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Assessing radiation-associated mutational risk to the germline: repetitive DNA sequences as mutational targets and biomarkers

Bouffler, S. D., Bridges, B. A,, Cooper, David Neil, Dubrova, Y., MacMillan, T. J., Thacker, J., Wright, E. G. and Waters, R. 2006. Assessing radiation-associated mutational risk to the germline: repetitive DNA sequences as mutational targets and biomarkers. Radiation Research 165 (3) , pp. 249-268.

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Abstract

This review assesses recent data on mutational risk to the germline after radiation exposure obtained by molecular analysis of tandemly repeated DNA loci (TRDLs): minisatellites in humans and expanded simple tandem repeats in mice. Some studies, particularly those including exposure to internal emitters, indicate that TRDL mutation can be used as a marker of human radiation exposure; most human studies, however, are negative. Although mouse studies have suggested that TRDL mutation analysis may be more widely applicable in biomonitoring, there are important differences between the structure of mouse and human TRDLs. Mutational mechanisms probably differ between the two species, and so care should be taken in predicting effects in humans from mouse data. In mice and humans, TRDL mutations are largely untargeted with only limited evidence of dose dependence. Transgenerational mutation has been observed in mice but not in humans, but the mechanisms driving such mutation transmission are unknown. Some minisatellite variants are associated with human diseases and may affect gene transcription, but causal relationships have not yet been established. It is concluded that at present the TRDL mutation data do not warrant a dramatic revision of germline or cancer risk estimates for radiation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
Publisher: Radiation Research Society
ISSN: 0033-7587
Last Modified: 04 Jun 2017 08:45
URI: http://orca.cf.ac.uk/id/eprint/84147

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