Skip Navigation



Hum. Reprod. Advance Access published online on June 10, 2008
Human Reproduction, doi:10.1093/humrep/den191
This Article
Right arrow Full Text
Right arrow Full Text (PDF )
Right arrow Supplementary Data
Right arrow All Versions of this Article:
23/9/2151    most recent
den191v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Jamsai, D.
Right arrow Articles by O'Bryan, M.K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jamsai, D.
Right arrow Articles by O'Bryan, M.K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Polymorphisms in the human cysteine-rich secretory protein 2 (CRISP2) gene in Australian men

D. Jamsai1,2, A. Reilly3, S.J. Smith1,2, G.M. Gibbs1, H.W.G. Baker4, R.I. McLachlan3, D.M. de Kretser1,2 and M.K. O'Bryan1,2,5

1 Centre for Reproduction and Development, Monash Institute of Medical Research, Monash University, Clayton, VIC, Australia 2 The Australian Research Council Centre of Excellence for Biotechnology and Development, Monash University, Clayton, VIC, Australia 3 Prince Henry's Institute, Monash Medical Centre, Clayton, VIC, Australia 4 Department of Obstetrics and Gynaecology, University of Melbourne, Carlton, VIC, Australia

5 Correspondence address. Tel +61-3-95947407; Fax: +61-3-95947439; E-mail: moira.obryan{at}med.monash.edu.au

BACKGROUND: Cysteine-rich secretory protein 2 (CRISP2) is localized to the human sperm acrosome and tail. It can regulate ryanodine receptors Ca2+ gating and binds to mitogen-activated protein kinase kinase kinase 11 in the acrosome and gametogenetin 1 (GGN1) in the tail.

METHODS AND RESULTS: In order to test the hypothesis that CRISP2 variations contribute to male infertility, we screened coding and flanking intronic regions in 92 infertile men with asthenozoo- and/or teratozoospermia and 176 control men using denaturing HPLC and sequencing. There were 21 polymorphisms identified, including 13 unreported variations. Three SNPs resulted in amino acid substitutions: L59V, M176I and C196R. All were only present in a heterozygous state and found in fertile men. However, the C196R polymorphism was of particular interest as it resulted in the loss of a strictly conserved cysteine involved in intramolecular disulphide bonding. Screening of an additional 637 infertile men identified 23 heterozygous C196R men to give an overall frequency of 3.6%, compared with 3.4% in control men. The functional significance of the C196R polymorphism was defined using a yeast two-hybrid assay. The C196R substitution resulted in the loss of CRISP2–GGN1 binding.

CONCLUSIONS: Although none of the many polymorphisms identified herein showed a significant association with male infertility, functional studies suggested that the C196R polymorphism may compromise CRISP2 function.

Key words: CRISP2/TPX1/GGN/male infertility/single-nucleotide polymorphism

Submitted on October 10, 2007; resubmitted on March 25, 2008; accepted on April 16, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.