HIGH-RESOLUTION CYTOGENETIC ANALYSIS OF X-RAY-INDUCED MUTATIONS OF THE HPRT GENE OF PRIMARY HUMAN FIBROBLASTS

We report cytogenetic analysis of X-ray induced mutants of the HPRT ge ne isolated from a primary human fibroblast line. The mutants were sho wn previously by molecular analysis to have total or partial HPRT gene deletions. Detailed analysis of the chromosomal region containing HPR T (the cytogenetic band Xq26) identified Xq26 aberrations in five of f ive total HPRT gene deletions but failed to detect any changes in two of two partial gene deletions. Four microdeletions were verified and q uantified by a method termed the band ratio, which compares the distan ce between bands encompassing Xq26 and an adjacent X-chromosome region in elongated chromosomes. These measurements were supported by the pr esence or absence of the sub-band Xq26.2. One total HPRT gene deletion was also associated with an X; 11 translocation involving band Xq26. The data strengthen earlier findings on the tolerance of the Xq26 regi on to large genetic changes (> 1 Mb), but also indicate that some muta tions are more complex than simple deletion of DNA sequence.