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Sample records for meets induced mutations

  1. Rice breeding with induced mutations II. Report of an FAO/IAEA research co-ordination meeting

    International Nuclear Information System (INIS)

    1970-01-01

    This report contains the proceedings of the fourth meeting of participants in the FAO/IAEA Co-ordinated Program of Research on the Use of Induced Mutations in Rice Breeding, a program which was initiated in 1964. The three previous meetings were reported as follows: First: proceedings published in the International Rice Commission Newsletter, Vol. XV, No. 1 (1966). Second: report presented to the IRC Working Party meeting at Lake Charles, Louisiana, 18-30 July 1966. Third: proceedings published by the IAEA as Technical Reports Series No. 86 under the title 'Rice breeding with induced mutations'. The fourth meeting was held at Oiso, Japan, on 12-14 August 1968. Co-operators from nine countries attended, together with scientists from five other countries, the International Rice Research Institute, the Rockefeller Foundation, the International Rice Commission, and the FAO and IAEA. In addition, a number of scientists from the host country were present. The purpose of the meeting was to present reports on research related to or carried out under the co-ordinated program in 1967/68, to review and co-ordinate research plans for 1968/69, and to draw up technical recommendations for future work

  2. Induced mutations in connection with biotechnology for crop improvement in Latin America. Proceedings of a final research co-ordination meeting

    International Nuclear Information System (INIS)

    2001-05-01

    This publication results from the second Co-ordinated Research Project (CRP) on Plant Breeding and Genetics organized on a regional basis in Latin America. The present CRP and the previous one were initiated and implemented in response to the pressing need to enhance the productivity of economic plants, viz. food crops, fruits and ornamentals. Improvement of crop production has become the highest priority in most countries of Latin America, as in other regions. Breeding superior varieties is often the only feasible solution where inputs are limited; well adapted varieties are required to meet specific agro-environmental conditions. Such varieties provide yield stability on an economically required level. The most important and common factors limiting crop production are abiotic, e.g. cold, salinity, soil aluminium toxicity and drought; as well as biotic, e.g. diseases and pests. Modern biotechnology and induced mutations offer new means and significant potential to breed desired varieties in a relatively short time. Additionally, both approaches facilitate the breeding of some vegetatively propagated crops which until now were improved mainly through selection of rare spontaneous mutants in natural or cultivated populations. Using some of these techniques it recently became possible to produce, in some crops, true-to-type mutated lines or clones within a few months. Biotechnology can also facilitate selection, description and molecular characterization of promising mutants. Currently used DNA markers, such as restriction fragment length polymorphism (RFLP), random amplified polymorphic DNA (RAPD) as well as other polymerase chain reaction (PCR)-based techniques, were included in this CRP to benefit the important crops of this region. Also included in this CRP were doubled haploids (DH), which are obtained from anther or microspore cultures and are very suitable biotechnology methods. In connection with radiation-induced mutations, they can speed up conventional

  3. Induced mutations in citrus

    International Nuclear Information System (INIS)

    Spiegel-Roy, P.; Vardi, Aliza

    1990-01-01

    Full text: Parthenocarpic tendency is an important prerequisite for successful induction of seedlessness in breeding and especially in mutation breeding. A gene for asynapsis and accompanying seedless fruit has been found by us in inbred progeny of cv. 'Wilking'. Using budwood irradiation by gamma rays, seedless mutants of 'Eureka' and 'Villafranca' lemon (original clone of the latter has 25 seeds) and 'Minneola' tangelo have been obtained. Ovule sterility of the three mutants is nearly complete, with some pollen fertility still remaining. A semi-compact mutant of Shamouti orange has been obtained by irradiation. A programme for inducing seedlessness in easy peeling citrus varieties and selections has been initiated. (author)

  4. Improvement of basic food crops in Africa through plant breeding, including the use of induced mutations. Proceedings of a final research co-ordination meeting

    International Nuclear Information System (INIS)

    1997-07-01

    The Co-ordinated Research Programme (CRP) on Improvement of Basic Food Crops in Africa Through Plant Breeding, Including the Use of Induced Mutations, funded by the Italian Government, was initiated in 1989 in the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture. The primary objective of this CRP was to breed improved varieties of stable food crops of Africa with the main emphasis on the indigenous species and their local cultivars. The fourth and final Research Co-ordination meeting under the CRP was held in Naples, Italy from 30 October - 3 November 1995. This publication includes the reports, conclusions and recommendations made by the participants. We hope that it will be of value to researchers, students and policy makers alike in their endeavour to promote plant breeding and increase food productions in Africa. Refs, figs, tabs

  5. Induced mutations in castor

    International Nuclear Information System (INIS)

    Ganesan, K.; Javad Hussain, H.S.; Vindhiyavarman, P.

    2001-01-01

    Castor (Ricinus communis L.) is an important oilseed crop in India. To create variability mutations were induced in two cultivars 'TMV5' (maturing in 130-140 days) and 'CO1' (perennial type). Gamma rays and diethyl sulphate and ethidium bromide were used for seed treatment. Ten doses, from 100 to 1000 Gy were employed. For chemical mutagenesis five concentrations of mutagenes from 10 to 50 mM were tried. No economic mutants could be isolated after treatment with the chemical mutagens. The following economic mutants were identified in the dose 300 Gy of gamma rays. Annual types from perennial CO 1 castor CO 1 is a perennial variety (8-10 years) with bold seeds (100 seed weight 90 g) and high oil content (57%). Twenty-one lines were isolated with annual types (160-180 days) with high yield potential as well as bold seeds and high oil content. These mutants, identified in M 3 generation were bred true in subsequent generations up to M 8 generation. Critical evaluation of the mutants in yield evaluation trials is in progress

  6. Induced mutations in sesame breeding

    International Nuclear Information System (INIS)

    Ashri, A.

    2001-01-01

    The scope of induced mutations in sesame (Sesamum indicum L.) breeding is reviewed. So far in Egypt, India, Iraq, Rep. of Korea, and Sri Lanka, 14 officially released varieties have been developed through induced mutations: 12 directly and 2 through cross breeding (one using the 'dt45' induced mutant from Israel). For another variety released in China there are no details. The induced mutations approach was adopted primarily in order to obtain genetic variability that was not available in the germplasm collection. The mutagens commonly applied have been gamma rays, EMS and sodium azide. Sesame seeds can withstand high mutagen doses, and there are genotypic differences in sensitivity between varieties. The mutants induced in the above named countries and others include better yield, improved seed retention, determinate habit, modified plant architecture and size, more uniform and shorter maturation period, earliness, resistance to diseases, genic male sterility, seed coat color, higher oil content and modified fatty acids composition. Some of the induced mutants have already given rise to improved varieties, the breeding value of other mutants is now being assessed and still others can serve as useful markers in genetic studies and breeding programmes. (author)

  7. Induced mutation of Dendrobium orchid

    International Nuclear Information System (INIS)

    Sakinah Ariffin; Mohd Nazir Basiran

    2000-01-01

    Dendrobiiim orchids serve as the main orchid cut flower export of Malaysia. The wide range of colour and forms presently available in the market are obtained through hybridisation. Induced mutation breeding program was initiated on a commercial variety Dendrobium 'Sonia Kai' to explore the possibilities of obtaining new colour and forms. Matured seeds from self pollination were cultured and irradiated at 35 Gy at the protocorm-like bodies (PLBS) stage. Selection of induced mutations was done after the first flowering of the plants regenerated from the irradiated protocorms. Results showed changes in flower colour, shape and size. Most of these chances are expressed in different combinations in the petals, sepals and lip of the flowers. Thus, resulting. in a very wide spectrum of mutations. Some of these chances are not stable. To date, mutants that showed stable characteristics changes are grouped into 11 categories based on flower colour and form. These results show that the combination of its vitro technique and induced mutation can be applied in orchid breeding to produce new interesting and attractive variety for the market

  8. In vitro techniques for selection of radiation induced mutations adapted to adverse environmental conditions. Proceedings of a final research co-ordination meeting

    International Nuclear Information System (INIS)

    2001-06-01

    The ever increasing human population and dwindling land and water resources worldwide make it essential to produce more food, fibre and fodder from less and less land. During the last century, plant breeding contributed remarkably to increasing food by producing varieties which give higher yield, have improved quality and nutrition, and resist diseases and pests. Nearly 50% of the increase in food production in Asia during the last fifty years can be attributed to the high yielding, short height varieties of rice and wheat, the remaining to the improved agronomic inputs and management. Many crops, such as cassava, potato, pineapple, sweet potato, sugarcane, banana and plantain are major food crops, and others such as sugarcane and pineapple are important to the economies of many developing countries. One of the solutions to have a sustainable and secure food production is to breed varieties which are tolerant of stress conditions during their growth and development. Hence a Co-ordinated Research Project on In vitro Techniques for Selection of Radiation Induced Mutations Adapted to Adverse Environmental Conditions was initiated and focused primarily on the improvement of vegetatively propagated plants. Since the inception of this project, several participating scientists established the optimal dose requirement for in vitro cultured material. Investigations were carried out on the effect of radiation to alter traits which affect survival under stress conditions and high temperature stress in potato, pineapple, sweet potato and garlic. The possibility to change traits such as tolerance to saline and water logged soils in sugarcane and gene regulation for salinity tolerance were studied. The limited number of available reports suggest that callus cultures are much more sensitive to radiation treatment and require much lower doses (2 to 5 Gy) than stem cuttings or seeds, and that relatively higher doses (15 to 20 Gy) cause necrosis or loss of regenerative capacity. The

  9. Induced Mutations in Thai Rice

    International Nuclear Information System (INIS)

    Klakhaeng, Kanchana

    2014-01-01

    Rice is the primary source of food for more than half of the world's population. It benefits greatly from technological inputs in the area of breeding such as induced mutation. Induced mutation can produce mutants with significant improvement in plant type, maturity, yields and protein ratio when compared to the parent. These improved traits enable the mutants to fit into farming systems with either shorter or longer growing seasons. Three induced mutant rice varieties, including RD6, RD10 and RD15, are well accepted by farmers and consumers in Thailand. RD6 and RD15 were aromatic, photosensitive varieties which were derived from KDML105 by acute irradiation of 20 and 15 kilorad gamma ray, respectively. After induced mutation, pedigree selection was applied. RD6 showed drought tolerance and also good grain quality including softness and good aroma with a higher average yield than the famous glutinous variety, San-Pah-Tong. Additionally, it was resistant to blast and brown spot diseases with an average yield of 4.19 tons/ha. RD15 showed drought tolerance and resistance to brown spot disease with the highest yield of 3.5 tons/ha. These two mutant varieties are currently the most famous aromatic rice varieties in Thailand. On the other hand, RD10 is a glutinous, photoperiod insensitive rice variety which was derived from RD1 by irradiation of 1 kilorad fast neutrons. RD10 showed good grain quality such as softness and stickiness with the yield of 4.25 tons/ha. As an on-going project, recommended rice varieties were irradiated with electron beam for anaerobic germination ability, submergence tolerance, stagnant-flood tolerance and also internode elongation.

  10. Induced mutation of soy by ionization mutation

    Energy Technology Data Exchange (ETDEWEB)

    Li, C.L.; Hsu, H.L.

    1975-09-01

    This article presents the results of experiments dealing with how 14 different doses of three types of ionization irradiation-roentgen rays, /sup 60/Co gamma rays, and thermal neutrons affect mutation of 14 types of soy beans and their hybrids. It was learned that with an increased dose the coefficient of seed germination decreases, the cotyledon becomes increasingly thicker, shoots develop more and more slowly, various deformities arise in the stalk, and fertility decreases. As far as M/sub 2/ mutation is concerned, a great variety has been discovered with regard to the height of the stem, the leaf formation, the color of the bloom, the color of the edge, the characteristics of the pod, the size of the seed and the color of the cicatrix. At the same time some specific characteristics having an important economic significance are being revealed, as for example, dwarf stems, the ability to withstand lodging, great pod density, increased inflorescence and short sprouts.

  11. Induced mutation to monocotyledony in periwinkle, Catharanthus ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 79; Issue 3. Induced mutation to monocotyledony in ... A recessive EMS-induced mutation inherited in Mendelian fashion caused monocotyledonous embryo formation and seed germination on high salt medium in Catharanthus roseus. Availability during embryo development of ...

  12. Radiation-induced mutation at minisatellite loci

    International Nuclear Information System (INIS)

    Dubrova, Y.E.; Nesterov, V.N.; Krouchinsky, N.G.

    1997-01-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of γ-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure 137 Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed

  13. Improvement of basic food crops in Africa through plant breeding, including the use of induced mutations. Report of the third research co-ordination meeting of FAO/IAEA/ITALY co-ordinated research programme. Working material

    International Nuclear Information System (INIS)

    1997-01-01

    A Co-ordinated Research Programme, on ''Improvement of basic food corps in Africa through plant breeding including the use of induced mutations'', funded by the Italian Governmnet, was initiated in the Joint Division of the Food and Agriculture Organization and International Atomic Energy Agency, Vienna. The primary objective of this CRP was to breed improved varieties of staple food crops of Africa with main emphasis on the indigenous species and local cultivars. The Third Research Co-ordination Meeting (RCM) under the FAO/IAEA/ITALY Co-ordinated Research Programme was held in Nairobi, Kenya, 20-24 September 1993 in which 24 persons participated and 18 scientific reports were presented. These included reports from 10 Research Contract holders from Africa, 3 Technical Contract holders from Italy and the update on the backstopping of research carried out at the IAEA Laboratories, Seibersdorf. The reports, and conclusions and recommendations made by the participants are presented in this publication. Refs, figs, tabs

  14. 2004 Environmental Mutagen Society Annual Meeting - Genes, Mutations and Disease: The Environmental Connection

    Energy Technology Data Exchange (ETDEWEB)

    Samson, Leona D.

    2004-08-23

    The Meeting consisted of 9 Symposia, 4 Keynote Lectures, 3 Platform Sessions and 4 Poster Sessions. In addition there were Breakfast Meetings for Special Interest Groups designed to inform attendees about the latest advances in environmental mutagenesis research. Several of the topics to be covered at this broad meeting will be of interest to the Department of Energy, Office of Science. The relevance of this meeting to the DOE derives from the fact that low dose radiation may represent one of the most significant sources of human mutations that are attributable to the environment. The EMS membership, and those who attended the EMS Annual Meeting were interested in both chemical and radiation induced biological effects, such as cell death, mutation, teratogenesis, carcinogenesis and aging. These topics thate were presented at the 2004 EMS Annual meeting that were of clear interest to DOE include: human variation in cancer susceptibility, unusual mechanisms of mutation, germ and stem cell mutagenesis, recombination and the maintenance of genomic stability, multiple roles for DNA mismatch repair, DNA helicases, mutation, cancer and aging, Genome-wide transcriptional responses to environmental change, Telomeres and genomic stability: when ends don?t meet, systems biology approach to cell phenotypic decision processes, and the surprising biology of short RNAs. Poster and platform sessions addressed topics related to environmental mutagen exposure, DNA repair, mechanisms of mutagenesis, epidemiology, genomic and proteomics and bioinformatics. These sessions were designed to give student, postdocs and more junior scientists a chance to present their work.

  15. Molecular mechanisms of induced-mutations

    International Nuclear Information System (INIS)

    Kato, Takeshi

    1985-01-01

    The outcome of recent studies on mechanisms of induced-mutations is outlined with particular emphasis on the dependence of recA gene function in Escherichia coli. Genes involved in spontaneous mutation and x-ray- and chemical-induced mutation and genes involved in adaptive response are presented. As for SOS mutagenesis, SOS-induced regulation mechanisms and mutagenic routes are described. Furthermore, specificity of mutagens themselves are discussed in relation to mechanisms of base substitution, frameshift, and deletion mutagenesis. (Namekawa, K.)

  16. Induced mutations - a tool in plant research

    International Nuclear Information System (INIS)

    1981-01-01

    These proceedings include 34 papers and 18 brief descriptions of poster presentations in the following areas as they are affected by induced mutations: advancement of genetics, plant evolution, plant physiology, plant parasites, plant symbioses, in vitro culture, gene ecology and plant breeding. Only a relatively small number of papers are of direct nuclear interest essentially in view of the mutations being induced by ionizing radiations. The papers of nuclear interest have been entered as separate and individual items of input

  17. Induced mutations for crop improvement

    International Nuclear Information System (INIS)

    Micke, A.; Donini, B.; Maluszynski, M.

    1990-01-01

    Mutation induction has become an established tool in plant breeding to supplement existing germ plasma and to improve cultivars in certain specific traits. Hundreds of improved varieties have been released to farmers for many different crop species, demonstrating the economic value of the technology. Limitations arise mainly from the large mutagenized populations to be screened and from the unsatisfactory selection methods. Both limitations may be eased to some extent by advances in techniques of plant in-vitro culture. (author). Refs, 1 fig., 7 tabs

  18. Induced mutations for human welfare through agriculture

    International Nuclear Information System (INIS)

    Patil, S.A.

    2009-01-01

    Full text: Use of induced mutation for crop improvement started in 1920's. It gained momentum in 1960's when IAEA and FAO started training and guidance and funds were made available for undertaking mutation breeding. IARI established a Gamma Garden and a separate institution was carved by name 'Nuclear Research Laboratory' in 1970's. ICAR Institutes and State Agriculture Universities started using this facility for crop improvement. Similarly, BARC started extending its help for irradiating the seed material specially X-rays and it became one of the major source of generating variability for crop improvement. Induced mutation has resulted in development of more than 3000 varieties of different food, feed, fruit, vegetables and flowers. Apart from direct use of mutants as cultivars, mutants have played a vital role in creating useful variation for application in basic research and gene discovery. It has helped in increasing yield through use of heterosis by inducing male sterility. It has been used for creating useful variation for changing grain composition to improve nutrition and grain quality parameters, for tolerance against abiotic and biotic stresses. Gene sequencing and related technologies have opened up new application of induced mutations. In model organisms induced mutations provide new opportunities for identification of genes/bio-chemical, cellular, developmental or functional pathways. The use of stable isotopes in basic research is of fundamental use in crop improvement. Apart from crop improvement the nuclear technology has been used for numerous other applications in Agriculture such as soil fertility, plant nutrition, use of fertilizer and irrigation, control of insect pest and storage. In recent decades BARC has come in a big way through funding for projects to State Agricultural Universities and ICAR Institutes and has signed MoU's with few of the Agriculture Universities for testing and popularizing their identified field crop varieties in

  19. Induced mutation in tropical fruit trees

    International Nuclear Information System (INIS)

    2009-05-01

    This publication is based on an FAO/IAEA coordinated research project (CRP) and provides insight into the application of induced mutation and in vitro techniques for the improvement of well known fruit trees such as citrus, mango, avocado and papaya, as well as more exotic fruit trees such as litchi, annona, jujube, carambola, pitanga and jaboticaba. The latter are of particular importance due to their adaptation to harsh environments and their high potential as basic food and micronutrient providers for populations in poorer and more remote regions. The findings of the CRP show that application of radiation induced mutation techniques in tropical and subtropical fruit trees can contribute to improving nutritional balance food security, and to enhancing the economic status of growers

  20. Gamma ray induced somatic mutations in rose

    International Nuclear Information System (INIS)

    Datta, S.K.

    1989-01-01

    Budwood of 32 rose cultivars (Rosa spp.) was exposed to 3-4 krad of gamma rays and eyes were grafted on Rosa indica var. odorata root stock. Radiosensitivity with respect to sprouting, survival and plant height, and mutation frequency varied with the cultivar and dose of gamma rays. Somatic mutations in flower colour/shape were detected as chimera in 21 cultivars. The size of the mutant sector varied from a narrow streak on a petal to a whole flower and from a portion of a branch to an entire branch. 14 mutants were detected in M 1 V 1 , four in M 1 V 2 and three in M 1 V 3 . Maximum number of mutations was detected following 3 krad treatment. Eyes from mutant branches were grafted again on root stock and non-chimeric mutants were aimed at by vegetative propagation. Mutants from 11 cultivars only could be isolated in pure form. Isolation of non-chimeric mutants sometimes is difficult due to weak growth of a mutant branch. In such a case, all normal looking branches are removed to force a better growth of the mutant branch. It is advisable to maintain irradiated plants at least for four years with drastic pruning in each year. Nine mutants viz. 'Sharada', 'Sukumari', 'Tangerine Contempo', 'Yellow Contempo', 'Pink Contempo', 'Striped Contempo', 'Twinkle', 'Curio' and 'Light Pink Prize' have already been released as new cultivars for commercialization [ref. MBNL No. 23 and 31] and others are being multiplied and assessed. The mutation spectrum appears to be wider for the cultivars 'Contempo' and 'Imperator'. Pigment composition of the original variety is relevant for the kind of flower colour mutations that can be induced

  1. Improvements of root and tuber crops in tropical countries of Asia by induced mutations. Proceedings of a final research co-ordination meeting held in Kagoshima, Japan, 22-26 February 1993

    International Nuclear Information System (INIS)

    1995-07-01

    Root and tuber crops like potato, sweet potato are important starchy foods in tropical countries. However, being vegetatively propagated or difficult to reproduce by seeds, these crops remained in a relatively primitive state in terms of plant breeding. This proceeding contains research papers that deal with the use of external irradiation or induced mutations techniques that are expected to broaden their genetic diversity, thus facilitating screening for desired characteristics. Refs, figs and tabs

  2. Heavy ion induced mutation in arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Tano, Shigemitsu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1997-03-01

    Heavy ions, He, C, Ar and Ne were irradiated to the seeds of Arabidopsis thaliana for inducing the new mutants. In the irradiated generation (M{sub 1}), germination and survival rate were observed to estimate the relative biological effectiveness in relation to the LET including the inactivation cross section. Mutation frequencies were compared by using three kinds of genetic loci after irradiation with C ions and electrons. Several interesting new mutants were selected in the selfed progenies of heavy ion irradiated seeds. (author)

  3. Induced mutations for quantitative traits in rice

    International Nuclear Information System (INIS)

    Chakrabarti, B.N.

    1974-01-01

    The characteristics and frequency of micro-mutations induced in quantitative traits by radiation treatment and the extent of heterozygotic effects of different recessive chlorophyll-mutant-genes on quantitative trait has been presented. Mutagenic treatments increased the variance for quantitative traits in all cases although the magnitude of increase varied depending on the treatment and the selection procedure adopted. The overall superiority of the chlorophyll-mutant heterozygotes over the corresponding wild homozygotes, as noted in consecutive two seasons, was not observed when these were grown at a high level of nitrogen fertiliser. (author)

  4. Mitochondrial DNA exhibits resistance to induced point and deletion mutations

    Science.gov (United States)

    Valente, William J.; Ericson, Nolan G.; Long, Alexandra S.; White, Paul A.; Marchetti, Francesco; Bielas, Jason H.

    2016-01-01

    The accumulation of somatic mitochondrial DNA (mtDNA) mutations contributes to the pathogenesis of human disease. Currently, mitochondrial mutations are largely considered results of inaccurate processing of its heavily damaged genome. However, mainly from a lack of methods to monitor mtDNA mutations with sufficient sensitivity and accuracy, a link between mtDNA damage and mutation has not been established. To test the hypothesis that mtDNA-damaging agents induce mtDNA mutations, we exposed MutaTMMouse mice to benzo[a]pyrene (B[a]P) or N-ethyl-N-nitrosourea (ENU), daily for 28 consecutive days, and quantified mtDNA point and deletion mutations in bone marrow and liver using our newly developed Digital Random Mutation Capture (dRMC) and Digital Deletion Detection (3D) assays. Surprisingly, our results demonstrate mutagen treatment did not increase mitochondrial point or deletion mutation frequencies, despite evidence both compounds increase nuclear DNA mutations and demonstrated B[a]P adduct formation in mtDNA. These findings contradict models of mtDNA mutagenesis that assert the elevated rate of mtDNA mutation stems from damage sensitivity and abridged repair capacity. Rather, our results demonstrate induced mtDNA damage does not readily convert into mutation. These findings suggest robust mitochondrial damage responses repress induced mutations after mutagen exposure. PMID:27550180

  5. Dominant cataract mutations and specific-locus mutations in mice induced by radiation or ethylnitrosourea

    International Nuclear Information System (INIS)

    Ehling, U.H.; Favor, J.; Kratochvilova, J.; Neuhaeuser-Klaus, A.

    1982-01-01

    In a combined experiment, dominant cataract mutations and specific-locus mutations were scored in the same offspring. In radiation experiments, a total of 15 dominant cataract and 38 specific-locus mutations was scored in 29396 offspring. In experiments with ethylnitrosourea (ENU), a total of 12 dominant cataracts and 54 specific-locus mutations was observed in 12712 offspring. The control frequency for dominant cataracts was 0 in 9954 offspring and for specific-locus mutations 11 in 169955 offspring. The two characteristic features of radiation-induced specific-locus mutations - the augmenting effect of dose fractionation and the quantitative differences in the mutation rates between spermatogonial and post-spermatogonial stages - can also be demonstrated for the induction of dominant cataracts. The dominant cataract mutations recovered can be categorized into 7 phenotypic classes. The only noteworthy difference observed between the radiation- and ENU-induced mutations recovered was that, of the 2 radiation-induced total lens opacities, both were associated with an iris anomaly and microphthalmia whereas the ENU-induced total opacities were not. (orig./MG)

  6. Induced mutation breeding by fast neutron

    International Nuclear Information System (INIS)

    Chen Zhengba; You Risheng

    1988-09-01

    The high-yield and long-grain new variety 'Zhongtie 31' was developed through five generations after irradiation of the rice variety 'Tieqiu 15' dried seeds by 14 MeV fast neutrons with a fluence of (1.33 ∼ 3.33) x 10 11 neutrons cm -2 . It matured earlier 3 to 5 days, the plant is higher 10 cm, bigger ear, more grain than its original variety 'tieqiu 15', and the yield increased by 19.2% to 30.7%. The source of new variety 'Zhongtie 31' was proved by the isoenzyme genetics. In field test, it increased by 7% to 10% as compared with high-yield variety 'Guichao No.2' and the hybrid rive 'Shanyou No.2', and is more palatable. The new variety was initiated by irradiation mutagensis routine rice, its well-grown and bumper-yield performances may be compared favourably with hybrid rice variety. In July 1986, the new variety 'Zhongtie 31' was obtained by inducing mutation with fast neutron. The same year, the planted area of 'Zhongtie 31' has achieved upto 250 thousand mu (1.67 x 10 8 cm 2 )

  7. Radiation-induced mutations in fish

    International Nuclear Information System (INIS)

    Schroeder, J.H.

    1980-01-01

    X-ray-induced mutations in teleostean fish were studied from the point of social behavior. A significant reduction in male aggression was found in the postirradiated F 1 generation after the irradiation of parental oogonia and spermatogonia, with 2 x 500 R (24 hr apart) of x-rays, but did not alter the aggression of F 1 females. A study on backcross generation of irradiated line fitted with a two-factor model of dominant genetic factors, high- and low-aggressive, which co-acted additively in repressing the male aggression. Social cohesiveness was compared between F 1 convict cichlides (C. nigrofasciatum) exposed by 0, 250, 500, 750, 1000, and 2000 R of x-rays. The best response was observed in males with 500 R and in females with 750 R. While an increase in cohesiveness was observed in F 1 males with 500 R, the cohesiveness of F 1 females decreased with 750 and 200 R, suggesting that the increase in male was associated with a reduction of inter-male aggression. A new ''guppy male courtship activity test'' was carried out in the offsprings of irradiated guppy, maintained in seawater and in freshwater. The mean values of both the frequency and the duration of four behavioral traits of the male guppy increased in postirradiated F 1 generation of the seawater substrain but were unchanged in that of freshwater's. In F 2 generation the mean values of the same behavioral characters decreased in both seawater and freshwater substrains. (Nakanishi, T.)

  8. Induced mutations for soybean rust resistance

    International Nuclear Information System (INIS)

    Smutkupt, S.; Wongpiyasatid, A.; Lamseejan, S.

    1983-01-01

    Soybean mutation experiments for inducing rust resistance in the cultivars G 8375, Wakashima mutant number 10, Taichung N, S.J.2, S.J.4, BM 50, BM 98, G 8377, G 8586 and G 8587 have been carried out since 1979. Six pods from each of 4438 control and 43,907 M 1 plants were randomly harvested. M 2 seeds of each cultivar of different doses were bulked (M 2 bulk). In addition, 270 good M 1 plants were selected and threshed singly (M 2 single). M 2 -bulk and M 2 -single seeds were advanced to M 3 . Both, M 3 -bulk and M 3 -single plants, together with the remaining M 2 -bulk seeds were screened for rust resistance in the rainy season of 1980 in Nong Hoi Valley (altitude about 1000 m above sea level) and at Mae Joe Station, both in Chiang Mai Province (latitude 18 deg. 31'-19 deg. N). Based on the IWGSR rating system, soybean plants with slow growth of rust were selected from both locations. The results were as follows: Six plants were selected from a total of 2802 control plants, and 115 from a total of 28,834 M 2 and M 3 plants. Further evaluation of these selections for rust resistance will be carried out in the rainy season of 1981 in Nong Hoi Valley, Chiang Mai. (author)

  9. Carcinogenic oestrogens induce respiration deficiency mutation in yeast

    OpenAIRE

    Stopper, Helga; Metzler, M.

    2012-01-01

    In addition to hormonal activity, genetic darnage has been proposed as an important factor in oestrogen-mediated carcinogenesis. However, as short-term tests for oestrogens usually fail to show DNA mutations, lesions other than dassie nuclear DNA mutation have to be considered. Oestrogeninduced mitochondrial darnage was studied in the yeast Saccharomyces cerevisiae. Stilbene-type, but not steroidal, oestrogens were found to induce respiration-dcficient petite mutation. The effect was inversel...

  10. Carcinogenic oestrogens induce respiration deficiency mutation in yeast.

    Science.gov (United States)

    Stopper, H; Metzler, M

    1991-01-01

    In addition to hormonal activity, genetic damage has been proposed as an important factor in oestrogen-mediated carcinogenesis. However, as short-term tests for oestrogens usually fail to show DNA mutations, lesions other than classic nuclear DNA mutation have to be considered. Oestrogen-induced mitochondrial damage was studied in the yeast Saccharomyces cerevisiae. Stilbene-type, but not steroidal, oestrogens were found to induce respiration-deficient petite mutation. The effect was inversely correlated with cytotoxicity and required aromatic hydroxyl groups at the stilbene molecule. It only occurred under growth conditions and apparently was not due to the ATPase inhibitory qualities of stilbene oestrogens. Other studies have shown that petite mutation clones, which can be induced by a variety of substances, contain altered mitochondrial DNA. The mechanism of petite mutation induction might be important in tumorigenesis by also acting on nuclear DNA or facilitating carcinogenesis by disturbance of mitochondrial function.

  11. R and D activities on radiation induced mutation breeding

    International Nuclear Information System (INIS)

    Lapade, A.G.; Asencion, A.B.; Santos, I.S.; Grafia, A.O.; Veluz, AM.S.; Barrida, A.C.; Marbella, L.J.

    1996-01-01

    This paper summarizes the accomplishments, prospects and future plans of mutation breeding for crop improvement at the Philippine Nuclear Research Institute (PNRI). Mutation induction has become a proven way creating variation within a crop variety and inducing desired attributes that cannot be found in nature or have been lost during evolution. Several improved varieties with desirable traits were successfully developed through induced mutation breeding at our research institute. In rice, mutation breeding has resulted in the development of new varieties: (1) PARC 2, (2) Milagrosa mutant, (3) Bengawan mutant and (4) Azmil mutant. Mutation breeding in leguminous crops has led to the induction of an improved L 114 soybean mutant that is shorter that the original variety but yield about 40% more. Several PAEC mungbean varieties characterized with long pods that are non-shattering were also induced. In asexually propagated crops, an increase in yield and chlorophyll mutants were obtained in sweet potatos. Likewise, chlorophyll mutant which look-like 'ornamental bromeliads' and a mutant with reduced spines have been developed in pineapple Queen variety. At present, we have started a new project in mutation breeding in ornamentals. Tissue culture is being utilized in our mutation breeding program. In the near future, radiation induced mutagenesis coupled with in vitro culture techniques on protoplast culture and somatic hybridization will be integrated into our mutation breeding program to facilitate the production of new crop varieties. (author)

  12. Achievements and trends of using induced mutations in crop improvement

    International Nuclear Information System (INIS)

    Nichterlein, K.; Maluszynski, M.; ); Bohlmann, H.; Nielen, S.; )

    2000-01-01

    Mutation techniques have been employed for the genetic improvement of crops and ornamentals leading to the official release of more than 2200 improved varieties. Some of them have made a major impact on crop productivity and achieved great economic success. Induced mutations play an important role in plant genome research to understand the function of genes aiming to improve food security and diversity. (author)

  13. Induced mutation for tungro resistance in rice

    International Nuclear Information System (INIS)

    Ikeda, R.; Yumol, R.R.; Taura, S.

    2001-01-01

    Tungro is the most serious virus disease of rice in South and Southeast Asia. It is a composite disease of two kinds of viruses, rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV). Damage to the plant is mostly caused by RTBV, while RTSV acts to facilitate RTBV acquisition and transmission by insect vector. Both viruses are transmitted mainly by green leafhopper (GLH). Resistance to GLH is common in rice germplasm but extremely rare for the two viruses. To induce mutations for tungro resistance, a susceptible variety IR22 was treated with N-methyl-N-nitrosourea (MNH) following the procedure of Satoh and Omura. The panicles of rice variety 'IR22' were soaked in 1 mM MNH solution for 45 minutes at 16 to 18 hours after flowering. Two thousand six hundred and forty fertile M 1 plants were produced. From these plants M 2 lines with 10 or more seedlings were planted in the field to evaluate their reaction against tungro under natural conditions in the 1990 dry season on the IRRI central research farm, Los Banos, the Philippines. Of these, 124 M 2 lines were selected by visual evaluation. Five plants were harvested individually from each selected line. A bulk was also made from all the remaining plants in the line. In the M 3 generation, each family consisted of five sister lines and one bulked line. One line (M 3 -723) showed no tungro symptoms and its related bulk segregated for resistance but all other M 3 lines from the same family were susceptible to tungro. The resistant line, M 3 -723, showed low infection with RTBV and RTSV when leaves were tested by enzyme-linked immunosorbent assay (ELISA) to diagnose tungro infection. All M 4 lines from M 3 -723 showed uniform resistance in the field. They were not infected with RTBV and were resistant to RTSV infection

  14. Studies on induced mutations in garlic

    International Nuclear Information System (INIS)

    Selvaraj, N.; Natarajan, S.; Ramaraj, B.

    2001-01-01

    Garlic (Allium sativum L.) is the second most widely cultivated Allium - after onion. It has been recognised world-wide as a valuable spice for foods and a popular remedy for various ailments and physiological disorders. The available types of garlic exhibit low variability due to repeated vegetative propagation. As garlic flowers are mostly sterile, restoration of fertility is a difficult process and hence there exists little scope for genetic improvement through hybridization. Induced mutagenesis with gamma rays has helped to overcome these genetic barriers. Ethyl methanesulphonate (EMS) and their combination treatments attempted to improve bulb yield in garlic varieties 'Mettupalayam' and 'Ooty-1' at the Horticultural Research Station, Ooty in Nilgiris. Based on radiosensitivity studies, two doses of gamma rays (2.5 and 5.0 Gy), four concentrations of EMS (15, 20, 25 and 30 mM for 8 h at temperature 25±2 deg. C) and four combined treatments (2.5 Gy + 20 mM, 2.5 Gy + 25 mM, 5.0 Gy + 20 mM and 5.0 Gy + 25 mM) were employed. Garlic bulb and clove characteristics and the varietal response were significantly influenced by the physical, chemical mutagens and their combination treatments. The spectrum of chlorophyll mutants identified in the present study are comprised of, albina, chlorina, straita, viridis and xantha. The proportion of the various mutants varied with the varieties and mutagen treatments. Increasing doses of gamma rays, EMS or combination treatments increased the rate of lethality, injury and clove sterility of treated populations. Mutations for plant, leaf and shoot morphology were more frequent than bulb characters in both varieties. Non-viable mutants were dose dependant and this increased with higher doses. Gamma treatments caused more non-viable mutants (mottled and crinkled leaves) followed by combined and EMS treatments

  15. Development of Trombay pulse crop varieties mutation through induced mutation

    International Nuclear Information System (INIS)

    Dhole, V.J.; Reddy, K.S.

    2016-01-01

    The food prices including pulses were beginning to increase from 2008, something that was not expected to happen before 2020. It was due to climate change, a scarcity of good arable land, water and nutrients. With these obstacles, we must produce almost double than what we are producing now to achieve food security by 2050. It can be achieved through crop improvement. Crop improvement is the art and science of changing the genetic make of crop plant in desire direction through various method of plant breeding. Mutation breeding is one of the techniques which utilize the physical and chemical mutagens to create genetic variability. Till date more than 3200 mutant varieties have been developed worldwide in which two physical mutagens i.e. X-rays and gamma rays have major contributions. Bhabha Atomic Research Centre is one of the leading institutes in India where nuclear energy is used for crop improvement, which resulted in to development of 43 improved high yielding varieties in different crops including 19 varieties of pulse crops. These varieties are contributing significantly to production of pulses and ultimately to national food security. (author)

  16. Use of induced mutations in soybean breeding

    International Nuclear Information System (INIS)

    Zakri, A.H.; Jalani, B.S.; Ng, K.F.

    1981-01-01

    Artificial induction of mutation in plants is carried out using #betta#-irradiation and ethyl metanesulphonate (EMS) to expand the genetic variability of locally-grown soybean. This aspect of mutation breeding complements of conventional breeding approach undertaken by the Joint Malaysia Soybean Breeding Project group. Recovery of agronomically-important mutants such as earliness, lateness, bigger seed size and improved plant architecture were recorded. The significance of these findings is discussed. (author)

  17. Protective effect of selenium on radiation-induced HPRT mutation

    International Nuclear Information System (INIS)

    Fan Feiyue; Yang Suxia; Cao Zhenshan; Li Yu; Liu Guolian

    2000-01-01

    Mutation of HPRT in human embryo lung cells induced by γ-ray was analyzed by way of CB. Efficiency of HPRT mutation was gradually increased with increasing of γ-ray doses after-irradiation. The relationship between mutation efficiency and radiation dose showed linear relative. The efficiency of HPRT mutation in cells exposed to γ-ray and selenium was lower than that in cells exposed to γ-ray only. This indicated that selenium possessed protective effect on HPRT mutation induced by γ-ray. This protective effect of selenium was more efficient when the cells were exposed to lower dose of γ-ray than to higher dose. The character of protective effect of selenium is very significant in medical protection on people exposed to low dose of radiation

  18. Characterization of carbon ion-induced mutations in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Shikazono, N.; Suzuki, C.; Kitamura, S.; Watanabe, H.; Tano, S.; Tanaka, A.

    2003-01-01

    Full text: Irradiation of Arabidopsis thaliana by carbon ions was carried out to investigate the mutational effect of ion particles in higher plants. The averaged mutation rate of carbon ions was 2.0 X 10 -6 / Gy, which was 18-fold higher than that of electrons. PCR analysis of the carbon ion-induced mutants showed that, out of 28 mutant alleles, 14 had point-like mutations within the gene, while 14 contained large structural alterations. In the case of 12 electron-induced mutants, 9 had point-like mutations within the gene, while 3 contained large structural alterations. These results suggest that carbon ions are more likely to induce large structural alterations compared with electrons. Further sequence analysis revealed that most of the point-like mutations induced by carbon ions were short deletions. In the case of rearrangements, DNA strand breaks were found to be rejoined using, if present, short homologous sequences for both types of radiation. After carbon ion-irradiation, small deletions were frequently observed around the breakpoints, whereas duplications of terminal sequence were found after electron-irradiation. These results suggest that non-homologous end joining (NHEJ) pathway operates after plant cells are exposed to both ion particles and electrons but that different mode of rejoining deals with the broken ends produced by each radiation. From the present results, it seems reasonable to assume that carbon ions could predominantly induce null mutations in Arabidopsis. The fact that the molecular nature of carbon ion-induced mutation was different from that of electrons and that the molecular mechanisms of cells to induce mutations appeared to be also different implicates that ion particle is not only valuable as a new mutagen but also useful as a new tool to study repair mechanisms of certain types of DNA damage

  19. Induced mutations in pomoid trees breeding

    International Nuclear Information System (INIS)

    Hamed, Faysal

    1986-01-01

    Induction of mutations in fruit trees by ionizing radiation complements a cross-breeding program. The objectives are: 1) the improvements of methods of induction, identification and selection of useful mutations, and 2) the initiation of useful mutations either for immediate use as improved cultivars or as a parent material for conventional cross-breeding. The induction of mutants in pomoid fruits, with special emphasis on apple, was realized by gamma-ray treatment of dormant scions subsequently propagated on a rootstoch in the nursery. The aim was to obtain compacts, presuming the feasibility of selecting compact shoots formed by the irradiated scions in the first vegetative generation and also assuming that chance of finding (e.g. fruit mutants) would be thus increased rather than lessened. Selection was carried out on one-season old shoots, formed on the same material for two or three seasons, by using a cut-back at the end of the first and second season. The procedure was highly effective. Moderate exposures, resulting in 60% survival gave high mutation frequencies. Buds 6-10 on the primary shoot gave higher frequencies of recognizable mutations than either buds 1-5 or 11-15. Preliminary results seem to indicate that, at least in some apple cultivars, there is opportunity to obtain compact growth types with good biological characteristics. 8 refs. (author)

  20. Induced mutations in chickpea (Cicer arietinum L.) II. frequency and spectrum of chlorophyll mutations

    International Nuclear Information System (INIS)

    Kharkwal, M.C.

    1998-01-01

    A comparative study of frequency and spectrum of chlorophyll mutations induced by two physical (gamma rays, fast neutrons) and two chemical mutagens (NMU, EMS) in relation to the effects in M1 plants and induction of mutations in M2 was made in four chickpea (Cicer arietinum L.) varieties, two desi (G 130 & H 214) one Kabuli (C 104) and one green seeded (L 345). The treatments included three doses each of gamma rays (400, 500 & 600 Gy) and fast neutrons (5, 10 & 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU [0.01% (20h), & 0.02% (8h)] and EMS [0.1% (20h) & 0.2% (8h)]. The frequencies and spectrum of three different kinds of induced chlorophyll mutations in the order albina (43.5%), chlorina (27.3%) and xantha (24.2%) were recorded. Chemical mutagens were found to be efficient in inducing chlorophyll mutations in chickpea. Highest frequency of mutations was observed in green seeded var. L 345 (83% of M1 families and 19.9/1000 M2 plants). Kabuli var. C 104 was least responsive for chlorophyll mutations

  1. Advances and prospects for induced mutation breeding in Helongjiang Province

    International Nuclear Information System (INIS)

    Sun Guangzu

    1995-12-01

    Induced mutation breeding employed on soybean, spring wheat, maize, millet, fiber flax, chinese cabbage, kidney been and garlic in Heilongjiang province. Thirty-six new varieties had introduced and released from 1980 to 1994, made up 20.6% of total released varieties for the same period, accumulated cultivated area of 3.746 million hm 2 , and increased the income of formers to US dollar 168 million; 72 mutants having specific and utilizing values and traits have also been bred in the province. Basic research such as radiation breeding in combination with distant hybridization, biotechnology, and application new induced factors, improving selection methods, have been achieved; 91 articles have been published. These researches play an important role for increasing induced mutation breeding. Three items of suggestion to develop induced mutation breeding are made. (1 tab.)

  2. Alkylating agent (MNU)-induced mutation in space environment.

    Science.gov (United States)

    Ohnishi, T; Takahashi, A; Ohnishi, K; Takahashi, S; Masukawa, M; Sekikawa, K; Amano, T; Nakano, T; Nagaoka, S

    2001-01-01

    In recent years, some contradictory data about the effects of microgravity on radiation-induced biological responses in space experiments have been reported. We prepared a damaged template DNA produced with an alkylating agent (N-methyl-N-nitroso urea; MNU) to measure incorrect base-incorporation during DNA replication in microgravity. We examined whether mutation frequency is affected by microgravity during DNA replication for a DNA template damaged by an alkylating agent. Using an in vitro enzymatic reaction system, DNA synthesis by Taq polymerase or polymerase III was done during a US space shuttle mission (Discovery, STS-91). After the flight, DNA replication and mutation frequencies were measured. We found that there was almost no effect of microgravity on DNA replication and mutation frequency. It is suggested that microgravity might not affect at the stage of substrate incorporation in induced-mutation frequency. c2001 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  3. Mutation induced with ion beam irradiation in rose

    Science.gov (United States)

    Yamaguchi, H.; Nagatomi, S.; Morishita, T.; Degi, K.; Tanaka, A.; Shikazono, N.; Hase, Y.

    2003-05-01

    The effects of mutation induction by ion beam irradiation on axillary buds in rose were investigated. Axillary buds were irradiated with carbon and helium ion beams, and the solid mutants emerged after irradiation by repeated cutting back. In helium ion irradiation, mutations were observed in plants derived from 9 buds among 56 irradiated buds in 'Orange Rosamini' and in plants derived from 10 buds among 61 irradiated buds in 'Red Minimo'. In carbon ion, mutations were observed in plants derived from 12 buds among 88 irradiated buds in 'Orange Rosamini'. Mutations were induced not only in higher doses but also in lower doses, with which physiological effect by irradiation was hardly observed. Irradiation with both ion beams induced mutants in the number of petals, in flower size, in flower shape and in flower color in each cultivar.

  4. Induced mutations in Petunia hybrida Hort

    International Nuclear Information System (INIS)

    Kashikar, S.G.; Khalatkar, A.S.

    1980-01-01

    The seeds of a white flowering strain of Petunia hybrida hort. were treated with different concentrations of ethyl methane-sulphonate, sodium azide, diethyl sulphate, N-methyl-N'-nitro-N-nitrosoguanidine, ethylene imine and gamma radiations. A large number of flower colour and morphological mutants superior to the parental variety were obtained. The flower colour mutations took the form of sectors and whole colour changes. The latter included a large spectrum of colours from light to deep magenta, pink, purple and violet coloured petals. The anthocyanin analysis of these mutants showed different patterns of pigments responsible for the various colours. In addition to these, a broad spectrum of morphological mutations of ornamental value included dwarfs, unbranched, cristata, densa, campyloflora and velutiniflora types. The inheritance of horticulturally important characters was investigated in M 3 and M 4 generations. (author)

  5. ENU-induced phenovariance in mice: inferences from 587 mutations

    Directory of Open Access Journals (Sweden)

    Arnold Carrie N

    2012-10-01

    Full Text Available Abstract Background We present a compendium of N-ethyl-N-nitrosourea (ENU-induced mouse mutations, identified in our laboratory over a period of 10 years either on the basis of phenotype or whole genome and/or whole exome sequencing, and archived in the Mutagenetix database. Our purpose is threefold: 1 to formally describe many point mutations, including those that were not previously disclosed in peer-reviewed publications; 2 to assess the characteristics of these mutations; and 3 to estimate the likelihood that a missense mutation induced by ENU will create a detectable phenotype. Findings In the context of an ENU mutagenesis program for C57BL/6J mice, a total of 185 phenotypes were tracked to mutations in 129 genes. In addition, 402 incidental mutations were identified and predicted to affect 390 genes. As previously reported, ENU shows strand asymmetry in its induction of mutations, particularly favoring T to A rather than A to T in the sense strand of coding regions and splice junctions. Some amino acid substitutions are far more likely to be damaging than others, and some are far more likely to be observed. Indeed, from among a total of 494 non-synonymous coding mutations, ENU was observed to create only 114 of the 182 possible amino acid substitutions that single base changes can achieve. Based on differences in overt null allele frequencies observed in phenotypic vs. non-phenotypic mutation sets, we infer that ENU-induced missense mutations create detectable phenotype only about 1 in 4.7 times. While the remaining mutations may not be functionally neutral, they are, on average, beneath the limits of detection of the phenotypic assays we applied. Conclusions Collectively, these mutations add to our understanding of the chemical specificity of ENU, the types of amino acid substitutions it creates, and its efficiency in causing phenovariance. Our data support the validity of computational algorithms for the prediction of damage caused by

  6. Inducible repair system in Haemophilus influenzae unaccompanied by mutation

    International Nuclear Information System (INIS)

    Notani, N.K.; Setlow, J.K.

    1980-01-01

    Weigle reactivation of ultraviolet-irradiated HPlc1 phage was observed after ultraviolet or mitomycin C treatment of Haemophilus influenzae cells. The amount of reactivation was considerably increased when the treated cells were incubated in growth medium before infection. The presence of chloramphenicol during this incubation abolished the reactivation. No mutation of this phage accompanied the reactivation. When cells were treated so as to produce a maximal reactivation of phage, neither reactivation nor mutation of cells was observed. It is concluded that H. influenzae has an inducible repair system that is not accompanied by mutation

  7. Investigation of mutations induced by radiation and restriction endonucleases

    Science.gov (United States)

    Haworth, Kim E.

    The effects of gamma radiation and restriction endonuclease (RE) induced DNA double strand breaks (dsb) upon the mutation frequency and the surviving fraction of three Chinese hamster cell lines V79-4, CHO-K1 and an X-ray sensitive dsb repair deficient cell line xrs-5 were studied. The X-ray sensitive xrs-5 cell line was shown to be more sensitive to both the lethal and the mutagenic effects of gamma radiation having a substantially lower surviving fraction and a higher thymidine kinase (tk) mutation frequency per unit dose than the parental CHO-K1 cells. The frequency of induced hprt- mutations in the V79-4 cell line was comparable to the induced frequency of tk mutations in the CHO-K1 cells. The effect of blunt- and cohesive- ended dsb upon the surviving fraction and the induced mutation frequency was studied by porating different Chinese hamster cell lines (CHO-K1, V79-4 and xrs-5) with RE using Streptolysin O (SLO). The surviving fraction of the different cell lines was reduced with increasing concentrations of Pvu II. Increases in the concentration of Pvu II produced increases in the frequency of hypoxyanthine guanine phosphoribosyl transferase (hprt) mutations in the V79-4 cells and tk mutations in the CHO-K1 and xrs-5 cells. However, the xrs-5 cells were shown to be hypomutable to Pvu II compared with the parental CHO-K1 cells. EcoR1 was ineffective at inducing tk mutations in the CHO-Kl cells but was as effective as Pvu II at inducing hprt mutations in the V79-4 cells. None of the spontaneously induced V79-4 hprt- mutant cells were shown to have observable molecular deletions when analysed by PCR deletion screening. One third of the radiation induced hprt - mutants were shown to be deletions. However, too few mutant cells were analysed for any non-random distribution of deletions to be observed. Half of the hprt- mutants induced by SLO poration alone were shown to be due to deletions of oi\\e or more exons. The distribution of the DNA deletions in SLO hprt

  8. Gamma Radiation-Induced Mutations in Soybeans

    International Nuclear Information System (INIS)

    Smutkupt, S.

    1998-01-01

    The main objective of soybean radiation experiments was to create genetic variability in soybeans of various cultivars, mutants and mutation-derived lines with the aim of producing superior breeding lines with resistance to soybean rust (Phakopsora pachyhrizi Syd.) It took altogether 12 generations over six years after gamma irradiation if soybean seeds to produce the best resistant line (81-1-038) which a variety could be developed from it. This Line 81-1-038 showed a very good specific resistance to soybean rust, Thai race 2 and moderately resistance to Thai race 1. In the rainy season of 1985, Line 81-1-038 out yielded S.J.4 (a mother line) by 868 kg/ha in a yield trail at Suwan Farm, Pak Chong, Nakorn Rajchasima. This soybean rust mutant was later named D oi Kham

  9. Induced mutations for resistance to leaf rust in wheat

    International Nuclear Information System (INIS)

    Borojevic, K.

    1983-01-01

    Problems related to the induction of mutations for disease resistance were investigated under several aspects, using the wheat/leaf rust system. Previously selected mutant lines, tested in M 11 and M 13 , were found to differ with regard to infection type and disease severity from the original varieties. To verify the induced-mutation origin, these mutants were examined further using test crosses with carriers of known genes for leaf rust resistance and electrophoresis. A separate experiment to induce mutations for leaf rust resistance in the wheat varieties Sava, Aurora and Siete Cerros, using gamma rays, fast neutrons and EMS, yielded mutants with different disease reaction in the varieties Sava and Aurora at a frequency of about 1x10 - 3 per M 1 plant progenies. (author)

  10. Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

    Science.gov (United States)

    Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

    2015-01-01

    Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

  11. Induced mutations of rust resistance genes in wheat

    International Nuclear Information System (INIS)

    McIntosh, R.A.

    1983-01-01

    Induced mutations are being used as a tool to study genes for resistance in wheat. It was found that Pm1 can be separated from Lr20 and Sr15, but these two react like a single pleiotropic gene. Mutants were further examined in crosses and backmutations have been attempted. (author)

  12. A radiation-induced compact type Granny Smith apple mutation

    International Nuclear Information System (INIS)

    Hurter, N.; Van Tonder, M.J.

    1982-01-01

    More successful compact mutant clones of Granny Smith apple are being sought, for those that have so far arisen naturally have undesirable tree and fruit charateristics. For this purpose, gamma rays from a Cobalt-60 radiation unit were used to induce mutant types artificially. One compact mutation of Granny Smith was produced via re-irradiation

  13. Induced mutation in the improvement of beans

    International Nuclear Information System (INIS)

    Avila, R.L.; Murty, B.R.

    1984-01-01

    A program on mutational rectification was undertaken in 1978 utilizing gamma radiation, as seed treatment for three local cultivars of compea, Vigna unguiculata plus one cultivar of mungbean, Vigna radiata. The selection criteria were compact plant type with determinate habit, early maturity, resistance to Macrophomina and high yield. The selected material now in M 7 generation, selection being made in M 2 for plant type. In subsequent generations selections were made for resistance to Macrophomina, stability of plant type, uniform pod filling, seed size, good nodulation, synchronous flowering and productivity under close spacing conditions. Simultaneous studies on root development were made at seedling stage. In mungbean, emphasis on non-shattering was made. Finally 12 mutants were selected in M 5 , with uniformity for the cited characters and higher yields than the parental material, ranging from 20 to 110% superior yield in some mutants and sowing dates. Multilocation trials are being conducted to test the wide adaptability of these mutants. Chemical mutagenesis using sodium azide with and without gamma radiation was also used. From these trials nonnodulating mutants were recovered. These materials are being multiplied to be used in basic studies of the Rhizobium - legume symbiosis. Ecophysiological studies of the promising mutants have been carried out under different sowing dates at 45 day intervals. These results are of wide interest in studies of tropical adaptation of grain legumes, on which very few reports are available so far. These results are discussed with particular reference to yield and its stability for the cropping system in Venezuela. (author)

  14. Induced mutations in mungbean- variety BM-4

    International Nuclear Information System (INIS)

    Chavan, A.A.; Patil, V.D.; Pawar, R.B.

    2000-01-01

    Mung bean (Vigna radiata) is an important crop. Marathwada Agricultural University has developed and released a variety BM4 for Western Zone. This variety has got yield potential of 1200-1300 kg/ha. However it has small grain size and dull green colour resulting in less dahl recovery and less market price. To improve these parameters, a mutation breeding programme was taken up. Dry seeds of variety BM4 were treated with 10, 15, 25 kR gamma rays at BARC Mumbai. In M 1 generation, germination decreased with increased dose of gamma rays. Twenty five kR showed lowest germination, 10 and 15 kR showed satisfactory germination. Individual plants were harvested and plant to row progenies were grown in M 2 in augmented block design. Range of mean was 39.8 to 77.2, 6.3 to 45.4, 1.85 to 3.25 and 9.2 to 60.0 for plant height (cm), number of pods/plant, test weight (g) and yield/plant(g) respectively. Out of 3 doses of gamma rays 10 kR proved more effective in increasing seed size, number of pods and seed yield/plant. (author)

  15. Induced mutations of winged bean in Ghana

    International Nuclear Information System (INIS)

    Klu, G.Y.P.; Quaynor-Addy, M.; Dinku, E.; Dikumwin, E.

    1989-01-01

    Winged bean (Psophocarpus tetragonolobus (L.) D.C.) was introduced into Ghana about two decades ago and not long after a high quality baby food was compounded from it. Germplasm collections are established at the Kade Agricultural Research Station of the University of Ghana and the University of Cape Coast. In 1980 a mutation breeding project was initiated at the University of Cape Coast under FAO/IAEA research contract and among various mutants a single erect stem mutant, a multiple branched bush type and a mutant with extra long pods were obtained. A similar programme was started at the National Nuclear Research Centre Kwabenya in 1982. Seeds of accessions UPS 122 and Kade 6/16 were gamma irradiated (100-400 Gy). In M 2 a mutant was obtained that did not flower throughout a growing period of five months. This mutant had very few leaves but developed an underground tuber weighing ca. 100 g. The parent, UPS 122, although normally tuber producing did not form tubers at Kwabenya within the period studied. In M 3 , mutants with variations in seed size and seed coat colour have been detected

  16. Sucrose and IQ induced mutations in rat colon by independent

    DEFF Research Database (Denmark)

    Hansen, Max; Hald, M. T.; Autrup, H.

    2004-01-01

    Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions in colon and liver of rats and to increase the number of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To investigate a possible interaction between sucrose and IQ...... on the genotoxicity in rat liver and colon, we gave Big Blue rats(TM) a diet containing sucrose (0%, 3.45% or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ increased the mutation frequency in the colon. The effect of combined treatments with IQ and sucrose on the mutation frequencies...... was additive indicating that sucrose and IQ act independently. This was supported by the mutation spectra where sucrose expands the background mutations in the colon, whereas IQ, in other studies, more specifically has induced G:C --> T:A transversions. In the liver IQ increased the mutation frequency, whereas...

  17. Specific gene mutations induced by heavy ions

    International Nuclear Information System (INIS)

    Freeling, M.; Karoly, C.W.; Cheng, D.S.K.

    1980-01-01

    This report summarizes our heavy-ion research rationale, progress, and plans for the near future. The major project involves selecting a group of maize Adh1 mutants induced by heavy ions and correlating their altered behavior with altered DNA nucleotide sequences and sequence arrangements. This research requires merging the techniques of classical genetics and recombinant DNA technology. Our secondary projects involve (1) the use of the Adh gene in the fruit fly, Drosophila melanogaster, as a second system with which to quantify the sort of specific gene mutants induced by heavy ions as compared to x rays, and (2) the development of a maize Adh1 pollen in situ monitor for environmental mutagens

  18. Improvement of rice through induced mutations

    International Nuclear Information System (INIS)

    Miah, A.J.; Mansur, M.A.; Jalal Uddin, M.

    1981-01-01

    In a field trial conducted in randomized blocks with 4 replications during November to April 1977-78, 4 radiation-induced mutants of rice (Oryza sativa Linn.) were found to be 23 to 41 days earlier than 'IR 8'. 'Mut 1-2' gave the highest grain yield (2,884 kg/ha), followed by 'Mut 1-1' (2, 183 kg/ha) and 'BR 3' (1,825 kg/ha). Though all the mutant lines were suceptible to bacterial leaf-blight in greenhouse, in the field 'Mut 1-2' was moderately resistant and 'Mut 1-1' moderately susceptible. (auth.)

  19. Molecular analysis of radiation-induced mutations in vitro

    International Nuclear Information System (INIS)

    Kronenberg, A.

    1996-01-01

    This review will focus on the nature of specific locus mutations detected in mammalian cells exposed in vitro to different types of ionizing radiations. Ionizing radiation has been shown to produce a wide variety of heritable alterations in DNA. These range from single base pair substitutions to stable loss or translocation of large portions of whole chromosomes. Data will be reviewed for certain test systems that reveal different mutation spectra. Techniques for the analysis of molecular alterations include applications of the polymerase chain reaction, some of which may be coupled with DNA sequence analysis, and a variety of hybridization-based techniques. The complexity of large scale rearrangements is approached with cytogenetic techniques including high resolution banding and various applications of the fluorescence in situ hybridization (FISH) technique. Radiation-induced mutant frequencies and mutation spectra are a function of the linkage constraints on the recovery of viable mutants for a given locus and test system. 44 refs

  20. Radiation induced mutations for breeding of sorghum

    International Nuclear Information System (INIS)

    Bretaudeau, A.

    1997-01-01

    Several sorghum cultivars of Mali were irradiated with different doses of gamma rays and compared with the Caudatum types. Radio-sensitivity studies suggested that the local types were less sensitive to radiation than the introduced types. Whereas the local varieties survived dose of 300 Gy, in Caudatum types, seed germination and growth were significantly reduced at 200 Gy. Several agronomically important mutants were obtained among the progeny of the local types. Some of the mutants were shorter and had improved panicle characteristics. Radiation-induced variation was observed in several characters such as plant height, resistance to lodging, plant architecture, drought tolerance, panicle length and compactness, seed size and color, seed quality (viterous or floury) and protein content, glume color and structure, flowering data (early and late maturity), and tillering capacity. One mutant was drought tolerant. Promising mutants were selected and are presently under evaluation in the National List Trials to confirm their potential and future release. Selected variants have been also crossed with local types to obtain promising material. (author). 8 refs, 2 tabs

  1. Use of induced mutations for cotton breeding in India

    International Nuclear Information System (INIS)

    Raut, R.N.

    1980-01-01

    A large number of studies have been reported in recent years on the use of induced mutations in the improvement of food crops and ornamentals. Similar investigations on fibre crops like cotton have, however, been relatively few. The fact that most of the economically useful characters in cotton are under polygenic control appears to be the main limiting factor. Inspite of this there are reports of radiation induced useful mutations used as commercial varieties. As early as 1950 a X-ray induced mutant variety of G. hirsutum cotton Indore-2 was released for commercial cultivation in Madhya Pradesh and covered more than one lac hectares. More recently an early maturing mutant variety MCU-7 was released for cultivation in summer rice fallows of Tamil Nadu and covers nearly 10,000 acres. Other promising mutant strains found suitable b.v large scale trials and recommended for cultivation under specific conditions are Okra leaf mutant, photoinsensitive mutant of MCU-5 (named Rasmi) and Jassid tolerant early maturing mutant 4-1 (Pusa Ageti). In addition improved varieties like Badnaawar-1, Khandwa-2 and M64 have been evolved by utilizing mutant lines in cross breeding. The scope of induced mutation method as a breeding technique for cotton improvement in India is very wide. (author)

  2. Induced Mutations for Improving Production on Bread and Durum Wheat

    International Nuclear Information System (INIS)

    Stamo, Ilirjana; Ylli, Ariana; Dodbiba, Andon

    2007-01-01

    Wheat is a very important crop and has been bred for food and its improvement is continuous from cross-breeding. Radiation and chemically induced mutations have provided variability in selection for novel varieties. Four bread and one durum wheat cultivars were exposed to gamma rays, Cs 137 with doses 10, 15 and 20 krad (2000 seeds of each dose and cultivars). We have isolated mutant plants with height reduced and on cv Progress spike without chaff

  3. Induced mutation in soybean (Glycine max L.) breeding

    International Nuclear Information System (INIS)

    Tulmann Neto, A.; Menten, J.O.M.; Ando, A.

    1984-01-01

    The induced mutation in soybean (Glycine max, L.) breeding is studied. Seed treatment with gamma-rays or methanesulfonic acid ethyl ester (EMs) is used in the following varieties: Parana, Santa Rosa, UFV-1, Foscarin 31 and IAC-8. The study to obtain resistance to the soybean bud blight virus and mutants resistant to rust was done. Early mutants are also researched. (M.A.C.) [pt

  4. Plant breeding: Induced mutation technology for crop improvement

    International Nuclear Information System (INIS)

    Novak, F.J.; Brunner, H.

    1992-01-01

    Plant breeding requires genetic variation of useful traits for crop improvement, but the desired variation is often lacking. Mutagenic agents, such as radiation and certain chemicals, can be used to induce mutations and generate genetic variations from which desirable mutants may be selected. After a brief summary of the methods currently employed in plant breeding, especially those inducing genetic engineering, this article describes the activities of the Plant Breeding Unit of the IAEA Laboratories at Seibersdorf, summarizing the research and development areas currently being pursued. The banana plant is chosen to exemplify the Laboratories' research

  5. Utilization of induced mutations in improving legumes in Egypt

    International Nuclear Information System (INIS)

    Abo-Hegazi, A. M. T.

    1993-01-01

    More than one hundred articles published by Egyptian research workers dealing with the improvement of some seed-legumes through radiation, radioisotopes, chemical mutagens and induced mutations are briefly summarized and discussed from the point of view of a mutation breeder working in this field since 1961. Articles on faba bean (Vicia faba L.), soybean (Glycine Max L.), lentils (Lens culinaris), chick-pea (Cicer arietinum L.), lupin (Lupinus termis), peas=pea (Pisum sativum L.), cowpea (Vigna sinensis, savi), and fenugreek-helba (Trigonella foenum gracum L.) are reviewed. A very few number of promising mutations have been induced. However, none of them are utilized neither in conventional breeding programs nor as cultivars. This may be due to the lack of central plans and organization between efforts or research work being carried in various institutions. Joint plants and cooperation between research institutions, not only in Egypt but also among the Arab countries, are required in this field which may help in closing the wide gab between production and consumption os seed legumes. (author)

  6. Radiation-induced mutation and sexual incompatibility in flowering plants

    International Nuclear Information System (INIS)

    Pandey, K.K.

    1976-01-01

    The origin and features of the various types of mutations than can be induced at the incompatibility loci of higher plants is discussed. It is shown how nuclear techniques can be used for understanding the phenomena of incompatibility and for modifying the breeding system of cultivated species, producing F 1 hybrid seed or breaking down interspecific isolation. The efficiency of mutagenic treatments for inducing self-compatibility mutations essentially depends upon the incompatibility system considered, the stage treated and the tolerance of the species towards the loss of the S-locus or of elements associated to it. Pollen-part and stylar-part mutations can be induced and detected in a relatively large number of plant species characterized by gametophytic monofactorial self-incompatibility. Certain methods, essentially based upon the use of inbreeding techniques, in vitro culture, intergenomic translocations or intercrossing between unrelated self-compatible forms, may prove to be effective for establishing, transferring or activating a functional self-incompatibility system in certain self-pollinated species or for producing, in species normally characterized by monofactorial gametophytic self-incompatibility, diploid inbred lines where more than two different S-alleles are expressed simultaneously by each inbred plant. Recent studies in the United Kingdom, Australia and New Zealand on the determination of sporophytic incompatibility and on the effects of ionizing radiations suggest new possibilities for by-passing interspecific incompatibility by means of mixed pollinations, radiation treatments or manipulations of developing anthers. Radiation treatments, applied at high dosages to pollen grains, may induce or allow the transfer of certain genetic determinants of the pollen tube to the egg cell of the recipient species

  7. Stability Test For Sorghum Mutant Lines Derived From Induced Mutations with Gamma-Ray Irradiation

    Directory of Open Access Journals (Sweden)

    S. Human

    2011-12-01

    Full Text Available Sorghum breeding program had been conducted at the Center for the Application of Isotopes and Radiation Technology, BATAN. Plant genetic variability was increased through induced mutations using gamma-ray irradiation. Through selection process in successive generations, some promising mutant lines had been identified to have good agronomic characteristics with high grain yield. These breeding lines were tested in multi location trials and information of the genotypic stability was obtained to meet the requirements for officially varietal release by the Ministry of Agriculture. A total of 11 sorghum lines and varieties consisting of 8 mutant lines derived from induced mutations (B-100, B-95, B-92, B-83, B-76, B-75, B-69 and Zh-30 and 3 control varieties (Durra, UPCA-S1 and Mandau were included in the experiment. All materials were grown in 10 agro-ecologically different locations namely Gunungkidul, Bantul, Citayam, Garut, Lampung, Bogor, Anyer, Karawaci, Cianjur and Subang. In each location, the local adaptability test was conducted by randomized block design with 3 replications. Data of grain yield was used for evaluating genotypic stability using AMMI approach. Results revealed that sorghum mutation breeding had generated 3 mutant lines (B-100, B-76 and Zh-30 exhibiting grain yield significantly higher than the control varieties. These mutant lines were genetically stable in all locations so that they would be recommended for official release as new sorghum varieties to the Ministry of Agriculture

  8. Induced plasmon mutations affecting the growth habit of peanuts, A. hypogaea L

    International Nuclear Information System (INIS)

    Levy, A.; Ashri, A.

