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DNA studies of the children of atomic-bomb survivors (1985-present)

DNA studies of survivor families make use of Epstein-Barr-virus transformed cell lines established from peripheral blood B lymphocytes. Cells come from parents and all available children of 1,000 families, 500 with one or both parents exposed to doses of 0.01 Gy or greater and 500 with neither parent exposed to significant doses. Uncultured lymphocytes and polymorphonuclear leukocytes are also preserved. New techniques for DNA analysis such as DNA chip technology are currently being developed.

A pilot study has been initiated to examine DNA in 100 families, 50 exposed and 50 controls. Minisatellite genes comprise high tandem repeats of core sequences (more than a few base pairs), which are located at many places in the genome, and are known as highly polymorphic in its repeat number (or total length). As such genes are highly unstable in nature and the spontaneous mutation rate is high, genetic effect of radiation can be detected with tests of a relatively small number of offspring. The results by eight probes and DNA fingerprints analysed by a multilocus probe, 33.15, are shown in Tables 1 and 2. No effects attributable to radiation have yet been observed. Among new mutations at minisatellite loci, more than 80% are derived from male parents (the production of sperm involves many times more cell divisions than that of eggs). RERF results on the minisatellite mutations are in contrast to the results obtained by an English group on radiation-exposed families (but the exposed doses are much smaller than those in A-bomb survivors) after Chernobyl nuclear power plant accident etc., but the reasons are not yet understood.

Recently, a pilot study was conducted that used microarrays as one of the DNA studies related to genetic effects of radiation. The microarray used consisted of about 2,500 DNA clones (termed PAC or BAC) that were selected among the huge number of clones prepared for human genome project. The array could detect copy-number changes (CNV; deletion or duplication) of sufficient length (>30 kb) in the genome. Among the 80 offspring examined, 251 CNVs were detected but all of them were inherited from either parent. No suspected case was found that could have occurred newly following parental expo sure to A-bomb radiation. Further studies are under consideration.
Table 1. Mutations at minisatellite loci in children of A-bomb survivors
New mutations/gametes examined
<0.01 Gy ≥0.01 Gy*
λMS-1 11/183 1/65
CEB-1 11/183 4/65
Pc-1 0/183 0/65
B6.7 6/160 3/56
CEB-15 7/182 0/63
*Weighted mean dose 1.9 Gy

Table 2. Mutations in DNA fingerprints
<0.01 Gy
≥0.01 Gy
Total bands examined
New mutations*
*Detected by a multilocus probe, 33.15
References about this subject
Kodaira M, Izumi S, et al.: No evidence of radiation effect on mutation rate at hypervariable minisatellite loci in the germ cells of atomic-bomb survivors. Radiation Research 2004; 162:350-6
Asakawa J, Nakamura N, et al.: Estimation of mutation induction rates in AT-rich sequences using a genome scanning approach after X irradiation of mouse spermatogonia. Radiation Research 2007; 168:158-67
Kodaira M, Satoh C, et al.: Lack of effects of atomic-bomb radiation on genetic instability of tandem-repetitive elements in human germ cells. American Journal of Human Genetics 1995; 57:1275-83
Satoh C, Kodaira M: Effects of radiation on children. Nature 1996; 383:226 (Scientific correspondence)
Takahashi N, Tsuyama N, Kodaira M, Satoh Y, Kodama Y, Sugita K, Katayama H: Segmental copy-number variation observed in Japanese by array-CGH. Annals of Human Genetics 2007; 71:1-12