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Search for Mutations Altering Protein Charge and/or Function in Children of Atomic Bomb Survivors: Final Report
Pages 363-376

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From page 363...
... a suitable comparison group have been examined for the occurrence of mutations altering the electrophoretic mobility or activity of a series of 30 proteins. The examination of the equivalent of 667,404 locus products in the children of proximally exposed persons yielded three mutations altering electrophoretic mobility; the corresponding figure for the comparison group was three mutations in 466,881 tests.
From page 364...
... The first entails the molecular basis of the chromosomal lesions that occur spontaneously or are induced by Xrays; the second entails some empirical observations on the offspring of irracliated mice. With respect to the first development, we note that some 20%-40% of the spontaneous germinal and somatic cell mutations at the hypoxanthine phosphoribosy~transferase, adenine phosphoribosy~transferase, thymidine kinase, factor VIII, and Duchenne muscular dystrophy loci can be shown with the Southern blot technique to involve readily detectable genomic alterations, whereas the proportion of such readily detected lesions among X-ray-induced mutations at these loci in somatic cells is more like 50%-60%, the results clif THE CHILDREN OF ATOMIC BOMB SURVIVORS 364
From page 365...
... Thus, nucleotide substitutions resulting in mild or no loss of gene-product function, substitutions that might alter electrophoretic mobility, would not be detected in these systems. The recent extension of studies of this type to the sequencing of mutant loci failing to exhibit abnormalities on Southern blotting analysis should greatly clarify this question of the molecular basis for the mutations at these loci (see Grosovsky et al.
From page 366...
... Because the number of children born to distally exposed parents is much greater than the number born to proximally exposed parents, cohort 2 has been reduced to a manageable size for this study by selecting at random from the children of the distally exposed a subset matching cohort 1 as to sex and year of birth. At the time this study was designed, individuals >2,500 m from the hypocenter ATB were thought to have received no or negligible (~0.01 Gy)
From page 367...
... , it will be apparent that there are substantially more locus tests on the children of proximally exposed par ents than on the children of distally exposed parents. This is in part because the cohort of children of the distally exposed parents was somewhat smaller than the cohort having proximally exposed parents, but to a lesser extent it is because the children of the distally exposed parents (and the parents themseIves)
From page 368...
... 1965 were the factors influencing the amount of radiation that was received by the survivors of the atomic bombings thought to be sufficiently well understood that individual dose estimates, termed Tentative 1965 Doses (T65) , could be assigned to survivors (Milton and Shohoji 1968; Auxier 1975; Hashizume and Marnyama 1975~.
From page 369...
... With this convention, all of the determinations of a polypeptide for which no variants have been encountered are credited as contributing to locus tests. Among the children of proximally exposed persons, there were five with an electrophoretic variant not observed in either parent; but for two of these children, the test battery described earlier indicated a discrepancy between legal and biological parentage.
From page 370...
... was detected in a male child of proximally exposed Nagasaki parents. The abnormal phenotype consisted of both a set of bands associated with the NP 1 phenotype and a set of rapidly migrating bands that exhibited a mobility similar to that of the bands associated with the NP 2 phenotype, a he THE CHILDREN OF ATOMIC BOMB SURVIVORS 370
From page 371...
... As shown in table 4, the estimated mutation rate on the basis of these findings is 0.45 x 10-5/Iocus/ generation, with the 95% confidence interval, calculated on the assumption that the number of mutations corresponds to a Poisson variant, being between 0.1 x 10-Sand1.3 x 10-s.Themutationrateinthe children of the distally exposed (control) cohort, as based on three mutations in 539,170 effective locus tests, was previously reported to be 0.56 x 10-s/ locus/generation, with 95% confidence intervals between 0.1 x 1O-s and 1.6 x 10-5 (Nee!
From page 372...
... to those of the electrophoretic series (3,3~. This results in a mutation frequency of 4 in 667,404 locus tests conducted on the children of proximally exposed persons and of 3 in 466,881 locus tests among the children of distally exposed persons; expressed in conventional fashion, these are rates of 0.60 and0.64 x 10-S/Iocus/generation,respectively.
From page 373...
... Since, as noted, for a child to be classified as born to proximally exposed parents, only one parent need have been <2,000 m from the hypocenter ATB, in the calculation of this average some parents are included who were distally exposed or even not in the cityATB. Assigning, as discussed earlier, an RBE of 20 to the neutron component of these exposures, we find that the average radiation doses to gonads become the following: Hiroshima parents, 0.495 Sv; and Nagasaki parents, 0.459 Sv.
From page 374...
... One indication of this is that the conjoint parental exposure in the parents of these four mutants averages 0.213 Sv, below the mean for the proximally exposed group rather than above the mean, as would be expected if the mutations were radiation induced. Given the assumption that the mutations encountered in the children of proximally exposed persons are really spontaneous in nature, we can pool these mutations with the mutations in the children of distally exposed (i.e., nonrafdiated)
From page 375...
... 1980. Search for mutations affecting protein structure in children of atomic bomb survivors: preliminary report.
From page 376...
... 1982. Genetic effects of atomic bombs.


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