title: Additional deletion in sex-determining region of human Y chromosome resolves paradox of X,t(Y;22) female.
abstract: Whether a human embryo develops as a male or a female is determined by the presence of the Y chromosome. The sex-determining function lies entirely in interval 1A, inasmuch as most XX individuals with descended testes and normal male external genitalia carry this small region of the Y chromosome. We have localized an essential part of the sex-determining function to a portion of interval 1A, on the basis of the discovery of a female with a reciprocal Y;22 translocation and part of 1A deleted at the translocation breakpoint. Recently, a paradox has arisen with the report of four partially masculinized XX individuals who carry only a portion of interval 1A--a portion that does not overlap the deletion in the X,t(Y;22) female. These recent findings imply that the sex-determining function lies in the portion of 1A present in the four XX intersexes and not in the portion deleted in the X,t(Y;22) female. To explain the X,t(Y;22) individual, it was proposed that she was female because of a chromosomal position effect or delayed development of the gonadal soma. Here we report that the X,t(Y;22) female has a deletion of a second portion of interval 1A--a portion corresponding closely to that present in the XX intersexes. This resolves the apparent contradiction. Nonetheless, phenotype-genotype correlations suggest that two or more genetic elements in interval 1A may contribute to the sex-determining function of the Y chromosome. The X,t(Y;22) female lacks the ZFY gene but does not exhibit the complex phenotype known as Turner's syndrome, arguing against the hypothesis that ZFY is the Turner's syndrome gene on the Y chromosome.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
authors.forename: D C
authors.initials: DC
authors.lastname: Page
authors.forename: E M
authors.initials: EM
authors.lastname: Fisher
authors.forename: B
authors.initials: B
authors.lastname: McGillivray
authors.forename: L G
authors.initials: LG
authors.lastname: Brown
mesh_terms: D002872:Chromosome Deletion; D015342:DNA Probes; D005260:Female; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D012732:Sex Determination Analysis; D014178:Translocation, Genetic; D014424:Turner Syndrome / Q000235:genetics; D014998:Y Chromosome
chemical_list: D015342:DNA Probes