ABNORMAL XY INTERCHANGE BETWEEN A NOVEL ISOLATED PROTEIN-KINASE GENE,PRKY, AND ITS HOMOLOG, PRKX, ACCOUNTS FOR ONE 3RD OF ALL (Y-)XY FEMALES()XX MALES AND (Y)

XX males and XY females have a sex reversal disorder which can be caus ed by an abnormal interchange between the X and the Y chromosomes. We have isolated and characterized a novel gene on the Y chromosome, PRKY . This gene is highly homologous to a previously isolated gene from Xp 22.3, PRKX, and represents a member of the cAMP-dependent serine threo nine protein kinase gene family. Abnormal interchange can occur anywhe re on Xp/Yp proximal to SRY. We can show that abnormal interchange hap pens particularly frequently between PRKX and PRKY. In a collection of 26 XX males and four XY females, between 27 and 35% of the interchang es take place between PRK homologues but at different sites within the gene. PRKY and PRKX are located far from the pseudoautosomal region w here XY exchange normally takes place. The unprecedented high sequence identity and identical orientation of PRKY to its homologous partner on the X chromosome, PRKX, explains the high frequency of abnormal pai ring and subsequent ectopic recombination, leading to XX males and XY females and to the highest rate of recombination outside the pseudoaut osomal region.