Associations of Y-chromosome subdeletion gr/gr with the prevalence of Y-chromosome haplogroups in infertile patients

Microdeletions in azoospermia factor (AZF) region on distal Yq are associated with male infertility and spermatogenic failure due to intra-chromosomal homologous recombination between large nearly identical repeat amplicons and are found in similar to 10% of azoospermic and severe oligozoospermic cases. Although AZFc is deleted in azoospermia or oligozoospermia, no definitive conclusion has been drawn for the role of partial AZFc deletions to spermatogenic failure. Therefore, this study is planned to investigate the role of gr/gr subdeletions in individuals with spermatogenic failure and to find its relationship with Y chromosome haplogroups (HGs) in infertile men from Indian population. It is a case-control study involving 236 azoospermic, 182 oligospermic and 240 healthy normozoospermic men. We found 18 gr/gr, 11 b1/b3 and 2 b2/b3 subdeletions in azoospermic patients and 12 gr/gr, 5 b1/b3 and 4 b2/b3 subdeletions in oligospermic patients. However, we also found seven gr/gr deletions in normozoospermic men. Seven patients each with spermatogenic arrest and oligospermia who carry gr/gr subdeletions have deleted DAZ3/DAZ4 genes. A total of 11 patients with sertoli cell-only syndrome (SCOS) and 5 oligospermic patients with gr/gr subdeletions also have DAZ1/DAZ2 genes deleted indicating that deletions of DAZ genes contributed differently to damage to spermatogenic process. L1 HG is found in patients showing b1/b3 subdeletions, whereas HG H1a2 and H1b were found in normozoospermic individuals with gr/gr subdeletions. Our results provide evidence of association between the occurrence of subdeletions and male infertility as well as the severity of the spermatogenic failure. European Journal of Human Genetics (2011) 19, 23-29; doi:10.1038/ejhg.2010.151; published online 8 September 2010