An extremely polymorphic locus on the short arm of the human X chromosome with homology to the long arm of the Y chromosome

Abstract

A genomic DNA clone named CRI-S232 reveals an array of highly polymorphic restriction fragments on the X chromosome as well as a set of non-polymorphic fragments on the Y chromosome. Every individual has multiple bands, highly variable in length, in every restriction enzyme digest tested. One set of bands is found in all males, and co-segregates with the Y chromosome in families. These sequences have been regionally localized by deletion mapping to the long arm of the Y chromosome. Segregation analysis in families shows that all of the remaining fragments co-segregate as a single locus on the X chromosome, each haplotype consisting of three or more polymorphic fragments. This locus (designated DXS278) is linked to several markers on Xp, the closest being dic56 (DXS143) at a distance of 2 cM. Although it is outside the pseudoautosomal region, the S232 X chromosome locus shows linkage to pseudoautosomal markers in female meiosis. In determining the X chromosome S232 haplotypes of 138 offspring among 19 families, we observed three non-parental haplotypes. Two were recombinant haplotypes, consistent with a cross-over among the S232-hybridizing fragments in maternal meiosis. The third was a mutant haplotype arising on a paternal X chromosome. The locus identified by CRI-S232 may therefore be a recombination and mutation hotspot.

Long-range restriction map of the terminal part of the short arm of the human X chromosome.

“…By analogy, it has been suggested that such X-specific genes from Xp22.3, which are at least partially insensitive to X-inactivation, are remnants of an ancestral pseudoautosomal region that once extended more proximally on Xp22.3. This is further supported by the pseudoautosomal location of murine STS (6) and, in man, by the existence of numerous sequence homologies between Xp22.3 and different parts of the Y chromosome (7)(8)(9)(10)(11)(12).…”

“…Based on linkage data reported by others (10,30), it has been proposed that locus DXS278 detected by probe CRI-S232 maps between STS and DXS143.…”

“…While in male meiosis the genetic map expansion in the pseudoautosomal region is dramatic (21)(22)(23)(24), in female meiosis no such expansion has been observed (21,24). However, map expansions in more subtelomeric parts of Xp22.3 cannot be excluded, and the occurrence of a recombination hot spot within locus DXS278 from Xp22.3 has been proposed (10).…”

“…1 (12,16 (29). Interval 6 was further subdivided into 6a and 6b as deduced from genetic linkage data (10). The loci are assigned to one interval; their probes are indicated in parentheses.…”

Chromosomal localization of ZFX—A human gene that escapes X inactivation—and its murine homologs

“…Many of the same three-generation families had pre- viously been typed for several pseudoautosomal and strictly X-linked RFLPs, from which genetic linkage maps of Xp were constructed by multipoint analysis (Drayna and White, 1985;Page et al, 198713;DonisKeller et al, 1987;Knowlton et al, 1989). We also included in the analysis X-linked RFLP data from 19 families segregating X-linked diseases (A.C. and colleagues, unpublished results).…”