Abstract

The structure and function of the human Y chromosome have been approached by molecular genetics. The use of Y-derived DNA probes to analyze the Y chromosome of patients with sexual differentiation abnormalities allowed the construction of a deletion map localizing TDF (testis determining factor) in the terminal part of the short arm. These studies culminated recently in the isolation of a candidate gene for the TDF locus. Nevertheless, the existence of a related locus on the X chromosome does not fit with the simple hypothesis of a single Y-located gene for testis differentiation. The finding of a strictly homologous region at the tip of the short arms of X and Y chromosomes allowed the characterization of another major property of the sex chromosomes. These so called pseudoautosomal DNA sequences show only a partial sex linkage and can be exchanged between X and Y chromosomes during male meiosis. Genetic analysis and determination of the physical length of the pseudoautosomal region show that it is subjected in male meiosis, to a recombination rate about 20 times higher than the mean value of the human genome. In 1966, Ferguson-Smith proposed that an abnormal cross-over was responsible for both types of sex inversions in humans: XX males and XY females. Segregation analysis of the pseudoautosomal loci in these patients has demonstrated the validity of this hypothesis and shown the existence of sex inversions unrelated to the TDF locus. The construction of a detailed map of the human Y chromosome enables the search for new genes (H-Y antigen, fertility gene(s]. The finding of several homologous regions on the sex chromosomes confirms the hypothesis of a common origin and should help to understand the establishment of sex determination and X inactivation mechanisms during mammalian evolution.