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  • Title: Genetic instability on chromosome 16 in a human B lymphoblastoid cell line.
    Author: Smith LE, Grosovsky AJ.
    Journal: Somat Cell Mol Genet; 1993 Nov; 19(6):515-27. PubMed ID: 7907433.
    Abstract:
    Mutagenesis at the aprt locus in TK6 human lymphoblasts has been found to occur at an unusually high rate (1.2 x 10(-9)) for a homozygous diploid locus. Evaluation of linked microsatellite polymorphisms demonstrated that loss of heterozygosity (LOH) accompanies conventional intragenic sequence alterations in each APRT- mutant. LOH occurred without allele preference. The extent of loss was highly uniform, ranging from 16q12 to 16qter in 36/38 APRT- mutants. Fluorescence in situ hybridization (FISH), used in conjunction with microsatellite analysis, demonstrated that the loss was not attributable to physical deletion, nondisjunction, or nondisjunction with reduplication of the remaining chromosome. LOH thus appears to be recombinationally mediated. FISH analysis also detected translocations affecting chromosome 16 in 4/20 APRT- mutants examined. APRT- mutants appear to arise as part of a genetic instability phenomenon since three distinct genetic alterations affecting chromosome 16 are recovered in single clones at a detectable rate. These events may be mechanistically related to early events in gene amplification.
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