    1978-01-01

    The effectiveness of the acridines ethidium bromide (EB) and acriflavine in inducing plasmon mutations was compared with the alkylating agents ethyl methanesulphonate (EMS) and diethyl sulphate and to γ-rays. The growth habit (trailing versus bunch) of peanuts (A. hypogaea), controlled by genic-cytoplasmic interactions, was utilized. Breeding tests distinguishing nuclear from plasmon mutations were developed and are described in detail. Plasmon mutations were induced, but there were differences in mutation yields between the cultivars and the mutagens. (Auth.)

  9. Induced mutations for improvement of grain legume production

    International Nuclear Information System (INIS)

    1980-11-01

    After an introduction on plant science research in Malaysia concerning crop breeding, 22 research reports are presented, 17 of which are analyzed individually and constitute separate INIS references. The remaining 5 were essentially concerned with only future applications of nuclear technology: a paper by V.L. Chopra (India) on mutation breeding for partial disease resistance of wheat; by H.H. Hoppe (Federal Republic of Germany) on mechanisms of resistance against Uromyces in Phaseolus vulgaris; by I.S. Santos (Philippines) on induction evaluation and utilization of beneficial mutations in the winged bean (Psophocarpus tetragonolobus), where gamma rays and fast neutrons will be used as well as other mutagens; by F. Saccardo (Italy) on breeding for disease resistance in peas and other vegetables (short communication only); and by E. Balazs and I. Sziraki (Hungary) on in vitro studies on virus resistance of legumes, including virus-host interaction studies involving gamma irradiation (short communication only). The conclusions and recommendations of the Regional Seminar on Induced Mutations for the Improvement of Grain Legumes in S.E. Asia 1975 (IAEA-203, 1977) were considered and generally endorsed, with some clarification. Conclusions and recommendations are given on p.121-126

  10. Molecular characterization of microbial mutations induced by ion beam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ichida, Hiroyuki [Graduate School of Science and Technology, Chiba University, Matsudo, Chiba 271-8510 (Japan); Accelerator Applications Research Group, Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan)], E-mail: ichida@riken.jp; Matsuyama, Tomoki [Cellular Biochemistry Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama 351-0198 (Japan); Ryuto, Hiromichi [Accelerator Operation Group, Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan); Hayashi, Yoriko [Accelerator Applications Research Group, Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan); Fukunishi, Nobuhisa [Accelerator Operation Group, Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan); Abe, Tomoko [Accelerator Applications Research Group, Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan); Koba, Takato [Graduate School of Science and Technology, Chiba University, Matsudo, Chiba 271-8510 (Japan)

    2008-03-01

    A positive selection system for gene disruption using a sucrose-sensitive transgenic rhizobium was established and used for the molecular characterization of mutations induced by ion beam irradiations. Single nucleotide substitutions, insertions, and deletions were found to occur in the sucrose sensitivity gene, sacB, when the reporter line was irradiated with highly accelerated carbon and iron ion beams. In all of the insertion lines, fragments of essentially the same sequence and of approximately 1188 bp in size were identified in the sacB regions. In the deletion lines, iron ions showed a tendency to induce larger deletions than carbon ions, suggesting that higher LET beams cause larger deletions. We found also that ion beams, particularly 'heavier' ion beams, can produce single gene disruptions and may present an effective alternative to transgenic approaches.

  11. Gamma-ray induced mutation breeding in tree fruit crops

    International Nuclear Information System (INIS)

    Ito, Yuji

    1998-01-01

    In many vegetatively propagated crops and tree fruit crops, spontaneous mutations have played an important role in the development of cultivars. Thus, induced mutation breeding has been thought to be a promising way to improve commercially important cultivars. At the Institute of Radiation Breeding (IRB), studies on induced mutation breeding of temperate zone fruit trees using gamma-rays have been performed since 1962. Black spot disease, caused by Alternaria alternata Japanese pear pathotype, is one of the most serious diseases of Japanese pear (Pyrus pyrifolia NAKAI var. culta NAKAI) in Japan. It is known that some Japanese pear cultivars are completely resistant to the disease. The pathogenic fungi produces host-specific toxins (named AK-toxin) (Tanaka 1993, Otani et al. 1973). The susceptibility of Japanese pear is controlled by a single dominant gene (Kozaki 1973). To improve the Japanese pear cultivar 'Nijisseiki', which is highly susceptible to black spot disease, young grafted plants of 'Nijisseiki' have been irradiated chronically in the Gamma Field of the IRB since 1962. In 1981, one twig of a tree planted at a distance of 53 m from the 60 Co source with an exposure rate of 0.138 Gy/day (20hr-irradiation) was selected as the first resistant mutant. It was designated as cultivar 'Gold Nijisseiki' and released in 1990. A selection method for mutants resistant to black spot disease using the pathogen produced toxin and pear leaf disks was established. It is a simple and stable selection method. Up to the present, three mutant cultivars resistant to black spot disease have been bred at the IRB by chronic and acute gamma-ray irradiation. They showed intermediate resistance compared with the completely resitan cultivar 'Choujuurou' and highly susceptible cultivar 'Nijisseiki'. We obtained some apple mutants resistant to alternaria leaf blotch disease using toxin and leaf disks and are also attempting to obtain mutant resistant to some disease in other temperate

  12. 70 years induced mutations - To be reconsidered? Topic for discussion

    International Nuclear Information System (INIS)

    Micke, A.

    1996-01-01

    According to the prevailing concept at that time, ''qualitative traits'' were assumed to be controlled by one or very few genes, ''quantitative traits'' by many genes. One had already learned that genes could freely recombine, unless they were tightly linked in a chromosomal section. Great attention was paid to ''gene/environment interactions'', separating traits with ''high heritability'' from those with ''low heritability''. Mutagenesis, however, was supposed to be capable of altering all genes irrespective of their chromosomal location, linkage group or level of heritability. Those with ''high heritability'' of course were easier to handle and identified as the more promising targets for mutation induction. When plant breeders speak about gene/environment interactions, the environment is usually considered under the aspect of physical and chemical conditions outside the plant (e.g. location, year, stress), supporting or restricting performance. This neglects the fact that interaction among genes creates some kind of ''genetic environment''. Plant breeders tend to focus on particular genes assumed to be responsible for traits relevant for cultivar improvement. The other genes are downgraded by being lumped into the ''genetic background''. This thinking also prevailed so far in application of induced mutations in breeding programmes

  13. DNA sequence analysis of X-ray induced Adh null mutations in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Mahmoud, J.; Fossett, N.G.; Arbour-Reily, P.; McDaniel, M.; Tucker, A.; Chang, S.H.; Lee, W.R.

    1991-01-01

    The mutational spectrum for 28 X-ray induced mutations and 2 spontaneous mutations, previously determined by genetic and cytogenetic methods, consisted of 20 multilocus deficiencies (19 induced and 1 spontaneous) and 10 intragenic mutations (9 induced and 1 spontaneous). One of the X-ray induced intragenic mutations was lost, and another was determined to be a recombinant with the allele used in the recovery scheme. The DNA sequence of two X-ray induced intragenic mutations has been published. This paper reports the results of DNA sequence analysis of the remaining intragenic mutations and a summary of the X-ray induced mutational spectrum. The combination of DNA sequence analysis with genetic complementation analysis shows a continuous distribution in size of deletions rather than two different types of mutations consisting of deletions and 'point mutations'. Sequencing is shown to be essential for detecting intragenic deletions. Of particular importance for future studies is the observation that all of the intragenic deletions consist of a direct repeat adjacent to the breakpoint with one of the repeats deleted

  14. Improving protein quality of soybean through induced mutations

    International Nuclear Information System (INIS)

    Manjaya, J.G.

    2011-01-01

    Soybean is one of the most economical and nutritious food packed with basic nutrients that combat diseases stemming from mal- and under-nutrition. Despite its rich nutritional profile, use of soybean in food has been limited because soybean proteins are often associated with compounds, which could exert a negative impact on the nutritional quality of the protein. Trypsin inhibitor (TI) is one of the important anti-nutritional factors that exert negative effect by causing growth inhibition. Soybean cultivar VLS-2 was irradiated with 250 Gy gamma rays in a gamma cell (200) with 60 Co source installed at BARC to induce mutations for low trypsin inhibitor content. Three mutants with lower levels of TI content were identified and can be utilized for developing elite varieties of soybean. (author)

  15. Jatropha curcas improvement Induced mutation: Thies University Senegal

    International Nuclear Information System (INIS)

    Diédhiou, Ibrahima

    2011-06-01

    The objectives are: 1. to collect accessions of Jatropha curcas in Senegal and establish the genetic variability of this collection. 2. to improve the oil yield of Jatropha curcas by using radiation induced mutation methods to produce highly productive genotypes adapted to local conditions. The choice of Jatropha Curcas is explained by: * Intensive cultivation of Jatropha curcas initiated in many countries of West Africa to produce biodiesel. *There is a craze of private companies to promote this new agricultural value chain. * Jobs and substantial revenues are expected for the rural. *Unfortunately, there is little reliable knowledge to support this dynamic development. Also, the preliminary results showed a high variability of agro-morphological traits in local accessions which could affect negatively the profitability.

  16. Collateral damage: Spread of repeat-induced point mutation from a ...

    Indian Academy of Sciences (India)

    2004-10-16

    Oct 16, 2004 ... Repeat-induced point mutation (RIP) is an unusual genome defense mechanism that was discovered in Neurospora crassa. RIP occurs during a sexual cross and induces numerous G : C to A : T mutations in duplicated DNA sequences and also methylates many of the remaining cytosine residues.

  17. Induced mutation for the improvement of soybean (Glycine max L.)

    International Nuclear Information System (INIS)

    Asencion, A.B.; Lapade, A.G.; Grafia, A.O.; Barrida, A.C.; Veluz, A.M.; Marbella, L.J.

    2004-01-01

    A study on the use of gamma radiation in the induction of mutations in eight varieties of soybean was conducted. The radiosensitivity of the seeds of both local and introduced soybean varieties was determined. The effects of gamma radiation in the M1 generation were evaluated. Percentage germination was not affected by doses of 200 and 250 Gy gamma radiation in all the eight soybean varieties. No significant differences in seedling height were observed at 200 Gy and the control except for the 250 Gy in BPI-Sy4, PSB-Sy4 and PSB-Sy5. In the Vietnamese varieties, significant differences in seedling height were obtained in doses of 200, 250 Gy and the control except for the variety AKO 6. There was significant difference in plant height of mature plants between the control and treatment dose of 250 Gy in varieties DT 95 and AKO 6. Likewise, significant differences in mature plant height were noted between the control and those at 250 Gy in local varieties BPI-Sy4, PSB-Sy5 and NSIC-Sy8. The number of days to flower was not affected by gamma radiation in both the local and introduced varieties. There were significant differences in the number of pods per plant between the control and a low dose of 200 Gy in Vietnamese variety DT 96 and the local varieties PSB-Sy4, PSB-Sy5 and NSIC-Sy8. The 3 types of chlorophyll mutation induced by gamma rays in the local varieties were: chlorina, striatia,and spotted yellow. Only chlorina mutant was induced in the introduced varieties. Desirable mutants that are early and high yielding were selected. Results of the drought tolerance tests indicated that the number of days to flowering of the control and 8 varieties was not affected by the duration of irrigation withdrawals 20,30,40 and 50 days after planting. Significant differences in seed weight among the different varieties were noted only in 20 and 30 day irrigation withdrawal treatment. When the effects of the different treatments were analyzed on a per variety bases, some of the

  18. Mutation Breeding Newsletter. No. 37

    International Nuclear Information System (INIS)

    1991-01-01

    This newsletter contains a brief account of FAO/IAEA meetings held in 1990 on plant breeding involving the use of induced mutations. It also features a list of commercially available plant cultivars produced by such techniques. Refs and tabs

  19. Oilseed cultivars developed from induced mutations and mutations altering fatty acid composition

    International Nuclear Information System (INIS)

    Bhatia, C.R.; Nichterlein, K.; Maluszynski, M.

    1999-01-01

    One hundred and sixty-three cultivars of annual oilseed crops, developed using induced mutations, have been officially approved and released for cultivation in 26 countries. The maximum number of cultivars have been released in soybean (58), followed by groundnut (44), sesame (16), linseed (15), rapeseed (14), Indian mustard (8), castorbean (4), white mustard (3) and sunflower (1). The majority (118 of 163) of the cultivars have been developed as direct mutants and 45 of 163 by using the induced mutants in a crossing programme. While in soybean 53 out of 58 cultivars were selected as direct mutants, in groundnut 22 from 44 were developed after hybridization. Eighty-three cultivars were developed directly by exposing seeds to gamma or X-rays. Attempts have been made to infer the successful dose range, defined as the range which led to the development, registration and release of the maximum number of mutant cultivars for gamma and X-rays. The successful dose ranges in Gy for the main oilseed crops are: soybean 100-200, groundnut 150-250, rapeseed 600-800, Indian mustard 700 and sesame 100-200. The main characteristics of the new cultivars, besides higher yield, are altered plant type, early flowering and maturity and oil content. Mutants altering fatty acid composition have been isolated in soybean, rapeseed, sunflower, linseed and minor oil crops. New cultivars having altered fatty acid composition have been released in rapeseed, sunflower and linseed. The latter, previously grown for non-edible oil, has been converted to a new edible oil crop. (author)

  20. Grain legume cultivars derived from induced mutations, and mutations affecting nodulation

    International Nuclear Information System (INIS)

    Bhatia, C.R.; Maluszynski, M.; Nichterlein, K.; Zanten, L. van

    2001-01-01

    Two hundred and sixty-five grain legume cultivars developed using induced mutations have been released in 32 countries. A maximum number of cultivars have been released in soybean (58), followed by common bean (50), groundnut (44), pea (32) and mungbean (14). Gamma or x-ray exposures of seeds led to the direct development of 111 cultivars, while neutron and chemical mutagen treatments resulted in 8 and 36 cultivars respectively. One hundred and three cultivars have been developed using mutants in cross breeding. Attempts have been made to estimate the successful dose range for gamma and x-rays, defined as the dose range, which led to the development, registration and release of a maximum number of mutant cultivars. Exposures to seeds ranging between 100-200 Gy in all grain legumes, except faba bean, resulted in 49 out of 111 cultivars being developed as direct mutants. Successful doses reported for faba bean are lower than 100 Gy. Modified crop plant characters are listed. Besides the development of new cultivars, a large number of induced mutants that show altered nodulation pattern have been isolated in grain legumes. Such mutants have made a significant contribution in basic studies on host-symbiont interactions and towards cloning of plant genes related to symbiosis and nitrogen fixation. Their exploitation in breeding programs for enhancing nitrogen fixation is just beginning. Available information on nodulation mutants in grain legume crops is summarised. Mainly, four types of nodulation mutants have been isolated. They show either: no nodulation (nod -), few nodules (nod +/-), ineffective nodulation (Fix-), hypernodulation (nod ++) or hypernodulation even in the presence of otherwise inhibitory nitrate levels (nts). Hypernodulating and nts mutants are of great interest. A soybean cultivar incorporating nts trait has been released in Australia. (author)

  1. Improvement of some ornamental plants by induced somatic mutations at National Botanical Research Institute

    International Nuclear Information System (INIS)

    Gupta, M.N.

    1980-01-01

    Research work on improvement of some ornamental plants by induced somatic mutations has been in progress at the National Botanical Research Institute, Lucknow, since 1964. The methods of treatments with gamma rays, detection, isolation and multiplication of induced somatic mutations have been given for Bougainvillea, Chrysanthemum, perennial Portulaca, rose and tuberose. During the last 15 years, a total of 38 new cultivars of different ornamentals evolved by gamna induced somatic mutations have been released. They include Bougainvillea 1; Chrysanthemum 28; perennial portulaca 6; rose 1 and tuberose 2. Descriptions of the original cultivars and their gamma induced mutants are given along with other pertinent details. (author)

  2. Effects of the umuC36 mutation on ultraviolet-radiation-induced base-change and frameshift mutations in Escherichia coli

    International Nuclear Information System (INIS)

    Kato, T.; Nakano, E.

    1981-01-01

    The effects of the umuC36 mutation on the induction of base-change and frameshift mutations were studied. An active umuC gene was necessary in either the uvr + or uvr - strains of Escherichia coli K12 for UV- and X-ray-induced mutations to His + , ColE and Spc, which are presumably base-change mutations, but it was not essential for ethyl methanesulphonate or N-methyl-N'-nitro-N-nitrosoguanidine-induced His + mutations. In contrast, only 1 out of 13 trp - frameshift mutations examined was UV reversible, and the process of mutagenesis was umuC + -dependent, whereas a potent frameshift mutagen, ICR191, effectively induced Trp + mutations in most of the strains regardless of the umu + or umuC genetic background. These results suggest that base substitutions are a major mutational type derived from the umuC + -dependent pathway of error-prone repair. (orig.)

  3. Application of DNA based marker mutations for improvement of cereals and other sexually reproduced crop plants. Proceedings of a final research co-ordination meeting

    International Nuclear Information System (INIS)

    1998-03-01

    The Co-ordinated Research Programme (CRP) on the Application of DNA Based Marker Mutations for Improvement of Cereals and Other Sexually Reproduced Crop Plants represents the first of three CRPs dealing with the application of molecular markers to mutations and plant breeding and was implemented between 1992 and 1996. A second companion CRP entitled Use of Novel DNA Fingerprinting Techniques for the Detection and Characterization of Genetic Variation in Vegetatively Propagated Crops devoted to the application of molecular markers in vegetatively propagated crops species was implemented between 1993 and 1997. One positive consequence of these two CRPs has been the implementation of a third CRP entitled Radioactively Labeled DNA Probes for Crop Improvement, which began in 1995 and aims to provide enabling technologies, in the form of probes and primers, to laboratories in developing countries. The rapid development of molecular marker technologies has also resulted in a dramatic increase in request from developing Member States for technical co-operation projects utilizing molecular markers to improve local varieties for biotic and abiotic stresses and other traits of relevance. With the intensified use of induced mutations in genetic studies, it will be important to continue the important work of understanding induced mutations at the molecular level. Evidence of the progress made in implementing molecular marker technologies in laboratories around the world is presented in this publication, which contains the results presented by the participants at the fourth and final Research Co-ordination Meeting of the CRP held in Vienna, 4-8 November 1996. The FAO and IAEA wish to express their sincere appreciation to the participants of the meeting for their work during the project period resulting in the summary and scientific reports presented in this publication

  4. Rice improvement through radiation-induced mutation for cultivation in South Vietnam

    International Nuclear Information System (INIS)

    Do Khac Thinh; Hung Phi Oanh; Nguyen Thi Cuc; Nguyen Ngoc Quynh

    2001-01-01

    For past years, rice varieties cultivated in South Vietnam originated from domestic hybridisation or from IRRI. Rice mutation breeding has been initiated for recent years. To meet the requirement of rice production diversification in different agro-ecological areas and rice genetic resources, from 1993 Institute of Agricultural Science of South Vietnam has carried out rice improvement by induced mutation of radiation. The mutagen was gamma rays of 60 Co. The goal is to create inherited variations, which cannot be obtained from other breeding methods, specially important characters of rice varieties (high tolerance to acid sulfate soil, lodging resistance combined with early maturity), which were difficult to gain by hybridisation. With 60 Co gamma rays, doses of 10-20 krad, dose rate of 280 krad/h, dry and germinated seeds of introduced and local rice varieties (IR 64, IR 9729, IR 50404, IR 59606, Jasmine 85, Nang Huong, Tam Xoan) were irradiated. The irradiated seeds were immediately sown within 24 and 94 hrs for wet seeds and dry seeds after treatment, respectively. Population of 10,000-15,000 plants were established and evaluated by IRRI evaluation standard from M2-M7 generations. 365 lines, varieties were selected with better behaviours than original varieties as lodging resistance, earliness, potential yield, leaf characters, tolerant ability to adverse conditions etc. Some good varieties (VND95-19, VND95-20) have been approved as leading national varieties and released for large-scale production in South Vietnam. (author)

  5. Rice improvement through radiation-induced mutation for cultivation in South Vietnam

    Energy Technology Data Exchange (ETDEWEB)

    Do Khac Thinh; Hung Phi Oanh; Nguyen Thi Cuc; Nguyen Ngoc Quynh [Institute of Agricultural Science of South Vietnam, Ho Chi Minh (Viet Nam)

    2001-03-01

    For past years, rice varieties cultivated in South Vietnam originated from domestic hybridisation or from IRRI. Rice mutation breeding has been initiated for recent years. To meet the requirement of rice production diversification in different agro-ecological areas and rice genetic resources, from 1993 Institute of Agricultural Science of South Vietnam has carried out rice improvement by induced mutation of radiation. The mutagen was gamma rays of {sup 60}Co. The goal is to create inherited variations, which cannot be obtained from other breeding methods, specially important characters of rice varieties (high tolerance to acid sulfate soil, lodging resistance combined with early maturity), which were difficult to gain by hybridisation. With {sup 60}Co gamma rays, doses of 10-20 krad, dose rate of 280 krad/h, dry and germinated seeds of introduced and local rice varieties (IR 64, IR 9729, IR 50404, IR 59606, Jasmine 85, Nang Huong, Tam Xoan) were irradiated. The irradiated seeds were immediately sown within 24 and 94 hrs for wet seeds and dry seeds after treatment, respectively. Population of 10,000-15,000 plants were established and evaluated by IRRI evaluation standard from M2-M7 generations. 365 lines, varieties were selected with better behaviours than original varieties as lodging resistance, earliness, potential yield, leaf characters, tolerant ability to adverse conditions etc. Some good varieties (VND95-19, VND95-20) have been approved as leading national varieties and released for large-scale production in South Vietnam. (author)

  6. Intercellular distribution of mutations induced in oopcytes of Drosophila melanogaster by chemical and physical mutagens

    International Nuclear Information System (INIS)

    Traut, H.

    1979-01-01

    When females of Drosophila melanogaster are treated with chemical or physical mutagens, not only in one but also in both of the two homologous X chromosomes of a given oocyte, a recessive sex-linked lethal mutation may be induced. A method is described that discriminates between such single and double mutations. A theory is developed to show how a comparison betweeen the expected and the observer frequency of double mutations yields an indication of the intercellular distribution (random or nonrandom) of recessive lethal mutations induced by mutagenic agents in oocytes and, consequently, of the distribution (homogenous or nonhomogeneous) of those agents. Three agents were tested: FUdR (12.5, 50.0 and 81.0 μg/ml), mitomycin C (130.0 μg/ml) and x rays (2000 R, 150 kV). After FUdR feeding, no increase in the mutation frequency usually observed in D. melanogaster without mutagenic treatment was obtained (u = 0.13%, namely three single mutations among 2332 chromosomes tested). After mitomycin C feeding 104 single and three double mutations were obtained. All of the 50 mutations observed after x irradiation were single mutations. The results obtained in the mitomycin C and radiation experiments favor the assumption of a random intercellular distribution of recessive lethal mutations induced by these two agents in oocytes of D. melanogaster. Reasons are discussed why for other types of mutagenic agents nonrandom distributions may be observed with our technique

  7. Mutational analysis of root characters in food plants. Proceedings of a final research coordination meeting

    International Nuclear Information System (INIS)

    2006-04-01

    genomics and proteomics to address important agricultural issues, supporting successful agricultural production with minimal impact on the environment. Improvements in screening techniques and development of molecular markers are ways to alleviate the need for direct root assessment and speed up selection in plant breeding programmes. Root architecture models provide a tool to address the space-time dynamics of the soil/plant system. Genetic analysis of quantitative traits and methods in forward and reverse genetics will also contribute to breeding crops with root systems suitable for a range of agricultural environments. Recent evidence indicates that plant stresses are mediated by changes at the root system level. In this context, mutants and mutational analysis of root characters are becoming significant elements in research that seeks to clarify the ways by which root structure and function respond to environmental cues and alleviate the impact of stress. This publication summarizes the results presented at the third and final Research Coordination meeting (RCM) of the CRP, which was held in Antalya, Turkey, 11-15 October 2004

  8. N-acetoxy-N-2-acetylaminofluorene induced frameshift mutations: a comparison between the DNA modification spectrum and the mutation spectrum

    International Nuclear Information System (INIS)

    Fuchs, R.P.P.; Koffel-Schwartz, N.; Daune, M.

    1983-01-01

    We describe the analysis of forward mutations induced in the tetracycline resistance gene of the plasmid pBR322 by directing the reaction of the carcinogen N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF) to a small restriction fragment (BamHI, SalI) that is located in the proximal part of the antibiotic-resistance gene. Mutant plasmids obtained both in wild type and excision repair deficient (uvrA) bacterial cells are compared. Preliminary data showing the distribution of the -AAF adducts along this restriction fragments are discussed in relation to the observed spectrum of mutations. 20 references, 4 figures

  9. Influence of temperature on spontaneous and radiation-induced somatic mutations in Tradescantia stamen hairs

    International Nuclear Information System (INIS)

    Nauman, C.H.; Schairer, L.A.; Sparrow, A.H.

    1978-01-01

    Three diploid clones of Tradescantia which are heterozygous or hemizygous for flower color, and which exhibit a 35-fold range in spontaneous mutation frequency, have been compared in their response to increased temperatures. The endpoint studied is the expression of pink and colorless mutations, which arise in stamen hair cells spontaneously and following exposure to ionizing radiation and chemical mutagens. Increased temperature (26.5 or 28 0 vs. 16 or 19 0 ) significantly increased the spontaneous pink mutation frequency in stamen hair cells of all three clones. Colorless mutations in clone 0106 were not increased significantly at the higher temperature. The influence of increased temperature on radiation-induced pink mutation frequency was examined in clone 02. Temperatures in the range of 16-28 0 did not influence the magnitude of mutation response after exposure to 100 rad of X-rays; however, the timing of the mutation response was altered both in time of onset and duration. (Auth.)

  10. Induced mutation breeding for the improvement of rice in Malaysia

    International Nuclear Information System (INIS)

    Rusli Ibrahim; Abdul Rahim Harun; Ramli Othman; Farazi Johari; Asnah Hassan

    2002-01-01

    The first application of nuclear technology in mutation breeding for the improvement of rice was undertaken by the Malaysian Institute for Nuclear Technology Research (MINT) in December, 1984 for a Coordinated Research Programme under RCA/IAEA/FAO entitled Semi Dwarf Mutants for Rice Improvement in Asia and Pacific. The main objective was to generate semi dwarf mutants in both native and improved cultivars for possible use as new released cultivars or as parents in cross breeding programmes. Within five years, 101 semi dwarf mutants which have the potential to be used as new cultivars or as parents in cross breeding were identified. Twenty nine of the semi dwarf mutants have grain yield between 6000-7300 kg/ha which were classified as potentially good yielding mutants. The parent, Manik yielded about 5700 kg/ha. Forty seven mutants have grain yield between 5000 6000 kg/ha and 25 mutants yielded in the range of 4300-5000 kg/ha. Twelve mutants are resistant to BPH (brown planthopper) but only one, mutant ML15 has grain yield (6300 kg / ha) better than the parent. One of the most striking effects of radiation (gamma ray) was the formation of glutinous rice (Manik 817) with both good yield and head recovery. It is also interesting to note that one of the mutants (MA 03) shows a drastic change in its characteristics and performs better than the parent and other mutant lines. This mutant was late popularly known as mutant Tongkat Ali because of its: outstanding agronomic features such as very erect panicle even after grain filling, very strong culm and resistance to lodging. Even though this mutant was not officially released, due to its unique characteristics and high yield, it has been planted commercially by several farmers especially in the northern parts of Malaysia. More collaborative research programmes using induced mutation breeding have been carried out between MINT, MADA and also MARDI with the aim of producing new potential varieties with high yield, disease

  11. Molecular analysis of carbon ion-induced mutations in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Shikazono, Naoya; Tanaka, Atsushi; Watanabe, Hiroshi; Tano, Shigemitsu; Yokota, Yukihiko

    1998-01-01

    In order to elucidate the characteristics of the mutations induced by ion particles at the molecular level in plants, mutated loci in carbon ion-induced mutants of Arabidopsis were investigated by PCR and Southern blot analyses. In the present study, two lines of gl1 mutant and two lines of tt4 mutant were isolated after carbon ion-irradiation. Out of four mutants, one had a deletion, other two contained rearrangements, and one had a point-like mutation. From the present result, it was suggested that ion particles induced different kinds of alterations of the DNA and therefore they could produce various types of mutant alleles in plants. (author)

  12. Specialists meeting on LMFBR flow induced vibrations. Summary report

    International Nuclear Information System (INIS)

    1977-12-01

    A Specialists' Meeting on LMFBR Flow-Induced Vibrations was held at ANL in the United States which was sponsored by the International Atomic Energy Agency (IAEA) on the recommendations of the International Working Group on Fast Reactors (IWGFR). It was attended by participants from France, the Federal Republic of Germany, Italy, Japan, Netherlands, the United Kingdom, the Union of Soviet Socialist Republics, the United States and the IAEA. The purpose of the meeting was to provide, for the first time, a common forum for the exchange of information on flow-induced vibration programs of the member countries. As this was a first meeting, information was sought in the broad areas of: 1. Design Criteria and Problem Areas in LMFBR Design; 2. Current Design Procedures; and 3. Ongoing Research. A session was devoted to each of the above topics wherein papers were presented and discussed followed by open discussions on the session topic. The objective of the open discussions was to identify, from a review of specific reactor designs, (a) flow induced vibration problem areas (expected and observed) and their potential for occurrence; (b) failure modes and associated design criteria; (c) specific components that are susceptible to flow induced vibration; and (d) probable excitation mechanisms. It was aimed to assess the current state-of-the-art in designing to avoid flow induced vibration with consideration of licensing requirements; to evaluate existing methods of analysis, testing, and surveillance, along with their limitations and to identify areas requiring research and review ongoing research programmes relative to these research needs

  13. Collateral damage: Spread of repeat-induced point mutation from a ...

    Indian Academy of Sciences (India)

    Unknown

    [Vyas M and Kasbekar D P 2005 Collateral damage: Spread of repeat-induced point mutation from a duplicated DNA sequence into an ad- joining single-copy gene in Neurospora ... 9⋅3 kb DNA sequence. Approximately 170–200 copies of ..... progeny inheriting a RIP-mutated erg-3 allele. Since the hph-marked transgene ...

  14. Role of combined use of classical induced mutation breeding and biotechnology in development of new flower colour/form in ornamentals

    International Nuclear Information System (INIS)

    Datta, SK.

    2001-01-01

    In floriculture trade there is always demand and necessity of new and novel ornamental varieties. Flower colour is one of the most important component of novelties. Induced somatic mutation techniques by using ionizing radiations and other mutagens have successfully produced quite a large number of new promising varieties (50 Nos.) in different ornamental (Bougainvillea, Chrysanthemum, Hibiscus, Rose, Tuberose, Lantana depressa etc.) plants by bringing about genetic changes at Floriculture Section, National Botanical Research Institute, India. For inducing novelties in flower colour of different plants the technique of selection of proper type/state of plant material for experiment, suitable dose, detection of mutation at right stage of development, isolation and multiplication of chimeric tissue have been standardised. The capability of the technique is well understood from significant number of new varieties developed via direct mutation breeding in already adapted, modern genotypes and enriched the germplasm. The mutations in flower lour/shape were detected as chimera in M1v1, M1v2, M1v3 generations. The mutation frequency varied with the cultivar and exposure of gamma rays. The main bottleneck of mutation breeding is that the mutation appears as chimera. When the entire branch is mutated, mutants can be isolated through conventional propagation techniques while small sectorial mutation in the floret cannot be isolated using existing conventional techniques. Therefore, many new flower colour/shape mutants are lost due to the lack of a suitable propagation technique. By applying biotechnological technique on the same mutagen treated gamma rays population a novel tissue culture technique hasbeen standardised to regenerate plants directly from such mutated sectors (ray florets) of Chrysanthemum. A number of somatic flower colour/shape mutants have been developed in Chrysanthemum by using this in vitro technique. Combination of classical mutation breeding and

  15. Mutations induced by ultraviolet radiation affecting virulence in Puccinia striiformis

    International Nuclear Information System (INIS)

    Shang Hongsheng; Jing Jinxue; Li Zhenqi

    1994-01-01

    Uredospores of parent culture, cy 29-1, were treated by ultraviolet radiation and mutations to virulent were tested on resistant wheat cultivars inoculated with treated spores. 7 mutant cultures virulent to the test cultivars were developed with estimated mutation rate 10~6~10~4. The virulence of mutant cultures was different from the all known races of stripe rust. Resistance segregation to mutant cultures was detected in two test cultivars. The results suggested that mutation was important mechanism of virulence variation operative in asexual population of rust fungi

  16. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    National Research Council Canada - National Science Library

    Rosenstein, Barry

    2003-01-01

    The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced RTOG/EORTC grade 3/4 subcutaneous late tissue morbidity possess a mutated ATM gene...

  17. The effects of microgravity on induced mutation in Escherichia coli and Saccharomyces cerevisiae.

    Science.gov (United States)

    Takahashi, A; Ohnishi, K; Takahashi, S; Masukawa, M; Sekikawa, K; Amano, T; Nakano, T; Nagaoka, S; Ohnishi, T

    2001-01-01

    We examined whether microgravity influences the induced-mutation frequencies through in vivo experiments during space flight aboard the space shuttle Discovery (STS-91). We prepared dried samples of repair-deficient strains and parental strains of Escherichia (E.) coli and Saccharomyces (S.) cerevisiae given DNA damage treatment. After culture in space, we measured the induced-mutation frequencies and SOS-responses under microgravity. The experimental findings indicate that almost the same induced-mutation frequencies and SOS-responses of space samples were observed in both strains compared with the ground control samples. It is suggested that microgravity might not influence induced-mutation frequencies and SOS-responses at the stages of DNA replication and/or DNA repair. In addition, we developed a new experimental apparatus for space experiments to culture and freeze stocks of E. coli and S. cerevisiae cells. c2001 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  18. Breeding high yielding varieties of pigeon pea, mungbean and black gram using induced mutations

    International Nuclear Information System (INIS)

    Pawar, S.E.; Wanjari, K.B.

    1994-01-01

    The present communication emphasis the developing of high yielding varieties of pigeon pea, mungbean and black gram using induced mutation with disease resistance in these crops. This would help in stabilisation of the higher yield potential

  19. Particle-induced chromosome aberrations and mutations: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, S. [Gesellschaft fuer Schwerionenforschung, Darmstadt (Germany)

    1997-09-01

    This overview will focus on progress in chromosome and mutation studies achieved by the application of new techniques. Furthermore, recent relevant data on longterm genetic effects of densely ionizing radiation will be summarized. (orig./MG)

  20. Sample preparation method for induced mutation on orchid

    International Nuclear Information System (INIS)

    Suhaimi Musa; Sakinah Ariffin

    2005-01-01

    Studies on the induction of mutation in Dendrobium orchid at MINT has produced a number of new orchid mutant cultivars. Tissue culture techniques on orchid seeds and meristem cloning are employed in preparing the samples for the mutation induction. Solid medium based on the Murashige and Skoog (1962) and liquid medium based on Vacin and Went (1949) were found to be suitable in producing protocorm like bodies (PLBs) that are required for the irradiation treatment. (Author)

  1. The role of radiation induced mutations in crop Improvement

    International Nuclear Information System (INIS)

    Souframanien, J.

    2017-01-01

    Sudden, heritable changes in the genetic material, DNA, are known as mutations. Selection of naturally occurring mutations in wild, ancestral species helped humans in the domestication and further improvement of today's crop plants. Gregor Mendel in 1865 used several such natural mutants in his experiments with garden pea to formulate the laws of inheritance. The term mutation itself was used for the first time by Hugo de Vries in 1901 in his mutation theory. Plant breeding based on the science of genetics, as practiced over the past 100 years, exploited the available genetic variability in the primary gene pool of crop plants, and sometimes in related species. Primarily, simple selection of desirable offspring and cross breeding were the earlier methods of breeding and this utilized the occurrence of spontaneous mutations. In nature, occurrence of natural variability in the form of spontaneous mutations is extremely low (about 10 -6 ), which can be enhanced several fold (∼10 -3 ) by using ionizing radiations or chemical mutagens

  2. Global impact of induced mutation in plant breeding

    International Nuclear Information System (INIS)

    Bhatia, R.

    2001-01-01

    Sudden, heritable changes in the genetic material, DNA, are known as mutations. Selection of naturally occurring mutations in wild, ancestral species helped humans in the domestication and further improvement of today's crop plants. Although Charles Darwin was unaware in 1859 of variation and mutations in living organisms, his theory of evolution by natural selection assumed variability. Much later, it was established that mutations are the source of biodiversity, and the driving force for evolution. Gregor Mendel in 1865 also used several mutants in his experiments with garden pea to formulate the laws of inheritance. The term mutation itself was used for the first time by Hugo de Vries in 1901 in his mutation theory. Plant breeding based on the science of genetics, as practiced over the past 100 years, exploited the available genetic variability in the primary gene pool of crop plants, and sometimes in related species. This approach enlarged the yield potential of crops several fold. It also a) improved the stability of yield by incorporating resistance to various biotic and abiotic stresses; b) improved quality of the produce; and c) altered the adaptability of crop species, providing opportunities to grow new crops for food security outside their traditional range. Genetically improved seed (or other planting material) is the most significant input for developing sustainable cropping systems for food security and economic growth. Half of the increased productivity of today's crop plants comes from genetic improvements. The other half is contributed by inputs and management practices

  3. Development of breeding materials in rice by use of induced mutation

    International Nuclear Information System (INIS)

    Amano, Etsuo

    1988-01-01

    On this 25th Gamma Field Symposium, it may be worth while to review the world situation of mutation breeding, the possibility expected to mutation methods suggested by the ever progressing genetics in rice plant, and some of the activities in the Institute of Radiation Breeding. By the help of a small computer, the key word search analysis of 'Mutation Breeding Newsletter and Mutation Breeding Review' was tried, and the results are included in this review to see the present status. The studies on artificially induced mutation suggested that the possibility of dominant mutation is less. It might be probable that the inactivation of genes is the mechanism of mutation. Still the possibility of using mutation breeding techniques for many genetic characters was suggested. After the experience for 25 years, detailed genetical and fine structure analyses became important. The studies on the expression of mutant phenotypes including molecular genetics will help to develop radiation breeding into an effective means to enrich the genetic resources for breeding. The situation in the world, the genes reported in rice, the possibility to induce useful mutants against environmental stress, the mutation in the protein content in grains, the mutants of storage carbohydrate, the possibility to widen gene resources and so on are reported. (Kako, I.)

  4. Induced mutation for accelerated domestication: a case study of winged bean (Psophocarpus tetragonolobus (L.) (DC)

    International Nuclear Information System (INIS)

    Klu, G. Y. P.

    2000-01-01

    Induced mutations have the ability to increase the rate of domestication of the many under exploited species of plants that may be potentially useful as source of food, forage and industrial raw materials. The process of domestication has been conditioned by single or major gene mutations. The role of mutagenesis in speeding up domestication, which is species dependent, is outlined in this paper. A case study of the role of induced mutations in the domestication of winged bean (Psophocarpus tetragonobolus) is also presented (au)

  5. Plant cultivars derived from mutation induction or the use of induced mutants in cross breeding

    International Nuclear Information System (INIS)

    Micke, A.; Maluszynski, M.; Donini, B.

    1985-01-01

    Since 1969 we have collected information on cultivated varieties of plants, developed by using induced mutations. Whenever we learn about a cultivar presumably derived from an induced mutant or from use of mutants in crosses. we mail a questionnaire to the breeder. The information gathered in this way is stored in our file on ''Mutant Varieties''. Excerpts are published regularly in the form of a list in the FAO/IAEA Mutation Breeding Newsletter. Our mutant variety list has repeatedly provided a basis for analyses on the value and prospects of mutation breeding

  6. Cellular and deafness mechanisms underlying connexin mutation induced hearing loss – A common hereditary deafness

    Directory of Open Access Journals (Sweden)

    Jeffrey C Wingard

    2015-05-01

    Full Text Available Hearing loss due to mutations in the connexin gene family which encodes gap junctional proteins is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2 mutations are responsible for ~50% of nonsyndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential (EP reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Additionally, there is no clear relationship between specific changes in connexin (channel functions and the phenotypes of mutation-induced hearing loss. Cx30, Cx29, Cx31, and Cx43 mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes and pathogeneses of specific-mutation induced hearing loss remain unclear. Finally, little information is available for humans. Further studies to address these deficiencies are urgently required.

  7. Understanding the role of p53 in adaptive response to radiation-induced germline mutations

    International Nuclear Information System (INIS)

    Langlois, N.L.; Quinn, J.S.; Somers, C.M.; Boreham, D.R.; Mitchel, R.E.J.

    2003-01-01

    Full text: Radiation-induced adaptive response is now a widely studied area of radiation biology. Studies have demonstrated reduced levels of radiation-induced biological damage when an 'adaptive dose' is given before a higher 'challenge dose' compared to when the challenge dose is given alone. It has been shown in some systems to be a result of inducible cellular repair systems. The adaptive response has been clearly demonstrated in many model systems, however its impact on heritable effects in the mammalian germline has never been studied. Expanded Simple Tandem Repeat (ESTR) loci have been used as markers demonstrating that induced heritable mutations in mice follow a dose-response relationship. Recent data in our laboratory show preliminary evidence of radiation-induced adaptive response suppressing germline mutations at ESTR loci in wild type mice. The frequency of heritable mutations was significantly reduced when a priming dose of 0.1 Gy was given 24 hours prior to a 1 Gy acute challenging dose. We are now conducting a follow-up study to attempt to understand the mechanism of this adaptive response. P53 is known to play a significant role in governing apoptosis, DNA repair and cancer induction. In order to determine what function p53 has in the adaptive response for heritable mutations, we have mated radiation treated Trp53+/- male mice (C57Bl) to untreated, normal females (C57Bl). Using DNA fingerprinting, we are investigating the rate of inherited radiation-induced mutations on pre- and post-meiotic radiation-treated gametocytes by examining mutation frequencies in offspring DNA. If p53 is integral in the mechanism of adaptive response, we should not see an adaptive response in radiation-induced heritable mutations in these mice. This research is significant in that it will provide insight to understanding the mechanism behind radiation-induced adaptive response in the mammalian germline

  8. Radiation induced mutations in sweet cherry (Prunus avium L.)

    International Nuclear Information System (INIS)

    Saamin, S.

    1989-01-01

    Full text: Shoot apices of cv. ''Napoleon'' and ''Bing'' were irradiated. The overall mutation rate in M 1 V 2 was ca. 7%, including reduced growth. The use of buds 11-30 on M 1 V 1 shoots is recommended for the efficient recovery of mutants. (author)

  9. Base substitutions, frameshifts, and small deletions constitute ionizing radiation-induced point mutations in mammalian cells

    International Nuclear Information System (INIS)

    Grosovsky, A.J.; de Boer, J.G.; de Jong, P.J.; Drobetsky, E.A.; Glickman, B.W.

    1988-01-01

    The relative role of point mutations and large genomic rearrangements in ionizing radiation-induced mutagenesis has been an issue of long-standing interest. Recent studies using Southern blotting analysis permit the partitioning of ionizing radiation-induced mutagenesis in mammalian cells into detectable deletions and major genomic rearrangements and into point mutations. The molecular nature of these point mutations has been left unresolved; they may include base substitutions as well as small deletions, insertions, and frame-shifts below the level of resolution of Southern blotting analysis. In this investigation, we have characterized a collection of ionizing radiation-induced point mutations at the endogenous adenine phosphoribosyltransferase (aprt) locus of Chinese hamster ovary cells at the DNA sequence level. Base substitutions represented approximately equal to 2/3 of the point mutations analyzed. Although the collection of mutants is relatively small, every possible type of base substitution event has been recovered. These mutations are well distributed throughout the coding sequence with only one multiple occurrence. Small deletions represented the remainder of characterized mutants; no insertions have been observed. Sequence-directed mechanisms mediated by direct repeats could account for some of the observed deletions, while others appear to be directly attributable to radiation-induced strand breakage

  10. Somatic mutations in leafs of tobacco seedlings induced by ionizing radiation and pesticide

    International Nuclear Information System (INIS)

    Shin, H. S.; Kim, J. K.; Song, H. S.; Lee, Y. I.

    2001-01-01

    Somatic mutations induced by the combined treatment of pesticide and ionizing radiation were analyzed in the leaves of tobacco seedlings. The pesticide (1,5 and 10 ppm of parathion) was sprayed directly onto the seedlings. The seedlings, with or without pretreatment of pesticide, were irradiated with 0.1 ∼10 Gy of gamma ray. The difference in the somatic mutation frequencies were not significant among groups treated with different concentration of pesticide. The somatic mutations in tobacco seedlings irradiated with gamma-ray showed a clear dose-response relationship in a range of 0.1 to 10 Gy. However, the combined treatment of pesticide and radiation did not cause any synergistic enhancement in the mutation frequencies. The highest efficiency in the induction of somatic mutations could be obtained by irradiating the seedlings with 5 Gy, 12 hours after 1 ppm of pesticide treatment, or 24 hours after 5 ppm of pesticide treatment

  11. Irradiation-induced mutation experiments with eiploid and tetraploid tomato plants

    International Nuclear Information System (INIS)

    Boda, J.

    1979-01-01

    Tomato mutation experiments are described. The tomatoes used in the experiment were the diploid Reziszta and its autotetraploid variety. The experimental plants were exposed to an irradiation of 5000 rsd for 1-2 days, and after transplantation into the gamma field, to chronic irradiation during the whole growing season. The chronic treatment heavily reduced fertility in the generations of tetraploid tomato plants. Recurrent treatment of tetraploid led to further deterioration in fertility. Several berries were formed with few seeds or with no seeds at all. After three irradiations, the chlorophyll mutation frequency increased in the diploid and tetraploid tomato plants. For diploids, treatment applied at the seedling stage gave a lower chlorophyll mutation frequency. With tetraploids the same treatment induced similar chlorophyll mutation frequency. As regards to phenotypic variability of quantitative characteristics in diploid and tetraploid tomatoes, the single and repeated chronic irradiation induced no increase in the variability of properties like flowering time, weight, height etc. (author)

  12. Frequency and spectrum of mutations induced by gamma irradiation in single, double and triple dwarf wheats

    International Nuclear Information System (INIS)

    Dhonukshe, B.L.

    1981-01-01

    Induced mutation studies were carried with three dwarf wheat varieties viz., ''Sonalika'', ''Chhoti Lerma'' and ''Hira'', considered to be single, double and trible dwarfs, respectively. Gamma-rays were used as a source of irradiation. Frequency of chlorophyll mutations were comparatively low and the spectrum was narrow. Chlorophyll mutations were altogether absent in the variety ''Sonalika''. A very wide spectrum of viable mutations affecting stem, leaf, ear growth habit, maturity and fertility characteristics was observed in the M 2 . The cumulative frequency of all the mutants together was quite high, which varied with the varieties. There were varietal differences in the composition and width of the spectrum induced by gamma-rays. The dwarf mutants having desirable leaf and spike characters were isolated in all the three varieties. (author)

  13. Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli

    International Nuclear Information System (INIS)

    Crosby, R.M.; Richardson, K.K.; Craft, T.R.; Benforado, K.B.; Liber, H.L.; Skopek, T.R.

    1988-01-01

    The molecular nature of formaldehyde (HCHO)-induced mutations was studied in both human lymphoblasts and E. coli. Thirty HPRT - human lymphoblast colonies induced by eight repetitive 150 μM HCHO treatments were characterized by Southern blot analysis. Fourteen of these mutants (47%) had visible deletions of some or all of the X-linked HPRT bands, indicating that HCHO can induce large losses of DNA in human lymphoblasts. In E. coli., DNA alterations induced by HCHO were characterized with use of the xanthine guanine phosphoribosyl transferase (gpt) gene as the genetic target. Exposure of E. coli to 4 mM HCHO for 1 hr induced large insertions (41%), large deletions (18%), and point mutations (41%). Dideoxy DNA sequencing revealed that most of the point mutations were transversions at GC base pairs. In contrast, exposure of E. coli to 40 mM HCHO for 1 hr produced 92% point mutations, 62% of which were transitions at a single AT base pair in the gene. Therefore, HCHO is capable of producing different genetic alterations in E. coli at different concentrations, suggesting fundamental differences in the mutagenic mechanisms operating at the two concentrations used. Naked pSV2gpt plasmid DNA was exposed to 3.3 or 10 mM HCHO and transformed into E. coli. Most of the resulting mutations were frameshifts, again suggesting a different mutagenic mechanism

  14. Analysis of chlorophyll mutations induced by γ-rays in barley (hordeum vulgare)

    International Nuclear Information System (INIS)

    Wang Cailian; Shen Mei; Xu Gang; Zhao Kongnan; Chen Qiufang

    1991-06-01

    Thirty varieties of dormant barley seeds were irradiated with 137 Cs γ-rays. Dose-effect relations of chlorophyll mutation frequency in M 2 seedling and differences resulting from cultured types or radiosensitive types were investigated. Experimental results show that the relations between chlorophyll mutation frequency and doses can be fitted by a linear regression equation Y = A + BX. According to analysis of covariance, there is no considerable difference in various cultured types, but the difference of five different radiosensitive types is remarkable. The sensitive and intermediate types need much lower doses than other types to induce maximum chlorophyll mutation

  15. Novel allelic mutations in murine Serca2 induce differential development of squamous cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Toki, Hideaki; Minowa, Osamu; Inoue, Maki; Motegi, Hiromi; Karashima, Yuko; Ikeda, Ami [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Kaneda, Hideki [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Sakuraba, Yoshiyuki [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Saiki, Yuriko [Department of Molecular Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi (Japan); Wakana, Shigeharu [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Suzuki, Hiroshi [Department of Biochemistry, Asahikawa Medical University, Asahikawa, Hokkaido (Japan); Gondo, Yoichi [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Shiroishi, Toshihiko [Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka (Japan); Noda, Tetsuo, E-mail: tnoda@jfcr.or.jp [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Department of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo (Japan)

    2016-08-05

    Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1–4] and humans to Darier disease (DD) [14–17]. In this study, we generated mice harboring N-ethyl-N-nitrosourea (ENU)-induced allelic mutations in Serca2: three missense mutations and one nonsense mutation. Mice harboring these Serca2 mutations developed tumors that were categorized as either early onset squamous cell tumors (SCT), with development similar to null-type knockout mice [2,4] (aggressive form; M682, M814), or late onset tumors (mild form; M1049, M1162). Molecular analysis showed no aberration in Serca2 mRNA or protein expression levels in normal esophageal cells of any of the four mutant heterozygotes. There was no loss of heterozygosity at the Serca2 locus in the squamous cell carcinomas in any of the four lines. The effect of each mutation on Ca{sup 2+}-ATPase activity was predicted using atomic-structure models and accumulated mutated protein studies, suggesting that putative complete loss of Serca2 enzymatic activity may lead to early tumor onset, whereas mutations in which Serca2 retains residual enzymatic activity result in late onset. We propose that impaired Serca2 gene product activity has a long-term effect on squamous cell carcinogenesis from onset to the final carcinoma stage through an as-yet unrecognized but common regulatory pathway. -- Highlights: •Novel mutations in murine Serca2 caused early onset or late onset of tumorigenesis. •They also caused higher or lower incidence of Darier Disease phenotype. •3D structure model suggested the former mutations led to severer defect on ATPase. •Driver gene mutations via long-range effect on Ca2+ distributions are suggested.

  16. Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.

    Directory of Open Access Journals (Sweden)

    Foad J Rouhani

    2016-04-01

    Full Text Available The accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50-70 de novo single nucleotide variants (SNVs between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs, their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer.

  17. DNA sequence analysis of methylene chloride-induced HPRT mutations in Chinese hamster ovary cells: comparison with the mutation spectrum obtained for 1,2-dibromoethane and formaldehyde.

    Science.gov (United States)

    Graves, R J; Trueman, P; Jones, S; Green, T

    1996-05-01

    Glutathione-S-transferase-mediated metabolism of methylene chloride (MC) generates S-chloromethylglutathione, which has the potential to react with DNA, and formaldehyde, which is a known mutagen. MC-induced mutations in the HPRT gene of Chinese hamster ovary cells have been sequenced and compared with the mutations induced by 1, 2-dibromoethane (1,2-DEB), which is known to act through a glutathione conjugate, and formaldehyde. All three compounds induced primarily point mutations, with a small number of insertion and deletion events. The most common point mutations induced by MC were GC-->AT transitions (4/8), with two GC-->CG transversions and two AT-->TA transversions. This pattern of mutations showed greater similarity with 1,2-DBE, where the dominant point mutations were GC-->AT transitions (7/9), than formaldehyde, where all mutations were single base transversions and 5/6 occurred from AT base pairs. The mutation sequence results for MC suggest that S-chloromethylglutathione plays a major role in MC mutagenesis, with only a limited contribution from formaldehyde. The involvement of a glutathione (GSH) conjugate in MC mutagenicity would be analogous to the well-characterized pathway of activation of 1,2-DBE.

  18. Improvement of bambara groundnut production using induced mutations

    International Nuclear Information System (INIS)

    Amoatey, H.M.; Klu, G.Y.P.

    1997-01-01

    Induction of variation in bambara groundnut using gamma radiation has been tried before. However, no mutants with the desired determinate flowering habit and synchronous pod maturity were obtained. This project is aimed at: conducting a nationwide exploration exercise to collect germplasm of bambara groundnut for agronomic evaluation with respect to flowering and fruiting characteristics and their effects on yield; and, applying the technique of mutation induction to create variability (if this is not found in the germplasm to be collected) from which mutants with determinate flowering and fruiting habit may be selected for use in breeding. 6 refs

  19. Most ultraviolet irradiation induced mutations in the nematode Caenorhabditis elegans are chromosomal rearrangements

    International Nuclear Information System (INIS)

    Stewart, H.I.; Rosenbluth, R.E.; Baillie, D.L.

    1991-01-01

    In this study the utility of 254-nm ultraviolet light (UV) as a magnetic tool in C.elegans is determined. It is demonstrated that irradiation of adult hermaphrodites provides a simple method for the induction of heritable chromosomal rearrangements. A screening protocol was employed that identifies either recessive lethal mutations in the 40 map unit region balanced by the translocation eT1(III;V), or unc-36(III) duplications. Mutations were recovered in 3% of the chromosomes screened after a dose of 120 J/m 2 . This rate resembles that for 1500 R γ-ray-induced mutations selected in a similar manner. The mutations were classified either as lethals [mapping to Linkage Group (LG)III or LGV] or as putative unc-36 duplications. In contrast to the majority of UV-induced mutations analysed in micro-organisms, a large fraction of the C.elegans UV-induced mutations were found to be not simple intragenic lesions, but deficiencies for more than one adjacent gene or more complex events. Preliminary evidence for this conclusion came from the high frequency of mutations that had a dominant effect causing reduced numbers of adult progeny. Subsequently 6 out of 9 analysed LGV mutations were found to be deficiencies. Other specific rearrangements also identified were: one translocation, sT5(II;III), and two unc-36 duplications, sDp8 and sDp9. It was concluded that UV irradiation can easily be used as an additional tool for the analysis of C.elegans chromosomes, and that C.elegans should prove to be a useful organism in which to study the mechanisms whereby UV acts as a mutagen in cells of complex eukaryotes. (author). 46 refs.; 5 figs.; 4 tabs

  20. Ancient genes establish stress-induced mutation as a hallmark of cancer.

    Directory of Open Access Journals (Sweden)

    Luis Cisneros

    Full Text Available Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1 Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]; and 2 genes that are frequently mutated in cancer and whose mutations are functionally important for the emergence of the cancer phenotype evolved within the past 1000 million years, and thus would exhibit an age distribution that is skewed to younger genes. In order to investigate these hypotheses we estimated the evolutionary ages of all human genes and then studied the probability of mutation and their biological function in relation to their age and genomic location for both normal germline and cancer contexts. We observed that under a model of uniform random mutation across the genome, controlled for gene size, genes less than 500 MY were more frequently mutated in both cases. Paradoxically, causal genes, defined in the COSMIC Cancer Gene Census, were depleted in this age group. When we used functional enrichment analysis to explain this unexpected result we discovered that COSMIC genes with recessive disease phenotypes were enriched for DNA repair and cell cycle control. The non-mutated genes in these pathways are orthologous to those underlying stress-induced mutation in bacteria, which results in the clustering of single nucleotide variations. COSMIC genes were less common in regions where the probability of observing mutational clusters is high, although they are approximately 2-fold more likely to harbor mutational clusters compared to other human genes. Our results suggest this ancient mutational

  1. Observation on gamma ray induced viable mutations in vegetable cowpea

    International Nuclear Information System (INIS)

    Mohanasundaram, M.; Thamburaj, S.; Natarajan, S.

    2001-01-01

    Two cowpea (Vigna unguiculata L. Walp) varieties 'Pusa Komal' and 'Co 2' were irradiated with gamma rays at 200, 300, 400 and 500 Gy. After mutagenic treatment, M 1 generation was raised. Ten M 1 plants in each treatment and in the control were advanced to M 2 generation. The M 2 seedling progenies were examined for viable mutants. In a population of 3,199 and 3,538 plants in Pusa Komal and Co 2 respectively, a total number of 140 mutants were observed for variation in cotyledonary leaves in the early stage of growth to abberants possessing modified plant structure, leaf morphology, pod size, pod color and seed coat color. In the progeny of Pusa Komal variety, the percentage of viable mutation was the highest at 300 Gy while in Co 2, at 500 Gy. Mutants for plant habit have also been reported in greengram. The data on mutagenic effectiveness and efficiency are given. In Pusa Komal, the effectiveness for viable mutation ranged from 4.22 to 12.45 and in Co 2 ranged from 6.60 to 13.35. The effectiveness and efficiency were decreased with increased doses of gamma rays as was also noted for mungbean

  2. Nature of induced mutations affecting disease reaction in wheat

    International Nuclear Information System (INIS)

    McIntosh, R.A.

    1977-01-01

    Three genes, Lr20, Sr15 and Pml conferring resistance to some strains of Puccinia recondita, P. graminis tritici and Erysiphe graminis tritici, respectively, have never been observed to undergo genetic recombination. Since genotypes possessing one of the alleles always possessed the other two, the hypothesis of one gene with pleiotropic effects was tested. Seeds of a homozygous line possessing the gene(s) in coupling with a recessive chlorophyll marker, cn-Ala, were treated with three levels of EMS. Very high rates of mutation were observed. Changes with respect to Pml were independent of changes with respect to Lr20 and Sr15 indicating molecular independence of the product of the Pml allele. On the other hand, all instances of change with respect to Lr20 were associated with changes of Sr15. With both Lr20 and Sr15 a range of variation in infection types produced by the mutant lines was established but the rankings of the degree of change monitored by the respective pathogens were not identical. It is suggested that the same host gene product is recognized by the products of the avirulence alleles of the two rust pathogens. Screening with virulent counterparts of the three pathogens failed to detect instances of obvious mutations producing new resistances. The results are considered in relation to the gene-for-gene hypothesis. (author)

  3. Use of ionizing radiation induced mutation in the genetic development of plants

    International Nuclear Information System (INIS)

    Barragan, Raul; Rubio, Santiago

    1993-01-01

    The objective of this article is to present a general focus on the use of induced mutations in the improvement of plants. This article describes some basic aspects that must be well known by the breeder that hopes to incorporate in his programm the technique of induced mutation by radiations. In this paper are included the results of two trials done by the researchers of the department of plant breeding so that it can be used as reference to determinate the importance of this technique

  4. Effects of a chromosome-3 mutator gene on radiation-induced mutability in Drosophila melanogaster females

    International Nuclear Information System (INIS)

    Sankaranarayanan, K.

    1982-01-01

    A series of X-irradiation experiments was carried out using Drosophila melanogaster females homozygous for a third chromosome mutator gene and females which had a similar genetic background except that the mutator-bearing third chromosomes were substituted by normal wild-type chromosomes. In the present work, the sensitivity of the pre-meiotic germ cells of mutator and normal females to the X-ray induction (2000 R) of sex-linked recessive lethals was studied. In addition, experiments were conducted to examine the sensitivity of the immature (stage 7; prophase I of meiosis) oocytes of both kinds of females to the induction of dominant lethals, X-linked recessive lethals and X-chromosome losses. The results show that in pre-meiotic germ cells, the frequencies of radiation-induced recessive lethals are similar in both kinds of females. However, the proportion of these mutations that occur in clusters of size 3 and higher, is higher in mutator than in normal females. In stage-7 oocytes, the frequencies of radiation-induced dominant lethals and sex-linked recessive lethals were similar in both kinds of females. The X-loss frequencies however, were consistently higher in mutator females although statistical significance was obtained only at higher exposures (3000 and 3750 R) and not at lower ones (750-2250 R). Possible reasons for the discrepancy between the present results and those of Gold and Green with respect to pre-meiotic germ cells are discussed. (orig./MG)

  5. Break-Induced Replication Is a Source of Mutation Clusters Underlying Kataegis

    Directory of Open Access Journals (Sweden)

    Cynthia J. Sakofsky

    2014-06-01

    Full Text Available Clusters of simultaneous multiple mutations can be a source of rapid change during carcinogenesis and evolution. Such mutation clusters have been recently shown to originate from DNA damage within long single-stranded DNA (ssDNA formed at resected double-strand breaks and dysfunctional replication forks. Here, we identify double-strand break (DSB-induced replication (BIR as another powerful source of mutation clusters that formed in nearly half of wild-type yeast cells undergoing BIR in the presence of alkylating damage. Clustered mutations were primarily formed along the track of DNA synthesis and were frequently associated with additional breakage and rearrangements. Moreover, the base specificity, strand coordination, and strand bias of the mutation spectrum were consistent with mutations arising from damage in persistent ssDNA stretches within unconventional replication intermediates. Altogether, these features closely resemble kataegic events in cancers, suggesting that replication intermediates during BIR may be the most prominent source of mutation clusters across species.

  6. Induced mutations in apomictic variety of maize-tripsacum hybrid

    International Nuclear Information System (INIS)

    Yudin, B.F.; Lukina, L.A.

    1983-01-01

    Three generations of six mutants obtained by γ- and x-irradiation of seeds of highly apomictic variety of 38 chromosome maize-tripsacum hybrid have been studied. Radiomutants detected in M 2 preserved the mother type and constance in M 3 and M 4 . One of the mutants, as an exception, manifested somatic splitting, which resulted in the appearance of a new apomictic clone. Irradiation and mutation in some cases were accompanied by the appearance of seedlings with high chromosome numbers in mutant posterity, including apomicts with doubled number of chromosomes, as well as the increase of total part of sexual reproduction; the latter circumstance is considered as a result of modificator balance change caused by treatments. Doubling of chromosome number in 38-chromosome apomicts, according to preliminary data, does not affect significantly the way of reproduction; 76-chromosome forms preserve a high degree of a regular apomixis

  7. Induced mutations for fasciation in lentil (Lens culinaris Med.)

    International Nuclear Information System (INIS)

    Tyagi, B.S.; Gupta, P.K.

    1992-01-01

    A mutant with fascination in the upper part of stem was isolated in lentil (Lens culinaris) following combined treatment of gamma rays and EMS (200 Gy + 0.1% EMS). During the later stages of plant growth, due to slight flattening of stem and branches at the shoot apex, the plant appeared like a cluster of closely fused branches. Unlike earlier reported fascinated mutants in lentil, which were sterile [1], these fascinated mutants were fully fertile having normal reproductive organs, and thus are being maintained in homozygous state. Pods per bunch ranged from 2–10 as against 1–3 in the control. The mutants also differed from control in chlorophyll a and b content and other quantitative characters. The segregation data suggested monogenic recessive nature of the mutation

  8. Induced mutations in Iraqi bread wheat cv. Saber Beg

    International Nuclear Information System (INIS)

    Ibrahim, I.F.; Haidar, H.O.

    1989-01-01

    ''Saber Beg'', is a local wheat cultivar important in the semi-arid zone of Iraq where the rainfall is less than 450 mm per year. This cultivar has a good baking quality, but is of low productivity, high susceptibility to common bunt (Tilletia spp.) and to leaf rust (Puccinia recondita Rob. ex Desm.), but only in the rainy season. A mutation breeding programme using gamma irradiation has been started in 1978 to improve this cultivar. Seeds of all main tillers from M 1 plants were harvested and artificially inoculated with teliospores of Tilletia spp. All the seeds from healthy M 2 plants were inoculated again and sown in the same area. Out of 22920 M 3 plants, 244 resistant ones were selected. During subsequent screening for 4 generations, however, only 3 mutants were confirmed

  9. Improvement of quinoa and barley through induced mutations and biotechnology

    International Nuclear Information System (INIS)

    Siles, A.Z.; Miranda, L.S.

    2001-01-01

    The main cropping problems in the Bolivian highlands are the long growing period of barley, high degree of environmental influence on the performance of quinoa, and low soil moisture at sowing time, leading to low germination rate and poor stands, and frost or chilling damages. The program aimed to establish protocols for induction of mutations with X rays and chemical mutagens (NaN 3 , MNH, EMS) in quinoa, barley, native forage species and forest plants and to obtain mutant lines, especially in barley and quinoa; and to establish callus regeneration in quinoa and micropropagation of kenua (Polilepis). The project is still in its study stages, hence further evaluations are needed before firm conclusions are drawn. (author)

  10. Pesticide-induced gene mutations and Parkinson disease risk: a meta-analysis.

    Science.gov (United States)

    Liu, Xiaowei; Ma, Tao; Qu, Bo; Ji, Yan; Liu, Zhi

    2013-11-01

    Increasing scientific evidence suggests that pesticide-induced gene mutations may contribute to increasing susceptibility to Parkinson disease (PD), but many existing studies have yielded inconclusive results. This meta-analysis aims at assessing the exact roles of pesticide-induced gene mutations in the development of PD. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratio with 95% confidence interval was calculated. Ten case-control studies were included with a total of 1248 PD patients and 1831 healthy controls. Our meta-analysis revealed that PD patients with pesticide exposure had higher gene mutation rates than those of healthy controls. Subgroup analysis by gene type indicated that the mutation rates in the GSTP1, SLC6A3, and MDR1 genes of PD patients with pesticide exposure were higher than those of healthy controls. No publication bias was detected in this meta-analysis. The current meta-analysis indicates that pesticide-induced gene mutations may contribute to increasing susceptibility to PD, especially in the GSTP1, SLC6A3, and MDR1 genes.

  11. Timing of the uv mutagenesis in yeast: a pedigree analysis of induced recessive mutation

    International Nuclear Information System (INIS)

    James, A.P.; Kilbey, B.J.

    1977-01-01

    The mechanism of uv-induced mutation in eukaryotes was studied in individual yeast cells by a procedure that combined pedigree analysis and tetrad analysis. The technique involved the induction of recessive lethals and semilethals in G1 diploid cells. Induced frequencies were 25 and 61% at survival levels of 90 and 77%, respectively. No evidence of gross chromosome aberrations was detected. Recessive mutations that affect only one strand or that affect both strands of the DNA molecule are induced much at random among a population of cells, and both types can occur within the same cell. However, the data confirm that two-strand mutations are in the majority after a low level of irradiation. The simplest explanation involves a mechanism whereby most mutations are fixed in both strands prior to the first round of post-irradiation DNA replication. The recessive mutational consequences of irradiation are exhausted at the conclusion of the first post-irradiation cell division, although dominant-lethal sectoring continues at a high level through the second post-irradiation division. It is concluded that pyrimidine dimers that persist to the second round of DNA replication are rare or ineffective

  12. Use of gamma radiation in floriculture industry for development of new varieties through induced mutation

    International Nuclear Information System (INIS)

    Datta, S.K.

