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Sample records for induced mutation combined

  1. Some results on the combined use of induced mutations and heterosis breeding

    International Nuclear Information System (INIS)

    Stoilov, M.; Daskaloff, S.

    1976-01-01

    The literature on the combined use of induced mutations and heterosis in cultivated species is reviewed. Data from studies of the general and specific combining ability of induced mutations for gene markers both obtained and used in hybrid seed production, translocation lines for development of seedless fruits, male sterile forms, etc., are supplied. The authors give data from their own experimental material for use of mutant lines in heterosis breeding and hybrid seed production. It is concluded that the combined use of induced mutations and heterosis in both self- and cross-pollinating species is very promising. (author)

  2. 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

  3. 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

  4. Combination of the mutation process with the sensitization and repair processes leading to increased frequencies of mutations in algal populations

    International Nuclear Information System (INIS)

    Necas, J.

    1977-01-01

    The possibility of combining the mutation process with the induction of the repair processes was studied to increase the mutation frequencies in algal populations after UV treatment. The repair process induced by visible light was found to be much more effective than the dark repair processes in the chlorococcal algae used. In these algae, visible light possibly does not induce only those repair processes which affect their DNA, but probably also certain recovery processes which affect their damaged structures and physiological functions. A suitable combination of the sensitization of algae cells by a DNA-base analogue before UV treatment and the induction of the light repair and recovery processes resulted in a rather high increase of viable mutations in chlorococcal algae. These findings may be useful in breeding chlorococcal algae, which have no possibility of hybridization other than somatic. (author)

  5. 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.)

  6. 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.)

  7. Mutations induced by ultraviolet light

    International Nuclear Information System (INIS)

    Pfeifer, Gerd P.; You, Young-Hyun; Besaratinia, Ahmad

    2005-01-01

    The different ultraviolet (UV) wavelength components, UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm), have distinct mutagenic properties. A hallmark of UVC and UVB mutagenesis is the high frequency of transition mutations at dipyrimidine sequences containing cytosine. In human skin cancers, about 35% of all mutations in the p53 gene are transitions at dipyrimidines within the sequence 5'-TCG and 5'-CCG, and these are localized at several mutational hotspots. Since 5'-CG sequences are methylated along the p53 coding sequence in human cells, these mutations may be derived from sunlight-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. Cyclobutane pyrimidine dimers (CPDs) form preferentially at dipyrimidines containing 5-methylcytosine when cells are irradiated with UVB or sunlight. In order to define the contribution of 5-methylcytosine to sunlight-induced mutations, the lacI and cII transgenes in mouse fibroblasts were used as mutational targets. After 254 nm UVC irradiation, only 6-9% of the base substitutions were at dipyrimidines containing 5-methylcytosine. However, 24-32% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of these mutations were transitions. Thus, CPDs forming preferentially at dipyrimidines with 5-methylcytosine are responsible for a considerable fraction of the mutations induced by sunlight in mammalian cells. Using mouse cell lines harboring photoproduct-specific photolyases and mutational reporter genes, we showed that CPDs (rather than 6-4 photoproducts or other lesions) are responsible for the great majority of UVB-induced mutations. An important component of UVB mutagenesis is the deamination of cytosine and 5-methylcytosine within CPDs. The mutational specificity of long-wave UVA (340-400 nm) is distinct from that of the shorter wavelength UV and is characterized mainly by G to T transversions presumably arising through mechanisms involving oxidized DNA

  8. 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

  9. Combining Single Strand Oligodeoxynucleotides and CRISPR/Cas9 to Correct Gene Mutations in β-Thalassemia-induced Pluripotent Stem Cells.

    Science.gov (United States)

    Niu, Xiaohua; He, Wenyin; Song, Bing; Ou, Zhanhui; Fan, Di; Chen, Yuchang; Fan, Yong; Sun, Xiaofang

    2016-08-05

    β-Thalassemia (β-Thal) is one of the most common genetic diseases in the world. The generation of patient-specific β-Thal-induced pluripotent stem cells (iPSCs), correction of the disease-causing mutations in those cells, and then differentiation into hematopoietic stem cells offers a new therapeutic strategy for this disease. Here, we designed a CRISPR/Cas9 to specifically target the Homo sapiens hemoglobin β (HBB) gene CD41/42(-CTTT) mutation. We demonstrated that the combination of single strand oligodeoxynucleotides with CRISPR/Cas9 was capable of correcting the HBB gene CD41/42 mutation in β-Thal iPSCs. After applying a correction-specific PCR assay to purify the corrected clones followed by sequencing to confirm mutation correction, we verified that the purified clones retained full pluripotency and exhibited normal karyotyping. Additionally, whole-exome sequencing showed that the mutation load to the exomes was minimal after CRISPR/Cas9 targeting. Furthermore, the corrected iPSCs were selected for erythroblast differentiation and restored the expression of HBB protein compared with the parental iPSCs. This method provides an efficient and safe strategy to correct the HBB gene mutation in β-Thal iPSCs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Mutations induced in plant breeding

    International Nuclear Information System (INIS)

    Barriga B, P.

    1984-01-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented. (Author)

  11. Mutations induced in plant breeding

    Energy Technology Data Exchange (ETDEWEB)

    Barriga B, P. (Universidad Austral de Chile, Valdivia. Inst. de Produccion y Sanidad Vegetal)

    1984-10-01

    The most significant aspects of the use of ionizing radiations in plant breeding are reviewed. Aspects such as basic principles of mutation, expression and selection in obtention of mutants, methods for using induced mutations and sucess achieved with this methodology in plant breeding are reviewed. Results obtained in a program of induced mutation on wheat for high content of protein and lysine at the Universidad Austral de Chile are presented.

  12. 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...

  13. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Do Huu At; Bui Huy Thuy; Nguyen Van Bich; Tran Duy Quy [Agricultural Genetics Institute, Division of Genetics and Hybrid Rice Technology, Hanoi (Viet Nam); Nguyen Minh Cong [Hanoi No. 1 Teacher Training Univ., Department of Genetics (Viet Nam)

    2001-03-01

    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)

  15. 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)

  16. Hyperthermia-induced alteration of yeast susceptibility to mutation

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Morrison, D.P.

    1985-01-01

    Diploid yeast (s. cerevisiae) were examined for alterations in susceptibility to induced mutation following hyperthermia treatment. In cells grown at 23 0 C, a non-lethal heat exposure (38 0 C, 30 min) markedly suppressed mutation induced by a subsequent non-killing dose of MNNG of MNU. Mutation by ENU, 8-MOP + UVA, or γ-rays was not affected. An intermediate level of mutation suppression was observed for mutation by 254nm UV or MMS. Mutation by MNNG was not suppressed by the same heat treatment delivered after the mutagen exposure. In a split dose experiment (two MNNG treatments separated by a heat exposure) no suppression of mutation was observed. Treatment with cycloheximide mimicked the effect of heat treatment. These data suggest that mutation induction by MNNG or MNU is protein synthesis dependent, i.e. an error-prone repair system is induced by exposure to MNNG or MNU but not by ENU, 8-MOP+UVA or γ-irradiation. We propose that hyperthermia treatment, by inducing stress protein synthesis at the expense of normal protein synthesis, precludes induction of this error-prone system. Therefore, in heat treated cells, DNA lesions produced by MNNG or MNU exposure must be resolved by an essentially constitutive system which is less error-prone than the inducible one

  17. 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

  18. Radiation induced chlorophyll mutations in rice

    International Nuclear Information System (INIS)

    Bari, G.; Mustafa, G.; Soomro, A.M.; Baloch, A.W.

    1985-01-01

    Air dried grains of four local varieties of rice were treated with gamma-rays and fast neutrons for determining their mutagenic effectiveness through the occurence of chlorophyll mutations. Fast neutrons were more effective in inducing chlorophyll mutations and the rice variety Basmati 370 produced maximum number of mutations followed by varieties Sonahri Sugdasi, Jajai 77 and Sada Gulab. The highest frequency of chlorophyll mutations was that of albina types followed by striata types. The xantha, viridis and tigrina types of mutations were less frequent. (authors)

  19. Saccharomyces cerevisiae mutants with enhanced induced mutation and altered mitotic gene conversion.

    Science.gov (United States)

    Ivanov, E L; Kovaltzova, S V; Korolev, V G

    1989-08-01

    We have developed a method to isolate yeast (Saccharomyces cerevisiae) mutants with enhanced induced mutagenesis based on nitrous acid-induced reversion of the ade2-42 allele. Six mutants have been isolated and designated him (high induced mutagenesis), and 4 of them were studied in more detail. The him mutants displayed enhanced reversion of the ade2-42 allele, either spontaneous or induced by nitrous acid, UV light, and the base analog 6-N-hydroxylaminopurine, but not by gamma-irradiation. It is worth noting that the him mutants turned out not to be sensitive to the lethal effects of the mutagens used. The enhancement in mutation induced by nitrous acid, UV light, and 6-N-hydroxylaminopurine has been confirmed in a forward-mutation assay (induction of mutations in the ADE1, ADE2 genes). The latter agent revealed the most apparent differences between the him mutants and the wild-type strain and was, therefore, chosen for the genetic analysis of mutants, him mutations analyzed behaved as a single Mendelian trait; complementation tests indicated 3 complementation groups (HIM1, HIM2, and HIM3), each containing 1 mutant allele. Uracil-DNA glycosylase activity was determined in crude cell extracts, and no significant differences between the wild-type and him strains were detected. Spontaneous mitotic gene conversion at the ADE2 locus is altered in him1 strains, either increased or decreased, depending on the particular heteroallelic combination. Genetic evidence strongly suggests him mutations to be involved in a process of mismatch correction of molecular heteroduplexes.

  20. New mutations affecting induced mutagenesis in yeast.

    Science.gov (United States)

    Lawrence, C W; Krauss, B R; Christensen, R B

    1985-01-01

    Previously isolated mutations in baker's yeast, Saccharomyces cerevisiae, that impair induced mutagenesis were all identified with the aid of tests that either exclusively or predominantly detect base-pair substitutions. To avoid this bias, we have screened 11 366 potentially mutant clones for UV-induced reversion of the frameshift allele, his4-38, and have identified 10 mutants that give much reduced yields of revertants. Complementation and recombination tests show that 6 of these carry mutations at the previously known REV1, REV1 and REV3 loci, while the remaining 4 define 3 new genes, REV4 (2 mutations), REV5 and REV6. The rev4 mutations are readily suppressed in many genetic backgrounds and, like the rev5 mutation, impart only a limited deficiency for induced mutagenesis: it is likely, therefore that the REV4+ and REV5+ gene functions are only remotely concerned with this process. The rev6 mutants have a more general deficiency, however, as well as marked sensitivity to UV and an increased spontaneous mutation rate, properties that suggest the REV6 gene is directly involved in mutation induction. The REV5 gene is located about 1 cM proximal to CYC1 on chromosome X.

  1. 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

  2. Studies on induced mutation frequency in Catharanthus roseus (L.) G. Don by gamma rays and EMS individually and in combination

    International Nuclear Information System (INIS)

    Venkateswarlu, M.; Susheelamma, B.N.; Kumar, P.; Subhash, K.

    1988-01-01

    Seeds of pink flowered (PF) and white flowered (WF) Catharanthus roseus were soaked in distilled water for 24 h and treated with gamma rays and 0.1% EMS separately and in combination. Six types of chlorophyll mutations, viz., xantha, albina, chlorina, viridis, maculata and tigrina were recovered to M 2 generation of both forms. The frequency of chlorophyll mutations was found to be dependent on the dose, of gamma rays and duration of treatment with EMS. Higher frequency of chlorophyll mutations was noticed in PF, which is mutagenically more sensitive than WF. It was also noticed that the combination treatments of gamma rays and EMS enhanced the frequency of chlorophyll mutations

  3. Induced polygenic variability using combination treatment of gamma ...

    African Journals Online (AJOL)

    Induced mutation in plant improvement has been proven to be one of the alternative ways to generate new sources of genetic variation in blackgram. In this study, dry seeds of VBN 4 blackgram were treated with combination treatment of both gamma rays (400, 500 and 600 Gy) and ethyl methane sulphonate (EMS) (50, ...

  4. Mutator suppression and escape from replication error-induced extinction in yeast.

    Directory of Open Access Journals (Sweden)

    Alan J Herr

    2011-10-01

    Full Text Available Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10⁻³ inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer.

  5. 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

  6. The timing of UV mutagenesis in yeast: a pedigree analysis of induced recessive mutation.

    Science.gov (United States)

    James, A P; Kilbey, B J

    1977-10-01

    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 percent at survival levels of 90 and 77 percent, 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.

  7. Radiation-induced mutations in mammals

    International Nuclear Information System (INIS)

    Ehling, U.H.

    1993-01-01

    The aims of the proposed project are to provide a better basis for extrapolation of animal data to man. Genetic endpoint, strain and species comparisons are made, which will provide critical experimental data regarding strategies in extrapolating laboratory animal data to man. Experiments were conducted to systematically compare the spontaneous and radiation-induced mutation rates for recessive specific-locus, dominant cataract and enzyme activity alleles in the mouse as well as a comparison of the mutation rate in the mouse and hamster for dominant cataract and enzyme activity alleles. The comparison of the radiation-dose response for recessive specific-locus and dominant cataract mutations are extended. Selected mutations are characterized at the genetic, biochemical and molecular levels. (R.P.) 5 refs., 3 tabs

  8. 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

  9. 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

  10. Effect of AC magnetic fields on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Ager, D.D.; Radul, J.A.

    1994-01-01

    The ability of 60-Hz magnetic fields to induce genetic damage in Saccharomyces cerevisiae was studied. The frequencies of induced mutation, gene conversion, and reciprocal mitotic crossing over were measured for exposures to 1-millitesla magnetic fields alone or in combination with various preliminary exposures to 254-nm ultraviolet light at intensities of 2-50 J/m 2 . These experiments were performed using a repair-proficient strain as well as a strain incapable of excising ultraviolet-induced thymine dimers. Magnetic field exposures did not induce mutation, gene conversion, or reciprocal mitotic crossing over in either of these strains, nor did the fields influence the frequencies of ultraviolet-induced genetic events. 32 refs., 4 tabs

  11. 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

  12. 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

  13. Use of induced mutations in improving sorghum hybrids

    Energy Technology Data Exchange (ETDEWEB)

    Shashidhar, L S; Patil, S S; Goud, J V [University of Agricultural Sciences, Dharwad (India)

    1990-01-01

    Full text: The established male sterile line '296A' and a restorer line '5501' were mutagenised using 0.05% MMS, and the mutagenised populations were involved in the following cross combinations: 296A x 5501 (M{sub 1} and M{sub 2}), 296A (M{sub 1}) x 5501, 296A (M{sub 1}) x 5501 (M{sub 1}). The derived F{sub 1} populations of these combinations were compared with control F{sub 1} populations with respect to yield/plant. Induced mutations increased combining ability of the restorer parent as evidenced by an increase in the mean of the derived F{sub 1} populations, involving M{sub 1} and M{sub 2} populations of 5501 as males. On the contrary, the mean combining ability of 296A remained unchanged. However, variability in all these derived F{sub 1} populations was increased over that of control F{sub 1} indicating that selection can be practiced for mutants with better combining ability. (author)

  14. Radiation induced mutations for plant selection

    International Nuclear Information System (INIS)

    Brunner, H.

    1994-01-01

    The successful use of plant breeding for improving crops requires the existence of genetic variation of useful traits. Unfortunately, the desired variation is often lacking. However, radiation can be used to induce mutations and thereby generate genetic variation from which desired mutants may be selected. Mutation induction has become a proven way of creating variation within a crop variety. It offers the possibility of inducing desired attributes that either cannot be expressed in nature or have been lost during evolution. More than 1700 mutant cultivars of crop plants with significantly improved attributes such as increased yield, improved quality, disease and stress resistance, have been released worldwide in the last thirty years. The Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has contributed to these achievements through the promotion of research and development in mutation breeding techniques using nuclear and related biotechnological methods and the provision of in plant breeding is then transferred to Member States of the IAEA and the FAO through training in mutation breeding methods and the provision of technical advice. Moreover, radiation treatment services are provided to foster applications of nuclear techniques in crop improvement programmes of member states and more specifically to render direct support to plant breeders by efficient generation of mutations. Plant materials are standardized prior to radiation exposure to warrant reproducibility of the induced effects within practical limits and a radiosensitivity test is implemented to affirm useful doses for applied objectives of a request. This review deals with irradiation methods applied at the IAEA laboratories for the efficient induction of mutations in seeds, vegetative propagules and tissue and cell cultures and the establishment of genetically variable populations upon which selection of desired traits can be based. 3 tabs., 18 refs. (author)

  15. 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)

  16. 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

  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. Radiation-induced mutations and plant breeding

    International Nuclear Information System (INIS)

    Naqvi, S.H.M.

    1985-01-01

    Ionizing radiation could cause genetic changes in an organism and could modify gene linkages. The induction of mutation through radiation is random and the probability of getting the desired genetic change is low but can be increased by manipulating different parameters such as dose rate, physical conditions under which the material has been irradiated, etc. Induced mutations have been used as a supplement to conventional plant breeding, particularly for creating genetic variability for specific characters such as improved plant structure, pest and disease resistance, and desired changes in maturity period; more than 200 varieties of crop plants have been developed by this technique. The Pakistan Atomic Energy Commission has used this technique fruitfully to evolve better germplasm in cotton, rice, chickpea, wheat and mungbean; some of the mutants have become popular commercial varieties. This paper describes some uses of radiation induced mutations and the results achieved in Pakistan so far

  19. 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

  20. Induced mutations for crop improvement- the generation next

    International Nuclear Information System (INIS)

    Bhatia, C.R.

    2000-01-01

    Experiments to use induced mutations for the improvement of crop plants were initiated in the country in mid nineteen fifties. After forty five years and reasonably good success stories, it is no longer an attractive subject for bright young graduate students. The areas of intellectually satisfying, contemporary, plant genetics based on induced mutations that can also bring social and commercial benefits are identified. These are: nodulation mutants in legumes, altering fatty acid composition in oil crops, modification of root characters, altering host-pathogen interactions, flowering time, day length insensitivity and some changes in modulation pattern involve mutations

  1. Effect of 60-Hz magnetic fields on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ager, D D; Radul, J A

    1992-12-01

    The purpose of this study was to examine the effect of extremely low frequency (ELF) magnetic fields on the induction of genetic damage. In general, mutational studies involving ELF magnetic fields have proven negative. However, studies examining sister-chromatid exchange and chromosome aberrations have yielded conflicting results. In this study, we have examined whether 60-Hz magnetic fields are capable of inducing mutation or mitotic recombination in the yeast Saccharomyces cerevisiae. In addition we determined whether magnetic fields were capable of altering the genetic response of S. cerevisiae to UV (254 nm). We measured the frequencies of induced mutation, gene conversion and reciprocal mitotic crossing-over for exposures to magnetic fields alone (1 mT) or in combination with various UV exposures (2-50 J/m2). These experiments were performed using a repair-proficient strain (RAD+), as well as a strain of yeast (rad3) which is incapable of excising UV-induced thymine dimers. Magnetic field exposures did not induce mutation, gene conversion or reciprocal mitotic crossing-over in either of these strains, nor did the fields influence the frequencies of UV-induced genetic events.

  2. 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.

  3. Specificity of mutations induced by carbon ions in budding yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Matuo, Youichirou; Nishijima, Shigehiro; Hase, Yoshihiro; Sakamoto, Ayako; Tanaka, Atsushi; Shimizu, Kikuo

    2006-01-01

    To investigate the nature of mutations induced by accelerated ions in eukaryotic cells, the effects of carbon-ion irradiation were compared with those of γ-ray irradiation in the budding yeast Saccharomyces cerevisiae. The mutational effect and specificity of carbon-ion beams were studied in the URA3 gene of the yeast. Our experiments showed that the carbon ions generated more than 10 times the number of mutations induced by γ-rays, and that the types of base changes induced by carbon ions include transversions (68.7%), transitions (13.7%) and deletions/insertions (17.6%). The transversions were mainly G:C → T:A, and all the transitions were G:C → A:T. In comparison with the surrounding sequence context of mutational base sites, the C residues in the 5'-AC(A/T)-3' sequence were found to be easily changed. Large deletions and duplications were not observed, whereas ion-induced mutations in Arabidopsis thaliana were mainly short deletions and rearrangements. The remarkable feature of yeast mutations induced by carbon ions was that the mutation sites were localized near the linker regions of nucleosomes, whereas mutations induced by γ-ray irradiation were located uniformly throughout the gene

  4. Bibliography. Examples of literature related to the use of induced mutations in cross-breeding

    International Nuclear Information System (INIS)

    Micke, A.

    1976-01-01

    The bibliography contains about 400 references arranged alphabetically under the following 20 headings: Genetic analysis of mutants; Mutant gene combination and interaction; Pleiotropy versus linkage; Genetic background; Heterosis and overdominance; Mutations in heterozygous plants such as vegetatively propagated plants; Mutations in hybrids of self-pollinators; Distant hybridization; Increasing recombination; Alteration in the reproductive system; Alteration of photoperiodic response; Self and cross-incompatibility; Male or female sterility; Adaptability of mutants and mutant hybrids; Mutation induction in cross pollinators; Dwarfing mutant genes in cross-breeding; Protein mutants in cross-breeding; Disease resistant mutants in cross-breeding; Practical cross-breeding programmes using mutants; Spontaneous versus induced genetic diversity

  5. 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.)

  6. Specificity of mutations induced by carbon ions in budding yeast Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Matuo, Youichirou [Graduate School of Engineering, Osaka University, Yamada-oka 2-1, Suita, Osaka 565-0871 (Japan); Nishijima, Shigehiro [Graduate School of Engineering, Osaka University, Yamada-oka 2-1, Suita, Osaka 565-0871 (Japan); Hase, Yoshihiro [Radiation-Applied Biology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency (JAEA), Watanuki-machi 1233, Takasaki, Gunma 370-1292 (Japan); Sakamoto, Ayako [Radiation-Applied Biology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency (JAEA), Watanuki-machi 1233, Takasaki, Gunma 370-1292 (Japan); Tanaka, Atsushi [Radiation-Applied Biology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency (JAEA), Watanuki-machi 1233, Takasaki, Gunma 370-1292 (Japan); Shimizu, Kikuo [Radioisotope Research Center, Osaka University, Yamada-oka 2-4, Suita, Osaka 565-0871 (Japan)]. E-mail: shimizu@rirc.osaka-u.ac.jp

    2006-12-01

    To investigate the nature of mutations induced by accelerated ions in eukaryotic cells, the effects of carbon-ion irradiation were compared with those of {gamma}-ray irradiation in the budding yeast Saccharomyces cerevisiae. The mutational effect and specificity of carbon-ion beams were studied in the URA3 gene of the yeast. Our experiments showed that the carbon ions generated more than 10 times the number of mutations induced by {gamma}-rays, and that the types of base changes induced by carbon ions include transversions (68.7%), transitions (13.7%) and deletions/insertions (17.6%). The transversions were mainly G:C {sup {yields}} T:A, and all the transitions were G:C {sup {yields}} A:T. In comparison with the surrounding sequence context of mutational base sites, the C residues in the 5'-AC(A/T)-3' sequence were found to be easily changed. Large deletions and duplications were not observed, whereas ion-induced mutations in Arabidopsis thaliana were mainly short deletions and rearrangements. The remarkable feature of yeast mutations induced by carbon ions was that the mutation sites were localized near the linker regions of nucleosomes, whereas mutations induced by {gamma}-ray irradiation were located uniformly throughout the gene.

  7. 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.

  8. Mutation induced with ion beam irradiation in rose

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, H. E-mail: yhiroya@nias.affrc.go.jp; 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.

  9. Present status of rice breeding by induced mutations in Taiwan, Republic of China

    Energy Technology Data Exchange (ETDEWEB)

    Hu, C H [Taiwan Provincial Chung-Hsing University, Taichung, Taiwan (China); Wu, H P; Li, H W [Academia Sinica, Nankang, Taipei, Taiwan (China)

    1970-03-01

    Since 1957, fourteen varieties, including both indica and japonica, have been treated with X-rays, gamma rays, thermal neutrons and EMS for inducing mutations. The objectives are: (1) To obtain erectoid mutants of good lodging resistance from the tall native varieties which can be adapted for intensive culture; (2) To obtain early maturing mutants with at least the same yield as the original variety, so that the multiple cropping system of Taiwan can be easily handled; and (3) To obtain disease-resistant mutants. The results obtained suggest that after a useful gene such as erectoid has been obtained by induced mutation, it can be used immediately. But in general, it will be more useful to combine this character into other genotypic backgrounds by cross-breeding. Henceforth, further breeding must be carried out by cross-breeding. A number of promising lines were selected from induced mutants after being crossed with local varieties and the advanced test of these lines is being carried on at present. (author)

  10. Present status of rice breeding by induced mutations in Taiwan, Republic of China

    International Nuclear Information System (INIS)

    Hu, C.H.; Wu, H.P.; Li, H.W.

    1970-01-01

    Since 1957, fourteen varieties, including both indica and japonica, have been treated with X-rays, gamma rays, thermal neutrons and EMS for inducing mutations. The objectives are: (1) To obtain erectoid mutants of good lodging resistance from the tall native varieties which can be adapted for intensive culture; (2) To obtain early maturing mutants with at least the same yield as the original variety, so that the multiple cropping system of Taiwan can be easily handled; and (3) To obtain disease-resistant mutants. The results obtained suggest that after a useful gene such as erectoid has been obtained by induced mutation, it can be used immediately. But in general, it will be more useful to combine this character into other genotypic backgrounds by cross-breeding. Henceforth, further breeding must be carried out by cross-breeding. A number of promising lines were selected from induced mutants after being crossed with local varieties and the advanced test of these lines is being carried on at present. (author)

  11. Novel mutations and mutation combinations of ryanodine receptor in a chlorantraniliprole resistant population of Plutella xylostella (L.)

    Science.gov (United States)

    Guo, Lei; Liang, Pei; Zhou, Xuguo; Gao, Xiwu

    2014-01-01

    A previous study documented a glycine to glutamic acid mutation (G4946E) in ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this study, a field population collected in Yunnan province, China, exhibited a 2128-fold resistance to chlorantraniliprole. Sequence comparison between resistant and susceptible P. xylostella revealed three novel mutations including a glutamic acid to valine substitution (E1338D), a glutamine to leucine substitution (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly conserved regions of RyR. Frequency analysis of all four mutations in this field population showed that the three new mutations showed a high frequency of 100%, while the G4946E had a frequency of 20%. Furthermore, the florescent ligand binding assay revealed that the RyR containing multiple mutations displayed a significantly lower affinity to the chlorantraniliprole. The combined results suggested that the co-existence of different combinations of the four mutations was involved in the chlorantraniliprole resistance. An allele-specific PCR based method was developed for the diagnosis of the four mutations in the field populations of P. xylostella. PMID:25377064

  12. Induced mutation in tropical fruit trees

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-05-15

    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.

  13. 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

  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. 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

  16. Use of γ-ray-induced mutations in the genome era in rice

    International Nuclear Information System (INIS)

    Kusaba, Makoto

    2007-01-01

    Ionizing radiation has been used for inducing mutations and improving crops since the discovery by STADLER (1928) that X-rays could induce mutations in barley. At the end of 2004, the whole genome sequence of rice was determined (INTERNATIONAL RICE GENOME SEQUENCING PROJECT, 2005). What can γ-ray-induced mutations contribute now that this has been achieved? One answer could be the elucidation of the functions of the numerous genes revealed by the complete sequence of the rice genome. This includes identification of mutants through reverse genetics and the isolation of genes containing mutations through forward genetics using molecular markers and sequence information. Another answer could be mutation breeding using reverse genetics. But first we must know what kind of DNA lesions are caused by γ-rays. In this article, I describe the production of DNA lesions, and then discuss how γ-ray-induced mutations can contribute to the elucidation of gene function and to mutation breeding. (author)

  17. Induced skeletal mutations

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

  18. 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)

  19. 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

  20. 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)

  1. 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)

  2. Current study on ionizing radiation-induced mitochondial DNA damage and mutations

    International Nuclear Information System (INIS)

    Zhou Xin; Wang Zhenhua; Zhang Hong

    2012-01-01

    Current advance in ionizing radiation-induced mitochondrial DNA damage and mutations is reviewed, in addition with the essential differences between mtDNA and nDNA damage and mutations. To extent the knowledge about radiation induced mitochondrial alterations, the researchers in Institute of Modern Physics, Chinese Academy of Sciences developed some technics such as real-time PCR, long-PCR for accurate quantification of radiation induced damage and mutations, and in-depth investigation about the functional changes of mitochondria based on mtDNA damage and mutations were also carried out. In conclusion, the important role of mitochondrial study in radiation biology is underlined, and further study on mitochondrial study associated with late effect and metabolism changes in radiation biology is pointed out. (authors)

  3. 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)

  4. International symposium on induced mutations in plants (ISIM). Book of abstracts

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    The year 2008 will mark the 80th anniversary of mutation induction in crop plants. The application of mutation techniques, i.e. gamma rays and other physical and chemical mutagens, has generated a vast amount of genetic variability and has played a significant role in plant breeding and genetic studies. The widespread use of induced mutants in plant breeding programmes throughout the world has led to the official release of more than 2600 mutant crop varieties. A large number of these varieties (including cereals, pulses, oil, root and tuber crops, and ornamentals) have been released in developing countries, resulting in enormous positive economic impacts. The International Symposium on Induced Mutations in Plants (ISIM) will be the eighth in the Joint FAO/IAEA Programme's Symposium series dedicated exclusively to harnessing and disseminating information on current trends in induced mutagenesis in plants, the first of which was held in 1969 and the last in 1995. These previous symposia dealt with themes relating to the development of efficient protocols for induced mutagenesis and their role in the enhancement of quality traits, as well as resistance to biotic and abiotic stresses in crops and the integration of in vitro and molecular genetic techniques in mutation induction. Since 1995, there has been an increased interest within the scientific community, not only in the use of induced mutations for developing improved crop varieties and for the discovery of genes controlling important traits and in the understanding the functions and mechanisms of actions of these genes, but also in deciphering the biological nature of DNA damage, repair and mutagenesis. A symposium that brings together the key players in basic research, as well as in the development and application of technologies relating to the efficient use of induced mutations for crop improvement and empirical genetic studies, is therefore justified and necessary. Topics addressed at the symposium

  5. 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.)

  6. The effect of spermine on spontaneous and UV-induced mutations in Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    Prendergast, J.A.; Kamra, O.P.; Nasim, A.

    1984-01-01

    The effect of different concentrations of spermine on spontaneous and UV-induced mutation in the adenine forward mutation system of Schizosaccharomyces pombe was investigated. The effect of spermine on spontaneous mutation was studied in 5 mutator strains (mut 1-4, mut 1-23, mut 2-9, mut 2-20 and mut 3-21) and on UV-induced mutation in a pigmented adenine-requiring strain and its radiation-sensitive derivative (rad 13). The effect of spermine exposure on mutation induction before and after UV irradiation was also investigated. Spermine increased spontaneous forward mutation in the mut 1-4 strain by 47% and enhanced UV-induced forward mutation 2-fold in the rad 13 and normal pigmented strains. No antimutagenic effect of spermine was seen in any of the strains tested. This is in marked contrast to the antimutagenic effect of spermine observed with bacteria. (Auth.)

  7. 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

  8. 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)

  9. 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.

  10. Mutation induction in haploid yeast after split-dose radiation exposure. II. Combination of UV-irradiation and X-rays.

    Science.gov (United States)

    Keller, B; Zölzer, F; Kiefer, J

    2004-01-01

    Split-dose protocols can be used to investigate the kinetics of recovery from radiation damage and to elucidate the mechanisms of cell inactivation and mutation induction. In this study, a haploid strain of the yeast, Saccharomyces cerevisiae, wild-type with regard to radiation sensitivity, was irradiated with 254-nm ultraviolet (UV) light and then exposed to X-rays after incubation for 0-6 hr. The cells were incubated either on nutrient medium or salt agar between the treatments. Loss of reproductive ability and mutation to canavanine resistance were measured. When the X-ray exposure immediately followed UV-irradiation, the X-ray survival curves had the same slope irrespective of the pretreatment, while the X-ray mutation induction curves were changed from linear to linear quadratic with increasing UV fluence. Incubations up to about 3 hr on nutrient medium between the treatments led to synergism with respect to cell inactivation and antagonism with respect to mutation, but after 4-6 hr the two treatments acted independently. Incubation on salt agar did not cause any change in the survival curves, but there was a strong suppression of X-ray-induced mutation with increasing UV fluence. On the basis of these results, we suggest that mutation after combined UV and X-ray exposure is affected not only by the induction and suppression of DNA repair processes, but also by radiation-induced modifications of cell-cycle progression and changes in the expression of the mutant phenotype. Copyright 2004 Wiley-Liss, Inc.

  11. 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)

  12. Re-analysis of radiation-induced specific locus mutations in the mouse

    International Nuclear Information System (INIS)

    Abrahamson, S.; Wolff, S.

    1976-01-01

    It is stated that a re-analysis of published data on mouse mutation rates induced by x-and gamma rays suggests that the kinetics of induction can be analysed by fitting that data to a parabolic curve. This is interpreted to mean that a substantial proportion of the induced mutations results from gross chromosomal changes such as deletions, some of which are one-track and some of which are two-track. This analysis is based on the assumption that the shape of the dose curve, which in the female is concave upward, reflects the manner in which the mutations are induced rather than representing a one-track (linear) curve whose shape has been modified by differential repair. (author)

  13. In-vitro mutation breeding technology in maize

    International Nuclear Information System (INIS)

    Nesticky, M.

    1988-08-01

    Gamma-irradiation and in-vitro culture, separately or combined, as a tool for inducing mutation in maize were evaluated. This type of research has been hampered in maize because (i) maize is a cross pollinating crop and highly heterozygous and (ii) embryogenesis and plant regeneration of plants from in-vitro culture have been difficult. In the present study, carefully designed and elaborated experiments were conducted using an inbred line CH1 31 which is capable of somatic embryogenesis for the subject of mutagenesis and another line Bu 8Ro 2 for the test cross partner. Results showed: 1) Both the regeneration of plants from in-vitro culture and gamma-irradiation induced a similar spectrum of morphological variation. Although the variation with somaclones was more frequent that radiation induced mutations under the conditions used, combination of explant irradiation and in-vitro culture gave the highest frequencies of genetic variation. 2) Some of the mutations in quantitative characters can be recogned in heterozygous state. 3) Mutation can cause variation in combining ability (extent of heterosis). 4) Efficiency at embryogenesis differs with genotypes of maize. 3 refs, 11 figs, 4 tabs

  14. Use of induced mutations for potato improvement

    International Nuclear Information System (INIS)

    Kishore, H.; Das, B.; Subramanyam, K.N.; Chandra, R.; Upadhya, M.D.

    1975-01-01

    The investigations aim at the utilization of induced mutations for potato improvement. The effect of γ-rays was tested on selfed seeds and hybrid seeds as well as on tubers of several potato varieties. Chemical mutagens have been successfully employed to produce daylength neutral clones. An attempt to induce resistance against Pseudomonas solanacearum did not give conclusive results. Potato improvement in relation of yield and other characters of economic significance like maturity and attributes of tubers has been handicapped by several technical considerations world over. The crux of the problem lies in the narrow genetic base (variability) for potato breeders to work with. The use of mutation breeding, therefore, offers a good tool for this. Improvement by mutation breeding for the quantitative characters besides the resistance to disease and pest has been demonstrated in other crops like white mustard variety Primex (Anderson and Olsson, 1954), barley (Gustafsson, 1965) and peanut (Gregory, 1956). Keeping these in view and the success we had in isolating photoperiod insensitive types (Upadhaya et al, 1973, 1974) study was enlarged to use mutagens to increase as wide a spectrum as possible of the variability for quantative and qualitative characters. (author)

  15. Radiation-induced dominant skeletal mutations in mice

    International Nuclear Information System (INIS)

    Selby, P.B.

    1979-01-01

    Skeletons were chosen for the attempt to determine the overall damage by radiation to one body system largely bacause they can be prepared readily for detailed study. Dominant mutations were of special interest because they are the type of mutations that would account for almost all damage induced in the early generations. The male offsprings derived from spermatogonial irradiation were used in the mutation-rate experiment, and the mutation frequency of 1.4% per gamete was found. The general dominant skeletal mutations are 1) the fusions of bones or other changes in individual bones, 2) the gross changes in bone shapes, usually caused by incomplete or too extensive bone growth, or 3) the shifts in the relative positions of bones. The recessive lethality in the period between implantation and birth can be recognized by the expected high death rate of implants in approximately 1/4 of the crosses that are between heterozygotes for a given mutation. The recessive lethal mutations may account for an important fraction of human genetic disorders owing to their dominant deleterious effects which represent only a small fraction, but because of their easy detection, they have been studied more than other dominants. At least 45, or 27%, of 164 dominant visibles in mice, ignoring those concerned with enzyme polymorphisms and immunological traits, appear to be recessive lethals. (Yamashita, S.)

  16. 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

  17. Gamma ray, EMS and sodium azide induced effectiveness and efficiency of chlorophyll mutations in basmati rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Singh, Sanjeev; Singh, J.; Singh, R.K.

    2001-01-01

    The effectiveness and efficiency of gamma ray, EMS, sodium azide alone or in combination in relation to chlorophyll mutations in two varieties of Basmati rice (Oryza sativa L.) in M 2 generation were studied. The chlorophyll mutations were induced by all the doses of mutagens alone or in combination relatively at a fair frequency in both the varieties in M 2 generation. In general, it was found that combination treatments of gamma rays and EMS were observed to be more efficient in Taraori Basmati, while EMS alone and combination treatment of gamma rays and EMS were more efficient in Pusa Basmati 1 on sterility and growth injury basis both. Sodium azide at 0.5 mM was found as the most effective dose in both Taraori Basmati and Pusa Basmati 1 cultivars. (author)

  18. 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

  19. The rad2 mutation affects the molecular nature of UV and acridine-mustard-induced mutations in the ADE2 gene of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Ivanov, E.L.; Kovaltzova, S.V.; Kassinova, G.V.; Gracheva, L.M.; Korolev, V.G.; Zakharov, I.A.

    1986-01-01

    The authors have studied the molecular nature of ade2 mutations induced by UV light and bifunctional acridine-mustard (BAM) in wild-type (RAD) and in excision-deficient (rad2) strains of the yeast, Saccharomyces cerevisiae. In the RAD strain, UV causes 45% GC → AT transitions among all mutations; in the rad2 strain this value is 77%. BAM was shown to be highly specific for frameshift mutagenesis: 60% frameshifts in the RAD strain, and as many as 84% frameshifts in the rad2 strain were induced. Therefore, the rad2 mutation affects the specificity of UV- and BAM-induced mutagenesis in yeast. Experimental data agree with the view that the majority of mutations in the RAD strain are induced by a prereplicative mechanism, whereas mutations in the rad2 strain are predominantly postreplicative events. (Auth.)

  20. 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

  1. 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.)

  2. 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

  3. 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

  4. 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)

  5. Genetic improvement of 'NPq' rice with induced mutations

    International Nuclear Information System (INIS)

    Ram, Mahabal

    1974-01-01

    Exposure of the seeds of rice to different doses of gamma-rays increased the total mutation frequency with an increase in the dose rate, and the most economic mutations occurred around 30 kr. Induced mutants with dwarf plant type, early maturity, fine grain, high-yielding ability, and resistance to lodging and major diseases were isolated in the M, and M generations. Genetical studies indicated that height is controlled by 4 pairs of additive genes, grass-clumps by 2 pairs of non-allelic interacting genes (inhibitory), and chlorophyll mutations such as albina by 2 pairs of duplicate genes and xantha by a single gene pair. (author)

  6. 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

  7. 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

  8. 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)

  9. Genetic improvement of Sesamun indicum through induced mutations

    International Nuclear Information System (INIS)

    Rajput, M.A.; Khan, Z.H.; Jafri, K.A.; Fazal Ali, J.A.

    2001-01-01

    Pakistan is chronically deficient in the production of edible oils. To enhance local production of edible oils, a mutation breeding project entitled ''Genetic improvement of Sesamum indicum through induced mutations'' was initiated for developing high yielding and widely adapted varieties of sesame. Quite a few mutants having earliness, short stature, semi-indehiscence, compact plant type, heavy bearing and high seed yield have been developed. The true breeding mutant lines developed have exhibited impressive yield potential. (author)

  10. p53 gene mutation hotspots in skin cancer and ultraviolet induced mutation

    International Nuclear Information System (INIS)

    Ikehata, Hironobu

    1998-01-01

    Presence of certain hotspots is known in the mutation of p53 gene in skin cancer, which are codons 177, 196, 245, 248, 278 and 282 located in the exon 5-8. In these regions, mutations like C to T and CC to TT are frequent and thereby suggest that they are resulted from pyrimidine-dimers produced by ultraviolet light (UV). In cyclobutane pyrimidine dimerization (CPD), conversion of cytosine to thymine by deamination is suggested to be the primary reaction. Although studies using UVC (254 nm) suggesting that the mutation hotspots are low repair efficiency regions could not completely explain the all hotspots, those using UVB and sunlight (UVB and UVA) revealed that CPD was efficiently produced even in such regions as not explained by studies with UVC alone. Therefore, the latter studies are conceivably reasonable since the skin cancer is induced by natural sunlight. Exon 5-8 DNA is completely methylated and the absorption coefficient of 5-methylcytosine is 5-6 times as large as that of cytosine at wavelength around 290 nm. These indicate the importance of UVB in mutation of mammalian cells possessing the ability to methylate DNA. (K.H.)

  11. 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

  12. Combined effect of gamma irradiation methods and in vitro explant sources on mutation induction of flower color in Chrysanthemum morifoliun Ramat

    International Nuclear Information System (INIS)

    Nagatomi, Shigeki; Miyahira, Eiken; Degi, Konosuke

    1997-01-01

    Effective radiation breeding method was searched by establishing an effective exposure method to induce a mutation involved in flower color of chrysanthemum and clarifying the effects of its combined use with cultured explants. A chrysanthemum 'Taihei', a variety suitable for cut-flower use was used as the subject, which was irradiated at a dose ranging from 0.25-1.5 Gy/day for 20 days. The floral petals, buds and leaves were used as the explants for callus induction culture. The flower color was evaluated using Japanese Standard Color chart for Horticultural Plants. The color spectrum of the adaxial surface of a petal was recorded by spectro-photometer TC-1800 MK-2. Thus, six mutants of flower color were registered as new varieties. Either of these mutants was derived from chronic irradiation. Three varieties from petal culture, two from bud one and one from cutting culture were obtained, showing that the combined method of chronic irradiation and organ culture is useful in practice for mutation breeding of flower species. Further, this method is applicable for production of non-chimeric mutants, enhancement of the mutation rate and widening the mutation spectra in vegetatively propagated plants. (M.N.)

  13. 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)

  14. 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)

  15. Radiation-Induced Mutation and Crop Improvement

    International Nuclear Information System (INIS)

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

    1987-01-01

    Radiation induced mutations have not only been used directly as a cultivar in crop plants, but also indirectly as a genetic resource that is essential to conventional plant breeding. M 1 plant survivals of three rice cultivars treated with gamma rays of 200-350 Gy varied from 30-40%. The survival of the Sawing variety was less sensitive to radiation, but its fertility was more sensitive in comparison with Seomjin and Sponging. Various dwarf or semi-dwarf mutants and early=matured mutants have been selected in the M 2 and M 3 generations of the three rice cultivars irradiated with gamma rays. Other desirable mutants also have been selected, such as high-yielding, high-tailoring and disease-resistant. The genetic nature of most of the selected short calm and earliness mutants was fixed in M 2 or M 3 generations. Dwarfism of IEAR 308 and Monogynol 10 were found to have a single recessive gene. However, the dwarf of IEAR 308 has a recessive deficit phenomenon. The highest genetic heritability of plant height was observed in the cross combination of Monogynol 10 Χ Pawling

  16. Chloroplast mutations induced by 9-aminoacridine hydrochloride are independent of the plastome mutator in Oenothera.

    Science.gov (United States)

    GuhaMajumdar, M; Baldwin, S; Sears, B B

    2004-02-01

    Oenothera plants homozygous for the recessive plastome mutator allele ( pm) show chloroplast DNA (cpDNA) mutation frequencies that are about 1,000-fold higher than spontaneous levels. The pm-encoded gene product has been hypothesized to have a function in cpDNA replication, repair and/or mutation avoidance. Previous chemical mutagenesis experiments with the alkylating agent nitroso-methyl urea (NMU) showed a synergistic effect of NMU on the induction of mutations in the pm line, suggesting an interaction between the pm-encoded gene product and one of the repair systems that corrects alkylation damage. The goal of the experiments described here was to examine whether the pm activity extends to the repair of damage caused by non-alkylating mutagens. To this end, the intercalating mutagen, 9-aminoacridine hydrochloride (9AA) was tested for synergism with the plastome mutator. A statistical analysis of the data reported here indicates that the pm-encoded gene product is not involved in the repair of the 9AA-induced mutations. However, the recovery of chlorotic sectors in plants derived from the mutagenized seeds shows that 9AA can act as a mutagen of the chloroplast genome.

  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. Feeding the world with induced mutations and biotechnology

    International Nuclear Information System (INIS)

    Mohan Jain, S.

    2002-01-01

    The paper discussed the following subjects: biotechnology - somaclonal variation, somatic embryogenesis, somatic cell hybridization; induced mutations - in banana, ornamental plants; in vitro mutagenesis; T-DNA insertional mutagenesis. Suggestions for improving biotechnology in the developing countries also presented in the paper

  19. SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.

    Science.gov (United States)

    Inoue, D; Kitaura, J; Matsui, H; Hou, H-A; Chou, W-C; Nagamachi, A; Kawabata, K C; Togami, K; Nagase, R; Horikawa, S; Saika, M; Micol, J-B; Hayashi, Y; Harada, Y; Harada, H; Inaba, T; Tien, H-F; Abdel-Wahab, O; Kitamura, T

    2015-04-01

    Mutations in ASXL1 are frequent in patients with myelodysplastic syndrome (MDS) and are associated with adverse survival, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) is not fully understood. Recently, it has been found that deletion of Asxl1 or expression of C-terminal-truncating ASXL1-MTs inhibit myeloid differentiation and induce MDS-like disease in mice. Here, we find that SET-binding protein 1 (SETBP1) mutations (SETBP1-MT) are enriched among ASXL1-mutated MDS patients and associated with increased incidence of leukemic transformation, as well as shorter survival, suggesting that SETBP1-MT play a critical role in leukemic transformation of MDS. We identify that SETBP1-MT inhibit ubiquitination and subsequent degradation of SETBP1, resulting in increased expression. Expression of SETBP1-MT, in turn, inhibited protein phosphatase 2A activity, leading to Akt activation and enhanced expression of posterior Hoxa genes in ASXL1-mutant cells. Biologically, SETBP1-MT augmented ASXL1-MT-induced differentiation block, inhibited apoptosis and enhanced myeloid colony output. SETBP1-MT collaborated with ASXL1-MT in inducing acute myeloid leukemia in vivo. The combination of ASXL1-MT and SETBP1-MT activated a stem cell signature and repressed the tumor growth factor-β signaling pathway, in contrast to the ASXL1-MT-induced MDS model. These data reveal that SETBP1-MT are critical drivers of ASXL1-mutated MDS and identify several deregulated pathways as potential therapeutic targets in high-risk MDS.

  20. Induced mutations and marker assisted breeding in soybean

    Energy Technology Data Exchange (ETDEWEB)

    Chotechuen, Somsong [Prachinburi Rice Research Center, Prachinburi (Thailand); Srisombun, Somsak [Department of Agriculture, Field Crops Research Institute, Bangkok (Thailand); Lamseejan, Siranut [Kasetsart Univ., Department of Applied Radiation and Isotopes, Bangkok (Thailand)

    2002-02-01

    Soybean is one of the important crops in Thailand. Constraints to soybean production include low yield potential, susceptibility to diseases and insects, and non-adoption of appropriate management practices. Mutation induction has been used to improve soybean yield and resistance to major diseases such as rust, purple seed, crinkle leaf, anthracnose and green seed. This paper reviews previous work and achievements of induced mutations in soybean. Successful examples are the release of a soybean variety, Doi Kham, and the development of a mutant CM 60-10kr-71; both are resistant to rust disease. The paper also gives example of the use of soybean SSR markers to identify QTL associated with pod shattering, and emphasizes the integration of mutation techniques and marker assisted selection for soybean improvement. (author)

  1. 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)

  2. 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

  3. 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.)

  4. Effect of hsm mutations enhancing spontaneous mutability on induced mutagenesis and mitotic recombination in Saccharomyces cerevisiae yeast

    International Nuclear Information System (INIS)

    Fedorova, I.V.; Koval'tsova, S.V.; Ivanov, E.L.

    1993-01-01

    The authors have studied the effect of five nonallelic hms1-hms5 mutations on the incidence of direct mutations in loci ADE1 and ADE2, induced by UV-radiation, 6-hydroxyl-aminopurine, and nitrosomethylurea. All hms mutants were found to be insensitive to the lethal action of these mutagens. The frequency of UV-induced mutations to adenine dependence was increased in mutants hsm2-1, hsm3-1, hsm5-1, and particularly in hsm1-1, but remained unchanged in hsm4-1 compared to HSM. Mutagenesis induced by 6-hydroxylaminopurine was increased in all mutants studied, particularly in mutant hsm3-1. The authors did not detect any appreciable effect of hsm mutations on mutagenesis induced by nitrosomethylurea. The frequency of spontaneous mitotic conversion to prototrophy was studied in diploids heteroallelic to gene ADE2 and homo- and heterozygous for hsm mutations. Mutation hsm5-1 considerably increased the frequency of conversion for all heteroalleles studied, mutations hsm1-1 and hsm3-1 also considerably increased the conversion frequency, while mutations hsm1-1 and hsm4-1 had little effect on this process. The study of the properties of hsm mutations revealed joint genetic control of spontaneous and induced mutagenesis and recombination in yeast. The possibility that hsm mutations belong to the class of mutations impairing correction of unpaired DNA bases is discussed. 25 refs., 3 figs., 3 tabs

  5. 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)

  6. Genetic improvement of black gram using induced mutations

    International Nuclear Information System (INIS)

    Pawar, S.E.; Manjaya, J.G.; Souframanien, J.; Bhatkar, S.M.

    2000-01-01

    Induced mutagenesis is an important tool for creating genetic variability in crop plants and has played a significant role in the development of many crop varieties. Genetic improvement of black gram (Vigna mungo L. Hepper) through induced mutations has been in progress at BARC for the past three decades. Mutation studies of genotype EC-168200 have resulted in isolating large number of mutants with distinct morphological characters. TAU-5, an early maturing mutant was identified as a resistant donor for yellow mosaic virus (YMV) disease by the All India Pulse Improvement Project, ICAR, Kanpur. TAU-5 was used in cross breeding with elite cultivars like T-9, TPU-4 and LBG-17. Twelve selections with high yield potential suitable for both kharif and rabi cultivation have been developed. One of the selections TU94-2 has been released for commercial cultivation for southern zone during 1999. The work on the development of YMV resistant genotypes is in progress and will be discussed. (author)

  7. Effect of combined mutagenic treatments on sensitivity and mutation frequency in rice

    International Nuclear Information System (INIS)

    Gopinathan Nair, V.

    1977-01-01

    Rice seeds were subjected to two sets of combination treatments of radiations and NMH. The effects of mutagenic treatments in the M 1 and M 2 generations were recorded and discussed. Mutation frequencies estimated as number of mutations per 100 M 1 years were not higher than the values expected on the basis of additive effects. When estimated as number of mutants per 100 M 2 plants, the frequencies revealed more than additive effects. The synergistic effect on mutant frequencies was due to increase in the segregation ratio of mutants. This effect was more pronounced at the higher dose combinations of fast neutrons and NMH. (author)

  8. 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

  9. Radiation induced mutations in Phaseolus vulgaris L

    International Nuclear Information System (INIS)

    Al-Rubeai, M.A.F.

    1982-01-01

    A selection of various macro- and micro-mutations was undertaken in the M2 generation of Phaseolus vulgaris cultivars after seed exposure to acute gamma radiation doses of 2.5, 5, 7, 10 and 15 Kr. The chlorophyll mutation was positively correlated with dose. Nevertheless, the highest frequency was at 7 Kr. Several interesting morphological mutants were observed. There were dwarf, stiff stem, shiny small leaf, narrow leaf and green giant mutants. Two selected micromutants were superior in seed yield capacity to their parents. The high yields were related to the high number of pods per plant. In 'The Prince' (seed color: red with beige marbling) several mutants with seeds of black color marbled with beige were selected. These seeds gave M3 segregants exhibiting a range of seed colors including white. Many of these M3 plants were short, early flowering and highly sterile. The work demonstrated that the pigmentation character can readily be changed, and confirmed that the variability induced by radiation can be exploited to obtain desirable mutations. (Author) [pt

  10. Cytosine arabinoside enhancement of gamma irradiation induced mutations in human T-lymphocytes

    International Nuclear Information System (INIS)

    O'Neill, J.P.; Sullivan, L.M.; Hunter, T.C.; Nicklas, J.A.

    1991-01-01

    The frequency of 6-thioguanine resistant (TGr) mutants induced in human G0 phase T-lymphocytes by 200 cGy of gamma irradiation is greatly enhanced by incubation with cytosine arabinoside (ara-C) after irradiation. The mutant frequency increased with increasing incubation time in ara-C for up to 2 hr. This mutation induction required a phenotypic expression time of 5-8 days mass culture growth, similar to that found with mutants induced by 300 cGy of irradiation alone. Southern blot analysis of 40 isolated mutant clones revealed 8 independent mutations by T-cell receptor (TCR) gene rearrangement patterns. Four of these eight showed hprt gene structural alterations (0.50). An alternative method to allow phenotypic expression was developed to minimize the isolation of hprt/TCR sibling mutants. The use of in situ expression in the microtiter dish wells resulted in the isolation of 17 independent mutations in 19 mutant clones. Ten of these 17 mutations showed hprt structural alterations (0.59). The high fraction of mutations involving structural alterations detected by Southern blot analysis is consistent with the known induction of chromosome aberrations by irradiation plus ara-C treatment. We propose that both the increase in Mf and the increase in the incidence of hprt gene structural alterations are due to the accumulation of strand breaks in repairing regions of DNA under these conditions of ara-C induced inhibition of repair. We further propose that upon release of the ara-C inhibition, these repairing regions can interact to yield both gene mutations and chromosome aberrations

  11. Cellular repair and its importance for UV-induced mutations

    Energy Technology Data Exchange (ETDEWEB)

    Slamenova, D [Slovenska Akademia Vied, Bratislava (Czechoslovakia). Vyskumny Ustav Onkologicky

    1975-01-01

    Current knowledge is briefly surveyed of the mechanism of the biological repair of injuries induced in DNA cells by the action of various factors, mainly ultraviolet radiation. Genetic loci determining the sensitivity of cells to UV radiation are defined and principal reparation processes are explained; excision repair is described more fully. The role of biological repair is discussed in view of UV-induced mutations in DNA cells.

  12. 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.

  13. 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

  14. Case report of a KIT-mutated melanoma patient with an excellent response to apatinib and temozolomide combination therapy

    Directory of Open Access Journals (Sweden)

    Luo C

    2017-09-01

    Full Text Available Cong Luo,1 Jiayu Shen,2 Jieer Ying,1 Xianhua Fang,3 Xiaohong Wang,1 Zhixuan Fu,4 Peng Liu5 1Department of Abdominal Oncology, Zhejiang Cancer Hospital, 2The Second Clinical Medical College, Zhejiang Chinese Medical University, 3Department of Pathology, 4Department of Colorectal Surgery, 5Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Abstract: Malignant melanoma is one kind of malignant disease which has high rates of mortality, metastasis, and poor prognosis. The therapeutic landscape is rapidly changing with the development of novel agents in recent decades, such as anti-PD-1 agents, anti-CTLA-4 agents, and BRAF inhibitors. However, since most of these novel agents are very expensive, not all patients can afford them. Apatinib is a novel oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2 and may also be effective on Ret, c-KIT, and c-src. Temozolomide (TMZ is a second-generation alkylating agent and a cytotoxic drug for melanoma treatment. In this work, we reported a case of metastatic melanoma with an excellent response to apatinib/TMZ combination therapy with progression-free survival for more than one year. This patient showed high expression of CD117, VEGFR-3, and KIT mutation in exon 11, suggesting that apatinib may induce clinical response via inhibiting VEGFR and c-KIT. Apatinib/TMZ combination therapy could be a new option for the treatment of advanced melanoma with KIT mutation. Keywords: advanced melanoma, KIT mutation, apatinib, temozolomide, combination therapy

  15. Induced mutations for improvement of grain legume production II

    International Nuclear Information System (INIS)

    1982-02-01

    Out of 18 papers presented, 15 fall within the INIS subject scope. Other topics covered were: mutagenic efficiency of ethylmethane sulphonate in soybean; induced mutations for rust resistance in soybean; and nitrogen fixation-potentials for improvement in legumes

  16. 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)

  17. 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

  18. 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)

  19. 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

  20. 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

  1. 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

  2. Mutation breeding research of wheat (T. aestivum) in China

    International Nuclear Information System (INIS)

    Wang, L.; Zhang, B.; Shi, J.; Tao, S.; Fan, Q.

    1990-01-01

    Full text: 78 cultivars and various valuable strains have been obtained through induced genic mutation and chromosome translocation. Irradiation of hybrid seeds, gametes, zygotes and in vitro cultured cells, gave increased mutation frequency and expanded spectrum. Various physical agents were examined either singly or in combination with chemical agents. Combined use of γ-irradiation by low dose and in vitro culture proved effective in raising the percentage of seed-set in wide-crosses. (author)

  3. 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)

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

    Science.gov (United States)

    Cisneros, Luis; Bussey, Kimberly J; Orr, Adam J; Miočević, Milica; Lineweaver, Charles H; 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 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 response to

  5. 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

  6. 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

  7. 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

  8. Fate of induced mutations in higher plants with special emphasis on sexually reproducing species

    International Nuclear Information System (INIS)

    Cornu, Andre

    1978-01-01

    A mutation induced in a plant somatic cell has to overcome quite many difficulties before being isolated and utilized as a marker in a mutated line. If induced in a meristem, three conditions must be fulfilled for the mutation to be transmitted to the subsequent generation: it must be compatible with normal cell multiplication, it must be located in a cell mass that will provide an inflorescence, and it must be in the sporogenetic layer (t2). Under these conditions, or if it is induced in a gamete or in a zygote, the mutation enters a first cycle of sexual reproduction. Meiosis and the subsequent haploid phase constitute severe screening steps for many chromosome aberrations. Studies on Petunia performed by means of marker genes show that male and female gametic viabilities are drastically impaired by deletions. However, a deficient chromosome can be transmitted when the losss of information is compensated for by homologous information as, for example, diploid gametes from tetraploids or disomic gametes resulting from non-disjunction. If partial or complete sterility, whether sporo- or gametophytic, is avoided, then the mutation can be transmitted to the next generation in heterozygous state. When becoming homozygous, the mutation may have effects such that its use can be most difficult. This is the case when this mutation causes rather early lethality or severe sterility. Thus, in higher plants, one faces several cases of powerful and efficient selection against mutations. On the basis of experiments carried out on Petunia, the per locus mutation rate of practical interest ranges between I and 5/10000M 1 plants. Practical conclusions are drawn about which organ should be treated, which mutagen at what dose should be used according to the scope of the research undertaken [fr

  9. 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)

  10. Induced mutations in highly heterozygous vegetatively propagated grasses

    International Nuclear Information System (INIS)

    Powell, J.B.

    1976-01-01

    Experience with mutation induction of turf and forage grasses indicates that much progress can be achieved by this method. More than 300 mutations have been produced in our laboratory in the cultivars Tifgreen and Tifdwarf bermudagrass (Cynodon sp.). In the Tifway and Tifcote bermudagrasses we have demonstrated similar mutation responses. The first three clones are triploids and Tifcote is a probable tetraploid. No seeds are set on these clones. Two clones of bermudagrass, Coastal and Coastcross-1, occupy millions of hectares in the USA. Both are mutable and are known to be hybrids with 36 chromosomes. Biotypes of dallisgrass (Paspalum dilatatum Poir.) exist with 40 and 50 chromosomes and reproduce as sexual and obligate apomictic forms. Gamma-ray and thermal-neutron treatment of seed of these biotypes produced mutants that maintained the maternal characteristics in subsequent generations. Bahiagrass (Paspalum notatum Fluegge) also has sexual and apomictic biotypes. Some success was indicated for increased seed set by mutagen treatment. Kentucky bluegrass (Poa pratensis L.) is a facultative apomict with varying numbers of chromosomes in different cultivars. Gamma-ray mutagen treatment of rhizomes produced numerous mutations for plant type and disease reaction. Most mutations perpetuate themselves through the seed. The characteristic in common with all these grasses is their heterozygosity, which is maintained by the vegetative propagation or apomictic mode of reproduction. The experience in using ionizing radiation to induce heritable changes in these vegetatively propagated grasses is one of considerable success. Mutation rates in some of these irradiated grasses exceeded 65% and aberrant plants with characteristics previously never observed were found. Numerous hemizygous and heterozygous loci seem to be a sensitive target for mutagens. (author)

  11. Rice breeding with induced mutations

    Energy Technology Data Exchange (ETDEWEB)

    1968-06-01

    The Joint FAO/IAEA Division of Atomic Energy in Food and Agriculture decided in 1964 to organize a co-ordinated research programme on the use of induced mutations in rice breeding. The programme was organized within the framework of activities of the International Rice Commission. This is a report of the Third Co-ordination Meeting of the participants, which was held in Taipei, 5-9 June 1967. As the projects, which together make up the co-ordinated programme, are at different stages of progress, the report contains a variety of papers including completed studies, field and progress reports, and highlights of the discussions with some additional recommendations prepared by the participants. Refs, figs and tabs.

  12. Lack of chemically induced mutation in repair-deficient mutants of yeast

    International Nuclear Information System (INIS)

    Prakash, L.

    1974-01-01

    Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), β-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents. (auth)

  13. Lack of chemically induced mutation in repair-deficient mutants of yeast.

    Science.gov (United States)

    Prakash, L

    1974-12-01

    Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), beta-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents.

  14. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Micke, A; Maluszynski, M; Donini, B [Joint FAO/IAEA Division, Plant Breeding and Genetics Section, Vienna (Austria)

    1985-05-01

    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.

  16. 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.)

  17. Mutation induction in rice by radiation combined with chemical protectants and mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A [Agricultural College, University of Sao Paulo, Sao Paulo (Brazil)

    1970-03-01

    Seeds of the rice variety 'Dourado Precoce' were treated with different combinations of gamma rays, cysteine and EMS or gamma rays, cysteine and dES. Cysteine showed some protection against the effects of gamma radiation and combined gamma-ray + chemical treatments with regard to germination, seedling height and fertility. There are also indications of changes in the spectra of chlorophyll mutations. (author)

  18. 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

  19. 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

  20. 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

  1. A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome.

    Science.gov (United States)

    Khateb, Samer; Zelinger, Lina; Mizrahi-Meissonnier, Liliana; Ayuso, Carmen; Koenekoop, Robert K; Laxer, Uri; Gross, Menachem; Banin, Eyal; Sharon, Dror

    2014-07-01

    Usher syndrome (USH) is a heterogeneous group of inherited retinitis pigmentosa (RP) and sensorineural hearing loss (SNHL) caused by mutations in at least 12 genes. Our aim is to identify additional USH-related genes. Clinical examination included visual acuity test, funduscopy and electroretinography. Genetic analysis included homozygosity mapping and whole exome sequencing (WES). A combination of homozygosity mapping and WES in a large consanguineous family of Iranian Jewish origin revealed nonsense mutations in two ciliary genes: c.3289C>T (p.Q1097*) in C2orf71 and c.3463C>T (p.R1155*) in centrosome-associated protein CEP250 (C-Nap1). The latter has not been associated with any inherited disease and the c.3463C>T mutation was absent in control chromosomes. Patients who were double homozygotes had SNHL accompanied by early-onset and severe RP, while patients who were homozygous for the CEP250 mutation and carried a single mutant C2orf71 allele had SNHL with mild retinal degeneration. No ciliary structural abnormalities in the respiratory system were evident by electron microscopy analysis. CEP250 expression analysis of the mutant allele revealed the generation of a truncated protein lacking the NEK2-phosphorylation region. A homozygous nonsense CEP250 mutation, in combination with a heterozygous C2orf71 nonsense mutation, causes an atypical form of USH, characterised by early-onset SNHL and a relatively mild RP. The severe retinal involvement in the double homozygotes indicates an additive effect caused by nonsense mutations in genes encoding ciliary proteins. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. The Pattern and 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

  3. 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.

  4. Genetic and molecular analyses of UV radiation-induced mutations in the fem-3 gene of Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P S; De Wilde, D; Dwarakanath, V N [Texas Christian Univ., Fort Worth, TX (United States). Dept. of Biology

    1995-06-01

    The utility of a new target gene (fem-3) is described for investigating the molecular nature of mutagenesis in the nematode Caenorhabditis elegans. As a principal attribute, this system allows for the selection, maintenance and molecular analysis of any type of mutation that disrupts the gene, including deletions. In this study, 86 mutant strains were isolated, of which 79 proved to have mutations in fem-3. Twenty of these originally tested as homozygous inviable. Homozygous inviability was expected, as Stewart and coworkers had previously observed that, unlike in other organisms, most UV radiation-induced mutations in C. elegans are chromosomal rearrangements of deficiencies (Mutat. Res 249, 37-54, 1991). However, additional data, including Southern blot analyses on 49 of the strains, indicated that most of the UV radiation-induced fem-3 mutations were not deficiencies, as originally inferred from their homozygous inviability. Instead, the lethals were most likely ``coincident mutations`` in linked, essential genes that were concomitantly induced. As such, they were lost owing to genetic recombination during stock maintenance. As in mammalian cells, yeast and bacteria, the frequency of coincident mutations was much higher than would be predicted by chance. (Author).

  5. Second-line combination therapies in nonsmall cell lung cancer without known driver mutations

    Directory of Open Access Journals (Sweden)

    Maria-Virginia Bluthgen

    2015-12-01

    Full Text Available In advanced nonsmall cell lung cancer (NSCLC patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies. In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Frequencies of aneuploidy and dominant lethal mutations in young female mice induced by low dose γ-rays

    International Nuclear Information System (INIS)

    Yao Suyan; Zhang Chaoyang; Dai Lianlian; Gao Changwen

    1991-01-01

    Relationship between aneuploidy, dominant lethal mutations and doses in young feral mice induced by low dose γ-rays was examined. The results suggest that the frequencies of aneuploidy of embryos increased at 0.15 Gy, but increases at over 0.50 Gy after irradiation in groups. The frequencies of aneuploidy and dominant lethal mutations increased with increasing doses and fitted linear relationship. This dose-response relationship of trisomic was not significant. The frequency of dominant lethal mutations induced by 60 Co γ irradiation is 5.59%. The effect of dominant lethal mutation is higher than that of the aneuploidy

  12. 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

  13. Modification of radiation-induced sex-linked recessive lethal mutation frequency by tocopherol

    International Nuclear Information System (INIS)

    Beckman, C.; Roy, R.M.; Sproule, A.

    1982-01-01

    The present study evaluates the effect of supplementing culture medium with α-tocopherol acetate on the yield of sex-linked recessive lethal mutants induced by X-irradiation in mature sperm of Drosophila. Although tocopherol treatment of males had no impact on the yield of mutations, a drastic reduction in mutation frequency was observed when irradiated males were mated to females raised and subsequently maintained on tocopherol-enriched diet. (orig./MG)

  14. Mutations induced by the action of metal ions in Pisum

    Energy Technology Data Exchange (ETDEWEB)

    von Rosen, G

    1957-01-01

    Simple metal ions may induce both radiomimetic effects and genuine gene mutations of the same type which occurs from ionizing radiation and from treatment with some chemical agencies as e.g., mustard gas. The main material during the experiments has been species of Pisum. The biochemical principle which lies behind these reactions is the complex-forming ability among those reactive bivalent metal elements. The author assumes that interruptions of the chelate formation in the cell synthesis form the real background to the observed activity of the metal ions. The possible role in the evolution of the plant- and animal kingdom and the probable value for plant-breeding of the mutation activity observed are suggested. A new field for mutation experiments may here be opened and the results must hitherto be judged as interesting and promising. 13 references, 7 figures, 4 tables.

  15. Research progress in plant mutation by combining ion beam irradiations and tissue culture

    International Nuclear Information System (INIS)

    Zhou Linbin; Li Wenjian; Qu Ying; Li Ping

    2007-01-01

    About a new mutation breeding method which combines plant tissue culture technique with heavy ion beam irradiations were discussed in this paper with the principles, operation steps, molecular mechanisms, etc. The mutation method developed a few advantages coming from plant tissue culture, which can produce offspring by asexual ways. Meanwhile, using this method, the study of biological effects of high energy particles with different linear energy transfer values on plant tissues or cells can be explored and optimized in theory or practice. (authors)

  16. 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)

  17. Mutation direction by irradiation in rice

    International Nuclear Information System (INIS)

    Wang Cailian; Chen Qiufang; Jin Wei; Lu Yimei

    2001-01-01

    The mutation directions of rice were studied. The results indicated that the mutation directions of rice induced by 14 C were invert correlation to their genetic backgrounds of tested rice varieties, i.e. early mature and short stem varieties produced later mature and higher stem mutation; late mature and high stem varieties produced earlier mature and shorter stem mutation; the varieties of middle maturity and height produced both direction mutations of earlier and later maturity or shorter and higher stem. The mutation directions induced by 14 C were also related to treated doses and stages. Frequency of earlier maturity mutation by protons treatment were higher than those induced by other mutagens. Frequency of later maturity by γ-rays were higher than those induced by other mutagens. Frequency of short stem mutation by synchronous irradiation (soft X-rays) were higher than those induced by other mutagens. Frequency of beneficial mutation induced by proton treatment were higher than those induced by γ-rays

  18. Molecular nature of X-ray-induced mutations compared with that of spontaneous ones in human c-hprt gene integrated into mammalian chromosomal DNA

    International Nuclear Information System (INIS)

    Kimura, Hiroshi; Kato, Takesi.

    1992-01-01

    X-ray-induced mutations were analysed at molecular levels in comparison with spontaneous mutations. Altered sequences were determined tentatively of 30 independent X-ray-induced mutations in a cDNA of the human hprt gene which was integrated into mammalian chromosome as a part of a shuttle vector. Mutations consisted of base substitutions (37 %), frameshifts (27 %), deletions (27 %) and others (10 %). All these mutational events were distributed randomly over the gene without there being hot spots. The spectrum and distribution of X-ray-induced mutations resembled those of spontaneous mutations. Among base substitutions, transversions were predominant and base substitution mutations occurred more at A:T sites than at G:C sites, which is also the case in spontaneous mutations. Most of the frameshift and deletion mutations induced by X-rays, as well as those spontaneously arising, were characterized by the existence of short direct repeats of several identical bases in a row at the sites of the mutations. A slippage misalignment mechanism in replication well accounts for the generation of these classes of mutations. Judging from the data accumulated so far, it can be concluded that X-ray-induced mutations at molecular levels are similar to those spontaneously occurring. (author)

  19. 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)

  20. New approaches for effective mutation induction in gamma field

    Energy Technology Data Exchange (ETDEWEB)

    Nagatomi, Shigeki [National Institute of Agrobiological Resources, Institute of Radiation Breeding, Omiya, Ibaraki (Japan)

    2001-03-01

    The purpose of the report is to clarify the effects of chronic irradiation using in vitro culture on inducing the mutation of two model plants. Culture technique combined with irradiation can overcome the problem of chimera formation and provided 10 times greater mutation efficiency than conventional method. Proper mutagenic treatment using cultured materials is indispensable to effective mutation induction. The chronic culture method showed the widest color spectrum in chrysanthemum and extended toward not only the negative but positive direction. However, the acute culture methods indicated a relatively low mutation rate and a very limited flower color spectrum. Flower color mutation of the regenerations could be induced more from petals and buds than from leaves. These facts is supposed that the gene loci fully expressed on floral organs may be unstable for mutation by mutagenesis or culture. It may be likely to control a direction of desired mutation. One possible reason why the chronic culture methods showed higher frequencies is that most of the cells composing the tissue and organs continually irradiated into a cell division which was highly sensitive and more mutable to irradiation. Under these conditions, many mutated sectors may accumulate in the cells of the growing organs. Regenerated mutant lines show remarkable decrease of chromosome numbers by irradiation. It is a proper indicator to monitor radiation damage. In this study, the six flower color mutant varieties registered were derived from chronic irradiation. The combined method of chronic irradiation with floral organ cultures proved to be of particularly great practical use in mutation breeding for not only flower species but any other species. (author)

  1. New approaches for effective mutation induction in gamma field

    International Nuclear Information System (INIS)

    Nagatomi, Shigeki

    2001-01-01

    The purpose of the report is to clarify the effects of chronic irradiation using in vitro culture on inducing the mutation of two model plants. Culture technique combined with irradiation can overcome the problem of chimera formation and provided 10 times greater mutation efficiency than conventional method. Proper mutagenic treatment using cultured materials is indispensable to effective mutation induction. The chronic culture method showed the widest color spectrum in chrysanthemum and extended toward not only the negative but positive direction. However, the acute culture methods indicated a relatively low mutation rate and a very limited flower color spectrum. Flower color mutation of the regenerations could be induced more from petals and buds than from leaves. These facts is supposed that the gene loci fully expressed on floral organs may be unstable for mutation by mutagenesis or culture. It may be likely to control a direction of desired mutation. One possible reason why the chronic culture methods showed higher frequencies is that most of the cells composing the tissue and organs continually irradiated into a cell division which was highly sensitive and more mutable to irradiation. Under these conditions, many mutated sectors may accumulate in the cells of the growing organs. Regenerated mutant lines show remarkable decrease of chromosome numbers by irradiation. It is a proper indicator to monitor radiation damage. In this study, the six flower color mutant varieties registered were derived from chronic irradiation. The combined method of chronic irradiation with floral organ cultures proved to be of particularly great practical use in mutation breeding for not only flower species but any other species. (author)

  2. 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)

  3. A population genetic analysis of the potential for a crude oil spill to induce heritable mutations and impact natural populations

    Energy Technology Data Exchange (ETDEWEB)

    Cronin, M.A. [LGL Alaska Research Associates Inc., Anchorage, AK (United States); Bickham, J.W. [Texas A and M University, College Station, TX (United States). Dept. of Wildlife and Fisheries Sciences; LGL Ecological Genetics Inc., Bryan, TX (United States)

    1998-07-01

    The primary environmental impact following an oil spill typically is acute toxicity to fish and wildlife. However, multigenerational effects through toxicant-induced heritable mutations might also occur. Some polycyclic aromatic hydrocarbon (PAH) components of crude oil are potentially mutagenic, although specific components and doses that induce mutations are poorly known. We applied population genetics concepts to assess the extent of mortality and the persistence of deleterious heritable mutations resulting from exposure to potential mutagens, such as crude oil. If lethal mutations are induced, the population will experience some mortality, but the mutations are quickly removed or reduced to low frequency by natural selection. This occurs within one or a few generations when mutations are dominant or partially recessive. Totally recessive alleles persist in low frequency for many generations, but result in relatively little impact on the population, depending on the number of mutated loci. We also applied population genetics concepts to assess the potential for heritable mutations induced by the Exxon Valdez oil spill in Prince William Sound, Alaska, to affect pink salmon populations. We stress that breeding units (e.g., streams with distinct spawning populations of salmon) must be considered individually to assess heritable genetic effects. For several streams impacted by the oil spill, there is inconsistency between observed egg mortality and that expected if lethal heritable mutations had been induced by exposure to crude oil. Observed mortality was either higher or lower than expected depending on the spawning population, year, and cohort considered. Any potential subtle effect of lethal mutations induced by the Exxon Valdez oil spill is overridden by natural environmental variation among spawning areas. We discuss the need to focus on population-level effects in toxicological assessments because fish and wildlife management focuses on populations, not

  4. 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)

  5. Combining zygotic embryo culture and mutation induction to improve salinity tolerance in avocado (Persea americana Mill)

    Energy Technology Data Exchange (ETDEWEB)

    Fuentes, J. L.; Santiago, L.; Alvarez, A.; Valdés, Y.; Vernhe, M.; Guerra, M.; Altanez, S.; Prieto, E. F. [Centro de Aplicaciones Tecnológicas y Desarrollo Nuclear (CEADEN), Miramar, Playa, C. Habana (Cuba); Rodríguez, N. N.; Arbelo, O. Coto; Velázquez, B.; Rodríguez, J. A.; Sourd, D. G.; Fuentes, V. R. [Instituto de Investigaciones de Fruticultura Tropical (IICF), Miramar, Playa, C. Habana (Cuba); Leal, M. R. [Departamento de Microbiología, Facultad de Biología, Universidad de la Habana, Vedado, C. Habana (Cuba)

    2009-05-15

    Mutation induction and biotechnological techniques are some of the current approaches used in plant breeding. In the present work radiation-induced mutation followed by in vitro culture of zygotic embryos and high osmotic pressure selection methods to improve salt tolerance in avocado are investigated. The in vitro germination, rooting, bud multiplication and plantlet acclimatization of Cuban avocado varieties were recorded. The germination rates of whole embryos in vitro were found to be higher when using mature rather than immature embryos. Almost 80% of the whole embryos derived plantlets produced were successfully acclimatized under greenhouse conditions. An in vitro propagation method for avocado breeding purposes was optimized and documented. However, in vitro multiplication results indicated the need to improve bud multiplication methods in avocado. The survival rates of gamma rays irradiated and salt pressured avocado embryos were also investigated. Both mutagenic (LD{sub 50} = 27-28 Gy) and selective (LD{sub 20} = 157 mM of NaCl) doses were established. A procedure combining zygotic embryo culture and mutation induction was used to obtain. Putative mutant lines derived from salt tolerant rootstocks were developed. Putative M{sub 1}V{sub 3} progenies were planted in the field for segregation analysis. An avocado gene bank was established under the same study. Therefore this methodology appears as an alternative to traditional breeding methods, particularly for improving agronomic characteristics such as salt tolerance in avocado. (author)

  6. Effect of tumor promoters on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Kunz, B.A.; Hannan, M.A.; Haynes, R.H.

    1980-01-01

    Recently, it has been suggested that mitotic recombination is involved in tumor promotion. On this basis, one might expect tumor promoters to be recombinagenic. D7 is a diploid strain of yeast in which both mutation and mitotic recombination can be measured. We have used this strain to assay the known tumor promoters, iodacetate, anthralin, and 12-0-tetradecanoylphorbol-13-acetate, and the cocarcinogen, catechol, for mutagenicity, recombinagenicity, and the ability to enhance ultraviolet light (UV)-induced genetic events. In the absence of preirradiation with UV, iodoacetate was found to be recombinagenic whereas catechol was mutagenic; however, in both cases, the effects were small. Iodoacetate, anthralin, and catechol potentiated UV-induced mitotic crossing-over, aberrant colony formation, and mutation, while catechol also increased UV-induced gene conversion. We were unable to detect any mutagenic or recombinagenic effect of 12-0-tetradecanoyl-phorbol-13-acetate in either whole cells or spheroplasts. Our results do not indicate any consistent correlation between tumor-promoting activity and the ability of an agent to induce mitotic recombination in yeast. However, the ability to potentiate UV-induced mutation and mitotic recombination may reflect the cocarcinogenic activity of certain promoters

  7. HPRT gene locus mutation in peripheral blood lymphocytes induced by internal exposure to radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Jingyong, Zhao; Yongzhong, Xu; Tao, Zhao; Fengmei, Cui; Liuyi, Wang; Qinhua, Lao [Suzhou Univ., Suzhou (China). Radiation Medicine Department

    2001-07-01

    HPRT gene locus mutation in peripheral blood lymphocytes induced by internal exposure to radionuclides was performed and the relationships between mutation frequency and dose were studied. Rats were injected intravenously with radionuclides, the blood was sampled at different time after injection; HPRT gene locus mutation frequency (GMF) were examined by methods of multi-nucleus cell and Brdurd assay, working out the Dose-response function. GMF rose with the increase of dose and dose-rates and were clearly interrelated. The HPRT gene locus mutation is very sensitive to radiation and may be used as a biological dosimeter.

  8. 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.

  9. 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

  10. Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics

    DEFF Research Database (Denmark)

    Pakula, Kevin K; Hansen, Lykke H; Vester, Birte

    2017-01-01

    . The presence of Cfr has a very minor influence on the growth rate. The resistance of the transformants to linezolid, tiamulin, florfenicol, and Synercid (a combination of quinupristin and dalfopristin [Q-D]) was measured by MIC assays. The resistance from Cfr was, in all cases, stronger than the effects...... of the L3 mutations, but various effects were obtained with the combinations of Cfr and L3 mutations ranging from a synergistic to an antagonistic effect. Linezolid and tiamulin susceptibility varied greatly among the L3 mutations, while no significant effects on florfenicol and Q-D susceptibility were...

  11. Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kakinuma, Shizuko, E-mail: skakinum@nirs.go.jp [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Amasaki, Yoshiko; Takada, Mayumi; Yamauchi, Kazumi; Sudo, Satomi; Shang, Yi [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Doi, Kazutaka; Yoshinaga, Shinji [Regulatory Sciences Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shimada, Yoshiya [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2012-09-01

    Ionizing radiation is a well-known carcinogen, but its potency may be influenced by other environmental carcinogens, which is of practical importance in the assessment of risk. Data are scarce, however, on the combined effect of radiation with other environmental carcinogens and the underlying mechanisms involved. We studied the mode and mechanism of the carcinogenic effect of radiation in combination with N-ethyl-N-nitrosourea (ENU) using doses approximately equal to the corresponding thresholds. B6C3F1 mice exposed to fractionated X-irradiation (Kaplan's method) followed by ENU developed T-cell lymphomas in a dose-dependent manner. Radiation doses above an apparent threshold acted synergistically with ENU to promote lymphoma development, whereas radiation doses below that threshold antagonized lymphoma development. Ikaros, which regulates the commitment and differentiation of lymphoid lineage cells, is a critical tumor suppressor gene frequently altered in both human and mouse lymphomas and shows distinct mutation spectra between X-ray- and ENU-induced lymphomas. In the synergistically induced lymphomas, we observed a low frequency of LOH and an inordinate increase of Ikaros base substitutions characteristic of ENU-indcued point mutations, G:C to A:T at non-CpG, A:T to G:C, G:C to T:A and A:T to T:A. This suggests that radiation doses above an apparent threshold activate the ENU mutagenic pathway. This is the first report on the carcinogenic mechanism elicited by combined exposure to carcinogens below and above threshold doses based on the mutation spectrum of the causative gene. These findings constitute a basis for assessing human cancer risk following exposure to multiple carcinogens.

  12. 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

  13. Gamma-ray-induced dominant mutations that cause skeletal abnormalities in mice

    International Nuclear Information System (INIS)

    Selby, P.B.; Selby, P.R.

    1977-01-01

    Male mice were exposed to 100 R + 500 R γ-rays (60 R/min) with a 24-h fractionation interval. Skeletons of F 1 sons were examined for abnormalities, and, if any were found, the skeletons of their descendants were also examined. Of 2646 sons from treated spermatogonia, 37, or 1.4%, were diagnosed as carriers of autosomal dominant mutations affecting the skeleton, 31 by breeding tests, and six by other criteria for identifying mutations in F 1 's having no progeny. Many mutations caused a large number of anomalies in different regions of the skeleton. Most regions of the skeleton were affected by at least one mutation, and the mutations had incomplete penetrance for some or all of their effects. Three of the mutations affected skeletal size only. If certain assumptions are made, these skeletal data can be used to derive an estimate of induced genetic damage from dominant mutations affecting all parts of the body. When applied to man, the resultant risk estimate is not inconsistent with that made for dominant and irregularly inherited diseases by the BEIR Committee, by use of the doubling-dose method. Since most of the mutations can be characterized as models of irregularly inherited conditions in man, the data directly relate to the controversy over the relative importance of mutation pressure and balanced selection in maintaining man's large burden of irregularly inherited disease. Contrary to a recent hypothesis by H.B. Newcombe that man's large burden of irregularly inherited disease is maintained almost exclusively by balanced selection, these results suggest that at least an important fraction of the irregularly inherited conditions are maintained by mutation pressure. Therefore, this finding does not support the major changes in the estimate of genetic hazard to man that would be required on the basis of Newcombe's hypothesis

  14. Comparison of somatic mutation frequencies at HGPRT locus induced by radiation and chemical pollutant from energy system

    International Nuclear Information System (INIS)

    Xu Honglan; Cao Yi; Duan Zhikai; Wu Qiqing; Chen Ying; Zhang Shuxian

    1998-12-01

    The somatic induction frequencies of mutation at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus induced by 60 Co γ-rays and Benzo-a-pyrene (B(a)P), which are representative of hazardous emission and pollutant from nuclear energy cycle and fossil-fuelled energy cycle respectively, were detected by using forward mutation assay and cloning technique in both V 79 Chinese hamster cells and human peripheral blood T-lymphocytes. Resistant mutants were selected with 6-thioguanine (6-TG). Dose-response curves and mathematical expressions were obtained for mutation frequencies and survival following γ-ray and B(a)P(+S 9 ) treatments. The dose ranges for the two mutagens were compared when they induced the same mutation frequencies. In V 79 /HGPRT assay system, when the mutation frequencies were 5∼35 mutants/10 6 cells the response of γ-rays in the dose range from 0.93∼4.96 Gy at dose rate of 1.16 Gy/min is nearly equivalent to that in the B(a)P dose range from 0.52∼4.27 μg/ml. By using cloning technique in T-lymphocytes, when the mutation frequencies were 1∼14 mutants/10 5 cells the response of γ-rays in the dose range from 0.05∼4.77 Gy at dose rate of 1.03 Gy/min is nearly equivalent to that in the B(a)P dose range from 0.15∼7.36 μg/ml. When the survival fraction is 37%, the mutation frequency induced by B(a)P is higher than that induced by 60 Co γ-rays

  15. 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)

  16. 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

  17. 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

  18. 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

  19. Induction of spontaneous and UV-induced mutations during commitment to meiosis in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Machida, I.; Nakai, S.

    1980-01-01

    Inductions of reversions of nonsense, missense and frameshift-type mutations were investigated in a diploid cell population of Saccharomyces cerevisiae during commitment to meiosis, by using the medium-transfer technique from sporulation medium to vegetative medium. The yields of spontaneous reverse mutations obtained from the cells that were committed to different stages during meiosis were rather constant irrespective of the alleles tested, although the yields of both intergenic and intragenic recombinations markedly increased. The susceptibilities to UV-induced reverse mutations examined during commitment to meiosis were not changed appreciably. It is concluded that induction of base-change-type mutations in meiosis is not essentially different from that in mitosis. (orig.)

  20. [Mutants of the yeast Saccharomyces cerevisiae characterized by enhanced induced mutagenesis. III. Effect of the him mutation on the effectiveness and specificity of UF-induced mutagenesis].

    Science.gov (United States)

    Ivanov, E L; Koval'tsova, S V; Korolev, V G

    1987-09-01

    We have studied the influence of him1-1, him2-1, him3-1 and himX mutations on induction frequency and specificity of UV-induced adenine-dependent mutations in the yeast Saccharomyces cerevisiae. Him mutations do not render haploid cells more sensitive to the lethal action of UV-light; however, in him strains adenine-dependent mutations (ade1, ade2) were induced more frequently (1.5--2-fold), as compared to the HIM strain. An analysis of the molecular nature of ade2 mutants revealed that him1-1, him2-1 and himX mutations increase specifically the yield of transitions (AT----GC and GC----AT), whereas in the him3-1 strain the yield of transversions was enhanced as well. We suggest him mutations analysed to affect specific repair pathway for mismatch correction.

  1. New advances of wheat mutation breeding in Heilongjiang Province

    International Nuclear Information System (INIS)

    Sun Guangzu

    1991-09-01

    Five wheat varieties have been released between 1980 and 1990, these varieties possess early maturity, high yield, good quality, disease resistance and wide adaptability. They have been cultivated on 373 330 ha. Some of them are proved to be very valuable germ plasma for cross breeding. Technique of induced wheat mutation have been studied. Since selecting adaptable irradiation conditions, using combination of radiation with hybridization, irradiating male gamete, female gamete and zygote, soaking treatment with KH+2 32 PO 4 , etc., the efficiency of induced mutation have been increased. By combining radiation with distant hybridization, F 0 unfruitfulness and F 1 sterility have been overcome, and 21 wheat-rye translocation lines have been selected. One of them, 6BS/6RL translocation line, which is called Longfumai No. 4, was released in 1987. The procedure of inducting and identifying translocation lines has been raised already. Mature embryos, anthers and young embryos of wheat were irradiated and inoculated as explants. The rude toxin of Bipoloris sorokiniana, as a screening factor, was added to different medi and finally 3 lines with resistance to Bipoloris sorokiniana were selected. It was established that technical system for in-vitro radiation induced mutation and screening wheat mutants of resistance to disease. The biochemical identify methods for mutants have been studied already

  2. 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

  3. 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)

  4. 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)

  5. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Halliday, Gary M. [Dermatology Research Laboratories, Division of Medicine, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at the University of Sydney, Sydney, NSW (Australia)]. E-mail: garyh@med.usyd.edu.au

    2005-04-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.

  6. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    International Nuclear Information System (INIS)

    Halliday, Gary M.

    2005-01-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans

  7. 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)

  8. 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

  9. Insight on Mutation-Induced Resistance from Molecular Dynamics Simulations of the Native and Mutated CSF-1R and KIT.

    Directory of Open Access Journals (Sweden)

    Priscila Da Silva Figueiredo Celestino Gomes

    Full Text Available The receptors tyrosine kinases (RTKs for the colony stimulating factor-1, CSF-1R, and for the stem cell factor, SCFR or KIT, are important mediators of signal transduction. The abnormal function of these receptors, promoted by gain-of-function mutations, leads to their constitutive activation, associated with cancer or other proliferative diseases. A secondary effect of the mutations is the alteration of receptors' sensitivity to tyrosine kinase inhibitors, compromising effectiveness of these molecules in clinical treatment. In particular, the mutation V560G in KIT increases its sensitivity to Imatinib, while the D816V in KIT, and D802V in CSF-1R, triggers resistance to the drug. We analyzed the Imatinib binding affinity to the native and mutated KIT (mutations V560G, S628N and D816V and CSF-1R (mutation D802V by using molecular dynamics simulations and energy calculations of Imatinib•target complexes. Further, we evaluated the sensitivity of the studied KIT receptors to Imatinib by measuring the inhibition of KIT phosphorylation. Our study showed that (i the binding free energy of Imatinib to the targets is highly correlated with their experimentally measured sensitivity; (ii the electrostatic interactions are a decisive factor affecting the binding energy; (iii the most deleterious impact to the Imatinib sensitivity is promoted by D802V (CSF-1R and D816V (KIT mutations; (iv the role of the juxtamembrane region, JMR, in the imatinib binding is accessory. These findings contribute to a better description of the mutation-induced effects alternating the targets sensitivity to Imatinib.

  10. The estimation of risks from the induction of recessive mutations after exposure to ionising radiation

    International Nuclear Information System (INIS)

    Searle, A.G.; Edwards, J.H.

    1986-01-01

    Induced recessive mutations can cause harm by (1) partnership with a defective allele already established in the population; (2) partnership with another recessive mutation induced at the same locus; (3) the formation of homozygous descendants, that is, identify by descent; and (4) heterozygous effects. Calculations based on a combination of data from observations on human populations and from mouse experiments suggest that an extra genetically significant dose of 1 cGy X or γ irradiation received by each parent in a stable population with a million liveborn offspring would induce up to 1200 extra recessive mutations. From partnership effects, about one extra case of recessive disease would be expected in the following 10 generations. Homozygosity resulting from identity by descent could not normally occur until the fourth generation after exposure but, on certain assumptions, about ten extra cases of recessive disease would be expected from this cause by the tenth generation. In the same period, about 250 recessive alleles would be eliminated in heterozygotes given 2.5% heterozygous disadvantage. These deleterious heterozygous effects should not be combined with those of dominants, as has been done in some previous risk estimates. It is considered unlikely that many radiation induced recessives would show heterozygous advantage. Certain dominants should be excluded from calculations of mutational risk because they are unlikely to be maintained by mutation. (author)

  11. High-resolution melting curve analysis for rapid detection of mutations in a Medaka TILLING library

    Directory of Open Access Journals (Sweden)

    Deguchi Tomonori

    2010-09-01

    Full Text Available Abstract Background During the last two decades, DNA sequencing has led to the identification of numerous genes in key species; however, in most cases, their functions are still unknown. In this situation, reverse genetics is the most suitable method to assign function to a gene. TILLING (Targeting Induced Local Lesions IN Genomes is a reverse-genetic strategy that combines random chemical mutagenesis with high-throughput discovery of the induced mutations in target genes. The method has been applied to a variety of plant and animal species. Screening of the induced mutations is the most important step in TILLING. Currently, direct sequencing or nuclease-mediated screening of heteroduplexes is widely used for detection of mutations in TILLING. Both methods are useful, but the costs are substantial and turnaround times are relatively long. Thus, there is a need for an alternative method that is of higher throughput and more cost effective. Results In this study, we developed a high resolution melting (HRM assay and evaluated its effectiveness for screening ENU-induced mutations in a medaka TILLING library. We had previously screened mutations in the p53 gene by direct sequencing. Therefore, we first tested the efficiency of the HRM assay by screening mutations in p53, which indicated that the HRM assay is as useful as direct sequencing. Next, we screened mutations in the atr and atm genes with the HRM assay. Nonsense mutations were identified in each gene, and the phenotypes of these nonsense mutants confirmed their loss-of-function nature. Conclusions These results demonstrate that the HRM assay is useful for screening mutations in TILLING. Furthermore, the phenotype of the obtained mutants indicates that medaka is an excellent animal model for investigating genome stability and gene function, especially when combined with TILLING.

  12. Radiation-induced germ-line mutations detected by a direct comparison of parents and children DNA sequences containing SNPs

    International Nuclear Information System (INIS)

    Morimyo, M.; Hongo, E.; Higashi, T.; Wu, J.; Matsumoto, I.; Okamoto, M.; Kawano, A.; Tsuji, S.

    2003-01-01

    Full text: Germ-line mutation is detected in mice but not in humans. To estimate genetic risk of humans, a new approach to extrapolate from animal data to humans or to directly detect radiation-induced mutations in man is expected. We have developed a new method to detect germ-line mutations by directly comparing DNA sequences of parents and children. The nucleotide sequences among mouse strains are almost identical except SNP markers that are detected at 1/1000 frequency. When gamma-irradiated male mice are mated with female mice, heterogeneous nucleotide sequences induced in children DNA are a candidate of mutation, whose assignment can be done by SNP analysis. This system can easily detect all types of mutations such as transition, transversion, frameshift and deletion induced by radiation and can be applied to humans having genetically heterogeneous nucleotide sequences and many SNP markers. C3H male mice of 8 weeks of gestation were irradiated with gamma rays of 3 and 1 Gy and after 3 weeks, they were mated with the same aged C57BL female mice. After 3 weeks breeding, DNA was extracted from parents and children mice. The nucleotide sequences of 150 STS markers containing 300-900 bp and SNPs of parents and children DNA were determined by a direct sequencing; amplification of STS markers by Taq DNA polymerase, purification of PCR products, and DNA sequencing with a dye-terminator method. At each radiation dose, a total amount of 5 Mb DNA sequences were examined to detect radiation-induced mutations. We could find 6 deletions in 3 Gy irradiated mice but not in 1 Gy and control mice. The mutation frequency was about 4.0 x 10 -7 /bp/ Gy or 1.6 x 10 -4 /locus/Gy, and suggested the non-linear increase of mutation rate with dose

  13. Mutations of the resistance to 6-thioguanine after exposure of Chinese hamster cells at G1 phase to x-radiation and subsequent treatment with cytosine arabinoside combined with hydroxyurea

    International Nuclear Information System (INIS)

    Elisova, T.V.; Feoktistova, T.P.; Stavrakova, N.M.

    1988-01-01

    A study was made of the effect of two-hour treatment of Chinese hamster cells with cytosine arabinoside (AraC) combined with hydroxyurea (HU) at the G 1 phase of the cell cycle on lethal and mutagenic effects of X-radiation (50 to 400 cGy). The inhibitors were shown to increase a spontaneous mutation level of the resistance to 6-thioguanine: this increase augmented by 3 times as the time the treatment increased from 1-2 to 6 h. However, while shorply enhancing the inactivating effect of X-radiation (the enhancement coefficient was 2.6) Arac+HU caused an additive, or a somewhat lesser, effect as estimated by the yield of mutations. It is suggested that AraC combined with hydroxyurea fail to modify the radiation-induced premutation damages

  14. Introduction to mutation breeding and genetic research of soybean in China

    International Nuclear Information System (INIS)

    Zhan Mingkui; Zhao Jingrong

    1988-01-01

    This paper summarized the achievements and developments in mutation breeding and genetic research of soybean. The optimal irradiation dosage was determined for 22 varieties of soybean which have been released and popularized so far. Analyses of mutants, mutant characters and mutation frequency in the generations of M 1 , M 2 and M 3 of soybean were carried out and a procedure of mutation breeding was described. Discussion of the effect of different radiant agents, the selection of progeny induced by radiation, the breeding method by combining mutation with hybridization and resistant varieties with good quality ones have been conducted

  15. Mutation breeding in vegetable crops

    International Nuclear Information System (INIS)

    Yamaguchi, Takashi

    1984-01-01

    Vegetables breed by seeds and vegetative organs. In main vegetables, the differentiation of clopping types, the adoption of monoculture and year-round production and shipment are carried out, adapting to various socio-economic and cultivation conditions. Protected agriculture has advanced mainly for fruit vegetables, and the seeds for sale have become almost hybrid varieties. Reflecting the situation like this, the demand for breeding is diversified and characteristic, and the case of applying mutation breeding seems to be many. The present status of the mutation breeding of vegetables is not yet well under way, but about 40 raised varieties have been published in the world. The characters introduced by induced mutation and irradiation were compact form, harvesting aptitude, the forms and properties of stems and leaves, anti-lodging property, the size, form and uniformity of fruits, male sterility and so on. The radiation sources used were mostly gamma ray or X-ray, but sometimes, combined irradiation was used. As the results obtained in Japan, burdocks as an example of gamma ray irradiation to seeds, tomatoes as an example of inducing the compound resistance against disease injury and lettuces as an example of internal beta irradiation are reported. (Kako, I.)

  16. Improvement of new and traditional industrial crops by induced mutations and related biotechnology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-08-01

    Industrial crops are an important source of income for many small landholders in developing countries and contribute directly or indirectly to food security in rural areas. Crop diversification, finding alternative crops, development of new uses for existing crops and introduction of new crops are important components in the efforts to meet the demand for food, pharmaceuticals, chemical raw materials, fibres and fuel in developing and developed countries. Plant breeding efforts combining genetic resources and induced mutations using classical, in vitro and innovative molecular approaches have been responsible for much of the development of industrial crops. This co-ordinated research project (CRP) was initiated in 1994. It focused on developing mutagenesis approaches for previously unstudied species, screening procedures for agricultural and industrial requirements and suitable genotypes of traditional industrial crops adapted to new areas and for new needs. The industrial crops selected for improvement under this CRP were oilseeds and fibre plants. The potential of induced mutations to affect critical steps in various biosynthetic pathways leading to oil quality and other metabolic modifications was investigated. The success of this CRP is evidenced by the application of mutation techniques, in combination with in vitro and molecular techniques in genetic improvement of oilseed crops such as soybean, rapeseed, sunflower, linseed, cuphea, meadowfoam and fibre plants such as cotton and jute. As a result, improved breeding lines are available in all the industrial crops that the CRP focused on. Novel oil types were developed in cuphea with potential use as a renewable, economical and safe energy source and in linseed with increased levels of saturated fatty acids. Genes of fatty acid synthesis were isolated from one species and used for modification of quality of other oilseeds. Disease and pest resistance was improved in oilseeds and fibre crops through transgenesis

  17. Improvement of new and traditional industrial crops by induced mutations and related biotechnology

    International Nuclear Information System (INIS)

    2003-08-01

    Industrial crops are an important source of income for many small landholders in developing countries and contribute directly or indirectly to food security in rural areas. Crop diversification, finding alternative crops, development of new uses for existing crops and introduction of new crops are important components in the efforts to meet the demand for food, pharmaceuticals, chemical raw materials, fibres and fuel in developing and developed countries. Plant breeding efforts combining genetic resources and induced mutations using classical, in vitro and innovative molecular approaches have been responsible for much of the development of industrial crops. This co-ordinated research project (CRP) was initiated in 1994. It focused on developing mutagenesis approaches for previously unstudied species, screening procedures for agricultural and industrial requirements and suitable genotypes of traditional industrial crops adapted to new areas and for new needs. The industrial crops selected for improvement under this CRP were oilseeds and fibre plants. The potential of induced mutations to affect critical steps in various biosynthetic pathways leading to oil quality and other metabolic modifications was investigated. The success of this CRP is evidenced by the application of mutation techniques, in combination with in vitro and molecular techniques in genetic improvement of oilseed crops such as soybean, rapeseed, sunflower, linseed, cuphea, meadowfoam and fibre plants such as cotton and jute. As a result, improved breeding lines are available in all the industrial crops that the CRP focused on. Novel oil types were developed in cuphea with potential use as a renewable, economical and safe energy source and in linseed with increased levels of saturated fatty acids. Genes of fatty acid synthesis were isolated from one species and used for modification of quality of other oilseeds. Disease and pest resistance was improved in oilseeds and fibre crops through transgenesis

  18. Reversal or protection by light of the ethidium bromide induced petite mutation in yeast

    International Nuclear Information System (INIS)

    Hixon, S.C.; Burnham, A.D.; Irons, R.L.

    1979-01-01

    An intermediate in the ethidium bromide (EB) induced petite mutation pathway may be destabilized by daylight light to cause a reversion to the normal grande phenotype. Starved cells preincubated in the dark for up to 6 h with 100μg/ml EB could be reverted to grandes after one hour of light exposure, whereas similarly treated cells maintained in the dark expresse the petite mutation in more than 80 percent of the population. In addition, the production of petite mutants by EB in buffer could be prevented if cell suspensions were exposed to light immediately upon the addition of EB. Photoreversal of the EB-derived petite mutation in growing cells as less efficient presumably because the availability of an energy source caused a continuation of mutation events beyond the light revertible step to a non-reversible fixation of the mutation. Cells treated with EB in growth and reversal of the mutation. This may be due to the cold inhibition of an enzyme which comes into play beyond the light sensitive step in the mutation pathway. (orig.) [de

  19. 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

  20. Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics.

    Science.gov (United States)

    Pakula, Kevin K; Hansen, Lykke H; Vester, Birte

    2017-09-01

    Several groups of antibiotics inhibit bacterial growth by binding to bacterial ribosomes. Mutations in ribosomal protein L3 have been associated with resistance to linezolid and tiamulin, which both bind at the peptidyl transferase center in the ribosome. Resistance to these and other antibiotics also occurs through methylation of 23S rRNA at position A2503 by the methyltransferase Cfr. The mutations in L3 and the cfr gene have been found together in clinical isolates, raising the question of whether they have a combined effect on antibiotic resistance or growth. We transformed a plasmid-borne cfr gene into a uL3-depleted Escherichia coli strain containing either wild-type L3 or L3 with one of seven mutations, G147R, Q148F, N149S, N149D, N149R, Q150L, or T151P, expressed from plasmid-carried rplC genes. The L3 mutations are well tolerated, with small to moderate growth rate decreases. The presence of Cfr has a very minor influence on the growth rate. The resistance of the transformants to linezolid, tiamulin, florfenicol, and Synercid (a combination of quinupristin and dalfopristin [Q-D]) was measured by MIC assays. The resistance from Cfr was, in all cases, stronger than the effects of the L3 mutations, but various effects were obtained with the combinations of Cfr and L3 mutations ranging from a synergistic to an antagonistic effect. Linezolid and tiamulin susceptibility varied greatly among the L3 mutations, while no significant effects on florfenicol and Q-D susceptibility were seen. This study underscores the complex interplay between various resistance mechanisms and cross-resistance, even from antibiotics with overlapping binding sites. Copyright © 2017 American Society for Microbiology.

  1. UVA-induced mutational spectra in the laci gene from transgenic mouse skin

    International Nuclear Information System (INIS)

    Gorelick, N.J.; O'Kelly, J.A.; Biedermann, K.A.

    1995-01-01

    The UVB (295-320 nm) component of sunlight was once thought to be the sole cause of photoaging and skin cancer. However, there is now compelling evidence to suggest that chronic irradiation with UVA (320-400 nm) is a significant component of the etiologies of these diseases. To identify acute markers of UVA damage, we investigated UVA-induced mutagenesis in vivo by using a lacI transgenic mouse mutation assay. The backs of adult female C57BL/6 Big Blue reg-sign mice were shaved and exposed daily to a low or a high dose of UVA for 5 consecutive days. One group remained unexposed. The high dose of UVA significantly increased the mutant frequency in skin determined 12 days after the last exposure. Mutant frequencies were (Avg ± SEM, n=7-8/group): 6.1 ± 0.5 x 10 -5 (high dose). DNA sequence analysis of mutant lacI genes demonstrated that the high dose of UVA produced a different mutational spectrum compared to control. The mutational spectrum from the low dose mutants was not different from the control spectrum in skin generated previously; the predominant classes of recovered mutations were GC→At transitions at CpG sites (11/35) and GC →TA transversions (12/35). In contrast, in the high dose group, GC →AT transitions at non-CpG sites predominated (61/97 mutations); three tandem base substitutions (1 GG →AA; 2 CC→TT) were uniquely recovered; and an increased frequency of recovered GC→CG substitutions was observed (12/97 vs. none in controls). The recovered high dose spectrum is consistent with the types of DNA damage generated by UVA as well as by reactive oxygen species. These studies demonstrate that UVA is mutagenic in vivo and that this assay can be used to study early events in UVA-induced skin damage

  2. Enlargement of induced variations by combined method of chronic irradiations with callus culture in sugarcane

    International Nuclear Information System (INIS)

    Nagatomi, Shigeki

    1993-01-01

    The present study was conducted to elucidate the effects of gamma ray irradiation and callus culture upon induced variation of the regeneratives. The populations regenerated from young leaf tissue of chronic irradiated plnats grown under a gamma field receiving a total dose of 300 and 100 Gy, showed rather wider variation on quantitative characters than plants from populations of the non-irradiated. This variation extended in both negative and positive directions. Analysis of variance also revealed that variation and heritability in broad sense of most agronomic characters increased significantly among the subclones as the irradiation done rose. Principal component analysis also indicated that the subclones from the irradiated population were more variable than the non-irradiated. Such variation with higher heritability could be transmitted to the following generations by clonal propagation and utilized as genetic sources in mutation breeding. The combined method with chronic irradiation followed by tissue culture is evaluated as an effective method of widening mutation spectrum and increasing mutation frequency in regenerated plants. In addition, this method is valid to improve any crop species which can regenerate plants through callus culture. (author)

  3. 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

  4. 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.

  5. 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

  6. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Sankaranarayanan, K. (Rijksuniversiteit Leiden (Netherlands). Dept. of Radiation Genetics and Chemical Mutagenesis; Cohen (J.A.) Inst. voor Radiopathologie en Stralenbescherming, Leiden (Netherlands))

    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.

  8. Spectrum and frequency of chlorophyll mutations in urdbean (Vigna mungo L. Hepper) induced by EMS and gamma rays

    International Nuclear Information System (INIS)

    Sharma, A.K.; Singh, V.P.; Sarma, M.K.

    2006-01-01

    In mutation breeding experiment, plants with altered characteristics such as chlorophyll changes, sterility, plant lethality etc. could be the marker of the mutability of a variety. In fact, spectrum and frequency of chlorophyll mutations have been studied in the great detail. The chlorophyll mutation is the clear-cut indication of non-directional nature of mutation and possibility of induction of useful mutations. The spectrum and frequency of chlorophyll mutation was estimated by using gamma rays (100, 200, 300 and 400 Gy doses), EMS (0.2, 0.4, 0.6 and 0.8%) and combination of gamma rays (100, 200, 300 400 Gy) with 0.2 % concentration EMS on two cultivars, namely, Pant Urd-19 and Pant Urd-30 of urdbean ( Vigna mungo L. Hepper). Five different types of chlorophyll mutations viz., albina, xantha, viridis, chlorina and maculata were identified in both the cultivars. Almost all the combination treatments produced maximum frequency and wider spectrum of chlorophyll mutations followed by single treatment of gamma rays or EMS. The frequency of chlorophyll mutation increased with higher doses of mutagens but decreased at highest dose. Proc. Nat. Acad. Sci. India. 76(8), I, 2006. 64-68. (author)

  9. 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

  10. Mutation induction by and mutational interaction between monochromatic wavelength radiations in the near-ultraviolet and visible ranges

    International Nuclear Information System (INIS)

    Tyrrell, R.M.

    1980-01-01

    The induction of mutations (reversion to tryptophan independence) by various UV (254, 313, 334 and 365 nm) and visible (405 and 434 nm) wavelengths was measured in exponential phase populations of Escherichia coli B/r thy trp and B/r thy trp uvr A by assay of irradiated populations on semi-enriched media. No mutations were induced in the repair proficient strain at wavelengths longer than 313 nm. Mutations were induced to the excisionless strain at wavelengths as long as 405 nm but less than expected from the known amount of DNA damage induced. Irradiation at the long wavelenths (434, 405, 365 and 334 nm) suppressed the appearance of 254- or 313 nm-induced mutations in the repair competent strain but not in the excision deficient strain. The relative dose-requirement for mutation suppression was related to the relative efficiency of these wavelengths in inducing growth delay. These results suggest that the growth delay induced by near-UV and visible wavelenghts allows more time for the 'error-free' excision repair process to act on the potentially mutagenic lesions induced by 254- and 313-nm radiations, thereby reducing the mutation frequency observed in the repair-proficient strain. The level of near-UV mutation induced in the excision deficient strain is lower than expected from the DNA damage known to be induced. It is possible that near-UV radiation induces a class of lethal lesions that are not susceptible to error-prone repair. (author)

  11. 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)

  12. Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients

    International Nuclear Information System (INIS)

    Dumaz, N.; Drougard, C.; Sarasin, A.; Daya-Grosjean, L.

    1993-01-01

    The UV component of sunlight is the major carcinogen involved in the etiology of skin cancers. The authors have studied the rare, hereditary syndrome xeroderma pigmentosum (XP), which is characterized by a very high incidence of cutaneous tumors on exposed skin at an early age, probably due to a deficiency in excision repair of UV-induced lesions. It is interesting to determine the UV mutation spectrum in XP skin tumors in order to correlate the absence of repair of specific DNA lesions and the initiation of skin tumors. The p53 gene is frequently mutated in human cancers and represents a good target for studying mutation spectra since there are >100 potential sites for phenotypic mutations. Using reverse transcription-PCR and single-strand conformation polymorphism to analyze >40 XP skin tumors (mainly basal and squamous cell carcinomas), the authors have found that 40% (17 out of 43) contained at least one point mutation on the p53 gene. All the mutations were located at dipyrimidine sites, essentially at CC sequences, which are hot spots for UV-induced DNA lesions. Sixty-one percent of these mutations were tandem CC → TT mutations considered to be unique to UV-induced lesions; these mutations are not observed in internal human tumors. All the mutations, except two, must be due to translesion synthesis of unrepaired dipyrimidine lesions left on the nontranscribed strand. These results show the existence of preferential repair of UV lesions [either pyrimidine dimers or pyrimidine-pyrimidone (6-4) photoproducts] on the transcribed strand in human tissues

  13. Mutagenesis applied to improve fruit trees. Techniques, methods and evaluation of radiation-induced mutations

    International Nuclear Information System (INIS)

    Donini, B.

    1982-01-01

    Improvement of fruit tree cultivars is an urgent need for a modern and industrialized horticulture on which is based the economic importance of many countries. Both the cross breeding and the mutation breeding are regarded as the methods to be used for creating new varieties. Research carried out at the CNEN Agriculture Laboratory on mutagenesis to improve vegetatively propagated plants, under the FAO-IAEA Co-ordinated Research Programme, has dealt with methods of exposure, types of radiations, conditions during and after the irradiation, mechanisms of mutation induction, methodology of isolation of somatic mutations and evaluation of radiation-induced mutations in fruit trees. Problems associated with these aspects have been evaluated, which is very important for the more efficient use of radiation in the mutation breeding. Mutants of agronomical importance (plant size reduction, early ripening, fruit colour change, nectarine fruit, self-thinning fruit) have been isolated in cherry, grape, apple, olive and peach and they are ready to be released. (author)

  14. P53 Gene Mutation as Biomarker of Radiation Induced Cell Injury and Genomic Instability

    International Nuclear Information System (INIS)

    Mukh-Syaifudin

    2006-01-01

    Gene expression profiling and its mutation has become one of the most widely used approaches to identify genes and their functions in the context of identify and categorize genes to be used as radiation effect markers including cell and tissue sensitivities. Ionizing radiation produces genetic damage and changes in gene expression that may lead to cancer due to specific protein that controlling cell proliferation altered the function, its expression or both. P53 protein encoded by p53 gene plays an important role in protecting cell by inducing growth arrest and or cell suicide (apoptosis) after deoxyribonucleic acid (DNA) damage induced by mutagen such as ionizing radiation. The mutant and thereby dysfunctional of this gene was found in more than 50% of various human cancers, but it is as yet unclear how p53 mutations lead to neoplastic development. Wild-type p53 has been postulated to play a role in DNA repair, suggesting that expression of mutant forms of p53 might alter cellular resistance to the DNA damage caused by radiation. Moreover, p53 is thought to function as a cell cycle checkpoint after irradiation, also suggesting that mutant p53 might change the cellular proliferative response to radiation. P53 mutations affect the cellular response to DNA damage, either by increasing DNA repair processes or, possibly, by increasing cellular tolerance to DNA damage. The association of p53 mutations with increased radioresistance suggests that alterations in the p53 gene might lead to oncogenic transformation. Current attractive model of carcinogenesis also showed that p53 gene is the major target of radiation. The majority of p53 mutations found so far is single base pair changes ( point mutations), which result in amino acid substitutions or truncated forms of the p53 protein, and are widely distributed throughout the evolutionary conserved regions of the gene. Examination of p53 mutations in human cancer also shows an association between particular carcinogens and

  15. Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

    Science.gov (United States)

    Kuzin, Boris A; Nikitina, Ekaterina A; Cherezov, Roman O; Vorontsova, Julia E; Slezinger, Mikhail S; Zatsepina, Olga G; Simonova, Olga B; Enikolopov, Grigori N; Savvateeva-Popova, Elena V

    2014-01-01

    Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

  16. Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

    Directory of Open Access Journals (Sweden)

    Boris A Kuzin

    Full Text Available Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

  17. Therapy-Induced Growth and Sexual Maturation in a Developmentally Infantile Adult Patient with a PROP1 Mutation

    Directory of Open Access Journals (Sweden)

    Ludmila Brunerova

    2017-11-01

    Full Text Available BackgroundHypopituitarism as a result of PROP1 (prophet of PIT1 mutation represents the most common genetic cause of combined deficiency of pituitary hormones and due to growth retardation it is typically diagnosed in childhood.Case descriptionWe present a unique case report of a prepubertal woman with growth retardation in whom combined pituitary hormone deficiency [central hypopituitarism, hypogonadism, and growth hormone (GH deficiency] caused by homozygous mutation c.150delA in the PROP1 gene was diagnosed late in young adulthood due to unfavorable life circumstances. Through cautiously combined GH therapy and sex hormone therapy, she has achieved better than expected height (exceeding predictions based on family height and sexual maturation, including regular menstrual cycles.ConclusionEarly diagnosis of panhypopituitarism due to PROP1 mutation is essential for successful treatment; however, our case report shows that carefully titrated GH treatment and sex hormone substitution, although initiated in adulthood, enable restoration of physiological growth and sexual development in a hormonally infantile adult woman with a PROP1 mutation.

  18. A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells

    NARCIS (Netherlands)

    Kuijpers, Taco W.; van Leeuwen, Ester M. M.; Barendregt, Barbara H.; Klarenbeek, Paul; Aan de Kerk, Daan J.; Baars, Paul A.; Jansen, Machiel H.; de Vries, Niek; van Lier, René A. W.; van der Burg, Mirjam

    2013-01-01

    Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined

  19. 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

  20. Mutations in plant breeding: a glance back and a look forward

    International Nuclear Information System (INIS)

    Gustafsson, A.

    1975-01-01

    This brief retrospect of previous shortcomings and procedures really indicates the need for a better co-ordination and co-operation in plant breeding. We now know which mutagens are essential in practical mutation work, and we include radiations as well as chemicals. We now know that there is no principal difference between natural and induced variation. We can easily induce mutational events covering the gap between gross chromosomal rearrangements and DNA-base substitutions. We also know that induced variation may in the future fill and replace the loss of natural variability, or may even extend the limits of variation. We know that mutation and recombination--as evidenced, for instance, by the successful work in barley--will be united into routine procedures, also leading to new breakthroughs in plant improvement. Moreover, ingenious techniques of mass testing are under way, combining traditional and prospective ideas. The mutation method has come to stay, not alone but with gene recombination, with heterosis and with polyploidy. We say that the present is the past's future. To glance back is then to look forward; failures give rise to progress. A synthesis of breeding methods is around the corner

  1. X irradiation combined with TNF alpha-related apoptosis-inducing ligand (TRAIL) reduces hypoxic regions of human gastric adenocarcinoma xenografts in SCID mice

    International Nuclear Information System (INIS)

    Takahashi, Momoko; Yasui, Hironobu; Ogura, Aki; Asanuma, Taketoshi; Inanami, Osamu; Kubota, Nobuo; Tsujitani, Michihiko; Kuwabara, Mikinori

    2008-01-01

    Our previous study showed that X irradiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines under not only normoxia but also hypoxia. X irradiation combined with TNF α-related apoptosis-inducing ligand (TRAIL), which is the ligand of DR5, induced apoptosis in vitro (Takahashi et al., (2007) Journal of Radiation Research, 48: 461-468). In this report, we examined the in vivo antitumor efficacy of X irradiation combined with TRAIL treatment in tumor xenograft models derived from human gastric adenocarcinoma MKN45 and MKN28 cells in severe combined immunodeficiency (SCID) mice. X irradiation combined with TRAIL synergistically suppressed the tumor growth rates in the xenograft models derived from MKN45 and MKN28 cells, which have wild type Tp53 and mutated Tp53, respectively, indicating that the antitumor effects occurred in a Tp53-independent manner. Histological analysis showed that the combination of X irradiation and TRAIL induced caspase-3-dependent apoptotic cell death. Moreover, the immunohistochemical detection of hypoxic regions using the hypoxic marker pimonidazole revealed that caspase-3-dependent apoptosis occurred in the hypoxic regions in the tumors. These results indicated that X irradiation combined with TRAIL may be a useful treatment to reduce tumor growth in not only normoxic but also hypoxic regions. (author)

  2. The latest progress of TILLING technique and its prospects in irradiation mutation breeding

    International Nuclear Information System (INIS)

    Du Yan; Yu Lixia; Liu Qingfang; Zhou Libin; Li Wenjian

    2011-01-01

    TILLING (Targeting Induced Local Lesions IN Genomes) is a novel, high-throughput and low-cost reverse genetics technique. In recent years, with innovation of the mutation screening techniques, TILLING platform has become more diversified, which makes the operation of TILLING technique more simple and rapid. For this reason, it is widely used in crop breeding research. In this paper, we summarized the latest progress of TILLING technique, meanwhile, we also discussed the prospect of combining irradiation mutation with the high-throughput TILLING technique in mutation breeding. (authors)

  3. Combining structural modeling with ensemble machine learning to accurately predict protein fold stability and binding affinity effects upon mutation.

    Directory of Open Access Journals (Sweden)

    Niklas Berliner

    Full Text Available Advances in sequencing have led to a rapid accumulation of mutations, some of which are associated with diseases. However, to draw mechanistic conclusions, a biochemical understanding of these mutations is necessary. For coding mutations, accurate prediction of significant changes in either the stability of proteins or their affinity to their binding partners is required. Traditional methods have used semi-empirical force fields, while newer methods employ machine learning of sequence and structural features. Here, we show how combining both of these approaches leads to a marked boost in accuracy. We introduce ELASPIC, a novel ensemble machine learning approach that is able to predict stability effects upon mutation in both, domain cores and domain-domain interfaces. We combine semi-empirical energy terms, sequence conservation, and a wide variety of molecular details with a Stochastic Gradient Boosting of Decision Trees (SGB-DT algorithm. The accuracy of our predictions surpasses existing methods by a considerable margin, achieving correlation coefficients of 0.77 for stability, and 0.75 for affinity predictions. Notably, we integrated homology modeling to enable proteome-wide prediction and show that accurate prediction on modeled structures is possible. Lastly, ELASPIC showed significant differences between various types of disease-associated mutations, as well as between disease and common neutral mutations. Unlike pure sequence-based prediction methods that try to predict phenotypic effects of mutations, our predictions unravel the molecular details governing the protein instability, and help us better understand the molecular causes of diseases.

  4. The breeding of Japonica Yanjing 10 rice mutant induced by space mutation

    International Nuclear Information System (INIS)

    Wang Jianhua; Chen Xiulan; Zhang Rong; Wang Jinrong; Liu Jian; Jiao Juan; He Zhentian; Wang Lin

    2011-01-01

    The dry seed of mid-maturing Japonica rice Yanjing 10 was used for space mutation breeding which was carried by a satellite for 15 days in 2006. Through three generations of breeding, a group of mutants were obtained. In the article, we reported in detail the breeding procedures, proposed the breeding technical method for space mutation for rice improvement. Planting multiple seedlings per hill to prohibit tillering at SP 1 generation, and bulked selection in combination with directional selection at the SP 2 ∼ SP 3 generation were the two key points of the breeding methods. (authors)

  5. The combination of heteroduplex analysis and protein truncation test for exact detection of the APC gene mutations

    International Nuclear Information System (INIS)

    Tomka, M.; Kirchhoff, T.; Stefurkova, V.; Zajac, V.; Kulcsar, L.

    1998-01-01

    Familial adenomatous polyposis (FAP) is usually associated with mutation in the adenomatous polyposis coli (APC) gene. To examine the occurrence of these mutations in the number of FAP suspected families from the whole Slovakia effectively, we have applied heteroduplex analysis (HDA) and protein truncation test (PTT) for the analyses of 2-5 base pair deletions and point mutations of the APC gene. In the analyzed exon 15 of the APC gene determined by the primers 15Efor-15Grev for HDA and 15ET7-15J3 for PTT more than 70% of mutations should be deletions [3, 12], which are detectable by HDA. In our collection of 5 FAP families mutations in the APC gene were found in families 10, 27 and 41 using HDA. By PTT test the formation of truncated APC protein in FAP families 2, 10, 16 and 27 were revealed. The necessity of combination of at least HDA and PTT techniques for exact detection of APC mutations in analyzed APC region is discussed. (authors)

  6. 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

    Inhalation of particles has been shown to induce mutations in the male germline in mice following both prenatal and adult exposures in several experiments. In contrast, the effects of particles on female germ cell mutagenesis are not well established. Germline mutations are induced during active...... cell division, which occurs during fetal development in females. We investigated the effects of prenatal exposure to carbon black nanoparticles (CB) on induction of mutations in the female mouse germline during fetal development, spanning the critical developmental stages of oogenesis. Pregnant C57BL/6...... 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....

  7. Synergistic effects of methyl methanesulfonate and X rays in inducing somatic mutations in the stamen hairs of Tradescantia clones, KU 27 and BNL 4430

    International Nuclear Information System (INIS)

    Ichikawa, Sadao; Yamaguchi, Akihiko; Okumura, Mikiko

    1993-01-01

    Young influorescences of Tradescantia clones KU 27 and BNL 4430, the both of which are blue/pink heterozygotes and have been demonstrated to be highly sensitive to alkylating agents, were exposed either to aqueous solutions of methyl methanesulfonate (MMS) for 16 hr alone (at 0.005 to 0.02% for KU 27 and at 0.005% for BNL 4430) or to acute 150 kVp X rays alone (161 to 531 mGy for Ku 27 and 501 to 976 mGy for BNL 4430), or in combinations (134 to 448 mGy for KU 27 and 458 to 865 mGy for BNL 4430 after the 0.005% MMS treatment). The induced somatic pink mutation frequencies per hair-cell division were studied and compared, and clone BNL 4430 was found to be nearly two times more sensitive to MMS than clone KU 27, while the X-ray-induced mutation frequencies in the latter was about 1.5 times higher than those in the former. The lower sensitivity to MMS of clone KU 27 (as compared with BNL 4430) was nevertheless about 5.6 times higher as compared with the responses of clone BNL 02 to MMS reported earlier, proving the high sensitivities of the two clones used in the present study. Clear synergistic effects of MMS and X rays were observed in the both clones, indicating that the mechanisms of inducing mutations are common at least in part between MMS and X rays. (author)

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

    Science.gov (United States)

    Stamo, Ilirjana; Ylli, Ariana; Dodbiba, Andon

    2007-04-01

    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.

  9. 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

  10. Multi-mutational model for cancer based on age-time patterns of radiation effects: 2. Biological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L.; Pierce, P.A.

    1997-09-04

    Biological properties of relevance when modeling cancers induced in the atom bomb survivors include the wide distribution of the induced cancers across all organs, their biological indistinguishability from background cancers, their rates being proportional to background cancer rates, their rates steadily increasing over at least 50 years as the survivors age, and their radiation dose response being linear. We have successfully described this array of properties with a modified Armitage-Doll model using 5 to 6 somatic mutations, no intermediate growth, and the dose-related replacement of any one of these time-driven mutations by a radiation-induced mutation. Such a model is contrasted to prevailing models that use fewer mutations combined with intervening growth. While the rationale and effectiveness of our model is compelling for carcinogenesis in the atom bomb survivors, the lack of a promotional component may limit the generality of the model for other types of human carcinogenesis.

  11. 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.

  12. 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

  13. RGE of fission neutrons under the recessive mutation induction in Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Aleksandrov, I.D.; Aleksandrova, M.V.; Lapidus, I.L.; Korablinova, S.V.; )

    2001-01-01

    The RCR-analysis of 81 γ- and neutron-induced vg recessive mutations in ripe sperm of Drosophila melanogaster males of combined with complementation assay with the vg[nw83b27] deletion mutation is used to detect precisely the RGE values of neutrons (0.85 MeV) under the chromosome and point mutation induction. The results obtained show that all genetic end-points increase linearly with γ-ray and neutron dose. Thereby, the efficacy of neutrons is found to be twice (and more) as large as that of γ-rays under the all macro- and micro-aberration mutation induction. Unlike that, the RGE of neutrons are more than twice as low as that of γ-rays under the gene/point mutation induction [ru

  14. Mutation breeding in vegetable crops

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Takashi

    1984-03-01

    Vegetables breed by seeds and vegetative organs. In main vegetables, the differentiation of clopping types, the adoption of monoculture and year-round production and shipment are carried out, adapting to various socio-economic and cultivation conditions. Protected agriculture has advanced mainly for fruit vegetables, and the seeds for sale have become almost hybrid varieties. Reflecting this situation, the demand for breeding is diversified and characteristic. The present status of mutation breeding of vegetables is not yet well under way, but reports of about 40 raised varieties have been published in the world. The characters introduced by induced mutation and irradiation are compact form, harvesting aptitude, the forms and properties of stems and leaves, anti-lodging property, the size, form and uniformity of fruits, male sterility and so on. The radiation sources used were mostly gamma ray or X-ray, but sometimes, combined irradiation was used. Results obtained in Japan include: burdocks as an example to gamma ray irradiation of seeds; tomatoes as an example of inducing compound resistance against disease injury; and lettuce as an example of internal beta irradiation. (Kako, I.).

  15. Elastatinal and leupeptin: effects on u.v.-induced mutation and sister-chromatid exchanges in Chinese hamster cells

    International Nuclear Information System (INIS)

    Paul, P.; Fujiwara, Y.

    1981-01-01

    Microbial protease inhibitors elastatinal and leupeptin were tested for cytotoxicity and for effects on spontaneous and u.v.-induced 6-thioguanine-resistant (6TGsup(r)) mutation and sister-chromatid exchange (SCE) in V79 Chinese hamster cells. Continuous treatment with elastatinal exhibited marked cytotoxicity, while leupeptin was almost non-cytotoxic. Elastatinal rapidly induced cytotoxic effects as a function of its concentration and time of exposure. Near maximum cytotoxicity was reached after exposures of 6-8 h and this was partially abolished by the presence of 2.5 μg cycloheximide per ml. Concentrations of either protease inhibitor which gave 60-80% survival had no appreciable effects on u.v. survival and frequencies of spontaneous and u.v.-induced 6TGsup(r) mutation and SCE. However, reconstruction experiments revealed that pretreatments of 6TGsup(r) and 6TGsup(s) (wild-type) cells with these inhibitors for 6 days tended to block metabolic co-operation in their co-cultures. Thus, elastatinal and leupeptin are neither clastogenic nor mutagenic by themselves, and do not alter mutation fixation and expression. (author)

  16. Elastatinal and leupeptin: effects on u.v.-induced mutation and sister-chromatid exchanges in Chinese hamster cells

    International Nuclear Information System (INIS)

    Paul, P.; Fujiwara, Y.

    1981-01-01

    Microbial protease inhibitors elastatinal and leupeptin were tested for cytotoxicity and for effects on spontaneous and u.v.-induced 6-thioguanine-resistant (6TGr) mutation and sister-chromatid exchange (SCE) in V79 Chinese hamster cells. Continuous treatment with elastatinal exhibited marked cytotoxicity, while leupeptin was almost non-cytotoxic. Elastatinal rapidly induced cytotoxic effects as a function of its concentration and time of exposure. Near maximum cytotoxicity was reached after exposure of 6-8 h and this was partially abolished by the presence of 2.5 micrograms cycloheximide per ml. Concentrations of either protease inhibitor which gave 60-80% survival had no appreciable effects on u.v. survival and frequencies of spontaneous and u.v.-induced 6TGr mutation and SCE. However, reconstruction experiments revealed that pretreatments of 6TGr and 6TGs (wild-type) cells with these inhibitors for 6 days tended to block metabolic co-operation in their co-cultures. Thus, elastatinal and leupeptin are neither clastogenic mutagenic by themselves, and do not alter mutation fixation and expression

  17. Effect of genes controlling radiation sensitivity on chemically induced mutations in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Prakash, L.

    1976-01-01

    The effect of 16 different genes (rad) conferring radiation sensitivity on chemically induced reversion in the yeast Saccharomyces cerevisiae was determined. The site of reversion used was a well-defined chain initiation mutant mapping in the structural gene coding for iso-1-cytochrome c. High doses of EMS and HNO 2 resulted in decreased reversion of cyc1-131 in rad6, rad9 and rad15 strains compared to the normal RAD + strains. In addition, rad52 greatly decreased EMS reversion of cyc1-131 but had no effect on HNO 2 -induced reversion; rad18, on the other hand, increased HNO 2 -induced reversion but did not alter EMS-induced reversion. When NQO was used as the mutagen, every rad gene tested, except for rad18, had an effect on reversion; rad6, rad9, rad15, rad17, rad18, rad22, rev1, rev2, and rev3 lowered NQO reversion while rad1, rad2, rad3, rad4, rad10, rad12, and rad16 increased it compared to the RAD + strain. The effect of rad genes on chemical mutagenesis is discussed in terms of their effect on uv mutagenesis. It is concluded that although the nature of the repair pathways may differ for uv- and chemically-induced mutations in yeast, a functional repair system is required for the induction of mutation by the chemical agents NQO, EMS, and HNO 2

  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. 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)

  20. 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.

  1. Embryonic left-right separation mechanism allows confinement of mutation-induced phenotypes to one lateral body half of bilaterians.

    Science.gov (United States)

    Ma, Kun

    2013-12-01

    A fundamental question in developmental biology is how a chimeric animal such as a bilateral gynandromorphic animal can have different phenotypes confined to different lateral body halves, and how mutation-induced phenotypes, such as genetic diseases, can be confined to one lateral body half in patients. Here, I propose that embryos of many, if not all, bilaterian animals are divided into left and right halves at a very early stage (which may vary among different types of animals), after which the descendants of the left-sided and right-sided cells will almost exclusively remain on their original sides, respectively, throughout the remaining development. This embryonic left-right separation mechanism allows (1) mutations and the mutation-induced phenotypes to be strictly confined to one lateral body half in animals and humans; (2) mothers with bilateral hereditary primary breast cancer to transmit their disease to their offspring at twofold of the rate compared to mothers with unilateral hereditary breast cancer; and (3) a mosaic embryo carrying genetic or epigenetic mutations to develop into either an individual with the mutation-induced phenotype confined unilaterally, or a pair of twins displaying complete, partial, or mirror-image discordance for the phenotype. Further, this left-right separation mechanism predicts that the two lateral halves of a patient carrying a unilateral genetic disease can each serve as a case and an internal control, respectively, for genetic and epigenetic comparative studies to identify the disease causations. © 2013 Wiley Periodicals, Inc.

  2. Frequency and spectrum of chlorophyll-deficient mutations in rice after treatment with radiation and alkylating agents

    International Nuclear Information System (INIS)

    Bhan, A.K.; Kaul, M.L.H.

    1976-01-01

    Three varieties of rice were treated with gamma rays and two alkylating agents EMS and DES, separately and in combinations, with a view to finding out the frequency and spectrum of chlorophyll mutations in relation to the genotype and the nature of the mutagen. Chlorophyll mutation frequency was enhanced with increasing dose but dropped at very high doses (doses that induced over 90% seeding lethality in M 1 ). The fall was attributed to either the increased mutated sector and diplontic selection after exposure to very high doses or relatively high resistance of some of the seeds. Among chlorophyll mutants in M 2 induced by radiations as well as alkylating agents, the albina type formed the majority class. EMS induced a significantly higher proportion of albinas than did gamma rays

  3. Bystander effect-induced mutagenicity in HPRT locus of CHO cells following BNCT neutron irradiation: Characteristics of point mutations by sequence analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kinashi, Yuko [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka (Japan)], E-mail: kinashi@rri.kyoto-u.ac.jp; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka (Japan)

    2009-07-15

    To investigate bystander mutagenic effects induced by alpha particles during boron neutron capture therapy (BNCT), we mixed cells that were electroporated with borocaptate sodium (BSH), which led to the accumulation of {sup 10}B inside the cells, with cells that did not contain the boron compound. BSH-containing cells were irradiated with {alpha} particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction, whereas cells without boron were only affected by the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. The frequency of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus was examined in Chinese hamster ovary (CHO) cells irradiated with neutrons (Kyoto University Research Reactor: 5 MW). Neutron irradiation of 1:1 mixtures of cells with and without BSH resulted in a survival fraction of 0.1, and the cells that did not contain BSH made up 99.4% of the surviving cell population. Using multiplex polymerase chain reactions (PCRs), molecular structural analysis indicated that most of the mutations induced by the bystander effect were point mutations and that the frequencies of total and partial deletions induced by the bystander effect were lower than those resulting from the {alpha} particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction or the neutron beam from the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. The types of point mutations induced by the BNCT bystander effect were analyzed by cloning and sequencing methods. These mutations were comprised of 65.5% base substitutions, 27.5% deletions, and 7.0% insertions. Sequence analysis of base substitutions showed that transversions and transitions occurred in 64.7% and 35.3% of cases, respectively. G:C{yields}T:A transversion induced by 8-oxo-guanine in DNA occurred in 5.9% of base substitution mutants in the BNCT bystander group. The characteristic mutations seen in this group, induced by BNCT {alpha} particles

  4. 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

  5. Elucidating the Interdependence of Drug Resistance from Combinations of Mutations.

    Science.gov (United States)

    Ragland, Debra A; Whitfield, Troy W; Lee, Sook-Kyung; Swanstrom, Ronald; Zeldovich, Konstantin B; Kurt-Yilmaz, Nese; Schiffer, Celia A

    2017-11-14

    HIV-1 protease is responsible for the cleavage of 12 nonhomologous sites within the Gag and Gag-Pro-Pol polyproteins in the viral genome. Under the selective pressure of protease inhibition, the virus evolves mutations within (primary) and outside of (secondary) the active site, allowing the protease to process substrates while simultaneously countering inhibition. The primary protease mutations impede inhibitor binding directly, while the secondary mutations are considered accessory mutations that compensate for a loss in fitness. However, the role of secondary mutations in conferring drug resistance remains a largely unresolved topic. We have shown previously that mutations distal to the active site are able to perturb binding of darunavir (DRV) via the protein's internal hydrogen-bonding network. In this study, we show that mutations distal to the active site, regardless of context, can play an interdependent role in drug resistance. Applying eigenvalue decomposition to collections of hydrogen bonding and van der Waals interactions from a series of molecular dynamics simulations of 15 diverse HIV-1 protease variants, we identify sites in the protease where amino acid substitutions lead to perturbations in nonbonded interactions with DRV and/or the hydrogen-bonding network of the protease itself. While primary mutations are known to drive resistance in HIV-1 protease, these findings delineate the significant contributions of accessory mutations to resistance. Identifying the variable positions in the protease that have the greatest impact on drug resistance may aid in future structure-based design of inhibitors.

  6. 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)

  7. Selection of the Mutants with High Hydroquinone Degradation Ability of Serratia Marcesscen by Plasma Mutation

    International Nuclear Information System (INIS)

    Yao Risheng; You Qidong; He Weijing; Zhu Huixia

    2009-01-01

    In this study, an efficient way by plasma induced mutation was applied to improve the hydroquinone degradation capacity of Serratia marcescens AB 90027 (SM27). The results showed that combined with the selection of hydroquinone tolerance, the mutant with high hydroquinone degradation ability induced by plasma could be achieved. The best dose for plasma mutation was 15 s, which showed a 47.0% higher positive mutation ratio. Besides, the aimed mutant was markedly different from the parent strain (SM27) in colonial traits while cultivated on Kings media. Finally, the hydroquinone degradation ratio reached 70.5% using the induced mutant strain with 1500 mg/L hydroquinone (HQ) after 15 days of cultivation as the selective conditions; however, it was only 46.7% for SM27. The improvement of the degradation capacity by the induced mutant with a high concentration of HQ selection was attributed to its faster growth and higher hydroquinone tolerance compared with that of the parent strain.

  8. 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

  9. Mutation profiles of phenylketonuria in Quebec populations: Evidence of stratification and novel mutations

    Energy Technology Data Exchange (ETDEWEB)

    Rozen, R.; Mascisch, A.; Scriver, C.R. (McGill Univ., Montreal (Canada)); Lambert, M. (Hopital Ste-Justine, Montreal (Canada)); Laframboise, R. (Centre Hospitalier Universite Laval, Quebec (Canada))

    1994-08-01

    Independent phenylketonuria (PKU) chromosomes (n=109) representing 80% of a proband cohort in Quebec province carry 18 different identified mutations in 20 different mutation/haplotype combinations. The study reported here, the third in a series on Quebec populations, was done in the Montreal region and predominantly on French Canadians. It has identified three novel mutations (A309D, D338Y, and 1054/1055delG [352fs]) and one unusual mutation/RFLP haplotype combination (E280K on Hp 2). The relative frequencies and distribution of PKU mutations were then compared in three regions and population subsets (eastern Quebec, French Canadian; western Quebec, French Canadian; and Montreal, non-French Canadian). The distributions of the prevalent and rare mutations are nonrandom and provide evidence for genetic stratification. The latter and the presence of eight unusual mutation/haplotype combinations in Quebec families with European ancestries (the aforementioned four and M1V, 165T, S349P, and R408W on Hp 1) corroborate demographic and anthropologic evidence, from elsewhere, for different origins of French Canadians in eastern and western Quebec. 29 refs., 1 fig., 1 tab.

  10. DNA replication in necessary for fixing induced mutations to streptomycin-resistance in UV-irradiated Escherichia coli cells

    Energy Technology Data Exchange (ETDEWEB)

    Dubinin, N P; Filippov, V D

    1986-01-01

    A suspension of E.coli cells has been subjected to UV radiation, then it has been incubated in the growth medium for 15 min. After that one of the portions was incubated with nalidixic acid (NA), and the other one without it in the presence of an antibiotic. Frequency of mutations depending on or irrespective of photoactivation, has been determined. Dependence of Str mutation fixing, induced by low UV radiation doses, on DNA synthesis is determined. Results indicate that both photoreactivation of mutations and its senstivity to mfd system are simultaneously lost.

  11. Formaldehyde-induced mutations in Drosophila melanogaster in dependence of the presence of acids

    Energy Technology Data Exchange (ETDEWEB)

    Stumm-Tegethoff, B F.A.

    1969-01-01

    The mutagenic activity of various combinations of formaldehyde, formic acid, acetic acid and hydrochloric acid was investigated by a sex-linked lethal test. All combinations were mutagenic and showed a mutation pattern from which it is concluded that in feeding experiments spermatocytes I are especially sensitive to the pairs of chemicals tested. In vapour experiments all germ cell stages were found to be susceptible. The presence of volatile acids was found to be necessary for the mutagenic activity of formaldehyde in the vapour state. Mutagenic effects were also observed in larval feeding experiments, in which only these acids were added to the medium. Experiments with stabilized pH at 7.5 did not show a significant mutagenic effect of formaldehyde. It is postulated that the tested agents are catalase inhibitors, which promote the formation of peroxides or free radicals which interfere with DNA replication, thus producing mutations.

  12. The induction of somatic mutations by high-LET radiations using the drosophila assay system

    International Nuclear Information System (INIS)

    Yoshikawa, Isao; Takatsuji, Toshihiro

    2004-01-01

    Two types of somatic mutation in Drosophila melanogaster were examined to evaluate the relative biological effectiveness (RBE) of 252 Cf neutrons and heavy ions (carbon ions and neon ions) accelerated with a synchrotron for inducing mutations as a function of linear energy transfer (LET). One is the loss of heterozygosity for wing-hair mutations and the other the reversion of the mutant white-ivory. The measurements were made using a combined mutation assay system; so that induced mutant wing-hair clones as well as revertant eye-color clones could be detected simultaneously in the same fly. Larvae were irradiated at the age of 3 days post-oviposition. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots is very high, RBE=8.5, but that for eye-color mosaic spot is almost equal (RBE=1.2) to that of 137 Cs γ-rays. RBE-LET relationships were obtained for the induction of wing-hair and eye-color mosaic spots. The RBE of carbon and neon ions for producing wing-hair mosaic spots increased with increasing LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damage such as non-rejoinable strand breaks or clustered double strand breaks that increase with LET may be responsible for inducing the wing-hair mutation, while simpler forms of molecular damage may induce reversion in the white-ivory allele. (author)

  13. Application of induced mutations and modern technologies for rice improvement at the Philippine Rice Research Institute (PhilRice)

    International Nuclear Information System (INIS)

    Padolina, Thelma F.

    2015-01-01

    The application of mutation techniques, i.e. gamma rays and other physical and chemical mutagens has generated a vast amount of genetic variability and has played a significant role in plant breeding and genetics. The widespread use of mutation techniques in plant breeding programs throughout the world has led to the official release of more than 3000 mutant varieties from different plant species. These varieties provide higher yields, better quality, resistance to diseases and resilience to climate change and variability. In the Philippine Rice Research Institute (PhilRice), classical induced mutagenesis and/or in combination with modern technologies as an important tool in rice breeding have been widely utilized by breeders. These recent advances offered new and exciting challenges for the development of new varieties. Moreover, it has the advantage of free regulatory restrictions imposed on genetically modified organisms. To date, high generation of new varieties, elite lines and pre-breeding materials have been derived from chemical and physical mutagenesis, another culture, in vitro mutagenesis, and molecular marker technologies. Directly benefitting the farmers are three Philippine released varieties: PSB Rc78 developed through gamma ray induction in year 2000; and NSIC Rc272 (2011) and Rc346 (2013) developed by combination of Co60 induction and another culture technology. These varieties are intended for the lowlands. In the current works, diverse mutant lines and pre-breeding materials of different target traits were generated and are now under evaluation as potential varieties and/or for use in the inbred and hybrid breeding programs. These genetic materials are in the background of traditional and modern rice varieties. