LARGE DELETIONS PARTIALLY EXTERNAL TO THE HUMAN HPRT GENE RESULT IN CHIMERIC TRANSCRIPTS

We postulated that gene fusions sometimes occur in normal cells as a r esult of gene rearrangements as have been observed involving oncogene loci in tumours. To test this, we searched for fusion-gene transcripts in selected human T-lymphocyte large deletion mutations of the hypoxa nthine-guanine phosphoribosyltransferase (hprt) gene using the 3' rapi d amplification of cDNA ends (RACE) technique. Aberrant hprt-containin g transcripts were observed in seven out of 19 mutants (similar to 36% ) indicating that a surprising number of these rearrangements code for processed mRNAs. RNA splicing and polyadenylation occurred downstream of the non-deleted hprt sequence in chimeric transcripts and the majo rity resulted from mutants with fusions of hprt into regions containin g a repetitive element (Alu, LINE or microsatellite).