    2002-01-01

    Nuclear radiation (gamma rays) can create changes in genetic make up of plant material through mutation. Gamma ray induced mutation is now an established method for crop improvement. It is well known that the crops which are propagated vegetatively are very suitable for the application of mutation breeding methods. In floriculture industry there is always demand and necessity of new and novel ornamental varieties. Flower colour and shape are the most important components of novelties. Gamma rays have been most successfully use to produce quite a large number of new promising,varieties in different ornamental (Bougainvillea - 4, Perennial portulaca-6, Chrysanthemum-43, Hibiscus-1, Rose-16, Tuberose-2, Lantana depressa-3 etc.) plants by bringing about genetic changes at Floriculture Section, National Botanical Research. Institute, Lucknow, India. Research carried out covers radiosensitivity, selection of materials, methods of exposure to gamma rays, suitable dose of gamma rays, detection of mutants, isolation of mutants and commercial exploitation of mutants. A good number of mutant varieties have been well accepted in the floriculture industry. The mutant varieties are with new flower colour and shape. More than three decades of applied mutation breeding work has now established beyond doubt that mutation breeding will constitute an excellent supplement to the conventional methods for development of new varieties . Detection of somatic, mutations in flower colour/shape in different vegetative generations (M 1 V 1 , M 1 V 2 , M 1 V 3 and even in later vegetative generations), mutation frequency and spectrum relationship with dose of gamma radiation have been precisely determined. Studies have clearly proved that mutation breeding technique can be exploited for the creation of new and novel ornamental cultivars of commercial importance by inducing genetic variation in already adapted, modern genotypes and can also enrich the germplasm of ornamental horticulture

  13. Is low-energy-ion bombardment generated X-ray emission a secondary mutational source to ion-beam-induced genetic mutation?

    International Nuclear Information System (INIS)

    Thongkumkoon, P.; Prakrajang, K.; Thopan, P.; Yaopromsiri, C.; Suwannakachorn, D.; Yu, L.D.

    2013-01-01

    Highlights: ► Detected X-ray emission from metal, plastic and biological samples. ► Characteristic X-ray emission was detected from metal but not from non-metals. ► Low-energy ion bombarded bacteria held in different sample holders. ► Bacteria held in metal holder had higher mutation rate than in plastic holder. ► Ion-beam-induced X-ray from biological sample is not a basic mutation source. -- Abstract: Low-energy ion beam biotechnology has achieved tremendous successes in inducing crop mutation and gene transfer. However, mechanisms involved in the related processes are not yet well understood. In ion-beam-induced mutation, ion-bombardment-produced X-ray has been proposed to be one of the secondary mutation sources, but the speculation has not yet been experimentally tested. We carried out this investigation to test whether the low-energy ion-beam-produced X-ray was a source of ion-beam-induced mutation. In the investigation, X-ray emission from 29-keV nitrogen- or argon- ion beam bombarded bacterial Escherichia coli (E. coli) cells held in a metal or plastic sample holder was in situ detected using a highly sensitive X-ray detector. The ion beam bombarded bacterial cells held in different material holders were observed for mutation induction. The results led to a conclusion that secondary X-ray emitted from ion-beam-bombarded biological living materials themselves was not a, or at least a negligible, mutational source, but the ion-beam-induced X-ray emission from the metal that made the sample holder could be a source of mutation

  14. Is low-energy-ion bombardment generated X-ray emission a secondary mutational source to ion-beam-induced genetic mutation?

    Energy Technology Data Exchange (ETDEWEB)

    Thongkumkoon, P. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Prakrajang, K. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Faculty of Science, Maejo University, Chiang Mai 50290 (Thailand); Thopan, P.; Yaopromsiri, C. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Suwannakachorn, D. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Yu, L.D., E-mail: yuld@fnrf.science.cmu.ac.th [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand)

    2013-07-15

    Highlights: ► Detected X-ray emission from metal, plastic and biological samples. ► Characteristic X-ray emission was detected from metal but not from non-metals. ► Low-energy ion bombarded bacteria held in different sample holders. ► Bacteria held in metal holder had higher mutation rate than in plastic holder. ► Ion-beam-induced X-ray from biological sample is not a basic mutation source. -- Abstract: Low-energy ion beam biotechnology has achieved tremendous successes in inducing crop mutation and gene transfer. However, mechanisms involved in the related processes are not yet well understood. In ion-beam-induced mutation, ion-bombardment-produced X-ray has been proposed to be one of the secondary mutation sources, but the speculation has not yet been experimentally tested. We carried out this investigation to test whether the low-energy ion-beam-produced X-ray was a source of ion-beam-induced mutation. In the investigation, X-ray emission from 29-keV nitrogen- or argon- ion beam bombarded bacterial Escherichia coli (E. coli) cells held in a metal or plastic sample holder was in situ detected using a highly sensitive X-ray detector. The ion beam bombarded bacterial cells held in different material holders were observed for mutation induction. The results led to a conclusion that secondary X-ray emitted from ion-beam-bombarded biological living materials themselves was not a, or at least a negligible, mutational source, but the ion-beam-induced X-ray emission from the metal that made the sample holder could be a source of mutation.

  15. Improvement of root and tuber crops by induced mutations

    International Nuclear Information System (INIS)

    1987-03-01

    The aim of the FAO/IAEA Co-ordinated Research Programme is to breed cultivars which are more productive, more resistant to diseases and pests and which have better quality. Two Research Co-ordination Meetings in this programme were convened. They reviewed in detail the status and breeding research needs of the major root and tuber crops and other vegetatively propagated corps, viz. cassava, yam, sweet potato, potato and sugar cane. The participants presented their research achievements and difficulties, exchanged information, co-ordinated their future research and made recommendations

  16. Neutron-induced mutation experiments. Comprehensive report, March 1, 1977-August 31, 1980

    International Nuclear Information System (INIS)

    Abrahamson, S.

    1981-02-01

    Neutron-induced X-linked lethal mutations were induced in Drosophila melanogaster oogonia at energies of .43, .66, 2, and 6 MeV. The 37 irradiations were carried out at the RARAF facility at Brookhaven National Laboratory. RBE's (relative to x-ray data similarly collected) were calculated to be .43 MeV to 4.8; .66 MeV to 4.0; 2 MeV to 3.2; and 6 MeV to 2.9. The dose/frequency response curves for all energies best fit a linear rather than a linear-quadratic model following regression analyses. Control data for specific locus mutations (420,000 tests) were gathered. This data, combined with other data (both X-linked lethal and specific locus) has been used to estimate the number of loci on the X-chromosome of Drosophila which can mutate to recessive lethals

  17. Kinetics of gene and chromosome mutations induced by UV-C in yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Koltovaya, N.; Kokoreva, A.; Senchenko, D.; Shvaneva, N.; Zhuchkina, N.

    2017-01-01

    The systematic study of the kinetics of UV-induced gene and structural mutations in eukaryotic cells was carried out on the basis of model yeast S. cerevisiae. A variety of genetic assays (all types of base pair substitutions, frameshifts, forward mutations canl, chromosomal and plasmid rearrangements) in haploid strains were used. Yeast cells were treated by UV-C light of fluence of energy up to 200 J/m 2 . The kinetics of the induced gene and structural mutations is represented by a linear-quadratic and exponential functions. The slope of curves in log-log plots was not constant, had the value 2-4 and depended on the interval of doses. It was suggested that it is the superposition and dynamics of different pathways form the mutagenic responses of eukaryotic cells to UV-C light that cause the high-order curves. [ru

  18. Research highlights on: the use of induced mutations for plant improvement in Malaysia

    International Nuclear Information System (INIS)

    1998-01-01

    Nuclear techniques play an increasingly valuable role in agricultural research and development. The collaborative work of IAEA and FAO has been instrumental to the progress. The nuclear techniques are now used in a wide range of applications including crop improvement. In the initial years, many plant breeders had difficulty in believing that induced mutations through radiation had any relevance to their conventional procedures. But attitudes have greatly changed, in great part due to the Joint Division's programmes. The result was a high number of improved new varieties bred to date with the help of induced mutations, including some in this country. This publication is intended primarily to gather and put in order all information on the research and work on the use of induced mutations for plant breeding in the country. Its main purpose is to see if ensuing research efforts could be better coordinated, focused and enhanced in order to supplement the plant improvement programmes in the country. The task of collating the relevant information was not without difficulty since many of the work had been carried out long time ago; their objectives generally were quite broad; and the results essentially not published, with some exceptions. Section I begins with thefntroduction, giving a brief account of the developments of induced mutations in Malaysia, the facilities available in various institutions and the role played by the National Committee on the Use of Mutations in Plant Breeding. The collaborative efforts of IAEA and IFNCC are also briefly described here, together with all the activates which they had supported in the past. Section 11 briefly describes the induced mutations and how they are produced and utilised in the plant improvement programmes, taking into consideration the safety precautions required, and the requirements of different crop species. Section III describes in greater details all the research that had been carried out in the country. The

  19. Gamma radiation-induced heritable mutations at repetitive DNA loci in out-bred mice

    International Nuclear Information System (INIS)

    Somers, C.M.; Sharma, R.; Quinn, J.S.; Boreham, D.R.

    2004-01-01

    Recent studies have shown that expanded-simple-tandem-repeat (ESTR) DNA loci are efficient genetic markers for detecting radiation-induced germ line mutations in mice. Dose responses following irradiation, however, have only been characterized in a small number of inbred mouse strains, and no studies have applied Esters to examine potential modifiers of radiation risk, such as adaptive response. We gamma-irradiated groups of male out-bred Swiss-Webster mice with single acute doses of 0.5 and 1.0 Gy, and compared germ line mutation rates at ESTR loci to a sham-irradiated control. To test for evidence of adaptive response we treated a third group with a total dose of 1.1 Gy that was fractionated into a 0.1 Gy adapting dose, followed by a challenge dose of 1.0 Gy 24 h later. Paternal mutation rates were significantly elevated above the control in the 0.5 Gy (2.8-fold) and 1.0 Gy (3.0-fold) groups, but were similar to each other despite the difference in radiation dose. The doubling dose for paternal mutation induction was 0.26 Gy (95% CI = 0.14-0.51 Gy). Males adapted with a 0.1 Gy dose prior to a 1.0 Gy challenge dose had mutation rates that were not significantly elevated above the control, and were 43% reduced compared to those receiving single doses. We conclude that pre-meiotic male germ cells in out-bred Swiss-Webster mice are sensitive to ESTR mutations induced by acute doses of ionizing radiation, but mutation induction may become saturated at a lower dose than in some strains of inbred mice. Reduced mutation rates in the adapted group provide intriguing evidence for suppression of ESTR mutations in the male germline through adaptive response. Repetitive DNA markers may be useful tools for exploration of biological factors affecting the probability of heritable mutations caused by low-dose ionizing radiation exposure. The biological significance of ESTR mutations in terms of radiation risk assessment, however, is still undetermined

  20. Mutated N-ras does not induce p19 arf in CO25 cell line | Saleh ...

    African Journals Online (AJOL)

    The mouse cell line (CO25) used in this study was transfected with a glucocorticoid inducible mutated human N-ras oncogene under transcriptional control of the steroid-sensitive promoter of the mouse mammary tumors virus long terminal repeat MMTV-LTR. This study was aimed to investigate the expression of p19arf and ...

  1. Collateral damage: Spread of repeat-induced point mutation from a ...

    Indian Academy of Sciences (India)

    2004-10-16

    Oct 16, 2004 ... Home; Journals; Journal of Biosciences; Volume 30; Issue 1. Collateral damage: Spread of repeat-induced point mutation from a duplicated DNA sequence into an adjoining single-copy gene in Neurospora crassa. Meenal Vyas Durgadas P Kasbekar. Volume 30 Issue 1 February 2005 pp 15-20 ...

  2. Advances in improvement of stress tolerance by induced mutation and genetic transformation in alfalfa

    International Nuclear Information System (INIS)

    Huang Xin; Ye Hongxia; Shu Xiaoli; Wu Dianxing

    2008-01-01

    In order to provide references for stress-tolerant breeding of alfalfa, genetic basis of stress-tolerant traits was briefly introduced and advanced in improvement of stress-tolerance by induced mutation and genetic transformation in alfalfa were reviewed. (authors)

  3. Induced mutations in beans and peas for resistance to rust

    International Nuclear Information System (INIS)

    Fadl, F.A.M.

    1983-01-01

    Gamma rays and ethyl methanesulphonate (EMS) were applied in a mutation-induction programme for rust resistance in bean and pea. Bean and pea seeds were pre-soaked 2 hours before irradiation with 9, 10 and 12 krad. For chemical mutagen treatments bean and pea seeds were pre-soaked for 8 hours and treated with 0.5 and 1.5% EMS for four hours. M 2 seeds of beans and peas were planted in 1979. Resistant M 2 plants were selected for their rust resistance and other morphological characters. M 3 seeds of selected plants were planted in 1980. In 1980 more seeds of the same varieties of beans and peas were treated with 0.1 and 0.3% EMS with the aim to produce rust-resistant mutants. Seed germination was reduced by gamma rays or EMS. Dwarf, malformed and abnormal plants were noticed. Some resistant M 2 plants selected gave high grain yields. Some were different in morphological characters. In the M 3 of selected plants various other mutant characters appeared, such as different height of plants, early and late flowering, resistance to powdery mildew in peas, altered grain yield, thickness of stem, pod shape and flower colour. (author)

  4. A shifting mutational landscape in 6 nutritional states: Stress-induced mutagenesis as a series of distinct stress input-mutation output relationships.

    Directory of Open Access Journals (Sweden)

    Ram P Maharjan

    2017-06-01

    Full Text Available Environmental stresses increase genetic variation in bacteria, plants, and human cancer cells. The linkage between various environments and mutational outcomes has not been systematically investigated, however. Here, we established the influence of nutritional stresses commonly found in the biosphere (carbon, phosphate, nitrogen, oxygen, or iron limitation on both the rate and spectrum of mutations in Escherichia coli. We found that each limitation was associated with a remarkably distinct mutational profile. Overall mutation rates were not always elevated, and nitrogen, iron, and oxygen limitation resulted in major spectral changes but no net increase in rate. Our results thus suggest that stress-induced mutagenesis is a diverse series of stress input-mutation output linkages that is distinct in every condition. Environment-specific spectra resulted in the differential emergence of traits needing particular mutations in these settings. Mutations requiring transpositions were highest under iron and oxygen limitation, whereas base-pair substitutions and indels were highest under phosphate limitation. The unexpected diversity of input-output effects explains some important phenomena in the mutational biases of evolving genomes. The prevalence of bacterial insertion sequence transpositions in the mammalian gut or in anaerobically stored cultures is due to environmentally determined mutation availability. Likewise, the much-discussed genomic bias towards transition base substitutions in evolving genomes can now be explained as an environment-specific output. Altogether, our conclusion is that environments influence genetic variation as well as selection.

  5. A shifting mutational landscape in 6 nutritional states: Stress-induced mutagenesis as a series of distinct stress input-mutation output relationships.

    Science.gov (United States)

    Maharjan, Ram P; Ferenci, Thomas

    2017-06-01

    Environmental stresses increase genetic variation in bacteria, plants, and human cancer cells. The linkage between various environments and mutational outcomes has not been systematically investigated, however. Here, we established the influence of nutritional stresses commonly found in the biosphere (carbon, phosphate, nitrogen, oxygen, or iron limitation) on both the rate and spectrum of mutations in Escherichia coli. We found that each limitation was associated with a remarkably distinct mutational profile. Overall mutation rates were not always elevated, and nitrogen, iron, and oxygen limitation resulted in major spectral changes but no net increase in rate. Our results thus suggest that stress-induced mutagenesis is a diverse series of stress input-mutation output linkages that is distinct in every condition. Environment-specific spectra resulted in the differential emergence of traits needing particular mutations in these settings. Mutations requiring transpositions were highest under iron and oxygen limitation, whereas base-pair substitutions and indels were highest under phosphate limitation. The unexpected diversity of input-output effects explains some important phenomena in the mutational biases of evolving genomes. The prevalence of bacterial insertion sequence transpositions in the mammalian gut or in anaerobically stored cultures is due to environmentally determined mutation availability. Likewise, the much-discussed genomic bias towards transition base substitutions in evolving genomes can now be explained as an environment-specific output. Altogether, our conclusion is that environments influence genetic variation as well as selection.

  6. Genomic mutation study for long-term cells induced by carbon ions

    International Nuclear Information System (INIS)

    Wang, X.; Furusawa, Y.; Suzuki, M.; Hirayama, R.; Matsumoto, Y.; Qin, Y.

    2007-01-01

    Complete text of publication follows. Objective: Densely ionizing (high LET) radiation can increase the relative biological effectiveness of cell and tissue. Astronauts in the space exploration have the potential exposure of chronic low-dose radiations in the field of low-flux galactic cosmic rays (GCR) and the subsequent biological effects have become one of the major concerns of space science. Furthermore, Heavy ions also are used new radiation therapy owing increased lethal effectiveness of high LET radiation. During radiation therapy, normal tissues also are exposed to ionizing radiation. Radiation can induce genomic mutation and instability in descendants of irradiated cells. Induction of genomic instability can represent one of the initiating steps leading to malignant transformation. Higher frequencies of mutation can be expected to provide higher rates of carcinogenicity with human exposure. Therefore, the study of radiation induced genomic mutation and instability is relevant to the estimates of the risk of secondary malignancies associated with radiation therapy and the carcinogenic effects of space environmental radiation. The hypoxanthine-guanine phosphoribosyltransferase (hprt) locus has been the most commonly used as a target gene for mutation detection studies. In this study, we investigated the generation expression dependence of mutation induction on HPRT locus in CHO cells irradiated with carbon ions. Methods: Chinese hamster ovary (CHO) cells were irradiated with graded doses of carbon ions (290MeV/u, LET:13kev/um) accelerated with Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences(NIRS). The survival effect of cells plated immediately after irradiation was measured with cell colony formation assay. After irradiation, cells were continues reseeding and cultures for lone-term proliferation. Cell samples were collected at 6, 12, 18, 24, 30, 37 and 44 days post irradiation. Mutation induction of cell

  7. Current status and outlook perspectives of induced mutations for plant improvement

    International Nuclear Information System (INIS)

    Liu Luxiang; Guo Huijun; Zhao Linshu; Li Junhui; Gu Jiayu; ZZhao Shirong; Wang Jing

    2009-01-01

    Since 1928, induced mutations have played a significant role in solving world food and nutritional security problems through mutant germplasm enhancement and new mutant variety development. According to incomplete statistics, up to September 2009, induced mutations have officially released 3088 mutant cultivars in more than 170 crop species by more than 60 countries in the world. China tanks the first in the world, which has have released 802 mutant cultivars in 45 crop species, and takes more than a quarter of the total number of mutant varieties in the FAO/IAEA database. The maximum annually accumulated planting area of the mutant varieties was 9 million hectares, with an additional increase of 1.5 billion kilograms to national output of grain, cotton, oil, being converted to social and economic benefits of more than 2 billion RMB. The recent development and application of accelerator ion beam irradiation, the spaceflight environment and the other new mutation means, as well as the effective use of traditional radiation mutagenesis are becoming more active in crop improvement and new gene discovery. The advent of plant genomics and high throughput DNA techniques, such as TILLING, have opened a new era of molecular mutation breeding, which will overcome the limitations of conventional mutation breeding and play a significant role in solving China and world food security. (authors)

  8. Induced mutations for disease resistance in wheat and field beans

    International Nuclear Information System (INIS)

    Abdel-Hak, T.M.; Kamel, A.H.

    1976-01-01

    Wheat disease in Egypt is reviewed and results of mutation breeding by γ irradiation for disease resistance in wheat and field beans are described. Wheat mutants of the variety Giza 155 resistant to leaf rust, Giza 156 resistant to both leaf and yellow rusts, and Tosson with a reasonable level of combined resistance to the three rusts in addition to mutants of the tetraploid variety Dakar 52 with a good level of stem and yellow rust resistance are required. Their seeds were subjected to 10, 15 and 20 krad. Of 3000-3700 M 2 plants from each variety and dosage, 22 plants from both Giza 155 and Giza 156, although susceptible, showed a lower level of disease development. In 1975, M 3 families of these selected plants and 6000 plants from bulked material were grown from each variety and dosage at two locations. Simultaneously, an additional population consisting of 3000 mutagen-treated seeds was grown to have a reasonable chance of detecting mutants; 2 heads from each plant were harvested. These will be grown next season (1976) to make a population of 25,000-30,000 M 2 plants and screened to composite cultures of specific rusts. Vicia faba seeds of field bean varieties Giza 1, Giza 2 and Rebaya 40, equally susceptible to rust and chocolate spot, were subjected to 3, 5 and 7 krad of 60 Co gamma radiation and 800 M 1 plants were grown in 1972 per variety and dose. Up to this later growing season (M 3 ) no resistance was detected in M 3 plank

  9. The improvement of cisantana rice variety through induced mutation

    International Nuclear Information System (INIS)

    Mugiono; Lilik Harsanti; Azri Kusuma Dewi

    2009-01-01

    The continuous improvement for rice through breeding is necessary to obtain new varieties with good quality and quantity. Cisantana variety hairy tips could be improved by mutation breeding. Seeds of Cisantana variety was irradiated by gamma rays ( 60 Co) at doses of 0.10, 0.20 and 0.30 kGy respectively at the Center for Application of Isotope and Radiation (CAIR) - Batan, Pasar Jumat, Jakarta. There after the irradiated seeds were planted as M1 plants at the CAIR’S experiment field in the dry season of 2000. Selection was carried out at the M2 generation and stressed on early maturity and bald spike. This was done at the experiment field at Pusakanegara - Subang in the Wet season of 2001/2002. From this population 19 mutants having early maturity and bald spike lets were selected. Purification in the next generation obtained 10 mutants which were homogeneous and without segregation. From these 10 mutants two mutant lines Obs-1688/PsJ and Obs-1692/PsJ were further tested. These two mutant lines showed good productivity and adaptability when tested at several locations. The resistance test for brown plant hopper and bacterial leaf blight disease showed that these two mutant lines are resistant to biotype 1 and 2, and medium resistant to biotype 3 of brown plant hopper, and also resistant to strain 3 and medium resistant to strain IV of bacterial leaf blight disease. These two mutant lines have good rice quality and were gelatinous. The Obs-1688/PsJ and Obs-1692/PsJ mutant lines were released as new rice varieties by the Minister of Agriculture and officially address as Mira-1 at 2006 and Bestari at 2008, respectively. (author)

  10. Somatic mutations in stilbene estrogen-induced Syrian hamster kidney tumors identified by DNA fingerprinting

    Directory of Open Access Journals (Sweden)

    Roy Deodutta

    2004-01-01

    Full Text Available Abstract Kidney tumors from stilbene estrogen (diethylstilbestrol-treated Syrian hamsters were screened for somatic genetic alterations by Random Amplified Polymorphic DNA-polymerase chain-reaction (RAPD-PCR fingerprinting. Fingerprints from tumor tissue were generated by single arbitrary primers and compared with fingerprints for normal tissue from the same animal, as well as normal and tumor tissues from different animals. Sixty one of the arbitrary primers amplified 365 loci that contain approximately 476 kbp of the hamster genome. Among these amplified DNA fragments, 44 loci exhibited either qualitative or quantitative differences between the tumor tissues and normal kidney tissues. RAPD-PCR loci showing decreased and increased intensities in tumor tissue DNA relative to control DNA indicate that loci have undergone allelic losses and gains, respectively, in the stilbene estrogen-induced tumor cell genome. The presence or absence of the amplified DNA fragments indicate homozygous insertions or deletions in the kidney tumor DNA compared to the age-matched normal kidney tissue DNA. Seven of 44 mutated loci also were present in the kidney tissues adjacent to tumors (free of macroscopic tumors. The presence of mutated loci in uninvolved (non-tumor surrounding tissue adjacent to tumors from stilbene estrogen-treated hamsters suggests that these mutations occurred in the early stages of carcinogenesis. The cloning and sequencing of RAPD amplified loci revealed that one mutated locus had significant sequence similarity with the hamster Cyp1A1 gene. The results show the ability of RAPD-PCR to detect and isolate, in a single step, DNA sequences representing genetic alterations in stilbene estrogen-induced cancer cells, including losses of heterozygosity, and homozygous deletion and insertion mutations. RAPD-PCR provides an alternative molecular approach for studying cancer cytogenetics in stilbene estrogen-induced tumors in humans and experimental

  11. Studies on physically and chemically induced soybean mutations of high protein and oil content and their genetic pattern

    International Nuclear Information System (INIS)

    Qiu Ghengjian; Gao Shan

    1988-01-01

    In 1983, two different varieties were treated with five doses of fast neutrons and two concentrations of ethyl methane-sulphonate (EMS) in order to study the effects of different mutagens on the production of mutations with high protein and oil content. The experiment seems to show that EMS had a better effect in inducing such mutations. It showed not only a large variation in extent, but also a higher frequency of mutations. Fast neutrons could also induce mutations with high protein and oil content, but the rate was lower than for EMS. For high protein and oil content mutations induced by fast neutrons, the correlation between the M 2 and M 3 generations was unstable; it is difficult to forecast the protein and oil content of subsequent generations from seeds of the M 2 generation. The high protein and oil content mutations induced by EMS showed a high hereditary value in the M 2 and M 3 lines. The values of such parameters as hereditary variation, the hereditary variance coefficient, the hereditary capacity and the genetic advance of high protein content mutations were higher than those for high oil content mutations. Thus, it seems easier to induce mutations with high protein rather than high oil content. (author). 8 refs, 2 figs, 4 tabs

  12. UV-induced tandem double mutations in the trpA gene of E. coli

    International Nuclear Information System (INIS)

    Piechocki, R.; Langhammer, R.

    1980-01-01

    The ultraviolet light induction of tandem double mutations in a reverse mutation system was shown using trpA mutants which are characterized by the codon sequences GAA and AAG in codon position 211. Among 597 Trp + independent revertants of the trpA (AAG211) strain 3 full revertants were detected arising from UV-induced tandem double base exchanges. In the codon unit 211 full revertants due to single base exchanges are at least 20 times as frequent as full revertants due to tandem double base exchanges. (author)

  13. Herpesvirus telomerase RNA (vTR with a mutated template sequence abrogates herpesvirus-induced lymphomagenesis.

    Directory of Open Access Journals (Sweden)

    Benedikt B Kaufer

    2011-10-01

    Full Text Available Telomerase reverse transcriptase (TERT and telomerase RNA (TR represent the enzymatically active components of telomerase. In the complex, TR provides the template for the addition of telomeric repeats to telomeres, a protective structure at the end of linear chromosomes. Human TR with a mutation in the template region has been previously shown to inhibit proliferation of cancer cells in vitro. In this report, we examined the effects of a mutation in the template of a virus encoded TR (vTR on herpesvirus-induced tumorigenesis in vivo. For this purpose, we used the oncogenic avian herpesvirus Marek's disease virus (MDV as a natural virus-host model for lymphomagenesis. We generated recombinant MDV in which the vTR template sequence was mutated from AATCCCAATC to ATATATATAT (vAU5 by two-step Red-mediated mutagenesis. Recombinant viruses harboring the template mutation replicated with kinetics comparable to parental and revertant viruses in vitro. However, mutation of the vTR template sequence completely abrogated virus-induced tumor formation in vivo, although the virus was able to undergo low-level lytic replication. To confirm that the absence of tumors was dependent on the presence of mutant vTR in the telomerase complex, a second mutation was introduced in vAU5 that targeted the P6.1 stem loop, a conserved region essential for vTR-TERT interaction. Absence of vTR-AU5 from the telomerase complex restored virus-induced lymphoma formation. To test if the attenuated vAU5 could be used as an effective vaccine against MDV, we performed vaccination-challenge studies and determined that vaccination with vAU5 completely protected chickens from lethal challenge with highly virulent MDV. Taken together, our results demonstrate 1 that mutation of the vTR template sequence can completely abrogate virus-induced tumorigenesis, likely by the inhibition of cancer cell proliferation, and 2 that this strategy could be used to generate novel vaccine candidates

  14. Transformation and mutation of golden hamster embryo cells induced by low doses of x-rays

    International Nuclear Information System (INIS)

    Watanabe, M.; Suzuki, N.; Nikaido, O.

    1982-01-01

    A new cell system which makes quantitative analysis possible in both mutation and transformation induced by low doses of X-rays was described and the frequencies of both mutation and transformation were compared in relation to DNA repair which takes place in X-irradiated cells. Golden hamster embryo (GHE) cells were employed to show the availability of the system for the efficient detection of both mutants and transformants concomitantly. The mutation frequency of the cell population irradiated with various doses of X-rays was expressed as the ratio of the number of 8-azaguanine resistant colonies to the 10 5 colonies formed in normal medium. A linear increase in mutation frequency with increasing dose was observed at doses ranging from 100 to 600 rad. There was no significant increase in mutation frequency with doses below 100 rad. On the other hand, the transformation frequency of the cells was expressed as the ratio of the number of the transformed colonies to the total number of colonies counted. A drastic increase in the transformation frequency was observed when cells were irradiated with less than 100 rad of X-rays. DNA repair might be involved in modifying transformation frequency and survivals of GHE cells, and DNA synthesis might be involved in inducing transformation in GHE cells. It seems that the repair of potentially lethal damage taking place in density-inhibited GHE cells within 24 hours after X-irradiation decreases the frequencies of both transformation and mutation. Furthermore, it is evident that the system using GHE cells is sensitive enough to assess the transformational effect of low doses of X-rays. (Namekawa, K.)

  15. Induced mutations for the improvement of grain legumes in South East Asia (1975)

    International Nuclear Information System (INIS)

    1977-01-01

    The report is divided into seven sections containing papers on the following subjects: regional cooperation for improving grain legume production in South-East Asia and the role of FAO in this connection; national reports on the production and consumption of grain legumes (mainly beans, soybeans, peas, peanuts) in various Asian countries (separate reports for Pakistan, India, Sri Lanka, Bangladesh, Burma, Philippines, Indonesia, Papua New Guinea, Taiwan, and Australia). Specific papers are presented on the following: modifications of field pea; chickpea breeding at ICRISAT; mutation breeding in winged bean; mutation breeding in improving groundnut cultivars; and the consumption of grain legumes in Singapore. Finally, some conclusions and recommendations adopted by the participants of the meeting are presented

  16. Plant type improvement of indigenous rice cultivars through induced mutations

    International Nuclear Information System (INIS)

    Kihupi, A.

    1997-01-01

    A high yielding, locally adapted cultivar 'Afaa Mwanza 1/159' of rice (Oryza sativa L.) which is tall and late in maturity, was irradiated with gamma rays at doses of 170, 210 and 250 Gy to shorten plant height and time of maturity. Twelve mutants were selected, and evaluated for yield performance in field trials from M 6 to M 9 generations. All the mutants were shorter in plant height, and gave higher mean yield than the parent. Correlation coefficient analysis showed that the number of productive tillers, number of panicles per square meter and grain filling in the panicle were important characters which influenced yield. On the other hand, panicle length had negative influence on yield. Cv. 'Supa India' and 'Salama' were also irradiated with doses of 170, 210, 240 Gy gamma rays. Analysis of M 2 populations of these cultivars indicated that mutagenesis created a lot of variation in plant height, maturity, spikelet fertility and panicle length. The induced variation shall be useful in selecting desired plant types. (author). 16 refs, 12 tabs

  17. Induced Mutations Unleash the Potentials of Plant Genetic Resources for Food and Agriculture

    Directory of Open Access Journals (Sweden)

    Chikelu Mba

    2013-03-01

    Full Text Available The options for increasing food production by at least 70% over the next four decades so as to keep pace with a rapidly increasing human population are bedeviled by erratic climatic conditions, depleted arable lands, dwindling water resources and by the significant environmental and health costs for increasing the use of agrochemicals. Enhanced productivities through “smart” crop varieties that yield more with fewer inputs is a viable option. However, the genetic similarities amongst crop varieties—which render entire cropping systems vulnerable to the same stresses—coupled with unvarying parental materials limit the possibilities for uncovering novel alleles of genes and, hence, assembling new gene combinations to break yield plateaux and enhance resilience. Induced mutation unmasks novel alleles that are harnessed to breed superior crop varieties. The historical antecedents, theoretical and practical considerations, and the successes of induced mutations in crop improvement are reviewed along with how induced mutagenesis underpins plant functional genomics. The roles of cell and molecular biology techniques in enhancing the efficiencies for the induction, detection and deployment of mutation events are also reviewed. Also, the integration of phenomics into induced mutagenesis and the use of pre-breeding for facilitating the incorporation of mutants into crop improvement are advocated.

  18. Effects of smoke and tea on radiation-induced bone marrow cell mutation and marrow inhibition

    International Nuclear Information System (INIS)

    Gao Yong; Zhang Weiguang

    2004-01-01

    Objective: To provide scientific information for the prevention and treatment of the radiation damage by analyzing the effects of smoke and tea on radiation-induced bone marrow cell mutation and marrow inhibition. Methods: 7 group mice were exposed to smoke and/or tea and/or radiation respectively. There were also b blank control group and a cyclophosphamide positive control group. The frequencies of micronucleated polychromatic erythrocytes (MPCE), the ratio of polychromatic erythrocytes (PCE) to mature erythrocytes (RBC) in marrow, and the count of peripheral blood hemoleukocyte were observed. Results: The frequencies of MPCE in the groups irradiated with γ-rays were significantly higher than that in the blank control group (P<0.05 or 0.01). The smoke + radiation group's frequency was significantly higher than single radiation group (P<0.05). The ratios of PCE to RBC in the groups irradiated were significantly lower than that in the blank control group (P<0.01). The counts of peripheral blood hemoleukocyte in the groups irradiated were significantly lower than the blank control group (P<0.01). Conclusion: Radiation were able to cause marrow cell mutation and induce marrow inhibition. Smoke increases the effect of radiation-induced marrow cell mutation. Tea and smoke could not affect radiation-induced bone marrow inhibition

  19. Radiation-induced cell mutations as a function of dose rate

    International Nuclear Information System (INIS)

    Kiefer, J.

    1987-01-01

    A brief review of the data in the literature is presented and forms the background of the experimental data given by the author obtained with exponential long-term cultures of V79 hamster cells exposed over a period of up to 35 days to different dose rates of gamma radiation. The experimental results show that at a dose rate of 40 mGy/hour the number of induced mutations is reduced, - which is in agreement with literature data - , but a dose rate of less than 30 mGy/hour makes the induced mutations leap to a value clearly higher than those induced by acute irradiation. As in addition to the mutations recombination is a significant factor of the radiation risk, experiments with a heterozygotic yeast strain have been made, as there is to date no reliable mammalian cell system available for this kind of research. Long-term radiation exposure of the yeast cells over a period of six weeks drastically increased the rate of recombinations, to a value higher by a factor of about 4 than that induced by acute irradiation. (orig.) [de

  20. RFLP analysis of rice semi-dwarf mutation induced by high energy argon ion radiation

    International Nuclear Information System (INIS)

    Zhuang Chuxiong; Hu Weimin; Mei Mantong

    1997-01-01

    Two Indica rice varieties, Bianpizhan and Xiangzhan, and their semi-dwarf mutants induced by high energy argon ion radiation, Ar-10, and Xiang-Ar-1, were examined with restriction fragment length polymorphism (RFLP) analysis by using 97 rice single copy genomic clones mapped on 12 chromosomes of molecular genetic map, combined with 5 restriction enzymes. Among the markers screened, 9 detected polymorphism were between Bianpizhen and Ar-10, and 11 detected polymorphism were between Xiangzhan and Xiang-Ar-1. Moreover, two or more restriction enzymes could generate RFLP patterns when screened with a given marker for several polymorphic markers. Based on the polymorphic allelic loci, the mutation frequencies were estimated as 5.15% and 6.39% for Ar-10 and Xiang-Ar-1 respectively. These results suggested that the nature of mutation on the DNA level was probably large genetic changes rather than point mutation. Genetic analysis and gene tagging of semi-dwarf mutation in one of the mutant line, Ar-10, indicated that this mutation was controlled by a major recessive gene, which was preliminary located on chromosome 4

  1. RFLP Analysis of rice semi dwarf mutation induced by high energy argon ion radiation

    International Nuclear Information System (INIS)

    Zhuang Chuxiong; Hu Weimin; Mei Mantong

    1997-01-01

    Two Indica rice varieties, Bianpizhan and Xiangzhan, and their semi dwarf mutants induced by high energy argon ion radiation, Ar 10, and Xiang Ar 1, were examined with restriction fragment length polymorphism(RFLP)analysis by using 97 rice single copy genomic clones mapped on 12 chromosomes of molecular genetic map, combined with 5 restriction enzymes.Among the markers screened, 9 detected polymorphism were between Bianpizhan and Ar 10, and 11 detected polymorphism were between Xiangzhan and Xiang Ar 1.Moreover, two or more restriction enzymes could generate RFLP patterns when screened with a given marker for several polymorphic markers. Based on the polymorphic allelic loci, the mutation frequencies were estimated as 5 15% and 6 39% for Ar 10 and Xiang Ar 1 respectively.These results suggested that the nature of mutation on the DNA level was probably large genetic changes rather than point mutation.Genetic analysis and gene tagging of semi dwarf mutation in one of the mutant line, Ar 10, indicated that this mutation was controlled by a major recessive gene, which was preliminary located on chromosome 4. (author)

  2. Male-fertility-restorer mutation induced by x-rays in wheat

    International Nuclear Information System (INIS)

    Sasaki, Mutsuo; Nakata, Noboru; Yasumuro, Yoshimasa

    1982-01-01

    Some male-fertility restoring mutants were obtained by X-irradiation (20 or 25 kR, 105.3 R/min) of the air-dried seed of cytoplasmic male-sterile (cms) wheat, (timopheevi)-Bison. These X-ray induced male-fertility restoring mutant (Rfx) lines restored the male fertility of F 1 hybrids with cms (timopheevi)-Bison as female, but their fertility-restoring ability was not superior to that of known restorers such as Gironde, Primepi, and (t)-H30. The Rfx lines were also different from the original (timopheevi)-Bison, in many characters. The study on these multicharacter mutations with 18 morphological and physiological characters of the 7 M 6 line groups derived from the 7M 2 plants, revealed that each M 2 progenitor plant of each M 6 line-group had the mutant genes for almost all these characters, and that the mutation for at least half of all these mutant genes was induced in the original cell of the gamates of each X-irradiated M 1 plant. Considering the multicharacter mutations of the Rfx lines, a backcross method for the mutation breeding of male-fertility restorers in wheat was proposed. (Kaihara, S.)

  3. X-ray-induced recessive lethal mutations in adult and foetal female mice

    International Nuclear Information System (INIS)

    Luening, K.G.; Eiche, A.

    1982-01-01

    Tests of X-ray-induced recessive lethal mutations in adult and foetal mouse females were performed. The tests were based on family analysis which provided a possibility of making a distinction between pre-existing recessive lethal mutations and newly arisen (spontaneous + induced) ones. The way the tests were carried out provided material for the estimation of the frequency of spontaneous lethal mutations per genome. The two different estimates from this material, 0.72 and 0.91%, respectively, are similar and fall within the range previously suggested by Luening. The difference, though statistically non-significant, between data from irradiated mature and maturing oocytes in adult females and material from the unirradiated part, indicates a mutation rate of 13 x 10 -5 per rad per gamete according to one estimate and 8-12 x 10 -5 according to the other in comparison with 9 x 10 -5 from irradiated spermatogonia. In the limited data obtained after foetal irradiation, there is no indication of oogonia and developing oocytes being more sensitive to irradiation than oocytes in adult females fertilized within 6 weeks of treatment. (orig.)

  4. Antagonism of proteasome inhibitor-induced heme oxygenase-1 expression by PINK1 mutation.

    Directory of Open Access Journals (Sweden)

    Xiang-Jun Sheng

    Full Text Available PTEN-induced putative kinase 1 (PINK1 is an integral protein in the mitochondrial membrane and maintains mitochondrial fidelity. Pathogenic mutations in PINK1 have been identified as a cause of early-onset autosomal recessive familial Parkinson's disease (PD. The ubiquitin proteasome pathway is associated with neurodegenerative diseases. In this study, we investigated whether mutations of PINK1 affects the cellular stress response following proteasome inhibition. Administration of MG132, a peptide aldehyde proteasome inhibitor, significantly increased the expression of heme oxygenase-1 (HO-1 in rat dopaminergic neurons in the substantia nigra and in the SH-SY5Y neuronal cell line. The induction of HO-1 expression by proteasome inhibition was reduced in PINK1 G309D mutant cells. MG132 increased the levels of HO-1 through the Akt, p38, and Nrf2 signaling pathways. Compared with the cells expressing WT-PINK1, the phosphorylation of Akt and p38 was lower in those cells expressing the PINK1 G309D mutant, which resulted in the inhibition of the nuclear translocation of Nrf2. Furthermore, MG132-induced neuronal death was enhanced by the PINK1 G309D mutation. In this study, we demonstrated that the G309D mutation impairs the neuroprotective function of PINK1 following proteasome inhibition, which may be related to the pathogenesis of PD.

  5. Development of radiation-induced mutation techniques and functional genomics studies

    International Nuclear Information System (INIS)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek

    2012-01-01

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative·structural·functional genomics studies for useful traits

  6. Analysis of mutations in the human HPRT gene induced by accelerated heavy-ion irradiation

    International Nuclear Information System (INIS)

    Kagawa, Yasuhiro; Yatagai, Fumio; Hanaoka, Fumio; Suzuki, Masao; Kase, Youko; Kobayashi, Akiko; Hirano, Masahiko; Kato, Takesi; Watanabe, Masami.

    1995-01-01

    Multiplex PCR analysis of HPRT(-) mutations in human embryo (HE) cells induced by 230 keV/μm carbon-ion irradiation showed no large deletion around the exon regions of the locus gene in contrast to the irradiations at different LETs. To identify these mutations, the sequence alterations in a cDNA of hprt gene were determined for 18 mutant clones in this study. Missing of exon 6 was the most frequent mutational event (10 clones), and missing of both exons 6 and 8 was next most frequent event (6 clones), then base substitutions (2 clones). These characteristics were not seen in a similar analysis of spontaneous mutations, which showed base substitution (5 clones), frameshift (2 clones), missing of both exons 2 and 3 (2 clones), and a single unidentified clone. Direct sequencing and restriction enzyme digestion of the genomic DNA of the mutants which showed missing of exons 6 and 8 in the cDNA, supports the possibility that they were induced by aberrant mRNA splicing. (author)

  7. Deficiency of the DNA repair protein nibrin increases the basal but not the radiation induced mutation frequency in vivo

    International Nuclear Information System (INIS)

    Wessendorf, Petra; Vijg, Jan; Nussenzweig, André; Digweed, Martin

    2014-01-01

    Highlights: • lacZ mutant frequencies measured in vivo in mouse models of radiosensitive Nijmegen Breakage Syndrome. • Spontaneous mutation frequencies are increased in lymphatic tissue due to Nbn mutation. • Single base transitions, not deletions, dominate the mutation spectrum. • Radiation induced mutation frequencies are not increased due to Nbn mutation. - Abstract: Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50. The complex is associated particularly with the repair of DNA double strand breaks and with the regulation of cell cycle check points. Hypomorphic mutation of components of the complex leads to human disorders characterised by radiosensitivity and increased tumour occurrence, particularly of the lymphatic system. We have examined here the relationship between DNA damage, mutation frequency and mutation spectrum in vitro and in vivo in mouse models carrying NBN mutations and a lacZ reporter plasmid. We find that NBN mutation leads to increased spontaneous DNA damage in fibroblasts in vitro and high basal mutation rates in lymphatic tissue of mice in vivo. The characteristic mutation spectrum is dominated by single base transitions rather than the deletions and complex rearrangements expected after abortive repair of DNA double strand breaks. We conclude that in the absence of wild type nibrin, the repair of spontaneous errors, presumably arising during DNA replication, makes a major contribution to the basal mutation rate. This applies also to cells heterozygous for an NBN null mutation. Mutation frequencies after irradiation in vivo were not increased in mice with nibrin mutations as might have been expected considering the radiosensitivity of NBS patient cells in vitro. Evidently apoptosis is efficient, even in the absence of wild type nibrin

  8. Age-related increase in the rate of spontaneou and γ-ray-induced hprt mutations in mouse spleen lymphocytes

    International Nuclear Information System (INIS)

    Gazlev, A.I.; Podlutskii, A.Ya.; Bradbury, R.

    1994-01-01

    Endogenous and exogenous factors continually afflict DNA of cells of organisms. A certain amount of the damage is accumulated causing mutations, increasing the risk of malignacies, impairing cell functions, and upsetting the body's homeostasis. The research reported here studies the rates of spontaneous hprt nmutationsand those induced you ggammairradiation in the splenocytes of mice at various ages. The rate of spontaneous and induced hprt gene mutations increases with aging. In gamma irradiated mice the rate of radiation-induced mutations depended on the absorbed dose and age, with the rate 2.3-3.0 fold higher in 104-110 week old mice than in younger pups. 15 refs., 1 tab

  9. Somatic mutation and recombination induced with reactor thermal neutrons in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Zambrano A, F.; Guzman R, J.; Paredes G, L.; Delfin L, A.

    1997-01-01

    The SMART test of Drosophila melanogaster was used to quantify the effect over the somatic mutation and recombination induced by thermal and fast neutrons at the TRIGA Mark III reactor of the ININ at the power of 300 k W for times of 30, 60 and 120 minutes with total equivalent doses respectively of 20.8, 41.6 and 83.2 Sv. A linear relation between the radiation equivalent dose and the frequency of the genetic effects such as mutation and recombination was observed. The obtained results allow to conclude that SMART is a sensitive system to the induced damage by neutrons, so this can be used for studying its biological effects. (Author)

  10. Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Sligh, James [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Janda, Jaroslav [University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Jandova, Jana, E-mail: jjandova@email.arizona.edu [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States)

    2014-11-15

    Highlights: • Alterations in mitochondrial DNA are commonly found in various human cancers. • Mutations in BALB mitochondrial DNA induce up-regulation of chemokine CCL20. • Increased growth and motility of mtBALB cells is associated with CCL20 levels. • mtDNA changes in BALB induce in vivo tumor growth through CCL20 up-regulation. • Mutations in mitochondrial DNA play important roles in keratinocyte neoplasia. - Abstract: mtDNA mutations are common in human cancers and are thought to contribute to the process of neoplasia. We examined the role of mtDNA mutations in skin cancer by generating fibroblast cybrids harboring a mutation in the gene encoding the mitochondrial tRNA for arginine. This somatic mutation (9821insA) was previously reported in UV-induced hyperkeratotic skin tumors in hairless mice and confers specific tumorigenic phenotypes to mutant cybrids. Microarray analysis revealed and RT-PCR along with Western blot analysis confirmed the up-regulation of CCL20 and its receptor CCR6 in mtBALB haplotype containing the mt-Tr 9821insA allele compared to wild type mtB6 haplotype. Based on reported role of CCL20 in cancer progression we examined whether the hyper-proliferation and enhanced motility of mtBALB haplotype would be associated with CCL20 levels. Treatment of both genotypes with recombinant CCL20 (rmCCL20) resulted in enhanced growth and motility of mtB6 cybrids. Furthermore, the acquired somatic alteration increased the in vivo tumor growth of mtBALB cybrids through the up-regulation of CCL20 since neutralizing antibody significantly decreased in vivo tumor growth of these cells; and tumors from anti-CCL20 treated mice injected with mtBALB cybrids showed significantly decreased CCL20 levels. When rmCCL20 or mtBALB cybrids were used as chemotactic stimuli, mtB6 cybrids showed increased motility while anti-CCL20 antibody decreased the migration and in vivo tumor growth of mtBALB cybrids. Moreover, the inhibitors of MAPK signaling and NF

  11. Generation and Characterization of Induced Pluripotent Stem Cells from Patients with mtDNA Mutations.

    Science.gov (United States)

    Hämäläinen, Riikka H; Suomalainen, Anu

    2016-01-01

    Generation of induced pluripotent stem cells from patient cells has revolutionized disease modeling in recent years. One research area, where disease models have previously been scarce, is disorders with mutations in mitochondrial DNA. These are a common cause for human disease and often cause very tissue specific phenotypes with vast clinical heterogeneity. iPS technology has now opened up new possibilities for mechanistic studies of these diseases.

  12. Radiation-Induced Germ Cell Mutations-Their Detection and Modification.

    Science.gov (United States)

    1987-06-30

    and mating. 0 Female mice were hormonally stimulated to ovulate according to schedule. Two days before mating they were injected with Pregnant Mares ...induction kinetics and therefore data must be accumulated at several doses. The doubling dose (the dose to induce twice the background mutation frequency...possible. The female mouse has a maximum of about 900 oocytes three days after birth after which they steadily decline by random atresia and ovulation (56

  13. Comparative study on germ cell mutation induced by urethane (ethyl carbamate) gas and X-rays in drosophila melanogaster

    International Nuclear Information System (INIS)

    Nomura, Taisei; Kurokawa, Nobuo

    1997-01-01

    Although its mutagenicity has not been confirmed in mouse germ cells, urethane (ethyl carbamate) gas induces a significant increase of X-linked recessive lethal mutations in the germ cells of Drosophila melanogaster. The mutation frequency increased as the exposure time was changed from 3.5 to 5.5 h. Mutations were also induced by X-rays (20 to 40 Gy) and N-methyl-N-nitrosourea (MNU) (0.06 to 0.10%). However, no significant increase of chromosomal changes (partial loss of the Y chromosome, total loss of X or Y, and translocations) was produced by urethane, although these were readily induced by X-rays. There were large and significant increases in chromosomal changes caused by X-rays (20 Gy) compared to urethane (5.5 h) or MNU (0.06%). In contrast, there were no substantial differences among these three treatments as regards recessive lethal mutations. Urethane-induced DNA lesions detected as recessive lethals appear to be intragenic mutations. Complementation analysis with 15 reference single-site loci (cistrons) in the zeste-white region of the X chromosome revealed that 29 of 723 urethane-induced recessive lethals were located in the zeste-white region and all were restricted to a single locus. However, among 28 of 890 X-ray-induced lethals, 2 were non-complementary to 2 or 3 adjacent loci, indicating deletions encompassing 2 or 3 loci. In addition, 3 of these lethal chromosomes included mutations outside the zeste-white region. Another difference between urethane and X-rays was in the distribution of mutation sites. Urethane-induced mutations were strikingly non-random with two hot spots at zw-1 and zw-2, whereas the distribution of X-ray-induced mutations was more nearly random. (author)

  14. X-ray-induced bystander response reduce spontaneous mutations in V79 cells

    International Nuclear Information System (INIS)

    Maeda, Munetoshi; Kobayashi, Katsumi; Matsumoto, Hideki; Usami, Noriko; Tomiya, Masanori

    2013-01-01

    The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm 2 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10 -5 (background level), and the frequency decreased to 5.3 × 10 -6 with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations. (author)

  15. Evolution of high yielding chickpea varieties, having improved plant type and disease resistance, through induced mutations

    International Nuclear Information System (INIS)

    Sadiq, M.; Hussan, M.; Haq, M.A.

    1989-01-01

    The breeding programme on the use of induced mutations, in chickpea for genetic variability for better plant type, grain yield and disease resistance has been started. The chickpea mutant variety is one of the leading varieties being extensively grown throughout Pakistan and has played its role in stabilizing the chickpea production in the country. Four chickpea varieties were treated, each with two dosed of gamma rays. The main purpose of the mutagenic treatment of these varieties/cultivars, was induce multiple resistance. (A.B.)

  16. Meeting

    Indian Academy of Sciences (India)

    At the invitation of the Physical Research. Laboratory, the 58th Annual Meeting of the. Academy was held at Ahmedabad from 6 to 9. November 1992. The meetings were held at the. Physical Research Laboratory (PRL) and the. Space Applications Centre (SAC) and were organized by PRl, in cooperation with ~AC, the.

  17. X-ray-induced mutations in Escherichia coli K-12 strains with altered DNA polymerase I activities

    International Nuclear Information System (INIS)

    Nagata, Yuki; Kawata, Masakado; Komura, Jun-ichiro; Ono, Tetsuya; Yamamoto, Kazuo

    2003-01-01

    Spectra of ionizing radiation mutagenesis were determined by sequencing X-ray-induced endogenous tonB gene mutations in Escherichia coli polA strains. We used two polA alleles, the polA1 mutation, defective for Klenow domain, and the polA107 mutation, defective for flap domain. We demonstrated that irradiation of 75 and 50 Gy X-rays could induce 3.8- and 2.6-fold more of tonB mutation in polA1 and polA107 strains, respectively, than spontaneous level. The radiation induced spectrum of 51 tonB mutations in polA1 and 51 in polA107 indicated that minus frameshift, A:T→T:A transversion and G:C→T:A transversion were the types of mutations increased. Previously, we have reported essentially the same X-ray-induced tonB mutation spectra in the wild-type strain. These results indicate that (1) X-rays can induce minus frameshift, A:T→T:A transversion and G:C→T:A transversion in E. coli and (2) presence or absence of polymerase I (PolI) of E. coli does not have any effects on the process of X-ray mutagenesis

  18. Application of Induced Mutation by Using Gamma Ray Treatment in Study Breeding for Orchid (Phalaenopsis) Varieties

    International Nuclear Information System (INIS)

    Do Khac Thinh; Nguyen Thanh Huyen; Pham Duc Tuan; Ngo Thi Bich

    2011-01-01

    Aim to breed new orchid varieties adapted to climate of Vietnam for domestic use and export, national orchid breeding program has been established for some years. In our study, application of induced mutation by using 60 Co. gamma ray treatment was set up to breed new varieties of Phalaenopsis orchid. Different dosages of 60 Co. gamma rays were 0, 20, 40, 60, 100 Gy doses with dose rate of 90 Gy/h. Three years after radiation treatment, result showed that the use of 60 Co. gamma rays for treatment had conspicuously influenced to growth, mutation frequencies in morphological and physiological traits of Phalaenopsis varieties. Survival rate and growth vigor of treated plants reduced while total variation ratio increased by higher doses. The useful variations were the highest in 20 Gy and next to 40 Gy radiation treatments. In this study, LD 50 dose in radiation treatment for Phalaenopsis orchid variety was at dose 40 Gy. Suitable doses in radiation treatment which made wide diversity for Phalaenopsis orchid was at doses 20-40 Gy. At present, selected Phalaenopsis lines are being conducted to research segregating mutated traits, mutation frequencies in inbred Phalaenopsis lines and multiplication of promising mutant lines. (author)

  19. Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations.

    Science.gov (United States)

    Zhong, Ping; Hu, Zhixing; Jiang, Houbo; Yan, Zhen; Feng, Jian

    2017-05-02

    Locomotor symptoms in Parkinson's disease (PD) are accompanied by widespread oscillatory neuronal activities in basal ganglia. Here, we show that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents (sEPSCs) in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations, but not normal subjects. Overexpression of wild-type parkin, but not its PD-causing mutant, abolishes the oscillatory activities in patient neurons. Dopamine induces a delayed enhancement in the amplitude of spontaneous, but not miniature, EPSCs, thus increasing quantal content. The results suggest that presynaptic regulation of glutamatergic transmission by dopamine D1-class receptors is significantly potentiated by parkin mutations. The aberrant dopaminergic regulation of presynaptic glutamatergic transmission in patient-specific iPSC-derived midbrain neurons provides a mechanistic clue to PD pathophysiology, and it demonstrates the usefulness of this model system in understanding how mutations of parkin cause movement symptoms in Parkinson's disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Molecular cytogenetics of radiation-induced gene mutations in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Aleksandrov, I.D.; Aleksandrova, M.V.; Lapidus, I.L.; Karpovskij, A.L.

    1996-01-01

    The classical paradigm of spatially unrelated lesions for gene mutations and chromosomal exchange breakpoints induced by ionizing radiations in eukaryotic cells was re-examined in the experiments on the mapping of gamma-ray- or neutron-induced breakpoints in and outside of white (w) and vestigial (vg) genes of Drosophila melanogaster using the in situ hybridization of the large fragments of the genes under study with the polythene chromosomes of the relevant mutants. The results for the random sample of 60 inversion and translocation breakpoints analysed to date have shown that (i) 50% of them are mapped as the hot spots within big introns of both the genes, and (ii) 21 of 60 breaks (35%) are located outside of genes. It is important to note that 26% (16/60) of the breakpoints analysed are flanked by the deletions, the sizes of which vary from the quarter to a whole of the gene. It was found that the deletions flank both the inversion and translocation breakpoints and arise more often after action of neutrons than photons. An unexpectedly high frequency of the multiple-damaged w and vg mutants that have the gene/point mutation and additional, but separate, chromosome exchange (the so-called double- or triple-site mutants) has shown that the genetic danger of ionizing radiation is higher than usually accepted on the base of single gene/point mutation assessments. 11 refs., 3 figs

  1. Occurrence of mutations in the epidermal growth factor receptor gene in X-ray-induced rat lung tumors

    International Nuclear Information System (INIS)

    Kitahashi, Tsukasa; Takahashi, Mami; Yamada, Yutaka

    2008-01-01

    Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with amino acid substitution were observed in exons 18 and 21 (4/12, 33%), but no activating mutation of K-ras was detected. In addition, one and four silent mutations were identified in K-ras (exon 1) and Egfr (exons 18, 20 and 21), respectively. Most mutations in both Egfr and K-ras were G/C→A/T transitions (7/8, 88% and 31/34, 91%, respectively). Although, the mutational patterns in equivalent human lesions were not completely coincident, this first report of Egfr mutations in an experimental lung tumor model suggests that X-rays or other factors producing oxygen radicals could cause EGFR mutations in some proportion of lung cancers in humans. (author)

  2. Comparison of space flight and heavy ion radiation induced genomic/epigenomic mutations in rice (Oryza sativa)

    Science.gov (United States)

    Shi, Jinming; Lu, Weihong; Sun, Yeqing

    2014-04-01

    Rice seeds, after space flight and low dose heavy ion radiation treatment were cultured on ground. Leaves of the mature plants were obtained for examination of genomic/epigenomic mutations by using amplified fragment length polymorphism (AFLP) and methylation sensitive amplification polymorphism (MSAP) method, respectively. The mutation sites were identified by fragment recovery and sequencing. The heritability of the mutations was detected in the next generation. Results showed that both space flight and low dose heavy ion radiation can induce significant alterations on rice genome and epigenome (P < 0.05). For both genetic and epigenetic assays, while there was no significant difference in mutation rates and their ability to be inherited to the next generation, the site of mutations differed between the space flight and radiation treated groups. More than 50% of the mutation sites were shared by two radiation treated groups, radiated with different LET value and dose, while only about 20% of the mutation sites were shared by space flight group and radiation treated group. Moreover, in space flight group, we found that DNA methylation changes were more prone to occur on CNG sequence than CG sequence. Sequencing results proved that both space flight and heavy ion radiation induced mutations were widely spread on rice genome including coding region and repeated region. Our study described and compared the characters of space flight and low dose heavy ion radiation induced genomic/epigenomic mutations. Our data revealed the mechanisms of application of space environment for mutagenesis and crop breeding. Furthermore, this work implicated that the nature of mutations induced under space flight conditions may involve factors beyond ion radiation.

  3. Utilization of induced mutation techniques in rice improvement in the Philippines

    Energy Technology Data Exchange (ETDEWEB)

    Asencion, A.B.; Santos, I.S.; Barrida, A.C.; Medina, F.I.S. III [Philippine Nuclear Research Institute, Atomic Research Center (Philippines)

    2001-03-01

    Rice is one of the most important food crops in the Philippines, as such, efforts have been made consistently to improve the varieties released to the farmers for planting. Both conventional and induced mutation techniques were utilized to solve some of the problems. Varieties with improved qualities, resistance to pests and diseases, reduced height, early maturity and non-photoperiod sensitive were developed using either physical or chemical mutagen. Other methods were also tried to enhance variability like combination of gamma irradiation and biotechnology. Irradiation of F1 seeds was also initiated including the use of mutants in crosses to transfer their improved mutated characters. Promising selections were already tested and six lines from the F1 irradiation out-yielded both C4-63G and IR 1561-288-3, their parents. (author)

  4. Utilization of induced mutation techniques in rice improvement in the Philippines

    International Nuclear Information System (INIS)

    Asencion, A.B.; Santos, I.S.; Barrida, A.C.; Medina, F.I.S. III

    2001-01-01

    Rice is one of the most important food crops in the Philippines, as such, efforts have been made consistently to improve the varieties released to the farmers for planting. Both conventional and induced mutation techniques were utilized to solve some of the problems. Varieties with improved qualities, resistance to pests and diseases, reduced height, early maturity and non-photoperiod sensitive were developed using either physical or chemical mutagen. Other methods were also tried to enhance variability like combination of gamma irradiation and biotechnology. Irradiation of F1 seeds was also initiated including the use of mutants in crosses to transfer their improved mutated characters. Promising selections were already tested and six lines from the F1 irradiation out-yielded both C4-63G and IR 1561-288-3, their parents. (author)

  5. Detection of induced male germline mutation: Correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays

    International Nuclear Information System (INIS)

    Singer, Timothy M.; Lambert, Iain B.; Williams, Andrew; Douglas, George R.; Yauk, Carole L.

    2006-01-01

    Several rodent assays are capable of monitoring germline mutation. These include traditional assays, such as the dominant lethal (DL) assay, the morphological specific locus (SL) test and the heritable translocation (HT) assay, and two assays that have been developed more recently-the expanded simple tandem repeat (ESTR) and transgenic rodent (TGR) mutation assays. In this paper, we have compiled the limited amount of experimental data that are currently available to make conclusions regarding the comparative ability of the more recently developed assays to detect germline mutations induced by chemical and radiological agents. The data suggest that ESTR and TGR assays are generally comparable with SL in detecting germline mutagenicity induced by alkylating agents and radiation, though TGR offered less sensitivity than ESTR in some cases. The DL and HT assays detect clastogenic events and are most susceptible to mutations arising in post-spermatogonial cells, and they may not provide the best comparisons with TGR and ESTR instability. The measurement of induced ESTR instability represents a relatively sensitive method of identifying agents causing germline mutation in rodents, and may also be useful for bio-monitoring exposed individuals in the human population. Any future use of the TGR and ESTR germline mutation assays in a regulatory testing context will entail more robust and extensive characterization of assay performance. This will require substantially more data, including experiments measuring multiple endpoints, a greatly expanded database of chemical agents and a focus on characterizing stage-specific activity of mutagens in these assays, preferably by sampling epididymal sperm exposed at defined pre-meiotic, meiotic and post-meiotic stages of development

  6. Detection of induced male germline mutation: Correlations and comparisons between traditional germline mutation assays, transgenic rodent assays and expanded simple tandem repeat instability assays

    Energy Technology Data Exchange (ETDEWEB)

    Singer, Timothy M. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ont., K1S 5B6 (Canada); Lambert, Iain B. [Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ont., K1S 5B6 (Canada); Williams, Andrew [Biostatistics and Epidemiology Division, Safe Environments Programme, 6604B, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Douglas, George R. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada); Yauk, Carole L. [Mutagenesis Section, Environmental and Occupational Toxicology Division, Safe Environments Programme, 0803A, Health Canada, Ottawa, Ont., K1A 0K9 (Canada)]. E-mail: carole_yauk@hc-sc.gc.ca

    2006-06-25

    Several rodent assays are capable of monitoring germline mutation. These include traditional assays, such as the dominant lethal (DL) assay, the morphological specific locus (SL) test and the heritable translocation (HT) assay, and two assays that have been developed more recently-the expanded simple tandem repeat (ESTR) and transgenic rodent (TGR) mutation assays. In this paper, we have compiled the limited amount of experimental data that are currently available to make conclusions regarding the comparative ability of the more recently developed assays to detect germline mutations induced by chemical and radiological agents. The data suggest that ESTR and TGR assays are generally comparable with SL in detecting germline mutagenicity induced by alkylating agents and radiation, though TGR offered less sensitivity than ESTR in some cases. The DL and HT assays detect clastogenic events and are most susceptible to mutations arising in post-spermatogonial cells, and they may not provide the best comparisons with TGR and ESTR instability. The measurement of induced ESTR instability represents a relatively sensitive method of identifying agents causing germline mutation in rodents, and may also be useful for bio-monitoring exposed individuals in the human population. Any future use of the TGR and ESTR germline mutation assays in a regulatory testing context will entail more robust and extensive characterization of assay performance. This will require substantially more data, including experiments measuring multiple endpoints, a greatly expanded database of chemical agents and a focus on characterizing stage-specific activity of mutagens in these assays, preferably by sampling epididymal sperm exposed at defined pre-meiotic, meiotic and post-meiotic stages of development.

  7. Development of radiation-induced mutation techniques and functional genomics studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek [KAERI, Daejeon (Korea, Republic of); and others

    2012-01-15

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative{center_dot}structural{center_dot}functional genomics studies for useful traits.

  8. A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness

    Science.gov (United States)

    Bardien, Soraya; Human, Hannique; Harris, Tashneem; Hefke, Gwynneth; Veikondis, Rene; Schaaf, H Simon; van der Merwe, Lize; Greinwald, John H; Fagan, Johan; de Jong, Greetje

    2009-01-01

    Background South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB) in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population. Methods A multiplex method using the SNaPshot technique was used to screen for five mutations in the MT-RNR1 gene: A1555G, C1494T, T1095C, 961delT+C(n) and A827G. A total of 204 South African control samples, comprising 98 Mixed ancestry and 106 Black individuals were screened for the presence of the five mutations. Results A robust, cost-effective method was developed that detected the presence of all five sequence variants simultaneously. In this pilot study, the A1555G mutation was identified at a frequency of 0.9% in the Black control samples. The 961delT+C(n) variant was present in 6.6% of the Black controls and 2% of the Mixed ancestry controls. The T1095C, C1494T and A827G variants were not identified in any of the study participants. Conclusion The frequency of 0.9% for the A1555G mutation in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. Future larger studies are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. The high frequencies of the 961delT+C(n) variant observed in the controls suggest that this change is a common non-pathogenic polymorphism. This genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is important in a low-resource country like South Africa where, despite their adverse side-effects, aminoglycosides will continue to be used

  9. A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness

    Directory of Open Access Journals (Sweden)

    Greinwald John H

    2009-01-01

    Full Text Available Abstract Background South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population. Methods A multiplex method using the SNaPshot technique was used to screen for five mutations in the MT-RNR1 gene: A1555G, C1494T, T1095C, 961delT+C(n and A827G. A total of 204 South African control samples, comprising 98 Mixed ancestry and 106 Black individuals were screened for the presence of the five mutations. Results A robust, cost-effective method was developed that detected the presence of all five sequence variants simultaneously. In this pilot study, the A1555G mutation was identified at a frequency of 0.9% in the Black control samples. The 961delT+C(n variant was present in 6.6% of the Black controls and 2% of the Mixed ancestry controls. The T1095C, C1494T and A827G variants were not identified in any of the study participants. Conclusion The frequency of 0.9% for the A1555G mutation in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. Future larger studies are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. The high frequencies of the 961delT+C(n variant observed in the controls suggest that this change is a common non-pathogenic polymorphism. This genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is important in a low-resource country like South Africa where, despite their adverse side-effects, aminoglycosides will

  10. Repeat-Induced Point Mutation and Other Genome Defense Mechanisms in Fungi.

    Science.gov (United States)

    Gladyshev, Eugene

    2017-07-01

    Transposable elements have colonized the genomes of nearly all organisms, including fungi. Although transposable elements may sometimes provide beneficial functions to their hosts their overall impact is considered deleterious. As a result, the activity of transposable elements needs to be counterbalanced by the host genome defenses. In fungi, the primary genome defense mechanisms include repeat-induced point mutation (RIP) and methylation induced premeiotically, meiotic silencing by unpaired DNA, sex-induced silencing, cosuppression (also known as somatic quelling), and cotranscriptional RNA surveillance. Recent studies of the filamentous fungus Neurospora crassa have shown that the process of repeat recognition for RIP apparently involves interactions between coaligned double-stranded segments of chromosomal DNA. These studies have also shown that RIP can be mediated by the conserved pathway that establishes transcriptional (heterochromatic) silencing of repetitive DNA. In light of these new findings, RIP emerges as a specialized case of the general phenomenon of heterochromatic silencing of repetitive DNA.

