REFINING THE GENETIC-MAP FOR THE REGION FLANKING THE X-LINKED HYPOPHOSPHATEMIC RICKETS LOCUS (XP22.1-22.2)

We have screened fourteen kindreds with X-linked hypophosphataemic ric kets with four microsatellite markers, viz. AFM163yh2, DXS999 (AFM234y f12), DXS443 and DXS365, in order to refine the genetic map flanking t he gene, and to define a close flanking interval for the construction of a yeast artificial chromosome (YAC) and cosmid contig. The genetic data were enhanced after the isolation of a large 1.2-megabase YAC der ived from AFM163yh2, in which marker DXS274 was present but not DXS365 or DXS443. Against HYP, DXS365, AFM163yh2 and DXS443 showed no recomb inants (Z(max) = 18.1, Z(max) = 9.9, and Z(max) = 16.0 respectively). DXS999 gave Z(max) = 9.6 at 4% recombination and lies distal to HYP bu t proximal to DXS197 and DXS43. The disease gene and markers AFM163yh2 and DXS365 are flanked by DXS443 and DXS274. Combining the genetic an d physical data, we are able to propose the following gene marker orde r: Dxs443-[(DXS365-AFM163yh2),HYP]-DXS274-DXS41-Xcen.