Inversion of Chromosome 7 in Ataxia Telangiectasia Is Generated by a Rearrangement Between T - Cell Receptor 9 and T - Cell Receptor y Genes

Specific and recurrent chromosomal rearrangements are often observed in the karyotypes of phytohemagglutininstimulated lymphocytes. The percentage of cells demonstrating these rearrangements is dramatically increased in the genetic disease ataxia telangiectasia. Inversion of chromosome 7 represents approximately half of the chromosomal rearrangements in this disease. Because the chromosomal locations of the inv(7) breakpoints coincide precisely with those of the T-cell antigen receptor (TCR) fi S INCE 1975 it has been known that recurrent chromosome abnormalities occur in phytohemagglutinin-stimulated peripheral lymphocytes of normal individuals.’3 Most of these rearrangements involve chromosomes 7 or 14 or both and are most frequently inversions of chromosome 14 (inv[14J) or t(7;14) translocations. The recurrent breakpoints of these rearrangements are located on bands I 4q12, 1q35, lpl4, and 14q32 within the precise chromosomal bands where the genes for the a-#{244}, fi and ‘y chains of the T-cell receptor (TCRa, TCR#{212},TCR/3, TCRy) and the immunoglobulin heavy chain (IgH) have been mapped.4 We, and other investigators,2’5’6 have therefore speculated that these rearrangements may occur by recombination between these different genes. In patients with ataxia telangiectasia (AT), the frequency of metaphases carrying chromosomal rearrangements is dramatically increased.7 Inversion of chromosome 7 (inv[7]) in this disease is a frequent abnormality, often accounting for approximately 1% to 5% of the observed metaphases,7 whereas it is observed approximately 100-foki less frequently in normal individuals.3 This high frequency of specific cytogenetic abnormalities is highly characteristic of AT. We wished to determine the structure of inv(7) to gain insight into this aspect of AT. Our approach was to establish a cell line carrying the inv(7) from an AT patient, to determine the molecular structure of the rearrangement, and finally to prove that the same rearrangement was present in the peripheral blood of this same patient.