  11. Molecular alterations underlying the spontaneous and γ-ray-induced point mutations at the white locus of Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Aleksandrova, M.V.; Lapidus, I.L.; Aleksandrov, I.D.; Karpovskij, A.L.

    1996-01-01

    The white locus in D.Melanogaster was selected as a target gene for the study of the mutational spectra of spontaneously arising and radiation-induced gene mutations in a whole organism. Analysis of 6 spontaneous and 73 γ-ray-induced white mutations by a combination of cytological, genetic and molecular techniques revealed that on the chromosomal and genetic levels all spontaneous mutations showed themselves to be point mutants. The share of such mutants among all heritable radiation-induced gene mutations is about 40%, whereas the rest ones are due to exchange breaks (8%) as well as multilocus, single-locus or partial-locus (intragenic) deletions (52%). The DNAs from 4 spontaneous and 17 γ-ray-induced point mutants were analysed by Southern blot-hybridization. The three spontaneous and 7 radiation mutants showed an altered DNA sequence at the left (distal) half of the white gene due to insertion or DNA rearrangement. The rest (58%) of the radiation-induced point mutations did not indicate any alternations in this part of the gene as detected by this technique and probes employed. 15 refs., 3 figs., 1 tab

  12. Hypothesizing an ancient Greek origin of the GJB2 35delG mutation: can science meet history?

    Science.gov (United States)

    Kokotas, Haris; Grigoriadou, Maria; Villamar, Manuela; Giannoulia-Karantana, Aglaia; del Castillo, Ignacio; Petersen, Michael B

    2010-04-01

    One specific mutation of the GJB2 gene that encodes the connexin 26 protein, the 35delG mutation, has become a major interest among scientists who focus on the genetics of nonsyndromic hearing loss. The mutation accounts for the majority of GJB2 mutations detected in Caucasian populations and represents one of the most frequent disease mutations identified so far. The debate was so far between the arguments whether or not the 35delG mutation constitutes a mutational hot-spot or a founder effect; however, it was recently clarified that the latter seems the most likely. In an attempt to explore the origin and propagation of the 35delG mutation, several groups have reported the prevalence of the mutation and the carrier rates in different populations worldwide. It is now certain that the theory of a common founder prevails and that the highest carrier frequencies of the 35delG mutation are observed in southern European populations, giving rise to a discussion regarding the origin of the 35delG mutation. In this study, we discuss data previously published by our and other groups and also compare the haplotype distribution of the mutation in southern Europe, trying to understand the pathways of science and history and the conflict between them.

  13. Genome-Wide Mutation Avalanches Induced in Diploid Yeast Cells by a Base Analog or an APOBEC Deaminase

    Science.gov (United States)

    Lada, Artem G.; Stepchenkova, Elena I.; Waisertreiger, Irina S. R.; Noskov, Vladimir N.; Dhar, Alok; Eudy, James D.; Boissy, Robert J.; Hirano, Masayuki; Rogozin, Igor B.; Pavlov, Youri I.

    2013-01-01

    Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP) or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis. PMID:24039593

  14. Modeling the induced mutation process in bacterial cells with defects in excision repair system

    Science.gov (United States)

    Bugay, A. N.; Vasilyeva, M. A.; Krasavin, E. A.; Parkhomenko, A. Yu.

    2015-12-01

    A mathematical model of the UV-induced mutation process in Escherichia coli cells with defects in the uvrA and polA genes has been developed. The model describes in detail the reaction kinetics for the excision repair system. The number of mismatches as a result of translesion synthesis is calculated for both wild-type and mutant cells. The effect of temporal modulation of the number of single-stranded DNA during postreplication repair has been predicted. A comparison of effectiveness of different repair systems has been conducted.

  15. Improvement of pulse crops through induced mutations: Reconstruction of plant type

    International Nuclear Information System (INIS)

    Rao, C.H.; Tickoo, J.L.; Ram, H.; Jain, H.K.

    1975-01-01

    Many species of grain legumes, because of their cultivation under marginal conditions for centuries, have retained a number of semi-wild characteristics, such as a bushy and spreading growth, which contribute to their adaptability but reduce their yields. The observations presented here indicate that induced mutations may prove effective in generating new plant-types in these crops, which are marked by an improvement in the harvest index and which will show a response to increased plant densities. The present report describes observations on the M 2 progenies of pigeon pea and mung bean on which work has been initiated. (author)

  16. Targeted mutations induced by a single acetylaminofluorene DNA adduct in mammalian cells and bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Moryia, M.; Takeshita, M.; Johnson, F.; Peden, K.; Will, S.; Grollman, A.P.

    1988-03-01

    Mutagenic specificity of 2-acetylaminofluorene (AAF) has been established in mammalian cells and several strains of bacteria by using a shuttle plasmid vector containing a single N-(deoxyguanosin-8-yl)acetylaminofluorene (C8-dG-AAF) adduct. The nucleotide sequence of the gene conferring tetracycline resistance was modified by conservative codon replacement so as to accommodate the sequence d(CCTTCGCTAC) flanked by two restriction sites, Bsm I and Xho I. The corresponding synthetic oligodeoxynucleotide underwent reaction with 2-(N-acetoxy-N-acetylamino)-fluorene (AAAF), forming a single dG-AAF adduct. This modified oligodeoxynucleotide was hybridized to its complementary strand and ligated between the Bsm I and Xho I sites of the vector. Plasmids containing the C8-dG-AAF adduct were used to transfect simian virus 40-transformed simian kidney (COS-1) cells and to transform several AB strains of Escherichia coli. Colonies containing mutant plasmides were detected by hybridization to /sup 32/P-labeled oligodeoxynucleotides. Presence of the single DNA adduct increased the mutation frequency by 8-fold in both COS cells and E. coli. Over 80% of mutations detected in both systems were targeted and represented G x C ..-->.. C x G or G x C ..-->.. T x A transversions or single nucleotide deletions. The authors conclude that modification of a deoxyguanosine residue with AAF preferentially induces mutations targeted at this site when a plasmid containing a single C8-dG-AAF adduct is introduced into mammalian cells or bacteria.

  17. Analysis of esterase isozyme and SSR for mutagenic progenies induced by space mutation in mustard

    International Nuclear Information System (INIS)

    Shen Jinjuan; Liu Yihua; Zhang Zhaorong; Ran Guangkui; Zhao Shouzhong; Xiao Li

    2012-01-01

    Seeds of five mustard (Brassica juncea Coss) varieties were carried into outer space by 'Shijian No.8' satellite. After five years' consecutive planting and selection, ten relatively stable mutant lines were obtained, which had significant variation in agronomic and economic characters. The mutant lines and their original varieties without space mutation treatment as control were studied by esterase isozyme and SSR analyses. Electrophoresis analysis of esterase isozymes indicated that there were differences between mutant lines and their controls in enzyme types and enzyme activity. Different mustard varieties had different enzymographs, and so did the mutants induced by space mutation, which shows different sensitivity among different mustard varieties. The SSR analysis showed that large differences were found in the SSR loci between mutant lines and their original variety, the variation frequency was between 9.52% and 57.14% with an average frequency of 26.19% for all the mutant lines. Among the mutant SSR loci, about 56.36% showed changes in band number and 43.64% in molecular weight. These results indicated that the ten mutant lines had large genetic difference in phenotype, genomic sequence and gene expression, and the outer space mutation would be an effective method to develop new mustard germplasm and variety. (authors)

  18. Inactivation and inducible oncogenic mutation of p53 in gene targeted pigs.

    Directory of Open Access Journals (Sweden)

    Simon Leuchs

    Full Text Available Mutation of the tumor suppressor p53 plays a major role in human carcinogenesis. Here we describe gene-targeted porcine mesenchymal stem cells (MSCs and live pigs carrying a latent TP53(R167H mutant allele, orthologous to oncogenic human mutant TP53(R175H and mouse Trp53(R172H, that can be activated by Cre recombination. MSCs carrying the latent TP53(R167H mutant allele were analyzed in vitro. Homozygous cells were p53 deficient, and on continued culture exhibited more rapid proliferation, anchorage independent growth, and resistance to the apoptosis-inducing chemotherapeutic drug doxorubicin, all characteristic of cellular transformation. Cre mediated recombination activated the latent TP53(R167H allele as predicted, and in homozygous cells expressed mutant p53-R167H protein at a level ten-fold greater than wild-type MSCs, consistent with the elevated levels found in human cancer cells. Gene targeted MSCs were used for nuclear transfer and fifteen viable piglets were produced carrying the latent TP53(R167H mutant allele in heterozygous form. These animals will allow study of p53 deficiency and expression of mutant p53-R167H to model human germline, or spontaneous somatic p53 mutation. This work represents the first inactivation and mutation of the gatekeeper tumor suppressor gene TP53 in a non-rodent mammal.

  19. The potential role of biotechnology and induced mutations in plant breeding

    International Nuclear Information System (INIS)

    Rubluo, A.; Brunner, I.; Palomino, G.; Rodriguez Garay, B.

    2001-01-01

    Although conventional techniques including mutation induction have increased the productivity of crops, the application of biotechnological tools such as tissue culture and molecular markers can speed up crop improvement. Through the application of in vitro culture techniques in Mammilaria san-angelensis, an ornamental cactus severely endangered, we proved through flow cytometry, genetic uniformity in massive in vitro derived plantlets and after irradiation we were able to regenerate it up to M1V4 generation. Solid mutants are expected if somatic embryos are treated with mutagenic agents due to its unicellular origin. Somatic embryogenesis was successfully achieved in Agave tequilana and after irradiation of embryogenic callus cultures, survivors were challenged with pathogenic crude bacterial extracts allowing the selection of resistant or tolerant individuals. Specially important are studies on neglected crops due to the interruption of its domestication and they are locally important for indigenous people as marginal crops. The trend now is to combine biotechnology and induced mutations to overcome problems with this highly promising crops. Chenopodium quinoa exhibits a strong constraint as food due to the undesirable production of saponins. The mutation induction strategy has enabled the reduction of this compounds in M5 generation, but further research is needed to overcome productivity and adaptability problems. Here the use of molecular markers (RAPDS) and flow cytometry techniques acquire relevance in the study of related species such as Chenopodium berlandieri in order to design an inter-specific breeding programme among selected mutants and outstanding local races to combine productivity, adaptability and grain quality

  20. The Pattern, Distribution of Induced Mutations in J. curcas Using Reduced Representation Sequencing

    Directory of Open Access Journals (Sweden)

    Fatemeh Maghuly

    2018-04-01

    Full Text Available Mutagenesis in combination with Genotyping by Sequencing (GBS is a powerful tool for introducing variation, studying gene function and identifying causal mutations underlying phenotypes of interest in crop plant genomes. About 400 million paired-end reads were obtained from 82 ethylmethane sulfonate (EMS induced mutants and 14 wild-type accessions of Jatropha curcas for the detection of Single Nucleotide Polymorphisms (SNPs and Insertion/Deletions (InDels by two different approaches (nGBS and ddGBS on an Illumina HiSeq 2000 sequencer. Using bioinformatics analyses, 1,452 induced SNPs and InDels were identified in coding regions, which were distributed across 995 genes. The predominantly observed mutations were G/C to A/T transitions (64%, while transversions were observed at a lower frequency (36%. Regarding the effect of mutations on gene function, 18% of the mutations were located in intergenic regions. In fact, mutants with the highest number of heterozygous SNPs were found in samples treated with 0.8% EMS for 3 h. Reconstruction of the metabolic pathways showed that in total 16 SNPs were located in six KEGG pathways by nGBS and two pathways by ddGBS. The most highly represented pathways were ether-lipid metabolism and glycerophospholipid metabolism, followed by starch and sucrose metabolism by nGBS and triterpenoid biosynthesis as well as steroid biosynthesis by ddGBS. Furthermore, high genome methylation was observed in J. curcas, which might help to understand the plasticity of the Jatropha genome in response to environmental factors. At last, the results showed that continuously vegetatively propagated tissue is a fast, efficient and accurate method to dissolve chimeras, especially for long-lived plants like J. curcas. Obtained data showed that allelic variations and in silico analyses of gene functions (gene function prediction, which control important traits, could be identified in mutant populations using nGBS and ddGBS. However, the

  1. Meeting

    Indian Academy of Sciences (India)

    The organization and arrangements for the scientific meetings, cultural event and the visits to Lothal and SAC were superb. The Academy is grateful to the Physical Research Laboratory particularly R K Varma, Director, PRL, to the. Institute for Plasma Research and its Director. P K Kaw, to the Space Applications Centre and.

  2. Meeting

    Indian Academy of Sciences (India)

    the Defence Minister, Government of India on some of his experiences in technology development in India. A summary of his lecture appears in this issue. In the afternoon the .... of steel armour for our Light Tank which has found wide application to meet the ... basic issues: how information is encoded in the structure of DNA ...

  3. Meeting

    Indian Academy of Sciences (India)

    1985-11-07

    Nov 7, 1985 ... Business Meeting of Fellows. Evening Lecture. Architecture of the universe- R Cowsik ... and technical capabilities to plan, design and build satellites for earth observations, such as. Bhaskara I and II have ... Water Resources Systems Planning-. Some case studies for India. Edited by. Mahesh C Chaturvedi ...

  4. Selective Breeding under Saline Stressed Conditions of Canola Mutations Induced by Gamma Rays

    International Nuclear Information System (INIS)

    Amer, I.M.; Moustafa, H.A.M.; Mansour, M.F.

    2009-01-01

    Mutation breeding program has been initiated for inducing canola mutations tolerance to saline stressed conditions for growing at harsh land in Egypt. Therefore, seed lots of three cultivars and exotic variety (Bactol, Serow 4, Serow 6 and Evita) were subjected to 100,400 and 600 Gy of gamma rays. Mass selection with 20 % intensity for high number of pods per plant has been done in each treatment in M2 generation. However, individually plants with high number of pods / plant were selected from each variety in M3 generation for test under saline stressed conditions at Ras Sudr region in M4 (8600 and 8300 ppm salinity for soil and irrigation, respectively). The obtained results revealed that eight mutated families from 12- test families in M4 generation surpassed their parents in seed yield / plant and related characters ( plant height ,fruiting zone length , No. of branches , No. of pods / plant ). In addition, the mutant F93 characterized by fast growing and non shuttering pods reflecting 50.4% over Evita control in seed yield/ plant. Twelve mutant lines in M5 represented the mutant families were grown in sandy-loam soil at Inshas region. The three mutant lines (L 22, L 38 and L 45) continuously surpassed their parents in seed yield and related characters, but the increases were less than the previous generation. The increase was 22.3 %, 38.7 % and 36.7 % over seed yield of respective parents. Moreover, mutant L66 exhibited an increase in its yield components in M5 at Inshas only, suggesting that gene expression and genomic structure extremely influenced by environmental factors. Genetic stability for the obtained mutations could be done at different environmental conditions in further studies

  5. On the effect of hyperaldosteronism-inducing mutations in Na/K pumps.

    Science.gov (United States)

    Meyer, Dylan J; Gatto, Craig; Artigas, Pablo

    2017-11-06

    Primary aldosteronism, a condition in which too much aldosterone is produced and that leads to hypertension, is often initiated by an aldosterone-producing adenoma within the zona glomerulosa of the adrenal cortex. Somatic mutations of ATP1A1, encoding the Na/K pump α1 subunit, have been found in these adenomas. It has been proposed that a passive inward current transported by several of these mutant pumps is a "gain-of-function" activity that produces membrane depolarization and concomitant increases in aldosterone production. Here, we investigate whether the inward current through mutant Na/K pumps is large enough to induce depolarization of the cells that harbor them. We first investigate inward currents induced by these mutations in Xenopus Na/K pumps expressed in Xenopus oocytes and find that these inward currents are similar in amplitude to wild-type outward Na/K pump currents. Subsequently, we perform a detailed functional evaluation of the human Na/K pump mutants L104R, delF100-L104, V332G, and EETA963S expressed in Xenopus oocytes. By combining two-electrode voltage clamp with [ 3 H]ouabain binding, we measure the turnover rate of these inward currents and compare it to the turnover rate for outward current through wild-type pumps. We find that the turnover rate of the inward current through two of these mutants (EETA963S and L104R) is too small to induce significant cell depolarization. Electrophysiological characterization of another hyperaldosteronism-inducing mutation, G99R, reveals the absence of inward currents under many different conditions, including in the presence of the regulator FXYD1 as well as with mammalian ionic concentrations and body temperatures. Instead, we observe robust outward currents, but with significantly reduced affinities for intracellular Na + and extracellular K + Collectively, our results point to loss-of-function as the common mechanism for the hyperaldosteronism induced by these Na/K pump mutants. © 2017 Meyer et al.

  6. Tn5-induced pBS286 plasmid mutations blocking early stages of napthalene oxidation

    International Nuclear Information System (INIS)

    Kosheleva, I.A.; Tsoi, T.V.; Ivashina, T.V.; Selifonov, S.A.; Starovoitov, I.I.; Boronin, A.M.

    1988-01-01

    The authors present data on the further analysis of the structural and functional organization of the nah region of plasmid pBS286 controlling the constitutive oxidation of naphthalene by Pseudomonas putida cells. They have studied Tn5-induced mutations blocking early stages of naphthalene oxidation. They present and discuss data providing evidence that, in contrast to plasmid NAH7, the mechanism of regulation of the nahl operon of plasmid NPL-1, the parent plasmid of plasmid pBS286, with inducible synthesis of naphthalene dioxygenase can include elements of a negative control with participation of the regulatory locus R, located proximal to the structural nah genes and closely linked to or overlapped by the inverted control DNA segment (4.2 kb). They also present data on the possibility of regulation of the activity of the catechol-splitting meta-pathway genes with the participation of products of early stages of naphthalene oxidation

  7. A comparison of mutations induced by accelerated iron particles versus those induced by low earth orbit space radiation in the FEM-3 gene of Caenorhabditis elegans

    Science.gov (United States)

    Hartman, P. S.; Hlavacek, A.; Wilde, H.; Lewicki, D.; Schubert, W.; Kern, R. G.; Kazarians, G. A.; Benton, E. V.; Benton, E. R.; Nelson, G. A.

    2001-01-01

    The fem-3 gene of Caenorhabditis elegans was employed to determine the mutation frequency as well as the nature of mutations induced by low earth orbit space radiation ambient to Space Shuttle flight STS-76. Recovered mutations were compared to those induced by accelerated iron ions generated by the AGS synchrotron accelerator at Brookhaven National Laboratory. For logistical reasons, dauer larvae were prepared at TCU, transported to either Kennedy Space Center or Brookhaven National Laboratory, flown in space or irradiated, returned to TCU and screened for mutants. A total of 25 fem-3 mutants were recovered after the shuttle flight and yielded a mutation frequency of 2.1x10(-5), roughly 3.3-fold higher than the spontaneous rate of 6.3x10(-6). Four of the mutations were homozygous inviable, suggesting that they were large deletions encompassing fem-3 as well as neighboring, essential genes. Southern blot analyses revealed that one of the 25 contained a polymorphism in fem-3, further evidence that space radiation can induce deletions. While no polymorphisms were detected among the iron ion-induced mutations, three of the 15 mutants were homozygous inviable, which is in keeping with previous observations that high LET iron particles generate deficiencies. These data provide evidence, albeit indirect, that an important mutagenic component of ambient space radiation is high LET charged particles such as iron ions.

  8. Mistranslation induced by streptomycin provokes a RecABC/RuvABC-dependent mutator phenotype in Escherichia coli cells.

    Science.gov (United States)

    Balashov, Sergey; Humayun, M Zafri

    2002-01-25

    Translational stress-induced mutagenesis (TSM) refers to the mutator phenotype observed in Escherichia coli cells expressing a mutant allele (mutA or mutC) of the glycine tRNA gene glyV (or glyW). Because of an anticodon mutation, expression of the mutA allele results in low levels of Asp-->Gly mistranslation. The mutA phenotype does not require lexA-regulated SOS mutagenesis functions, and appears to be suppressed in cells defective for RecABC-dependent homologous recombination functions. To test the hypothesis that the TSM response is mediated by non-specific mistranslation rather than specific Asp-->Gly misreading, we asked if streptomycin (Str), an aminoglycoside antibiotic known to promote mistranslation, can provoke a mutator phenotype. We report that Str induces a strong mutator phenotype in cells bearing certain alleles of rpsL, the gene encoding S12, an essential component of the ribosomal 30 S subunit. The phenotype is strikingly similar to that observed in mutA cells in its mutational specificity, as well as in its requirement for RecABC-mediated homologous recombination functions. Expression of Str-inducible mutator phenotype correlates with mistranslation efficiency in response to Str. Thus, mistranslation in general is able to induce the TSM response. The Str-inducible mutator phenotype described here defines a new functional class of rpsL alleles, and raises interesting questions on the mechanism of action of Str, and on bacterial response to antibiotic stress. Copyright 2002 Academic Press.

  9. An inducible mouse model of podocin-mutation-related nephrotic syndrome.

    Directory of Open Access Journals (Sweden)

    Mansoureh Tabatabaeifar

    Full Text Available Mutations in the NPHS2 gene, encoding podocin, cause hereditary nephrotic syndrome. The most common podocin mutation, R138Q, is associated with early disease onset and rapid progression to end-stage renal disease. Knock-in mice carrying a R140Q mutation, the mouse analogue of human R138Q, show developmental arrest of podocytes and lethal renal failure at neonatal age. Here we created a conditional podocin knock-in model named NPHS2 R140Q/-, using a tamoxifen-inducible Cre recombinase, which permits to study the effects of the mutation in postnatal life. Within the first week of R140Q hemizygosity induction the animals developed proteinuria, which peaked after 4-5 weeks. Subsequently the animals developed progressive renal failure, with a median survival time of 12 (95% CI: 11-13 weeks. Foot process fusion was observed within one week, progressing to severe and global effacement in the course of the disease. The number of podocytes per glomerulus gradually diminished to 18% compared to healthy controls 12-16 weeks after induction. The fraction of segmentally sclerosed glomeruli was 25%, 85% and 97% at 2, 4 and 8 weeks, respectively. Severe tubulointerstitial fibrosis was present at later disease stage and was correlated quantitatively with the level of proteinuria at early disease stages. While R140Q podocin mRNA expression was elevated, protein abundance was reduced by more than 50% within one week following induction. Whereas miRNA21 expression persistently increased during the first 4 weeks, miRNA-193a expression peaked 2 weeks after induction. In conclusion, the inducible R140Q-podocin mouse model is an auspicious model of the most common genetic cause of human nephrotic syndrome, with a spontaneous disease course strongly reminiscent of the human disorder. This model constitutes a valuable tool to test the efficacy of novel pharmacological interventions aimed to improve podocyte function and viability and attenuate proteinuria

  10. Comparative study of the antimutagenic properties of vitamins C and E against mutation induced by norfloxacin.

    Science.gov (United States)

    Alba, Myriam Arriaga; Sánchez, Roberto Rivera; Pérez, Nancy Jannet Ruíz; Navarrete, Jaime Sánchez; Paz, Rocío Flores; Montoya-Estrada, Araceli; Gómez, Juan José Hicks

    2008-02-11

    Norfloxacin like other fluoroquinolones, is known to mbe mutagenic for Salmonella typhimurium TA102 strain. This mutagenic effect is due to free oxygen radicals (ROS), because it is inhibited by antioxidants such as beta-carotene and naturally occurring antioxidants of Roheo discolor and other plants. The aim of this work was to evaluate combination therapy with norfloxacin and vitamins C and E, to reduce the possible genotoxic risk associated with fluoroquinolones. The antimutagenicity of alpha-tocoferol (Vitamin E) and ascorbic acid (Vitamin C) against norfloxacin-induced mutation was evaluated on S. typhimurium TA102, using the aroclor-1254-induced S9 rat liver homogenate. The minimum inhibitory concentration (MIC) a measure of the bactericidal effect of norfloxacin, was obtained in vitro by the plate dilution method. Vitamin E (0.5 mg per Petri dish) induced a statistically significant reduction (P norfloxacin, whereas Vitamin C (1 mg per Petri dish) had no such effect. Neither of these vitamins altered the MIC for norfloxacin against 25 uropathogenic strains of Escherichia coli. These results suggest that Vitamin E is a potent antimutagen that would be worthwhile being used in conjunction with fluoroquinolone treatment. The minimal antimutagenic effect of Vitamin C observed under these experimental conditions may have been because Vitamin C in the Ames test induces a Fenton reaction, and if divalent cations are present, it can act as a pro-oxidant rather than an antioxidant. Ascorbic acid should be further evaluated in the presence of different divalent cations concentrations.

  11. The nature of radiation-induced mutations at the white locus of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Pastink, A.; Schalet, A.P.; Vreeken, C.; Eeken, J.C.J.; Paradi, E.

    1987-01-01

    X-ray- and neutron-induced mutations at the white locus of Drosophila melanogaster were used to study the nature of radiation-induced genetic damage. Genetic analysis showed the presence of multi-locus deficiencies in 15 out of 31 X-ray mutants and in 26 out of 35 mutants induced by neutrons. The DNA from 11 X-ray and 4 neutron mutants, which were not multi-locus deficiencies, was analyzed by Southern blot-hybridization. Deletions were observed in 2 X-ray and 1 neutron mutant. In combination with cytogenetic techniques, chromosomal rearrangements affecting the white locus (translocations, inversions, etc.) were identified in 3 X-ray and in 2 neutron mutants. A hot-spot for translocation breakpoints was identified in the left arm of the third chromosome. 5 X-ray mutants, which apparently did not contain large deletions, were subjected to further analysis by the nuclease S1 protection method, after cloning of the white gene. In 4 mutants a small deletion could indeed be detected in this way. Thus it seems that by far the main part of X-ray- and neutron-induced white mutants have arisen through large changes in the white gene, especially deletions. (Auth.)

  12. Induced mutations to develop sources of resistance to rice blast, Pyricularia grisea Sacc

    International Nuclear Information System (INIS)

    Correa-Victoria, F.J.

    2001-01-01

    Rice blast caused by Pyricularia grisea is the most important disease limiting yields worldwide. The pathogen has many virulent forms or pathotypes, hence durable blast resistance is lacking. Studies on strategy to develop durable blast resistance based on defining the genetic structure of the population, using DNA-fingerprinting, and virulence diversity are described. This strategy is leading to the identification of resistance genes/sources against all isolates within a genetic family of the pathogen. Combinations of genes showing complementary resistance to different genetic families of the fungus exclude any compatible interaction with a blast isolate. Identification of complementary resistance genes is based on detecting those virulence factors whose combinations in individual isolates within the pathogen population have a frequency near zero. Identifying and combining resistance genes to which combinations of corresponding virulence genes are absent in the pathogen population should confer more durable resistance than that previously obtained. The use of induced mutations in the development of resistance was limited, since in most cases single gene changes were responsible for the induced resistance against all the pathogen population. The main objective here is to develop many mutants, each with a gene resistant to just one or a few families of the blast pathogen; and crossing them can accumulate the different resistance genes. A total of 201 Latin American commercial cultivars, including Cuban, Brazilian and Venezuelan were analyzed with different genetic families of the blast pathogen to identify potential sources of resistance to blast and identify complementary resistance sources. Characterization of the resistance of 37 mutants of the Colombian rice cultivar Oryzica 1 was conducted in collaboration with the INEA in Colombia. Results suggested that mutations for resistance to genetic families to which Oryzica 1 is susceptible were induced, although one

  13. Radiation-induced point mutations, deletions and micronuclei in lacI transgenic mice

    International Nuclear Information System (INIS)

    Winegar, Richard A.; Hamer, Janice D.; O'Loughlin, Kathleen G.; Mirsalis, Jon C.; Lutze, Louise H.

    1994-01-01

    The development of transgenic mutagenesis systems has now made it possible to study the effects of ionizing radiation at both the molecular and chromosomal levels in the same animal. In this report we present preliminary data on the response of Big Blue TM lacI transgenic mice to ionizing radiation as measured by lacI mutations and micronuclei. C57Bl/6 transgenic mice were irradiated with 137 Cs γ-rays at doses ranging from 0.1 to 14 Gy, and expression times ranging from 2 to 14 days. Dose-related increases in the mutant frequency were observed after irradiations with longer expression times. Mutant plaques were analyzed by restriction enzyme digestion to detect large structural changes in the target sequence. Of 34 γ-ray- induced mutations analyzed, 4 were large-scale rearrangements. Three of these rearrangements were deletions within the lacI gene characterized by the presence of short regions of homology at the breakpoint junctions. The fourth rearrangement was a deletion that extended from within the αlacZ gene into downstream sequences and that had 43 bp of homology at the junction. These data indicate that the Big Blue TM lacI transgenic mouse system is sensitive to the types of mutations induced by ionizing radiation. To determine whether the presence of the transgene affects micronucleus induction we compared the response of nontransgenic to hemizygous transgenic B6C3F1 mice and the response of nontransgenic to hemizygous and homozygous transgenic C57Bl/6 mice. The presence or absence of the lacI transgene had no effect on spontaneous micronucleus frequencies for either strain. However, radiation-induced micronucleus frequencies were significantly higher in hemizygous lacI B6C3F1 mice than in nontransgenic litter mates; the converse was true in C57Bl/6 mice. These data suggest that the lacI transgene does not cause chromosome instability as measured by spontaneous micronucleus levels. However, the response of these transgenic mice to a variety of

  14. Tritiated uracil, tritiated thymidine, and bromodeoxyuridine induced mutations in eucaryotic cells

    International Nuclear Information System (INIS)

    Burki, H.J.; Moustacchi, E.; Cleaver, J.E.

    1979-02-01

    The induction of gene conversion at the ARG-4 locus in strain BZ34 of Saccharomyces cerevisiae was examined after the cells incorporated y- 3 H uracil under optimum growth conditions for 16 hours, and then received damage at 4 0 C from tritium decays at very low dose rates of 1.4 to 27.6 tritium decays per hour. The results were compared to the results of gene conversion induced by 60 Co. The induction of resistance to 6TG in Chinese hamster ovary (CHO) cells has been studied after incorporation of 3 H-methyl thymidine, 6- 3 H-thymidine, and bromodeoxyuridine under several experimental conditions. The induction of mutations by incorporated 6- 3 H-thymidine is about three times as effective as the induction of mutations by tritiated-methyl thymidine. These results suggest that the determination of the RBE for tritium decays in model eucaryotic systems like yeast and cultured Chinese hamster cells will be influenced by the precise experimental conditions employed. In particular, experiments with mammalian cells will be affected by hot times for mutagenesis in the cell cycle and hot positions within the DNA in the nucleus, and also by the position of tritium decay within the DNA-incorporated molecule

  15. A triple-helix forming oligonucleotide targeting genomic DNA fails to induce mutation.

    Science.gov (United States)

    Reshat, Reshat; Priestley, Catherine C; Gooderham, Nigel J

    2012-11-01

    Purine tracts in duplex DNA can bind oligonucleotide strands in a sequence specific manner to form triple-helix structures. Triple-helix forming oligonucleotides (TFOs) targeting supFG1 constructs have previously been shown to be mutagenic raising safety concerns for oligonucleotide-based pharmaceuticals. We have engineered a TFO, TFO27, to target the genomic Hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus to define the mutagenic potential of such structures at genomic DNA. We report that TFO27 was resistant to nuclease degradation and readily binds to its target motif in a cell free system. Contrary to previous studies using the supFG1 reporter construct, TFO27 failed to induce mutation within the genomic HPRT locus. We suggest that it is possible that previous reports of triplex-mediated mutation using the supFG1 reporter construct could be confounded by DNA quadruplex formation. Although the present study indicates that a TFO targeting a genomic locus lacks mutagenic activity, it is unclear if this finding can be generalised to all TFOs and their targets. For the present, we suggest that it is prudent to avoid large purine stretches in oligonucleotide pharmaceutical design to minimise concern regarding off-target genotoxicity.

  16. A UV-induced mutation in neurospora that affects translational regulation in response to arginine

    International Nuclear Information System (INIS)

    Freitag, M.; Dighde, N.; Sachs, M.S.

    1996-01-01

    The Neurospora crassa arg-2 gene encodes the small subunit of arginine-specific carbamoyl phosphate synthetase. The levels of arg-2 mRNA and mRNA translation are negatively regulated by arginine. An upstream open reading frame (uORF) in the transcript's 5' region has been implicated in arginine-specific control. An arg-2-hph fusion gene encoding hygromycin phosphotransferase conferred arginine-regulated resistance to hygromycin when introduced into N. crassa. We used an arg-2-hph strain to select for UV-induced mutants that grew in the presence of hygromycin and arginine, and we isolated 46 mutants that had either of two phenotypes. One phenotype indicated altered expression of both arg-2-hph and arg-2 genes; the other, altered expression of arg-2-hph but not arg-2. One of the latter mutations, which was genetically closely linked to arg-2-hph, was recovered from the 5' region of the arg-2-hph gene using PCR Sequence analyses and transformation experiments revealed a mutation at uORF codon 12 (Asp to Asn) that abrogated negative regulation. Examination of the distribution of ribosomes on arg-2-hph transcripts showed that loss of regulation had a translational component, indicating the uORF sequence was important for Arg-specific translational control. Comparisons with other uORFs suggest common elements in translational control mechanisms

  17. Studies on Drosophila radiosensitive strains. 7 Influence of maternal genotype on the rates of recessive and dominant lethal mutations induces by γ-rays in males

    International Nuclear Information System (INIS)

    Varentsova, E.P.

    1984-01-01

    Basc line males have been γ-irradiated and hybridized either with females of radiosensitive mutant rad (2)201sup(G1) of with females of control line Canton-S. Recessive sex linkage lethal mutations (RSLLM) and dominiant lethal mutations (DLM) have been considered. Mother genotype is shown to affect formation of mutations induced in males of tester line. The level of spontaneous and induced dominant lethalies was slightly higher after crotsing with females of radiosenssitive mutant as compared with control line. Differences are not disclosed by spontaneous level of recessive lethal mutations, but the effect of rad (2)201sup(G1) mutation on yield of recessive lethal mutations induces in males is revealed; dose dependence of frequency of arising this type of mutations differs from linear dependence described in literature

  18. Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events.

    Science.gov (United States)

    Nagashima, Haruki; Shiraishi, Kumiko; Ohkawa, Saori; Sakamoto, Yuki; Komatsu, Kenshi; Matsuura, Shinya; Tachibana, Akira; Tauchi, Hiroshi

    2017-10-19

    It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >0.15 Gy. In contrast, mutant frequencies at doses of 0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  19. Next-Gen Sequencing-Based Mapping and Identification of Ethyl Methanesulfonate-Induced Mutations in Arabidopsis thaliana.

    Science.gov (United States)

    Zhang, Xue-Cheng; Millet, Yves; Ausubel, Frederick M; Borowsky, Mark

    2014-10-01

    Forward genetic analysis using ethyl methanesulfonate (EMS) mutagenesis has proven to be a powerful tool in biological research, but identification and cloning of causal mutations by conventional genetic mapping approaches is a painstaking process. Recent advances in next-gen sequencing have greatly invigorated the process of identifying EMS-induced mutations corresponding to a specific phenotype in model genetic hosts, including the plant Arabidopsis thaliana and the nematode Caenorhabditis elegans. Next-gen sequencing of bulked F2 mutant recombinants produces a wealth of high-resolution genetic data, provides enhanced delimitation of the genomic location of mutations, and greatly reduces hands-on time while maintaining high accuracy and reproducibility. In this unit, a detailed procedure to simultaneously map and identify EMS mutations in Arabidopsis is described. Copyright © 2014 John Wiley & Sons, Inc.

  20. The use of induced mutation combined with crossing in high quality rice breeding

    International Nuclear Information System (INIS)

    Do Huu At; Bui Huy Thuy; Nguyen Van Bich; Tran Duy Quy; Nguyen Minh Cong

    2001-01-01

    The high quality rice varieties: Tam thom mutant rice Var., DT17 rice Var, DT21 glutinous rice Var were formed by induced mutation combined with crossing. Tam thom mutant rice Var. lost photosensitivity, could be planted 2 crops/year. DT17 rice Var with high yielding capacity, suitable for growth on lowland in summer crop, is replacing step-by-step Moctuyen rice Var. in North Vietnam. DT21 glutinous rice Var. could be planted 2 crops/year and had short growth duration, average yield was 4.0-4.5 tons/ha. These three ones had good quality, soft and scent cooked rice, suitable for customers and export requirements. Tam thom mutant rice Var. DT17 rice Var., DT21 and glutinous rice Var. were adopted for regional production by Ministry of Agriculture and Rural Development and allowed to be in trial production. (author)

  1. Chemotherapy-induced amenorrhea in patients with breast cancer with a BRCA1 or BRCA2 mutation.

    Science.gov (United States)

    Valentini, Adriana; Finch, Amy; Lubinski, Jan; Byrski, Tomasz; Ghadirian, Parviz; Kim-Sing, Charmaine; Lynch, Henry T; Ainsworth, Peter J; Neuhausen, Susan L; Greenblatt, Ellen; Singer, Christian; Sun, Ping; Narod, Steven A

    2013-11-01

    To determine the likelihood of long-term amenorrhea after treatment with chemotherapy in women with breast cancer who carry a BRCA1 or BRCA2 mutation. We conducted a multicenter survey of 1,954 young women with a BRCA1 or BRCA2 mutation who were treated for breast cancer. We included premenopausal women who were diagnosed with invasive breast cancer between 26 and 47 years of age. We determined the age of onset of amenorrhea after breast cancer for women who were and were not treated with chemotherapy, alone or with tamoxifen. We considered chemotherapy-induced amenorrhea to have occurred when the patient experienced ≥ 2 years of amenorrhea, commencing within 2 years of initiating chemotherapy, with no resumption of menses. Of the 1,426 women who received chemotherapy, 35% experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea. The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed before age 30 years, 33% for women age 31 to 44 years, and 79% for women diagnosed after age 45 years (P trend amenorrhea was higher for women who received tamoxifen than for those who did not (52% v 29%; P amenorrhea in women who carry a BRCA1 or BRCA2 mutation. The risk of induced long-term amenorrhea does not seem to be greater among mutation carriers than among women who do not carry a mutation.

  2. Absence of p53 gene mutations in mice colon pre-cancerous stage induced by o-nitrotoluene

    Directory of Open Access Journals (Sweden)

    Nahed A Hussien

    2014-01-01

    Conclusion: The results from the present study indicate that point mutations in the p53 gene, in the coding region (exons 5-8 and outside it (exons 10, 11, are not involved in the development of the colon precancerous stage induced by o-nt in mice.

  3. Collagen XI mutation lowers susceptibility to load-induced cartilage damage in mice.

    Science.gov (United States)

    Holyoak, Derek T; Otero, Miguel; Armar, Naa Shidaa; Ziemian, Sophia N; Otto, Ariana; Cullinane, Devinne; Wright, Timothy M; Goldring, Steven R; Goldring, Mary B; van der Meulen, Marjolein C H

    2018-02-01

    Interactions among risk factors for osteoarthritis (OA) are not well understood. We investigated the combined impact of two prevalent risk factors: mechanical loading and genetically abnormal cartilage tissue properties. We used cyclic tibial compression to simulate mechanical loading in the cho/+ (Col11a1 haploinsufficient) mouse, which has abnormal collagen fibrils in cartilage due to a point mutation in the Col11a1 gene. We hypothesized that the mutant collagen would not alter phenotypic bone properties and that cho/+ mice, which develop early onset OA, would develop enhanced load-induced cartilage damage compared to their littermates. To test our hypotheses, we applied cyclic compression to the left tibiae of 6-month-old cho/+ male mice and wild-type (WT) littermates for 1, 2, and 6 weeks at moderate (4.5 N) and high (9.0 N) peak load magnitudes. We then characterized load-induced cartilage and bone changes by histology, microcomputed tomography, and immunohistochemistry. Prior to loading, cho/+ mice had less dense, thinner cortical bone compared to WT littermates. In addition, in loaded and non-loaded limbs, cho/+ mice had thicker cartilage. With high loads, cho/+ mice experienced less load-induced cartilage damage at all time points and displayed decreased matrix metalloproteinase (MMP)-13 levels compared to WT littermates. The thinner, less dense cortical bone and thicker cartilage were unexpected and may have contributed to the reduced severity of load-induced cartilage damage in cho/+ mice. Furthermore, the spontaneous proteoglycan loss resulting from the mutant collagen XI was not additive to cartilage damage from mechanical loading, suggesting that these risk factors act through independent pathways. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:711-720, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. Mutation studies in mung bean (Phaseolus aureus). V. Induced polygenic variability after seed irradiation

    International Nuclear Information System (INIS)

    Khan, I.A.

    1983-01-01

    Studies were undertaken to explore the possibility of inducing micromutations in quantitative characters of mung bean (Phaseolus aureus Roxb.) after seed irradiation. The characters studied were as follows: pod length, seeds per pod, 100-seed weight, and total plant yield. These characters were analyzed quantitatively to assess the extent of variation in M 1 , M 2 , and M 3 generations. All characters varied significantly in the M 2 generation. In the M 3 generation, pod length, seeds per pod, and 100-seed weight were found significant at the 1% level; plant yield was only significant at 20 and 40 kR (1R = 2.58 × 10 −4 C/kg) of gamma rays. Gamma ray treatments shifted the mean values of all characters, mostly in a positive direction in the M 2 and M 3 generations. The range of variability also increased positively. There was a considerable increase in genotypic variances, heritability, and genetic advances indicating the effectiveness of gamma doses in inducing polygenic mutations governing quantitative traits. The genetic variability increased at all dose levels but it was not linear with dose. Estimates of heritability and genetic advance increased in all characters but the different traits responded differently to the mutagenic treatments

  5. Mutations in cancer genes of UV-induced skin tumors of hairless mice.

    Science.gov (United States)

    van Kranen, H J; de Gruijl, F R

    1999-12-01

    Ultraviolet (UV) radiation is a very common carcinogen in our environment. Epidemiological data on the relationship between skin cancers and ambient solar UV radiation are very limited. Hairless mice provide the possibility to study the process of UV carcinogenesis in more detail. Experiments with this animal model have yielded quantitative data on how tumor development depends on dose, time and wavelength of the UV radiation. In addition, at the molecular level the interactions between UV, specific cancer genes-like the Ras oncogene family and the p53 tumor suppressor gene, together with the role of DNA repair in this process have been addressed recently. In wildtype hairless mice mutations in the p53 gene are clearly linked to UVB but not to UVA radiation. Furthermore, the p53 alterations seem to be essential early in tumor development. However, in Xpa-deficient mice this dependency on p53 alterations appeared to be different as is the tumor type induced by UVB. Research using genetically modified hairless mice should enable us to further unravel the mechanisms of UV-induced skin cancer.

  6. CRISPR/Cas9-induced knockout and knock-in mutations in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Shin, Sung-Eun; Lim, Jong-Min; Koh, Hyun Gi; Kim, Eun Kyung; Kang, Nam Kyu; Jeon, Seungjib; Kwon, Sohee; Shin, Won-Sub; Lee, Bongsoo; Hwangbo, Kwon; Kim, Jungeun; Ye, Sung Hyeok; Yun, Jae-Young; Seo, Hogyun; Oh, Hee-Mock; Kim, Kyung-Jin; Kim, Jin-Soo; Jeong, Won-Joong; Chang, Yong Keun; Jeong, Byeong-Ryool

    2016-06-13

    Genome editing is crucial for genetic engineering of organisms for improved traits, particularly in microalgae due to the urgent necessity for the next generation biofuel production. The most advanced CRISPR/Cas9 system is simple, efficient and accurate in some organisms; however, it has proven extremely difficult in microalgae including the model alga Chlamydomonas. We solved this problem by delivering Cas9 ribonucleoproteins (RNPs) comprising the Cas9 protein and sgRNAs to avoid cytotoxicity and off-targeting associated with vector-driven expression of Cas9. We obtained CRISPR/Cas9-induced mutations at three loci including MAA7, CpSRP43 and ChlM, and targeted mutagenic efficiency was improved up to 100 fold compared to the first report of transgenic Cas9-induced mutagenesis. Interestingly, we found that unrelated vectors used for the selection purpose were predominantly integrated at the Cas9 cut site, indicative of NHEJ-mediated knock-in events. As expected with Cas9 RNPs, no off-targeting was found in one of the mutagenic screens. In conclusion, we improved the knockout efficiency by using Cas9 RNPs, which opens great opportunities not only for biological research but also industrial applications in Chlamydomonas and other microalgae. Findings of the NHEJ-mediated knock-in events will allow applications of the CRISPR/Cas9 system in microalgae, including "safe harboring" techniques shown in other organisms.

  7. Breeding sesame for diseases and shatter resistant high yielding varieties with induced mutations

    International Nuclear Information System (INIS)

    Kang, C.W.

    2001-01-01

    ''Suwon 144'', derived from the cross between ''Danbaeckkae'' and mutant MY-74-2 and in spite of its higher yield and quality compared to the check variety, did not pass the nomination to the Committee of Main Crops New Varieties under the Ministry of Agriculture and Forestry, due to the decision of the committee to limit the number of new varieties in sesame as a minor crop in Korea. ''Suwon 144'' will be released again for a fifth year to RYT in 1998. 5,282 cross combinations and 4,341 lines including 1,388 crossings of F 1 were crossed and released to the experimental field of NCES in 1997. Mutants and their cross combinations were released and constituted more than half among them. Seeds of ''Suwon 152'' were treated with NaN 3 and tested for germinability. The other seeds were released and harvested in the experimental field and 419 mutant lines were selected among all the mutant lines. Mutants or materials from cross breeding with mutants occupied 71% (675) among a total of 952 promising lines in yield trials of OYT, PYT, AYT and RYT. For variability of NaN 3 induced genetic male sterile (GMS) mutants and development of restorer/s of GMS, GMS lines were planted, and male sterility (MS) expression evaluated on each line. The selected 4 MS lines with 50% MS were crossed in 22 combinations with 7 recommended varieties. For development of genic-cytoplasmic MS (GCMS) using NaN 3 induced GMS mutants, 40 recommended local Korean and introduced cultivars were crossed in 57 combinations with 4 selected GMS lines expressing 50% male sterility. Various and many sources of unique characteristics have been continuously created through induced mutations, such as determinate; dwarf, lodging,- Phytophthora blight- and shatter- resistant; indehiscent, seamless, taller, stronger thick stems, dense capsule bearing type, semi-dwarf, better maturity, male sterility, smaller seeds, pure white seed coat color and high yields. Lines with these induced desirable characteristics were

  8. Characterization of ultraviolet light-induced diphtheria toxin-resistant mutations in normal and Xeroderma pigmentosum human fibroblasts

    International Nuclear Information System (INIS)

    Glover, T.W.

    1979-01-01

    Quantitative mutagenesis studies in human cells have been severely limited by the lack of reliable genetic markers. Experiments were therefore performed to develop and characterize a better quantitative mutation assay for human cells. The uv-induction of diphtheria toxin resistant (DT/sup r/) mutations in normal and excision repair defective xeroderma pigmentosum (XP) fibroblasts has been quantitatively characterized. A concentration of diphtheria toxin to use in the selection of resistant mutants was determined whereby DT/sup r/ cells are cross-resistant to Pseudomonas aeurginosa exotoxin A, indicating mutants have altered elongation factor-2 (EF-2) which is not susceptible to ADP-ribosylation by either toxin. Results of this study indicate that XP fibroblasts have higher uv-induced mutation frequencies per unit uv-dose but similar frequencies per unit survival compared to normal cells as measured using a new genetic marker for quantitative mutagenesis. Furthermore, these results support a prediction of the mutation theory of cancer, namely, that cells from individuals with certain human syndromes that predispose the individual to cancer will have higher induced mutation frequencies than cells from non-susceptible individuals. This newly characterized genetic marker should be useful in quantitative mutagenesis studies in human cells

  9. Mutations induced by X-radiation in the yeast Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    Loprieno, N.; Barale, R.; Baroncelli, S.; Cammellini, A.; Melani, M.; Nieri, R.; Nozzolini, M.; Rossi, A.M.; Pisa Univ.

    1975-01-01

    Experiments on strains of yeast with different genetic backgrounds were done to evaluate the kinetics of inactivation and mutation induction by X-radiation. A system of forward mutation induction in five loci was used and a specific mutation rate was evaluated for the wild type. From a comparison of observations with wild type and radiation-sensitive strains, it may be assumed that in this yeast, mutations are mainly the result of a repair-active process. The range of genotypic and phenotypic influence upon the specific locus mutation rate was evaluated with appropriate biological material and experiments

  10. The rare nonsense mutation in p53 triggers alternative splicing to produce a protein capable of inducing apoptosis.

    Directory of Open Access Journals (Sweden)

    Evgeny M Makarov

    Full Text Available P53 protein is more frequently mutated in human tumours compared with the other proteins. While the majority of the p53 mutations, especially within its DNA-binding domain, lead to the loss of the wild-type function, there are accumulating data demonstrating that the p53 mutants gain tumour promoting activities; the latter triggers a revitalised interest in functional analysis of the p53 mutants. A systematic screening for p53 mutations in surgical materials from patients with glioma revealed a 378C>G mutation that creates a stop codon at the position of amino acid residue 126. The mutation eliminates the recognition site for the restriction endonuclease Sca I that allowed us to carry out RFLP analysis of DNA extracted from the clinical samples and suggests that this mutation is more frequent than is documented in the p53 databases. Both the ECV-304 and EJ cell lines, that probably originate from the bladder carcinoma T24 cell line, were confirmed to contain the homozygous 378C>G mutation but were shown to produce the p53 protein of expected full-length size detected by Western blotting. We provide evidence that the 378C>G mutation generates an alternative 3' splice site (ss which is more often used instead of the authentic upstream 3' ss, driving the production of mRNA encoding the protein with the single amino acid deletion (p53ΔY126. Using endogenous expression, we demonstrated that the p53ΔY126 protein is nearly as active as the wild type protein in inducing the p21/Waf1 expression and apoptosis.

  11. ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects

    International Nuclear Information System (INIS)

    Iannuzzi, Christopher M.; Atencio, David P.; Green, Sheryl; Stock, Richard G.; Rosenstein, Barry S.

    2002-01-01

    Purpose: Mutation of the ATM gene may be associated with enhanced radiosensitivity and increased radiation-induced morbidity. Denaturing high performance liquid chromatography (DHPLC) is a powerful new technique proven to be sensitive and accurate in the detection of missense mutations, as well as small deletions and insertions. We screened female breast cancer patients for evidence of ATM gene alterations using DHPLC. This study attempted to determine whether breast cancer patients who develop severe radiotherapy (RT)-induced effects are more likely to possess ATM mutations than patients who display normal radiation responses. Methods and Materials: Forty-six patients with early-stage breast carcinoma underwent limited surgery and adjuvant RT. DNA was isolated from blood lymphocytes, and each coding exon of the ATM gene was amplified using polymerase chain reaction. Genetic variants were identified using DHPLC by comparing test patterns with a known wild-type pattern. All variants were subjected to DNA sequencing and compared with wild-type sequences for evidence of a mutation. A retrospective review was performed, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer acute and late morbidity scoring schemes for skin and subcutaneous normal tissues were applied to quantify the radiation-induced effects. Results: Nine ATM mutations were identified in 6 patients (8 novel and 1 rare). The median follow-up was 3.2 years (range 1.3-10.3). A significant correlation between ATM mutation status and the development of Grade 3-4 subcutaneous late effects was found. All 3 of the patients (100%) who manifested Grade 3-4 subcutaneous late sequelae possessed ATM mutations, whereas only 3 (7%) of the 43 patients who did not develop this form of severe toxicity harbored an ATM mutation (p=0.001). One ATM mutation carrier developed Grade 4 soft tissue necrosis after RT and required hyperbaric oxygen. All 3 patients manifesting Grade 3

  12. Establishment of induced pluripotent stem cell line (ZZUi010-A from an Alzheimer's disease patient carrying an APP gene mutation

    Directory of Open Access Journals (Sweden)

    Zhilei Wang

    2017-12-01

    Full Text Available Alzheimer's disease (AD is one of the most common neurodegenerative disorders. Previous studies have identified mutations in several genes, such as amyloid precursor protein (APP, presenilin-1 (PSEN1, and presenilin-2 (PSEN2, in patients with early-onset (<65 years familial AD. Recently, a patient with an APP gene mutation was identified; the dermal fibroblasts of the patient were obtained and a line of induced pluripotent stem cells (iPSCs was successfully generated using the Sendai-virus (SeV delivery system. The iPSC line will be useful for further study of the pathomechanism and drug screening for AD.

  13. Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection.

    Directory of Open Access Journals (Sweden)

    Eun-Young Kim

    2014-07-01

    Full Text Available Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1 cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection.

  14. Analysis of dominant and recessive sex-linked lethal mutations induced by low radiation doses in genetically different strains of Drosophila melanogaster w and MS

    International Nuclear Information System (INIS)

    Aslanyan, M.M.; Kim, A.I.; Magomedova, M.A.; Fatkulbayanova, N.L.

    1994-01-01

    Frequencies of induced recessive sex-linked lethal mutations (RSLLM) and dominant lethal mutations (DLM) were analyzed in genetically different Drosophila melanogaster strains w and MS after their exposure to radiation on radioactive soil in laboratory conditions. The RSLLM test applied to males after their 14-day radiation exposure yielded controversial results. An analysis of induced and spontaneous DLM demonstrated an increase in the frequency of early embryonic lethal mutations in the experiment (radiation exposure) in comparison with the control (spontaneous mutation rate) in both strains examined

  15. Neutron-induced mutation experiments and total radiation-induced genetic damage in entire genomes of Drosophila melanogaster. Final report, November 1, 1967-August 31, 1980

    International Nuclear Information System (INIS)

    Abrahamson, S.

    1981-02-01

    Neutron-induced mutation experiments with Drosophila oogonia were conducted at the University of Wisconsin, with irradiations being carried out at the RARAF facility at Brookhaven National Laboratory. X-linked recessive lethals and specific locus mutations were studied. Using the α value of the weighted linear regression equation for lethal data, RBE's relative to X-rays were calculated for the energies of neutrons studied. They are: 15 MeV to 2.0; 6 MeV to 2.9; 2 MeV to 3.2; .66 MeV to 4.0; .43 MeV to 4.8. The dose/frequency response curves for lethal data of all neutron energies studied was suggestive of a quadratic component. All data best fit a linear hypothesis, however. Control data for specific locus mutations was used to estimate the number of loci on the X-chromosome which are capable of mutating to lethals. Neutron-induced data for specific locus mutation was inconclusive due to the high error inherent in the frequencies obtained

  16. Homologous leaf mutations induced in small- and large seeded lentils and their effect on some economic characters

    International Nuclear Information System (INIS)

    Sharma, S.K.; Sharma, B.

    1978-01-01

    Large-seeded 'L 1492' and small-seeded 'L 235' varieties of lentil (Lens culinaris Medic.) were treated with gamma-rays and NMU (N-nitroso-N-methyl urea.). The leaves of the 2 groups are also usually large and small respectively. Some homologous leaf mutations were isolated in both the varieties. In the small-seeded variety, leaf mutations similar to the large-seeded variety were induced and vice versa. The leaf mutations in the 2 groups did not show any change in pod or seed size. Thus the genes responsible for taxonomic differentiation of the small and large-seeded types seem to be different from those reported here, which simply modify the leaf morphology. The seed yield of all the leaf mutants was less than that of the parent varieties. (author)

  17. NanoTIO2 (UV-Titan) does not induce ESTR mutations in the germline of prenatally exposed female mice

    DEFF Research Database (Denmark)

    Boisen, Anne Mette Zenner; Shipley, Thomas; Hougaard, Karin Sørig

    2012-01-01

    Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR) loci in mice are sensitive markers of mutagenic effects...... on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development). Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed...... exposed by whole-body inhalation to the nanoTiO2 UV-Titan L181 (~42.4 mg UV-Titan/m3) or filtered clean air on gestation days (GD) 8–18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates...

  18. The use of radiations to induce useful mutations in fruit trees

    International Nuclear Information System (INIS)

    Donini, B.

    1976-01-01

    The researches carried out at Casaccia in this field had covered the problems of technique of mutagenic treatment, mechanism of mutation induction and methodology of somatic mutation isolation. To enhance the efficiency of somatic mutation induction several conditions during and after the treatment have been studied. More experience has been gained with regard to the induction of somatic mutation which raises from genetical event or by tissue arrangement of a chimaeric shoot apex. To increase the size of mutated sector treatment have been carried out on the primordia in a very early stages and to improve the methodology of somatic mutation special techniques have been adapted of handling the material in the propagation. Possibility for early detection of mutants has been explored in cherry by establishing a correlation between mutants and hormonal content. By using the above mentioned techniques, useful mutants have been isolated in cherries, grapes, olives and peaches. (author)

  19. The carcinogenic air pollutant 3-nitrobenzanthrone induces GC to TA transversion mutations in human p53 sequences.

    Science.gov (United States)

    vom Brocke, Jochen; Krais, Annette; Whibley, Catherine; Hollstein, Monica C; Schmeiser, Heinz H

    2009-01-01

    3-Nitrobenzanthrone (3-NBA) is a potent mutagen and a suspected human carcinogen present in particulate matter of diesel exhaust and ambient air pollution. Employing an assay with human p53 knock-in (Hupki) murine embryonic fibroblasts (HUFs), we examined p53 mutations induced by 3-NBA and its active metabolite, N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA). Twenty-nine immortalized cultures (cell lines) from 89 HUF primary cultures exposed at passage 1 for 5 days to 2 microM 3-NBA harboured 22 different mutations in the human DNA-binding domain sequence of the Hupki p53 tumour suppressor gene. The most frequently observed mutation was GC to TA transversion (46%), corroborating previous mutation studies with 3-NBA, and consistent with the presence of persistent 3-NBA-guanosine adducts found in DNA of exposed rodents. Six of the transversions found solely in 3-NBA-treated HUFs have not been detected thus far in untreated HUFs, but have been found repeatedly in human lung tumours. (32)P-post-labelling adduct analysis of DNA from HUF cells treated with 2 microM 3-NBA for 5 days showed a pattern similar to that found in vivo, indicating the metabolic competence of HUF cells to metabolize 3-NBA to electrophilic intermediates. Total DNA binding was 160 +/- 56 per 10(7) normal nucleotides with N(2)-guanosine being the major adduct. In contrast, identical treatment with N-OH-3-ABA resulted in a 100-fold lower level of specific DNA adducts and no carcinogen-specific mutation pattern in the Hupki assay. This indicates that the level of DNA adduct formation by the mutagen is critical to obtain specific mutation spectra in the assay. Our results are consistent with previous experiments in Muta Mouse and are compatible with the possibility that diesel exhaust exposure contributes to mutation load in humans and to lung cancer risk.

  20. Improvement of traditional local rice varieties through induced mutations using nuclear techniques

    International Nuclear Information System (INIS)

    Pham Van Ro; Do Huu At

    2001-01-01

    'Improvement of local rice varieties for high yield, resistance to disease and insect pests (brown plant hopper and rice blast) and export quality through induced mutations for the Mekong Delta' started in 1993. After six years, it showed effecting on the field in the MD as well as at the south of Vietnam. TNDB-100 manifest very wide adaptation and yield stable variety. THDB is suitable for deepwater rice region, coastal area, where rice cultivation effected by acid sulphate and salinity conditions. Both varieties are good example for the method. Thank to good Co-operation from extension center from provinces, hundred classes of extension were organized to recommend to the farmers. And thank to the strongly supporting from IAEA so that nearly 400,000 ha of TNDB-100 occupied at the south of Vietnam as well as nearly 15,000 ha of THDB grown in the coastal as well as rainfed lowland rice areas at the South of Vietnam. To continue the rice improvement by this technique, seeds of six traditional local varieties were exposed under different dose of gamma rays to create new mutants. At present day hundred improved breeding lines were selected, a dozen of uniform lines were isolated and entranced the yield trail as well as regional testing program. From these improved varieties would be selected to contribute to the rice cultivation at the south of Vietnam in the next years. (author)

  1. Induced mutations in ornamental plants by 'in vitro' irradiation of Petunia hybrida meristems

    International Nuclear Information System (INIS)

    Gonzalez-Jimenez, J.

    1993-01-01

    In recent decades it has been observed that for the induction of mutation in ornamental plants we can obtain better results when the plants are irradiated in vegetative state and even better 'in vitro' that when its are irradiated 'in vivo'. In this work the possibilities are showed to avoid the best use of a new biotechnology: the gamma irradiations on the meristem 'in vitro'. A tissue culture method was described for the best vegetative propagation of Petunia hybrid hort through morphogenesis induction of meristem. These were planted in the Murashige and Skoog's basic medium added with BAP and ANA. The pH was adjusted to 6.5 prior autoclaving at 121 Centigrade degree and 1.1 Kg/ cm 2 for 15 minutes. Latter the meristem of plantules in immature and mature physiology stated were irradiated with gamma ray doses ranging from 1.0 at 10.0 Gy. The meristem were then subcultived aseptically with the following results: 1) The immature stage was higher radio sensibilities. 2) The LD 50 for the matured plants was to ranged from 1.0 at 9.0 Gy. and immature 1.0 at 8.0 Gy. 3) The better doses was at 7.5 Gy. 4) The meristem gamma irradiation at 7.5 Gy. showed in the first culture: the adventitious bud induced and the multi meristem formation. 5) In the second cultured the results reveals the 'variegadas' plants formations and the new purples flowers. (Author)

  2. Possible contribution of induced mutations on breaking the rice yield barrier

    International Nuclear Information System (INIS)

    Sobrizal and Moch Ismachin

    2006-01-01

    At The World Rice Research Conference in Tsukuba, Japan, on 4 — 7 November 2004, there was an active discussion on how to increase the world rice yield production. Breeders agreed that after IR8, the yield potential of rice varieties could not increase drastically. From the breeding point of view, there were two approaches that already started in three to one decade ago, but it is still unfinished yet. These two approaches were to do breeding for hybrid rice varieties or breeding for new plant idiotype varieties. The idea to produce hybrid rice was stimulated by the success of hybrid corn, onion, and sorghum on commercial basis. Among the countries that are working for producing hybrid rice varieties, China was the leading one. China produced hybrid rice varieties and which are planted already in very large area. This success influenced other countries to do the same, including Indonesia. Now Indonesia has already released 11 hybrid rice varieties. Knowing so many characters that are already present in the rice collection, the idea to produce new plant idiotype appears. It seems not difficult to unite selected characters to become a new plant idiotype. In fact, however, up to now there are still a lot of obstacles that make those two approaches could not reach the real goal. This paper will discuss the possible contribution of induced mutations toward the success of these two approaches. (author)

  3. Improvement of traditional local rice varieties through induced mutations using nuclear techniques

    Energy Technology Data Exchange (ETDEWEB)

    Pham Van Ro; Do Huu At [Cuu Long Delta Rice Research Institute (Viet Nam)

    2001-03-01

    'Improvement of local rice varieties for high yield, resistance to disease and insect pests (brown plant hopper and rice blast) and export quality through induced mutations for the Mekong Delta' started in 1993. After six years, it showed effecting on the field in the MD as well as at the south of Vietnam. TNDB-100 manifest very wide adaptation and yield stable variety. THDB is suitable for deepwater rice region, coastal area, where rice cultivation effected by acid sulphate and salinity conditions. Both varieties are good example for the method. Thank to good Co-operation from extension center from provinces, hundred classes of extension were organized to recommend to the farmers. And thank to the strongly supporting from IAEA so that nearly 400,000 ha of TNDB-100 occupied at the south of Vietnam as well as nearly 15,000 ha of THDB grown in the coastal as well as rainfed lowland rice areas at the South of Vietnam. To continue the rice improvement by this technique, seeds of six traditional local varieties were exposed under different dose of gamma rays to create new mutants. At present day hundred improved breeding lines were selected, a dozen of uniform lines were isolated and entranced the yield trail as well as regional testing program. From these improved varieties would be selected to contribute to the rice cultivation at the south of Vietnam in the next years. (author)

  4. Somatic mutation and neoplastic transformation induced by [methyl-3H]thymidine

    International Nuclear Information System (INIS)

    Lin, S.L.; Takii, M.; Ts'o, P.O.P.

    1982-01-01

    A system for the study of neoplastic transformation as induced by the incorporation of [methyl- 3 H]thymidine is described. Normal diploid golden Syrian hamster embryo fibroblasts were exposed to [methyl- 3 H]thymidine for 17 hr, followed by a brief chase with deoxycytidine- and thymidine-containing growth medium. Analysis of cell curves suggested multihit mechanism with D/sub q/ and D/sub o/ equal to 0.012 and 0.04 μCi/ml, respectively. Transformation studies demonstrate that expression of specific neoplastic phenotypes occurs at different post-treatment population doublings (PTPD), beginning with morphological alteration (PTPD 3-4), followed by enhanced fibrinolytic activity (PTPD 11-16) and the ability to clone in both medium containing 1% serum (PTPD 18-32) and soft agar (PTPD 25-32). All treated lines displayed tumorigenicity when examined at PTPD 46, whereas control cultures did not. Two tumor lines obtained from tumor explants were further characterized. Cells treated with equivalent tritium concentrations of [5- 3 H]uridine display neither elevated somatic mutation nor enhanced morphological transformation. DNA damage occurring as a result of [ 3 H]thymidine incorporation was shown via mutagenicity studies at loci coding for hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) (HPRT) and the NA + /K + ATPase (EC 3.6.1.3). [methyl- 3 H]thymidine incorporation resulted in induction of HPRT but not ouabain-resistant mutants. Present studies substantiate the importance of specific DNA/nuclear damage, induced by incorporation of tritiated thymidine, as a cause of neoplastic transformation

  5. Uptake of tritiated 1,2-dibromoethane by Tradescantia floral tissues: relation to induced mutation frequency in stamen hair cells

    International Nuclear Information System (INIS)

    Nauman, C.H.; Klotz, P.J.; Schairer, L.A.

    1979-01-01

    Inflorescences of two clones of Tradescantia (02 and 4430) have been exposed to the gaseous form of tritium-labeled 1,2-dibromoethane (DBE). A comparison of chemical exposure concentration and tissue dose for various exposure periods indicated that DBE readily and rapidly penetrated through the outer sepal and petal tissues to the critical stamen hair cells - the targets for mutation induction. Bud and open flower tissues of both clones contained generally similar amounts of [ 3 H]-DBE after similar exposures; thus, a differential penetration or uptake of the mutagen into the tissues of these clones cannot account for the 7 to 9 fold difference between clones in pink mutation frequency elicited by DBE exposure. Autoradiographs of stamen hair cells showed clearly that the DBE was not localized, but distributed randomly throughout the cytoplasm and nucleus. Comparison of [ 3 H]-DBE-induced pink mutation-response curves to those derived previously with unlabeled DBE revealed that the rad dose of tritium could not account entirely for the elevated mutation response following exposure to the [ 3 H]-DBE. Plots of the total exposure to [ 3 H]-DBE vs both tissue molar concentration of [ 3 H]-DBE and pink mutation incidence following exposure to DBE made possible the construction of true target-tissue dose-response curves. (author)

  6. Induced mutations in chickpea (Cicer arietinum L.) I. comparative mutagenic effectiveness and efficiency of physical & chemical mutagens

    International Nuclear Information System (INIS)

    Kharkwal, M.C.

    1998-01-01

    Mutagenic effectiveness usually means the rate of mutation as related to dose. Mutagenic efficiency refers to the mutation rate in relation to damage. Studies on comparative mutagenic effectiveness and efficiency of two physical (gamma rays and fast neutrons) and two chemical mutagens (NMU and EMS) on two desi (G 130 & H 214), one kabuli (C 104) and one green seeded (L 345) chickpea (Cicer arietinum L.) have been reported. The treatments included three doses each of gamma rays (400, 500 and 600 Gy) and fast neutrons (5, 10 and 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU 0.01% 20h and 0.02% 8h) and EMS (0.1% 20h and 0.2% 8h). Results indicated that chemical mutagens, particularly NMU are not only more effective but also efficient than physical mutagens in inducing mutations in chickpea. Mutagenic effectiveness and efficiency showed differential behaviour depending upon mutagen and varietal type. Chemical mutagens were more efficient than physical in inducing cholorophyll as well as viable and total number of mutations. Among the mutagens NMU was the most potent, while in the physical, gamma rays were more effective. Out of four mutagens, NMU was the most effective and efficient in inducing a high frequency and wide spectrum of chlorophyll mutations in the M2 followed by fast neutrons. While gamma rays showed least effectiveness, EMS was least efficient mutagens. Major differences in the mutagenic response of the four cultivars were observed. The varieties of desi type were more resistant towards mutagenic treatment than kabuli and green seeded type

  7. Correlation of oxidative stress in patients with HBV-induced liver disease with HBV genotypes and drug resistance mutations.

    Science.gov (United States)

    Xianyu, Jianbo; Feng, Jiafu; Yang, Yuwei; Tang, Jie; Xie, Gang; Fan, Lingying

    2018-05-01

    This study aims to explore the correlation of oxidative stress (OxS) in patients with chronic hepatitis B (CHB) and the disease severity with HBV genotypes and drug resistance mutations. A total of 296 patients with CHB were enrolled into the study. PCR-reverse dot-blot hybridization was used to detect the HBV genotypes (B, C, and D) and the drug resistance-causing HBV mutant genes. In addition, the total oxidative stress (TOS) and total antioxidant status (TAS) were determined, and oxidative stress index (OSI) was calculated and compared. Serum levels of TOS and OSI, the B/C ratio, and drug resistance mutation rate were increased along with the elevated disease severity degree (CHBHBV mutation had higher serum TOS and OSI levels, while lower serum TAS levels (P HBV-induced liver disease, and the damage degree is correlated with the HBV genotype and drug resistance mutation. Oxidative stress might be a useful indicator of the progression of HBV-induced liver disease in patients. Copyright © 2018. Published by Elsevier Inc.

  8. Induced mutation in dwarf growth habits of apple trees by gamma rays and its evaluation in practical uses

    International Nuclear Information System (INIS)

    Ikeda, Fukio

    1979-01-01

    A series of mutation breeding experiments on apple has been made. The dwarf type mutants having dwarfing rootstock effects on top varieties were developed in the gamma field. In this paper, the induction efficiency that the desirable spur type mutants for top, and the effective dwarf type mutants for rootstocks are produced in a gamma field in comparison with acute irradiation, and some evaluation of the induced mutants for practical purposes are described. A large number of the spur type mutants of apple trees having dwarf growth habit and a desirable tree form for high density planting have been induced by chronic or acute irradiation of gamma-ray since 1962. The mutation with dwarf growth habit including spur types was detected in the grafts on the clonal rootstocks of Marubakaido Malus prunifolia. No useful mutation toward the trees with dwarf growth habit and favorable fruit quality was recognized in the mutants derived from acute irradiation. Chronic treatment has been conducted in the uninjurious area in the gamma field on settled trees. High mutability in the dwarf growth of aged resting buds of settled trees was examined by twice-repeated cutting back treatments. In conclusion, for the induction of useful mutants or effective dwarfing mutants as clonal rootstocks, the artificial mutation breeding with gamma-ray should be conducted under chronic conditions and by planned cutting back treatments, in order to avoid various chromosomal aberrations and intrasomatic selection. (Kato, T.)

  9. neu mutation in schwannomas induced transplacentally in Syrian golden hamsters by N-nitrosoethylurea: high incidence but low allelic representation.

    Science.gov (United States)

    Buzard, G S; Enomoto, T; Hongyo, T; Perantoni, A O; Diwan, B A; Devor, D E; Reed, C D; Dove, L F; Rice, J M

    1999-10-01

    Peripheral nerve tumors (PNT) and melanomas induced transplacentally on day 14 of gestation in Syrian golden hamsters by N-nitrosoethylurea were analyzed for activated oncogenes by the NIH 3T3 transfection assay, and for mutations in the neu oncogene by direct sequencing, allele-specific oligonucleotide hybridization, MnlI restriction-fragment-length polymorphism, single-strand conformation polymorphism, and mismatch amplification mutation assays. All (67/67) of the PNT, but none of the melanomas, contained a somatic missense T --> A transversion within the neu oncogene transmembrane domain at a site corresponding to that which also occurs in rat schwannomas transplacentally induced by N-nitrosoethylurea. In only 2 of the 67 individual hamster PNT did the majority of tumor cells appear to carry the mutant neu allele, in contrast to comparable rat schwannomas in which it overwhelmingly predominates. The low fraction of hamster tumor cells carrying the mutation was stable through multiple transplantation passages. In the hamster, as in the rat, specific point-mutational activation of the neu oncogene thus constitutes the major pathway for induction of PNT by transplacental exposure to an alkylating agent, but the low allelic representation of mutant neu in hamster PNT suggests a significant difference in mechanism by which the mutant oncogene acts in this species.

  10. A novel somatic mutation in ACD induces telomere lengthening and apoptosis resistance in leukemia cells.

    Science.gov (United States)

    Spinella, Jean-François; Cassart, Pauline; Garnier, Nicolas; Rousseau, Philippe; Drullion, Claire; Richer, Chantal; Ouimet, Manon; Saillour, Virginie; Healy, Jasmine; Autexier, Chantal; Sinnett, Daniel

    2015-09-07

    The identification of oncogenic driver mutations has largely relied on the assumption that genes that exhibit more mutations than expected by chance are more likely to play an active role in tumorigenesis. Major cancer sequencing initiatives have therefore focused on recurrent mutations that are more likely to be drivers. However, in specific genetic contexts, low frequency mutations may also be capable of participating in oncogenic processes. Reliable strategies for identifying these rare or even patient-specific (private) mutations are needed in order to elucidate more personalized approaches to cancer diagnosis and treatment. Here we performed whole-exome sequencing on three cases of childhood pre-B acute lymphoblastic leukemia (cALL), representing three cytogenetically-defined subgroups (high hyperdiploid, t(12;21) translocation, and cytogenetically normal). We applied a data reduction strategy to identify both common and rare/private somatic events with high functional potential. Top-ranked candidate mutations were subsequently validated at high sequencing depth on an independent platform and in vitro expression assays were performed to evaluate the impact of identified mutations on cell growth and survival. We identified 6 putatively damaging non-synonymous somatic mutations among the three cALL patients. Three of these mutations were well-characterized common cALL mutations involved in constitutive activation of the mitogen-activated protein kinase pathway (FLT3 p.D835Y, NRAS p.G13D, BRAF p.G466A). The remaining three patient-specific mutations (ACD p.G223V, DOT1L p.V114F, HCFC1 p.Y103H) were novel mutations previously undescribed in public cancer databases. Cytotoxicity assays demonstrated a protective effect of the ACD p.G223V mutation against apoptosis in leukemia cells. ACD plays a key role in protecting telomeres and recruiting telomerase. Using a telomere restriction fragment assay, we also showed that this novel mutation in ACD leads to increased

  11. Manifestation of x-radiation induced sex-linked recessive lethal mutation impairing the development of imaginal disks and gonads in Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Abeleva, Eh.A.; Ivanov, A.I.

    1982-01-01

    A study was made of Drosophila melanogaster mutations impairing the development of imaginal disks. The state of gonads in these mutants was not studied. Using X-radiation a lethal mutation in X chromosome was obtained that induced degeneration of imaginal disks at the 3d stage of larva development. The gonads of the mutants at this stage of development vary in size. The transplantation tests showed that the mutation manifests itself in both the imaginal disks and the gonads

  12. Gamma-ray induced mutations in Pisum arvense (L.s.s.)

    International Nuclear Information System (INIS)

    Jaranowski, J.K.

    1976-01-01

    The subject of the studies was the progeny of seven lines of field pea, treated with gamma rays (at the doses of 1, 6, 12, 15, 50 kR) in the generations M 2 - M 4 . Of the total number of analysed 15630 plants 249 mutants have been isolated which constituted 1.59% of the total population. The mutation frequency was significantly different depending on the line under study and on the radiation dose. In the mutation spectrum lethal and semilethal mutations were prevalent. The cause of these phenomena were either chlorophyll aberrations or disturbances in the development, growth and morphology of plants. These mutations died in different periods of vegetation or did not come to flowering and died. A number of morphologic-developmental mutations have been isolated; their genotypes have been established, cytologically examined and characterized. Some of the isolated fertile mutations are similar to those obtained at other research centres (e.g., cirrhifolialis, viciaefolialis, fasciata), others seem to be original (eg. pumilio, celeriter crescens, gynaecei, multiplicis). It is necessary, however, to perform identification tests to introduce these mutations into the Pisum Genebank, the more so, as most of papers on mutations concerned edible and garden peas (P. sativum L.), and in our work we considered field forms (P. arvense L.s.s.). (author)

  13. Point mutations in Aβ induce polymorphic aggregates at liquid/solid interfaces.

    Science.gov (United States)

    Yates, Elizabeth A; Cucco, Elena M; Legleiter, Justin

    2011-06-15

    A pathological hallmark of Alzheimer's disease (AD), a late onset neurodegenerative disease, is the development of neuritic amyloid plaques, composed predominantly of aggregates of the β-amyloid (Aβ) peptide. It has been demonstrated that Aβ can aggregate into a variety of polymorphic aggregate structures under different chemical environments, and a potentially important environmental factor in dictating aggregate structure is the presence of surfaces. There are also several mutations clustered around the central hydrophobic core of Aβ (E22G Arctic mutation, E22K Italian mutation, D23N Iowa mutation, and A21G Flemish mutation). These mutations are associated with hereditary diseases ranging from almost pure cerebral amyloid angiopathy (CAA) to typical Alzheimer's disease pathology. The goal of this study was to determine how these mutations influence the morphology of Aβ aggregates under free solution conditions and at an anionic surface/liquid interface. While the rate of formation of specific aggregates was altered by mutations in Aβ under free solution conditions, the respective aggregate morphologies were similar. However, aggregation occurring directly on a negatively charged mica surface resulted in distinct aggregate morphologies formed by different mutant forms of Aβ. These studies provide insight into the potential role anionic surfaces play in dictating the formation of Aβ polymorphic aggregate structures.

  14. Inducing Somatic Pkd1 Mutations in Vivo in a Mouse Model of Autosomal-Dominant Polycystic Kidney Disease

    Science.gov (United States)

    2016-10-01

    inducing homozygous mutations of Pkd2 during embryonic kidney development . Specifically, the Six2cre enhancer drives the expression of cre in the...Cristina Cebrian-Ligero Funded Period : July 15, 2016 to July 14, 2017 Amount: $40,000 What other organizations were involved as partners? No change...Disease PRINCIPAL INVESTIGATOR: Cristina Cebrian-Ligero CONTRACTING ORGANIZATION : Regents of the University of Michigan Ann Arbor, MI, 48109-1340

  15. How to catch all those mutations--the report of the third Human Variome Project Meeting, UNESCO Paris, May 2010

    DEFF Research Database (Denmark)

    Kohonen-Corish, Maija R J; Al-Aama, Jumana Y; Auerbach, Arleen D

    2010-01-01

    . The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current...

  16. Increase in radiation-induced HPRT gene mutation frequency after nonthermal exposure to nonionizing 60 Hz electromagnetic fields.

    Science.gov (United States)

    Walleczek, J; Shiu, E C; Hahn, G M

    1999-04-01

    It is widely accepted that moderate levels of nonionizing electric or magnetic fields, for example 50/60 Hz magnetic fields of about 1 mT, are not mutagenic. However, it is not known whether such fields can enhance the action of known mutagens. To explore this question, a stringent experimental protocol, which included blinding and systematic negative controls, was implemented, minimizing the possibility of observer bias or experimental artifacts. As a model system, we chose to measure mutation frequencies induced by 2 Gy gamma rays in the redox-sensitive hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in Chinese hamster ovary cells. We tested whether a 12-h exposure to a 60 Hz sinusoidally oscillating magnetic-flux density (Brms = 0.7 mT) could affect the mutagenic effects of ionizing radiation on the HPRT gene locus. We determined that the magnetic-field exposure induced an approximate 1.8-fold increase in HPRT mutation frequency. Additional experiments at Brms = 0.23 and 0.47 mT revealed that the effect was reduced at lower flux densities. The field exposure did not enhance radiation-induced cytotoxicity or mutation frequencies in cells not exposed to ionizing radiation. These results suggest that moderate-strength, oscillating magnetic fields may act as an enhancer of mutagenesis in mammalian cells.

  17. Nicotinamide starvation and inhibition of poly(ADP-Ribose) synthesis enhance the induced mutation in Chinese hamster V79 cells

    International Nuclear Information System (INIS)

    Okada, Gensaku; Kaneko, Ichiro; Mitsui, Hideki.

    1987-01-01

    The effects of nicotinamide (NA) deficiency and added NA and 3-aminobenzamide (3AB) on the cytotoxicity and the induction of mutations in Chinese hamster V79-14 cells were investigated. In NA deficiency the addition of NA (up to 4 mM) and 3AB (up to 7.5 mM) was not cytotoxic. The presence of NA prior to exposure to mitomycin C (MMC) or γ-rays produced a dose-dependent increase in the relative cloning ability of DNA-damaged cells. The lethality of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was significantly potentiated by pre-treatment with 5 mM 3AB, but no potentiation by 3AB was observed for MMC, ultraviolet (UV)-B light, or γ-rays. Among cells pre-cultured in NA-free medium there were increased frequencies of mutations at both the hypoxanthineguanine phosphoribosyltransferase (HGPRT) and the adenine phosphoribosyltransferase (APRT) loci following DNA damage. The enhancing effect by NA deficiency was time-dependent. Incubation with NA prior to DNA damage produced a significant reduction in the frequency of mutations. The addition of 3AB to the nicotinamide adenine dinucleotide (NAD + )-depleted cell cultures before or after the DNA damage also strongly increased the frequency of induced mutations, with increasing concentrations of 3AB up to 5 mM, but the frequency was reduced at higher concentrations. The interaction between NA deficiency and the addition of 3AB appears to act synergistically on mutation induction. A correlation was observed between the potential of inhibiting poly (ADP-ribose) polymerase and the enhancement of mutation frequency. (author)

  18. Molecular and biochemical characterization of an induced mutation conferring imidazolinone resistance in sunflower.

    Science.gov (United States)

    Sala, Carlos A; Bulos, Mariano; Echarte, Mariel; Whitt, Sherry R; Ascenzi, Robert

    2008-12-01

    A partially dominant nuclear gene conferring resistance to the imidazolinone herbicides was previously identified in the cultivated sunflower (Helianthus annuus L.) line CLHA-Plus developed by seed mutagenesis. The objective of this study was to characterize this resistant gene at the phenotypic, biochemical and molecular levels. CLHA-Plus showed a complete susceptibility to sulfonylureas (metsulfuron, tribenuron and chlorsulfuron) but, on the other hand, it showed a complete resistance to imidazolinones (imazamox, imazapyr and imazapic) at two rates of herbicide application. This pattern was in close association with the AHAS-inhibition kinetics of protein extracts of CLHA-Plus challenged with different doses of imazamox and chlorsulfuron. Nucleotide and deduced amino acid sequence comparisons between resistant and susceptible lines indicated that the imidazolinone-resistant AHAS of CLHA-Plus has a threonine codon (ACG) at position 122 (relative to the Arabidopsis thaliana AHAS sequence), whereas the herbicide-susceptible enzyme from BTK47 has an alanine residue (GCG) at this position. Since the resistance genes to AHAS-inhibiting herbicides so far characterized in sunflower code for the catalytic (large) subunit of AHAS, we propose to redesignate the wild type allele as ahasl1 and the incomplete dominant resistant alleles as Ahasl1-1 (previously Imr1 or Ar ( pur )), Ahasl1-2 (previously Ar ( kan )) and Ahasl1-3 (for the allele present in CLHA-Plus). The higher tolerance level to imidazolinones and the lack of cross-resistance to other AHAS-inhibiting herbicides of Ahasl1-3 indicate that this induced mutation can be used to develop commercial hybrids with superior levels of tolerance and, at the same time, to assist weed management where control of weedy common sunflower is necessary.

  19. How to catch all those mutations--the report of the third Human Variome Project Meeting, UNESCO Paris, May 2010

    DEFF Research Database (Denmark)

    Kohonen-Corish, Maija R J; Al-Aama, Jumana Y; Auerbach, Arleen D

    2010-01-01

    The third Human Variome Project (HVP) Meeting "Integration and Implementation" was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10-14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health...... disease-specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium........ The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current...

  20. IAEA specialist meeting on flow induced vibrations in fast breeder reactors, Paris, France, 22-24 October 1986

    International Nuclear Information System (INIS)

    Perez, M.A.

    1986-10-01

    The Specialists' Meeting on ''Flow Induced Vibrations in FBRs for LMFBR Applications'' was held in Paris under the auspices of the French CEA on 21-24 October 1982. The meeting was sponsored by the IAEA on the recommendation of the 14th Meeting of the IWGFR and was attended by 31 participants from France, the Federal Republic of Germany, India, Italy, Japan, the United Kingdom, the Union of Soviet Socialist Republics, the United States of America and one international organization (IAEA). The meeting was presided over by Pr. R.J. Gibert of France. After the first session on review of national positions in the subject field (7 papers), the meeting was divided into five technical sections as follows: fluid-structures interaction, calculation methods (3 papers); tubes bundles vibration and weir (4 papers); instability (6 papers); induced vibrations in the pumps (2 papers). A separate abstract was prepared for each of these papers

  1. Enhancement of the production of L-glutaminase, an anticancer enzyme, from Aeromonas veronii by adaptive and induced mutation techniques.

    Directory of Open Access Journals (Sweden)

    S Aravinth Vijay Jesuraj

    Full Text Available Microbial anti-cancer enzymes have been proven to be effective and economical agents for cancer treatment. Aeromonas veronii has been identified as a microorganism with the potential to produce L-glutaminase, an anticancer agent effective against acute lymphocytic leukaemia. In this study, a selective medium of Aeromonas veronii was used to culture the microorganism. Strain improvement was done by adaptive and induced mutational techniques. A selective minimal agar media was incorporated for the growth of the strain which further supports adaptive mutation. Strains were also UV-irradiated and successively treated with N-methyl-N'-nitro-N-nitrosoguanidine to find a resilient strain capable of producing L-glutaminase efficiently. The Plackett-Burman design and central composite designs were used to screen and optimize additional carbon and nitrogen sources. Adaptive mutation resulted in promising yield improvements compared to native strain (P<0.001. The mean yield of 30 treated colonies from the induced mutation was significantly increased compared to the non-induced strain (P< 0.001. The economically feasible statistical designs were found to reinforce each other in order to maximize the yield of the enzyme. The interactions of nutrient factors were understood from the 3D response surface plots. The model was found to be a perfect fit in terms of maximizing enzyme yield, with the productivity improving at every stage to a fourfold output of enzyme (591.11 ±7.97 IU/mL compared to the native strain (135±3.51 IU/mL.

  2. How to catch all those mutations--the report of the third Human Variome Project Meeting, UNESCO Paris, May 2010

    DEFF Research Database (Denmark)

    Kohonen-Corish, Maija R J; Al-Aama, Jumana Y; Auerbach, Arleen D

    2010-01-01

    The third Human Variome Project (HVP) Meeting "Integration and Implementation" was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10-14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health. Th...... disease-specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium....

  3. Translesion DNA synthesis and mutation induced in a plasmid with a single adduct of the environmental contaminant 3-nitrobenzanthrone in SOS-induced Escherichia coli

    International Nuclear Information System (INIS)

    Kawanishi, M.; Kanno, T.; Yagi, T.; Enya-Takamura, T.; Fuchs, R.P.

    2003-01-01

    Full text: 3-Nitrobenzanthrone (NBA) is a powerfully mutagenic nitrated aromatic hydrocarbon found in diesel exhaust and in airborne particulate matters. NBA forms an unusual DNA adduct in vitro that has a C-C bond between the C-8 position of deoxyguanosine and the C-2 position of NBA. We previously found that this adduct is also present in the human cells treated with NBA, and induces mutations in supF shuttle vector system. In this study, we analyzed translesion DNA synthesis (TLS) over a single adduct in lacZ' gene in a plasmid in uvrAmutS Escherichia coli. The result showed that the adduct blocked DNA replication and an observed TLS frequency was 5.4% in non-SOS-induced E. coli. All progenies after the TLS had no mutation. On the other hand, TLS increased to 11.3%, and 4.8% of them had mostly G to T mutations in SOS-induced E. coli. These results suggest that this unusual adduct would be one of causes of lung cancer that is increasing in the urban areas polluted with diesel exhaust. It must be interesting to reveal which DNA polymerase is involved in this TLS

  4. Coordinated Changes in Mutation and Growth Rates Induced by Genome Reduction

    Directory of Open Access Journals (Sweden)

    Issei Nishimura

    2017-07-01

    Full Text Available Genome size is determined during evolution, but it can also be altered by genetic engineering in laboratories. The systematic characterization of reduced genomes provides valuable insights into the cellular properties that are quantitatively described by the global parameters related to the dynamics of growth and mutation. In the present study, we analyzed a small collection of W3110 Escherichia coli derivatives containing either the wild-type genome or reduced genomes of various lengths to examine whether the mutation rate, a global parameter representing genomic plasticity, was affected by genome reduction. We found that the mutation rates of these cells increased with genome reduction. The correlation between genome length and mutation rate, which has been reported for the evolution of bacteria, was also identified, intriguingly, for genome reduction. Gene function enrichment analysis indicated that the deletion of many of the genes encoding membrane and transport proteins play a role in the mutation rate changes mediated by genome reduction. Furthermore, the increase in the mutation rate with genome reduction was highly associated with a decrease in the growth rate in a nutrition-dependent manner; thus, poorer media showed a larger change that was of higher significance. This negative correlation was strongly supported by experimental evidence that the serial transfer of the reduced genome improved the growth rate and reduced the mutation rate to a large extent. Taken together, the global parameters corresponding to the genome, growth, and mutation showed a coordinated relationship, which might be an essential working principle for balancing the cellular dynamics appropriate to the environment.

  5. Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing.

    Directory of Open Access Journals (Sweden)

    Dorothy Concepcion

    2009-05-01

    Full Text Available Cellular gene expression machinery has coevolved with molecular parasites, such as viruses and transposons, which rely on host cells for their expression and reproduction. We previously reported that a wild-derived allele of mouse Nxf1 (Tap, a key component of the host mRNA nuclear export machinery, suppresses two endogenous retrovirus-induced mutations and shows suggestive evidence of positive selection. Here we show that Nxf1(CAST suppresses a specific and frequent class of intracisternal A particle (IAP-induced mutations, including Ap3d1(mh2J, a model for Hermansky-Pudlak syndrome, and Atcay(hes, an orthologous gene model for Cayman ataxia, among others. The molecular phenotype of suppression includes approximately two-fold increase in the level of correctly-spliced mRNA and a decrease in mutant-specific, alternatively-processed RNA accumulating from the inserted allele. Insertional mutations involving ETn and LINE elements are not suppressed, demonstrating a high degree of specificity to this suppression mechanism. These results implicate Nxf1 in some instances of pre-mRNA processing, demonstrate the useful range of Nxf1(CAST alleles for manipulating existing mouse models of disease, and specifically imply a low functional threshold for therapeutic benefit in Cayman ataxia.

  6. Relationship of p53 Mutations to Epidermal Cell Proliferation and Apoptosis in Human UV-Induced Skin Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Janine G. Einspahr

    1999-11-01

    Full Text Available Human skin is continually subjected to UV-irradiation with the p53 gene playing a pivotal role in repair of UV-induced DNA damage and apoptosis. Consequently, p53 alterations are early events in human UV-induced skin carcinogenesis. We studied 13 squamous cell carcinomas (SCC, 16 actinic keratoses (AK, 13 samples adjacent to an AK (chronically sun-damaged, and 14 normal-appearing skin samples for p53 mutation, p53 immunostaining (IHC, apoptosis (in situ TUNEL and morphology, and proliferation (PCNA. The frequency of p53 mutation increased from 14% in normal skin, to 38.5% in sun-damaged skin, 63% in AK, and 54% in SCC. p53 IHC increased similarly. Apoptosis (TUNEL increased from 0.06 ± 0.02%, to 0.1 ± 0.2, 0.3 ± 0.3, and 0.4 ± 0.3 in normal skin, sun-damaged skin, AK, and SCC, respectively. Apoptosis was strongly correlated with proliferation (i.e., TUNEL and PCNA, r = 0.7, P < 0.0001, and proliferation was significantly increased in the progression from normal skin to SCC. Bax was significantly increased in SCC compared to AK. These data imply that apoptosis in samples with a high frequency of p53 mutation may not necessarily be p53-dependent. We suggest that there is a mechanism for apoptosis in response to increased cellular proliferation that is p53-independent.

  7. Molecular nature of mutations induced by high-LET irradiation with argon and carbon ions in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Hirano, Tomonari; Kazama, Yusuke; Ohbu, Sumie; Shirakawa, Yuki; Liu Yang; Kambara, Tadashi; Fukunishi, Nobuhisa; Abe, Tomoko

    2012-01-01

    Linear energy transfer (LET) is an important parameter to be considered in heavy-ion mutagenesis. However, in plants, no quantitative data are available on the molecular nature of the mutations induced with high-LET radiation above 101–124 keV μm −1 . In this study, we irradiated dry seeds of Arabidopsis thaliana with Ar and C ions with an LET of 290 keV μm −1 . We analyzed the DNA alterations caused by the higher-LET radiation. Mutants were identified from the M 2 pools. In total, 14 and 13 mutated genes, including bin2, egy1, gl1, gl2, hy1, hy3–5, ttg1, and var2, were identified in the plants derived from Ar- and C-ions irradiation, respectively. In the mutants from both irradiations, deletion was the most frequent type of mutation; 13 of the 14 mutated genes from the Ar ion-irradiated plants and 11 of the 13 mutated genes from the C ion-irradiated plants harbored deletions. Analysis of junction regions generated by the 2 types of irradiation suggested that alternative non-homologous end-joining was the predominant pathway of repair of break points. Among the deletions, the proportion of large deletions (>100 bp) was about 54% for Ar-ion irradiation and about 64% for C-ion irradiation. Both current results and previously reported data revealed that the proportions of the large deletions induced by 290-keV μm −1 radiations were higher than those of the large deletions induced by lower-LET radiations (6% for 22.5–30.0 keV μm −1 and 27% for 101–124 keV μm −1 ). Therefore, the 290 keV μm −1 heavy-ion beams can effectively induce large deletions and will prove useful as novel mutagens for plant breeding and analysis of gene functions, particularly tandemly arrayed genes.

  8. CHARACTERIZATION OF ENU-INDUCED MUTATIONS IN RED BLOOD CELL STRUCTURAL PROTEINS

    Directory of Open Access Journals (Sweden)

    Katrina Kildey

    2013-03-01

    Full Text Available Murine models with modified gene function as a result of N-ethyl-N-nitrosourea (ENU mutagenesis have been used to study phenotypes resulting from genetic change. This study investigated genetic factors associated with red blood cell (RBC physiology and structural integrity that may impact on blood component storage and transfusion outcome. Forward and reverse genetic approaches were employed with pedigrees of ENU-treated mice using a homozygous recessive breeding strategy. In a “forward genetic” approach, pedigree selection was based upon identification of an altered phenotype followed by exome sequencing to identify a causative mutation. In a second strategy, a “reverse genetic” approach based on selection of pedigrees with mutations in genes of interest was utilised and, following breeding to homozygosity, phenotype assessed. Thirty-three pedigrees were screened by the forward genetic approach. One pedigree demonstrated reticulocytosis, microcytic anaemia and thrombocytosis. Exome sequencing revealed a novel single nucleotide variation (SNV in Ank1 encoding the RBC structural protein ankyrin-1 and the pedigree was designated Ank1EX34. The reticulocytosis and microcytic anaemia observed in the Ank1EX34 pedigree were similar to clinical features of hereditary spherocytosis in humans. For the reverse genetic approach three pedigrees with different point mutations in Spnb1 encoding RBC protein spectrin-1β, and one pedigree with a mutation in Epb4.1, encoding band 4.1 were selected for study. When bred to homozygosity two of the spectrin-1β pedigrees (a, b demonstrated increased RBC count, haemoglobin (Hb and haematocrit (HCT. The third Spnb1 mutation (spectrin-1β c and mutation in Epb4.1 (band 4.1 did not significantly affect the haematological phenotype, despite these two mutations having a PolyPhen score predicting the mutation may be damaging. Exome sequencing allows rapid identification of causative mutations and development of

  9. Disruption of Transcriptional Coactivator Sub1 Leads to Genome-Wide Re-distribution of Clustered Mutations Induced by APOBEC in Active Yeast Genes

    Science.gov (United States)

    Dhar, Alok; Polev, Dmitrii E.; Masharsky, Alexey E.; Rogozin, Igor B.; Pavlov, Youri I.

    2015-01-01

    Mutations in genomes of species are frequently distributed non-randomly, resulting in mutation clusters, including recently discovered kataegis in tumors. DNA editing deaminases play the prominent role in the etiology of these mutations. To gain insight into the enigmatic mechanisms of localized hypermutagenesis that lead to cluster formation, we analyzed the mutational single nucleotide variations (SNV) data obtained by whole-genome sequencing of drug-resistant mutants induced in yeast diploids by AID/APOBEC deaminase and base analog 6-HAP. Deaminase from sea lamprey, PmCDA1, induced robust clusters, while 6-HAP induced a few weak ones. We found that PmCDA1, AID, and APOBEC1 deaminases preferentially mutate the beginning of the actively transcribed genes. Inactivation of transcription initiation factor Sub1 strongly reduced deaminase-induced can1 mutation frequency, but, surprisingly, did not decrease the total SNV load in genomes. However, the SNVs in the genomes of the sub1 clones were re-distributed, and the effect of mutation clustering in the regions of transcription initiation was even more pronounced. At the same time, the mutation density in the protein-coding regions was reduced, resulting in the decrease of phenotypically detected mutants. We propose that the induction of clustered mutations by deaminases involves: a) the exposure of ssDNA strands during transcription and loss of protection of ssDNA due to the depletion of ssDNA-binding proteins, such as Sub1, and b) attainment of conditions favorable for APOBEC action in subpopulation of cells, leading to enzymatic deamination within the currently expressed genes. This model is applicable to both the initial and the later stages of oncogenic transformation and explains variations in the distribution of mutations and kataegis events in different tumor cells. PMID:25941824

  10. Mutational spectrum of the lacI gene in Escherichia coli K12 induced by low-energy ion beam

    International Nuclear Information System (INIS)

    Tang Mingli; Wang Shun Chang; Wang Tao; Zhao Shiguang; Wu Yaojing; Wu Lijun; Yu Zengliang

    2006-01-01

    The mutational spectrum of the genomic lacI gene induced by low-energy nitrogen ion irradiation in wild type Escherichia coli strain W3110 were compared with the spontaneous and the vacuum controls. The mutant frequency of irradiated group was dose-dependent and reached 26.3 x 10 -6 at dose of 31.2 x 10 14 ions/cm 2 , which was about 18-fold over the background (1.5 x 10 -6 ) and 10-fold over the vacuum controls (2.6 x 10 -6 ). This result indicated that the low-energy ion irradiation was one of many effective mutagens, though the vacuum condition of low-energy ions contributed some low-level gene mutations. It was found that the difference between the spontaneous and the vacuum control was the increases of base-pair substitutions in the vacuum control group. The spectra of irradiated group were quite similar to that of oxygen free-radical induced in the same strain, suggesting free-radicals and other adducts generated by low-energy ions might play an important role in the mutagenesis in vivo. When the spontaneous and the vacuum control group were compared, base-pair substitutions, deletions and additions of the irradiated group were significantly increased, and the +TGGC or -TGGC at hot spot was decreased from 82 to 48%. But the remarkable increase in absolute MF of the +TGGC or -TGGC at hot spot in the irradiated group suggested that low-energy ions did induce the mutations of this type. The spectra of our irradiated group had relative low-level base-pair substitutions, high-level ±TGGC and high proportion additions than those of γ-radiation induced, implying there were some different effects or processes between them

  11. Phonic and induced level of mutations and mutagenicity in bioorganisms habitating in the environs of Ignalina APP

    International Nuclear Information System (INIS)

    Lekevichius, R.; Morkunas, V.; Knabikas, A.

    1992-01-01

    The investigation of the extracts from the water, mud and hydrobionts of the lake Drukshiai before the construction of the Ignalina atomic power plant (1982-1984) and after its construction enabled to detect the moment of the build-up of mutagens in the hydrobionts (in 1986), when the extracts began to induce spot mutations in Salmonella typhimurium and exchanges of sister chromatids in human leukocytes in vitro. The mutagenicity of rain water, sewerage water and water from the cooler of the atomic power plant to drosophila and Salmonella typhimurium has been detected. The increments of mutations in the populations of Larus ridibundus and Microtus arvalis inhabiting the surroundings of the atomic power plant has not been noticed. (author). 4 figs., 4 refs

  12. Induced pluripotent stem cells (iPSCs derived from cerebrotendinous xanthomatosis (CTX patient's fibroblasts carrying a R395S mutation

    Directory of Open Access Journals (Sweden)

    Philip Höflinger

    2016-09-01

    Full Text Available Induced pluripotent stem cells (iPSCs were generated from dermal fibroblasts from a 60-year-old cerebrotendinous xanthomatosis (CTX patient, carrying a homozygous mutation c. [1183C>A]; p. R395S in CYP27A1. Episomal plasmids encoding the pluripotency genes OCT4, SOX2, KLF4, L-MYC and LIN28 were introduced via electroporation. The generated line iPS-CTX-R395S has no sign of plasmid integration or chromosomal aberration and retained the mutation site in CYP27A1. Furthermore, iPSCs express pluripotency markers and are able to differentiate in all germ layers in vitro. The generated line may be a useful tool for disease modelling of CTX.

  13. NanoTIO2 (UV-Titan does not induce ESTR mutations in the germline of prenatally exposed female mice

    Directory of Open Access Journals (Sweden)

    Boisen Anne Mette

    2012-06-01

    Full Text Available Abstract Background Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR loci in mice are sensitive markers of mutagenic effects on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development. Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed to radiation has previously been reported. Here we investigate the effects of nanoparticles on the female germline. Since pulmonary exposure to nanosized titanium dioxide (nanoTiO2 produces a long-lasting inflammatory response in mice, it was chosen for the present study. Findings Pregnant C57BL/6 mice were exposed by whole-body inhalation to the nanoTiO2 UV-Titan L181 (~42.4 mg UV-Titan/m3 or filtered clean air on gestation days (GD 8–18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates in this generation were estimated from full pedigrees (mother, father, offspring of F1 female mice (192 UV-Titan-exposed F2 offspring and 164 F2 controls. ESTR mutation rates of 0.029 (maternal allele and 0.047 (paternal allele in UV-Titan-exposed F2 offspring were not statistically different from those of F2 controls: 0.037 (maternal allele and 0.061 (paternal allele. Conclusions We found no evidence for increased ESTR mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8-18 relative to control females.

  14. Mutation breeding of oil seed crops. Proceedings of a final research co-ordination meeting of an FAO/IAEA co-ordinated research programme held in Vienna, 11-15 January 1993

    International Nuclear Information System (INIS)

    1994-12-01

    The document contains 19 papers presented at the final Research Co-ordination Meeting on 'Mutation Breeding of Oil Seed Crops' held in Vienna between 11-15 January 1993. A separate abstract was prepared for each paper. Refs, figs and tabs

  15. CRISPR/Cas9-mediated mutation of tyrosinase (Tyr) 3' UTR induce graying in rabbit.

    Science.gov (United States)

    Song, Yuning; Xu, Yuxin; Deng, Jichao; Chen, Mao; Lu, Yi; Wang, Yong; Yao, Haobin; Zhou, Lina; Liu, Zhiquan; Lai, Liangxue; Li, Zhanjun

    2017-05-08

    The 3' untranslated regions (UTRs), located at the end of mRNA molecules, are believed to play a role in RNA replication and/or protein translation. Mutations in the tyrosinase (Tyr) gene are known to cause recessive albinism in humans and other species. In this study, to test whether the CRISPR/Cas9 system works on the mutation of the UTRs regulatory region in rabbit, the 3' UTR of the rabbit Tyr gene was deleted by a dual sgRNA directed CRISPR/Cas9 system. As expected, gray coat color and reduced melanin in hair follicles and irises was found in the mutated rabbit, thus increasing confidence in the association of the mutation of the Tyr 3' UTR with graying in rabbit. The graying phenotype was also found in the F1 generation, suggesting that the mutated allele can be stably inherited by the offspring. Thus, we provide the first evidence that reduced melanin and graying can be caused by deletion of the Tyr 3' UTR in rabbits. Additionally, CRISPR/Cas9-mediated large fragment deletions can facilitate genotype to phenotype studies of UTRs or non-coding RNAs in future.

  16. A switch from high-fidelity to error-prone DNA double-strand break repair underlies stress-induced mutation.

    Science.gov (United States)

    Ponder, Rebecca G; Fonville, Natalie C; Rosenberg, Susan M

    2005-09-16

    Special mechanisms of mutation are induced in microbes under growth-limiting stress causing genetic instability, including occasional adaptive mutations that may speed evolution. Both the mutation mechanisms and their control by stress have remained elusive. We provide evidence that the molecular basis for stress-induced mutagenesis in an E. coli model is error-prone DNA double-strand break repair (DSBR). I-SceI-endonuclease-induced DSBs strongly activate stress-induced mutations near the DSB, but not globally. The same proteins are required as for cells without induced DSBs: DSBR proteins, DinB-error-prone polymerase, and the RpoS starvation-stress-response regulator. Mutation is promoted by homology between cut and uncut DNA molecules, supporting a homology-mediated DSBR mechanism. DSBs also promote gene amplification. Finally, DSBs activate mutation only during stationary phase/starvation but will during exponential growth if RpoS is expressed. Our findings reveal an RpoS-controlled switch from high-fidelity to mutagenic DSBR under stress. This limits genetic instability both in time and to localized genome regions, potentially important evolutionary strategies.

  17. A sucrose-rich diet induces mutations in the rat colon

    DEFF Research Database (Denmark)

    Dragsted, Lars O.; Daneshvar, Bahram; Vogel, Ulla

    2002-01-01

    affecting the overall energy and carbohydrate intake. We observed a dose-dependent increase in the mutation frequency at the cII site in the colonic mucosa with increased sucrose levels, reaching a 129% increase at the highest dose level. This would indicate a direct or indirect genotoxic effect...... of a sucrose-rich diet. No significant increase in mutations was observed in the liver. To seek an explanation for this finding, a variety of parameters were examined representing different mechanisms, including increased oxidative stress, changes in oxidative defense, effects on DNA repair, or changes......, but the background level of DNA adducts (I-compounds) as determined by (32)P postlabeling was significantly decreased in colon. This decrease in colon I-compounds correlated inversely with both mutation frequency and ERCC1 DNA repair gene expression. Dietary sucrose did not change liver apoptosis or cell turnover...

  18. The influence of large deletions on the mutation frequency induced by tritiated water and X-radiation in male Drosophila melanogaster post-meiotic germ cells

    International Nuclear Information System (INIS)

    Fossett, N.G.; Byrne, B.J.; Kelley, S.J.; Tucker, A.B.; Arbour-Reily, P.; Lee, W.R.

    1994-01-01

    Tritium beta radiation ( 3 H β-radiation) in the form of tritiated water was used to induce mutations at the alcohol dehydrogenase (Adh) locus in male Drosophila melanogaster post-meiotic germ cells. All 23 Adh null mutations were large deletions (>20 kb), determined by genetic complementation and Southern blot analyses. 27 Adh null mutations have been induced by 100-kVp X-rays and have been genetically and molecularly characterized. In contrast to 3 H β-radiation, 100-kVp X-rays induced a bimodal distribution of Adh null mutations, intragenic mutations, ≤250 bp, and large deletions, >100 kb. A statistically significant difference was observed between the frequency of large deletions (23/23 or 1.0) induced by 3 H β-radiation and the frequency of large deletions (19/27 or 0.7) induced by 100-kVp X-rays. However, a statistical difference was not observed between the size distribution of the large deletions induced by 3 H β-radiation and X-rays. The relative deletion frequency (RDF) induced by 3 H β-radiation and 100-kVp X-rays was (1.0/0.7=1.4). The relative biological effectiveness (RBE) of these two radiation sources was 1.4, determined from the ratio of the regression coefficients of the respective 3 H β-radiation and X-ray sex-linked recessive lethal (SLRL) dose-response data. The large difference in size between the two classes of X-ray-induced Adh null mutations and the increase in mutation frequency and deletion frequency for 3 H β-radiation with respect to X-rays may indicate that the relative deletion frequency (RDF) is the molecular biological basis for the increase in the RBE for radiation sources with a mean LET value ≤10 keV/μm

  19. Gsp mutation in acromegaly and its influence on TRH-induced paradoxical GH response.

    Science.gov (United States)

    Goto, Yuko; Kinoshita, Manabu; Oshino, Satoru; Arita, Hideyuki; Kitamura, Tetsuhiro; Otsuki, Michio; Shimomura, Iichiro; Yoshimine, Toshiki; Saitoh, Youichi

    2014-05-01

    We recently reported that paradoxical GH response to TRH administration reflects biological characteristics in patients with acromegaly. The aim of this study is to elucidate the relationship between gsp mutations and the paradoxical GH response to TRH. Sixty-seven patients with acromegaly were included for analysis. Paradoxical increase in serum GH level to TRH, GH suppression by octreotide and bromocriptine, radiological profiles and histopathological findings were analysed with respect to tumour gsp-mutation status. Twenty-six (38·8%) gsp mutations were detected, and the number of paradoxical GH responders to TRH, defined as an increase of 100% or more in GH after TRH, was 49 (73·1%). Among the paradoxical GH responders to TRH, 21 patients (42·9%) had a gsp mutation and 28 patients (57·1%) did not. The percentage of paradoxical GH responders to TRH in gsp-positive and gsp-negative patients was not significantly different (80·8% and 68·3%, respectively). The gsp-positive group showed a significantly higher paradoxical increase in serum GH level by TRH administration (1830% vs 650% GH increase, P = 0·045) and greater GH suppression by octreotide (88·7% vs 75·4% GH decrease, P = 0·003) than the gsp-negative group. Paradoxical GH response to TRH was observed regardless of gsp mutation, although the rate of increase was significantly higher in gsp-positive patients. These results suggest that gsp mutation is not sufficient to cause the paradoxical GH response to TRH, while other unidentified factors have a strong influence on paradoxical GH response to TRH in patients with acromegaly. © 2013 John Wiley & Sons Ltd.

  20. Singlet oxygen-induced mutations in M13 lacZ phage DNA.

    OpenAIRE

    Decuyper-Debergh, D; Piette, J; Van de Vorst, A

    1987-01-01

    The mutagenic consequences of damages to M13 mp19 RF DNA produced by singlet oxygen have been determined in a forward mutational system capable of detecting all classes of mutagenic events. When the damaged M13 mp19 RF DNA is used to transfect competent E. coli JM105 cells, a 16.6-fold increase in mutation frequency is observed at 5% survivors when measured as a loss of alpha-complementation. The enhanced mutagenicity is largely due to single-nucleotide substitutions, frameshift events and do...

  1. The Number of Point Mutations in Induced Pluripotent Stem Cells and Nuclear Transfer Embryonic Stem Cells Depends on the Method and Somatic Cell Type Used for Their Generation.

    Science.gov (United States)

    Araki, Ryoko; Mizutani, Eiji; Hoki, Yuko; Sunayama, Misato; Wakayama, Sayaka; Nagatomo, Hiroaki; Kasama, Yasuji; Nakamura, Miki; Wakayama, Teruhiko; Abe, Masumi

    2017-05-01

    Induced pluripotent stem cells hold great promise for regenerative medicine but point mutations have been identified in these cells and have raised serious concerns about their safe use. We generated nuclear transfer embryonic stem cells (ntESCs) from both mouse embryonic fibroblasts (MEFs) and tail-tip fibroblasts (TTFs) and by whole genome sequencing found fewer mutations compared with iPSCs generated by retroviral gene transduction. Furthermore, TTF-derived ntESCs showed only a very small number of point mutations, approximately 80% less than the number observed in iPSCs generated using retrovirus. Base substitution profile analysis confirmed this greatly reduced number of point mutations. The point mutations in iPSCs are therefore not a Yamanaka factor-specific phenomenon but are intrinsic to genome reprogramming. Moreover, the dramatic reduction in point mutations in ntESCs suggests that most are not essential for genome reprogramming. Our results suggest that it is feasible to reduce the point mutation frequency in iPSCs by optimizing various genome reprogramming conditions. We conducted whole genome sequencing of ntES cells derived from MEFs or TTFs. We thereby succeeded in establishing TTF-derived ntES cell lines with far fewer point mutations. Base substitution profile analysis of these clones also indicated a reduced point mutation frequency, moving from a transversion-predominance to a transition-predominance. Stem Cells 2017;35:1189-1196. © 2017 AlphaMed Press.

  2. The Cancer Mutation D83V Induces an α-Helix to β-Strand Conformation Switch in MEF2B.

    Science.gov (United States)

    Lei, Xiao; Kou, Yi; Fu, Yang; Rajashekar, Niroop; Shi, Haoran; Wu, Fang; Xu, Jiang; Luo, Yibing; Chen, Lin

    2018-04-13

    MEF2B is a major target of somatic mutations in non-Hodgkin lymphoma. Most of these mutations are non-synonymous substitutions of surface residues in the MADS-box/MEF2 domain. Among them, D83V is the most frequent mutation found in tumor cells. The link between this hotspot mutation and cancer is not well understood. Here we show that the D83V mutation induces a dramatic α-helix to β-strand switch in the MEF2 domain. Located in an α-helix region rich in β-branched residues, the D83V mutation not only removes the extensive helix stabilization interactions but also introduces an additional β-branched residue that further shifts the conformation equilibrium from α-helix to β-strand. Cross-database analyses of cancer mutations and chameleon sequences revealed a number of well-known cancer targets harboring β-strand favoring mutations in chameleon α-helices, suggesting a commonality of such conformational switch in certain cancers and a new factor to consider when stratifying the rapidly expanding cancer mutation data. Copyright © 2018. Published by Elsevier Ltd.

  3. Induced androgenesis in vitro in mutated populations of barley, Hordeum vulgare

    Czech Academy of Sciences Publication Activity Database

    Vagera, Jiří; Novotný, J.; Ohnoutková, Ludmila

    2004-01-01

    Roč. 77, č. 1 (2004), s. 55-61 ISSN 0167-6857 R&D Projects: GA MZe QF4133; GA ČR GA521/03/0113; GA MZe QE1093 Institutional research plan: CEZ:AV0Z5038910 Keywords : anther culture * chlorophyll mutations * enhanced embryogenesis Subject RIV: GE - Plant Breeding Impact factor: 1.028, year: 2004

  4. Ab initio prediction of mutation-induced cryptic splice-site activation and exon skipping

    Czech Academy of Sciences Publication Activity Database

    Divina, Petr; Kvitkovicova, Andrea; Buratti, E.; Vorechovsky, I.

    2009-01-01

    Roč. 17, č. 6 (2009), s. 759-765 ISSN 1018-4813 Institutional research plan: CEZ:AV0Z50520514 Keywords : mutation * cryptic splice site * exon skipping Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.564, year: 2009

  5. Ancient Genes Establish Stress-Induced Mutation as a Hallmark of Cancer

    NARCIS (Netherlands)

    Cisneros, L; Bussey, K; Orr, A; Miočević, M.; Lineweaver, C; Davies, Paul

    2017-01-01

    Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms

  6. Proteomic analysis of the low mutation rate of diploid male gametes induced by colchicine in Ginkgo biloba L.

    Directory of Open Access Journals (Sweden)

    Nina Yang

    Full Text Available Colchicine treatment of G. biloba microsporocytes results in a low mutation rate in the diploid (2n male gamete. The mutation rate is significantly lower as compared to other tree species and impedes the breeding of new economic varieties. Proteomic analysis was done to identify the proteins that influence the process of 2n gamete formation in G. biloba. The microsporangia of G. biloba were treated with colchicine solution for 48 h and the proteins were analyzed using 2-D gel electrophoresis and compared to protein profiles of untreated microsporangia. A total of 66 proteins showed difference in expression levels. Twenty-seven of these proteins were identified by mass spectrometry. Among the 27 proteins, 14 were found to be up-regulated and the rest 13 were down-regulated. The identified proteins belonged to five different functional classes: ATP generation, transport and carbohydrate metabolism; protein metabolism; ROS scavenging and detoxifying enzymes; cell wall remodeling and metabolism; transcription, cell cycle and signal transduction. The identification of these differentially expressed proteins and their function could help in analysing the mechanism of lower mutation rate of diploid male gamete when the microsporangium of G. biloba was induced by colchicine.

  7. Alterations of the immunosuppressive IL4I1 enzyme activity induced by naturally occurring SNP/mutations.

    Science.gov (United States)

    Molinier-Frenkel, V; Mestivier, D; Castellano, F

    2016-03-01

    The immunosuppressive phenylalanine oxidase interleukin 4-induced gene 1 (IL4I1), primarily produced by antigen-presenting cells, inhibits T-cell proliferation and promotes the generation of Foxp3(+) regulatory T cells in vitro. Highly expressed by tumour-associated macrophages from human cancers, IL4I1 has a potential role in immune evasion from the anti-tumour immune response. We have reviewed single-nucleotide polymorphisms (SNPs) and mutations described for the exon 4 of the IL4I1 isoform 1, which is expressed in lymphoid tissue. Two of them were expressed in an exogenous system to analyse their effect on the enzymatic activity. The N92D SNP leads to a hyperactive enzyme, while the R102G mutation is hypomorphic. Moreover, we show that IL4I1 activity is not only directed against phenylalanine, as initially described, but also at a lower level against arginine. These data pave the way to more extensive analyses of the mutational state of IL4I1 in pathological conditions such as cancer, where its participation in immune system dysfunctions may have therapeutic implications.

  8. Exon Skipping and Gene Transfer Restore Dystrophin Expression in Human Induced Pluripotent Stem Cells-Cardiomyocytes Harboring DMD Mutations

    Science.gov (United States)

    Dick, Emily; Kalra, Spandan; Anderson, David; George, Vinoj; Ritso, Morten; Laval, Steven H.; Barresi, Rita; Aartsma-Rus, Annemieke; Lochmüller, Hanns

    2013-01-01

    With an incidence of ∼1:3,500 to 5,000 in male children, Duchenne muscular dystrophy (DMD) is an X-linked disorder in which progressive muscle degeneration occurs and affected boys usually die in their twenties or thirties. Cardiac involvement occurs in 90% of patients and heart failure accounts for up to 40% of deaths. To enable new therapeutics such as gene therapy and exon skipping to be tested in human cardiomyocytes, we produced human induced pluripotent stem cells (hiPSC) from seven patients harboring mutations across the DMD gene. Mutations were retained during differentiation and analysis indicated the cardiomyocytes showed a dystrophic gene expression profile. Antisense oligonucleotide-mediated skipping of exon 51 restored dystrophin expression to ∼30% of normal levels in hiPSC-cardiomyocytes carrying exon 47–50 or 48–50 deletions. Alternatively, delivery of a dystrophin minigene to cardiomyocytes with a deletion in exon 35 or a point mutation in exon 70 allowed expression levels similar to those seen in healthy cells. This demonstrates that DMD hiPSC-cardiomyocytes provide a novel tool to evaluate whether new therapeutics can restore dystrophin expression in the heart. PMID:23829870

  9. Rapid identification of aminoglycoside-induced deafness gene mutations using multiplex real-time polymerase chain reaction.

    Science.gov (United States)

    Huang, Shasha; Xiang, Guangxin; Kang, Dongyang; Wang, Chen; Kong, Yanling; Zhang, Xun; Liang, Shujian; Mitchelson, Keith; Xing, Wanli; Dai, Pu

    2015-07-01

    Exposure to aminoglycoside antibiotics can induce ototoxicity in genetically susceptible individuals carrying certain mitochondrial DNA (mtDNA) mutations (C1494T and A1555G), resulting in hearing loss. So, a rapid diagnostic approach is needed to accurately identify subjects carrying such gene mutations. In the present study, we describe a rapid and reliable four-color, real-time quantitative polymerase chain reaction (qPCR) assay for simultaneously detecting two mtDNA 12S rRNA gene variants, A1555G and C1494T, which are prevalent in the Han Chinese population. This multiplex assay incorporates three allele-specific TaqMan probes labeled with different fluorophores in a single reaction, providing high genotyping accuracy for clinical blood samples. Tests with C1494T, A1555G and wild-type DNA exhibited high sensitivity, specificity, reproducibility and accuracy of discriminating mutations from wild-type. This study shows that this simple and inexpensive method can be used for routine molecular diagnostics and potentially for large-scale genetic screening. Copyright © 2015. Published by Elsevier Ireland Ltd.

  10. Single mutation induced H3N2 hemagglutinin antibody neutralization: a free energy perturbation study.

    Science.gov (United States)

    Zhou, Ruhong; Das, Payel; Royyuru, Ajay K

    2008-12-11

    The single mutation effect on the binding affinity of H3N2 viral protein hemagglutinin (HA) with the monoclonical antibody fragment (Fab) is studied in this paper using the free energy perturbation (FEP) simulations. An all-atom protein model with explicit solvents is used to perform an aggregate of several microsecond FEP molecular dynamics simulations. A recent experiment shows that a single mutation in H3N2 HA, T131I, increases the antibody-antigen dissociation constant Kd by a factor of approximately 4000 (equivalent to a binding affinity decrease of approximately 5 kcal/mol), thus introducing an escape of the antibody (Ab) neutralization. Our FEP result confirms this experimental finding by estimating the HA-Ab binding affinity decrease of 5.2 +/- 0.9 kcal/mol but with a somewhat different molecular mechanism from the experimental findings. Detailed analysis reveals that this large binding affinity decrease in the T131I mutant is mainly due to the displacement of two bridge water molecules otherwise present in the wild-type HA/Ab interface. The decomposition of the binding free energy supports this observation, as the major contribution to the binding affinity is from the electrostatic interactions. In addition, we find that the loss of the binding affinity is also related to the large conformational distortion of one loop (loop 155-161) in the unbound state of the mutant. We then simulate all other possible mutations for this specific mutation site T131, and predict a few more mutations with even larger decreases in the binding affinity (i.e., better candidates for antibody neutralization), such as T131W, T131Y, and T131F. As for further validation, we have also modeled another mutation, S157L, with experimental binding affinity available (Kd increasing approximately 500 times), and found a binding affinity decrease of 4.1 +/- 1.0 kcal/mol, which is again in excellent agreement with experiment. These large scale simulations might provide new insights into the

  11. Hypoxia-inducible factor-1α polymorphisms and TSC1/2 mutations are complementary in head and neck cancers

    Directory of Open Access Journals (Sweden)

    Nikitakis Nikolaos G

    2006-01-01

    Full Text Available Abstract Background Polymorphisms or mutations in hypoxia inducible factor-1 alpha (HIF-1alpha that increases its activity and stability under normoxia have recently been identified. Likewise, disruption of the TSC1/TSC2 complex through loss of TSC1 or TSC2 has been shown to result in abnormal accumulation of HIF-1α. Here, we investigate the novel polymorphisms in exon 12, that approximate the oxygen-dependent degradation domain of HIF-1alpha in five cell lines and 28 patients with oral squamous carcinomas. Moreover, we assess for the presence of polymorphisms and mutations in TSC1 and TSC2, to ascertain if dysregulation of such might complement HIF-1alpha expression. Results Denaturing high pressure liquid chromatography (DHPLC analysis on PCR fragments in exon 12 of HIF-1alpha from 28 patients with OSCC revealed that 6 of 28 patients had mismatched heteroduplex patterns. Genomic DNA was extracted from peripheral blood leukocytes and direct sequencing showed that in 5 of the six cases these changes represented polymorphisms while, one case was a somatic mutation. Analyses of TSC1 and TSC2 revealed heteroduplexes in exons: TSC1 exon 17; TSC2 exons 36,40, and 41. The relative levels of HIF-1alpha were significantly greater for tumors possessing a HIF-1alpha polymorphism or mutation within exon 12, whereas tumors possessing a deletion or polymorphism in TSC1/TSC2 displayed a trend for higher levels of HIF-1alpha. Western blot analyses for HIF-1alpha, TSC1 and TSC2 in five SCC cell lines revealed high levels of HIF-1alpha in SCC cells possessing TSC1 and/or TSC2 mutations. Wild-type TSC2 cells targeted with siRNA to TSC2 exhibited increased levels of HIF-1alpha. Transfection of a HIF-1alpha mutant produced higher levels of HIF-1alpha in TSC1/TSC2 mutant cell lines than in wild type cells. TSC1/TSC2 mutant cell lines administered Rapamycin blocked S6 phorphorylation and diminished the levels of HIF-1alpha to those observed in cell lines with wild

  12. Hypercholesterolemia Induced by a PCSK9 Gain-of-Function Mutation Augments Angiotensin II-Induced Abdominal Aortic Aneurysms in C57BL/6 Mice-Brief Report.

    Science.gov (United States)

    Lu, Hong; Howatt, Deborah A; Balakrishnan, Anju; Graham, Mark J; Mullick, Adam E; Daugherty, Alan

    2016-09-01

    Gain-of-function mutations of PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to hypercholesterolemia. This study was to determine whether infection of normocholesterolemic mice with an adeno-associated viral (AAV) vector expressing a gain-of-function mutation of mouse PCSK9 increased angiotensin II (AngII)-induced abdominal aortic aneurysms. In an initial study, male C57BL/6 mice were injected intraperitoneally with either an empty vector or PCSK9 gain-of-function mutation (D377Y). AAV at 3 doses and fed a saturated fat-enriched diet for 6 weeks. Two weeks after AAV injection, mice were infused with AngII for 4 weeks. Plasma PCSK9 concentrations were increased dose dependently in mice injected with AAV containing PCSK9D377Y mutation and positively associated with elevations of plasma cholesterol concentrations. Infection with intermediate and high doses of PCSK9D377Y.AAV led to equivalent increases of maximal width of abdominal aortas in C57BL/6 mice infused with AngII. Therefore, the intermediate dose was used in subsequent experiments. We then determined effects of PCSK9D377Y.AAV infection on 5 normolipidemic mouse strains, demonstrating that C57BL/6 mice were the most susceptible to this AAV infection. PCSK9D377Y.AAV infected male C57BL/6 mice were also compared with age-matched male low-density lipoprotein receptor(-/-) mice. Although plasma cholesterol concentrations were lower in mice infected with PCSK9D377Y.AAV, these mice had equivalent abdominal aortic aneurysmal formation, compared to low-density lipoprotein receptor(-/-) mice. In a separate study, reduced plasma PCSK9 concentrations by PCSK9 antisense oligonucleotides in male low-density lipoprotein receptor(-/-) mice did not influence AngII-induced abdominal aortic aneurysms. AAV-mediated infection with a mouse PCSK9 gain-of-function mutation is a rapid, easy, and efficient approach for inducing hypercholesterolemia and promoting abdominal aortic aneurysms in C57BL/6 mice infused with Ang

  13. Differential Effects of HRAS Mutation on LTP-Like Activity Induced by Different Protocols of Repetitive Transcranial Magnetic Stimulation.

    Science.gov (United States)

    Dileone, Michele; Ranieri, Federico; Florio, Lucia; Capone, Fioravante; Musumeci, Gabriella; Leoni, Chiara; Mordillo-Mateos, Laura; Tartaglia, Marco; Zampino, Giuseppe; Di Lazzaro, Vincenzo

    2016-01-01

    Costello syndrome (CS) is a rare congenital disorder due to a G12S amino acid substitution in HRAS protoncogene. Previous studies have shown that Paired Associative Stimulation (PAS), a repetitive brain stimulation protocol inducing motor cortex plasticity by coupling peripheral nerve stimulation with brain stimulation, leads to an extremely pronounced motor cortex excitability increase in CS patients. Intermittent Theta Burst Stimulation (iTBS) represents a protocol able to induce motor cortex plasticity by trains of stimuli at 50 Hz. In healthy subjects PAS and iTBS produce similar after-effects in motor cortex excitability. Experimental models showed that HRAS-dependent signalling pathways differently affect LTP induced by different patterns of repetitive synaptic stimulation. We aimed to compare iTBS-induced after-effects on motor cortex excitability with those produced by PAS in CS patients and to observe whether HRAS mutation differentially affects two different forms of neuromodulation protocols. We evaluated in vivo after-effects induced by PAS and iTBS applied over the right motor cortex in 4 CS patients and in 21 healthy age-matched controls. Our findings confirmed HRAS-dependent extremely pronounced PAS-induced after-effects and showed for the first time that iTBS induces no change in MEP amplitude in CS patients whereas both protocols lead to an increase of about 50% in controls. CS patients are characterized by an impairment of iTBS-related LTP-like phenomena besides enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling pathways have a differential influence on PAS- and iTBS-induced plasticity in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome.

    Science.gov (United States)

    Carmona-Mora, Paulina; Encina, Carolina A; Canales, Cesar P; Cao, Lei; Molina, Jessica; Kairath, Pamela; Young, Juan I; Walz, Katherina

    2010-08-25

    Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1). Little is known about the function of human RAI1. We generated the full-length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end) were able to localize into the nucleus but had no transactivation activity. Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains.

  15. Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1 mutations associated with Smith-Magenis Syndrome

    Directory of Open Access Journals (Sweden)

    Carmona-Mora Paulina

    2010-08-01

    Full Text Available Abstract Background Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1. Little is known about the function of human RAI1. Results We generated the full-length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end were able to localize into the nucleus but had no transactivation activity. Conclusion Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains.

  16. Sectoring patterns of spontaneous and radiation-induced somatic pink mutations in the stamen hairs of a temperature-sensitive mutable clone of Tradescantia

    International Nuclear Information System (INIS)

    Ichikawa, Sadao

    1994-01-01

    The sectoring patterns of somatic pink mutations were analyzed in the stamen hairs of Tradescantia clone KU 20, a temperature-sensitive mutable clone. This clone is a blue/pink heterozygote, and its spontaneous pink mutation frequency increases up to about 40-fold at lower temperature. In order to elucidate the mutable nature of this clone, the sectoring patterns were analyzed on 1,123 spontaneous pink mutant events and on 2,725 pink mutant events induced by 0.606 and 1.28 Gy of gamma rays. The average number of pink cells per terminal pink mutant event (a row of pink cells including the terminal cell of a hair) occurred spontaneously was 7.40, whereas the number for the terminal pink mutant event induced by gamma rays varied from 3.33 to 9.88 depending on the post-irradiation days, i.e., increased gradually as the number of days proceeded, then was stabilized at the level of spontaneous mutations after about three weeks. The average number of pink cells per interstitial pink mutant event (a single pink cell or two or more contiguous pink cells between blue cells was 1.97 for spontaneous mutations, while the number for induced mutations varied also depending on the post-irradiation days. The ratio of the number of interstitial pink mutant events against that of terminal pink mutant events was 1.35 for spontaneous mutations, but the ratio for induced mutations varied also with post-irradiation period reaching 2.89 at the peak, indicating that more interstitial pink mutant events are induced by gamma rays than terminal pink mutant events, as compared with spontaneous mutations. The frequency of multiple pink mutant sectors in a hair was more than four times higher than that expected from independent occurrences in case of spontaneous mutations, while the frequency was close to the expectation in induced mutations. suggesting that somatic recombination is involved as one of the major causes of spontaneous mutations in this mutable clone. (author)

  17. Genetic predisposition to radiation induced sarcoma: possible role for BRCA and p53 mutations.

    Science.gov (United States)

    Kadouri, Luna; Sagi, Michal; Goldberg, Yael; Lerer, Israela; Hamburger, Tamar; Peretz, Tamar

    2013-07-01

    The estimated incidence of radiation-associated sarcoma (RAS) is 0.03-0.2 % in 5 years post treatment. Most cancer predisposing genes are involved in DNA repair; therefore, elevated RAS risk in these patients is plausible. Cases of angiosarcoma post breast cancer treatment were reported in BRCA1 and BRCA2 carriers. We report the genetic evaluation of seven cases with suspected RAS from patients counseled in our cancer-genetic clinic. Of 2,885 breast cancer patient, 470 were BRCA1 or two mutation carriers and three were p53 mutation carriers. Of them seven developed sarcoma in the field of irradiation; five in the chest wall and two in other sites. Genetic evaluation revealed BRCA1 mutation in two, BRCA2 mutation in additional patient and a carrier of p53 mutation. The estimation of risk for RAS in patients with genetic predisposition is limited due to the rarity of this event, and the bias in referral to the clinic toward younger age. With these limitations the rate of RAS is 0.43 % (2/470, 95 % CI -0.17 to 1.02, SE = 0.3) in this group in a median follow-up of 8.2 years (range 1 month to 51 years). If we assume irradiation for the breast in 80 % of the patients than rate of RAS in group is proximately 0.53 % (2/376, 95 % CI -0.21 to 1.26, SE = 0.37). A BRCA1 carrier which had sarcoma after irradiation to head and neck carcinoma was not included in these analyses. In conclusion, we found a high frequency of BRCA1/2 mutation among our patients diagnosed with RAS. However, we estimated approximately twofold increase in the risk of RAS in BRCA1/2 carriers which was not significant compared to reports in general population. Therefore, RAS is a rare event in BRCA carriers as in the general population, and should not be considered in the decision regarding irradiation treatment in this population.

  18. 9,10-Phenanthrenequinone induces DNA deletions and forward mutations via oxidative mechanisms in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Rodriguez, Chester E; Sobol, Zhanna; Schiestl, Robert H

    2008-03-01

    The estimated cancer risk from diesel exhaust particles (DEP) in the air is approximately 70% of the cancer risk from all air pollutants. DEP is comprised of a complex mixture of chemicals whose carcinogenic potential has not been adequately assessed. The polycyclic aromatic hydrocarbon quinone 9,10-phenanthrenequinone (9,10 PQ) is a major component of DEP and a suspect genotoxic agent for DEP induced DNA damage. 9,10 PQ undergoes redox cycling to produce reactive oxygen species that can lead to oxidative DNA damage. We used two systems in the yeast Saccharomyces cerevisiae to examine possible differential genotoxicity of 9,10 PQ. The DEL assay measures intra-chromosomal homologous recombination leading to DNA deletions and the CAN assay measures forward mutations leading to canavanine resistance. Cells were exposed to 9,10 PQ aerobically and anaerobically followed by DNA damage assessment. The results indicate that 9,10 PQ induces DNA deletions and point mutations in the presence of oxygen while exhibiting negligible effects anaerobically. In contrast to the cytotoxicity observed aerobically, the anaerobic effects of 9,10 PQ seem to be cytostatic in nature, reducing growth without affecting cell viability. Thus, 9,10 PQ requires oxygen for genotoxicity while different toxicities exhibited aerobically and anaerobically suggest multiple mechanisms of action.

  19. Spectrum and Frequency of Mutations Induced by Gamma Radiations in Three Varieties of Nigerian Sesame (Sesamum indicum L.

    Directory of Open Access Journals (Sweden)

    Muhammad Liman MUHAMMAD

    2018-03-01

    Full Text Available Insufficient genetic variability is one of the major problems of plant breeding programmes, especially in sesame. Gamma radiation has been reported to be very effective in creating genetic variability in plants. Three varieties of Nigerian sesame were assessed for spectrum and frequency of mutation induced by Gamma radiations in M1 and M2 generations. The varieties (NCRIBEN-04E, NCRIBEN-01M and NCRIBEN-03L were treated with four different doses of gamma rays (250, 350, 450 and 550 Gy. The treated and untreated seeds (control were sown in planting bags (under field condition to raise M1 plants. Four treatments: V1D5, V2D3, V3D2 and V3D4 (from M1 plants were selected and bulked to obtain M2 populations. The results of M1 revealed four mutant fruit traits: multicarpellate capsule, multiple capsule per leaf axil, indehiscent capsule and terminal capsules. The highest frequencies of the traits in M1 generation were 2.50×10-2, 9.17×10-2, 1.67×10-2and3.33×10-2 respectively. The highest branching (7 was from NCRIBEN-01M, while the least (2 was from NCRIBEN-04E. The M2 plants were grouped into eight M2 lines. The dose range (250-550 Gy was proved to be effective in inducing viable mutations in sesame.

  20. Neutron-induced mutation experiments. Progress report, March 1, 1975--February 29, 1976

    International Nuclear Information System (INIS)

    Abrahamson, S.

    1975-11-01

    The relative mutagenic effectiveness of neutrons of different energies were compared with x radiation in mice and Drosophila oogonia employing X-linked recessive lethal and specific locus mutation tests. The energies and doses used were 0.68 MeV, 2 MeV, and 6 MeV (250 and 500 0 R), and 15 MeV (250, 500, and 1000 0 R). The data thus far collected from the recessive lethal test indicate that 0.68 MeV neutrons have the highest RBE among the energies tested, followed by 6 and 2 MeV. The specific locus mutation data also indicate the highest RBE for 0.68 MeV, followed respectively by 2 and 6 MeV. The 15 MeV data is as of now incompletely analyzed, as are some dose points of 2 and 6 MeV

  1. Evaluation of gamma radiation (60-Co) induced mutation in two Phaseolus vulgaris varieties

    International Nuclear Information System (INIS)

    Silva, R.M.

    1984-01-01

    Two varieties of Phaseolus vulgaris (Jutiapan and San Martin) were irradiated at 0, 8, 15, 20 and 30 kR doses in a 60-cobalt gamma source, to identify mutants and 20% lethality. M 2 plants showing morphogical mutations were selected. Differences in sensitivity to irradiation of the two varieties were noted, using data and physiological effects of M 1 . Selection and analysis for protein content were in M 3 as well as hereditary changes. (M.A.C.) [pt

  2. Does aerobic exercises induce mtDNA mutation in human blood ...

    African Journals Online (AJOL)

    The aim of this study was to determine the effect of eight weeks aerobic training on mitochondrial DNA (mtDNA) mutation in human blood leucocytes. Twenty untrained healthy students (training group: n =10, age = 20.7±1.5 yrs, weight = 67.7±10 kg, BF% = 17.5±7.35 & control group: n =10, age = 21±1.3 yrs, weight ...

  3. In Vivo Spectrum of UVC-induced Mutation in Mouse Skin Epidermis May Reflect the Cytosine Deamination Propensity of Cyclobutane Pyrimidine Dimers.

    Science.gov (United States)

    Ikehata, Hironobu; Mori, Toshio; Yamamoto, Masayuki

    2015-11-01

    Although ultraviolet radiation (UVR) has a genotoxicity for inducing skin cancers, the skin may tolerate UVC component because the epidermal layer prevents this short wavelength range from passing through. Here, UVC genotoxicity for mouse skin was evaluated in terms of DNA damage formation and mutagenicity. UVC induced UVR photolesions and mutations remarkably in the epidermis but poorly in the dermis, confirming the barrier ability of the epidermis against shorter UVR wavelengths. Moreover, the epidermis itself responded to UVC mutagenicity with mutation induction suppression, which suppressed the mutant frequencies to a remarkably low, constant level regardless of UVC dose. The mutation spectrum observed in UVC-exposed epidermis showed a predominance of UV-signature mutation, which occurred frequently in 5'-TCG-3', 5'-TCA-3' and 5'-CCA-3' contexts. Especially, for the former two contexts, the mutations recurred at several sites with more remarkable recurrences at the 5'-TCG-3' sites. Comparison of the UVC mutation spectrum with those observed in longer UVR wavelength ranges led us to a mechanism that explains why the sequence context preference of UV-signature mutation changes according to the wavelength, which is based on the difference in the mCpG preference of cyclobutane pyrimidine dimer (CPD) formation among UVR ranges and the sequence context-dependent cytosine deamination propensity of CPD. © 2015 The American Society of Photobiology.

  4. Suppression of spontaneous and hydrogen peroxide-induced mutations by a MutT-type nucleotide pool sanitization enzyme, the Escherichia coli Orf135 protein.

    Science.gov (United States)

    Kamiya, Hiroyuki; Iida, Emiko; Murata-Kamiya, Naoko; Yamamoto, Yoshihiro; Miki, Takeyoshi; Harashima, Hideyoshi

    2003-12-01

    We recently found that the Escherichia coli Orf135 protein, a MutT-type enzyme, hydrolysed 2-hydroxy-dATP (2-OH-dATP), and less efficiently, 8-hydroxy-dGTP. In this study, we examined the effects of the absence of the orf135 gene. Frequencies of spontaneous and H2O2-induced mutations were two- to three-fold higher in the orf135- strain than in the wild-type strain. These mutations include various mutations involving a G:C-->T:A transversion, the same type of mutation elicited by 2-OH-dATP. Over-expression of the Orf135 protein suppressed mutations even in the wild-type strain, as well as in the orf135- strain. The mutator phenotype of bacteria lacking the Orf135 protein suggests that this protein is involved in the suppression of mutations induced by oxidized deoxynucleotides in vivo and that various MutT-type enzymes contribute to nucleotide pool sanitization.

  5. A Molecular Modeling Study of the Hydroxyflutamide Resistance Mechanism Induced by Androgen Receptor Mutations

    Directory of Open Access Journals (Sweden)

    Hong-Li Liu

    2017-08-01

    Full Text Available Hydroxyflutamide (HF, an active metabolite of the first generation antiandrogen flutamide, was used in clinic to treat prostate cancer targeting androgen receptor (AR. However, a drug resistance problem appears after about one year’s treatment. AR T877A is the first mutation that was found to cause a resistance problem. Then W741C_T877A and F876L_T877A mutations were also reported to cause resistance to HF, while W741C and F876L single mutations cannot. In this study, molecular dynamics (MD simulations combined with the molecular mechanics generalized Born surface area (MM-GBSA method have been carried out to analyze the interaction mechanism between HF and wild-type (WT/mutant ARs. The obtained results indicate that AR helix 12 (H12 plays a pivotal role in the resistance of HF. It can affect the coactivator binding site at the activation function 2 domain (AF2, surrounded by H3, H4, and H12. When H12 closes to the AR ligand-binding domain (LBD like a lid, the coactivator binding site can be formed to promote transcription. However, once H12 is opened to expose LBD, the coactivator binding site will be distorted, leading to invalid transcription. Moreover, per-residue free energy decomposition analyses indicate that N705, T877, and M895 are vital residues in the agonist/antagonist mechanism of HF.

  6. Generation of an induced pluripotent stem cell line from a patient with hereditary multiple endocrine neoplasia 2A (MEN2A syndrome with RET mutation

    Directory of Open Access Journals (Sweden)

    J. Hadoux

    2016-07-01

    Currently, there is no satisfactory animal model recapitulating all the features of the disease especially at the level of stem cells. We generated induced pluripotent stem cells (iPSCs from a patient with RET mutation at codon 634 who developed pheochromocytoma and MTC. RETC634Y-mutated cells were reprogrammed by non-integrative viral transduction. These iPSCs had normal karyotype, harboured the RETC634Y mutation and expressed pluripotency hallmarks as well as RET. A comprehensive pathological assessment of teratoma was performed after injection in immunodeficient mice.

  7. Radiation-induced dominant skeletal mutations in mice: mutation rate, characteristics, and usefulness in estimating genetic hazard to humans from radiation

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    The work discussed in this paper represents a major advance in the difficult task of trying to estimate the effects that an increase in mutation frequency would have on human health. Male mice were bred to three females prior to being killed and skeleton studies made. Guidelines were instituted for checking progeny mutations. Surprising results showed a mutation frequency of 1.4% per gamete where none would have been expected. It is now clear that mice can be greatly deformed without showing external effects

  8. Analysis of relation between the mutation frequencies and somatic recombination induced by neutrons and the age of D. Melanogaster larvae

    International Nuclear Information System (INIS)

    Guzman R, J.; Zambrano A, F.; Paredes G, L.; Delfin L, A.; Quiroz R, C.

    1998-01-01

    Neutrons are subatomic particles with neutral electric charge, equal zero, which are emitted during the fissile material fission in nuclear reactors. It is known a little about biological effects induced by neutrons. There is a world interest in the use of reactors and accelerators for patients radiotherapy using neutrons with the purpose to destroy malignant cells of deep tumours where traditional methods have not given satisfactory results. There for it is required to do wide studies of biological effects of neutrons as well as their dosimetry. It was used the Smart test (Somatic Mutation and Recombination Test) of D. Melanogaster for quantifying the mutation induction and somatic recombination induced by neutrons of the National Institute of Nuclear Research reactor, at power of 300 and 1000 k W, with equivalent doses calculated 95.14 and 190.2 Sv for 300 k W and of 25.64 and 51.29 Sv for 1000 k W, using larvae with 72 or 96 hours aged. It was observed a linear relation between equivalent dose and genetic effects frequency, these last were greater when the reactor power was 1000 k W than those 300 k W. It was observed too that the damage was greater in 96 hours larvae than those 72 hours. The stain size presented an inverse relation with respect to larvae age. It is concluded that the Smart system is sensitive to neutrons effect and it responds of a directly proportional form to radiation dose, as well as to dose rate. It is noted more the effect when are used larvas in pre pupa stage where the irradiation target (imagal cells) is greater. The Smart is sensitive to damage induced by neutrons , thus can be used to studying its direct biological effects or by the use of chemical modulators. (Author)

  9. Application Of Induced Mutation Combined With Hybridization Method In Rice Improvement In Southern Vietnam

    International Nuclear Information System (INIS)

    Do Khac Thinh; Dao Minh So; Nguyen Thi Cuc; Hung Phi Oanh; Hoang Duc Dung

    2008-01-01

    Rice plays an important role of social-economic issues in Vietnam, especially in Mekong River Delta (MRD). Rice mutation breeding was not initiated until 1992 in Southern Vietnam. Therefore, no mutant rice varieties were cultivated in MRD before 1995. Dry and germinated seeds of varieties as IR64, Tam Xoan, Nang Huong were exposed to 60 Co gamma rays at doses of 200-300 Gy. Population of 10,000-15,000 M1 plants were established by direct seeded practice. Mutant elite lines were used in hybridization program, assessed according to the standard system for rice (IRRI 1996) from M2 - M7 generations. The promising selected lines were tested in multi-location trials. The mutated characters developed so far consist of better resistance to lodging, disease and insect damages, higher tolerance to soil stresses such as acid sulphate, drought etc, and also earliness and higher yield potential. Mutation techniques have shown very useful in rice improvement, especially for characters controlled by close linked genes that are difficult to break by recombination. Some best mutant varieties: VND95-19, VND95-20, VND99-3, TNDB-100 have been released for large-scale production in MRD. Among them, VND95-20 has become one of the top 5 varieties for export and grown annually about 300,000 ha in Southern Vietnam. In combination with hybridization method, some mutants gave promising recombinants in aroma, tolerance to BPH, Grassy Stunt Virus and Ragged Stunt Virus diseases. Selected varieties as VN121, VN24-4 are largely released into production in recent time. (author)

  10. Improvement of Chrysanthemum var 'Taipei' Through In Vitro Induced Mutation with Chronic and Acute Gamma Rays

    International Nuclear Information System (INIS)

    Lamseejan, Siranut; Jompuk, Peeranuch; Deeseepan, Surin

    2003-01-01

    The project on chrysanthemum improvement by using radiation and in vitro culture technique was initiated. In vitro cultures of Taihei variety were irradiated with chronic gamma rays of 62.8 and 112 Gy. The irradiated shoots were multiplied three times from single-node cutting. M 1 V 4 shoots and control were rooted, transferred to soil in the greenhouse and finally transplanted in the field in September 2000. Mutation investigation was done at flowering time. Changes in flower color, form and size were observed only on the irradiated plants. The flower color mutation frequency among the plants treated with 62.8 and 112 Gy was 7.5% and 9.3%, respectively. Sixteen variants were selected from M 1 V 4 plants treated with gamma-ray of 62.8% Gy, and fourteen variants were selected from M 1 V 4 population treated with gamma-ray of 112 Gy. Shoots obtained from selected plants were cultured in vitro and then planted in the field in October 2001. By culturing purple florets from selected tall plant resulting from 62.8 Gy treatment, a new dwarf mutant was obtained. In another experiment involving culturing floret rays of a large orange flower mutant treated with gamma-ray of 112 Gy, a new small yellow flower mutant was produced. The experiment on in vitro culture acute irradiation was carried out using two different methods of irradiation. The first method, applying acute irradiation treatment with 20 and 30 Gy, resulted in color mutation frequency of 1.3% and 1.8% respectively. Another experiment on in vitro culture irradiation with acute 30 Gy delivered as split dose at first 20 Gy and then 10 Gy after 53 days, resulted in flower color mutant frequency of 8.6%. In the same way, acute 40 Gy treatment was delivered as split dose, at first 20 Gy and then followed by 20 Gy after 53 days this resulted in flower color mutation frequency of 10.9%. Investigation and evaluation of the mutant flowers were carried out with the help of ornamental growers from Chiang Rai and Chiang Mai

  11. Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer

    Science.gov (United States)

    Adams, Peter D.; Jasper, Heinrich; Rudolph, K. Lenhard

    2015-01-01

    Aging is characterized by a decrease in genome integrity, impaired organ maintenance, and an increased risk of cancer, which coincide with clonal dominance of expanded mutant stem and progenitor cell populations in aging tissues, such as the intestinal epithelium, the hematopoietic system, and the male germline. Here we discuss possible explanations for age-associated increases in the initiation and/or progression of mutant stem/progenitor clones and highlight the roles of stem cell quiescence, replication-associated DNA damage, telomere shortening, epigenetic alterations, and metabolic challenges as determinants of stem cell mutations and clonal dominance in aging. PMID:26046760

  12. Identification of potential molecular markers of ionizing radiation-induced mutations at the hprt locus in CHO cells

    International Nuclear Information System (INIS)

    Schwartz, J.L.; Sun, J.; Porter, R.C.

    1995-01-01

    Using multiplex polymerase chain reaction-based exon deletion analysis, we have analyzed mutations at the hprt locus from independent CHO cell mutants isolated from untreated, 60 Co x-ray-, and 212 Bi-exposed CHO-K1 cello and its radiation-sensitive derivative, xrs-5. In the 71 spontaneous CHO-K1 mutants analyzed, 78% showed no change in exon number or size, 20% showed loss of 1-8 exons (partial deletion), and 3% showed loss of all nine hprt exons (total deletion). Exposure of CHO-K1 cells to 6 Gy of γ rays (10% survival) produced 45% of the 20 mutants analyzed showing partial deletion, and 30% showing total deletion. Exposure to an equitoxic dose of a radiation from 212 Bi, a 220 Rn daughter, resulted in a spectrum similar to the γ-ray spectrum in that more than 75% of the 49 mutants analyzed were deletions. The α-radiation, however, tended to produce larger intragenic deletions that γ radiation. Of the 87 spontaneous xrs-5 mutants analyzed for deletions 44% showed partial deletion, and 14% showed total deletion. Exposure to α radiation (10% survival) resulted in a deletion spectrum similar to that seen in CHO-K1 cells. Of the 49 mutants analyzed, 43% showed no change in exon number or size, 16% showed partial deletion, and 41% showed total deletion. While the defect in xrs-5 has a profound effect on spontaneous mutation spectra, it does not appear to affect α-induced mutation spectra

  13. Induced mutation of new cotton lines tolerant to verticillium wilt with improved characters

    International Nuclear Information System (INIS)

    Rastegary, G.; Hoseiny Neghad, Z.

    1998-01-01

    Induction of mutation for genetic variation has been used in crop improvement for many years. The mutant lines can be used either directly or as a new genetic source in cross breeding. In cotton 'eleven' and 'two' mutant varieties as new genetic sources have been evolved directly and indirectly, respectively. One of the major obstacles in cotton production in northern region of Iran, Gorgan and Gonbad (where they are known as the main cultivation area of this crop), is the presence of verticillium wilt fungal disease. Since this fungus is soil-born, and can not be controlled chemically, the most efficient way of combating against the disease is to breed for the tolerance/resistance of the species. For this purpose, a mutation breeding technique was applied using gamma radiation as mutagen. The seeds of four varieties (Shirpan, Tashkand, Bakhtegan, and Sahel) were irradiated after reaching a proper absorbed humidity. The radiation doses of 150 to 350 Gy were applied and the seeds were cultivated in two different locations (Varamin and Kordkuy) as M1 generation. The cotton balls of each individual healthy plant was harvested to attain the seeds of M2 rows. In M2, the plants with different degrees of tolerance to the disease were compared to the selected parents (taking into consideration that the soil was contaminated). The good yielding lines with different level of tolerance were taken up to the 5th generation, yielding 70 lines of superior qualitative and quantitative traits. (author)

  14. Characterization of Cat-2t, a radiation-induced dominant cataract mutation in mice

    International Nuclear Information System (INIS)

    Graw, J.; Bors, W.; Gopinath, P.M.; Merkle, S.; Michel, C.; Reitmeir, P.; Schaeffer, E.S.; Summer, K.H.; Wulff, A.

    1990-01-01

    A dominant cataract mutation was detected recently among the offspring of x-ray-irradiated male mice. The mutation, which causes total lens opacity, has provisionally been designated by the gene symbol Cat-2t. In the lenses of heterozygous and homozygous Cat-2t mutants, the epithelial and fiber cells were swollen and the lens capsule was ruptured. The histologic analysis demonstrated a complete destruction of the cellular organization of the lens, which might be caused by its altered developmental processes. The data derived from biochemical investigations indicate that biochemistry of the cataractous Cat-2t lenses is affected: the osmotic state as indicated by the increased water content and increased Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity; the energy state as indicated by the decreased adenosine triphosphate (ATP) concentration; and the redox state as indicated by the enhanced content of oxidized glutathione. Additionally, the lenticular protein composition is altered because of the presence of vimentin in the water-soluble fraction. This cannot be explained by the enhanced crosslinking activity of transglutaminase. The changes of the osmotic, energy, and redox states are considered to be secondary in relation to the altered lenticular development. In contrast, the variations concerning vimentin and transglutaminase might be a biochemical indication of the changed development. Possible similarities to other dominantly expressed murine cataract mutants are discussed

  15. Mu-seq: Sequence-Based Mapping and Identification of Transposon Induced Mutations

    Science.gov (United States)

    McCarty, Donald R.; Latshaw, Sue; Wu, Shan; Suzuki, Masaharu; Hunter, Charles T.; Avigne, Wayne T.; Koch, Karen E.

    2013-01-01

    Mutations tagged by transposon insertions can be readily mapped and identified in organisms with sequenced genomes. Collections of such mutants allow a systematic analysis of gene function, and can be sequence-indexed to build invaluable resources. Here we present Mu-seq (Mutant-seq), a high-throughput NextGen sequencing method for harnessing high-copy transposons. We illustrate the efficacy of Mu-seq by applying it to the Robertson’s Mutator system in a large population of maize plants. A single Mu-seq library, for example, constructed from 576 different families (2304 plants), enabled 4, 723 novel, germinal, transposon insertions to be detected, identified, and mapped with single base-pair resolution. In addition to the specificity, efficiency, and reproducibility of Mu-seq, a key feature of this method is its adjustable scale that can accomodate simultaneous profiling of transposons in thousands of individuals. We also describe a Mu-seq bioinformatics framework tailored to high-throughput, genome-wide, and population-wide analysis of transposon insertions. PMID:24194867

  16. Cytologic Investigations on Identification of Induced Mutation Effects in Sultani Çekirdeksiz ve Kalecik Karası Grape cvs. (Vitis vinifera L.)

    International Nuclear Information System (INIS)

    Karataş, Dilek Değİrmencİ; Kunter, Birhan

    2012-01-01

    The effects of induced mutation applied by 5 different doses of gamma irradiation (20, 25, 30, 40 ve 50 Gy) were cytologic investigated on Vitis vinifera L. cultivars, Sultani Çekirdeksiz (SÇ) ve Kalecik karası (KK). Mutant candidates were selected through the morphological observations of the mutation-induced phenotypic changes in the first (M1V1), second (M1V2) and third (M1V3) vegetations. In cytological studies, diploid cells (2n=38) were observed for both cultivars. Cells showing ploidy level other than diploidy were found only in the individual SÇ 30 Gy 34. (author) [tr

  17. Studies on mutation techniques in rice breeding

    International Nuclear Information System (INIS)

    Wang Cailian; Chen Qiufang; Jin Wei

    2001-01-01

    Synthetical techniques for improving rice mutation breeding efficiency were studied. The techniques consist of corresponding relationship between radiosensitivity and mutation frequency, choosing appropriate materials, combination of physical and chemical mutagens, mutagenic effects of the new mutagenic agents as proton, ions, synchronous irradiation and space mutation. These techniques and methods for inducing mutations are very valuable to increase inducing mutation efficiency and breeding level

  18. Sesame improvement by induced mutations. Final reports of an FAO/IAEA co-ordinated research project. 1993-1998

    International Nuclear Information System (INIS)

    2001-01-01

    Sesame (Sesamum indicum L.) is an ancient oil crop considered to be still at an early stage in breeding. The fact that sesame is a crop of mainly developing countries with limited available research funds for long term breeding programmes, resulted in very few breeding efforts in research stations. Furthermore, sesame is not a mandate crop of any of the international agriculture research centers. Until recently most of the released sesame varieties in countries such as China, India and the Republic of Korea were the product of selection and pedigree breeding. A major constraint in this approach was the lack of sufficient genetic variation within the existing germplasm collections, especially for traits such as resistance to various diseases and seed retention. This is where mutation techniques could offer a possible solution. The United Nations Food and Agriculture Organization (FAO) organized some expert consultations on sesame breeding between 1981 and 1987, which all recommended the use of mutation induction for the enhancement of genetic variability with a focus on the following traits: modified plant architecture, seed retention, and resistance to diseases and pests. As a result, most of these recommendations have been included in this five year co-ordinated research project (CRP) that started in 1993, organized by the Plant Breeding and Genetics Section of the Joint FAO/IAEA Division. This CRP focused on the induction of the above mentioned characters in different sesame improvement programmes, and on the enhancement of co-operation between sesame breeders in developed and developing countries. Each participant covered a number of traits important for their specific breeding needs. During regular meetings under this project the participants had the opportunity to jointly appraise and evaluate sesame mutants and varieties in demonstration fields, thus strengthening the mutual effort for the genetic improvement of sesame through mutation techniques. The success

  19. Time course of ultraviolet B-induced erythema in people with red hair harbouring homozygous melanocortin 1 receptor mutations.

    Science.gov (United States)

    Ha, Thomas K K; Waterston, Karen; Bisset, Yvonne; Ray, Amanda; Rees, Jonathan L

    2003-08-01

    It has previously been reported that the time course of erythema may be delayed in those with sun-sensitive skin types and those with skin cancer. One molecular explanation for this putative phenotype would be that it is caused by mutations of the melanocortin 1 receptor (MC1R). In the present study of 20 persons, 10 of whom were MC1R homozygous, we measured erythema over a 21-day period in response to a range of ultraviolet B doses using methods that improved on previous studies. We could detect no consistent differences in ultraviolet radiation-induced erythema between the groups studied. The pharmacological mechanisms underpinning such prolonged inflammatory responses merit further investigation.

  20. Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome

    Directory of Open Access Journals (Sweden)

    Jiaofeng Chen

    2016-01-01

    Full Text Available The patients with DiGeorge syndrome (DGS, caused by deletion containing dozens of genes in chromosome 22, often carry cardiovascular problem and hearing loss associated with chronic otitis media. Inside the deletion region, a transcription factor TBX1 was highly suspected. Furthermore, similar DGS phenotypes were found in the Tbx1 heterozygous knockout mice. Using ENU-induced mutagenesis and G1 dominant screening strategy, here we identified a nonsynonymous mutation p.W118R in T-box of TBX1, the DNA binding domain for transcription activity. The mutant mice showed deficiency of inner ear functions, including head tossing and circling, plus increased hearing threshold determined by audiometry. Therefore, our result further confirms the pathogenic basis of Tbx1 in DGS, points out the crucial role of DNA binding activity of TBX1 for the ear function, and provides additional animal model for studying the DGS disease mechanisms.

  1. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    National Research Council Canada - National Science Library

    Rosenstein, Barry

    2004-01-01

    The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

  2. [Malignant transformation of human fibroblasts by neutrons and by gamma radiation: Relationship to mutations induced

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    A brief overview if provided of selected reports presented at the International Symposium on Molecular Mechanisms of Radiation- and Chemical Carcinogen-Induced Cell Transformation held at Mackinac Island, Michigan on September 19-23, 1993.

  3. A recurrent mutation in bone morphogenetic proteins-2-inducible kinase gene is associated with developmental dysplasia of the hip.

    Science.gov (United States)

    Zhao, Lihua; Zhou, Zaiwei; Wang, Sun; Jiao, Qing; Wu, Jing; Ma, Feng; Fan, Lingyan; Chen, Mengjie; Ying, Hao

    2017-05-01

    Developmental dysplasia of the hip (DDH) is a complex disorder of the hip joint affecting 1-5‰ of newborns. While genetic influence on DDH has been long known, DDH has not been ascribed to any specific genetic event. The present study reported on variants contributing to DDH susceptibility in a family with four individuals affected across three generations. Whole-exome sequencing was performed in three affected and two unaffected individuals of a pedigree with DDH. Candidate variants were confirmed by Sanger sequencing and then validated in available family members and 37 sporadic DDH patients. Two novel heterozygous, inframe mutations causing multi-nucleotide substitution polymorphisms (c.1432_1440delCAGCAGCAG corresponding with p.Gln478_480del and c.1440_1441insCAG corresponding with p.Gln480ins) in exon 11 of chromosome 4 in bone morphogenetic proteins-2-inducible kinase (BMP2K) were identified; these were found in members of the pedigree affected by DDH and in the unaffected grandmother of the proband, who was deemed to be the carrier of potential mutations, but not in the unaffected normal control saunt of the proband. These two variants shared the same genomic coordinate but with different types of mutation in BMP2K. BMP2K is known to be associated with bone and cartridge development and heterozygous mutations were found to be present in 4/4 (100%) of the affected family members, 4/15 (26.7%) of the unaffected family members and 0/7 (0%) of the unaffected unrelated family members. Genotyping of 37 unrelated, sporadic DDH patients showed that three cases were positive for the BMP2K c.1432_1440delCAGCAGCAG variants (8.12%). These findings provided strong evidence for the role of BMP2K variants in causing DDH and demonstrated that the combination of pedigree information and next-generation sequencing is an effective method for identifying pathogenic sites associated with DDH.

  4. A yeast strain for simultaneous detection of induced mitotic crossing over, mitotic gene conversion and reverse mutation

    International Nuclear Information System (INIS)

    Zimmermann, F.K.; Kern, R.; Rasenberger, H.

    1975-01-01

    A diploid yeast strain of Saccharomyces cerevisiae is described which can be used to study induction of mitotic crossing-over, mitotic gene conversion and reverse mutation. Mitotic crossing-over can be detected visually as pink and red twin-sectored colonies which are due to the formation of homozygous cells of the genotype ade2-40/ade2-40 (deep red) and ade-2-119/ade2-119 (pink) from the originally heteroallelic condition ade2-40/ade2-119 which forms white colonies. Mitotic gene conversion is monitored by the appearance of tryptophan nonrequiring colonies on selective media. The alleles involved are trp5-12 and trp5-27 derived from the widely used strain D 4 . Mutation induction can be followed by the appearance of isoleucine nonrequiring colonies on selective media. D 7 is homoallelic ilvI-92. The isoleucine requirement caused by ilvI-92 can be alleviated by true reverse mutation and allele non-specific suppressor mutation. The effects of ethyl methanesulfonate (EMS), nitrous acid, ultraviolet light and hycanthone methanesulfonate were studied with D 7 stationary phase cells. Mitotic crossing-over as monitored by red/pink twin-sectored colonies was almost equally frequent among normal and convertant cells. This showed again that nitotic recombination is not due to the presence of a few cells committed to meiosis in an otherwise mitotic cell population. The dose-response curves for induction of mitotic gene conversion and reversion of the isoleucine requirement were exponential. In contrast to this, the dose-response curve for induction of twin sectored red and pink colonies reached a plateau at doses giving about 30% cell killing. This could partly be due to lethal segregation in the progeny of treated cells. None of the agents tested would induce only one type of mitotic recombination, gene conversion or crossing-over. There was, however, some mutagen specificity in the induction of isoleucine prototrophs

  5. Modulatory effects of Tabebuia impetiginosa (Lamiales, Bignoniaceae on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Neila C. de Sousa

    2009-01-01

    Full Text Available The wing Somatic Mutation and Recombination Test (SMART in D. melanogaster was used to study genotoxicity of the medicinal plant Tabebuia impetiginosa. Lapachol (naphthoquinone and β-lapachone (quinone are the two main chemical constituents of T. impetiginosa. These compounds have several biological properties. They induce apoptosis by generating oxygen-reactive species, thereby inhibiting topoisomerases (I and II or inducing other enzymes dependent on NAD(PH:quinone oxidoreductase 1, thus affecting cell cycle checkpoints. The SMART was used in the standard (ST version, which has normal levels of cytochrome P450 (CYP enzymes, to check the direct action of this compound, and in the high bioactivation (HB version, which has a high constitutive level of CYP enzymes, to check for indirect action in three different T. impetiginosa concentrations (10%, 20% or 40% w/w. It was observed that T. impetiginosa alone did not modify the spontaneous frequencies of mutant spots in either cross. The negative results observed prompted us to study this phytotherapeuticum in association with the reference mutagen doxorubicin (DXR. In co-treated series, T. impetiginosa was toxic in both crosses at higher concentration, whereas in the HB cross, it induced a considerable potentiating effect (from ~24.0 to ~95.0% on DXR genotoxity. Therefore, further research is needed to determine the possible risks associated with the exposure of living organisms to this complex mixture.

  6. Modulatory effects of Tabebuia impetiginosa (Lamiales, Bignoniaceae) on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster

    Science.gov (United States)

    2009-01-01

    The wing Somatic Mutation and Recombination Test (SMART) in D. melanogaster was used to study genotoxicity of the medicinal plant Tabebuia impetiginosa. Lapachol (naphthoquinone) and β-lapachone (quinone) are the two main chemical constituents of T. impetiginosa. These compounds have several biological properties. They induce apoptosis by generating oxygen-reactive species, thereby inhibiting topoisomerases (I and II) or inducing other enzymes dependent on NAD(P)H:quinone oxidoreductase 1, thus affecting cell cycle checkpoints. The SMART was used in the standard (ST) version, which has normal levels of cytochrome P450 (CYP) enzymes, to check the direct action of this compound, and in the high bioactivation (HB) version, which has a high constitutive level of CYP enzymes, to check for indirect action in three different T. impetiginosa concentrations (10%, 20% or 40% w/w). It was observed that T. impetiginosa alone did not modify the spontaneous frequencies of mutant spots in either cross. The negative results observed prompted us to study this phytotherapeuticum in association with the reference mutagen doxorubicin (DXR). In co-treated series, T. impetiginosa was toxic in both crosses at higher concentration, whereas in the HB cross, it induced a considerable potentiating effect (from ~24.0 to ~95.0%) on DXR genotoxity. Therefore, further research is needed to determine the possible risks associated with the exposure of living organisms to this complex mixture. PMID:21637695

  7. A sucrose-rich diet induces mutations in the rat colon

    DEFF Research Database (Denmark)

    Dragsted, L.O.; Daneshvar, B.; Vogel, Ulla Birgitte

    2002-01-01

    A sucrose-rich diet has repeatedly been observed to have cocarcinogenic actions in the colon and liver of rats and to increase the number of aberrant crypt foci in rat colon. To investigate whether sucrose-rich diets might directly increase the genotoxic response in the rat colon or liver, we have...... added sucrose to the diet of Big Blue rats, a strain of Fischer rats carrying 40 copies of the lambda-phage on chromosome 4. Dietary sucrose was provided to the rats for 3 weeks at four dose levels including the background level in the purified diet [3.4% (control), 6.9%, 13.8%, or 34.5%] without...... of a sucrose-rich diet. No significant increase in mutations was observed in the liver. To seek an explanation for this finding, a variety of parameters were examined representing different mechanisms, including increased oxidative stress, changes in oxidative defense, effects on DNA repair, or changes...

  8. Plant breeding for resistance to insect pests: Considerations about the use of induced mutations

    International Nuclear Information System (INIS)

    1978-01-01

    The Panel was intended to stimulate proposals on specific plant breeding objectives, for immediate and long term solution. Nine papers considered the host plant resistance to particular insect pests in a variety of cases. The desirability of achieving some measure of pest control via the development of disease-resistant mutants was discussed. In its conclusions, the Panel stressed the need to consider host plant resistance as one of the primary lines of defense in all pest management programmes. Consequently, resistance to insects was recommended to become an integral part of plant breeding programmes. Preference might need to be given to developing insect resistance in those crop plants for which practical control is lacking or where current methods of pest control present critical environmental hazards. The roles of the IAEA and FAO in such projects is outlined. Guidelines and recommendations on mutation breeding for resistance to insects are given in an appendix

  9. Induced mutation breeding in Cassava (Manihot esculenta Crantz) cultivar 'Bosom Nsia'

    International Nuclear Information System (INIS)

    Ahiabu, R.K.A.; Klu, G.Y.P.

    1997-01-01

    Cassava is one of the most important staple food crops in the lowland tropics. In most cassava producing countries, it is mainly utilized for human consumption. Cassava leaves are a good source of protein and vitamins, and are used as food in Africa. In Ghana, 'Bosom Nsia' is one of the most widely grown cultivars probably because of its good cooking quality and fast maturation in six months. However, this cultivar is highly susceptible to cassava mosaic virus disease (CMV), hence the need to improve its resistance to the disease. Various in vitro techniques have been developed for cassava research, Klu and Lamptey reported irradiation doses of 25 and 30 Gy to be ideal for in vitro mutagenesis of cassava. These doses were applied to in vivo and in vitro mutation for breeding CMV resistance in the cultivar 'Bosom Nsia'. 6 refs

  10. Mutations of the Corynebacterium glutamicum NCgl1221 Gene, Encoding a Mechanosensitive Channel Homolog, Induce l-Glutamic Acid Production▿

    Science.gov (United States)

    Nakamura, Jun; Hirano, Seiko; Ito, Hisao; Wachi, Masaaki

    2007-01-01

    Corynebacterium glutamicum is a biotin auxotroph that secretes l-glutamic acid in response to biotin limitation; this process is employed in industrial l-glutamic acid production. Fatty acid ester surfactants and penicillin also induce l-glutamic acid secretion, even in the presence of biotin. However, the mechanism of l-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in l-glutamic acid secretion without induction. In this study, we analyzed odhA disruptants and found that those which exhibited constitutive l-glutamic acid secretion carried additional mutations in the NCgl1221 gene, which encodes a mechanosensitive channel homolog. These NCgl1221 gene mutations lead to constitutive l-glutamic acid secretion even in the absence of odhA disruption and also render cells resistant to an l-glutamic acid analog, 4-fluoroglutamic acid. Disruption of the NCgl1221 gene essentially abolishes l-glutamic acid secretion, causing an increase in the intracellular l-glutamic acid pool under biotin-limiting conditions, while amplification of the wild-type NCgl1221 gene increased l-glutamate secretion, although only in response to induction. These results suggest that the NCgl1221 gene encodes an l-glutamic acid exporter. We propose that treatments that induce l-glutamic acid secretion alter membrane tension and trigger a structural transformation of the NCgl1221 protein, enabling it to export l-glutamic acid. PMID:17513583

  11. Isolation and propagation of mutations by in vitro culture. Part of a coordinated programme on improvement of vegetatively propagated crops and tree crops through radiation induced mutations

    International Nuclear Information System (INIS)

    Asahira, T.

    1974-01-01

    Tuberous roots of two Dahlia cultivars were irradiated with 1000 - 2000 R of x-rays. Chlorophyll and flower colour mutations were scored on M 1 plants and the subsequent vegetatively propagated generations. The project aimed at the development of experimental methods suitable for easy isolation of mutated tissue chimeras deriving from mutagen treatment. In comparing in vivo methods such as leaf bud cutting and root propagation with in vitro methods using explants from leaves and florets, the problems encountered by in vitro culture were so manifold, that this method is not considered to be at present of much promise. These experimental results should not discourage from developing and using in vitro culture methods for mutant isolation in other plant species, particularly those were in vivo adventitious bud techniques are not available. Besides the main result obtained, the following valuable observations were made: a) The genotype used for mutation induction is not only relevant for the number and the spectrum of mutations, but also size of chimerical sectors. b) Flower colour changes, which were investigated in some detail, revealed that pigments were lost as groups e.g. all buteins in one case and all cyanins plus pelargonins in another case. c) When using the leaf bud cutting method the greatest frequency of mutations was recovered from the axillary bud of the leaf, that is at the youngest primordial stage at the time of mutagen treatment

  12. Chemical inducible promoter used to obtain transgenic plants with a silent marker and organisms and cells and methods of using same for screening for mutations

    Science.gov (United States)

    Zuo, Jianru [New York, NY; Chua, Nam-Hai [Scarsdale, NY

    2007-06-12

    Disclosed is a chemically inducible promoter for transforming plants or plant cells with genes which are regulatable by adding the plants or cells to a medium containing an inducer or by removing them from such medium. The promoter is inducible by a glucocorticoid, estrogen or inducer not endogenous to plants. Such promoters may be used with any plant genes that can promote shoot regeneration and development to induce shoot formation in the presence of a glucocorticoid, estrogen or inducer. The promoter may be used with antibiotic or herbicide resistance genes or other genes which are regulatable by the presence or absence of a given inducer. Also presented are organisms or cells comprising a gene wherein the natural promoter of the gene is disrupted and the gene is placed under the control of a transgenic inducible promoter. These organisms and cells and their progeny are useful for screening for conditional gain of function and loss of function mutations.

  13. Induced Mutations for Crop Improvement in Africa. Proceedings of a Regional Seminar on the Utilization of Induced Mutations for Crop Improvement in Africa Held in Conjunction with an Advisory Group on the Role and Limitations of Induced Mutations in Plant Improvement

    International Nuclear Information System (INIS)

    1979-11-01

    This seminar has been arranged with the intention to give plant breeders and plant geneticists from African countries an opportunity for refreshing and updating their knowledge in a technology that can be a useful supplement to plant breeding programmes. There are some who had been participating in training courses or study tours organized by FAO and IAEA, others who had been studying abroad under a fellowship programme. Others are holding a research contract or are counterparts in a technical assistance project. Again, there are others who know about the subject of mutation induction and the utilization of induced mutants in plant breeding only from textbooks or university courses. Besides updating knowledge and exchanging experiences, the seminar should be an occasion to discuss the need for and the efficiency of training programmes, and other forms of assistance

  14. CADASIL-associated Notch3 mutations have differential effects both on ligand binding and ligand-induced Notch3 receptor signaling through RBP-Jk.

    Science.gov (United States)

    Peters, Nils; Opherk, Christian; Zacherle, Simone; Capell, Anja; Gempel, Petra; Dichgans, Martin

    2004-10-01

    Mutations in the NOTCH3 gene are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy leading to strokes and dementia. Pathogenic mutations remove or insert cysteine residues within epidermal growth factor (EGF) repeats in the extracellular domain of the Notch3 receptor (N3ECD). Vascular smooth muscle cells (VSMC) are the predominant site of Notch3 expression in adults. In CADASIL patients, VSMC degenerate and N3ECD is deposited within the vasculature. However, the mechanisms underlying VSMC degeneration and N3ECD accumulation are still unknown. In this study, we investigated the consequences of three pathogenic Notch3 mutations on the biological activity of the receptor by analyzing ligand (Delta-/Jagged-)-induced signaling via RBP-Jk. Two mutations (R133C and C183R) that are located outside the putative ligand binding domain (LBD) of the receptor were found to result in normal Jagged1-induced signaling in A7r5 VSMC, whereas the third mutation (C455R located within the putative LBD) showed strongly reduced signaling activity. Ligand binding assays with soluble Delta1 and Jagged1 revealed that C455R interferes with ligand binding through disruption of the LBD which, as we show here, is located in EGF repeats 10/11 of Notch3. All mutant receptors including Notch3C455R were targeted to the cell surface but showed an elevated ratio between the unprocessed full-length 280-kDa receptor and S1-cleaved receptor fragments. Taken together, these data indicate that CADASIL-associated Notch3 mutations differ with respect to their consequences both on ligand binding and ligand-induced signaling through RBP-Jk, whereas they have similar effects on receptor maturation. Moreover, the data suggest that ligand-induced receptor shedding may not be required for N3ECD deposition in CADASIL. Copyright 2004 Elsevier Inc.

  15. X-ray-induced specific-locus mutations in the ad-3 region of two-component heterokaryons of Neurospora crass

    International Nuclear Information System (INIS)

    De Serres, F.J.

    1990-01-01

    More extensive complementation tests than those performed initially on a series of 832 X-ray-induced specific-locus mutations in the adenine-4 (ad-3) region of a two-component heterokaryon (H-12) of Neurospora crassa showed that unexpectedly high frequencies of specific-locus mutations in the ad-3 region have additional, but separate, sites of recessive lethal damage in the immediately adjacent genetic regions. In the present paper, X-ray-induced irreparable ad-3 mutants of the folowing genotypes and numbers (ad-3A ad-3B, ad-3A ad-3B nic-2, and ad-3B nic-2) have also subjected to the same genetic fine structure analysis. These experiments, in the previous and present papers, were designed to determine the extent of the functional inactivation in the ad-3 and immediately adjacent genetic regions in individual mutants classified as presumptive multilocus deletions or multiplelocus mutations. The data in the present paper have shown that in Neurospora crassa most X-ray-induced irreparable mutants of genotype ad-3A ad-3B, ad-3A ad-3B nic-2, and ad-3 nic-2 map as a series of overlapping multilocus deletions. In addition, genetic fine structure analysis has shown that some of the mutants classified, initially, as multilocus deletions, are actually multiple-locus mutations: multilocus deletions with closely linked, and separate, sites of recessive lethal damage with a wide variety of genotyes. Combining data from the present experiments with previously published date, the frequency of multiple-locus mutations among X-ray-induced gene/point mutations and multilocus deletions in the ad-3 region is 6.2%. (author). 27 refs.; 4 figs.; 7 tab

  16. Human Induced Pluripotent Stem Cells Harbor Homoplasmic and Heteroplasmic Mitochondrial DNA Mutations While Maintaining Human Embryonic Stem Cell-like Metabolic Reprogramming

    NARCIS (Netherlands)

    Prigione, A.; Lichtner, B.; Kuhl, H.; Struys, E.A.; Wamelink, M.M.C.; Lehrach, H.; Ralser, M.; Timmermann, B.; Adjaye, J.

    2011-01-01

    Human induced pluripotent stem cells (iPSCs) have been recently found to harbor genomic alterations. However, the integrity of mitochondrial DNA (mtDNA) within reprogrammed cells has yet to be investigated. mtDNA mutations occur at a high rate and contribute to the pathology of a number of human

  17. Induced pluripotent stem cells (iPSCs) derived from a patient with frontotemporal dementia caused by a R406W mutation in microtubule-associated protein tau (MAPT)

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena E.; Hasholt, Lis F.

    2016-01-01

    Skin fibroblasts were obtained from a 59-year-old woman diagnosed with frontotemporal dementia. The disease is caused by a R406W mutation in microtubule-associated protein tau (MAPT). Induced pluripotent stem cells (iPSCs) were established by electroporation with episomal plasmids containing hOCT4...

  18. Generation of induced pluripotent stem cells (iPSCs) from an Alzheimer's disease patient carrying a M146I mutation in PSEN1

    DEFF Research Database (Denmark)

    Li, Tong; Pires, Carlota; Nielsen, Troels Tolstrup

    2016-01-01

    Skin fibroblasts were obtained from a 46-year-old symptomatic man carrying a M146I mutation in the presenilin 1 gene (PSEN1), responsible for causing Alzheimer's disease (AD). Induced pluripotent stem cells (iPSCs) were derived via transfection with episomal vectors carrying hOCT4, hSOX2, hKLF2, hL-MYC...

  19. Generation of induced pluripotent stem cells (iPSCs) from an Alzheimer's disease patient carrying an A79V mutation in PSEN1

    DEFF Research Database (Denmark)

    Li, Tong; Pires, Carlota; Nielsen, Troels Tolstrup

    2016-01-01

    Skin fibroblasts were obtained from a 48-year-old presymptomatic woman carrying a A79V mutation in the presenilin 1 gene (PSEN1), causing Alzheimer's disease (AD). Induced pluripotent stem cell (iPSCs) were derived via transfection with episomal vectors carrying hOCT4, hSOX2, hKLF2, hL-MYC, hLIN28...

  20. Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific heterozygous mutation in CHMP2B

    DEFF Research Database (Denmark)

    Zhang, Yu; Schmid, Benjamin; Nielsen, Troels Tolstrup

    2016-01-01

    have generated an induced pluripotent stem cell (iPSC) line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into one of the alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B-dependent phenotypes of FTD3....

  1. Cytogenetic investigations of a narrow leaf garden bean mutation induced by gamma rays

    International Nuclear Information System (INIS)

    Zagorcheva, L.; Poryazov, I.; Nikolova, V.

    1988-01-01

    Narrow leaf mutations were found in M 2 after 80 and 100 Gy gamma irradiation of cv. Zarya seeds. They did not differ from one another neither in degree of character expression nor in pollen fertility. In M 3 and M 4 the mutants did not always preserve their type. The chromosomal behaviour of five narrow leaf mutants was followed. Data from investigations of meiosis showed that in 14.3% to 54.2% of the pollen mother cells (PMC) homologous chromosomes paired producing 11 bivalents. In 8.3 to 53.3% of PMC in four of the investigated mutants multivalents were found, represented mainly by quadrivalents and trivalents, while in 4.2% to 42.9% the chromosomes did not pair and produced univalents in diakinesis and MI. In three of the mutants investigated part of PMC had 11 bivalents and a supplementary small chromosome probably arising as a result of the observed structural chromosome changes. In MI it was included in the equatorial plate, in AI and AII it divided and its chromatides moved toward the poles of the division spindle to be included in daughter nuclei. 2 figs.; 1 tab.; 11 refs

  2. A single amino acid mutation in SNAP-25 induces anxiety-related behavior in mouse.

    Directory of Open Access Journals (Sweden)

    Masakazu Kataoka

    Full Text Available Synaptosomal-associated protein of 25 kDa (SNAP-25 is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC phosphorylates Ser(187 of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser(187 of SNAP-25 with Ala using "knock-in" technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects.

  3. Mutations in SYNGAP1 Cause Intellectual Disability, Autism, and a Specific Form of Epilepsy by Inducing Haploinsufficiency

    DEFF Research Database (Denmark)

    Berryer, Martin H; Hamdan, Fadi F; Klitten, Laura L

    2013-01-01

    De novo mutations in SYNGAP1, which codes for a RAS/RAP GTP-activating protein, cause nonsyndromic intellectual disability (NSID). All disease-causing point mutations identified until now in SYNGAP1 are truncating, raising the possibility of an association between this type of mutations and NSID...

  4. Identification of Epithelial-Mesenchymal Transition-related Target Genes Induced by the Mutation of Smad3 Linker Phosphorylation

    Science.gov (United States)

    Park, Sujin; Yang, Kyung-Min; Park, Yuna; Hong, Eunji; Hong, Chang Pyo; Park, Jinah; Pang, Kyoungwha; Lee, Jihee; Park, Bora; Lee, Siyoung; An, Haein; Kwak, Mi-Kyung; Kim, Junil; Kang, Jin Muk; Kim, Pyunggang; Xiao, Yang; Nie, Guangjun; Ooshima, Akira

    2018-01-01

    Background Smad3 linker phosphorylation plays essential roles in tumor progression and metastasis. We have previously reported that the mutation of Smad3 linker phosphorylation sites (Smad3-Erk/Pro-directed kinase site mutant constructs [EPSM]) markedly reduced the tumor progression while increasing the lung metastasis in breast cancer. Methods We performed high-throughput RNA-Sequencing of the human prostate cancer cell lines infected with adenoviral Smad3-EPSM to identify the genes regulated by Smad3-EPSM. Results In this study, we identified genes which are differentially regulated in the presence of Smad3-EPSM. We first confirmed that Smad3-EPSM strongly enhanced a capability of cell motility and invasiveness as well as the expression of epithelial-mesenchymal transition marker genes, CDH2, SNAI1, and ZEB1 in response to TGF-β1 in human pancreatic and prostate cancer cell lines. We identified GADD45B, CTGF, and JUNB genes in the expression profiles associated with cell motility and invasiveness induced by the Smad3-EPSM. Conclusions These results suggested that inhibition of Smad3 linker phosphorylation may enhance cell motility and invasiveness by inducing expression of GADD45B, CTGF, and JUNB genes in various cancers. PMID:29629343

  5. Novel synthetic chalcones induce apoptosis in the A549 non-small cell lung cancer cells harboring a KRAS mutation.

    Science.gov (United States)

    Wang, Yiqiang; Hedblom, Andreas; Koerner, Steffi K; Li, Mailin; Jernigan, Finith E; Wegiel, Barbara; Sun, Lijun

    2016-12-01

    A series of novel chalcones were synthesized by the Claisen-Schmidt condensation reaction of tetralones and 5-/6-indolecarboxaldehydes. Treatment of human lung cancer cell line harboring KRAS mutation (A549) with the chalcones induced dose-dependent apoptosis. Cell cycle analyses and Western blotting suggested the critical role of the chalcones in interrupting G2/M transition of cell cycle. SAR study demonstrated that substituent on the indole N atom significantly affects the anticancer activity of the chalcones, with methyl and ethyl providing the more active compounds (EC 50 : 110-200nM), Compound 1g was found to be >4-fold more active in the A549 cells (EC 50 : 110nM) than in prostate (PC3) or pancreatic cancer (CLR2119, PAN02) cells. Furthermore, compound 1l selectively induced apoptosis of lung cancer cells A549 (EC 50 : 0.55μM) but did not show measurable toxicity in the normal lung bronchial epithelial cells (hBEC) at doses as high as 10μM, indicating specificity towards cancer cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Genetic signatures from amplification profiles characterize DNA mutation in somatic and radiation-induced sports of chrysanthemum

    International Nuclear Information System (INIS)

    Trigiano, R.N.; Scott, M.C.; Caetano-Anolles, G.

    1998-01-01

    The chrysanthemum (Dendranthema grandiflora Tzvelev.) cultivars 'Dark Charm', 'Salmon Charm', 'Coral Charm' and 'Dark Bronze Charm' are either radiation-induced mutants or spontaneous sports of 'Charm' and constitute a family or series of plants that primarily differ in flower color. These cultivars, which were difficult to differentiate genetically by DNA amplification fingerprinting (DAF), were easily identified by using arbitrary signatures from amplification profiles (ASAP). Genomic DNA was first amplified with three standard octamer arbitrary primers, all of which produced monomorphic profiles. Products from each of these DNA fingerprints were subsequently reamplified using four minihairpin decamer primers. The 12 primer combinations produced signatures containing approximately 37% polymorphic character loci, which were used to estimate genetic relationships between cultivars. Forty-six (32%) unique amplification products were associated with individual cultivars. The number of ASAP polymorphisms detected provided an estimate of the mutation rate in the mutant cultivars, ranging from 0.03% to 1.6% of nucleotide changes within an average of 18 kb of arbitrary amplified DAF sequence. The ASAP technique permits the clear genetic identification of somatic mutants and radiation-induced sports that are genetically highly homogeneous and should facilitate marker assisted breeding and protection of plant breeders rights of varieties or cultivars

  7. Whole-Genome Sequencing and iPLEX MassARRAY Genotyping Map an EMS-Induced Mutation Affecting Cell Competition in Drosophila melanogaster.

    Science.gov (United States)

    Lee, Chang-Hyun; Rimesso, Gerard; Reynolds, David M; Cai, Jinlu; Baker, Nicholas E

    2016-10-13

    Cell competition, the conditional loss of viable genotypes only when surrounded by other cells, is a phenomenon observed in certain genetic mosaic conditions. We conducted a chemical mutagenesis and screen to recover new mutations that affect cell competition between wild-type and RpS3 heterozygous cells. Mutations were identified by whole-genome sequencing, making use of software tools that greatly facilitate the distinction between newly induced mutations and other sources of apparent sequence polymorphism, thereby reducing false-positive and false-negative identification rates. In addition, we utilized iPLEX MassARRAY for genotyping recombinant chromosomes. These approaches permitted the mapping of a new mutation affecting cell competition when only a single allele existed, with a phenotype assessed only in genetic mosaics, without the benefit of complementation with existing mutations, deletions, or duplications. These techniques expand the utility of chemical mutagenesis and whole-genome sequencing for mutant identification. We discuss mutations in the Atm and Xrp1 genes identified in this screen. Copyright © 2016 Lee et al.

  8. Whole-Genome Sequencing and iPLEX MassARRAY Genotyping Map an EMS-Induced Mutation Affecting Cell Competition in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Chang-Hyun Lee

    2016-10-01

    Full Text Available Cell competition, the conditional loss of viable genotypes only when surrounded by other cells, is a phenomenon observed in certain genetic mosaic conditions. We conducted a chemical mutagenesis and screen to recover new mutations that affect cell competition between wild-type and RpS3 heterozygous cells. Mutations were identified by whole-genome sequencing, making use of software tools that greatly facilitate the distinction between newly induced mutations and other sources of apparent sequence polymorphism, thereby reducing false-positive and false-negative identification rates. In addition, we utilized iPLEX MassARRAY for genotyping recombinant chromosomes. These approaches permitted the mapping of a new mutation affecting cell competition when only a single allele existed, with a phenotype assessed only in genetic mosaics, without the benefit of complementation with existing mutations, deletions, or duplications. These techniques expand the utility of chemical mutagenesis and whole-genome sequencing for mutant identification. We discuss mutations in the Atm and Xrp1 genes identified in this screen.

  9. Base substitution spectra of nalidixylate resistant mutations induced by monochromatic soft X and 60Co γ-rays in bacillus subtilis spores

    International Nuclear Information System (INIS)

    Takahashi, Nobuhiro; Hieda, Kotaro; Morohoshi, Fumiko; Munakata, Nobuo

    1999-01-01

    Bacillus subtilis spores were exposed to three types of photons, monochromatic soft X-rays with the energy corresponding to the absorption peak of phosphorus K-shell electron (2,153 eV) and with the slightly lower energy (2,147 eV), and 60 Co γ-rays. From the irradiated spores, 233 mutants exhibiting nalidixic acid resistance were isolated, and together with 94 spontaneous mutants, the sequence changes in the 5'-terminal region of the gyrA gene coding for DNA gyrase subunit A were determined. Among eighteen alleles of the gyrA mutations, eight were single-base substitutions, nine were tandem double-base substitutions, and one was a double substitution skipping a middle base pair. About 6% of the radiation-induced mutations were tandem double-base substitutions, whereas none was observed among the spontaneous ones. Among spontaneous mutations, A:T and G:C pairs were equally subjected to mutations, whereas the substitutions from G:C pairs and those to A:T pairs predominated among those induced with soft X-rays. The peak-energy X-rays were more effective in killing and causing mutations than the low-energy X-rays, however, there seemed no base-change events uniquely attributable to phosphorus K-shell absorption. (author)

  10. Molecular analysis of two mouse dilute locus deletion mutations: Spontaneous dilute lethal20J and radiation-induced dilute prenatal lethal Aa2 alleles

    International Nuclear Information System (INIS)

    Strobel, M.C.; Seperack, P.K.; Copeland, N.G.; Jenkins, N.A.

    1990-01-01

    The dilute (d) coat color locus of mouse chromosome 9 has been identified by more than 200 spontaneous and mutagen-induced recessive mutations. With the advent of molecular probes for this locus, the molecular lesion associated with different dilute alleles can be recognized and precisely defined. In this study, two dilute mutations, dilute-lethal20J (dl20J) and dilute prenatal lethal Aa2, have been examined. Using a dilute locus genomic probe in Southern blot analysis, we detected unique restriction fragments in dl20J and Aa2 DNA. Subsequent analysis of these fragments showed that they represented deletion breakpoint fusion fragments. DNA sequence analysis of each mutation-associated deletion breakpoint fusion fragment suggests that both genomic deletions were generated by nonhomologous recombination events. The spontaneous dl20J mutation is caused by an interstitial deletion that removes a single coding exon of the dilute gene. The correlation between this discrete deletion and the expression of all dilute-associated phenotypes in dl20J homozygotes defines the dl20J mutation as a functional null allele of the dilute gene. The radiation-induced Aa2 allele is a multilocus deletion that, by complementation analysis, affects both the dilute locus and the proximal prenatal lethal-3 (pl-3) functional unit. Molecular analysis of the Aa2 deletion breakpoint fusion fragment has provided access to a previously undefined gene proximal to d. Initial characterization of this new gene suggests that it may represent the genetically defined pl-3 functional unit

  11. Qualitative analysis of mouse specific-locus mutations: information on genetic organization, gene expression, and the chromosomal nature of induced lesions

    Energy Technology Data Exchange (ETDEWEB)

    Russell, L.B.

    1982-01-01

    Analysis of mouse specific-locus (SL) mutations at three loci has identified over 33 distinct complementation groups - most of which are probably overlapping deficiencies - and 13 to 14 new functional units. The complementation maps that have been generated for the d-se and c regions include numerous vital functions; however, some of the genes in these regions are non-vital. At such loci, hypomorphic mutants must represent intragenic alterations, and some viable nulls could conceivably be intragenic lesions also. Analysis of SL mutations has provided information on genetic expression. Homozygous deficiencies can be completely viable or can kill at any one of a range of developmental stages. Heterozygonus deficiencies of up to 6 cM or more in genetic length have been recovered and propagated. The time of death of homozygous and the degree of inviability of heterozygous deficiencies are related more to specific content of the missing segment than to its length. Combinations of deficiencies with x-autosome translocations that inactivate the homologous region in a mosaic fashion have shown that organismic lethals are not necessarily cell lethal. The spectrum of mutations induced depends on the nature of the mutagen and the type of germ cell exposed. Radiation of spermatogonia produces intragenic as well as null mutations. Spontaneous mutations have an admixture of types not present in populations of mutations induced in germ cells, and this raises doubts concerning the accuracy of doubling-dose calculations in genetic risk estimation. The analysis of SL mutations has yielded genetic tools for the construction of detailed gene-dosage series, cis-trans comparisons, the mapping of known genes and identification of new genes, genetic rescue of various types, and the identification and isolation of DNA sequences. (ERB)

  12. Qualitative analysis of mouse specific-locus mutations: information on genetic organization, gene expression, and the chromosomal nature of induced lesions

    International Nuclear Information System (INIS)

    Russell, L.B.

    1982-01-01

    Analysis of mouse specific-locus (SL) mutations at three loci has identified over 33 distinct complementation groups - most of which are probably overlapping deficiencies - and 13 to 14 new functional units. The complementation maps that have been generated for the d-se and c regions include numerous vital functions; however, some of the genes in these regions are non-vital. At such loci, hypomorphic mutants must represent intragenic alterations, and some viable nulls could conceivably be intragenic lesions also. Analysis of SL mutations has provided information on genetic expression. Homozygous deficiencies can be completely viable or can kill at any one of a range of developmental stages. Heterozygonus deficiencies of up to 6 cM or more in genetic length have been recovered and propagated. The time of death of homozygous and the degree of inviability of heterozygous deficiencies are related more to specific content of the missing segment than to its length. Combinations of deficiencies with x-autosome translocations that inactivate the homologous region in a mosaic fashion have shown that organismic lethals are not necessarily cell lethal. The spectrum of mutations induced depends on the nature of the mutagen and the type of germ cell exposed. Radiation of spermatogonia produces intragenic as well as null mutations. Spontaneous mutations have an admixture of types not present in populations of mutations induced in germ cells, and this raises doubts concerning the accuracy of doubling-dose calculations in genetic risk estimation. The analysis of SL mutations has yielded genetic tools for the construction of detailed gene-dosage series, cis-trans comparisons, the mapping of known genes and identification of new genes, genetic rescue of various types, and the identification and isolation of DNA sequences

  13. Imidacloprid and Thiamethoxam Induced Mutations in Internal Transcribed Spacer 2 (ITS2) of Anopheles stephensi

    OpenAIRE

    Bhinder, Preety; Chaudhry, Asha; Barna, Bhupinder; Kaur, Satvinderjeet

    2012-01-01

    The present article deals with the polymerase chain reaction (PCR)-based genotoxicity evaluation of neonicotinoid pesticides, imidacloprid and thiamethoxam, by using the genome of a mosquito Anopheles stephensi taken as an experimental model. After treatment of the second instar larvae with LC20 of the pesticides for 24 h, the induced nucleotide sequence variations in the internal transcribed spacer 2 (ITS2) of freshly hatched unfed control and treated individuals was studied from the sequenc...

  14. Induced mutation and radiation sensitivity in vitro culture of soybean (Glycine Max L. Merrill)

    International Nuclear Information System (INIS)

    Atak, C.; Alikamanoglu, S.; Yalcin, S.

    1999-01-01

    In our research, the seeds of J-357 soybean variety were irradiated with 50, 100, 200, 300 and 500 Gy of gamma rays. Callus and meristem cultures were established from the primary leaves and apical meristem of 5-day-old seeding from the irradiation seeds. The average callus fresh weight formed at the cultures were determined on the 30th day and GR 50 dose which reduces the callus fresh weight at the rate 50% in accordance with control was found as 250 Gy. The regenerated plants from meristem cultures were determined on the 28th day and LD 50 dose which decreases the regenerated plant percentage at the 50% in accordance with control was found as 220 Gy. Cytological investigation was done at the callus and meristem cultures obtained from both irradiated seeds and explants. At the seed and explant irradiations, gamma radiation dose between the ranges 50 to 200 Gy and 5 to 25 Gy; respectively were used. Observations were done at mitotic anaphase in the samples taken from meristem and callus cultures. In anaphase, two types of cytological aberrations, bridge and fragments were determined. The regenerated plants were grown in the climate chamber and the seeds were taken from each M1 plant and chlorophyll mutants were determined in M2 generation. The radiosensitivity of the meristem cultures established by irradiated seeds from view of plant regenerations and plant number which is taken seed was evaluated by comparing with the results of meristem cultures established from the irradiated explant from the point of in vitro mutation studies

  15. Mutation breeding newsletter. No. 33

    International Nuclear Information System (INIS)

    1989-01-01

    This issue of the newsletter reports a number of research news and research abstracts on application of radiation induced mutation techniques to increase mutagenesis and mutation frequency in plant breeding projects

  16. Mutation breeding newsletter. No. 45

    International Nuclear Information System (INIS)

    2001-07-01

    This issue of the Mutation Breeding newsletter contains 39 articles dealing with radiation induced mutations and chemical mutagenesis techniques in plant breeding programs with the aims of improving crop productivity and disease resistance as well as exploring genetic variabilities

  17. Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific homozygous mutation in CHMP2B

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2016-07-01

    Full Text Available Frontotemporal dementia (FTD is an early onset neurodegenerative disease. Mutations in several genes cause familial FTD and one of them is charged multivesicular body protein 2B (CHMP2B on chromosome 3 (FTD3, a component of the endosomal sorting complex required for transport III (ESCRT-III. We have generated an induced pluripotent stem cell (iPSC line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into both alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B-dependent phenotypes of FTD3.

  18. Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific homozygous mutation in CHMP2B

    DEFF Research Database (Denmark)

    Zhang, Yu; Schmid, Benjamin; Nielsen, Troels T.

    2016-01-01

    Frontotemporal dementia (FTD) is an early onset neurodegenerative disease. Mutations in several genes cause familial FTD and one of them is charged multivesicular body protein 2B (CHMP2B) on chromosome 3 (FTD3), a component of the endosomal sorting complex required for transport III (ESCRT-III). ...... have generated an induced pluripotent stem cell (iPSC) line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into both alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B-dependent phenotypes of FTD3....

  19. 'Abasin-95', a new oilseed rape cultivar developed through induced mutations

    International Nuclear Information System (INIS)

    Shah, S.A.; Ali, I.; Rahman, K.

    2001-01-01

    Brassica oilseeds are the second most important source of vegetable oil in Pakistan. Due to the low priority attached to these to these crops in the past, no systematic breeding work was undertaken to develop improved varieties of rapeseed/mustard, resulting in a narrow genetic base of these crops. At the Nuclear Institute for Food and Agriculture (NIFA), gamma radiation was used to induce genetic variability in traits of economic importance thus diversifying the genetic base of indigenous/exotic cultivars of Brassica oilseeds

  20. Attempts to induce mutations for resistance of wheat to mildew, stem rust and leaf rust

    International Nuclear Information System (INIS)

    Kiraly, Z.; Barabas, Z.

    1983-01-01

    Research carried out between 1971 and 1981 is summarized. Attempts to find induced mutants with full resistance to pathotype mixtures of the three pathogens were not successful. Reasons are discussed. Studies on wheat lines tolerant to stem rust infection led to the conclusion that this disease reaction may be often accompanied by a reduced number of infection sites and a longer lag period resulting in reduced spore production. Various selection methods have been evaluated. Selecting for the multigenic 'non race specific' way is promising. (author)

  1. Relative rates at which dominant-lethal mutations and heritable translocations are induced by alkylating chemicals in postmeiotic male germ cells of mice.

    Science.gov (United States)

    Generoso, W M; Huff, S W; Cain, K T

    1979-09-01

    There is a close relationship between the rates at which dominant lethal mutations and heritable translocations are induced by ethyl methanesulfonate (EMS) or triethylenemelamine (TEM) in male postmeiotic germ cells. This relationship does not hold for isopropyl methanesulfonate (IMS), which induced only negligible frequencies of heritable translocations at doses that induced high levels of dominant lethal mutations. Nor does IMS behave like EMS and TEM in the degree to which eggs of different stocks of females repair premutational lesions that are carried in the sperm-large differences between stocks for IMS treatment and small differences for EMS or TEM treatment. These dissimilarities between IMS and the other two alkylating chemicals are postulated to be attributable to differences in the types of lesions present at the time of repair activity and to whether or not chromosomal aberrations are already fixed prior to postfertilization pronuclear DNA synthesis.

  2. HorTILLUS—A Rich and Renewable Source of Induced Mutations for Forward/Reverse Genetics and Pre-breeding Programs in Barley (Hordeum vulgare L.

