HUMAN Y-CHROMOSOME AZOOSPERMIA FACTORS (AZF) MAPPED TO DIFFERENT SUBREGIONS IN YQ11

In a large collaborative screening project, 370 men with idiopathic az oospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11, In 12 individuals, we observed de novo microdeletion s involving several DNA loci, while an additional patient had an inher ited deletion, They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in pr oximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each s ubregion was similar in each patient analysed, In testis tissue sectio ns, disruption of spermatogenesis was shown to be at the same phase wh en the microdeletion occurred in the same Yq11 subregion but at a diff erent phase when the microdeletion occurred in a different Yq11 subreg ion, Therefore, we propose the presence of not one but three spermatog enesis loci in Yq11 and that each locus is active during a different p hase of male germ cell development, As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, A ZFb and AZFc. Their probable phase of function in human spermatogenesi s and candidate genes involved will be discussed.