Schematic representation of formation and organization of the ePAR.

(A) Normal pairing of the short arms of the X and Y chromosomes in male meiosis is limited to PAR1 (purple) such that homologous recombination can occur up to the canonical boundary as marked. However, mispairing of the PAR1 LTR6B element (yellow box) carried on a Y chromosome (blue) with one located more proximally on an X chromosome (pink) can result in non-allelic homologous recombination and the generation of gametes containing either an ePAR-carrying Y chromosome, or the reciprocal deleted X chromosome. Schematics not to scale. (B) Pairing and therefore homologous exchange between an ePAR Y chromosome and a normal X chromosome is predicted to extend proximally to a new boundary. The first three exons of the XG blood group gene fall within PAR1, while the remaining exons are carried on the X chromosome; men carrying the ePAR thus have two full-length XG genes like females. Similarly, whilst most men are hemizygous for the GYG2 gene, ePAR carriers have two copies of this gene.