    Directory of Open Access Journals (Sweden)

    Miriam E. Szurman-Zubrzycka

    2018-02-01

    Full Text Available TILLING (Targeting Induced Local Lesions IN Genomes is a strategy used for functional analysis of genes that combines the classical mutagenesis and a rapid, high-throughput identification of mutations within a gene of interest. TILLING has been initially developed as a discovery platform for functional genomics, but soon it has become a valuable tool in development of desired alleles for crop breeding, alternative to transgenic approach. Here we present the HorTILLUS (Hordeum—TILLING—University of Silesia population created for spring barley cultivar “Sebastian” after double-treatment of seeds with two chemical mutagens: sodium azide (NaN3 and N-methyl-N-nitrosourea (MNU. The population comprises more than 9,600 M2 plants from which DNA was isolated, seeds harvested, vacuum-packed, and deposited in seed bank. M3 progeny of 3,481 M2 individuals was grown in the field and phenotyped. The screening for mutations was performed for 32 genes related to different aspects of plant growth and development. For each gene fragment, 3,072–6,912 M2 plants were used for mutation identification using LI-COR sequencer. In total, 382 mutations were found in 182.2 Mb screened. The average mutation density in the HorTILLUS, estimated as 1 mutation per 477 kb, is among the highest mutation densities reported for barley. The majority of mutations were G/C to A/T transitions, however about 8% transversions were also detected. Sixty-one percent of mutations found in coding regions were missense, 37.5% silent and 1.1% nonsense. In each gene, the missense mutations with a potential effect on protein function were identified. The HorTILLUS platform is the largest of the TILLING populations reported for barley and best characterized. The population proved to be a useful tool, both in functional genomic studies and in forward selection of barley mutants with required phenotypic changes. We are constantly renewing the HorTILLUS population, which makes it a

  3. Prion protein with Y145STOP mutation induces mitochondria-mediated apoptosis and PrP-containing deposits in vitro

    International Nuclear Information System (INIS)

    Hachiya, Naomi S.; Watanabe, Kota; Kawabata, Makiko Y.; Jozuka, Akiko; Kozuka, Yoshimichi; Sakasegawa, Yuji; Kaneko, Kiyotoshi

    2005-01-01

    A pathogenic truncation of an amber mutation at codon 145 (Y145STOP) in Gerstmann-Straussler-Scheinker disease (GSS) was investigated through the real-time imaging in living cells, by utilizing GFP-PrP constructs. GFP-PrP(1-144) exhibited an aberrant localization to mitochondria in mouse neuroblastoma neuro2a (N2a) and HpL3-4 cells, a hippocampal cell line established from prnp gene-ablated mice, whereas full-length GFP-PrP did not. The aberrant mitochondrial localization was also confirmed by Western blot analysis. Since GFP-PrP(1-121), as previously reported, and full-length GFP-PrP do not exhibit such mitochondrial localization, the mitochondrial localization of GFP-PrP(1-144) requires not only PrP residues 121-144 (in human sequence) but also COOH-terminal truncation in the current experimental condition. Subsequently, the GFP-PrP(1-144) induced a change in the mitochondrial innermembrane potential (ΔΨ m ), release of cytochrome c from the intermembrane space into the cytosol, and DNA fragmentation in these cells. Non-fluorescent PrP(1-144) also induced the DNA fragmentation in N2a and HpL3-4 cells after the proteasomal inhibition. These data may provide clues as to the molecular mechanism of the neurotoxic property of Y145STOP mutation. Furthermore, immunoelectron microscopy revealed numerous electron-dense deposits in mitochondria clusters of GFP-PrP(1-144)-transfected N2a cells, whereas no deposit was detected in the cells transfected with full-length GFP-PrP. Co-localization of GFP/PrP-immunogold particles with porin-immunogold particles as a mitochondrial marker was observed in such electron-dense vesicular foci, resembling those found in autophagic vacuoles forming secondary lysosomes. Whether such electron-dense deposits may serve as a seed for the growth of amyloid plaques, a characteristic feature of GSS with Y145STOP, awaits further investigations

  4. Induced micro-mutations in rice - the frequency and spectrum of gamma ray induced height variations in rice variety-Jaya

    International Nuclear Information System (INIS)

    Nair, N.K.; Ninan, C.A.

    1975-01-01

    Seeds of rice variety, Jaya, treated with moderate doses of (10, 20 and 30 kR) gamma rays were subjected to study the relative magnitude of induced variability and the type of mutations induced for height of plant in M 2 and M 3 generations. Progenies of 3352 M 1 spikes, totalling to 35691 M 2 plants and their subsequent progenies in M 3 were analysed. To get wider variability, very large populations in all the generations were studied. The mean value, genetic variance and phenotypic frequency distribution with and between generations were studied. The treated population showed no significant shift in mean values from that of control. The variance was greater in the irradiated material compared to control. The variability was found to shift in both plus and minus direction from that of control with a higher frequency in the minus direction in M 2 . A high frequency of dwarf mutants was observed in 20 kR treated population in the M 2 generation. The segregation ratio was higher in M 2 compared to M 3 generation. (author)

  5. Effects of an epilepsy-causing mutation in the SCN1A sodium channel gene on cocaine-induced seizure susceptibility in mice.

    Science.gov (United States)

    Purcell, Ryan H; Papale, Ligia A; Makinson, Christopher D; Sawyer, Nikki T; Schroeder, Jason P; Escayg, Andrew; Weinshenker, David

    2013-07-01

    High doses of cocaine can elicit seizures in humans and in laboratory animals. Several mechanisms have been proposed for the induction of seizures by cocaine, including enhanced monoaminergic signaling, blockade of ion channels, and alterations in GABA and glutamate transmission. Mutations in the SCN1A gene, which encodes the central nervous system (CNS) voltage-gated sodium channel (VGSC) Nav1.1, are responsible for several human epilepsy disorders including Dravet syndrome and genetic (generalized) epilepsy with febrile seizures plus (GEFS+). Mice heterozygous for the R1648H GEFS+ mutation (RH mice) exhibit reduced interneuron excitability, spontaneous seizures, and lower thresholds to flurothyl- and hyperthermia-induced seizures. However, it is unknown whether impaired CNS VGSC function or a genetic predisposition to epilepsy increases susceptibility to cocaine-induced seizures. Our primary goal was to determine whether Scn1a dysfunction caused by the RH mutation alters sensitivity to cocaine-induced behavioral and electrographic (EEG) seizures. We also tested novelty- and cocaine-induced locomotor activity and assessed the expression of Nav1.1 in midbrain dopaminergic neurons. We found that RH mice had a profound increase in cocaine-induced behavioral seizure susceptibility compared to wild-type (WT) controls, which was confirmed with cortical EEG recordings. By contrast, although the RH mice were hyperactive in novel environments, cocaine-induced locomotor activity was comparable between the mutants and WT littermates. Finally, immunofluorescence experiments revealed a lack of Nav1.1 immunoreactivity in dopaminergic neurons. These data indicate that a disease-causing CNS VGSC mutation confers susceptibility to the proconvulsant, but not motoric, effects of cocaine.

  6. Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation.

    Science.gov (United States)

    Urbizu, Aintzane; Cuenca-León, Ester; Raspall-Chaure, Miquel; Gratacòs, Margarida; Conill, Joan; Redecillas, Susana; Roig-Quilis, Manuel; Macaya, Alfons

    2010-08-15

    We report two monochorionic twins that progressively developed, between ages 5 and 10, a combination of episodic neurological disorders including paroxysmal exercise-induced dyskinesia, migraine without or with aura, absence seizures and writer's cramp. CSF/serum glucose ratio was moderately decreased in both patients. Mutational analysis of SLC2A1 gene identified a de novo heterozygous missense mutation in exon 4. This novel mutation has been previously showed to disrupt glucose transport in vitro. Both patients showed immediate and near-complete response to ketogenic diet. This clinical observation suggests that a high index of suspicion for GLUT1 deficiency syndrome is warranted in evaluating patients with multiple neurological paroxysmal events. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  7. Generation of an induced pluripotent stem cell line from a patient with hereditary multiple endocrine neoplasia 2B (MEN2B) syndrome with "highest risk" RET mutation.

    Science.gov (United States)

    Bennaceur-Griscelli, A; Hadoux, J; Féraud, O; Opolon, P; Divers, D; Gobbo, E; Schlumberger, M; Griscelli, F; Turhan, A G

    2017-08-01

    Multiple Endocrine Neoplasia Type 2B (MEN2B) is a cancer-predisposing syndrome that affects patients with germline RET mutations. The clinical spectrum of the syndrome includes medullary thyroid carcinoma (MTC) and pheochromocytoma. Currently, there is no satisfactory model recapitulating all the features of the disease especially at the level of stem cells. We generated induced pluripotent stem cells (iPSCs) from a patient with RET mutation at codon 918 who developed pheochromocytoma and MTC. These iPSC had normal karyotype, harboured the RET M918T mutation and expressed pluripotency hallmarks. A comprehensive pathological assessment of teratoma was performed after injection in immunodeficient mice. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Human lymphoma mutations reveal CARD11 as the switch between self-antigen–induced B cell death or proliferation and autoantibody production

    Science.gov (United States)

    Jeelall, Yogesh S.; Wang, James Q.; Law, Hsei-Di; Domaschenz, Heather; Fung, Herman K.H.; Kallies, Axel; Nutt, Stephen L.

    2012-01-01

    Self-tolerance and immunity are actively acquired in parallel through a poorly understood ability of antigen receptors to switch between signaling death or proliferation of antigen-binding lymphocytes in different contexts. It is not known whether this tolerance-immunity switch requires global rewiring of the signaling apparatus or if it can arise from a single molecular change. By introducing individual CARD11 mutations found in human lymphomas into antigen-activated mature B lymphocytes in mice, we find here that lymphoma-derived CARD11 mutations switch the effect of self-antigen from inducing B cell death into T cell–independent proliferation, Blimp1-mediated plasmablast differentiation, and autoantibody secretion. Our findings demonstrate that regulation of CARD11 signaling is a critical switch governing the decision between death and proliferation in antigen-stimulated mature B cells and that mutations in this switch represent a powerful initiator for aberrant B cell responses in vivo. PMID:23027925

  9. Epistatic participation of REV1 and REV3 in the formation of UV-induced frameshift mutations in cell cycle-arrested yeast cells

    International Nuclear Information System (INIS)

    Heidenreich, Erich; Eisler, Herfried; Steinboeck, Ferdinand

    2006-01-01

    Mutations arising in times of cell cycle arrest may provide a selective advantage for unicellular organisms adapting to environmental changes. For multicellular organisms, however, they may pose a serious threat, in that such mutations in somatic cells contribute to carcinogenesis and ageing. The budding yeast Saccharomyces cerevisiae presents a convenient model system for studying the incidence and the mechanisms of stationary-phase mutation in a eukaryotic organism. Having studied the emergence of frameshift mutants after several days of starvation-induced cell cycle arrest, we previously reported that all (potentially error-prone) translesion synthesis (TLS) enzymes identified in S. cerevisiae did not contribute to the basal level of spontaneous stationary-phase mutations. However, we observed that an increased frequency of stationary-phase frameshift mutations, brought about by a defective nucleotide excision repair (NER) pathway or by UV irradiation, was dependent on Rev3p, the catalytic subunit of the TLS polymerase zeta (Pol ζ). Employing the same two conditions, we now examined the effect of deletions of the genes coding for polymerase eta (Pol η) (RAD30) and Rev1p (REV1). In a NER-deficient strain background, the increased incidence of stationary-phase mutations was only moderately influenced by a lack of Pol η but completely reduced to wild type level by a knockout of the REV1 gene. UV-induced stationary-phase mutations were abundant in wild type and rad30Δ strains, but substantially reduced in a rev1Δ as well as a rev3Δ strain. The similarity of the rev1Δ and the rev3Δ phenotype and an epistatic relationship evident from experiments with a double-deficient strain suggests a participation of Rev1p and Rev3p in the same mutagenic pathway. Based on these results, we propose that the response of cell cycle-arrested cells to an excess of exo- or endogenously induced DNA damage includes a novel replication-independent cooperative function of Rev1p and

  10. Mutated genes as research tool

    International Nuclear Information System (INIS)

    1981-01-01

    Green plants are the ultimate source of all resources required for man's life, his food, his clothes, and almost all his energy requirements. Primitive prehistoric man could live from the abundance of nature surrounding him. Man today, dominating nature in terms of numbers and exploiting its limited resources, cannot exist without employing his intelligence to direct natural evolution. Plant sciences, therefore, are not a matter of curiosity but an essential requirement. From such considerations, the IAEA and FAO jointly organized a symposium to assess the value of mutation research for various kinds of plant science, which directly or indirectly might contribute to sustaining and improving crop production. The benefit through developing better cultivars that plant breeders can derive from using the additional genetic resources resulting from mutation induction has been assessed before at other FAO/IAEA meetings (Rome 1964, Pullman 1969, Ban 1974, Ibadan 1978) and is also monitored in the Mutation Breeding Newsletter, published by IAEA twice a year. Several hundred plant cultivars which carry economically important characters because their genes have been altered by ionizing radiation or other mutagens, are grown by farmers and horticulturists in many parts of the world. But the benefit derived from such mutant varieties is without any doubt surpassed by the contribution which mutation research has made towards the advancement of genetics. For this reason, a major part of the papers and discussions at the symposium dealt with the role induced-mutation research played in providing insight into gene action and gene interaction, the organization of genes in plant chromosomes in view of homology and homoeology, the evolutionary role of gene duplication and polyploidy, the relevance of gene blocks, the possibilities for chromosome engineering, the functioning of cytroplasmic inheritance and the genetic dynamics of populations. In discussing the evolutionary role of

  11. A deletion mutation in nfxB of in vitro-induced moxifloxacin-resistant Pseudomonas aeruginosa confers multidrug resistance.

    Science.gov (United States)

    Thai, Van Chi; Pham, Hoang Vy; Nguyen, Duc Nhat Minh; Lambert, Peter; Nguyen, Thi Thu Hoai

    2017-09-01

    The modulation of efflux pump functions under fluoroquinolone (FQ) exposure is of great concern as it could result in occurrence of multidrug-resistant (MDR) bacterial strains. In this study, MDR mechanism in Pseudomonas aeruginosa induced via moxifloxacin (MOX) pressure was investigated. After serial MOX [concentration of 0.5 × the minimum inhibitory concentration (MIC)] exposure, the fully susceptible P. aeruginosa ATCC 9027 strain has increased its MIC not only toward MOX (1→128 mg/L) but also to other antibiotics. Furthermore, this MOX-exposed strain did not revert to antibiotic-sensitive phenotype when being cultured in antibiotic-free medium for 12 days. No mutation was observed for FQ-target (gyrA and parC) or most investigated efflux regulatory genes (mexT, mexR, and nalC) except nfxB in which a 100-bp deletion was found. This associated with the elevated expression of multidrug efflux pump operon (mexCD-oprJ) which could directly result in MDR phenotype.

  12. Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells.

    Science.gov (United States)

    Kalchschmidt, Jens S; Bashford-Rogers, Rachael; Paschos, Kostas; Gillman, Adam C T; Styles, Christine T; Kellam, Paul; Allday, Martin J

    2016-05-30

    Activation-induced cytidine deaminase (AID), the enzyme responsible for induction of sequence variation in immunoglobulins (Igs) during the process of somatic hypermutation (SHM) and also Ig class switching, can have a potent mutator phenotype in the development of lymphoma. Using various Epstein-Barr virus (EBV) recombinants, we provide definitive evidence that the viral nuclear protein EBNA3C is essential in EBV-infected primary B cells for the induction of AID mRNA and protein. Using lymphoblastoid cell lines (LCLs) established with EBV recombinants conditional for EBNA3C function, this was confirmed, and it was shown that transactivation of the AID gene (AICDA) is associated with EBNA3C binding to highly conserved regulatory elements located proximal to and upstream of the AICDA transcription start site. EBNA3C binding initiated epigenetic changes to chromatin at specific sites across the AICDA locus. Deep sequencing of cDNA corresponding to the IgH V-D-J region from the conditional LCL was used to formally show that SHM is activated by functional EBNA3C and induction of AID. These data, showing the direct targeting and induction of functional AID by EBNA3C, suggest a novel role for EBV in the etiology of B cell cancers, including endemic Burkitt lymphoma. © 2016 Kalchschmidt et al.

  13. Survival frequency and spectrum of induced mutations in Penicillium vermiculatum dangeard following

    International Nuclear Information System (INIS)

    Mitra, Jharna; Chaudhari, K.L.

    1974-01-01

    A comparative study on the sensitivity of UV, X-rays and gamma rays on conidia of Penicillium vermiculatum has been done. LD50 with UV-rays was shown with less than 60 second treatment at a dose of 6 x 10 3 ergs/mm 2 . Beyond 240 second treatment i.e. 2.4 x 10 4 ergs/mm 2 the survival percent remained almost the same, indicating resistance of surviving spores to the action of UV radiation. With X-rays an increase in the germination percent of conidia was noticed at dosages of 5 and 10 Kr. Abrupt fall in the survival percent was observed with increasing dosage of X-rays. A wide range of biochemical morphological mutants was obtained with UV irradiation as compared to those with X-rays. Nicotinic acid requiring mutants occurred frequently with X-rays and methionine requiring ones with gamma-rays. Compact colonial mutants were induced freely with X-rays and violet pigment producing ones with gamma-rays. (author)

  14. Influence of X-ray dose fractionation on the frequency of somatic mutations induced in Tradescantia stamen hairs

    International Nuclear Information System (INIS)

    McNulty, P.J.; Nauman, C.H.; Sparrow, A.H.; Schwemmer, S.S.; Schairer, L.A.

    1977-01-01

    X-rays were used to investigate the influence of dose fractionation on the induction of pink and colorless somatic mutations in stamen hair cells of Tradescantia clone 02. Inflorescences were exposed to a single acute dose of 60 rad, two acute doses of 30 rad, or three acute doses of 20 rad. The dose rate in all cases was 30 rad/min. Intervals between dose fractions were varied from 35 sec to 48 h and the mutation frequency was compared with that resulting after the single dose of 60 rad. The date show a reduction in mutation frequency for fractionation intervals longer than 15 and 6 min for pink and colorless mutations, respectively, but not for shorter intervals. One interpretation of the data predicts that pink mutation frequencies are reduced by 11% for fraction intervals of 30 min to 6 h, and that colorless mutation frequencies are reduced by 24% for intervals of 15 min to 6 h. The corresponding sparing effect of dose fractionation is equal to 6 rad for pink mutations and 9 rad at the colorless mutation endpoint. A calculation has been made which indicates that the percentages of the total repairable (presumably two-hit) damage that is repaired during fraction intervals up to 6 h, are 16 and 35% for pink and colorless mutations, respectively

  15. L-3-n-Butylphthalide Protects HSPB8 K141N Mutation-Induced Oxidative Stress by Modulating the Mitochondrial Apoptotic and Nrf2 Pathways

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Yang

    2017-07-01

    Full Text Available Charcot–Marie–Tooth disease (CMT, also known as hereditary motor and sensory neuropathy, is the most common inherited peripheral nerve disorder. Missense mutations, such as K141N, in the small heat shock protein HSPB8 are known to cause distal hereditary motor neuropathy 2A (dHMN2A or Charcot-Marie-Tooth neuropathy type 2L (CMT2L. However, of critical clinical significance, very few specific therapies for this disease exist. In the present study, we investigated the impact of mutant K141N HSPB8 on mitochondrial distribution and function in a cellular model of CMT2L. Our results indicate that K141N HSPB8 induced mitochondrial aggregation and caused increased oxidative stress injury. As an extraction from Chinese celery Apium graveolens Linn seeds, L-3-n-Butylphthalide (NBP, has been reported to exert many neuroprotective effects, we interrogated whether NBP could elicit a protective effect on the cell injury typically caused by HSPB8 K141N mutations. We found NBP could reverse the pathological processes induced by HSPB8 K141N mutation via an antioxidant effect, modulation of the Bax/Bcl-2 mitochondrial apoptotic and Nrf2 pathways. We propose a novel function of HSPB8, highlighting the consequence of the K141N pathogenic mutation. Furthermore, we suggest NBP may have promising therapeutic potential in the treatment of CMT2L.

  16. UV Signature Mutations

    Science.gov (United States)

    2014-01-01

    Sequencing complete tumor genomes and exomes has sparked the cancer field's interest in mutation signatures for identifying the tumor's carcinogen. This review and meta-analysis discusses signatures and their proper use. We first distinguish between a mutagen's canonical mutations – deviations from a random distribution of base changes to create a pattern typical of that mutagen – and the subset of signature mutations, which are unique to that mutagen and permit inference backward from mutations to mutagen. To verify UV signature mutations, we assembled literature datasets on cells exposed to UVC, UVB, UVA, or solar simulator light (SSL) and tested canonical UV mutation features as criteria for clustering datasets. A confirmed UV signature was: ≥60% of mutations are C→T at a dipyrimidine site, with ≥5% CC→TT. Other canonical features such as a bias for mutations on the non-transcribed strand or at the 3' pyrimidine had limited application. The most robust classifier combined these features with criteria for the rarity of non-UV canonical mutations. In addition, several signatures proposed for specific UV wavelengths were limited to specific genes or species; non-signature mutations induced by UV may cause melanoma BRAF mutations; and the mutagen for sunlight-related skin neoplasms may vary between continents. PMID:25354245

  17. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

    Directory of Open Access Journals (Sweden)

    Yukiko Ihara

    Full Text Available The hetero-tetrameric voltage-gated potassium channel Kv7.2/Kv7.3, which is encoded by KCNQ2 and KCNQ3, plays an important role in limiting network excitability in the neonatal brain. Kv7.2/Kv7.3 dysfunction resulting from KCNQ2 mutations predominantly causes self-limited or benign epilepsy in neonates, but also causes early onset epileptic encephalopathy. Retigabine (RTG, a Kv7.2/ Kv7.3-channel opener, seems to be a rational antiepileptic drug for epilepsies caused by KCNQ2 mutations. We therefore evaluated the effects of RTG on seizures in two strains of knock-in mice harboring different Kcnq2 mutations, in comparison to the effects of phenobarbital (PB, which is the first-line antiepileptic drug for seizures in neonates. The subjects were heterozygous knock-in mice (Kcnq2Y284C/+ and Kcnq2A306T/+ bearing the Y284C or A306T Kcnq2 mutation, respectively, and their wild-type (WT littermates, at 63-100 days of age. Seizures induced by intraperitoneal injection of kainic acid (KA, 12mg/kg were recorded using a video-electroencephalography (EEG monitoring system. Effects of RTG on KA-induced seizures of both strains of knock-in mice were assessed using seizure scores from a modified Racine's scale and compared with those of PB. The number and total duration of spike bursts on EEG and behaviors monitored by video recording were also used to evaluate the effects of RTG and PB. Both Kcnq2Y284C/+ and Kcnq2A306T/+ mice showed significantly more KA-induced seizures than WT mice. RTG significantly attenuated KA-induced seizure activities in both Kcnq2Y284C/+ and Kcnq2A306T/+ mice, and more markedly than PB. This is the first reported evidence of RTG ameliorating KA-induced seizures in knock-in mice bearing mutations of Kcnq2, with more marked effects than those observed with PB. RTG or other Kv7.2-channel openers may be considered as first-line antiepileptic treatments for epilepsies resulting from KCNQ2 mutations.

  18. Somatic mutation and recombination induced with reactor thermal neutrons in Drosophila melanogaster; Mutacion y recombinacion somaticas inducidas con neutrones termicos de reactor en Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Zambrano A, F.; Guzman R, J.; Paredes G, L.; Delfin L, A. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    The SMART test of Drosophila melanogaster was used to quantify the effect over the somatic mutation and recombination induced by thermal and fast neutrons at the TRIGA Mark III reactor of the ININ at the power of 300 k W for times of 30, 60 and 120 minutes with total equivalent doses respectively of 20.8, 41.6 and 83.2 Sv. A linear relation between the radiation equivalent dose and the frequency of the genetic effects such as mutation and recombination was observed. The obtained results allow to conclude that SMART is a sensitive system to the induced damage by neutrons, so this can be used for studying its biological effects. (Author)

  19. Induction and identification of somatic mutations with particular reference to perennial plants. Part of a coordinated programme on improvement of vegetatively propagated crops and tree crops through radiation-induced mutations

    International Nuclear Information System (INIS)

    Zubrzycki, H.M.

    1980-06-01

    An attempt was made to obtain resistance of oranges (Citrus sinensis L. Osbeck) and grapefruit (C. paradisi Macf.) to Tristeza virus by induced mutation breeding. Two methods were used. In one, buds were treated with X or gamma radiation. The detached sprouts were subsequently grafted. In the other, a number of chemical mutagens were used: diethyl sulfate or propylenoxide on buds; diethyl sulfate or nitrosemethylurethane on seeds (2400). The selection and isolation of mutants from treated buds and seeds, respectively, are described. Intermediate results only are given and discussed

  20. The effects of MSH2 deficiency on spontaneous and radiation-induced mutation rates in the mouse germline

    International Nuclear Information System (INIS)

    Burr, Karen L-A.; Duyn-Goedhart, Annemarie van; Hickenbotham, Peter; Monger, Karen; Buul, Paul P.W. van; Dubrova, Yuri E.

    2007-01-01

    Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of mismatch repair deficient Msh2 knock-out mice. Spontaneous mutation rates in homozygous Msh2 -/- males were significantly higher than those in isogenic wild-type (Msh2 +/+ ) and heterozygous (Msh2 +/- ) mice. In contrast, the irradiated Msh2 -/- mice did not show any detectable increases in their mutation rate, whereas significant ESTR mutation induction was observed in the irradiated Msh2 +/+ and Msh2 +/- animals. Considering these data and the results of other publications, we propose that the Msh2-deficient mice possess a mutator phenotype in their germline and somatic tissues while the loss of a single Msh2 allele does not affect the stability of heterozygotes

  1. Better plants through mutations

    International Nuclear Information System (INIS)

    1988-01-01

    This is a public relations film describing problems associated with the genetic improvement of crop plants through induced mutations. Mutations are the ultimate source of genetic variation in plants. Mutation induction is now established as a practical tool in plant breeding. The Joint FAO/IAEA Division and the IAEA's laboratory at Seibersdorf have supported research and practical implementation of mutation breeding of both seed propagated and vegetatively propagated plants. Plant biotechnology based on in vitro culture and recombinant DNA technology will make a further significant contribution to plant breeding

  2. An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor Uncoordinated-5C-induced Signaling That Merges with Amyloid β Precursor Protein Signaling.

    Science.gov (United States)

    Hashimoto, Yuichi; Toyama, Yuka; Kusakari, Shinya; Nawa, Mikiro; Matsuoka, Masaaki

    2016-06-03

    A missense mutation (T835M) in the uncoordinated-5C (UNC5C) netrin receptor gene increases the risk of late-onset Alzheimer disease (AD) and also the vulnerability of neurons harboring the mutation to various insults. The molecular mechanisms underlying T835M-UNC5C-induced death remain to be elucidated. In this study, we show that overexpression of wild-type UNC5C causes low-grade death, which is intensified by an AD-linked mutation T835M. An AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1, inhibit this death. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of death-associated protein kinase 1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid β precursor protein (APP). Notably, netrin1 also binds to APP and partially inhibits the death-signaling cascade, induced by APP. These results may provide new insight into the amyloid β-independent pathomechanism of AD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor Uncoordinated-5C-induced Signaling That Merges with Amyloid β Precursor Protein Signaling*

    Science.gov (United States)

    Hashimoto, Yuichi; Toyama, Yuka; Kusakari, Shinya; Nawa, Mikiro; Matsuoka, Masaaki

    2016-01-01

    A missense mutation (T835M) in the uncoordinated-5C (UNC5C) netrin receptor gene increases the risk of late-onset Alzheimer disease (AD) and also the vulnerability of neurons harboring the mutation to various insults. The molecular mechanisms underlying T835M-UNC5C-induced death remain to be elucidated. In this study, we show that overexpression of wild-type UNC5C causes low-grade death, which is intensified by an AD-linked mutation T835M. An AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1, inhibit this death. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of death-associated protein kinase 1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid β precursor protein (APP). Notably, netrin1 also binds to APP and partially inhibits the death-signaling cascade, induced by APP. These results may provide new insight into the amyloid β-independent pathomechanism of AD. PMID:27068745

  4. Mutation breeding newsletter. No. 43

    International Nuclear Information System (INIS)

    1997-10-01

    This issue of the Newsletter includes articles dealing with radiation induced mutation based plant breeding research findings aimed at improving productivity, disease resistance and tolerance of stress conditions

  5. Expression of R132H mutational IDH1 in human U87 glioblastoma cells affects the SREBP1a pathway and induces cellular proliferation.

    Science.gov (United States)

    Zhu, Jian; Cui, Gang; Chen, Ming; Xu, Qinian; Wang, Xiuyun; Zhou, Dai; Lv, Shengxiang; Fu, Linshan; Wang, Zhong; Zuo, Jianling

    2013-05-01

    Sterol regulatory element-binding protein-1a (SREBP1a) is a member of the SREBP family of transcription factors, which mainly controls homeostasis of lipids. SREBP1a can also activate the transcription of isocitrate dehydrogenase 1 (IDH1) by binding to its promoter region. IDH1 mutations, especially R132H mutation of IDH1, are a common feature of a major subset of human gliomas. There are few data available on the relationship between mutational IDH1 expression and SREBP1a pathway. In this study, we investigated cellular effects and SREBP1a pathway alterations caused by R132H mutational IDH1 expression in U87 cells. Two glioma cell lines, stably expressing mutational (U87/R132H) or wild type (U87/wt) IDH1, were established. A cell line, stably transfected with pcDNA3.1(+) (U87/vector), was generated as a control. Click-iT EdU assay, sulforhodamine B assay, and wound healing assay respectively showed that the expression of R132H induced cellular proliferation, cell growth, and cell migration. Western blot revealed that SREBP1 was increased in U87/R132H compared with that in U87/wt. Elevated SREBP1a and several its target genes, but not SREBP1c, were detected by real-time polymerase chain reaction in U87/R132H. All these findings indicated that R132H mutational IDH1 is involved in the regulation of proliferation, growth, and migration of glioma cells. These effects may partially be mediated by SREBP1a pathway.

  6. Point mutation in activated c-Ha-ras gene of a chemically induced transplantable human pancreas carcinoma

    International Nuclear Information System (INIS)

    Maheshwari, K.K.; Parsa, I.

    1986-01-01

    The authors have reported a model of human pancreas carcinogenesis where repeated treatment with MNU of explants results in the development of transplantable carcinoma. This report compares the endonuclease digests of DNAs from normal human pancreas (HP) and MNU-induced transplantable tumor (HP-T1) analyzed with 32 P-labelled Ha-ras probe prepared from clone BS-9. The hybridization patterns of BamHI, BglII, EcoRI and HindIII digests of HP were significantly different from those of HP-T1. In EcoRI digests a 3.0 kb fragments of HP-T1 DNA hybridized with Ha-ras probe instead of a 4.3 kb fragments seen in HP DNA. The pattern for HindIII digests was similar to those of EcoRI. The BgIII digests of HP DNA revealed two hybridizing fragments of 8.0 and 4.3 kb whereas those of HP-T1 DNA fragments measured 8.5 and 4.0 kb. BamHI treated HP DNA showed only hybridizing fragments of 6.6 kb while the HP-T1 DNA showed to hybridizing fragments of 6.8 and 7.2 kb. The digested DNAs by HhaI, HinfI, KpnI, pstI, PvuII, SaII, SstI, TaqI and XbaI showed similar hybridization profiles. The point mutation in c-Ha-ras was examined in the HpaII and MspI double digests of both DNAs by 0.6 Kb SmaI fragments of pEJ. The hybridized fragments measured 412 and 355 bp in DNA digests from tumor and normal pancreas respectively

  7. Ecology meets plant physiology: herbivore-induced plant responses and their indirect effects on arthropod communities

    NARCIS (Netherlands)

    Sabelis, M.W.; Takabayashi, J.; Janssen, A.; Kant, M.R.; van Wijk, M.; Sznajder, B.; Aratchige, N.S.; Lesna, I.; Belliure, B.; Schuurink, R.C.; Ohgushi, T.; Craig, T.P.; Price, P.W.

    2007-01-01

    Herbivory by arthropods induces a wealth of changes in the primary and secondary chemistry of plants (Karban and Baldwin 1997, Constabel 1999, Agrawal et al. 1999, Kessler and Baldwin 2002). These chemical changes in turn do not only affect the inducer, but also other herbivore species attacking the

  8. Improvement of local varieties of rice (Oryza glaberrima) for resistance to shattering and grain quality by induced mutations

    International Nuclear Information System (INIS)

    Cisse, F.; Dione, M.; Kelly, S.

    1997-01-01

    In Mali, a large area of rice is planted with the local rice, O. glaberrima which under conditions of low rainfall and flood water is more hardy to stress than the introduced O. sativa cultivars. A program to improve the local varieties of O. glaberrima by induced mutations was started in 1988. Ten local varieties were irradiated with 20 and 30 krad. In M 4 of cv. 'Gorbal', irradiated with 20 krads, 13 variants were selected. Five of these were evaluated in M 5 for their agronomic performance. The induced mutants in the remaining 9 varieties were highly sterile with 90% or more sterility in the M 2 and M 3 . Irradiation with 20-30 krad gave high survival (70-95%), and several mutants with white kernel were obtained from the red seeded types. Nearly two-third of the identified mutants had white caryopsis. There is better consumer acceptance of the white seeded type of rice than the red seeded varieties in Mali and the white seeded mutants may have an added premium in the market. The field performance of the M 5 mutants was investigated. Preliminary results showed that some of mutants derived from cv. 'Gorbal' were early in maturity and had more panicles per plant, but had a lower 1000-kernel weight, and did not differ from the parent in grain yield. Additional trials are planned to establish potential of the mutants for yield and quality. Three more cultivars of O. glaberrima - 'Haira', 'Tombo' and 'Yele' - were irradiated with 20 and 60 krads, and gave 75, 81 and 72% seed viability, respectively. M 1 showed reduced plant height. Selection for non-shattering of grains shall be carried out in M 2 . Any plants which are non-shattering but sterile shall be crossed with the parent to recover the mutant types. The taxonomic status of cv. 'Gorbal' is not very clear. Isozyme patterns suggest that this cultivar may belong to O. sativa and not to O. glaberrima. To establish its taxonomic status, crosses shall be made with O. sativa and O. glaberrima. (author). 2 tabs

  9. Effect of uvs1, uvs2 and xrs mutations on the radiosensitivity and the induced mitotic recombination frequency in diploid yeast cells

    International Nuclear Information System (INIS)

    Suslova, N.G.; Fedorova, I.V.; Zheleznyakova, N.Yu.

    1975-01-01

    The influence of the loci of radiosensitivity uvs1, uvs2, and xrs in the homozygous state at the diploid level on the sensitivity to UV and ionizing radiation and induced mitotic recombination was studied in the yeast Sacch. cerevisiae. Hypersensitivity to UV irradiation was detected in the diploids uvs2 uvs2 xrs xrs in comparision with the corresponding control. The diploid uvs1 uvs1 uvs2 uvs2 does not differ in UV sensitivity from the diploid uvs1 uvs1 UVS2 UVS2. These facts demonstrate that the uvs1 and uvs2 mutations, on the one hand, and the xrs mutations, on the other, normally control different pathways of elimination of UV-induced damages. It was shown that the diploid uvs2 uvs2 xrs3 xrs3 is far more sensitive to the lethal action of x rays than the control diploid UVS2 UVS2 xrs3 xrs3. Consequently, the mutations uvs2 and xrs3 block different modes of repair of damages induced by ionizing radiation. In all the double-mutant diploids, the frequency of mitotic recombination induced by UV rays increases sharply in comparison with that of the radioresistant diploids UVS UVS XRS XRS and the UV-sensitive diploids uvs2 uvs2 XRS XRS. Possible causes of the observed phenomenon are discussed. It was established that in a diploid homozygous for the loci uvs2 xrs5, the frequency of mitotic recombination induced by x rays increases extremely sharply. This fact confirms the hypothesis that the gene product of the locus uvs2 participates in the repair of DNA after the action of ionizing radiation. (author)

  10. Transfection with extracellularly UV-damaged DNA induces human and rat cells to express a mutator phenotype towards parvovirus H-1

    Energy Technology Data Exchange (ETDEWEB)

    Dinsart, C.; Cornelis, J.J.; Klein, B.; van der Eb, A.J.; Rommelaere, J.

    1984-02-01

    Human and rat cells transfected with UV-irradiated linear double-stranded DNA from calf thymus displayed a mutator activity. This phenotype was identified by growing a lytic thermosensitive single-stranded DNA virus (parvovirus H-1) in those cells and determining viral reversion frequencies. Likewise, exogenous UV-irradiated closed circular DNAs, either double-stranded (simian virus 40) or single-stranded (phi X174), enhanced the ability of recipient cells to mutate parvovirus H-1. The magnitude of mutator activity expression increased along with the number of UV lesions present in the inoculated DNA up to a saturation level. Unirradiated DNA displayed little inducing capacity, irrespective of whether it was single or double stranded. Deprivation of a functional replication origin did not impede UV-irradiated simian virus 40 DNA from providing rat and human cells with a mutator function. Our data suggest that in mammalian cells a trans-acting mutagenic signal might be generated from UV-irradiated DNA without the necessity for damaged DNA to replicate.

  11. Genetics of gamma-irradiation-induced mutations in Arabidopsis thaliana: large chromosomal deletions can be rescued through the fertilization of diploid eggs.

    Science.gov (United States)

    Vizir, I Y; Mulligan, B J

    1999-01-01

    Despite the demonstrated value of chromosomal deletions and deficiencies as tools in plant and animal genome research, in the genetic model plant species Arabidopsis thaliana, such mutations have not been extensively studied. For example, it is not known whether large deletions in different regions of the genome can be tolerated in diploid plants that are heterozygous for such mutations. Similarly the viability or inviability of monosomics has not been examined in detail. To investigate these questions, we have used gamma-irradiated haploid wild-type pollen to pollinate diploid and tetraploid multimarker lines of Arabidopsis. Examination of M1 progenies revealed that chromosome loss mutations and large deletions were induced in the irradiated pollen. Such mutations were eliminated in diploid M1 plants due to dominant lethality but could be rescued in triploid M1 progeny. The use of irradiated pollen and tetraploid marker lines of Arabidopsis is a convenient way of generating deletions and modified chromosomes and provides a genetic tool for deletion mapping and for analysis of chromosomal regions essential for chromosome maintenance.

  12. Dominant ER Stress-InducingWFS1Mutations Underlie a Genetic Syndrome of Neonatal/Infancy-Onset Diabetes, Congenital Sensorineural Deafness, and Congenital Cataracts.

    Science.gov (United States)

    De Franco, Elisa; Flanagan, Sarah E; Yagi, Takuya; Abreu, Damien; Mahadevan, Jana; Johnson, Matthew B; Jones, Garan; Acosta, Fernanda; Mulaudzi, Mphele; Lek, Ngee; Oh, Vera; Petz, Oliver; Caswell, Richard; Ellard, Sian; Urano, Fumihiko; Hattersley, Andrew T

    2017-07-01

    Neonatal diabetes is frequently part of a complex syndrome with extrapancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There are still patients with neonatal diabetes who have novel genetic syndromes. We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic etiology of a syndrome characterized by neonatal diabetes, sensorineural deafness, and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded. We identified 5 patients, including the initial case, with three heterozygous missense mutations in WFS1 (4/5 confirmed de novo). They had diabetes diagnosed before 12 months (2 before 6 months) (5/5), sensorineural deafness diagnosed soon after birth (5/5), congenital cataracts (4/5), and hypotonia (4/5). In vitro studies showed that these WFS1 mutations are functionally different from the known recessive Wolfram syndrome-causing mutations, as they tend to aggregate and induce robust endoplasmic reticulum stress. Our results establish specific dominant WFS1 mutations as a cause of a novel syndrome including neonatal/infancy-onset diabetes, congenital cataracts, and sensorineural deafness. This syndrome has a discrete pathophysiology and differs genetically and clinically from recessive Wolfram syndrome. © 2017 by the American Diabetes Association.

  13. PIEZO1 gene mutation in a Japanese family with hereditary high phosphatidylcholine hemolytic anemia and hemochromatosis-induced diabetes mellitus.

    Science.gov (United States)

    Imashuku, Shinsaku; Muramatsu, Hideki; Sugihara, Takashi; Okuno, Yusuke; Wang, Xinan; Yoshida, Kenichi; Kato, Ayako; Kato, Koichi; Tatsumi, Yasuaki; Hattori, Ai; Kita, Shinya; Oe, Keishi; Sueyoshi, Atsushi; Usui, Takeshi; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Ogawa, Seishi; Kojima, Seiji; Kanno, Hitoshi

    2016-07-01

    Hereditary xerocytosis (HX) or dehydrated hereditary stomatocytosis (DHS) [OMIM 194380], in which PIEZO1 gene mutation has recently been identified, is difficult to diagnose. We report here the discovery of a PIEZO1 gene mutation in a Japanese family (father, daughter, and son) who were previously diagnosed with hereditary high phosphatidylcholine hemolytic anemia (HPCHA). All of the affected family members had non-spherocytic hemolytic anemia associated with severe hemochromatosis-related diabetes mellitus. Although the causative correlation between HPCHA and PIEZO1-gene mutated HX/DHS remains to be clarified, our findings raise an important question as to whether any of the HPCHA cases previously diagnosed in Japan may have in fact been the form of hemolytic anemia known as HX/DHS with PIEZO1 gene mutation.

  14. Efforts to accelerate domestication of winged bean (Psophocarpus tetragonolobus (L.) DC.) by means of induced mutations and tissue culture

    NARCIS (Netherlands)

    Klu, G.Y.P.

    1996-01-01

    This thesis describes mutation breeding and tissue culture techniques developed for accelerated domestication of winged bean ( Psophocarpustetragonolobus (L.) DC.). The tissue culture techniques, which are the first steps towards genetic transformation of

  15. Molecular and Cellular Analysis of Human Immunodeficiency Virus-Induced Apoptosis in Lymphoblastoid T-Cell-Line-Expressing Wild-Type and Mutated CD4 Receptors

    Science.gov (United States)

    Moutouh, Laure; Estaquier, Jérôme; Richman, Douglas D.; Corbeil, Jacques

    1998-01-01

    We have previously shown that the presence of the CD4 cytoplasmic tail is critical for human immunodeficiency virus (HIV)-induced apoptosis (J. Corbeil, M. Tremblay, and D. D. Richman, J. Exp. Med. 183:39–48, 1996). We have pursued our investigation of the role of the CD4 transduction pathway in HIV-induced apoptosis. To do this, wild-type and mutant forms of the CD4 cytoplasmic tail were stably expressed in the lymphoblastoid T-cell line A2.01. Apoptosis was prevented when CD4 truncated at residue 402 was expressed; however, cells expressing mutated receptors that do not associate with p56lck (mutated at the dicysteine motif and truncated at residue 418) but which conserved proximal domains of the cytoplasmic tail underwent apoptosis like wild-type CD4. The differences between wild-type and mutated receptors in the induction of apoptosis were not related to levels of p56lck or NF-κB activation. Initial signaling through the CD4 receptor played a major role in the sensitization of HIV-infected T cells to undergo apoptosis. Incubation of HIV-infected cells with monoclonal antibody (MAb) 13B8-2, which binds to CD4 in a region critical for dimerization of the receptor, prevented apoptosis without inhibiting HIV replication. Moreover, the apoptotic process was not related to Fas-Fas ligand interaction; however, an antagonistic anti-Fas MAb (ZB-4) enhanced apoptosis in HIV-infected cells without inducing apoptosis in uninfected cells. These observations demonstrate that CD4 signaling mediates HIV-induced apoptosis by a mechanism independent of Fas-Fas ligand interaction, does not require p56lck signaling, and may involve a critical region for CD4 dimerization. PMID:9733846

  16. Generation of induced pluripotent stem cells (iPSCs from a Bernard–Soulier syndrome patient carrying a W71R mutation in the GPIX gene

    Directory of Open Access Journals (Sweden)

    Lourdes Lopez-Onieva

    2016-05-01

    Full Text Available We generated an induced pluripotent stem cell (iPSC line from a Bernard–Soulier Syndrome (BSS patient carrying the mutation p.Trp71Arg in the GPIX locus (BSS1-PBMC-iPS4F4. Peripheral blood mononuclear cells (PBMCs were reprogrammed using heat sensitive non-integrative Sendai viruses containing the reprogramming factors Oct3/4, SOX2, KLF4 and c-MYC. Successful silencing of the exogenous reprogramming factors was checked by RT-PCR. Characterization of BSS1-PBMC-iPS4F4 included mutation analysis of GPIX locus, Short Tandem Repeats (STR profiling, alkaline phosphatase enzymatic activity, analysis of conventional pluripotency-associated factors at mRNA and protein level and in vivo differentiation studies. BSS1-PBMC-iPS4F4 will provide a powerful tool to study BSS.

  17. Conjugation between quinolone-susceptible bacteria can generate mutations in the quinolone resistance-determining region, inducing quinolone resistance.

    Science.gov (United States)

    Pitondo-Silva, André; Martins, Vinicius Vicente; Silva, Carolina Fávero da; Stehling, Eliana Guedes

    2015-02-01

    Quinolones are an important group of antibacterial agents that can inhibit DNA gyrase and topoisomerase IV activity. DNA gyrase is responsible for maintaining bacteria in a negatively supercoiled state, being composed of subunits A and B. Topoisomerase IV is a homologue of DNA gyrase and consists of two subunits codified by the parC and parE genes. Mutations in gyrA and gyrB of DNA gyrase may confer resistance to quinolones, and the majority of resistant strains show mutations between positions 67 and 106 of gyrA, a region denoted the quinolone resistance-determining region (QRDR). The most frequent substitutions occur at positions 83 and 87, but little is known about the mechanisms promoting appearance of mutations in the QRDR. The present study proposes that some mutations in the QRDR could be generated as a result of the natural mechanism of conjugation between bacteria in their natural habitat. This event was observed following conjugation in vitro of two different isolates of quinolone-susceptible Pseudomonas aeruginosa, which transferred plasmids of different molecular weights to a recipient strain of Escherichia coli (HB101), also quinolone-susceptible, generating two different transconjugants that presented mutations in DNA gyrase and acquisition of resistance to all quinolones tested. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  18. K-ras mutation promotes ionizing radiation-induced invasion and migration of lung cancer in part via the Cathepsin L/CUX1 pathway.

    Science.gov (United States)

    Wang, Long; Zhao, Yifan; Xiong, Yajie; Wang, Wenjuan; Fei, Yao; Tan, Caihong; Liang, Zhongqin

    2018-01-15

    K-ras mutation is involved in cancer progression including invasion and migration, but the underlying mechanism is not yet clear. Cathepsin L is a lysosomal cysteine protease and has recently been associated with invasion and migration in human cancers when it is overexpressed. Our recent studies have shown that ionizing radiation (IR) enhanced expression of cathepsin L and increased invasion and migration of tumor cells, but the molecular mechanism is still unclear. In the present study, the effects of K-ras mutation and IR induced invasion and migration of lung cancer as well as the underlying mechanisms were investigated both in vitro and in vivo. Firstly, the levels of cathepsin L and epithelial mesenchymal transition (EMT) marker proteins remarkably changed in A549 (K-ras mutant) after irradiation compared with H1299 (K-ras wild), thereby promoting invasion and migration. Additionally, cathepsin L and its downstream transcription factor CUX1/p110 were increased after irradiation in A549 transfected with CUX1/p200, and the proteolytic processing of CUX1 by cathepsin L was remarkably increased after co-transfection of CUX1/p200 and cathepsin L-lentivirus in H1299. In addition, delivery of a mutant K-ras (V12) into HEK 293 cells stimulated EMT after irradiation due to the accumulation of cathepsin L. Moreover, mutated K-ras was associated with IR-induced cathepsin L and EMT in BALB/c nude mice. Finally, the level of cathepsin L expression was higher in samples carrying a K-ras mutation than in wild-type K-ras samples and the mesenchymal markers were upregulated in the samples of mutant K-ras, whereas the epithelial marker E-cadherin was downregulated in non-small cell lung cancers tissues. In conclusion, the findings demonstrated that mutated K-ras promotes cathepsin L expression and plays a pivotal role in EMT of human lung cancer. The regulatory effect of IR-induced cathepsin L on lung cancer invasion and migration was partially attributed to the Cathepsin L

  19. Improvement of measurements, theoretical computations and evaluations of neutron induced helium production cross sections. Summary report on the third and final research co-ordination meeting

    International Nuclear Information System (INIS)

    Pashchenko, A.B.

    1996-09-01

    The present report contains the Summary of the Third and Final IAEA Research Co-ordination Meeting (RCM) on ''Improvement of Measurements, Theoretical Computations and Evaluations of Neutron Induced Helium Production Cross Sections'' which was hosted by the Tohoku University and held in Sendai, Japan, from 25 to 29 September 1995. This RCM was organized by the IAEA Nuclear Data Section (NDS), with the co-operation and assistance of local organizers from Tohoku University. Summarized are the proceedings and results of the meeting. The List of Participants and meeting Agenda are included. (author)

  20. In utero exposure to nanosized carbon black (Printex90) does not induce tandem repeat mutations in female murine germ cells

    DEFF Research Database (Denmark)

    Boisen, Anne Mette Zenner; Shipley, Thomas; Jackson, Petra

    2013-01-01

    J mice were exposed four times during gestation by intratracheal instillation of 67μg/animal of nanosized carbon black Printex90 or vehicle (gestation days 7, 10, 15 and 18). Female offspring were raised to maturity and mated with unexposed CBA males. Expanded simple tandem repeat (ESTR) germline...... mutation rates in the resulting F2 generation were determined from full pedigrees (mother, father, offspring) of F1 female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in CB-exposed F2 female offspring were not statistically different from those of F2 female control offspring....

  1. Radiation-induced total-deletion mutations in the human hprt gene: a biophysical model based on random walk interphase chromatin geometry

    Science.gov (United States)

    Wu, H.; Sachs, R. K.; Yang, T. C.

    1998-01-01

    PURPOSE: To develop a biophysical model that explains the sizes of radiation-induced hprt deletions. METHODS: Key assumptions: (1) Deletions are produced by two DSB that are closer than an interaction distance at the time of DSB induction; (2) Interphase chromatin is modelled by a biphasic random walk distribution; and (3) Misrejoining of DSB from two separate tracks dominates at low-LET and misrejoining of DSB from a single track dominates at high-LET. RESULTS: The size spectra for radiation-induced total deletions of the hprt gene are calculated. Comparing with the results of Yamada and coworkers for gamma-irradiated human fibroblasts the study finds that an interaction distance of 0.75 microm will fit both the absolute frequency and the size spectrum of the total deletions. It is also shown that high-LET radiations produce, relatively, more total deletions of sizes below 0.5 Mb. The model predicts an essential gene to be located between 2 and 3 Mb from the hprt locus towards the centromere. Using the same assumptions and parameters as for evaluating mutation frequencies, a frequency of intra-arm chromosome deletions is calculated that is in agreement with experimental data. CONCLUSIONS: Radiation-induced total-deletion mutations of the human hprt gene and intrachange chromosome aberrations share a common mechanism for their induction.

  2. Analysis gives the temporary evolution the induced Mutations in alive in different organs mouse for sharp and fractional exhibition to X rays

    International Nuclear Information System (INIS)

    Martin, L.; Sierra, I.; Real, A.; De Vidania, R; Bauluz, C.

    1998-01-01

    In our laboratory we have come using, for but one year, one gives these animal models mutagenesis in alive, the model call Muta Mouse with object gives to study the mutagenic effect the ionizing radiation under different conditions exhibition, for its later application to the evaluation the risks associated to the radiation. Until the moment the temporary evolution has been analyzed (from 1 up to 60 days post-irradiation) the frequencies mutation induced in liver, bony marrow and spleen by sharp irradiations (1 and 4 Gy) and fractional (0,2 Gy/5 days and 0.8 Gy/5 days) X rays

  3. Tunnel effect in excited and ionized states of nucleic acid bases and some aspects of radiation-induced point gene mutations

    International Nuclear Information System (INIS)

    Pleticha-Lansky, R.

    1975-01-01

    Radiation induced perturbations of the genetic code are discussed from the standpoint of the frequency and specificity of mutations. According to Lowdin's theory of tautomeric rearrangement of nucleic acid base pairs through the tunnel effect, it is probable, that the proton potential in hydrogen bridges can be also effected by the incorporation of some radiolytic products of purines and pyrimidines into DNA as mistake bases. In this way it is possible, to eliminate any exo-or endogeneous energetic irradiation of the biological material and so to eliminate various undesirable damages of DNA. Thus higher specificity in the controlling of the genetic code changes would result. (F.G.)

  4. Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression

    Science.gov (United States)

    Rocha, Nuno; Bulger, David A; Frontini, Andrea; Titheradge, Hannah; Gribsholt, Sigrid Bjerge; Knox, Rachel; Page, Matthew; Harris, Julie; Payne, Felicity; Adams, Claire; Sleigh, Alison; Crawford, John; Gjesing, Anette Prior; Bork-Jensen, Jette; Pedersen, Oluf; Barroso, Inês; Hansen, Torben; Cox, Helen; Reilly, Mary; Rossor, Alex; Brown, Rebecca J; Taylor, Simeon I; McHale, Duncan; Armstrong, Martin; Oral, Elif A; Saudek, Vladimir; O’Rahilly, Stephen; Maher, Eamonn R; Richelsen, Bjørn; Savage, David B; Semple, Robert K

    2017-01-01

    MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies. DOI: http://dx.doi.org/10.7554/eLife.23813.001 PMID:28414270

  5. Visible Light-Responsive Platinum-Containing Titania Nanoparticle-Mediated Photocatalysis Induces Nucleotide Insertion, Deletion and Substitution Mutations.

    Science.gov (United States)

    Sun, Der-Shan; Tseng, Yao-Hsuan; Wu, Wen-Shiang; Wong, Ming-Show; Chang, Hsin-Hou

    2016-12-28

    Conventional photocatalysts are primarily stimulated using ultraviolet (UV) light to elicit reactive oxygen species and have wide applications in environmental and energy fields, including self-cleaning surfaces and sterilization. Because UV illumination is hazardous to humans, visible light-responsive photocatalysts (VLRPs) were discovered and are now applied to increase photocatalysis. However, fundamental questions regarding the ability of VLRPs to trigger DNA mutations and the mutation types it elicits remain elusive. Here, through plasmid transformation and β-galactosidase α-complementation analyses, we observed that visible light-responsive platinum-containing titania (TiO₂) nanoparticle (NP)-mediated photocatalysis considerably reduces the number of Escherichia coli transformants. This suggests that such photocatalytic reactions cause DNA damage. DNA sequencing results demonstrated that the DNA damage comprises three mutation types, namely nucleotide insertion, deletion and substitution; this is the first study to report the types of mutations occurring after photocatalysis by TiO₂-VLRPs. Our results may facilitate the development and appropriate use of new-generation TiO₂ NPs for biomedical applications.

  6. Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression

    DEFF Research Database (Denmark)

    Rocha, Nuno; Bulger, David A; Frontini, Andrea

    2017-01-01

    body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial...

  7. γ-ray-induced mutations of female primordial germ-cells during organogenesis in the silkworm (Bombyx mori L.)

    International Nuclear Information System (INIS)

    Miki, Mutsuo; Murakami, Akio.

    1979-01-01

    Developing silkworm embryos from 44 up 212 hr after oviposition were irradiated with a constant single dose of 1000 R of 137 Cs gamma rays (dose-rate at 300 R per min) and the change of the female primordial germ-cells in the sensitivity to mutation induction during the organogenesis. Egg-color specific locus method was used for the detection of the mutational incidences. The results obtained were summarized as follows: The mutation frequency increased gradually with the development of gonad in embryos from 68 to 116 hr after oviposition and there decreased until 188 hr when the mutation frequency was as low as in the 44 hr old embryo. The frequency increased slightly at 212 hr. The number of germ-cells increased at a rate of 30 hr/generation during the gonad formation in embryos from 68 to 128 hr after oviposition. Gonads were complete in 116 hr-old embryos. The multiplication of primordial germ-cells ceased temporarily after blastokinesis until the onset of gonial divisions in aged embryos 2 days before hatching. The change of primordial germ-cells in radiosensitivity appeared to depend on whether the germ-cells were in the process of multiplication. (author)

  8. Mutation breeding in peas

    International Nuclear Information System (INIS)

    Jaranowski, J.; Micke, A.

    1985-01-01

    The pea as an ancient crop plant still today has wide uses and is an import source of food protein. It is also an important object for genetic studies and as such has been widely used in mutation induction experiments. However, in comparison with cereals this ancient crop plant (like several other grain legumes) has gained relatively little from advances in breeding. The review focuses on the prospects of genetic improvement of pea by induced mutations, discusses principles and gives methodological information. (author)

  9. Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression.

    Science.gov (United States)

    Anandapadamanaban, Madhanagopal; Pilstål, Robert; Andresen, Cecilia; Trewhella, Jill; Moche, Martin; Wallner, Björn; Sunnerhagen, Maria

    2016-08-02

    MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 Å) presented here is closely similar to wild-type MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Mutation-induced quisqualic acid and ibotenic acid affinity at the metabotropic glutamate receptor subtype 4: ligand selectivity results from a synergy of several amino acid residues

    DEFF Research Database (Denmark)

    Hermit, Mette B; Greenwood, Jeremy R; Bräuner-Osborne, Hans

    2004-01-01

    The metabotropic glutamate receptors (mGluRs) are key modulators of excitatory neurotransmission in the central nervous system. The eight mGluR subtypes are seven trans-membrane-spanning proteins that possess a large extracellular amino-terminal domain in which the endogenous ligand binding pocket...... resides. In this study, we have identified four non-conserved amino acid residues that are essential for differentiating mGluR1 from mGluR4. Our approach has been to increase the affinity of the classic mGluR1 agonists, quisqualic acid and ibotenic acid, at mGluR4 by making various point mutations......, the mutations K74Y and K317R induced dramatic triple-order-of-magnitude increases in the affinity of ibotenic acid at mGluR4, making the affinity equivalent to that of mGluR1. Furthermore, the affinity of quisqualic acid at mGluR4 was increased to the same level as mGluR1 by the two double mutations, K74Y/K317R...

  11. In silico reversal of repeat-induced point mutation (RIP identifies the origins of repeat families and uncovers obscured duplicated genes

    Directory of Open Access Journals (Sweden)

    Hane James K

    2010-11-01

    Full Text Available Abstract Background Repeat-induced point mutation (RIP is a fungal genome defence mechanism guarding against transposon invasion. RIP mutates the sequence of repeated DNA and over time renders the affected regions unrecognisable by similarity search tools such as BLAST. Results DeRIP is a new software tool developed to predict the original sequence of a RIP-mutated region prior to the occurrence of RIP. In this study, we apply deRIP to the genome of the wheat pathogen Stagonospora nodorum SN15 and predict the origin of several previously uncharacterised classes of repetitive DNA. Conclusions Five new classes of transposon repeats and four classes of endogenous gene repeats were identified after deRIP. The deRIP process is a new tool for fungal genomics that facilitates the identification and understanding of the role and origin of fungal repetitive DNA. DeRIP is open-source and is available as part of the RIPCAL suite at http://www.sourceforge.net/projects/ripcal.

  12. Mutation in Transforming Growth Factor Beta Induced protein associated with Granular Corneal Dystrophy Type 1 Reduces the Proteolytic Susceptibility through Local Structural Stabilization#

    Science.gov (United States)

    Underhaug, Jarl; Koldsø, Heidi; Runager, Kasper; Nielsen, Jakob Toudahl; Sørensen, Charlotte S.; Kristensen, Torsten; Otzen, Daniel E.; Karring, Henrik; Malmendal, Anders; Schiøtt, Birgit; Enghild, Jan J.; Nielsen, Niels Chr.

    2014-01-01

    Hereditary mutations in the transforming growth factor beta induced (TGFBI) gene cause phenotypically distinct corneal dystrophies characterized by protein deposition in cornea. We show here that the Arg555Trp mutant of the fourth fasciclin 1 (FAS1-4) domain of the protein (TGFBIp/keratoepithelin/βig-h3), associated with granular corneal dystrophy type 1, is significantly less susceptible to proteolysis by thermolysin and trypsin than the WT domain. High-resolution liquid-state NMR of the WT and Arg555Trp mutant FAS1-4 domains revealed very similar structures except for the region around position 555. The Arg555Trp substitution causes Trp555 to be buried in an otherwise empty hydrophobic cavity of the FAS1-4 domain. The first thermolysin cleavage in the core of the FAS1-4 domain occurs on the N-terminal side of Leu558 adjacent to the Arg555 mutation. MD simulations indicated that the C-terminal end of helix α3′ containing this cleavage site is less flexible in the mutant domain, explaining the observed proteolytic resistance. This structural change also alters the electrostatic properties, which may explain increased propensity of the mutant to aggregate in vitro with 2,2,2-trifluoroethanol. Based on our results we propose that the Arg555Trp mutation disrupts the normal degradation/turnover of corneal TGFBIp, leading to accumulation and increased propensity to aggregate through electrostatic interactions. PMID:24129074

  13. Fast homozygosity mapping and identification of a zebrafish ENU-induced mutation by whole-genome sequencing.

    Science.gov (United States)

    Voz, Marianne L; Coppieters, Wouter; Manfroid, Isabelle; Baudhuin, Ariane; Von Berg, Virginie; Charlier, Carole; Meyer, Dirk; Driever, Wolfgang; Martial, Joseph A; Peers, Bernard

    2012-01-01

    Forward genetics using zebrafish is a powerful tool for studying vertebrate development through large-scale mutagenesis. Nonetheless, the identification of the molecular lesion is still laborious and involves time-consuming genetic mapping. Here, we show that high-throughput sequencing of the whole zebrafish genome can directly locate the interval carrying the causative mutation and at the same time pinpoint the molecular lesion. The feasibility of this approach was validated by sequencing the m1045 mutant line that displays a severe hypoplasia of the exocrine pancreas. We generated 13 Gb of sequence, equivalent to an eightfold genomic coverage, from a pool of 50 mutant embryos obtained from a map-cross between the AB mutant carrier and the WIK polymorphic strain. The chromosomal region carrying the causal mutation was localized based on its unique property to display high levels of homozygosity among sequence reads as it derives exclusively from the initial AB mutated allele. We developed an algorithm identifying such a region by calculating a homozygosity score along all chromosomes. This highlighted an 8-Mb window on chromosome 5 with a score close to 1 in the m1045 mutants. The sequence analysis of all genes within this interval revealed a nonsense mutation in the snapc4 gene. Knockdown experiments confirmed the assertion that snapc4 is the gene whose mutation leads to exocrine pancreas hypoplasia. In conclusion, this study constitutes a proof-of-concept that whole-genome sequencing is a fast and effective alternative to the classical positional cloning strategies in zebrafish.

  14. Fast homozygosity mapping and identification of a zebrafish ENU-induced mutation by whole-genome sequencing.

    Directory of Open Access Journals (Sweden)

    Marianne L Voz

    Full Text Available Forward genetics using zebrafish is a powerful tool for studying vertebrate development through large-scale mutagenesis. Nonetheless, the identification of the molecular lesion is still laborious and involves time-consuming genetic mapping. Here, we show that high-throughput sequencing of the whole zebrafish genome can directly locate the interval carrying the causative mutation and at the same time pinpoint the molecular lesion. The feasibility of this approach was validated by sequencing the m1045 mutant line that displays a severe hypoplasia of the exocrine pancreas. We generated 13 Gb of sequence, equivalent to an eightfold genomic coverage, from a pool of 50 mutant embryos obtained from a map-cross between the AB mutant carrier and the WIK polymorphic strain. The chromosomal region carrying the causal mutation was localized based on its unique property to display high levels of homozygosity among sequence reads as it derives exclusively from the initial AB mutated allele. We developed an algorithm identifying such a region by calculating a homozygosity score along all chromosomes. This highlighted an 8-Mb window on chromosome 5 with a score close to 1 in the m1045 mutants. The sequence analysis of all genes within this interval revealed a nonsense mutation in the snapc4 gene. Knockdown experiments confirmed the assertion that snapc4 is the gene whose mutation leads to exocrine pancreas hypoplasia. In conclusion, this study constitutes a proof-of-concept that whole-genome sequencing is a fast and effective alternative to the classical positional cloning strategies in zebrafish.

  15. DNA synthesis time in germinating rice and pattern of diethylsulphate induced mutations in pre-soaked seeds

    International Nuclear Information System (INIS)

    Narahari, P.

    1978-01-01

    DNA synthesis pattern in germinating rice seeds, pre-soaked in water for varying periods upto 48 hr, was determined by following the pulse incorporation of 3 H-thymidine into the TCA-insoluble nucleoprotein. Synthesis of DNA commenced at 24 hr, progressively increased to a first peak at about 38 hr, thereafter showed a 1/3rd drop and subsequently increased to a 2nd and still higher peak at 46 to 48 hr of pre-soaking. Treatments of diethylsulphate (dES) at a low concentration (0.2%-2hr) administered at various progressing stages of DNA synthesis resulted in decrease in seedling height and survival, and increase in mutation frequency at 45 hr. pre-soaking, maximum mutation frequencies of 20, 10 and 2% on M 1 plants, M 1 spikes and M 2 seedling bases, respectively were observed. Higher dES concentration (0.3%-2hr) given at later periods of pre-soaking showed near lethal effects and consequently decreased mutation frequencies. Treatments of sodium fluoride given singly or in combination with dES did not show any substantially different results as compared to those of the respective controls. Mutation spectra observed after dES treatments to germinating seeds, at different pre-soaking periods, were quite dissimilar. Specific mutations of economic importance like semi-dwarf mutants were isolated from the treatment of germinating seeds pre-soaked for 37.5 hr or more when shoot apex cells were undergoing DNA synthesis. (author)

  16. Derivation, Characterization, and Neural Differentiation of Integration-Free Induced Pluripotent Stem Cell Lines from Parkinson's Disease Patients Carrying SNCA, LRRK2, PARK2, and GBA Mutations

    DEFF Research Database (Denmark)

    Momcilovic, Olga; Sivapatham, Renuka; Oron, Tal Ronnen

    2016-01-01

    We report generation of induced pluripotent stem cell (iPSC) lines from ten Parkinson's disease (PD) patients carrying SNCA, PARK2, LRRK2, and GBA mutations, and one age-matched control. After validation of pluripotency, long-term genome stability, and integration-free reprogramming, eight...... not be sufficient to determine the cause or mechanism of the disease, and highlights the need to use more focused strategies for large-scale data analysis........ We further examined gene expression in a stress model (MPTP-induced dopaminergic neuronal death) using two clones from the SNCA triplication line, and detected changes in genes associated with mitophagy. Our data suggested that even a well-characterized line of a monogenic disease may...

  17. An Inducible Lentiviral Guide RNA Platform Enables the Identification of Tumor-Essential Genes and Tumor-Promoting Mutations In Vivo

    Directory of Open Access Journals (Sweden)

    Brandon J. Aubrey

    2015-03-01

    Full Text Available The CRISPR/Cas9 technology enables the introduction of genomic alterations into almost any organism; however, systems for efficient and inducible gene modification have been lacking, especially for deletion of essential genes. Here, we describe a drug-inducible small guide RNA (sgRNA vector system allowing for ubiquitous and efficient gene deletion in murine and human cells. This system mediates the efficient, temporally controlled deletion of MCL-1, both in vitro and in vivo, in human Burkitt lymphoma cell lines that require this anti-apoptotic BCL-2 protein for sustained survival and growth. Unexpectedly, repeated induction of the same sgRNA generated similar inactivating mutations in the human Mcl-1 gene due to low mutation variability exerted by the accompanying non-homologous end-joining (NHEJ process. Finally, we were able to generate hematopoietic cell compartment-restricted Trp53-knockout mice, leading to the identification of cancer-promoting mutants of this critical tumor suppressor.

  18. A case report: Becker muscular dystrophy presenting with epilepsy and dysgnosia induced by duplication mutation of Dystrophin gene.

    Science.gov (United States)

    Miao, Jing; Feng, Jia-Chun; Zhu, Dan; Yu, Xue-Fan

    2016-12-12

    Becker muscular dystrophy (BMD), a genetic disorder of X-linked recessive inheritance, typically presents with gradually progressive muscle weakness. The condition is caused by mutations of Dystrophin gene located at Xp21.2. Epilepsy is an infrequent manifestation of BMD, while cases of BMD with dysgnosia are extremely rare. We describe a 9-year-old boy with BMD, who presented with epilepsy and dysgnosia. Serum creatine kinase level was markedly elevated (3665 U/L). Wechsler intelligence tests showed a low intelligence quotient (IQ = 65). Electromyogram showed slight myogenic changes and skeletal muscle biopsy revealed muscular dystrophy. Immunohistochemical staining showed partial positivity of sarcolemma for dystrophin-N. Multiplex ligation-dependent probe amplification revealed a duplication mutation in exons 37-44 in the Dystrophin gene. The present case report helps to better understand the clinical and genetic features of BMD.

