title: Combined deletion of DAZ2 and DAZ4 copies of Y chromosome DAZ gene is associated with male infertility in Tunisian men.
abstract: The relationship between male infertility and AZFc micro-deletions that remove multiple genes of the Y chromosome varies among countries and populations. The purpose of this study was to analyze the prevalence and the characteristics of different Deleted in azoospermia (DAZ) gene copy deletions and their association with spermatogenic failure and male infertility in Tunisian men. 241 infertile men (30.7% azoospermic (n=74), 31.5% oligozoospermic (n=76) and 37.7% normozoospermic (n=91)) and 115 fertile healthy males who fathered at least one child were included in the study. Three DAZ-specific single nucleotide variant loci and six bi-allelic DAZ-SNVs (I-VI) were analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR. Our findings showed high frequencies of infertile men (73.85%) and controls (78.26%) having only three DAZ gene copies (DAZ1/DAZ2/DAZ3 or DAZ1/DAZ3/DAZ4 variants); so deletion of DAZ2 or DAZ4 were frequent both in infertile (36.5% and 37.3%, respectively) and fertile groups (33.9% and 44.3%, respectively) and removing DAZ4 copy was significantly more frequent in oligospermic than in normospermic men (p=0.04) in infertile group. We also report for the first time that simultaneous deletion of both DAZ2 and DAZ4 copies was significantly more common in infertile men (12.4%) than in fertile men (4.3%) (p=0.01). However, deletions of DAZ1/DAZ2 and DAZ3/DAZ4 clusters were very rare. Analysis of DAZ gene copies in Tunisian population, suggested that the simultaneous deletion of DAZ2 and DAZ4 gene copies is associated with male infertility, and that oligospermia seems to be promoted by removing DAZ4 copy.
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia. Electronic address: myriamgh29@gmail.com.
authors.forename: Myriam
authors.initials: M
authors.lastname: Ghorbel
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Siwar
authors.initials: S
authors.lastname: Baklouti-Gargouri
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Rim
authors.initials: R
authors.lastname: Keskes
authors.affiliation: Laboratory of Histology & Embryology, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Nozha
authors.initials: N
authors.lastname: Chakroun
authors.affiliation: Laboratory of Histology & Embryology, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Afifa
authors.initials: A
authors.lastname: Sellami
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
authors.affiliation: Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Ammar-Keskes
mesh_terms: D000328:Adult; D053713:Azoospermia / Q000235:genetics*; D016022:Case-Control Studies; D041322:Chromosomes, Human, Y / Q000235:genetics*; D000075364:Deleted in Azoospermia 1 Protein; D017353:Gene Deletion; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D014416:Tunisia
chemical_list: C095668:DAZ1 protein, human; C459440:DAZ2 protein, human; C543054:DAZ3 protein, human; C543055:DAZ4 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D016601:RNA-Binding Proteins
keywords: Deleted in azoospermia (DAZ) gene; Male infertility; Tunisian population; Y chromosome