Association of the deleted DAZ gene copy related to gr/gr and b2/b3 deletions with spermatogenic impairment / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of the deleted azoospermia (DAZ) gene copy related to gr/gr and b2/b3 deletions in the AZFc region with male spermatogenic impairment.</p><p><b>METHODS</b>This study included 121 infertile men with different de- grees of spermatogenic impairment and 95 healthy donors from the sperm bank. Using PCR, PCR-RFLP, and Y chromosome specific sequence tagged sites (STS) , we analyzed the association of DAZ gene copy deletions related to gr/gr and b2/b3 deletions in the AZFc region with spermatogenic impairment.</p><p><b>RESULTS</b>There were 15 cases of gr/gr deletion (12. 40% ) and 6 cases of b2/b3 deletion (4.96%) in the infertility group as compared with 13 cases of gr/gr deletion (13.68%) and 1 case of b2/b3 deletion (1.05%) in the control. Analysis of the DAZ-specific single nucleotide variant (SNV) loci revealed 11 gr/gr-DAZI/DAZ2 deletions (9.09%), 4 gr/gr-DAZ3/DAZ4 deletions (3.31%), and 6 b2/b3-DAZ1/DAZ2 deletions (4.96%) in the infertile men in comparison with 3 gr/ gr-DAZ1/DAZ2 deletions (3.16%), 10 gr/gr-DAZ3/DAZ4 deletions (10.53%), and 1 b2/b3- DAZ3/DAZ4 deletion (1.05%) in the control.</p><p><b>CONCLUSION</b>Partial deletions of gr/gr and b2/b3 exist in both healthy men and male patients with different degrees of spermatogenic impairment and cannot be considered as a risk factor for spermatogenesis impairment. However, deletions of different DAZ duplicons in gr/gr and b2/b3 deletions have different effects on spermatogenesis. DAZ1/DAZ2 instead of DAZ3/DAZ4 deletions might be associated with spermatogenesis impairment.</p>

Breakpoint localization of Y-chromosome massive deletions in 49 spermatogenesis dysfunction patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the characteristics of azoospermia factor(AZF) deletions in Y-chromosome.</p><p><b>METHODS</b>Based on the AZF microdeletion screening on 272 cases of azoospermia and 240 cases of severe oligozoo spermia, 49 cases were investigated using 23 sequence-tagged sites (STS) in AZFa, AZFb and AZFc. For some cases, single nucleotide rarians (SNV) method was applied to identify the single nucleotide polymorphism (SNPs) in four DAZ gene copies and to determine the copy number of the DAZ gene.</p><p><b>RESULTS</b>In 6 cases with deletions of AZFb+c, there was 1 case with sY98/sY1206 deletion, 4 cases with P5/distal-P1 recombination and 1 with P4/distal-P1 recombination. In 3 cases with deletions in AZFb, 1 case showed P5/P3 deletion and 2 cases showed P5/proximal-P1 recombination with DAZ1 and DAZ2 deletions. b2/b4 recombination was observed in all the 40 cases with deletions in AZFc. A fraction of patients with AZFb and AZFb+c deletions showed oligospermia and spermatogenic failure by testicular biopsy.</p><p><b>CONCLUSION</b>Breakpoint localization of deletions in AZF regions may help elucidating the mechanisms of microdeletions, and analysis of the characteristics and quantity of deleted genes essential for normal spermatogenesis may evaluate the association of phenotype with spermatogenic failure.</p>

Uniform deletion junctions of complete azoospermia factor region c deletion in infertile men in Taiwan / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To determine the deletion junctions of infertile men in Taiwan with azoospermia factor region c (AZFc) deletions and to evaluate the genotype/phenotype correlation.</p><p><b>METHODS</b>Genomic DNAs from 460 infertile men were examined. Bacterial artificial chromosome clones were used to verify the accuracy of polymerase chain reaction. Deletion junctions of the AZFc region were determined by analysis of sequence-tagged sites and gene-specific markers.</p><p><b>RESULTS</b>Complete AZFc deletions, including BPY2, CDY1 and DAZ genes, were identified in 24 men. The proximal breakpoints were clustered between sY1197 and sY1192, and the distal breakpoints were clustered between sY1054 and sY1125 in all but one of the 24 men. The testicular phenotypes of men with complete AZFc deletion varied from oligozoospermia, to hypospermatogenesis, to maturation arrest.</p><p><b>CONCLUSION</b>We identified a group of infertile men with uniform deletion junctions of AZFc in the Taiwan population. Despite this homogeneous genetic defect in the AZFc region, no clear genotype/phenotype correlation could be demonstrated.</p>