  19. Identification of the second mutation of BADH2 gene derived from rice mutant lines induced by gamma rays

    International Nuclear Information System (INIS)

    I Ishak

    2016-01-01

    The BADH2 gene acts as suppressor of 2-acetyl-1-pyrolline (2AP) biosynthesis in plants. 2AP is the volatile compound which provides fragrance in rice. Biosynthesis of 2AP occurs when BADH2 loses its function as suppressor gene. Aromatic rice cultivars naturally incur mutation of BADH2 gene at 8 bp. In this experiment, aromatic mutant rice lines derived from irradiation of Sintanur cultivar by gamma rays with dose of 100 Gy were studied in molecular level. These mutant lines were characterized at the M10 plantgeneration under the assumption that genetically these aromatic mutant rice lines were homozygotic. Several primers related to aroma in rice have been used for polymerase chain reaction (PCR) in a thermal cycler instrument. Gel electrophoreses were carried out using 1.5% agarose in TAE buffer. DNA fragments at 254 bp and 355 bp (base pair) were taken and amplified by primer for nucleotide sequencing of these fragments. Molecular identification and characterization after electrophoresis showed that the mutant line from AR1020 can be differentiated from AR.1080 at 254 bp. Nucleotide sequence data from of these DNA fragments showed that point mutations (deletions and substitutions) occurred at the BADH2 gene in exon 7; those are called second mutation and were caused by gamma rays effects. The Sintanur variety was used as check cultivar and its DNA sequence was compared to that of the AR.1020 mutant line. The results from both DNA sequences (from cv. Sintanur and AR.1020) derived from fragments at 254 bp show that point mutations occurred within exon 7 and earlier stop codon occurred in the AR.1020 mutant rice line. Further, the use of EA primer in PCR resulted in detection of deletion and substitution of nucleotides in the AR.1020 mutant line. (author)

  20. Cadmium induces DNA damage in tobacco roots, but no DNA damage, somatic mutations or homologous recombination in tobacco leaves

    Czech Academy of Sciences Publication Activity Database

    Gichner, Tomáš; Patková, Zdeňka; Száková, J.; Demnerová, K.

    2004-01-01

    Roč. 559, 1/2 (2004), s. 49-57 ISSN 1383-5718 R&D Projects: GA ČR GA526/02/0293; GA ČR GA521/02/0400; GA MŠk LN00B030 Institutional research plan: CEZ:AV0Z5038910 Keywords : beta-Glucuronidase * Chlorophyll mutations * Comet assay Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.020, year: 2004

  1. Changing in lipid profile induced by the mutation of Foxn1 gene: A lipidomic analysis of Nude mice skin.

    Science.gov (United States)

    Lanzini, Justine; Dargère, Delphine; Regazzetti, Anne; Tebani, Abdellah; Laprévote, Olivier; Auzeil, Nicolas

    2015-11-01

    Nude mice carry a spontaneous mutation affecting the gene Foxn1 mainly expressed in the epidermis. This gene is involved in several skin functions, especially in the proliferation and the differentiation of keratinocytes which are key cells of epithelial barrier. The skin, a protective barrier for the body, is essentially composed of lipids. Taking into account these factors, we conducted a lipidomic study to search for any changes in lipid composition of skin possibly related to Foxn1 mutation. Lipids were extracted from skin biopsies of Nude and BALB/c mice to be analyzed by liquid chromatography coupled to a high resolution mass spectrometer (HRMS). Multivariate and univariate data analyses were carried out to compare lipid extracts. Identification was performed using HRMS data, retention time and mass spectrometry fragmentation study. These results indicate that mutation of Foxn1 leads to significant modifications in the lipidome in Nude mice skin. An increase in cholesterol sulfate, phospholipids, sphingolipids and fatty acids associated with a decrease in glycerolipids suggest that the lipidome in mice skin is regulated by the Foxn1 gene. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  2. Report on eighth WHO meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses: Chicago, USA, 23-24 August 2016

    NARCIS (Netherlands)

    J.R. Ortiz (Justin R.); Hickling, J. (Julian); R. Jones (Rebecca); Donabedian, A. (Armen); Engelhardt, O.G. (Othmar G.); J. Katz (Jacqueline); Madhi, S.A. (Shabir A.); Neuzil, K.M. (Kathleen M.); G.F. Rimmelzwaan (Guus); Southern, J. (James); Spiro, D.J. (David J.); J. Hombach (Joachim)

    2017-01-01

    textabstractIn August 2016, the World Health Organization (WHO) convened the "Eighth meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses" to discuss the regulatory requirements and pathways for licensure of next-generation influenza vaccines,

  3. Insights into the activity change of spore photoproduct lyase induced by mutations at a peripheral glycine residue

    Science.gov (United States)

    Yang, Linlin; Li, Lei

    2017-03-01

    UV radiation triggers the formation of 5-thyminyl-5,6-dihydrothymine, i.e. the spore photoproduct (SP), in the genomic DNA of bacterial endospores. These SPs, if not repaired in time, may lead to genome instability and cell death. SP is mainly repaired by spore photoproduct lyase (SPL) during spore outgrowth via an unprecedented protein-harbored radical transfer pathway that is composed of at least a cysteine and two tyrosine residues. This mechanism is consistent with the recently solved SPL structure that shows all three residues are located in proximity and thus able to participate in the radical transfer process during the enzyme catalysis. In contrast, an earlier in vivo mutational study identified a glycine to arginine mutation at the position 168 on the B. subtilis SPL that was later found to be > 15 Å away from the enzyme active site. This mutation appears to abolish the enzyme activity because endospores carrying this mutant were sensitive to UV light. To understand the molecular basis for this rendered enzyme activity, we constructed two SPL mutations G168A and G168R, examined their repair of dinucleotide SP TpT, and found that both mutants exhibit reduced enzyme activity. Comparing with the wildtype (WT) SPL enzyme, the G168A mutant slows down the SP TpT repair by 3 4 fold while the G168R mutant by 80 fold. Both mutants exhibit a smaller apparent (DV) kinetic isotope effect (KIE) but a bigger competitive (DV/K) KIE than that by the WT SPL. Moreover, the G168R mutant also produces a large portion of the abortive repair product TpT-SO2-; the formation of which indicates that cysteine 141 is no longer well positioned as the H-donor to the thymine allylic radical intermediate. All these data imply that the mutation at the remote glycine 168 residue alters the enzyme 3D structure, subsequently reducing the SPL activity by changing the positions of the essential amino acids involved in the radical transfer process.

  4. Clinical and molecular analysis of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss associated with the mitochondrial 12S rRNA C1494T mutation

    International Nuclear Information System (INIS)

    Wang Qiuju; Li Qingzhong; Han Dongyi; Zhao Yali; Zhao Lidong; Qian Yaping; Yuan Hu; Li Ronghua; Zhai Suoqiang; Young Wieyen; Guan Minxin

    2006-01-01

    We report here the clinical, genetic, and molecular characterization of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. Five of nine matrilineal relatives had aminoglycoside-induced hearing loss. These matrilineal relatives exhibited variable severity and audiometric configuration of hearing impairment, despite sharing some common features: being bilateral and having sensorineural hearing impairment. Sequence analysis of mitochondrial DNA (mtDNA) in the pedigree identified 16 variants and the homoplasmic 12S rRNA C1494T mutation, which was associated with hearing loss in the other large Chinese family. In fact, the occurrence of the C1494T mutation in these genetically unrelated pedigrees affected by hearing impairment strongly indicated that this mutation is involved in the pathogenesis of aminoglycoside-induced and nonsyndromic hearing loss. However, incomplete penetrance of hearing loss indicated that the C1494T mutation itself is not sufficient to produce a clinical phenotype but requires the involvement of modifier factors for the phenotypic expression. Those mtDNA variants, showing no evolutional conservation, may not have a potential modifying role in the pathogenesis of the C1494T mutation. However, nuclear background seems to contribute to the phenotypic variability of matrilineal relatives in this family. Furthermore, aminoglycosides modulate the expressivity and penetrance of deafness associated with the C1494T mutation in this family

  5. Mutation Breeding Newsletter. No. 39

    International Nuclear Information System (INIS)

    1992-01-01

    This newsletter contains brief articles on the use of radiation to induce mutations in plants; radiation-induced mutants in Chrysanthemum; disrupting the association between oil and protein content in soybean seeds; mutation studies on bougainvillea; a new pepper cultivar; and the use of mutation induction to improve the quality of yam beans. A short review of the seminar on the use of mutation and related biotechnology for crop improvement in the Middle East and Mediterranean regions, and a description of a Co-ordinated Research Programme on the application of DNA-based marker mutations for the improvement of cereals and other sexually reproduced crop species are also included. Two tables are given: these are based on the ''FAO/IAEA Mutant Varieties Database'' and show the number of mutated varieties and the number of officially released mutant varieties in particular crops/species. Refs and tabs

  6. Characterization of a novel mutation in NS1 protein of influenza A virus induced by a chemical substance for the attenuation of pathogenicity.

    Directory of Open Access Journals (Sweden)

    Kohei Sasaki

    Full Text Available It is generally accepted that live attenuated influenza vaccine (LAIV has the potential for use as a vaccination against flu. In this study, we demonstrated the nature of an influenza A virus (IAV mutant induced by treating the IAV with a stable furan derivative, (1R,2R-1-(5'-methylfur-3'-ylpropane-1,2,3-triol (MFPT, which had been isolated from Streptomyces sp. strain FV60 with the objective of it being an LAIV candidate. The resulting MFPT-resistant (MFPTr IAVs possessed attenuated pathogenicity in vitro and in vivo when compared with that of the parent virus (H1N1 subtype, NWS strain. Sequencing analysis revealed that a novel mutation, C490U in ns gene (P164S in NS1, was detected in all MFPTr virus clones tested. Therefore, NS1 might be a main target of MFPT, and it was suggested that the P164S mutation contributed to the attenuated pathogenicity of the mutants. Although the phosphatidylinositol 3-kinase (PI3K/Akt signaling pathway is one of the targets of NS1, the MFPTr virus suppressed the phosphorylation of Akt when compared with the wild-type (WT virus. It was suggested that this might lead to the subsequent inhibition of the cleavage of PARP-1 and caspase-3, which is important for the progression of apoptosis. At the same time, nucleoprotein (NP was found to be retained in the nuclei in MFPTr virus-infected cells while nuclear export of NP was detected in WT virus-infected cells. In addition, the expression levels of interferon-β transcripts were significantly decreased in MFPTr virus-infected cells. From these results it can be shown that the mutation, NS1P164S, might be one of the key residues to control NS1 function concerning the induction of apoptosis. In conclusion, MFPT induced favorable mutation in the ns gene for the attenuation of IAV, and therefore might provide the novel methodology for preparing LAIVs.

  7. SH3BP2 cherubism mutation potentiates TNF-α-induced osteoclastogenesis via NFATc1 and TNF-α-mediated inflammatory bone loss

    Science.gov (United States)

    Mukai, Tomoyuki; Ishida, Shu; Ishikawa, Remi; Yoshitaka, Teruhito; Kittaka, Mizuho; Gallant, Richard; Lin, Yi-Ling; Rottapel, Robert; Brotto, Marco; Reichenberger, Ernst J.; Ueki, Yasuyoshi

    2014-01-01

    Cherubism (OMIM#118400) is a genetic disorder with excessive jawbone resorption caused by mutations in the signaling adaptor protein SH3BP2. Studies on the mouse model for cherubism carrying a P416R knock-in mutation have revealed that mutant SH3BP2 enhances TNF-α production and RANKL-induced osteoclast differentiation in myeloid cells. TNF-α is expressed in human cherubism lesions, which contain a large number of TRAP-positive multinucleated cells, and TNF-α plays a critical role in inflammatory bone destruction in homozygous cherubism mice (Sh3bp2KI/KI). The data suggest a pathophysiological relationship between mutant SH3BP2 and TNF-α-mediated bone loss by osteoclasts. Therefore, we investigated whether P416R mutant SH3BP2 is involved in TNF-α-mediated osteoclast formation and bone loss. Here, we show that bone marrow-derived M-CSF-dependent macrophages (BMMs) from the heterozygous cherubism mutant (Sh3bp2KI/+) mice are highly responsive to TNF-α and can differentiate into osteoclasts independently of RANKL in vitro by a mechanism that involves SYK and PLCγ2 phosphorylation, leading to increased nuclear translocation of NFATc1. The heterozygous cherubism mutation exacerbates bone loss with increased osteoclast formation in a mouse calvarial TNF-α injection model as well as in a human TNF-α transgenic mouse model (hTNFtg). SH3BP2 knockdown in RAW264.7 cells results in decreased TRAP-positive multinucleated cell formation. These findings suggest that the SH3BP2 cherubism mutation can cause jawbone destruction by promoting osteoclast formation in response to TNF-α expressed in cherubism lesions and that SH3BP2 is a key regulator for TNF-α-induced osteoclastogenesis. Inhibition of SH3BP2 expression in osteoclast progenitors could be a potential strategy for the treatment of bone loss in cherubism as well as in other inflammatory bone disorders. PMID:24916406

  8. Correction of Hirschsprung-Associated Mutations in Human Induced Pluripotent Stem Cells Via Clustered Regularly Interspaced Short Palindromic Repeats/Cas9, Restores Neural Crest Cell Function.

    Science.gov (United States)

    Lai, Frank Pui-Ling; Lau, Sin-Ting; Wong, John Kwong-Leong; Gui, Hongsheng; Wang, Reeson Xu; Zhou, Tingwen; Lai, Wing Hon; Tse, Hung-Fat; Tam, Paul Kwong-Hang; Garcia-Barcelo, Maria-Mercedes; Ngan, Elly Sau-Wai

    2017-07-01

    Hirschsprung disease is caused by failure of enteric neural crest cells (ENCCs) to fully colonize the bowel, leading to bowel obstruction and megacolon. Heterozygous mutations in the coding region of the RET gene cause a severe form of Hirschsprung disease (total colonic aganglionosis). However, 80% of HSCR patients have short-segment Hirschsprung disease (S-HSCR), which has not been associated with genetic factors. We sought to identify mutations associated with S-HSCR, and used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system to determine how mutations affect ENCC function. We created induced pluripotent stem cell (iPSC) lines from 1 patient with total colonic aganglionosis (with the G731del mutation in RET) and from 2 patients with S-HSCR (without a RET mutation), as well as RET +/- and RET -/- iPSCs. IMR90-iPSC cells were used as the control cell line. Migration and differentiation capacities of iPSC-derived ENCCs were analyzed in differentiation and migration assays. We searched for mutation(s) associated with S-HSCR by combining genetic and transcriptome data from patient blood- and iPSC-derived ENCCs, respectively. Mutations in the iPSCs were corrected using the CRISPR/Cas9 system. ENCCs derived from all iPSC lines, but not control iPSCs, had defects in migration and neuronal lineage differentiation. RET mutations were associated with differentiation and migration defects of ENCCs in vitro. Genetic and transcriptome analyses associated a mutation in the vinculin gene (VCL M209L) with S-HSCR. CRISPR/Cas9 correction of the RET G731del and VCL M209L mutations in iPSCs restored the differentiation and migration capacities of ENCCs. We identified mutations in VCL associated with S-HSCR. Correction of this mutation in iPSC using CRISPR/Cas9 editing, as well as the RET G731del mutation that causes Hirschsprung disease with total colonic aganglionosis, restored ENCC function. Our study demonstrates how human iPSCs can

  9. Identification of the modifier of Min 2 (Mom2) locus, a new mutation that influences Apc-induced intestinal neoplasia.

    Science.gov (United States)

    Silverman, Karen A; Koratkar, Revati; Siracusa, Linda D; Buchberg, Arthur M

    2002-01-01

    Min (Multiple intestinal neoplasia) mice carry a dominant mutation in the adenomatous polyposis coli (Apc) gene and develop multiple adenomas throughout their intestinal tract (Moser et al. 1990; Su et al 1992). Polyp multiplicity in Min mice is greatly influenced by genetic background. A modifier locus, Mom1 (Modifier of Min 1), was identified and localized to distal mouse chromosome 4 (Moser et al. 1992; Dietrich et al. 1993), and accounts for some of the genetic variance in polyp multiplicity. Mom1 is a semidominant modifier of polyp size and multiplicity in Min mice (Gould and Dove 1997), and encodes the secretory type II nonpancreatic phospholipase A2 (Pla2g2a) gene (MacPhee et al. 1995; Cornier et al. 1997, 2000). We now report the identification of a second Modifier of Min 2 (Mom2) locus that is the result of a spontaneous mutation. One resistant Mom2 allele can suppress 88%-95% of polyps detected in Apc(Min)/+ mice, indicating that Mom2 acts in a dominant fashion. Linkage analysis has localized Mom2 to distal mouse chromosome 18. The effects of the Mom2 locus on reducing polyp multiplicity are stronger than the effects of the Mom1 locus, in both the small and large intestines. Some Apc(Min)/+ mice that carried one resistant Mom2 allele were tumor-free at 21 weeks of age, even in the absence of a resistant Mom1 allele. Thus, the resistant Mom2 allele can, in some cases, completely suppress the penetrance of the Apc(Min) mutation.

  10. Novel ENU-Induced Mutation in Tbx6 Causes Dominant Spondylocostal Dysostosis-Like Vertebral Malformations in the Rat.

    Science.gov (United States)

    Abe, Koichiro; Takamatsu, Nobuhiko; Ishikawa, Kumiko; Tsurumi, Toshiko; Tanimoto, Sho; Sakurai, Yukina; Lisse, Thomas S; Lisse, Thomas; Imai, Kenji; Serikawa, Tadao; Mashimo, Tomoji

    2015-01-01

    Congenital vertebral malformations caused by embryonic segmentation defects are relatively common in humans and domestic animals. Although reverse genetics approaches in mice have provided information on the molecular mechanisms of embryonic somite segmentation, hypothesis-driven approaches cannot adequately reflect human dysmorphology within the population. In a N-ethyl-N-nitrosourea (ENU) mutagenesis project in Kyoto, the Oune mutant rat strain was isolated due to a short and kinked caudal vertebra phenotype. Skeletal staining of heterozygous rats showed partial loss of the cervical vertebrae as well as hemivertebrae and fused vertebral blocks in lumbar and sacral vertebrae. In homozygous embryos, severe displacement of the whole vertebrae was observed. The Oune locus was genetically mapped to rat chromosome 1 using 202 backcross animals and 50 genome-wide microsatellite markers. Subsequently, a miss-sense mutation in the Tbx6 gene was identified in the critical region. Although the mutation is located within the T-box domain near a predicted dimmer-interface, in vitro experiments revealed that the Tbx6 variant retains normal DNA binding ability and translational efficiency. However, the variant has decreased transcriptional activation potential in response to Notch-mediated signaling. Recently, it was reported that a dominant type of familial spondylocostal dysostosis is caused by a stoploss mutation in TBX6. Thus, we propose that partial dysfunction of Tbx6 leads to similar congenital vertebral malformations in both humans and rats. The Oune strain could be a unique animal model for dominant spondylocostal dysostosis and is useful for molecular dissection of the pathology of congenital vertebral malformations in humans.

  11. Novel ENU-Induced Mutation in Tbx6 Causes Dominant Spondylocostal Dysostosis-Like Vertebral Malformations in the Rat.

    Directory of Open Access Journals (Sweden)

    Koichiro Abe

    Full Text Available Congenital vertebral malformations caused by embryonic segmentation defects are relatively common in humans and domestic animals. Although reverse genetics approaches in mice have provided information on the molecular mechanisms of embryonic somite segmentation, hypothesis-driven approaches cannot adequately reflect human dysmorphology within the population. In a N-ethyl-N-nitrosourea (ENU mutagenesis project in Kyoto, the Oune mutant rat strain was isolated due to a short and kinked caudal vertebra phenotype. Skeletal staining of heterozygous rats showed partial loss of the cervical vertebrae as well as hemivertebrae and fused vertebral blocks in lumbar and sacral vertebrae. In homozygous embryos, severe displacement of the whole vertebrae was observed. The Oune locus was genetically mapped to rat chromosome 1 using 202 backcross animals and 50 genome-wide microsatellite markers. Subsequently, a miss-sense mutation in the Tbx6 gene was identified in the critical region. Although the mutation is located within the T-box domain near a predicted dimmer-interface, in vitro experiments revealed that the Tbx6 variant retains normal DNA binding ability and translational efficiency. However, the variant has decreased transcriptional activation potential in response to Notch-mediated signaling. Recently, it was reported that a dominant type of familial spondylocostal dysostosis is caused by a stoploss mutation in TBX6. Thus, we propose that partial dysfunction of Tbx6 leads to similar congenital vertebral malformations in both humans and rats. The Oune strain could be a unique animal model for dominant spondylocostal dysostosis and is useful for molecular dissection of the pathology of congenital vertebral malformations in humans.

  12. Induced mutagenesis in dam- mutants of Escherichia coli: A role for 6-methyladenine residues in mutation avoidance

    International Nuclear Information System (INIS)

    Glickmann, B.; Elsen, P. van den; Radmann, M.

    1978-01-01

    E. coli strains carrying the dam-3 and dam-4 mutations resulting in reduced levels of 6-methyladenine in the DNA have been found to be more sensitive to base analogue mutagenesis than dam + strains. Mutagenesis by EMS was also found to be enhanced in dam - strains. Dam - mutants, however, were not found to be hypermutable by UV light. It is concluded that the dam - strains are deficient in the correct repair of mispairing lesions. The data are consistent with the hypothesis that 6-methyladenine residues in the DNA are involved in strand discrimination during mismatch correction. (orig.) [de

  13. Herpes Simplex Virus 1 Mutant with Point Mutations in UL39 Is Impaired for Acute Viral Replication in Mice, Establishment of Latency, and Explant-Induced Reactivation.

    Science.gov (United States)

    Mostafa, Heba H; Thompson, Thornton W; Konen, Adam J; Haenchen, Steve D; Hilliard, Joshua G; Macdonald, Stuart J; Morrison, Lynda A; Davido, David J

    2018-04-01

    In the process of generating herpes simplex virus 1 (HSV-1) mutations in the viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a viral mutant, termed KOS-NA, that was severely impaired for acute replication in the eyes and trigeminal ganglia (TG) of mice, defective in establishing a latent infection, and reactivated poorly from explanted TG. To identify the secondary mutation(s) responsible for the impaired phenotypes of this mutant, we sequenced the KOS-NA genome and noted that it contained two nonsynonymous mutations in UL39 , which encodes the large subunit of ribonucleotide reductase, ICP6. These mutations resulted in lysine-to-proline (residue 393) and arginine-to-histidine (residue 950) substitutions in ICP6. To determine whether alteration of these amino acids was responsible for the KOS-NA phenotypes in vivo , we recombined the wild-type UL39 gene into the KOS-NA genome and rescued its acute replication phenotypes in mice. To further establish the role of UL39 in KOS-NA's decreased pathogenicity, the UL39 mutations were recombined into HSV-1 (generating UL39 mut ), and this mutant virus showed reduced ocular and TG replication in mice comparable to that of KOS-NA. Interestingly, ICP6 protein levels were reduced in KOS-NA-infected cells relative to the wild-type protein. Moreover, we observed that KOS-NA does not counteract caspase 8-induced apoptosis, unlike wild-type strain KOS. Based on alignment studies with other HSV-1 ICP6 homologs, our data suggest that amino acid 950 of ICP6 likely plays an important role in ICP6 accumulation and inhibition of apoptosis, consequently impairing HSV-1 pathogenesis in a mouse model of HSV-1 infection. IMPORTANCE HSV-1 is a major human pathogen that infects ∼80% of the human population and can be life threatening to infected neonates or immunocompromised individuals. Effective therapies for treatment of recurrent HSV-1 infections are limited, which emphasizes a critical need to understand in

  14. Recombination-Independent Recognition of DNA Homology for Repeat-Induced Point Mutation (RIP Is Modulated by the Underlying Nucleotide Sequence.

    Directory of Open Access Journals (Sweden)

    Eugene Gladyshev

    2016-05-01

    Full Text Available Haploid germline nuclei of many filamentous fungi have the capacity to detect homologous nucleotide sequences present on the same or different chromosomes. Once recognized, such sequences can undergo cytosine methylation or cytosine-to-thymine mutation specifically over the extent of shared homology. In Neurospora crassa this process is known as Repeat-Induced Point mutation (RIP. Previously, we showed that RIP did not require MEI-3, the only RecA homolog in Neurospora, and that it could detect homologous trinucleotides interspersed with a matching periodicity of 11 or 12 base-pairs along participating chromosomal segments. This pattern was consistent with a mechanism of homology recognition that involved direct interactions between co-aligned double-stranded (ds DNA molecules, where sequence-specific dsDNA/dsDNA contacts could be established using no more than one triplet per turn. In the present study we have further explored the DNA sequence requirements for RIP. In our previous work, interspersed homologies were always examined in the context of a relatively long adjoining region of perfect homology. Using a new repeat system lacking this strong interaction, we now show that interspersed homologies with overall sequence identity of only 36% can be efficiently detected by RIP in the absence of any perfect homology. Furthermore, in this new system, where the total amount of homology is near the critical threshold required for RIP, the nucleotide composition of participating DNA molecules is identified as an important factor. Our results specifically pinpoint the triplet 5'-GAC-3' as a particularly efficient unit of homology recognition. Finally, we present experimental evidence that the process of homology sensing can be uncoupled from the downstream mutation. Taken together, our results advance the notion that sequence information can be compared directly between double-stranded DNA molecules during RIP and, potentially, in other processes

  15. A comparative investigation of DNA strand breaks, sister chromatid exchanges and K-ras gene mutations induced by cadmium salts in cultured human cells

    International Nuclear Information System (INIS)

    Mouron, Silvana Andrea; Grillo, Claudia Alejandra; Dulout, Fernando Noel; Golijow, Carlos Daniel

    2004-01-01

    Cadmium (Cd) is a toxic heavy metal of continuing occupational and environmental concern with a wide variety of adverse effects. Several studies have shown that cadmium produces DNA strand breaks, DNA-protein cross-links, oxidative DNA damage, chromosomal aberrations, dysregulation of gene expression resulting in enhanced proliferation, depressed apoptosis and/or altered DNA repair. This study was undertaken to investigate the ability of cadmium chloride (CdCl 2 ) and cadmium sulphate (CdSO 4 ) to induce point mutations in codon 12 of the K-ras protooncogene assessed by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and RFLP-enriched PCR methods. Also their genotoxic effects were analyzed by the comet assay and sister chromatid exchanges test. The human lung fibroblast cell line MRC-5 was used for the experiments. Sister chromatid exchanges assay (SCEs) frequencies were significantly increased in cells exposed to cadmium salts in relation to controls (p < 0.001). Despite the slow increment observed in the three comet parameters considered when cells were treated with cadmium chloride, significant differences between groups were only found in the variable comet moment (CM) (p < 0.005). On the other hand, when cells were exposed to cadmium sulphate, the Kruskal-Wallis test showed highly significant differences between groups for migration, tail moment and comet moment parameters (p < 0.001). Nevertheless, a null or weak point mutation induction in K-ras protooncogene was detected using polymerase chain reaction-low ionic strength-single strand conformation polymorphisms (PCR-LIS-SSCP) and RFLP-enriched PCR methods when cells were treated with cadmium salts. Thus, inorganic cadmium produces genotoxicity in human lung fibroblast MRC-5 cells, in the absence of significant point mutation of the K-ras gene

  16. Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl

    Science.gov (United States)

    2010-01-01

    Background Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB) transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I. Results In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I) and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5) or imatinib-resistant (KBM5-T315I) CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways. Conclusion To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for further drug development to

  17. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak.

    Science.gov (United States)

    Olivas, Andrea D; Shogan, Benjamin D; Valuckaite, Vesta; Zaborin, Alexander; Belogortseva, Natalya; Musch, Mark; Meyer, Folker; Trimble, William L; An, Gary; Gilbert, Jack; Zaborina, Olga; Alverdy, John C

    2012-01-01

    The most feared complication following intestinal resection is anastomotic leakage. In high risk areas (esophagus/rectum) where neoadjuvant chemoradiation is used, the incidence of anastomotic leaks remains unacceptably high (≈ 10%) even when performed by specialist surgeons in high volume centers. The aims of this study were to test the hypothesis that anastomotic leakage develops when pathogens colonizing anastomotic sites become in vivo transformed to express a tissue destroying phenotype. We developed a novel model of anastomotic leak in which rats were exposed to pre-operative radiation as in cancer surgery, underwent distal colon resection and then were intestinally inoculated with Pseudomonas aeruginosa, a common colonizer of the radiated intestine. Results demonstrated that intestinal tissues exposed to preoperative radiation developed a significant incidence of anastomotic leak (>60%; pSNP) mutation in the mexT gene that led to a stop codon resulting in a non-functional truncated protein. Replacement of the mutated mexT gene in P2 with mexT from the original parental strain P1 led to reversion of P2 to the P1 phenotype. No spontaneous transformation was detected during 20 passages in TSB media. Use of a novel virulence suppressing compound PEG/Pi prevented P. aeruginosa transformation to the tissue destructive phenotype and prevented anastomotic leak in rats. This work demonstrates that in vivo transformation of microbial pathogens to a tissue destroying phenotype may have important implications in the pathogenesis of anastomotic leak.

  18. A desk evaluation review of project POL/5/006 plant breeding using induced mutations. Project desk evaluation

    International Nuclear Information System (INIS)

    1993-01-01

    Projects POL/5/006 was initiated in 1985 to assist the Government of Poland in improving the mutation breeding efforts in the country to promote the development of new and higher yielding crop varieties. The difficult economic situation in the country at this time restricted the procurement of special equipment, spare parts and supplies from abroad and, therefore, impeded research and development work in this field. The project was implemented using a distinctive approach and design characterized by having six recipient institutions and the establishment of one central gamma-irradiation facility to be made available to all participating institutions for mutation induction. The project was formally closed in 1989. The review of project POL/5/006 was undertaken in accord with the expressed wishes of the Board of Governors for selected ex-post evaluations of completed projects. The main purpose of the review was to ascertain if the project objectives were achieved, and to determine what impact the technical assistance provided may have had on continued post-project and current plant breeding programmes in Poland

  19. Temperature-dependent changes in neuronal dynamics in a patient with an SCN1A mutation and hyperthermia induced seizures

    Science.gov (United States)

    Peters, C.; Rosch, R. E.; Hughes, E.; Ruben, P. C.

    2016-09-01

    Dravet syndrome is the prototype of SCN1A-mutation associated epilepsies. It is characterised by prolonged seizures, typically provoked by fever. We describe the evaluation of an SCN1A mutation in a child with early-onset temperature-sensitive seizures. The patient carries a heterozygous missense variant (c3818C > T pAla1273Val) in the NaV1.1 brain sodium channel. We compared the functional effects of the variant vs. wild type NaV1.1 using patch clamp recordings from channels expressed in Chinese Hamster Ovary Cells at different temperatures (32, 37, and 40 °C). The variant channels produced a temperature-dependent destabilization of activation and fast inactivation. Implementing these empirical abnormalities in a computational model predicts a higher threshold for depolarization block in the variant, particularly at 40 °C, suggesting a failure to autoregulate at high-input states. These results reveal direct effects of abnormalities in NaV1.1 biophysical properties on neuronal dynamics. They illustrate the value of combining cellular measurements with computational models to integrate different observational scales (gene/channel to patient).

  20. Application of GAMMA ray for induction of mutation and combination with biotechnology for induce desirable genetic variation in Tangerine

    International Nuclear Information System (INIS)

    Rahimi, M.; Majd, F.; Rastegari, J.; Vedadi, S.; Naseri, M.; Jahangirzadeh, E.

    2002-01-01

    Combined application of physical mutagen and tissue culture for induction of somatic mutation in some characters without affecting the whole genome proved to be an efficient tool for improvement of plant trees.Up to now substantial breeding research has not been done on fruit trees in Iran. We are intending to begin a new era in fruit trees improvement through mutation and biotechnology. On this basis we selected tangerine as a well-adapted and highly consumed citrus fruit which has a disadvantage of too many seeds in it's flesh. Through this technique the aim is to produce seedless/less seeded tangerine in order to motivate increase in cultivation area and potential for export. We used physical mutagen (γ-ray) with doses of (30,35 and 40 Gy) for lateral bud in vivo and doses of (10, 15 and 20 Gy) for bud in-vitro. To produce explant free of pathogen we used shoot tip grafting (stg) technique, and micropropagation of bud in modified MS medium for multiplication of buds

  1. Effect of the uvr D3 mutation on ultraviolet radiation-induced DNA-repair replication in Escherichia coli K12

    International Nuclear Information System (INIS)

    Carlson, K.M.; Smith, K.C.

    1981-01-01

    Ultraviolet-radiation-induced DNA-repair replication was measured in wild-type, polA1, uvrD3, and polA1 uvrD3 strains of Escherichia coli K 12. A large stimulation of repair replication was observed in the uvrD3 strain, compared to the wild-type and polA1 strains. This enhanced repair replication was reduced in the polA1 uvrD3 strain. Therefore, a uvrD3 mutation appears to affect the amount of repair replication performed by DNA polymerase I. In the polA1 strain, there also appears to be an effect of the uvrD3 mutation on the amount of repair replication performed by DNA polymerase III (and/or II). The enhanced repair replication observed for the uvrD3 strains appears to be in response to the enhanced DNA degradation observed for these strains. (orig.)

  2. HDAC6 Inhibitors Rescued the Defective Axonal Mitochondrial Movement in Motor Neurons Derived from the Induced Pluripotent Stem Cells of Peripheral Neuropathy Patients with HSPB1 Mutation

    Directory of Open Access Journals (Sweden)

    Ji-Yon Kim

    2016-01-01

    Full Text Available The Charcot-Marie-Tooth disease 2F (CMT2F and distal hereditary motor neuropathy 2B (dHMN2B are caused by autosomal dominantly inherited mutations of the heat shock 27 kDa protein 1 (HSPB1 gene and there are no specific therapies available yet. Here, we assessed the potential therapeutic effect of HDAC6 inhibitors on peripheral neuropathy with HSPB1 mutation using in vitro model of motor neurons derived from induced pluripotent stem cells (iPSCs of CMT2F and dHMN2B patients. The absolute velocity of mitochondrial movements and the percentage of moving mitochondria in axons were lower both in CMT2F-motor neurons and in dHMN2B-motor neurons than those in controls, and the severity of the defective mitochondrial movement was different between the two disease models. CMT2F-motor neurons and dHMN2B-motor neurons also showed reduced α-tubulin acetylation compared with controls. The newly developed HDAC6 inhibitors, CHEMICAL X4 and CHEMICAL X9, increased acetylation of α-tubulin and reversed axonal movement defects of mitochondria in CMT2F-motor neurons and dHMN2B-motor neurons. Our results suggest that the neurons derived from patient-specific iPSCs can be used in drug screening including HDAC6 inhibitors targeting peripheral neuropathy.

  3. Aminoglycoside-induced and non-syndromic hearing loss is associated with the G7444A mutation in the mitochondrial COI/tRNASer(UCN) genes in two Chinese families

    International Nuclear Information System (INIS)

    Zhu Yi; Qian Yaping; Tang Xiaowen; Wang Jindan; Yang Li; Liao Zhisu; Li Ronghua; Ji Jinzhang; Li Zhiyuan; Chen Jianfu; Choo, Daniel I.; Lu Jianxin; Guan Minxin

    2006-01-01

    We report here the clinical, genetic, and molecular characterization of two Chinese families with aminoglycoside induced and non-syndromic hearing impairment. Clinical and genetic evaluations revealed the variable severity and age-of-onset in hearing impairment in these families. Strikingly, there were extremely low penetrances of hearing impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical G7444A mutation associated with hearing loss. Indeed, the G7444A mutation in the CO1 gene and the precursor of tRNA Ser(UCN) gene is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families and 164 Chinese controls. Their mitochondrial genomes belong to the Eastern Asian haplogroups C5a and D4a, respectively. In fact, the occurrence of the G7444A mutation in these several genetically unrelated subjects affected by hearing impairment strongly indicates that this mutation is involved in the pathogenesis of hearing impairment. However, there was the absence of other functionally significant mtDNA mutations in two Chinese pedigrees carrying the G7444A mutation. Therefore, nuclear modifier gene(s) or aminoglycoside(s) may play a role in the phenotypic expression of the deafness-associated G7444A mutation in these Chinese pedigrees

  4. Correlation of the UV-induced mutational spectra and the DNA damage distribution of the human HPRT gene: Automating the analysis

    International Nuclear Information System (INIS)

    Kotturi, G.; Erfle, H.; Koop, B.F.; Boer, J.G. de; Glickman, B.W.

    1994-01-01

    Automated DNA sequencers can be readily adapted for various types of sequence-based nucleic acid analysis: more recently it was determined the distribution of UV photoproducts in the E. coli laci gene using techniques developed for automated fluorescence-based analysis. We have been working to improve the automated approach of damage distribution. Our current method is more rigorous. We have new software that integrates the area under the individual peaks, rather than measuring the height of the curve. In addition, we now employ an internal standard. The analysis can also be partially automated. Detection limits for both major types of UV-photoproducts (cyclobutane dimers and pyrimidine (6-4) pyrimidone photoproducts) are reported. The UV-induced damage distribution in the hprt gene is compared to the mutational spectra in human and rodents cells

  5. The enhancement by caffeine of the frequency of lethal dominant mutation induced by gamma radiation in oocytes of Musca domestica

    International Nuclear Information System (INIS)

    Targa, H.J.; Rogatko, A.

    1982-01-01

    The results obtained, when a new technique for feeding insects is employed, on the effects of caffeine of the radiation - induced breaks of oocyte chromatids of Musca domestica are presented. (M.A.) [pt

  6. Targeted correction of a thalassemia-associated beta-globin mutation induced by pseudo-complementary peptide nucleic acids

    DEFF Research Database (Denmark)

    Lonkar, Pallavi; Kim, Ki-Hyun; Kuan, Jean Y

    2009-01-01

    Beta-thalassemia is a genetic disorder caused by mutations in the beta-globin gene. Triplex-forming oligonucleotides and triplex-forming peptide nucleic acids (PNAs) have been shown to stimulate recombination in mammalian cells via site-specific binding and creation of altered helical structures...... hindrance, pcPNAs are unable to form pcPNA-pcPNA duplexes but can bind to complementary DNA sequences via double duplex-invasion complexes. We demonstrate here that pcPNAs, when co-transfected with donor DNA fragments, can promote single base pair modification at the start of the second intron of the beta......-globin gene. This was detected by the restoration of proper splicing of transcripts produced from a green fluorescent protein-beta globin fusion gene. We also demonstrate that pcPNAs are effective in stimulating recombination in human fibroblast cells in a manner dependent on the nucleotide excision repair...

  7. Twenty year results on application of induced mutation in soybean (Glycine max (L.) Merr.) breeding at Agricultural Genetics Institute (AGI), Hanoi, Vietnam

    Energy Technology Data Exchange (ETDEWEB)

    Mai Quang Vinh; Phan Phai; Ngo Phuong Thinh; Tran Dinh Dong; Tran Thuy Oanh [Agricultural Genetics Institute (AGI), Hanoi (Viet Nam)

    2001-03-01

    Research on application of the induced mutation method combined with crossing in soybean breeding for 20 years (1980-2000) plays an important role in research work at AGI, (Ministry of Agriculture and Rural Development of Vietnam). 23 soybean varieties and hybrid lines (including 6 local cultivars, 14 selected and introduced varieties, 3 hybrid lines) were treated with Roentgen ray irradiation, Gamma Ray {sup 60}Co with doses 7, 10, 12, 15, 18, 20 krad, and with chemical mutagens: EI, NMU, DNMU, DES, EMS, DEU with various concentrations 0.008, 0.02, 0.04, 0.06, 0.08%. As the results, we obtained the important conclusions about the rule of induced mutation process in soybean in the natural conditions of Vietnam. 8 mutant varieties [1 National varieties (DT84) and 6 regional production varieties (DT83, DT90, DT94, DT95, DT99, AK06 (DT-55))]. Several promising varieties were selected and released for farmers to produce in the large areas that occupied 50-90% percentage of soybean cultivated areas in Vietnam. These varieties have high-yield 1.5-3.5 tons/ha, short growth duration 75-100 days, tolerance to cold and hot temperature and can be planted in 3 crops per year (Winter, Spring and Summer season) over 35-40 thousands ha/year. At present, the mutagens are being used for defect-orientated repair of some promising hybrid lines, in order to contribute new good varieties to soybean production in Vietnam. (author)

  8. Twenty year results on application of induced mutation in soybean (Glycine max (L.) Merr.) breeding at Agricultural Genetics Institute (AGI), Hanoi, Vietnam

    International Nuclear Information System (INIS)

    Mai Quang Vinh; Phan Phai; Ngo Phuong Thinh; Tran Dinh Dong; Tran Thuy Oanh

    2001-01-01

    Research on application of the induced mutation method combined with crossing in soybean breeding for 20 years (1980-2000) plays an important role in research work at AGI, (Ministry of Agriculture and Rural Development of Vietnam). 23 soybean varieties and hybrid lines (including 6 local cultivars, 14 selected and introduced varieties, 3 hybrid lines) were treated with Roentgen ray irradiation, Gamma Ray 60 Co with doses 7, 10, 12, 15, 18, 20 krad, and with chemical mutagens: EI, NMU, DNMU, DES, EMS, DEU with various concentrations 0.008, 0.02, 0.04, 0.06, 0.08%. As the results, we obtained the important conclusions about the rule of induced mutation process in soybean in the natural conditions of Vietnam. 8 mutant varieties [1 National varieties (DT84) and 6 regional production varieties (DT83, DT90, DT94, DT95, DT99, AK06 (DT-55). Several promising varieties were selected and released for farmers to produce in the large areas that occupied 50-90% percentage of soybean cultivated areas in Vietnam. These varieties have high-yield 1.5-3.5 tons/ha, short growth duration 75-100 days, tolerance to cold and hot temperature and can be planted in 3 crops per year (Winter, Spring and Summer season) over 35-40 thousands ha/year. At present, the mutagens are being used for defect- orientated repair of some promising hybrid lines, in order to contribute new good varieties to soybean production in Vietnam. (author)

  9. Oral exposure to commercially available coal tar‐based pavement sealcoat induces murine genetic damage and mutations

    Science.gov (United States)

    Watson, Margaret; Arlt, Volker M.; White, Paul A.

    2016-01-01

    Coal tar (CT) is a thick black liquid produced as a by‐product of coal carbonization to produce coke or manufactured gas. It is comprised a complex mixture of polycyclic aromatic compounds, including a wide range of polycyclic aromatic hydrocarbons (PAHs), many of which are genotoxic and carcinogenic. CT is used in some pavement sealants (also known as sealcoat), which are applied to pavement in order to seal and beautify the surface. Human exposure is known to occur not only during application, but also as a result of the weathering process, as elevated levels of PAHs have been found in settled house dust in residences adjacent to CT‐sealed surfaces. In this study we examined the genotoxicity of an extract of a commercially available CT‐based sealcoat in the transgenic Muta™Mouse model. Mice were orally exposed to 3 doses of sealcoat extract daily for 28 days. We evaluated genotoxicity by examining: (1) stable DNA adducts and (2) lacZ mutations in bone marrow, liver, lung, small intestine, and glandular stomach, as well as (3) micronucleated red blood cells. Significant increases were seen for each endpoint and in all tissues. The potency of the response differed across tissues, with the highest frequency of adducts occurring in liver and lung, and the highest frequency of mutations occurring in small intestine. The results of this study are the first demonstration of mammalian genotoxicity following exposure to CT‐containing pavement sealcoat. This work provides in vivo evidence to support the contention that there may be adverse health effects in mammals, and potentially in humans, from exposure to coal tar. Environ. Mol. Mutagen. 57:535–545, 2016. © 2016 Her Majesty the Queen in Right of Canada PMID:27473530

  10. Oral exposure to commercially available coal tar-based pavement sealcoat induces murine genetic damage and mutations.

    Science.gov (United States)

    Long, Alexandra S; Watson, Margaret; Arlt, Volker M; White, Paul A

    2016-08-01

    Coal tar (CT) is a thick black liquid produced as a by-product of coal carbonization to produce coke or manufactured gas. It is comprised a complex mixture of polycyclic aromatic compounds, including a wide range of polycyclic aromatic hydrocarbons (PAHs), many of which are genotoxic and carcinogenic. CT is used in some pavement sealants (also known as sealcoat), which are applied to pavement in order to seal and beautify the surface. Human exposure is known to occur not only during application, but also as a result of the weathering process, as elevated levels of PAHs have been found in settled house dust in residences adjacent to CT-sealed surfaces. In this study we examined the genotoxicity of an extract of a commercially available CT-based sealcoat in the transgenic Muta™Mouse model. Mice were orally exposed to 3 doses of sealcoat extract daily for 28 days. We evaluated genotoxicity by examining: (1) stable DNA adducts and (2) lacZ mutations in bone marrow, liver, lung, small intestine, and glandular stomach, as well as (3) micronucleated red blood cells. Significant increases were seen for each endpoint and in all tissues. The potency of the response differed across tissues, with the highest frequency of adducts occurring in liver and lung, and the highest frequency of mutations occurring in small intestine. The results of this study are the first demonstration of mammalian genotoxicity following exposure to CT-containing pavement sealcoat. This work provides in vivo evidence to support the contention that there may be adverse health effects in mammals, and potentially in humans, from exposure to coal tar. Environ. Mol. Mutagen. 57:535-545, 2016. © 2016 Her Majesty the Queen in Right of Canada. © 2016 Reproduced with the permission of the Government of Canada.

  11. Improvement of garlic (Allium Sativum L.) resistance to white rot and storability using gamma irradiation induced mutations

    International Nuclear Information System (INIS)

    Al-Safadi, B.; Mirali, N.; Arabi, M. I. E.

    2001-01-01

    A mutation program was conducted to improve garlic (Allium sativum) resistance to white rot (Sclerotium cepivorum) and to improve its storability under natural conditions. Cloves of two local garlic cultivars (Kisswany and Yabroudy) were irradiated with gamma ray doses 4, 5, 6, and 7 gray. The cloves were then planted in the field and plants were advanced for 4 generations in order to isolate mutations in stable form. The results indicated that the cultivar Yabroudy was more sensitive to gamma irradiation than Kisswany. Rate of morphological mutants increased with increasing gamma ray dosage. Selection pressure against white rot disease was applied starting in the second generation by adding infected garlic leaves to the soil. In the third and fourth generations, however, full selection pressure was applied by inoculating the cloves with the fungus sclerotia and planting them in a soil previously planted with infected garlic plants. healthy garlic bulbs were harvested and stored under natural conditions and then planted to obtain the next generation. By the end of the fourth generation, we have been able to improve garlic resistance to white rot disease and its storability. Twenty four mutant lines from each garlic cultivar have been selected. Out of the selected lines, twelve lines from cultivar Kisswany had only 3% infection percentage as compared to 29% in the control, and twelve lines from cultivar Yabroudy had less than 5% infection percentage as compared to 20% in the control. Also, we have been able to improve storability under natural conditions. Weight loss during storage decreased from 8.25% in the control to only 4% in some Kisswany lines and from 10% to 3% in some Yabroudy lines. However, we have not been able to increase the bulb weight over the control but the weights of the selected lines were comparable to those of the control. (author)

  12. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak.

    Directory of Open Access Journals (Sweden)

    Andrea D Olivas

    Full Text Available The most feared complication following intestinal resection is anastomotic leakage. In high risk areas (esophagus/rectum where neoadjuvant chemoradiation is used, the incidence of anastomotic leaks remains unacceptably high (≈ 10% even when performed by specialist surgeons in high volume centers. The aims of this study were to test the hypothesis that anastomotic leakage develops when pathogens colonizing anastomotic sites become in vivo transformed to express a tissue destroying phenotype. We developed a novel model of anastomotic leak in which rats were exposed to pre-operative radiation as in cancer surgery, underwent distal colon resection and then were intestinally inoculated with Pseudomonas aeruginosa, a common colonizer of the radiated intestine. Results demonstrated that intestinal tissues exposed to preoperative radiation developed a significant incidence of anastomotic leak (>60%; p<0.01 when colonized by P. aeruginosa compared to radiated tissues alone (0%. Phenotype analysis comparing the original inoculating strain (MPAO1- termed P1 and the strain retrieved from leaking anastomotic tissues (termed P2 demonstrated that P2 was altered in pyocyanin production and displayed enhanced collagenase activity, high swarming motility, and a destructive phenotype against cultured intestinal epithelial cells (i.e. apoptosis, barrier function, cytolysis. Comparative genotype analysis between P1 and P2 revealed a single nucleotide polymorphism (SNP mutation in the mexT gene that led to a stop codon resulting in a non-functional truncated protein. Replacement of the mutated mexT gene in P2 with mexT from the original parental strain P1 led to reversion of P2 to the P1 phenotype. No spontaneous transformation was detected during 20 passages in TSB media. Use of a novel virulence suppressing compound PEG/Pi prevented P. aeruginosa transformation to the tissue destructive phenotype and prevented anastomotic leak in rats. This work demonstrates that

  13. Mutation breeding newsletter. No. 44

    International Nuclear Information System (INIS)

    1999-04-01

    This issue of the Newsletter presents research reports on the role of radiation induced mutation and chemical mutagens in improving productivity, disease resistance; cold and salinity tolerance of various crops and ornamental plants

  14. Mutation breeding newsletter. No. 18

    International Nuclear Information System (INIS)

    1981-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  15. Mutation breeding newsletter. No. 6

    International Nuclear Information System (INIS)

    1975-08-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  16. Mutation breeding newsletter. No. 2

    International Nuclear Information System (INIS)

    1973-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  17. Mutation breeding newsletter. No. 5

    International Nuclear Information System (INIS)

    1975-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  18. Mutation breeding newsletter. No. 32

    International Nuclear Information System (INIS)

    1988-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  19. Mutation breeding newsletter. No. 9

    International Nuclear Information System (INIS)

    1977-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  20. Mutation breeding newsletter. No. 8

    International Nuclear Information System (INIS)

    1976-09-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  1. Mutation breeding newsletter. No. 10

    International Nuclear Information System (INIS)

    1977-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  2. Mutation breeding newsletter. No. 7

    International Nuclear Information System (INIS)

    1976-01-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  3. Mutation breeding newsletter. No. 36

    International Nuclear Information System (INIS)

    1990-07-01

    This issue of the Newsletter presents abstracts and short communications of research results on radiation and chemical induced mutation breeding projects. Positive traits such as disease resistance and increased productivity are highlighted

  4. Mutation breeding newsletter. No. 16

    International Nuclear Information System (INIS)

    1980-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  5. Mutation breeding newsletter. No. 3

    International Nuclear Information System (INIS)

    1974-01-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  6. Mutation breeding newsletter. No. 4

    International Nuclear Information System (INIS)

    1974-08-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  7. Mutation breeding newsletter. No. 19

    International Nuclear Information System (INIS)

    1982-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  8. Mutation breeding newsletter. No. 1

    International Nuclear Information System (INIS)

    1972-05-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  9. Mutation breeding newsletter. No. 24

    International Nuclear Information System (INIS)

    1984-07-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  10. Mutation breeding newsletter. No. 31

    International Nuclear Information System (INIS)

    1988-03-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  11. Mutation breeding newsletter. No. 30

    International Nuclear Information System (INIS)

    1987-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  12. Mutation breeding newsletter. No. 23

    International Nuclear Information System (INIS)

    1983-01-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  13. Mutation breeding newsletter. No. 34

    International Nuclear Information System (INIS)

    1989-07-01

    This issue of the Newsletter presents abstracts and short communications of research results on radiation and chemical induced mutation breeding projects. Positive traits such as disease resistance and increased productivity are highlighted

  14. Mutation breeding newsletter. No. 13

    International Nuclear Information System (INIS)

    1979-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  15. Mutation breeding newsletter. No. 17

    International Nuclear Information System (INIS)

    1981-03-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  16. Mutation breeding newsletter. No. 28

    International Nuclear Information System (INIS)

    1986-09-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  17. Mutation breeding newsletter. No. 27

    International Nuclear Information System (INIS)

    1986-02-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  18. Mutation breeding newsletter. No. 11

    International Nuclear Information System (INIS)

    1978-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  19. Mutation breeding newsletter. No. 20

    International Nuclear Information System (INIS)

    1982-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  20. Mutation breeding newsletter. No. 15

    International Nuclear Information System (INIS)

    1980-02-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  1. Mutation breeding newsletter. No. 12

    International Nuclear Information System (INIS)

    1978-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  2. Mutation breeding newsletter. No. 29

    International Nuclear Information System (INIS)

    1987-02-01

    This issue of the Newsletter presents reports and rea search abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  3. Mutation breeding newsletter. No. 26

    International Nuclear Information System (INIS)

    1985-10-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  4. Mutation breeding newsletter. No. 22

    International Nuclear Information System (INIS)

    1983-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  5. Mutation breeding newsletter. No. 25

    International Nuclear Information System (INIS)

    1985-01-01

    This issue of the Newsletter presents reports and research abstracts on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  6. Mutation breeding newsletter. No. 14

    International Nuclear Information System (INIS)

    1979-07-01

    This issue of the Newsletter presents new reports on mutation breeding programs using radiation or chemical mutagenesis to improve productivity, introduce disease resistance or induce morphological changes in crop plants

  7. Coexistence of mitochondrial 12S rRNA C1494T and CO1/tRNASer(UCN) G7444A mutations in two Han Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing loss

    International Nuclear Information System (INIS)

    Yuan Huijun; Chen Jing; Liu Xin; Cheng Jing; Wang Xinjian; Yang Li; Yang Shuzhi; Cao Juyang; Kang Dongyang; Dai Pu; Zha, Suoqiang; Han Dongyi; Young Wieyen; Guan Minxin

    2007-01-01

    Mutations in mitochondrial DNA are one of the important causes of hearing loss. We report here the clinical, genetic, and molecular characterization of two Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic bilateral hearing loss. Clinical evaluation revealed the wide range of severity, age-at-onset, and audiometric configuration of hearing impairment in matrilineal relatives in these families. The penetrances of hearing loss in these pedigrees were 20% and 18%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss in these seven pedigrees were 10% and 15%. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the presence of the deafness-associated 12S rRNA C1494T and CO1/tRNA Ser(UCN) G7444A mutations. Their distinct sets of mtDNA polymorphism belonged to Eastern Asian haplogroup C4a1, while other previously identified six Chinese mitochondrial genomes harboring the C1494T mutation belong to haplogroups D5a2, D, R, and F1, respectively. This suggested that the C1494T or G7444A mutation occurred sporadically and multiplied through evolution of the mitochondrial DNA (mtDNA). The absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in their mtDNA suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the 12S rRNA C1494T and CO1/tRNA Ser(UCN) G7444A mutations in those Chinese families. However, aminoglycosides and other nuclear modifier genes play a modifying role in the phenotypic manifestation of the C1494T mutation in these Chinese families

  8. Radon-induced lung cancer in smokers and non-smokers: risk implications using a two-mutation carcinogenesis model

    International Nuclear Information System (INIS)

    Leenhouts, H.P.

    1999-01-01

    Three sets of data (population statistics in non-smokers, data from an investigation of the smoking habits of British doctors and a study of Colorado uranium miners) were used to analyse lung cancer in humans as a function of exposure to radon and smoking. One of the aims was to derive implications for radon risk estimates. The data were analysed using a two-mutation radiation carcinogenesis model and a stepwise determination of the model parameters. The basic model parameters for lung cancer were derived from the age dependence fit of the spontaneous lung cancer incidence in non-smokers. The effect of smoking was described by two additional parameters and, subsequently, the effect of radon by three other parameters; these five parameters define the dependence of the two mutation steps on smoking and exposure to radon. Using this approach, a consistent fit and comprehensive description of the three sets of data have been achieved, and the parameters could, at least partly, be related to cellular radiobiological data. The model results explain the different effect of radon on non-smokers and smokers as seen in epidemiological data. Although the analysis was only applied to a limited number of populations, lung cancer incidence as a result of radon exposure is estimated to be about ten times higher for people exposed at the age of about 15 than at about 50, although this effect is masked (especially for smokers) by the high lung cancer incidence from smoking. Using the model to calculate the lung cancer risks from lifetime exposure to radon, as is the case for indoor radon, higher risks were estimated than previously derived from epidemiological studies of the miners' data. The excess absolute risk per unit exposure of radon is about 1.7 times higher for smokers of 30 cigarettes per day than for non-smokers, even though, as a result of the low spontaneous tumour incidence in the non-smokers, the excess relative risk per unit exposure for the smokers is about 20 times

  9. Evaluation of AgClNPs@SBA-15/IL nanoparticle-induced oxidative stress and DNA mutation in Escherichia coli.

    Science.gov (United States)

    Karimi, Farrokh; Dabbagh, Somayyeh; Alizadeh, Sina; Rostamnia, Sadegh

    2016-08-01

    The bactericidal effects of silver nanoparticles have been demonstrated in the past years. Recently, the new antimicrobial compounds of silver nanoparticles with different formulations have been developed. In this work, AgClNPs@SBA-15/IL as a new compound of Ag nanoparticles, was synthesized and characterized by XRD, TEM, SEM, FTIR, and EDX. The antibacterial activity and the molecular mechanism effects of AgClNPs@SBA-15/IL nanoparticles (SNPs) on Escherichia coli DH5α cells were investigated by analyzing the growth inhibitory, H2O2 level, catalase activity, DNA mutation, and plasmid copy number following treatment with AgClNPs@SBA-15/IL nanoparticles. In experimental results, the minimum inhibitory concentration (MIC) was observed in 75 μg/ml and the antibacterial efficacy (ABE) in CFU analysis was estimated 95.3 %. In bacterial cells treated with 75 and 100 μg/ml, H2O2 level significantly increased and catalase activity decreased compared with control. The random amplified polymorphic DNA (RAPD) was used to evaluate the effect of AgClNPs@SBA-15/IL nanoparticles in DNA damages and mutation in E. coli genome. RADP-PCR results indicated different banding patterns including appearance or disappearance of bands and differences in their intensity. Cluster analysis of the RAPD-PCR results based on genetic similarity showed genetic difference between E. coli cells treated with AgClNPs@SBA-15/IL nanoparticles, and control and phylogenetic tree were divided to two clusters. Plasmid copy number analysis indicated that after 8 h incubation of E. coli cells with 50, 75, and 100 μg/ml AgClNPs@SBA-15/IL nanoparticles, copy number of pET21a (+) significantly decreased compared with control which indicating DNA replication inhibition by Ag nanoparticles. In conclusion, the results of this study indicated that AgClNPs@SBA-15/IL nanoparticles can be used as an effective bactericidal agent against bacterial cells.

  10. Induced pluripotent stem cells (iPSCs) derived from a symptomatic carrier of a S305I mutation in the microtubule-associated protein tau (MAPT)-gene causing frontotemporal dementia

    DEFF Research Database (Denmark)

    Nimsanor, Natakarn; Jørring, Ida; Rasmussen, Mikkel A.

    2016-01-01

    Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the gene coding the microtubule-associated protein tau (MAPT) can cause FTDP-17 but the underlying mechanisms of the disease are still unknown. Induced...

  11. Induced pluripotent stem cells (iPSCs) derived from af pre-symptomatic carrier of a R406W mutation in microtubule-associated protein tau (MAPT) causing frontotemporal dementia

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena Elisabeth; Hasholt, Lis Frydenreich

    2016-01-01

    Skin fibroblasts were obtained from a 28-year-old pre-symptomatic woman carrying a R406W mutation in microtubule-associated protein tau (MAPT), known to cause frontotemporal dementia. Induced pluripotent stem cell (iPSCs) were established by electroporation with episomal plasmids containing hOCT4...

  12. Production and characterization of CSSI003 (2961 human induced pluripotent stem cells (iPSCs carrying a novel puntiform mutation in RAI1 gene, Causative of Smith–Magenis syndrome

    Directory of Open Access Journals (Sweden)

    Filomena Altieri

    2018-04-01

    Full Text Available Smith-Magenis syndrome (SMS is a complex genetic disorder characterized by developmental delay, behavioural problems and circadian rhythm dysregulation. About 90% of SMS cases are due to a 17p11.2 deletion containing retinoic acid induced1 (RAI1 gene, 10% are due to heterozygous mutations affecting RAI1 coding region. Little is known about RAI1 role.

  13. Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity

    DEFF Research Database (Denmark)

    Chadt, Alexandra; Leicht, Katja; Deshmukh, Atul

    2008-01-01

    We previously identified Nob1 as a quantitative trait locus for high-fat diet-induced obesity and diabetes in genome-wide scans of outcross populations of obese and lean mouse strains. Additional crossbreeding experiments indicated that Nob1 represents an obesity suppressor from the lean Swiss Jim...

  14. Analysis of UV-induced mutation spectra in Escherichia coli by DNA polymerase {eta} from Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Santiago, Maria Jesus [Departamento de Genetica, Facultad de Ciencias, Edificio Gregor Mendel, Campus Rabanales, Universidad de Cordoba (Spain); Alejandre-Duran, Encarna [Departamento de Genetica, Facultad de Ciencias, Edificio Gregor Mendel, Campus Rabanales, Universidad de Cordoba (Spain); Ruiz-Rubio, Manuel [Departamento de Genetica, Facultad de Ciencias, Edificio Gregor Mendel, Campus Rabanales, Universidad de Cordoba (Spain)]. E-mail: ge1rurum@uco.es

    2006-10-10

    DNA polymerase {eta} belongs to the Y-family of DNA polymerases, enzymes that are able to synthesize past template lesions that block replication fork progression. This polymerase accurately bypasses UV-associated cis-syn cyclobutane thymine dimers in vitro and therefore may contributes to resistance against sunlight in vivo, both ameliorating survival and decreasing the level of mutagenesis. We cloned and sequenced a cDNA from Arabidopsis thaliana which encodes a protein containing several sequence motifs characteristics of Pol{eta} homologues, including a highly conserved sequence reported to be present in the active site of the Y-family DNA polymerases. The gene, named AtPOLH, contains 14 exons and 13 introns and is expressed in different plant tissues. A strain from Saccharomyces cerevisiae, deficient in Pol{eta} activity, was transformed with a yeast expression plasmid containing the AtPOLH cDNA. The rate of survival to UV irradiation in the transformed mutant increased to similar values of the wild type yeast strain, showing that AtPOLH encodes a functional protein. In addition, when AtPOLH is expressed in Escherichia coli, a change in the mutational spectra is detected when bacteria are irradiated with UV light. This observation might indicate that AtPOLH could compete with DNA polymerase V and then bypass cyclobutane pyrimidine dimers incorporating two adenylates.

  15. Oriented tuning the photovoltaic properties of γ-RbGeX3 by strain-induced electron effective mass mutation

    Science.gov (United States)

    Yu, Zhuo-Liang; Ma, Qi-Rui; Liu, Biao; Zhao, Yu-Qing; Wang, Lin-Zhi; Zhou, Hong; Cai, Meng-Qiu

    2017-11-01

    Based on the concept of green environmental protection, we hope to find a substitute for lead perovskites to reduce the pollution and achieve high photoelectric conversion efficiency. In this paper, the structural, electronic and optical properties of γ-RbGeX3 (X  =  Cl, Br and I) hybrid perovskites are investigated by density functional theory (DFT) calculations. The result shows that the γ-RbGeI3 has direct band gap of 1.38 eV and exhibits strong optical absorption in the visible light spectrum. However, the electron effective mass in the z direction is larger, which restricts the carrier mobility in the (0 0 1) direction. The blemish can be overcome by applying the  ‑2% strain in the z direction, which causes the mutation of electron effective mass from 1.35 to 0.09 with little influence on the value of the band gap and the hole effective mass. These above findings also offer a new view to explore the inorganic perovskite for solar cell absorbers.

  16. Manual on mutation breeding. 2. ed.

    International Nuclear Information System (INIS)

    1977-01-01

    The manual is a compilation of work done on the use of induced mutations in plant breeding, and presents general methods and techniques in this field. The use of chemical mutagens and ionizing radiations (X-rays, gamma rays, α- and β-particles, protons, neutrons) are described as well as the effects of these mutagens. The different types of mutations achieved can be divided into genome mutations, chromosome mutations and extra nuclear mutations. Separate chapters deal with mutation techniques in breeding seed-propagated species and asexually propagated plants (examples of development of cultivars given). Plant characters which can be improved by mutation breeding include yield, ripening time, growth habit, disease resistance and tolerance to environmental factors (temperature, salinity etc.). The use of mutagens for some specific plant breeding problems is discussed and attention is also paid to somatic cell genetics in connection with induced mutations. The manual contains a comprehensive bibliography (60 p. references) and a subject index

  17. Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression

    Energy Technology Data Exchange (ETDEWEB)

    Kondo, Seiji; Wang, Binghe; Fujisawa, Hiroshi [Univ. of Toronto, Ontario (Canada)] [and others

    1995-10-15

    Tumor necrosis factor {alpha} (TNF-{alpha}) is a pleiotropic proinflammatory cytokine. TNF-{alpha} has been implicated in the pathogenesis of delayed-type hypersensitivity reactions such as allergic contact hypersensitivity and has been suggested as a mediator of ultraviolet B (UVB)-induced immunosuppression. Conflicting reports, however, exist concerning the effects of TNF-{alpha} on contact hypersensitivity (CHS). To determine the role of TNF-{alpha} in the generation and regulation of CHS, gene-targeted mutant mice lacking TNF-receptor (p55) gene (TNF-R1(-) mice) were treated with dinitrofluorobenzene (DNFB) to induce CHS. TNF-R1(-) mice showed significant hyperresponsiveness in CHS (152.8 {+-} 20.9%, p < 0.025) compared with normal syngeneic mice (C57BL/6) assessed by ear swelling. To determine whether UVB can induce suppression in TNF-R1(-) mice, mice were irradiated on the shaved abdomen with 96 ml/cm{sup 2} UVB and 3 days later they were painted with 0.5% DNFB (sensitization dose), followed 5 days later with 0.2% DNFB to the left ear (challenge dose). Significant suppression of CHS was observed both locally (sensitization on irradiated site) and systemically (sensitization on unirradiated site) in UVB-irradiated TNF-R1(-) mice as well as in normal mice. To rule out possible signaling through p75 TNF-R, the mice were treated with anti-TNF-{alpha} Ab (V1q), which can neutralize any TNF effects through either receptor. V1q had no effect on these phenomena observed in TNF-R1(-) mice. These results suggest that TNF-{alpha} plays a regulatory role in CHS but is not required to induce UVB-mediated immunosuppression. 45 refs., 5 figs.

  18. Mutations of the Corynebacterium glutamicum NCgl1221 Gene, Encoding a Mechanosensitive Channel Homolog, Induce l-Glutamic Acid Production▿

    OpenAIRE

    Nakamura, Jun; Hirano, Seiko; Ito, Hisao; Wachi, Masaaki

    2007-01-01

    Corynebacterium glutamicum is a biotin auxotroph that secretes l-glutamic acid in response to biotin limitation; this process is employed in industrial l-glutamic acid production. Fatty acid ester surfactants and penicillin also induce l-glutamic acid secretion, even in the presence of biotin. However, the mechanism of l-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in l-gluta...

  19. Dengue type four viruses with E-Glu345Lys adaptive mutation from MRC-5 cells induce low viremia but elicit potent neutralizing antibodies in rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Hsiao-Han Lin

    Full Text Available Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4 passaged in MRC-5 cells acquired a Glu345Lys (E-E345K substitution in the E protein domain III (E-DIII. The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development.

  20. Dengue type four viruses with E-Glu345Lys adaptive mutation from MRC-5 cells induce low viremia but elicit potent neutralizing antibodies in rhesus monkeys.

    Science.gov (United States)

    Lin, Hsiao-Han; Lee, Hsiang-Chi; Li, Xiao-Feng; Tsai, Meng-Ju; Hsiao, Hung-Ju; Peng, Jia-Guan; Sue, Shih-Che; Qin, Cheng-Feng; Wu, Suh-Chin

    2014-01-01

    Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development.