Radiation and germline mutation at repeat sequences: Are we in the middle of a paradigm shift?

Bridges, B. A. (2001) Radiation and germline mutation at repeat sequences: Are we in the middle of a paradigm shift? Radiation Research, 156 (5 Pt 2). pp. 631-641. ISSN 0964-7813

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Abstract

Two assumptions are commonly made in the estimation of genetic risk: (1) that the seven specific loci in the mouse constitute a suitable basis for extrapolation to genetic disease in humans, and (2) that mutations are induced by radiation damage (energy-loss events leading to double-stranded damage) occurring within the gene and are induced linearly with dose, at least at low doses. Recent evidence on the mutability of repeat sequences is reviewed that suggests that neither of these assumptions is as well founded as we like to think. Repeat sequences are common in the human genome, and alterations in them may have health consequences. Many of them are unstable, both spontaneously and after irradiation. The fact that changes in DNA repeat sequences can clearly arise as a result of radiation damage outside the sequence concerned and the likely involvement of some sort of signal transduction process mean that the nature of the radiation dose response cannot be assumed. While the time has not come to abandon the current paradigms, it would seem sensible to invest more effort in exploring the induction of changes in repeat sequences after irradiation and the consequences of such changes for health.

Item Type: Article
Additional Information: GDSC7
Keywords: Genetic Diseases, Inborn Germ-Line Mutation/*radiation effects Human Microsatellite Repeats/genetics/*radiation effects Minisatellite Repeats/genetics/*radiation effects Radiation Repetitive Sequences, Nucleic Acid/genetics/radiation effects 87&volume=156&issue=5&page=631
Schools and Departments: School of Life Sciences
Subjects: R Medicine > RC Internal medicine
Depositing User: Gee Wheatley
Date Deposited: 08 May 2007
Last Modified: 30 Nov 2012 16:51
URI: http://sro.sussex.ac.uk/id/eprint/1079
Google Scholar:29 Citations
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