Abstract
In a pilot study to detect the potential effects of atomic bomb radiation on germ-line instability, we screened 64 children from 50 exposed families and 60 from 50 control families for mutations at six minisatellite loci by using Southern blot analysis with Pc-1, lambda TM-18, ChdTC-15, p lambda 3, lambda MS-1, and CEB-1 probes. In the exposed families, one or both parents received a radiation dose > 0.01 Sv. Among the 64 children, only one child had parents who were both exposed. Thus, of a total of 128 gametes that produced the 64 children, 65 gametes were derived from exposed parents and 63 were from unexposed parents, the latter being included in a group of 183 unexposed gametes used for calculating mutation rates. The average parental gonadal dose for the 65 gametes was 1.9 Sv. We detected a total of 28 mutations at the p lambda g3, lambda MS-1, and CEB-1 loci, but no mutations at the Pc-1, lambda TM-18, and ChdTC-15 loci. We detected 6 mutations in 390 alleles of the 65 exposed gametes and 22 mutations in 1098 alleles of the 183 gametes from the unexposed parents. The mean mutation rate per locus per gamete in these six minisatellite loci was 1.5% in the exposed parents and 2.0% in the unexposed parents. We observed no significant difference in mutation rates in the children of the exposed and the unexposed parents (P = .37, Fisher's exact probability test).
Full text
PDF








Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Armour J. A., Patel I., Thein S. L., Fey M. F., Jeffreys A. J. Analysis of somatic mutations at human minisatellite loci in tumors and cell lines. Genomics. 1989 Apr;4(3):328–334. doi: 10.1016/0888-7543(89)90338-8. [DOI] [PubMed] [Google Scholar]
- Asakawa J., Satoh C., Yamasaki Y., Chen S. H. Accurate and rapid detection of heterozygous carriers of a deletion by combined polymerase chain reaction and high-performance liquid chromatography. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9126–9130. doi: 10.1073/pnas.89.19.9126. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dubrova Y. E., Jeffreys A. J., Malashenko A. M. Mouse minisatellite mutations induced by ionizing radiation. Nat Genet. 1993 Sep;5(1):92–94. doi: 10.1038/ng0993-92. [DOI] [PubMed] [Google Scholar]
- Henke J., Fimmers R., Baur M. P., Henke L. DNA-minisatellite mutations: recent investigations concerning distribution and impact on parentage testing. Int J Legal Med. 1993;105(4):217–222. doi: 10.1007/BF01642797. [DOI] [PubMed] [Google Scholar]
- Henke L., Cleef S., Zakrzewska M., Henke J. Population genetic data determined for five different single locus minisatellite probes. EXS. 1991;58:144–153. doi: 10.1007/978-3-0348-7312-3_11. [DOI] [PubMed] [Google Scholar]
- Hiyama K., Kodaira M., Satoh C. Detection of deletions, insertions and single nucleotide substitutions in cloned beta-globin genes and new polymorphic nucleotide substitutions in beta-globin genes in a Japanese population using ribonuclease cleavage at mismatches in RNA:DNA duplexes. Mutat Res. 1990 Aug;231(2):219–231. doi: 10.1016/0027-5107(90)90028-3. [DOI] [PubMed] [Google Scholar]
- Honma M., Mitani K., Mizusawa H., Sofuni T., Muramatsu M., Kominami R. A new VNTR-type RFLP probe (lambda TM-18) on chromosome 1 (D1S157). Hum Mol Genet. 1992 Oct;1(7):554–554. [PubMed] [Google Scholar]
- Jeffreys A. J., Royle N. J., Wilson V., Wong Z. Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA. Nature. 1988 Mar 17;332(6161):278–281. doi: 10.1038/332278a0. [DOI] [PubMed] [Google Scholar]
- Jeffreys A. J., Wilson V., Neumann R., Keyte J. Amplification of human minisatellites by the polymerase chain reaction: towards DNA fingerprinting of single cells. Nucleic Acids Res. 1988 Dec 9;16(23):10953–10971. doi: 10.1093/nar/16.23.10953. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeffreys A. J., Wilson V., Thein S. L. Hypervariable 'minisatellite' regions in human DNA. Nature. 1985 Mar 7;314(6006):67–73. doi: 10.1038/314067a0. [DOI] [PubMed] [Google Scholar]
- Kelly R., Bulfield G., Collick A., Gibbs M., Jeffreys A. J. Characterization of a highly unstable mouse minisatellite locus: evidence for somatic mutation during early development. Genomics. 1989 Nov;5(4):844–856. doi: 10.1016/0888-7543(89)90126-2. [DOI] [PubMed] [Google Scholar]
- Kodaira M., Hiyama K., Karakawa T., Kameo H., Satoh C. Duplication detection in Japanese Duchenne muscular dystrophy patients and identification of carriers with partial gene deletions using pulsed-field gel electrophoresis. Hum Genet. 1993 Oct 1;92(3):237–243. doi: 10.1007/BF00244465. [DOI] [PubMed] [Google Scholar]
- Lüning K. G., Searle A. G. Estimates of the genetic risks from ionizing irradiation. Mutat Res. 1971 Jul;12(3):291–304. doi: 10.1016/0027-5107(71)90017-0. [DOI] [PubMed] [Google Scholar]
