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  • Title: Molecular structure of mutations at an autosomal locus in human cells: evidence for interallelic homologous recombination.
    Author: Little JB, Benjamin MB.
    Journal: Ann Genet; 1991; 34(3-4):161-6. PubMed ID: 1809222.
    Abstract:
    A high proportion of spontaneous mutations at the heterozygous thymidine kinase (TK) locus in a human B-lymphoblast cell line involved loss of the entire active allele. Loss of heterozygosity often extended to other loci on chromosome 17q. The authors have developed a system for analysing the role of homologous recombination and gene conversion in such events. A heteroallelic (TK-/-) cell line containing single + 1 frameshifts in exons 4 and 7 was generated by repeated exposures to ICR-191. Revertant mutations to TK+/- were selected and analysed for the presence or absence or each frameshift as well as changes in linked polymorphic markers on 17q. The molecular changes associated with reversion to TK+ can thus be analysed. Preliminary results indicate that homologous recombination can be detected with this system, though it occurs at low frequency (less than 10(-7]. The authors believe this represents the first quantitative assay for measuring recombination between alleles of a specific intact gene in human cells. It should prove useful in evaluating the potency of various classes of mutagens in inducing recombinational and gene conversion events.
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