Skip Navigation


Hum. Reprod. Advance Access first published online on August 9, 2008
This version published online on September 24, 2008
Human Reproduction, doi:10.1093/humrep/den278
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF ) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
23/12/2835    most recent
den278v2
den278v1
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 Oldenburg, R.A.
Right arrow Articles by Bertoli-Avella, A.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oldenburg, R.A.
Right arrow Articles by Bertoli-Avella, A.M.
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

A genome-wide linkage scan in a Dutch family identifies a premature ovarian failure susceptibility locus

R.A. Oldenburg1, M.F. van Dooren1, B. de Graaf1, E. Simons1, L. Govaerts1, S. Swagemakers2, J.M.H. Verkerk2, B.A. Oostra1 and A.M. Bertoli-Avella1,3

1 Department of Clinical Genetics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands 2 Department of Bioinformatics, Erasmus Medical Center, Rotterdam, the Netherlands

3 Correspondence address. Tel: +31-10-7044628; Fax:+31-10-7044736; E-mail: a.bertoliavella{at}erasmusmc.nl

BACKGROUND: Premature ovarian failure (POF) is characterized by elevated gonadotrophins and amenorrhea before the age of 40 years and occurs approximately in 1% of women. POF etiology is highly heterogeneous with a wide spectrum of etiological pathogenic mechanisms including genetic causes. These mostly involve numerical, structural or monogenic defects on the X-chromosome. Mutations in a small number of autosomal genes (such as FOXL2 and NOBOX) have been identified as a cause of POF. However, in most cases, the disease underlying mechanisms are largely unknown.

METHODS: We performed a genome-wide linkage analysis in a relatively large Dutch family with seven patients suffering from POF, showing a dominant pattern of inheritance. A genome-wide analysis, using 50K single nucleotide polymorphism arrays, was combined with conventional parametric linkage analysis.

RESULTS: We identified three genomic regions on chromosomes 5, 14 and 18 yielding suggestive linkage (multipoint LOD score of 2.4 for each region). After inclusion of one elder unaffected family member, only the region on chromosome 5 remains as a putative POF locus. In addition, we investigated a second family (three living patients over three generations) for the regions on chromosome 5, 14 and 18. Haplotype analysis supported only the locus on chromosome 5q14.1–q15.

CONCLUSION: We performed the first genome-wide linkage search in familial POF and identified a region on chromosome 5q14.1–q15, which may harbor a novel POF susceptibility gene.

Key words: premature ovarian failure/linkage analysis/familial/SNPs/genome-wide search

This is a new version of this paper as Figure 4 has been corrected.

Submitted on February 15, 2008; resubmitted on April 4, 2008; accepted on April 17, 2008.


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


This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
A. Aboura, C. Dupas, G. Tachdjian, M.-F. Portnoi, N. Bourcigaux, D. Dewailly, R. Frydman, B. Fauser, N. Ronci-Chaix, B. Donadille, et al.
Array Comparative Genomic Hybridization Profiling Analysis Reveals Deoxyribonucleic Acid Copy Number Variations Associated with Premature Ovarian Failure
J. Clin. Endocrinol. Metab., November 1, 2009; 94(11): 4540 - 4546.
[Abstract] [Full Text] [PDF]


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.