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AZFc region of the Y chromosome shows singular structural organization

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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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Correspondence to Sher Ali.

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Responsible Editor: Wendy Bickmore

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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)

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Supplementary Figure 2

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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

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