Molecular and evolutionary analysis of the growth-controlling region on the human Y chromosome

The human Y chromosome has been predicted to harbour a locus termed GCY, affecting height in males. GCY has been positioned by deletion mapping to the pericentromeric region on the long arm of the Y chromosome. As the relevant gene has not been identified yet, we have carried out exon amplification and isolated nine different exon trap clones within the critical region. Gene prediction programs have proposed 17 different gene models and standard BLASTN searches with the genomic sequence detected significant homologies to six known genes/pseudogenes or expressed sequence tags. Large-scale cDNA library screening and reverse transcription of polyA(+) RNAs, however, could not demonstrate unequivocally the existence of a novel transcriptional unit. All potential transcriptional units are embedded in subintervals of the GCY critical region that have been transposed to the human Y during different stages of primate evolution. These results challenge our present view on the Y-chromosomal stature locus GCY, proposing the existence of an unusual gene with an extremely confined spatial and/or temporal expression pattern, albeit the structural impact of the nearby pericentromeric heterochromatin should not be excluded.