Genetic heterogeneity in ataxia-telangiectasia studied by cell fusion

Abstract

The effect of x-rays on the rate of semiconservative DNA replication was investigated by autoradiography in single cells obtained from normal individuals and from patients having ataxia-telangiectasia (AT). In the five AT cell strains studied, the rate of DNA synthesis was inhibited to a lesser extent that in two normal cell strains. By using this abnormal regulation of DNA replication in AT cells as a marker, an experimental procedure was developed that allowed genetic complementation analysis of AT. After Sendai virus-induced fusion of AT cells, the grains were counted over binucleate cells with both nuclei in S phase. In some cases, the inhibition of DNA synthesis caused by x-rays in the heterodikaryons was more pronounced than that in the parental homodikaryons and was comparable to that in normal binucleate cells, indicating complementation. By using this approach, the five AT cell strains that were investigated could be assigned to three complementation groups. The data suggest that extensive genetic heterogeneity exists in AT.