Abstract: The rates of spontaneous mutation to 6-thioguanine resistance were determined in fibroblasts derived from normal and two Bloom syndrome individuals (GM 2548 and GM 1492). Two methods were utilized to determine the rates. Method I obtained the spontaneous mutation rate from the increase in the mutation frequency of a cell population in logarithmic-phase growth over 10 days. The two Bloom syndrome strains had spontaneous mutation rates of 16 X 10(-6) and 17 X 10(-6) mutations per cell per generation, whereas two normal strains had rates of 1.5 X 10(-6) and 1.1 X 10(-6). Method II utilized fluctuation analysis to measure the rate of spontaneous mutation. This method resulted in rates of 19 X 10(-6) and 23 X 10(-6) mutations per cell per generation in Bloom syndrome cells, compared to rates of 4.6 X 10(-6) and 4.9 X 10(-6) in the control strains. These data suggest that Bloom syndrome may be a mutator mutation, a previously unrecognized phenomenon in humans, and that an elevated spontaneous mutation rate in vivo may be responsible for the clinical phenotype of primordial dwarfism and increased cancer incidence.

Abstract: Therates ofspontaneous mutation to6-thiogua- nine resistance weredetermined infibroblasts derived from nor- malandtwoBloom syndrome individuals (GM2548 andGM1492). Twomethods wereutilized todetermine therates. Method Iob- tained thespontaneous mutation rate fromtheincrease inthe mutation frequency ofacell population inlogarithmic-phase growth over 10days. ThetwoBloom syndrome strains hadspon- taneous mutation rates of16X 10-6 and17x10-6 mutations per cell pergeneration, whereas twonormal strains hadrates of1.5 X10-6 and1.1x10-6. Method IIutilized fluctuation analysis to measure therate ofspontaneous. mutation. This method resulted inrates of19x10-6 and23x10-6 mutations percell pergen- eration inBloom syndrome cells, compared torates of4.6X 10-6 and4.9X 10-6 inthecontrol strains. These data suggest that Bloom syndrome maybeamutator mutation, apreviously unrec- ognized phenomenon inhumans, andthatan elevated spontaneous mutation rate invivo mayberesponsible for theclinical phenotype ofprimordial dwarfism andincreased cancer incidence.

Abstract: It was investigated what potentialities for mutation breeding of potato are offered by using adventitious sprouts that arise in vitro from leaf explants (rachis, petiole, leaflet-disc) after X-irradiation. Mutation frequency and chimerism were studied in subterranean and aerial parts in three vegetative generations (vM1, vM2, vM3). Plants obtained from irradiated series produced a very high mutation frequency, a wide mutation spectrum and a very low rate of chimerism. Mutations were observed also in control series, especially in plants derived from the rachis and petiole explant group.

Abstract: The mutation component, M, is a measure of the proportion of the impact of a genetic condition that is attributable to recurrent mutation. For a trait maintained by balance between mutation and directional selection, M is approximately the broad-sense heritability; for a measured character where the mean and optimum coincide, M is about half the heritability. If the narrow-sense heritability is high, the impact changes relatively rapidly with a change in mutation rate. If the narrow-sense heritability is low, M cannot be predicted, but the change in impact following a change in mutation rate, if any, is very slow.

Abstract: The maize mutator system, Mu, behaves in a non-Mendelian manner that may be expected if it were an extremely active controlling-element system To test this hypothesis, the maize controlling-element systems, adtDt, DsAc ( MP), IEn, and rcuFcu were tested for mutation activity DsAc and rcuFcu tests were the only ones in which new mutants were induced, but at a frequency much lower than that found in Mu crosses The mutation frequency in these controlling-element systems does not differ statistically from that found in control (Non-Mu) populations Tests also were made to determine if Mu will substitute for the regulatory element of any of the 4 conotrolling-element All tests were negative, suggesting that, if Mu is a controlling-element system, it is a different one from those previously described

Abstract: By using a numerical method of solving stochastic difference equations, the level of genetic variability maintained in a finite population and the rate of gene substitution under several models of fluctuating selection intensities were studied. It is shown that mutation and random genetic drift both play an important role in determining genetic variability and the rate of gene substitution. Compared with the case of neutral mutations, the fluctuation of selection intensity caused by temporal and spatial heterogeneity of environments generally increases the rate of gene substitution, but the level of genetic variability may be increased or decreased, depending upon the model and the parameters used. Although such a type of selection per se can not be ruled out, when mutation is taken into account, it is difficult to explain both the observed amount of genetic variability and the rough constancy of evolutionary rate within a framework of fluctuating selection models.

