Monitoring of radiation-induced germline mutation in ... - Tchernobyl
by hybridisation with minisatellite probes. Mu- tants were identified as novel DNA fragments present in the offspring, and mutation rates in the germline of ...
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Peer reviewed article
Monitoring of radiation-induced germline mutation in humans Yuri E. Dubrova Department of Genetics, University of Leicester, United Kingdom
Summary Estimating the genetic hazards of radiation and other mutagens in humans depends on extrapolation from experimental systems. Recent data have shown that minisatellite loci provide a useful and sensitive experimental approach for monitoring radiation-induced mutation in humans. This review describes the progress made in
validating this approach and presents the results of recent publications on the analysis of minisatellite mutation rates in the irradiated families. Key words: germline mutation; minisatellite loci; ionising radiation; Chernobyl; Semipalatinsk
Introduction The detection of radiation-induced changes in germline mutation rate in human populations still remains extremely difficult [1]. In previous studies on the children of atomic bomb survivors and radiotherapy patients [2, 3], germline mutation rates were indirectly estimated by analysing the incidence of mortality and the occurrence of genetic diseases among the offspring of irradiated parents. It should be stressed that the sensitivity of these approaches for monitoring radiation-induced mutations remains highly uncertain [4]. That is why germline mutation induction in mice is still used as the main source of experimental data for evaluating the genetic risk of human exposure to ionising radiation [1, 5]. Such an extrapolation has not been experimentally validated and is consequently not proven. It therefore remains increasingly clear that the reliable estimates of the genetic risk of human exposure to ionising radiation can only be derived from the relevant experimental data on
germline mutation induction in human populations which, in turn, requires new experimental approaches for monitoring radiation-induced germline mutation. We have recently developed a novel system for monitoring radiation-induced mutation in mammalian germline, which is based on a set of hypervariable tandem repeat DNA loci [6–8]. The results of our studies have shown that changes in mutation rate in laboratory mice exposed to ionising radiation or chemical mutagens can be detected in very small population samples and at doses far lower than had been possible using standard approaches for monitoring germline mutation in mice [8–10]. These data raised the possibility that tandem repeat DNA loci can also provide a useful tool for monitoring radiation-induced mutation in humans. Here I present the summary of recent publications analysing mutation induction at human tandem repeat minisatellite loci.
Tandem repeat minisatellite loci
Supported by grants from the Wellcome Trust and by the INCOCopernicus grant from the European Commission.
Tandem repeat loci in the human genome are represented by relatively short microsatellites (
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