Disease relevance of DAZ1

• The Deleted in AZoospermia (DAZ) genes encode potential RNA-binding proteins that are expressed exclusively in prenatal and postnatal germ cells and are strong candidates for human fertility factors [1].
• The DAZ (Deleted in AZoospermia) and DAZLA (DAZ-like autosomal) genes may be determinants of male infertility [2].
• Although loss of DAZ family genes is associated with infertility in several organisms including humans, the identity of the transcripts regulated in vivo is unknown [3].
• RESULT(S): The frequency of complete AZF deletions was similar in idiopathic (13.3%) and cryptorchid men (11.6%), but partial DAZ deletions were found only in infertile subjects without cryptorchidism (7.1%) [4].
• RESULTS: Of the 10 Y chromosome specific genes DAZ gene expression was lacking in all prostate cancer cell lines but after demethylation treatment with 5-azaC DAZ expression was restored [5].

High impact information on DAZ1

• RBM1, but not DAZ or TSPY, has a Y-linked homologue in marsupials which is transcribed in the testis [6].
• The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned [7].
• Sequence analysis indicates that the Y-chromosomal DAZ cluster arose during primate evolution by (i) transposing the autosomal gene to the Y, (ii) amplifying and pruning exons within the transposed gene and (iii) amplifying the modified gene [7].
• Transmission of deletions from father to son has been observed in the case of DAZ, but neither gene family has been shown to be essential for spermatogenesis in human males [8].
• A candidate gene for the Y-chromosome azoospermia factor (AZF) has been identified and named Deleted in Azoospermia (DAZ) [9].

Chemical compound and disease context of DAZ1

• In six men with infertility after surgery for cryptorchidism, the adult karyotype and analyses for the DAZ gene, serum follicle-stimulating hormone, luteinizing hormone, and testosterone were performed from a peripheral blood sample [10].

Biological context of DAZ1

• Furthermore, the DAZ1/DAZ2 deletion has been detected as the primary subtype of the gr/gr deletion in East Asians, though this doublet has been considered as crucial for normal spermatogenesis in Europeans [11].
• Differences between incomplete (23.3%) and complete (4.5%) MA cases regarding AZFc and DAZ1/DAZ2 deletion frequencies, and between incomplete (58.3%) and complete (11.1%) SCOS cases for AZFc deletions, suggest that incomplete syndromes might represent an aggravation of the oligozoospermic phenotype [12].
• High frequency of DAZ1/DAZ2 gene deletions in patients with severe oligozoospermia [13].
• No DAZ homologous sequences have been found on the mouse Y chromosome [2].
• We report the isolation of the human DAZLA gene by screening a human testis cDNA library with a DAZ cDNA clone [2].

Anatomical context of DAZ1

• We identified proteins that interact with DAZ proteins to better understand their function in human germ cells [14].
• We have isolated a series of human testis poly(A) cDNA clones by cross-hybridization to SPGY1, a Y gene homologous to DAZ [15].
• A SPGY copy homologous to the mouse gene Dazla and the Drosophila gene boule is autosomal and expressed only in the human male gonad [15].
• Identification of a novel gene, DZIP (DAZ-interacting protein), that encodes a protein that interacts with DAZ (deleted in azoospermia) and is expressed in embryonic stem cells and germ cells [16].
• RESULTS: 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 [17].

Associations of DAZ1 with chemical compounds

• Fiber-FISH confirmed this outcome in C1-C4, but not in C5 who had an incomplete DAZ gene cluster [18].
• The men underwent then quantitative real-time PCR and C1 was arbitrarily selected as calibrator for the calculation of the DAZ gene signals because of the lowest variation in the threshold cycles [18].
• Y microdeletions were examined with 16 sequence-tagged site (STS) probes, including the RBM and DAZ genes, spanning the AZFb and AZFc subregions of Yq11, and related to the size of trinucleotide repeat encoding the AR polyglutamine tract [19].
• When cells were continuously exposed to each agent for 7 days, Ara-C was the most inhibitory, DAZ slightly less effective and AAC the least inhibitory on a molar basis [20].
• The doubling of DAZ allowed further increases in testosterone in hominids that resulted in the increased size and development of the brain [21].

Other interactions of DAZ1

• The deleted-in-azoospermia (DAZ) gene family constitutes the major candidate for the AZFc (azoospermia factor c) phenotype of male infertility, being deleted in about 10% of azoospermic and severely oligozoospermic subjects [22].

Analytical, diagnostic and therapeutic context of DAZ1

• We therefore conclude that the deletion of the DAZ1/DAZ2 gene doublet in five out of our 63 oligozoospermic patients (8%) is responsible for the patients' reduced sperm numbers [13].
• We report a quantitative real-time PCR application to evaluate partial deletions of the DAZ gene cluster [18].
• Quantitative evaluation of partial deletions of the DAZ gene cluster [18].
• Here, fluorescence in situ hybridization and characterization of BAC clones revealed four full-length DAZ genes on the human Y chromosome [23].
• Southern blot analysis showed that DAZLA is autosomal in all mammals tested and that DAZ has been recently translocated to the Y chromosome, sometime after the divergence of Old World and New World primates [24].

References