Alberto Ferlin

Localisation of the Y chromosome stature gene to a 700 kb interval in close proximity to the centromere

The sex related height difference in humans is thought to be caused mainly by two components: first, a hormonal component determined by the sex dimorphism of bioactive gonadal steroids, and, second, a genetic component attributed to a Y specific growth gene, GCY .1–3 Despite extensive mapping attempts for this gene on the human Y chromosome,4–7 its precise position remains unknown. We have recently provided evidence that inappropriate cytogenetic methodology in the characterisation of Y chromosomal terminal deletions has led to some of the difficulties in elucidating the GCY critical region. In order to circumvent these problems, we have decided to consider only patients presenting de novo interstitial deletions for GCY analysis on the Y chromosome.8 This approach allows the assignment of GCY to a particular chromosomal interval without excluding the presence of X0 mosaicism and/or i(Yp) and idic(Yq11) chromosomes in patients with terminal deletions. Indeed, the direct comparison of overlapping interstitial deletions in seven adult males with normal height, one male with borderline height, and one patient with short stature resulted in the confirmation of a GCY critical interval between markers DYZ3 and DYS11. This region roughly encompasses 1.6-1.7 Mb of genomic DNA. To improve the resolution in the region of interest close to the centromere, we established additional new STS markers specific for this part of the chromosome using our bacterial artificial chromosome (BAC)/P1 derived artificial chromosome (PAC) contig. Molecular deletion analysis using these new Y chromosomal STSs allowed us to exclude almost all of the Y chromosomal long arm as the putative location of the GCY growth gene and to narrow down the critical interval to a genomic region of 700 kb.nn### Selection of patientsnnAll nine patients are sterile and have deletions of either AZFa, AZFb, or AZFc or a combination thereof. They were otherwise …