A differentially methylated region of the DAZ1 gene in spermatic and somatic cells / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the methylation status of the deleted in azoospermia 1 (DAZ1) gene promoter region in different cell types.</p><p><b>METHODS</b>Using CpG island Searcher software, a CpG island was found in the promoter region of the DAZ1 gene. The methylation status of this region was analyzed in sperm and leukocytes by bisulfited sequencing.</p><p><b>RESULTS</b>The methylation status of the CpG island in the DAZ1 gene promoter region differed in leukocytes and sperm: it was methylated in leukocytes, but unmethylated in sperm.</p><p><b>CONCLUSION</b>A differentially methylated region of the DAZ1 gene exists in spermatic and somatic cells, suggesting that methylation of this region may regulate DAZ1 gene expression in different tissues.</p>

Important genetic etiology of infertile Chinese males: chromosome abnormality and deletion of DAZ gene copy in the AZFc region of Y chromosome / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of male infertility with abnormality of chromosomal quantity and construction and with the deletion of DAZ gene copy in the AZFc region of Y chromosome.</p><p><b>METHODS</b>Included in the study were 247 azoospermic and 206 severe oligozoospermic patients, as well as 210 fertile men as controls. Multi-PCR and PCR-RFLP were used to analyze the deletion of DAZ gene copies in the AZFc region of Y chromosome. Chromosomal quantity and construction were detected by G-band in the 453 patients.</p><p><b>RESULTS</b>In the azoospermic and severe oligozoospermic patients, the incidences of chromosomal abnormality were 12.6% and 8.3%; the rates of complete DAZ deletion were 7.7% and 11.2%, and the rates of DAZ1/DAZ2 deletion were 7.3% and 4.9% respectively, but no deletion was detected in the controls.</p><p><b>CONCLUSION</b>There is a high frequency of chromosomal abnormality and DAZ gene copy deletion in patients with azoospermia and oligospermia, which suggests that chromosomal abnormality and partial and complete deletion of DAZ gene copy might be important genetic causes of Chinese male infertility.</p>

Idiopathic male infertility and partial copy deletion of DAZ gene family / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the pattern and prevalence of partial copy deletion of deleted-in-azoospermia (DAZ) gene in the azoospermia factor C(AZFc) region of patients with idiopathic azoospermia or severe oligozoospermia.</p><p><b>METHODS</b>sY581 and sY587 in DAZ gene region were analyzed by polymerase chain reaction-restriction length polymorphism(PCR-RFLP) for its deletion in 197 patients with azoospermia, 166 patients with severe oligozoospermia, and 210 fertile men as controls.</p><p><b>RESULTS</b>Deletion of both DAZ1 and DAZ2 was detected in 18 patients with azoospermia and 10 with severe oligozoospermia, and the prevalence was 9.1% and 6.0% respectively. There was significant difference in deletion rate between the cases and controls.</p><p><b>CONCLUSION</b>The frequency of partial copy deletion of DAZ gene in Chinese idiopathic azoospermia or severe oligozoospermia patients is much higher than that of fertile controls, suggesting that the deletion of DAZ1/DAZ2 may be one of the important genetic etiological factors of spermatogenesis damage. The pattern and prevalence of DAZ partial copy deletion are similar to those of Caucasians populations, and detection of DAZ gene partial copy deletion by PCR-RFLP may be adopted as an additional clinical gene diagnostic measure after AZF microdeletion detection.</p>

Real-time fluorescent PCR for screening AZFc/DAZ microdeletions on the Y chromosome in male infertility patients / 中华男科学杂志

<p><b>OBJECTIVE</b>To develop a real-time fluorescent PCR protocol suitable for the routine screening of AZFc/DAZ microdeletions on the Y chromosome in azoospermic and oligozoospermic male infertility patients.</p><p><b>METHODS</b>A set of real-time fluorescent PCR was established. Eighty-seven azoospermic and ligozoospermic patients undergoing ICSI in the IVF center and 30 azoospermic men undergoing testicular biopsy in the clinic of urology surgery were screened for AZFc/DAZ microdeletions of Y chromosome.</p><p><b>RESULTS</b>Eleven cases (9.4%) of AZFc/DAZ microdeletions were found in 117 cases of azoospermic and oligozoospermic patients by screening of realtime fluorescent PCR. Four cases (6.6%) were found in 61 oligozoospermic patients, and 7 cases (12.5%) were found in 56 azoospermic patients.</p><p><b>CONCLUSION</b>The real-time fluorescent PCR protocol presented in this study is an easy and reliable method for detection of AZFc/DAZ microdeletions on the Y chromosome, which yields identical results to those of the multiplex PCR.</p>