A DOSAGE SENSITIVE LOCUS AT CHROMOSOME XP21 IS INVOLVED IN MALE TO FEMALE SEX REVERSAL

Male to female sex reversal has been observed in individuals with dupl ications of the short arm of the X chromosome. Here we demonstrate tha t sex reversal results from the presence of two active copies of an Xp locus rather than from its rearrangement and that alterations at this locus constitute one of the causes of sex reversal in individuals wit h a normal 46,XY karyotype. We have named this locus DSS (Dosage Sensi tive Sex reversal) and localized it to a 160 kilobase region of chromo some Xp21, adjacent to the adrenal hypoplasia congenita locus. The ide ntification of male individuals deleted for DSS suggests that this loc us is not required for testis differentiation. We propose that DSS has a role in ovarian development and/or functions as a link between ovar y and testis formation.