The gr/gr deletion(s): a new genetic test in male infertility?

Deletion of the AZFc region of the Y chromosome is the most frequent molecular genetic cause of oligo/ azoospermia. Within this region, partial deletions have been recently described, including the gr/gr deletion. A direct aetiopathogenic role has been suggested for the gr/gr deletion as it was absent in normozoospermic but present in oligospermic men. We studied a group of normospermic (n = 189) and oligo/azoospermic (n = 150) men using a sequence tagged site (STS) +/2 method. To gain insight into the molecular basis of the heterogeneous phenotype observed in men with the deletion we: (a) defined the type of DAZ and CDY1 genes deleted and the Y haplogroup, and (b) carried out a mutational screen of DAZL, the autosomal homologue of DAZ. We found that: (a) partial AZFc deletions are not specific for spermatogenic failure, and (b) gr/gr deletion can be considered as a risk factor because its frequency was significantly higher in the oligo/ azoospermic group (5.3%) than in controls (0.5%) p,0.012. Gene specific analysis revealed three distinct deletion patterns, indicating that further combined studies based on gene copy and haplogroup analysis are likely to provide a means for the distinction between pathogenic and neutral (or compensated by other Y factors) types of deletion.