Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathicazoospermia or severe oligozoospermia were analysed for deletions of 76 DNAloci in Yq11. In 12 individuals, we observed de novo microdeletionsinvolving several DNA loci, while an additional patient had an inheriteddeletion. They were mapped to three different subregions in Yq11. Onesubregion coincides to the AZF region defined recently in distal Yq11. Thesecond and third subregion were mapped proximal to it, in proximal andmiddle Yq11, respectively. The different deletions observed were notoverlapping but the extension of the deleted Y DNA in each subregion wassimilar in each patient analysed. In testis tissue sections, disruption ofspermatogenesis was shown to be at the same phase when the microdeletionoccurred in the same Yq11 subregion but at a different phase when themicrodeletion occurred in a different Yq11 subregion. Therefore, we proposethe presence of not one but three spermatogenesis loci in Yq11 and thateach locus is active during a different phase of male germ celldevelopment. As the most severe phenotype after deletion of each locus isazoospermia, we designated them as: AZFa, AZFb and AZFc. Their probablephase of function in human spermatogenesis and candidate genes involvedwill be discussed.