ABSENCE OF DAZ GENE-MUTATIONS IN CASES OF NON-OBSTRUCTED AZOOSPERMIA

Sequence-tagged site (STS) analysis of the Y chromosome long arm (Yq) of azoospermic males has identified a minimum common deleted region of several hundred kilobases in similar to 13% of cases. A candidate azo ospermia gene, DAZ (deleted in azoospermia), has been isolated from th is region. DAZ has also been shown to be absent in severely oligozoosp ermic males albeit at a much lower frequency. These data, although hig hly suggestive, do not constitute formal proof that DAZ actually plays a role in azoospermia, as no small intragenic deletions, rearrangemen ts or point mutations in the gene have been found. In this study we re port the screening of DNA from 168 azoospermic/oligospermic males for the presence of the DAZ gene. Deletions involving DAZ were detected in five out of 43 (11.6%) azoospermic males whereas none were found in t he remaining 125 oligospermic patients. We present the genomic structu re of the 5' end of the DAZ gene together with its sequence analysis i n 30 non-obstructed azoospermic males. No mutations in DAZ were found in any of the patients sequenced. These data provide no formal proof t hat DAZ is AZF. Thus the possibility is still valid that another gene( s) mapping to the minimum deletion interval may be responsible for, or contribute to, the observed phenotypes. Alternatively, if DAZ is AZF, they suggest that the most frequent cause of gene inactivation is via large deletions possibly mobilized by Y chromosome repetitive sequenc es.