Effect of parental age on endoreduplication of giant chromosomes and some quantitative traits in Drosophila melanogaster descendants

We studied the influence of parental age on the degree of polyteny of giant chromosomes and expressivity of mutation eyeless in Drosophila melanogaster descendants. The parental age equal to six days exerted an adverse effect on the function of endoreduplication of giant chromosomes in strain eyeless. The highest degree of polyteny was observed in descendants of four- and ten-day imago. The maximum reduction of eye facets was observed in descendants of four-day imago, while in the progeny of older parents, the mutation expressivity was sharply reduced. Relations between the changes in chromosome polyteny, expressivity of mutation eyeless, and earlier studied components of adaptation were statistically analyzed in descendants of aging parents of this Drosophila strain.     

Influence of Parental Age on Endoreduplication of Giant Chromosomes and Some Quantitative Traits in Drosophila melanogaster Descendants

We studied the influence of parental age on the degree of polyteny of giant chromosomes and expressivity of mutation eyeless in Drosophila melanogaster descendants. The parental age equal to six days exerted an adverse effect on the function of endoreduplication of giant chromosomes in straineyeless. The highest degree of polyteny was observed in descendants of four- and ten-day imago. The maximum reduction of eye facets was observed in descendants of four-day imago, while in the progeny of older parents, the mutation expressivity was sharply reduced. Relations between the changes in chromosome polyteny, expressivity of mutation eyeless, and earlier studied components of adaptation were statistically analyzed in descendants of aging parents of this Drosophila strain.     

The open-eyelid mutation, lidgap-Gates, is an eight-exon deletion in the mouse Map3k1 gene

The BALB/cGa mouse strain and its descendants, now called the SELH/Bc strain, have produced two waves of high frequency of spontaneous heritable mutations. One of these, the recessive lidgap-Gates (lg(Ga)) mutation, causes the same open-eyelids-at-birth phenotype as the gene knockout mutations of Map3k1 and co-maps to distal Chr 13. The lg(Ga) mutation is demonstrated to be a 27.5-kb deletion of exons 2-9 in the Map3k1 gene, the first spontaneous mutant allele described at this locus. The lg(Ga) mutation is consistent with a pattern suggesting that the waves of mutation in BALB/cGa and its descendants tend to be large deletions or ETn insertions, whose elevated rate of occurrence is due to an unknown mechanism.     

Proliferative activity, DNA synthesis and reproductive death of immediate and late progeny of irradiated cells

In experiments on HeLa cells a study was made of a change in the rate of DNA synthesis, proliferative activity and reproductive death of exposed cells and their descendants throughout a number of generations. The rate of DNA synthesis decreased in 4 postirradiation generations, and a maximum inhibition (by 50%) was registered 48 h following irradiation. The proliferative activity of the irradiated cell descendants markedly decreased throughout 18-20 generations resulting in an increased death rate and a loss of cells from a generation. It is suggested that even the distant descendants (18-20 generations) of expose cells exhibited some lesions which may, in time, become fatal events leading to cell death.     

Genetic Effects of Acute Spermatogonial X-Irradiation of the Laboratory Rat

The genetic effects of one generation of spermatogonial X-irradiation in rats, by a single dose of 600r in one experiment and by a fractionated dose of 450r in another, were measured in three generations of their descendants. Estimates of dominant lethal mutation rates—(2 to 3) x 10 ^-4/gamete/r—from litter size differences between irradiated and nonirradiated stock were consistent with previous estimates from rats and mice. Similar consistency was found for estimates of sex-linked recessive mutation rates—(1 to 2) x 10^-4 chromosome/r—from male proportions within strains; however, when measured in crossbreds the proportion of males was higher in the irradiated than in the nonirradiated lines. This inconsistency in results is in keeping with the contradictory results reported for recessive sex-linked lethal mutation rates in mice. The effects used to estimate recessive lethal mutation rates which were unusually high—(2 to 14) x 10^-4/gamete/r—were not significant. Other factors that could have contributed to the observed effects are postulated.     

