Highly homologous loci on the X and Y chromosomes are hot-spots for ectopic recombinations leading to XX maleness.

Abstract

In 80% of XX males, maleness is due to the presence of Y-specific DNA including the SRY gene and results from an abnormal terminal X-Y interchange during paternal meiosis. Here we address the molecular basis of this ectopic recombination through the analysis of the X-Y junction in two class 3 XX males. We show that each of the rearrangements has involved X-Y highly homologous loci on the sex-specific part of these chromosomes (98.7% and 96% sequence identity over 1.2 and 1.1 kb respectively). Moreover in five out of six other XX males, the X-Y junctions are located in the same rearranged restriction fragment as in either of these patients. These fragments thus define two hot-spots of ectopic recombination which together could account for about one third of XX males. Evolution of these loci in primates is discussed.