Abstract: In order to assess the impact on man of a sustained change in mutation rate that might be caused by ionizing radiation or a chemical mutagen in the environment, it is important to determine the current incidence of genetic disease, the rate at which deleterious mutations arise and the number of generations that mutations persist before eliminated by selection. From these data it should be possible to estimate both the increase in genetic disease in the first generation following the increase in mutation rate, and the rate at which a new equilibrium between mutation and selection would occur. In this paper the results of a survey to determine birth frequency, mutation rate and reproductive fitness for each of the important dominant and X-linked recessive disorders are described. It is estimated that these disorders affect about 0.6% of live-born individuals, including 0.1% of live-borns who carry a newly-arising mutation. These figures are approx. 50% lower than those used by the various committees that have assessed the genetic risk to man from ionizing radiation. If the mutation rate were to permanently double, the frequency of these disorders would be expected in increase in the first generation by 15%, to 0.7% of live-births. The increase in the first 2 generations would be 24% and a 50% increase would occur by the 9th generation. A calculation of the possible increase in dominant and X-linked recessive disorders due to exposure of a population to ionizing radiation indicates that the estimate made in 1977 by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) may be too high by a factor of 2-6 fold.

Abstract: We report female monozygotic twins with neurofibromatosis. The family history is unremarkable, and careful examination of other family members did not show evidence of the condition. It is concluded that the occurrence in this family is due to a spontaneous mutation arising in one of the parental gametes. This article examines the similarity and difference in manifestations of the disorder in this pair of monozygotic twins.

Abstract: A cold-sensitive mutant of Pseudomonas putida has been isolated which grows normally at 30 C but is unable to grow on mandelate as a source of carbon at 15 C. The mutation results in the inability of the strain to carry out the reaction catalyzed by cis,cis-muconate lactonizing enzyme at low temperature and must lie in the structural gene for that enzyme, because the mutant enzyme produced at 30 C shows altered thermal stability. The mutant enzyme is not intrinsically cold-labile, nor is it cold-labile at the moment of synthesis. The activity of the mutant enzyme is not inhibited at low temperature. Evidence is presented to establish that this mutation in the structural gene coding for cis,cis-muconate lactonizing enzyme results in the lack of expression of that gene at low temperature.

Abstract: The effects of a pleiotropic mutation ssd are described. This mutation results in decreased efficiency in the use of glucose and fructose as carbon source, inability to use succinate or to grow anaerobically, an alteration in the activity of enzymes responsible for the synthesis and degradation of L-serine, increased resistance to certain antibiotics, and a deficiency in proline transport. This mutation resembles various previously described mutations throught to affect ‘energy coupling factor’ and is located in the same region of the chromosome. While the gene product affected by this mutation is still unidentified, it is clear that L-serine metabolism cannot be understood merely in terms of providing L-serine and its derivatives.

Abstract: Any direct estimator of mutation in a human population is subject to error due to nonpaternity. This paper deals with the quantification of this error by producing, under certain assumptions, the probability for paternity. In addition, a new direct estimator of the mutation rate is introduced.

Abstract: With the aim of understanding the mechanism of maintenance of the Rh polymorphism in man, the probability and the first arrival time of an incompatibility mutant allele (recessive alleler) to reach a high frequency by genetic drift in a finite population and the allele frequency distribution under mutation pressure are studied. The deterministic changes in allele frequency in subdivided populations are also studied. The results obtained are as follows: (1) If the effective population size is 500–1,000, the probability of a single mutant allele to reach a frequency of 0.3 or 0.5 is quite small, and without recurrent mutation it is unlikely that the mutant allele becomes polymorphic. However, if the mutant allele happens to increase in frequency by genetic drift, the increase occurs quite rapidly. (2) In an infinitely large population the backward (u) and forward mutations (v) produce two stable equilibria, one of which has a frequency of 0.065 forh=0.05 and a frequency of 0.16 forh=0.01 whenu=v=10−4, whereh is the fitness reduction for the offspring from matingrr×RR. These frequencies are substantially higher than 0 but still lower than the frequencies in the European populations (0.3–0.6). In relatively small populations, however, the probability of the allele frequency being 0.3–0.6 becomes quite high ifh=0.01. (3) If a population is subdivided into subpopulations among which small migration occurs, stable equilibria may be developed. However, the equilibrium gene frequencies do not conform to the frequencies observed in the European populations. When the migration rate becomes higher, the stable equilibria disappear, but the gene frequency change in subdivided populations is generally much slower than that in a single random mating population, so that the Rh polymorphism may be maintained for a long time even if there are no stable equilibria. (4) If we consider all these factors together, it is possible to explain the Rh polymorphism in terms of the mutation-drift hypothesis without recourse to reproductive compensation. It seems that the Rh polymorphism is transient rather than stable.