A coalescent model of ancestry for a rare allele

In disequilibrium mapping from data on a rare allele, interest may focus on the ancestry of a random sample of current descendants of a mutation. The mutation is assumed to have been introduced into the population as a single copy a known time ago and to have reached a given copy number within the population. Theory has been developed to describe the ancestral distribution under arbitrary patterns of population expansion. Further results permit convenient realization of the ancestry for a random sample of copies of a rare allele within populations of constant size or within populations growing or shrinking at constant exponential rate. In this article, we present an efficient approximate method for realizing coalescence times under more general patterns of population growth. We also apply diagnostics, checking the age of the mutation. In the course of the derivation, some additional insight is gained into the dynamics of the descendants of the mutation.     

The influence of exogenous melanin on the development of female Wistar rats' posterity of first generation exposed to low doses at different dose rates during embryogenesis

To research a radio-protective effect of melanin on the reproductive system during its creation the development of first generation posterity (900 descendants) of 125 pubertal female Wistar rats was examined after the single gamma-irradiation with a dose of 1 Gy (mean dose rate of 0.03 mGy/h), which they have been exposed to on the day ten of pregnancy, and the chronic gamma-irradiation with a total dose of 1 Gy (mean dose rate of 5.31 mGy/h) which they have been being exposed to during the first 10 days of pregnancy. The melanin of natural animal origin has the anti-radial effectiveness with the single irradiation increasing the number of alive newborn descendants in a litter and doubling their survival during the first 30 days after the birth. The melanin's effect is less expressed with the chronic irradiation.     

Psychophysiological development of two generations of female rats chronically exposed to gamma-irradiation during pregnancy in the total dose of 1 Gy and its modification by melanin

The purpose of the work was to study the embryotoxic action of chronic gamma-irradiation of pregnant female rats (F0) during the first 10 days of pregnancy in the total dose of 1 Gy (mean dose rate of 5.31 mGy/hour) on psychophysiological development of posterity of the first (F1) and the second (F2) generations and its modification by natural pigment melanin (peroral 10 mg/kg once per day during the irradiation). 54 pregnant female Wistar rats were the objects of research were their 180 descendants of the first generation and about 400 descendants of the second generation of maternal and of paternal lines. Psychophysiological development and its correction by melanin estimated on ability to learning with the test of training a conditioned avoidance reflex in the shuttle box. Precise negative action of gamma-irradiation in the aforesaid dose on psychophysiological development of posterity of the first generation is established. At rats of the second generation the inferiority is shown mainly at descendants of maternal line. Application of melanin of natural origin in most cases diminished negative consequences of the irradiation.     

The action of low doses of gamma radiation on mammalian cells]

Effect of gamma irradiation in low doses (10, 20, 40 and 50 cGy) on HeLa cells was studied. The survival of cells exposed to the irradiation in the dose of 50 cGy was decreased while it remained unchanged in cells irradiated in the dose of 10-40 cGy and their descendants. Nonetheless, their survival following an additional treatment with a mixture of cytosine arabinoside and hydroxyurea was reduced. It was suggested that the genome stability was diminished in irradiated cells and their descendants.     

Characteristics of the descendants of male dogs exposed to chronic combined gamma-irradiation and in the postradiation period

A study was made of the descendants of 12 male dogs subjected to gamma-irradiation during six years at dose-rates of 0.0034 Gy/day and 0.0017 Gy/day + additional annual exposures to gamma-radiation three times a year each of 0.42 Gy. The observations were made during 3 years after the end of irradiation. It was shown that the descendants reflected the regularities of the disorders revealed in fathers' spermatogenesis. The radiobiological effects were function of dose--rate and cumulative radiation dose. The changes were mainly noted during embryogenesis and manifested by the sterility, mortinatality and the decreased number of puppies in the postreity.     

The application of a linear algebra to the analysis of mutation rates.

Cells and bacteria growing in culture are subject to mutation, and as this mutation is the ultimate substrate for selection and evolution, the factors controlling the mutation rate are of some interest. The mutational event is not observed directly, but is inferred from the phenotype of the original mutant or of its descendants; the rate of mutation is inferred from the number of such mutant phenotypes. Such inference presumes a knowledge of the probability distribution for the size of a clone arising from a single mutation. We develop a mathematical formulation that assists in the design and analysis of experiments which investigate mutation rates and mutant clone size distribution, and we use it to analyse data for which the classical Luria-Delbrück clone-size distribution must be rejected.     

