High spontaneous intrachromosomal recombination rates in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an inherited human disease associated with neurologic degeneration, immune dysfunction, and high cancer risk. It has been proposed that the underlying abnormality in A-T is a defect in genetic recombination that interferes with immune gene rearrangements and the repair of DNA damage. Recombination was studied in A-T and control human fibroblast lines by means of two recombination vectors. Unexpectedly, spontaneous intrachromosomal recombination rates were 30 to 200 times higher in A-T fibroblast lines than in normal cells, whereas extrachromosomal recombination frequencies were near normal. Increased recombination is thus a component of genetic instability in A-T and may contribute to the cancer risk seen in A-T patients.