Fine mapping of the chromosome 11q22–23 region using PFGE, linkage and haplotype analysis; localization of the gene for ataxia telangiectasia to a 5cM region flanked by NCAM/DRD2 and STMY/CJ52.75, ø2.22

Abstract Using pulsed-field gel electrophoresis, and a range of different enzyme digests, we have established that both markers of each of the pairs CJ52.208/YNB3.12, NCAM/DRD2, and STMY/CJ52.75, on chromosome 11q22-23, show physical linkage on a single DNA fragment. We have also shown, using genetic linkage and haplotype analyses, that these markers lie within a region of approximately 18cM, which, it has been shown previously, is likely to contain the A-T gene. The relative positions of these marker loci, and the distance between them was determined in order to construct a detailed map which has allowed a more precise localization of the A-T gene. We have shown that in pairwise linkage analysis the strongest support for linkage to the A-T gene was with the STMY/CJ52.75 locus (Z = 5.59, theta = 0.0). A three-point analysis using the results from STMY/CJ52.75 and the closely linked marker phi 2.22 gave Z = 5.55, theta = 0.03. Despite persisting evidence of some linkage to Thy-1 our results are consistent with the existence of a single A-T locus on chromosome 11q22-23 and our best estimate of the position of this locus places it between NCAM/DRD2 and (STMY/CJ52.75, F2.22) (Z = 6.74), a region of approximately 5cM in males.