GENETIC AND PHYSICAL MAPPING OF THE ATAXIA-TELANGIECTASIA LOCUS ON CHROMOSOME 11Q22-Q23

The identification of A-T gene(s) using both positional and functional cloning techniques has been a major objective in A-T research over th e past 10 years. Functional cloning, using complementation of the radi osensitivity phenotype, has met with some success, although technical problems remain to be overcome. Recent progress, however, in both gene tic and physical mapping of the A-T locus on chromosome 11q22-q23, des cribed in this review, suggests that the positional cloning of candida te genes should be achieved in the very near future. The region of the chromosome containing the gene(s) has been identified, and is no more than 1.6 Mb in size. The detailed physical characterization of this r egion, as a preliminary to candidate gene isolation, is now underway. There are, however, still some unresolved issues, most notably the exi stence of four A-T complementation groups, with the resulting supposit ion that these equate to a number of different genes. Although genetic linkage evidence does not support the hypothesis of genetic heterogen eity, the possibility of a cluster of genes at the 11q22-23 locus cann ot be ruled out. It is likely that the explanations for this and other problems such as discrepancies in expected levels of consanguinity, a nd difficulties in the classification of atypical phenotypes will beco me much more obvious once a gene or genes have been cloned.