{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies of the AZFc region on the Y chromosome have shown that deletion of specific gene segments, including the DAZ3/DAZ4 doublet, can occur in certain populations without impacting male fertility. For example, in haplogroup N men a common variant lacking the DAZ3/DAZ4 region was identified, leading to the conclusion that these genes are genetically redundant and are not indispensable for spermatogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMolecular investigations further reveal that all DAZ gene copies, DAZ1 through DAZ4, are actively expressed in the human testis, suggesting that despite their close sequence homology, the DAZ3 copy is transcriptionally active and functionally overlapping with its counterparts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, comprehensive analyses of AZFc subdeletions underscore a differential relationship between partial deletions within the DAZ gene family and male infertility risk. While deletions involving the DAZ1/DAZ2 cluster are significantly associated with spermatogenic impairments such as azoospermia and oligozoospermia, partial deletion of the DAZ3/DAZ4 cluster, which encompasses DAZ3, generally shows no significant correlation with infertility, although some variability may exist among different ethnic groups."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSupporting these observations, targeted studies in Chinese cohorts of normospermic and severely oligozoospermic men have demonstrated that while deletions of DAZ1/DAZ2 are more prevalent and constitute a risk factor for impaired spermatogenesis, DAZ3/DAZ4 deletions do not differ significantly between infertile and fertile subjects. This reinforces the notion that the DAZ3 gene, as part of the DAZ3/DAZ4 cluster, is less critical for maintaining male fertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S Fernandes, S Paracchini, L H Meyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A large AZFc deletion removes DAZ3/DAZ4 and nearby genes from men in Y haplogroup N."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/381132"}], "href": "https://doi.org/10.1086/381132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14639527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14639527"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Byunghyuk Kim, Youngbin Lee, Yeonwha Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphic expression of DAZ proteins in the human testis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dep032"}], "href": "https://doi.org/10.1093/humrep/dep032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19223287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19223287"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "María C Lardone, Daniela A Parodi, Mauricio Ebensperger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AZFc partial deletions in Chilean men with severe spermatogenic failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2007.01.038"}], "href": "https://doi.org/10.1016/j.fertnstert.2007.01.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17416365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17416365"}]}, {"type": "r", "ref": 4, "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"}]}, {"type": "r", "ref": 5, "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"}]}]}]}