Applications in Genetic Risk Estimation of Data on the Induction of Dominant Skeletal Mutations in Mice
The study of dominant skeletal mutations has major applications in genetic risk estimation and complements the specific-locus method with respect to the type of information provided. Specific-locus experiments are useful for determining whether heritable gene mutations are induced in mammalian germ cells by an agent. They can also be used quantitatively to make extrapolations to exposure levels encountered by humans, and they are particularly well suited for evaluating the effects of physical and biological variables on the frequency of transmitted mutations. They cannot, however, be used to determine the magnitude of damage that would be encountered in first-generation offspring. Two major reasons for this are (1) uncertainty as to how representative the few specific loci studied are of those genes that can mutate to cause dominant effects, and (2) uncertainty over how many genes can mutate to cause such effects. It is generally recognized that only those newly induced mutations that can cause damage in heterozygotes are of any significant importance for a great many generations to come [1, 2]. Studies on the induction of dominant skeletal mutations [4–6] and of dominant cataract mutations  have now provided means of estimating this type of damage. As more comparisons become possible between results obtained for dominant mutations and those for specific-locus mutations, a firmer basis will be established for extrapolating from specific-locus mutation-rate data to the magnitude of risk.
KeywordsToxicity Carbide Cage Cataract Kelly
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- 1.UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation), Sources and Effects of Ionizing Radiation, Report to the General Assembly, with Annexes, pp. 425–564. United Nations, New York, Sales No. E.77.IX.1. (1977).Google Scholar
- 2.BEIR III Committee (Advisory Committee on the Biological Effects of Ionizing Radiation of the United States National Academy of Sciences), The Effects on Populations of Exposure to Low Levels of Ionizing Radiation, pp. 91–180 in typescript ed. and pp. 71–134 in printed ed., Nat. Acad. Press, Washington, D.C. (1980).Google Scholar
- 7.W. L. Russell, Effect of radiation dose fractionation on mutation frequency in mouse spermatogonia, Genetics, 50:282 (1964)Google Scholar
- 8.W. L. Russell, in: “Peaceful Uses of Atomic Energy,” pp. 487–500, Intern. Atomic Energy Agency, Vienna (1972).Google Scholar
- 9.C. Ramel, J. Drake, and T. Sugimura, An evaluation of the genetic toxicity of dichlorvos, Mutation Res., 76:297–309 (1980)Google Scholar
- 11.P. B. Selby, in: “Mutagenicity: New Horizons in Genetic Toxicology,” J. A. Heddle, ed., pp. 385–406, Academic Press, New York (1982).Google Scholar
- 12.W. L. Russell, Studies in mammalian radiation genetics, Nucleonics, 23:53–56, 62 (1965).Google Scholar
- 14.W. L. Russell, P. R. Hunsicker, G. D. Raymer, M. H. Steele, K. F. Stelzner, and H. M. Thompson, Dose-response curve for specific-locus mutations induced by ethylnitrosourea in mouse spermatogonia, Proc. Natl. Acad. Sci. USA, submitted (1982).Google Scholar