- Mitani K., Takahashi Y., Kominami R. A GGCAGG motif in minisatellites affecting their germline instability. J Biol Chem. 1990 Sep 5;265(25):15203–15210. [PubMed] [Google Scholar]
- Nakamura Y., Leppert M., O'Connell P., Wolff R., Holm T., Culver M., Martin C., Fujimoto E., Hoff M., Kumlin E. Variable number of tandem repeat (VNTR) markers for human gene mapping. Science. 1987 Mar 27;235(4796):1616–1622. doi: 10.1126/science.3029872. [DOI] [PubMed] [Google Scholar]
- Neel J. V., Lewis S. E. The comparative radiation genetics of humans and mice. Annu Rev Genet. 1990;24:327–362. doi: 10.1146/annurev.ge.24.120190.001551. [DOI] [PubMed] [Google Scholar]
- Neel J. V., Satoh C., Goriki K., Asakawa J., Fujita M., Takahashi N., Kageoka T., Hazama R. Search for mutations altering protein charge and/or function in children of atomic bomb survivors: final report. Am J Hum Genet. 1988 May;42(5):663–676. [PMC free article] [PubMed] [Google Scholar]
- Neel J. V., Satoh C., Myers R. International Commission for Protection against Environmental Mutagens and Carcinogens. Report of a workshop on the application of molecular genetics to the study of mutation in the children of atomic bomb survivors. Mutat Res. 1993 Feb;291(1):1–20. doi: 10.1016/0165-1161(93)90012-o. [DOI] [PubMed] [Google Scholar]
- Neel J. V., Schull W. J., Awa A. A., Satoh C., Kato H., Otake M., Yoshimoto Y. The children of parents exposed to atomic bombs: estimates of the genetic doubling dose of radiation for humans. Am J Hum Genet. 1990 Jun;46(6):1053–1072. [PMC free article] [PubMed] [Google Scholar]
- Otake M., Schull W. J., Neel J. V. Congenital malformations, stillbirths, and early mortality among the children of atomic bomb survivors: a reanalysis. Radiat Res. 1990 Apr;122(1):1–11. [PubMed] [Google Scholar]
- Royle N. J., Clarkson R. E., Wong Z., Jeffreys A. J. Clustering of hypervariable minisatellites in the proterminal regions of human autosomes. Genomics. 1988 Nov;3(4):352–360. doi: 10.1016/0888-7543(88)90127-9. [DOI] [PubMed] [Google Scholar]
- Sadamoto S., Suzuki S., Kamiya K., Kominami R., Dohi K., Niwa O. Radiation induction of germline mutation at a hypervariable mouse minisatellite locus. Int J Radiat Biol. 1994 May;65(5):549–557. doi: 10.1080/09553009414550641. [DOI] [PubMed] [Google Scholar]
- Satoh C. A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Biochemical genetics study. J Radiat Res. 1991 Mar;32 (Suppl):378–384. doi: 10.1269/jrr.32.supplement_378. [DOI] [PubMed] [Google Scholar]
- Satoh C., Hiyama K., Takahashi N., Kodaira M., Neel J. V. Approaches to DNA methods for the detection of heritable mutations in humans. Prog Clin Biol Res. 1990;340C:197–206. [PubMed] [Google Scholar]
- Satoh C., Takahashi N., Asakawa J., Hiyama K., Kodaira M. Variations among Japanese of the factor IX gene (F9) detected by PCR-denaturing gradient gel electrophoresis. Am J Hum Genet. 1993 Jan;52(1):167–175. [PMC free article] [PubMed] [Google Scholar]
- Suzuki S., Mitani K., Kuwabara K., Takahashi Y., Niwa O., Kominami R. Two mouse hypervariable minisatellites: chromosomal location and simultaneous mutation. J Biochem. 1993 Aug;114(2):292–296. doi: 10.1093/oxfordjournals.jbchem.a124169. [DOI] [PubMed] [Google Scholar]
- Takahashi N., Hiyama K., Kodaira M., Satoh C. An improved method for the detection of genetic variations in DNA with denaturing gradient gel electrophoresis. Mutat Res. 1990 Apr;234(2):61–70. doi: 10.1016/0165-1161(90)90032-j. [DOI] [PubMed] [Google Scholar]
- Vergnaud G., Mariat D., Apiou F., Aurias A., Lathrop M., Lauthier V. The use of synthetic tandem repeats to isolate new VNTR loci: cloning of a human hypermutable sequence. Genomics. 1991 Sep;11(1):135–144. doi: 10.1016/0888-7543(91)90110-z. [DOI] [PubMed] [Google Scholar]
- Wong F. L., Yamada M., Sasaki H., Kodama K., Akiba S., Shimaoka K., Hosoda Y. Noncancer disease incidence in the atomic bomb survivors: 1958-1986. Radiat Res. 1993 Sep;135(3):418–430. [PubMed] [Google Scholar]
- Wong Z., Wilson V., Patel I., Povey S., Jeffreys A. J. Characterization of a panel of highly variable minisatellites cloned from human DNA. Ann Hum Genet. 1987 Oct;51(Pt 4):269–288. doi: 10.1111/j.1469-1809.1987.tb01062.x. [DOI] [PubMed] [Google Scholar]
- Yoshimoto Y., Neel J. V., Schull W. J., Kato H., Soda M., Eto R., Mabuchi K. Malignant tumors during the first 2 decades of life in the offspring of atomic bomb survivors. Am J Hum Genet. 1990 Jun;46(6):1041–1052. [PMC free article] [PubMed] [Google Scholar]
- Yoshimoto Y., Schull W. J., Kato H., Neel J. V. Mortality among the offspring (F1) of atomic bomb survivors, 1946-85. J Radiat Res. 1991 Dec;32(4):327–351. doi: 10.1269/jrr.32.327. [DOI] [PubMed] [Google Scholar]