A comparison of induced mutation at homologous alleles of the tk locus in human cells. II. Molecular analysis of mutants.

Previously we described the dose-response relationship for X-ray-induced mutation of the two homologous alleles of the thymidine kinase (tk) gene in a human lymphoblastoid cell line (Amundson and Liber, 1991). The two alleles were differentially mutable by X-rays, with one allele 6-10 times more mutable than the other. This difference was shown to be due to the virtual absence of the class of slow growth mutants from one allele. In the present report, restriction fragment length polymorphism (RFLP) analyses of informative markers along chromosome 17 have been used to delineate a region of chromosome 17 in which heterozygosity is lost with relatively high frequency among slow growth TK- mutants from the more mutable allele. However, loss of heterozygosity of this region has never been observed in normal growth mutants obtained from the more mutable allele, or in TK- mutants from the other, less mutable, allele. This may indicate the presence of a heterozygous essential gene on chromosome 17 distal to TK1.