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Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA

Abstract

Tandem-repetitive minisatellite regions in vertebrate DNA frequently show substantial allelic variation in the number of repeat units. This variation is thought to arise through processes such as unequal crossover or replication slippage1–12. We show here that the spontaneous mutation rate to new length alleles at extremely variable human minisatellites is sufficiently high to be directly measurable in human pedigrees. The mutation rate at different loci increases with variability in accord with the neutral mutation/random drift hypothesis, and rises to 5% per gamete for the most unstable human minisatellite isolated. Mutations are sporadic, occur with similar frequencies in sperm and oocytes, and can involve the gain or loss of substantial numbers of repeat units, consistent with length changes arising primarily by unequal exchange at meiosis. Germline instability must therefore be taken into account when using hypervariable loci as genetic markers, particularly in pedigree analysis and parenthood testing.

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References

  1. Bell, G. I., Selby, M. J. & Rutter, W. J. Nature 295, 31–35 (1982).

    Article  ADS  CAS  Google Scholar 

  2. Capon, D. J., Chen, E. Y., Levinson, A. D., Seeburg, P. H. & Goeddel, D. V. Nature 302, 33–37 (1983).

    Article  ADS  CAS  Google Scholar 

  3. Goodbourn, S. E. Y., Higgs, D. R., Clegg, J. B. & Weatherall, D. J. Proc. natn. Acad. Sci. U.S.A. 80, 5022–5026 (1983).

    Article  ADS  CAS  Google Scholar 

  4. Jeffreys, A. J., Wilson, V. & Thein, S. L. Nature 314, 67–73 (1985).

    Article  ADS  CAS  Google Scholar 

  5. Jeffreys, A. J., Wilson, V. & Thein, S. L. Nature 316, 76–79 (1985).

    Article  ADS  CAS  Google Scholar 

  6. Jarman, A., Nicholls, R. D., Weatherall, D. J., Clegg, J. B. & Higgs, D. R. EMBO J. 5, 1857–1863 (1986).

    Article  CAS  Google Scholar 

  7. Jeffreys, A. J., Wilson, V., Thein, S. L., Weatherall, D. J. & Ponder, B. A. J. Am. J. hum. Genet. 39, 11–24 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Wong, Z., Wilson, V., Jeffreys, A. J. & Thein, S. L. Nucleic Acids Res. 14, 4605–4616 (1986).

    Article  CAS  Google Scholar 

  9. Jeffreys, A. J. Biochem. Soc. Trans. 15, 309–317 (1987).

    Article  CAS  Google Scholar 

  10. Jeffreys, A. J. & Morton, D. B. Anim. Genet. 18, 1–15 (1987).

    Article  CAS  Google Scholar 

  11. Nakamura, Y. et al. Science 235, 1616–1622 (1987).

    Article  ADS  CAS  Google Scholar 

  12. Wong, Z., Wilson, V., Patel, I., Povey, S. & Jeffreys, A. J. Ann. hum. Genet. 51, 269–288 (1987).

    Article  CAS  Google Scholar 

  13. Bakker, E. et al. Nature 329, 554–556 (1987).

    Article  ADS  CAS  Google Scholar 

  14. Darras, B. T. & Francke, U. Nature 329, 556–558 (1987).

    Article  ADS  CAS  Google Scholar 

  15. Ohta, T. & Kimura, M. Genet. Res. 22, 201–204 (1973).

    Article  MathSciNet  CAS  Google Scholar 

  16. Kimura, M. Genet. Res. 11, 247–269 (1968).

    Article  CAS  Google Scholar 

  17. Morton, N. E. Outline of Genetics Epidemiology (Karger, Basel, 1982).

    Google Scholar 

  18. Vogel, F. & Rathenberg, R. Adv. hum. Genet. 5, 223–318 (1975).

    Article  CAS  Google Scholar 

  19. Levinson, G. & Guttman, G. A. Molec. Biol. Evol. 4, 203–221 (1987).

    CAS  PubMed  Google Scholar 

  20. Jeffreys, A. J., Brookfield, J. F. Y. & Semeonoff, R. Nature 317, 818–819 (1985).

    Article  ADS  CAS  Google Scholar 

  21. Baird, M. et al. Am. J. hum. Genet. 39, 489–501 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Siegel, S. Nonparametric Statistics for the Behavioural sciences (McGraw-Hill, Tokyo, 1956).

    MATH  Google Scholar 

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Jeffreys, A., Royle, N., Wilson, V. et al. Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA. Nature 332, 278–281 (1988). https://doi.org/10.1038/332278a0

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