Localization of Y chromosome sequences and X chromosomal replication studies in XX males

Abstract

By in situ hybridization, Y-specific DNA sequences were localized on Xp22.3-Xpter of one of the two X chromosomes in all of eleven XX males studied. In nine of the cases the presence of the Y-specific DNA did not affect random X inactivation in fibroblasts. Fibroblasts of the other two cases showed a preferential inactivation of the Y DNA-carrying X chromosome. In only one of these two exceptions blood lymphocytes could also be studied, and here, random inactivation of the Y DNA-carrying X chromosome occurred. Furthermore, the gene dosage of steroid sulfatase (STS) was examined by Southern blot analysis. In ten of the cases including the one showing random X-inactivation in lymphocytes but not in fibroblasts, a double dosage of the STS gene is present. The remaining case with non-random inactivation shows a single STS gene dosage. This case was reported previously to have STS enzyme activity in the male range. It is assumed that, as a consequence DNA sequences may result in the preferential inactivation of the Y DNA-carrying X chromosome.

Long-range restriction map of the terminal part of the short arm of the human X chromosome.

“…Among 24 cases of Y(+)XX males analyzed, 23 showed an X-chromosomal breakpoint distal to the DXS283 and DXF28S2 loci (12,31,33,34) and a single one proximal to STS (35). The physical map presented here indicates that these 23 breakpoints are localized in a region spanning 4 Mb from the telomere.…”

Two Males with SRY-Positive 46,XX Testicular Disorder of Sex Development

“…Both cases have the appearance of classical 46, XX, SRY positive male phenotypic features, namely, Kusz et al 1999;Boucekkine et al 1985;Schempp et al 1989], position effect [Sharp et al 2005] or presence of another Y linked gene [Bouayed Abdelmoula et al 2003] which may have a role in male sexual development at the translocated segment. Obligatory crossing over may take place between the X and Y chromosomes at the pseudoautosomal regions (PARs) during male meiosis.…”

“…Both patients showed a random inactivation pattern. The results of the XCI analysis in 46,XX testicular DSD patients are controversial [Bouayed Abdelmoula et al 2003;Kusz et al 1999;Boucekkine et al 1985;Schempp et al 1989;Vorona et al 2007]. Both random and nonrandom X chromosome inactivation patterns have been reported.…”

“…Our results revealed that there is no preferential silencing of der(X;Y) in peripheral blood and testes. Differences in the size of the translocated fragment could lead to discrepancies of X chromosome inactivation analysis [Allen et al 1992;Schempp et al 1989;Queipo et al 2002]. The length of the Y chromosome fragment in 46,XX male patients ranges from 40 kb to > 75% of the Yp.…”

Genetic characterization of two 46,XX males without gonadal ambiguities

“…The amount of translocated Y chromosome material and the pattern of X chromosome inactivation (XCI) have been proposed to play a role [21]. An association of skewed XCI against the Y-bearing X chromosome has often been observed in true hermaphrodites and in XX patients with gonadal ambiguity [7,12,14,18,29]. These patients normally have a small portion of the Y chromosome material translocated to the X, presumably allowing for XCI spreading and inactivating the SRY gene.…”