Chromosome Research

, Volume 18, Issue 4, pp 419–430 | Cite as

AZFc region of the Y chromosome shows singular structural organization

  • Sanjay Premi
  • Jyoti Srivastava
  • Jörg Thomas Epplen
  • Sher Ali
Article

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.

Keywords

Structural polymorphism Copy number variation AZFc configuration Autosomal homologies 

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

Notes

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.

Supplementary material

10577_2010_9123_MOESM1_ESM.doc (46 kb)
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)
10577_2010_9123_MOESM2_ESM.doc (26 kb)
Supplementary Table 2 List of Y chromosome specific STS markers (DOC 25 kb)
10577_2010_9123_MOESM3_ESM.doc (47 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)
10577_2010_9123_Fig7_ESM.jpg (96 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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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Sanjay Premi
    • 1
  • Jyoti Srivastava
    • 1
  • Jörg Thomas Epplen
    • 1
    • 2
  • Sher Ali
    • 1
  1. 1.Molecular Genetics LaboratoryNational Institute of ImmunologyNew DelhiIndia
  2. 2.Abteilung HumangenetikMA/5/142, Ruhr UniversitäteBochumGermany

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