Genomic heterogeneity and instability of the AZF locus on the human Y chromosome

Abstract

The spermatogenesis locus azoospermia factor (AZF) in Yq11 has been mapped to three microdeletion intervals designated as AZFa, AZFb, and AZFc. They are caused by intrachromosomal recombination events between large homologous repetitive sequence blocks, and AZFc microdeletions are now recognised as the most frequent known genetic lesion causing male infertility. However, in the same Y-region, large genomic heterogeneities are also observed in fertile men, and only complete AZFa and AZFb deletions are associated with a specific testicular pathology. Partial AZF deletions are associated with variable pathologies and partial AZFc deletions may even have no impact on male fertility. This suggests a genetic redundancy of the multi-copy genes in AZFb and AZFc and a causative relationship between the occurrence of first microdeletions then macrodeletions in the repetitive structure of Yq11 where large palindromes are probably promoting multiple gene conversions and AZF rearrangements.