As we first saw in Chapter 2, meiotic recombination between X-linked loci only occurs between the two homologous X chromosomes and is, therefore, restricted to females. X-linked loci do not participate in meiotic recombination in males, who have a Y chromo some and only one X chromosome. There are, however, a small number of contiguous loci, located at the tips of the p and q arms of the sex chromosomes, that are homologous between X and Y and recombine in male meiosis. As a consequence, during spermatogenesis, a pathogenic allele at one of these loci on the X chromo some can be transferred onto the Y chromosome and passed on to male offspring, thereby demonstrating the male-to-male transmission characteristic of autosomal inheritance. Because these unusual loci on the X and Y mimic autosomal inheritance but are not located on an autosome, they are referred to as pseudoautosomal loci; the segments of the X and Y chromosomes where they are located are referred to as the pseudoautosomal regions.
One example of a disease caused by a pathogenic variant at a pseudoautosomal locus is dyschondrosteosis, a dominantly inherited skeletal dysplasia with disproportionate short stature and deformity of the fore arms. Although a greater prevalence in females than in males initially suggested an X-linked dominant disorder, the presence of male-to-male transmission clearly ruled out strict X-linked inheritance (Fig. 1). Variants in the SHOX or SHOXY gene, located in the pseudoautosomal region on Xp and Yp, respectively, are responsible for this condition.
Fig1. Pedigree showing inheritance of dyschondrosteosis due to variants in SHOX, a pseudoautosomal gene on the X and Y chromosomes. The arrow shows a male who inherited the trait on his Y chromosome from his father. His father, however, inherited the trait on his X chromosome from his mother. From Shears DJ, Vassal HJ, Goodman FR, et al: Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis, Nat Genet 19:70–73, 1998.
