title: Abnormal XY interchange between a novel isolated protein kinase gene, PRKY, and its homologue, PRKX, accounts for one third of all (Y+)XX males and (Y-)XY females.
abstract: XX males and XY females have a sex reversal disorder which can be caused 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 Xp22.3, PRKX, and represents a member of the cAMP-dependent serine threonine protein kinase gene family. Abnormal interchange can occur anywhere on Xp/Yp proximal to SRY. We can show that abnormal interchange happens particularly frequently between PRKX and PRKY. In a collection of 26 XX males and four XY females, between 27 and 35% of the interchanges take place between PRK homologues but at different sites within the gene. PRKY and PRKX are located far from the pseudoautosomal region where 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 pairing and subsequent ectopic recombination, leading to XX males and XY females and to the highest rate of recombination outside the pseudoautosomal region.
authors.affiliation: Institute of Human Genetics, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schiebel
authors.forename: M
authors.initials: M
authors.lastname: Winkelmann
authors.forename: A
authors.initials: A
authors.lastname: Mertz
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: D C
authors.initials: DC
authors.lastname: Page
authors.forename: D
authors.initials: D
authors.lastname: Weil
authors.forename: C
authors.initials: C
authors.lastname: Petit
authors.forename: G A
authors.initials: GA
authors.lastname: Rappold
mesh_terms: D000782:Aneuploidy; D001483:Base Sequence; D018076:DNA, Complementary; D012734:Disorders of Sex Development; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013577:Syndrome; D014960:X Chromosome; D014998:Y Chromosome
chemical_list: D018076:DNA, Complementary; C109450:PRKX protein, human; C109449:PRKY protein, human; D017346:Protein Serine-Threonine Kinases