assistance.
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Supplementary Table 1
Details of the BAC and cosmid clones used as probes for FISH and PCR primers used for the authentication of the corresponding clones. (DOC 46 kb)
Supplementary Table 2
List of Y chromosome specific STS markers (DOC 25 kb)
Supplementary Table 3
List of SNVs and STSs used to ascertain the intactness of the DAZ genes and AZFc region. “+” denotes the presence of signal in the males analyzed (DOC 47 kb)
Supplementary Figure 1
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Supplementary Figure 2
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Supplementary Figure 3
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Supplementary Figure 4
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Premi, S., Srivastava, J., Epplen, J.T. et al. AZFc region of the Y chromosome shows singular structural organization. Chromosome Res 18, 419–430 (2010). https://doi.org/10.1007/s10577-010-9123-1
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DOI: https://doi.org/10.1007/s10577-010-9123-1