Human Y chromosome deletions in Yq11 and male fertility

An overview is given about the current knowledge and research activities on the molecular analysis of interstitial deletions in the euchromatic part of the long arm of the human Y chromosome (Yq11). These mutations are associated with the male specific phenotype of azoospermia and severe oligozoospermia. The fact is stressed that only "de novo" microdeletions in Yq11 are of any diagnostic value in the infertility clinic because numerous polymorphic deletion events in Yq11 have also been reported. Three different "de novo" Yq11 microdeletions associated with male infertility are now found repeatedly (31 cases) in more than 700 patients. They strongly support the presence of at least three spermatogenesis loci in Yq11. They have been designated as AZFa, AZFb, and AZFc. Each of them should contain at least one Y gene functional in spermatogenesis and, if mutated, it should induce the same sterile phenotype as the corresponding AZF locus. These genes have not yet been found. However, some candidate genes exist: RBM for AZFb. DAZ and SPGY for AZFc. It is remarkable that all three encode testis specific RNA binding proteins with a similar sequence structure. Their structure and potential relationship is disussed.