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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.
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Table 1. Mutations at minisatellite loci in children of A-bomb survivors
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Probes
|
New mutations/gametes examined
|
| <0.01 Gy |
≥0.01 Gy* |
|
| λTM-18
|
0/183
|
0/65 |
| ChdTC-15 |
0/183
|
0/65 |
| Pλg3 |
0/183
|
1/65 |
| 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 |
Total
(Frequency) |
35/1,440
(2.4%)
|
9/509
(1.8%) |
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*Weighted mean dose 1.9 Gy
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Table 2. Mutations in DNA fingerprints
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| Children
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60
|
64
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| Total bands examined |
1,041
|
1,111
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| New mutations* |
13
(1.2%)
|
12
(1.1%)
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*Detected by a multilocus probe, 33.15
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References about this subject
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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 |
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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 |
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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 |
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Satoh C, Kodaira M: Effects of radiation on children. Nature 1996; 383:226
(Scientific correspondence) |
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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 |
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