{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe Deleted in Azoospermia (DAZ) gene family, which includes DAZ1, plays an essential role in human spermatogenesis. Unlike the earlier‐acting DAZL protein that regulates primordial germ cell formation, DAZ1 and its family members function at later stages of germ cell development—facilitating the progression of meiosis and the development of haploid gametes. In part, these proteins exert their effect by activating translation; they interact with poly(A)-binding proteins to promote the initiation of translation of specific mRNAs that are otherwise dormant in germ cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and molecular analyses have underscored the clinical significance of DAZ1 dosage in spermatogenesis. Detailed investigations have revealed that partial deletions—most notably of the DAZ1/DAZ2 gene copies within the AZFc region of the Y chromosome—are consistently associated with spermatogenic failure and reduced sperm production (oligozoospermia) in affected men. Copy number assays and deletion screening in various populations have demonstrated that loss of DAZ1 (often accompanied by deletion of DAZ2) is a significant risk factor for male infertility, affirming the dosage-sensitive nature of this gene."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these findings highlight a dual role for DAZ1: as a molecular effector that modulates translation initiation during the critical post-meiotic phase of germ cell development and as a key genetic biomarker whose deletion predisposes to impaired spermatogenesis and male infertility. This integrated perspective reinforces the importance of assessing DAZ1 copy number and function during the diagnostic workup of infertile patients.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Frederick L Moore, Jadwiga Jaruzelska, Mark S Fox, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-like proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0234478100"}], "href": "https://doi.org/10.1073/pnas.0234478100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12511597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12511597"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Brian Collier, Barbara Gorgoni, Carolyn Loveridge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The DAZL family proteins are PABP-binding proteins that regulate translation in germ cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600738"}], "href": "https://doi.org/10.1038/sj.emboj.7600738"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16001084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16001084"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kehkooi Kee, Vanessa T Angeles, Martha Flores, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature08562"}], "href": "https://doi.org/10.1038/nature08562"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19865085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19865085"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "S Fernandes, K Huellen, J Goncalves, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High frequency of DAZ1/DAZ2 gene deletions in patients with severe oligozoospermia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/8.3.286"}], "href": "https://doi.org/10.1093/molehr/8.3.286"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11870237"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11870237"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yi-Wen Lin, Duyen Anh Doan Thi, Pao-Lin Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms associated with the DAZ genes on the human Y chromosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2005.07.003"}], "href": "https://doi.org/10.1016/j.ygeno.2005.07.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16085382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16085382"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yuan Yang, Cuiying Xiao, Sizhong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Preliminary study of the relationship between DAZ gene copy deletions and spermatogenic impairment in Chinese men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2005.09.025"}], "href": "https://doi.org/10.1016/j.fertnstert.2005.09.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16580401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16580401"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "F Zhang, Z Li, B Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A frequent partial AZFc deletion does not render an increased risk of spermatogenic impairment in East Asians."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1529-8817.2005.00231.x"}], "href": "https://doi.org/10.1111/j.1529-8817.2005.00231.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16674553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16674553"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zhou-Cun A, Yuan Yang, Si-Zhong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Study on DAZ gene copy deletion in severe oligozoospermia sperm donor for ICSI]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Yi Chuan (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1360/yc-006-1057"}], "href": "https://doi.org/10.1360/yc-006-1057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16963411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16963411"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "S Sen, P Ambulkar, I Hinduja, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-015-0520-4"}], "href": "https://doi.org/10.1007/s10815-015-0520-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26149076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26149076"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yuening Zhang, Muyan Li, Feifan Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of partial DAZ1/2 deletion and partial DAZ3/4 deletion on male infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2015.07.083"}], "href": "https://doi.org/10.1016/j.gene.2015.07.083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26232607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26232607"}]}]}]}