Y CHROMOSOME RELATED “GENOMIC DISORDERS”

7% of males from the general population are infertile and in the majority of cases infertility is caused by a primitive testicular failure. The most frequent known molecular genetic cause are Y chromosome microdeletions which occur in specific regions termed AZoospermia Factor (AZF) regions of the long arm of the Y chromosome (Yq). Classical AZF deletions are associated with oligo/azoospermia. Although in each of these regions candidate spermatogenesis genes have been identified, their function and role in spermatogenesis remains to be established. The peculiar structure of the AZFc region predispose to the formation of partial AZFc deletions and duplications and it is not clear whether dosage differences inside the AZFc region may influence spermatogenesis. The aim of this project is to i) define if do exist interindividual differences in the frequency of meiotic de novo AZF deletion rates. In particular, if subjects who fathered sons with AZF deletions or if carriers of AZF deletions/duplications are more susceptible to non allelic homologous recombination; ii) define the clinical and biological consequences of gr/gr deletions and partial AZFc duplications. A novel approach based on sperm mRNA fingerprinting will be used to get new insights into the biological consequences of AZFc gene dosage differences. Given that Y related anomalies will be obligatory transmitted to the male offspring (especially with the diffusion of assisted reproductive techniques) it is important to define their pathological role.