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Keywords:

  • repeat expansion disease;
  • triplet repeat instability;
  • Fragile X syndrome;
  • FMR1;
  • DNA repair;
  • oxidative damage;
  • 7;
  • 8-dihydro-8-oxo-guanine (8-oxoG)

Abstract

Tandem repeat expansion is responsible for the Repeat Expansion Diseases, a group of human genetic disorders that includes Fragile X syndrome (FXS). FXS results from expansion of a premutation (PM) allele having 55–200 CGG·CCG-repeats in the 5′ UTR of the FMR1 gene. The mechanism of expansion is unknown. We have treated FX PM mice with potassium bromate (KBrO3), a potent DNA oxidizing agent. We then monitored the germline and somatic expansion frequency in the progeny of these animals. We show here that KBrO3 increased both the level of 8-oxoG in the oocytes of treated animals and the germline expansion frequency. Our data thus suggest that oxidative damage may be a factor that could affect expansion risk in humans. Hum Mutat 31:1–6, 2010. Published 2010 Wiley-Liss, Inc.