Ataxia-telangiectasia: Linkage analysis of chromosome 11q22-23 markers in Turkish families

To further pinpoint the location of the genes for ataxia-telangiectasia on the long arm of chromosome 11, we performed linkage analysis and analysis of recombinants of genetic haplotypes on 14 Turkish families with ataxia-telangiectasia, 12 of which were consanguineous. These studies used more than 25 polymorphic genetic markers spanning a region of the long arm of chromosome 11 that is larger than 50 cM. Seven markers gave significant LOD scores to AT: CJ5, DRD2, CJ208, S144, CD3E, PBGD, and S147, as did haplotypes created with pairs of markers DRD2/CJ5 and S144/CJ208, giving recombination fractions (theta) of 0.00, 0.00, 0.05, 0.08, 0.03, 0.09, 0.07, 0.00, and 0.06, respectively. Monte Carlo analysis of these 14 Turkish families indicated the best location for a single AT gene to be within a 6 cM sex-averaged (3 cM male-specific) interval defined by STMY and CJ77; this was three times more likely than the next most likely location (peak III) at the DRD2 locus. The analysis also revealed a peak (peak II) between S147 and S133, which may represent the complementation group D gene. Recombinant analysis of haplotypes also localized an AT locus to the STMY-CJ77 interval. Taken together, these results suggest that at least two distinct AT loci exist (ATA and ATD) at 11q22-23, with perhaps a third locus, ATC, located very near to the ATA gene. This genetic heterogeneity further complicates plans to isolate the major ATA and ATC genes and to begin identifying AT carriers in the general population.