Identification of A-T heterozygotes

Abstract

Since the discovery of the abnormal response of cells from ataxia-telangiectasia (A-T) homozygotes to ionising radiation and free radical-generating chemicals (reviewed in Bridges and Harnden, 1982) the response of cells from heterozygotes has been investigated with many procedures (summarised by Weeks et al., 1991). Most techniques are able to detect a shift in the average response of heterozygote cells compared with normals but with considerable overlap between the two groups. The assay that has been reported to provide the best discrimination has been devised by K.K. Sanford and colleagues at the National Cancer Institute (NCI) and involves X-irradiating cells in the G₂ phase of the cell cycle and quantifying radiation-induced chromosome damage in these cells when they undergo mitosis. In comparisons between 52 controls and 29 obligate heterozygotes, 50 of the controls had lower chromosome aberration frequencies than any of the heterozygotes. These studies were on cultured skin fibroblasts (20 heterozygotes and 17 controls for which there was complete discrimination; Parshad et al., 1985; Shiloh et al., 1986; Shiloh et al., 1989) and peripheral blood lymphocytes (9 heterozygotes and 35 controls with overlap of 2 controls; Sanford and Parshad, 1990).