Array comparative genomic hybridization profiling analysis reveals deoxyribonucleic acid copy number variations associated with premature ovarian failure.

Abstract

INTRODUCTION:

Premature ovarian failure (POF) is defined by amenorrhea of at least 4- to 6-month duration, occurring before 40 yr of age, with two FSH levels in the postmenopausal range. Its etiology remains unknown in more than 80% of cases. Standard karyotypes, having a resolution of 5-10 Mb, have identified critical chromosomal regions, mainly located on the long arm of the X chromosome. Array comparative genomic hybridization (a-CGH) analysis is able to detect submicroscopic chromosomal rearrangements with a higher genomic resolution. We searched for copy number variations (CNVs), using a-CGH analysis with a resolution of approximately 0.7 Mb, in a cohort of patients with POF.

PATIENTS AND METHODS:

We prospectively included 99 women. Our study included a conventional karyotype and DNA microarrays comprising 4500 bacterial artificial chromosome clones spread on the entire genome.

RESULTS:

Thirty-one CNVs have been observed, three on the X chromosome and 28 on autosomal chromosomes. Data have been compared to control populations obtained from the Database of Genomic Variants (http://projects.tcag.ca/variation). Eight statistically significantly different CNVs have been identified in chromosomal regions 1p21.1, 5p14.3, 5q13.2, 6p25.3, 14q32.33, 16p11.2, 17q12, and Xq28.

CONCLUSION:

We report the first study of CNV analysis in a large cohort of Caucasian POF patients. In the eight statistically significant CNVs we report, we found five genes involved in reproduction, thus representing potential candidate genes in POF. The current study along with emerging information regarding CNVs, as well as data on their potential association with human diseases, emphasizes the importance of assessing CNVs in cohorts of POF women.

• Authors: Azzedine Aboura, Claire Dupas, Gérard Tachdjian, Marie-France Portnoï, Nathalie Bourcigaux, Didier Dewailly, René Frydman, Bart Fauser, Nathalie Ronci-Chaix, Bruno Donadille, Philippe Bouchard, Sophie Christin-Maitre
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 94 Issue 11 Pg. 4540-6 (Nov 2009) ISSN: 1945-7197 [Electronic] United States
• PMID: 19837940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Follicle Stimulating Hormone
• DNA

Topics

• Adult
• Chromosomes, Artificial, Bacterial
• Chromosomes, Human, X
• Comparative Genomic Hybridization (methods)
• DNA (genetics, isolation & purification)
• Female
• Follicle Stimulating Hormone (blood)
• Gene Expression Profiling (methods)
• Genetic Variation
• Genome, Human
• Humans
• Karyotyping
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Postmenopause
• Primary Ovarian Insufficiency (blood, genetics)
• Prospective Studies
• Translocation, Genetic