Deletions of 9p and the quest for a conserved mechanism of sex determination

Distal chromosome 9p contains a locus that, when deleted, is a cause of 46, XY gonadal dysgenesis in the absence of extragenital anomalies. This locus might account for the frequently observed cases of 46,XY pure gonadal dysge nesis who do not harbor mutations in SRY, the sex master regulator gene fou nd in mammalian species. The genomic organization of 9p positional candidat e genes is currently being studied and mutational screens are ongoing. Amon g other positional candidates, including two additional doublosex-related g enes, the evidence to support a role for the gene DMRT1 in vertebrate male sexual development is accumulating. Although formal proof of the requiremen t of DMRT1 in gonadal sex fate choice has not been obtained so far, the par ticular interest in this gene and perhaps other doublesex-related genes ide ntified in vertebrates lies in that they may provide an entry point to a co nserved mechanism of sex determination across animal phyla. We discuss rece nt results and emerging views on the genetics of sex determination, while s tressing that the majority of cases of 46,XY gonadal dysgenesis remain unex plained. The latter is likely to be efficiently addressed by positional clo ning efforts, particularly by considering the wealth of sequence data provi ded by the Human Genome Project. (C) 2000 Academic Press.