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Spectrum of spontaneous mutations in a cDNA of the human hprt gene integrated in chromosomal DNA

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Summary

Altered sequences were determined of 52 independent spontaneous mutations occuring in a cDNA of the human hypoxanthine phosphoribosyltransferase (hprt) gene, which was integrated into chromosomal DNA of the mouse cell as a part of the retroviral shuttle vector. Spontaneous mutations comprised a variety of events: base substitutions, frameshifts, deletions, duplications, and complex mutational events, and were distributed randomly over the coding region of the gene. Frameshifts were the most frequent mutational event (38%), and base substitutions were the next most frequent (25%), followed by deletions (19%). Frameshift and deletion mutations commonly occurred preferentially at sites flanked by short direct repeats. Short inverted repeats were frequently found to be associated with duplication and complex mutational events. Analysis of the sequence alterations in the mutant genes suggests that misalignment mutagenesis represents an important molecular mechanism for the generation of spontaneous mutations in eukaryotic cells.

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Author notes

  1. Hironobu Ikehata

    Present address: Laboratory of Radiation Biology, Faculty of Science, Kyoto University, 606, Kyoto, Japan

  2. Toshiaki Akagi

    Present address: Department of Internal Medicine, Hyogo College of Medicine, 663, Hyogo, Japan

Authors and Affiliations

  1. Department of Fundamental Radiology, Osaka University, Medical School, 530, Osaka, Japan

    Hironobu Ikehata, Toshiaki Akagi & Takesi Kato

  2. Department of Experimental Radiology, Shiga University of Medical Science, 520-21, Ohtsu, Shiga, Japan

    Hiroshi Kimura

  3. Division of Industrial Health, Osaka Prefectural Institute of Public Health, 537, Osaka, Japan

    Susumu Akasaka

Authors
  1. Hironobu Ikehata
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  2. Toshiaki Akagi
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  3. Hiroshi Kimura
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  4. Susumu Akasaka
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  5. Takesi Kato
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Communicated by R. Devoret

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Ikehata, H., Akagi, T., Kimura, H. et al. Spectrum of spontaneous mutations in a cDNA of the human hprt gene integrated in chromosomal DNA. Mol Gen Genet 219, 349–358 (1989). https://doi.org/10.1007/BF00259606

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