Old and new genetics help ordering loci at the telomere of the human X-chromosome long arm

Abstract

A Sardinian pedigree described in 1964 for having been found to segregate at the X-linked loci for the Xga antigen, G6PD deficiency, Protan and Deutan color blindness, with an instance of recombination between the last two loci, was re-examined with respect to four common X-linked DNA polymorphisms detected by molecular probes homologous to critical subregions of the human X chromosome. Two branches of this pedigree--including the one with the Protan-Deutan recombinant--were found to segregate also for the common BamHI polymorphism identified with the cDNA probe pHPT-2 or the HPRT gene (Xq26). The analysis of the chromosome haplotypes in the male offspring of the phase known penta-heterozygous mother suggests that the probable order of the relevant loci is HPRT, Deutan, G6PD, Protan, Xq telomere. Though we are fully aware of the risks of generalizing the significance of observations made on a single exceptional pedigree, we believe that this report outlines the potential of families of the type described as research tools to resolve the linear order of tightly X-linked loci and to investigate the biology of genetic recombination in humans.