Array comparative genomic hybridization (CGH) analysis of sperm DNA to detect copy number variations in infertile men with idiopathic azoospermia

Dimova Ivanka^1,4, Damyanova Vera², Nesheva Desislava¹, Hadjidekova Savina¹, Vatev Ilia², Stanislavov Romil³, Nikolova Vesela³ and

Toncheva Draga¹*

¹Department of Medical Genetics, Medical University – Sofia, Bulgaria.

²Department of Medical Biology, Medical University – Sofia, Bulgaria.

³Seminologic Laboratory, University Hospital of Obstetrics and Gynecology – Sofia, Bulgaria.

⁴Institute of Anatomy, University of Fribourg, CH-1700 Fribourg, Switzerland.

*Corresponding author. E-mail: dragatoncheva@yahoo.com. 

Tel/Fax: +359 2 952 03 57. 

Accepted 22 January, 2010

   Abstract

Epididymal and testicular spermatozoa of azoospermic patients are frequently used for intracytoplasmic sperm injection (ICSI), so they must be screened for genetic abnormalities. The objective of our study was to investigate whole genome imbalances in immature germ cells found in ejaculates of six males with idiopathic azoospermia and normal karyotype. We used for the first time the most powerful tool for genetic screening - microarray-based technology of comparative genomic hybridization (array CGH) with microarrays, covering all autosomes and sex-chromosomes at a mean density of 1 BAC clone/0.5 Mb. Sub-microscopic copy number variations were found in sperm DNA of all analyzed patients. The most consistent were aberrations in Y-chromosome - they occurred in 5 out of 6 patients (83.3%). These Y micro-aberrations included both micro-deletions and micro-duplications. In addition to Y chromosomal micro-imbalances, we detected several other affected loci. These included 1р36 deletion together with 14q24 gain, 16q24 deletion, 9q34 gain and 3q29 deletion. By array CGH analysis we determined cryptic whole genome imbalances in sperm cells and defined the most precisely the size and the boundaries of aberrations.

Key words: Male infertility, azoospermia, sperm aneuploidy, whole genome analysis, array CGH.