Mutability of the liver cells in the progeny of irradiated male rats

The descendants of the first generation of radiation exposed rat males exhibited an increased sensitivity of liver cells to the mutagenic effect of ionizing radiation as was determined by the incidence of chromosome aberrations. It is assumed that the stability of the hereditary apparatus of these animal cells is diminished due to the presence therein of radiation induced injuries of mutation and epigenomic origin at a heterozygous condition.     

Transgenerational genomic instability in the first generation offspring of mice exposed to low-intensity red and near-infrared irradiation in vivo

Transgenerational genomic instability in the first generation offspring of mice exposed to lowintensity infrared laser (632.8 nm) and light-emitting-diode infrared irradiation (850 nm) was investigated in vivo. It was found that the level of spontaneous damage in bone marrow according to the micronucleus test, the level of reactive oxygen species in whole blood, and the mass index of lymphoid organs in all of the descendants of irradiated mice did not increase. After additional X-ray exposure of the progeny at a dose rate of 1.5 Gy, a decrease in the level of damage and the absence of an adaptive response were revealed upon testing according to “radiosensitivity” and the radiation-induced adaptive-response scheme (0.1 + 1.5 Gy), respectively, compared to the descendants of nonirradiated mice. The rate of tumor growth in the offspring of irradiated mice did not differ from that in the descendants of nonirradiated mice, although inhibition of the tumor growth rate was observed in their irradiated parents. The survival rate after irradiation at a dose rate of 6.5 Gy did not differ from both the parents and the control.

     

Clonal origins of cells in the pigmented retina of the zebrafish eye

Mosaic analysis has been used to study the clonal basis of the development of the pigmented retina of the zebrafish, Brachydanio rerio. Zebrafish embryos heterozygous for a recessive mutation at the gol-1 locus were exposed to gamma-irradiation at various developmental stages to create mosaic individuals consisting of wild-type pigmented cells and a clone of pigmentless (golden) cells in the eye. The contribution of individual embryonic cells to the pigmented retina was measured and the total number of cells in the embryo that contributed descendants to this tissue was determined. Until the 32-cell stage, almost every blastomere has some descendants that participate in the formation of the pigmented retina of the zebrafish. During subsequent cell divisions, up to the several thousand-cell stage, the number of ancestral cells is constant: approximately 40 cells are present that will give rise to progeny in the pigmented retina. Analysis of the size of clones in the pigmented retina indicates that the cells of this tissue do not arise through a rigid series of cell divisions originating in the early embryo. The findings that each cleavage stage cell contributes to the pigmented retina and yet the contribution of such cells is highly variable are consistent with the interpretation that clonal descendants of different blastomeres normally intermix extensively prior to formation of the pigmented retina.     

Penetrance of von Recklinghausen neurofibromatosis: a distinction between predecessors and descendants.

This paper reviews the concepts of penetrance and expressivity and examines their application to the specific disorder von Recklinghausen neurofibromatosis. The data suggest that assessments of penetrance among predecessors to probands yield results different from those of assessments of penetrance among descendants to probands. For descendants at risk, penetrance is very close to 100%. For predecessors at risk, extremely variable expressivity may confound estimates of penetrance; as a specific example, a family is described in which two brothers have bona fide von Recklinghausen neurofibromatosis and their mother manifests the neurofibromatosis mutation only as iris Lisch nodules.     

Delayed and transgenerational molecular and genetic effects of prolonged influence of ionizing radiation in nuclear plant workers

Genome variability and changes in immune homeostasis, induced in man in the course of long-term industrial contact with ionizing radiation (IR) sources were studied by using unique biomaterials stored in the Radiobiological Repository for Human Tissues at the Southern Urals Biophysics Institute, FMBA. The biomaterials, peripheral blood samples and blood DNA were obtained from the "Mayak" PA employers occupationally exposed to prolonged external gamma-radiation and/or internal alpha-radiation from incorporated 239Pu in a wide range of accumulated doses. A significant increase in the polymorphism of microsatellite-associated peripheral blood DNA repeats was revealed in a group of persons with accumulated doses of external gamma-radiation above 2.0 Gy, as well as in the descendants of parents with preconceptive doses of higher than 2.0 Gy. In persons whose parents had a preconceptive dose above 2.0 Gy, an increase in the gene p53 mutation rate was observed, and descendants of persons with dose of 3.0 Gy and higher showed mtDNA heteroplasmy, regardless of the sex of an exposed parent. Changes in the expression of membrane markers for the effector and regulatory T-lymphocytes depending on radiation type and dose load were determined. The growth factor level variations (TGF-beta1, EGF, HGF, FGF) in peripheral blood serum in persons exposed to radiation from gamma- or alpha-sources, allow us to consider them as biomarkers of radiation-induced disturbances in immune homeostasis. The concentration changes of TGF-beta1, apoptosis proteins (p53, TPA-cyk, sAPO-1/Fas), and the adhesion molecule sCD27 in the case of cardiovascular diseases in the serum of both irradiated and non-irradiated "Mayak" PA employers point to the information value of these immune response characteristics as specific biomarkers of cardiac disorders. It is proposed that the revealed changes in immune homeostasis and in the variability of somatic cell genome may provoke development of tumors and cardiovascular diseases in man in delayed periods after prolonged exposure to IR.     

A "Fille du Roy" introduced the T14484C Leber hereditary optic neuropathy mutation in French Canadians

The predominance of the T14484C mutation in French Canadians with Leber hereditary optic neuropathy is due to a founder effect. By use of genealogical reconstructions of maternal lineages, a woman married in Quebec City in 1669 is identified as the shared female ancestor for 11 of 13 affected individuals, who were previously not known to be related. These individuals carry identical mitochondrial haplogroups. The current geographic distribution of French Canadian cases overlaps with that of the founder's female descendants in 1800. This is the first example of genealogical reconstruction to identify the introduction of a mitochondrial mutation by a woman in a founder population.     

Effect of local UV irradiation of the generative nuclei of Paramecium caudatum on the sexual functions of the cells]

A study has been made of the functional pattern of the micronucleus (Mi) during the sexual process in ciliates Paramecium caudatum which are descendants of those individuals whose Mi was locally irradiated with UV in dose of 3060 erg/mm2. It was demonstrated that these descendants (cells of UV-clones) were able to enter into the sexual process whatever morphological type of their Mi might be. In 4 of 14 tested clones, the initial mating type got changed for the opposite one, which may be associated with the Mi genome alteration following UV irradiation. The nuclear reorganization during the sexual process was studied in three UV irradiated clones. The local UV irradiated of the Mi is followed by the number of abnormalities in the derivates of Mi during the metagamic phase of the sexual process in clones whose Mi underwent serious changes. Exconjugants obtained from UV-clones with such changes in Mi and normal test-clones demonstrated a lower viability.     

The evolution of intergenerational discounting in offspring quality

Intergenerational effects occur when an individual's actions affect not only its own survivorship and reproduction but also those of its offspring and possibly later descendants. In the presence of intergenerational effects, short-term and long-term measures of success (such as the expected numbers of surviving offspring and of farther descendants, respectively) may be in conflict. When such conflicts occur, life-history theory normally takes long-term measures to predict the outcome of selection. This ignores the fact that, because traits change in time--through mutation, sex, and recombination--long-term relations disintegrate. We study this issue with numerical simulations and analytical models combining intergenerational effects and evolutionary change. In the models, the parental investment per offspring, as well as the total reproductive effort, stand for investments in future generations. The models show that the rate of evolutionary change determines the level of those investments. Higher rates of mutation and of sexual as opposed to parthenogenetic reproduction favor lower parental investment per offspring and lower total reproductive effort. It follows that the level of investment of ancestors in descendants responds to the genetic relatedness between the generations of the lineage, in a manner unaccounted for by preexisting theory.     

The assessment of no adverse effect doses for plant populations chronically exposed to radionuclides of uranium and thorium decay series

Dose rates cause no adverse effects on natural populations of Pinus sylvestris L. and Vicia cracca L. inhabiting territories contaminated by uranium mill tailings and radium production wastes (Vodny settlement, Komi Republic) were determined. A significant increase in embryonic lethal mutation frequency in V. cracca legumes and decrease in seedlings survival rate as compared with control values were registered at dose rate equal to 1.67 mGy/day, that is 280 times higher than the one calculated for the reference site. The adverse effects in P. sylvestris expressed in increased frequency of chromosome aberrations in meristematic root tips and decreased reproductive capacity of seeds were determined at absorbed dose rate equal to 0.083 mGy/day. Data obtained show that the decrease in plant reproductive capacity in case of chronic exposure of radionuclides of uranium and thorium decay series can observe at lower weighted absorbed dose rates than in case of environmental contamination by artificial radionuclides.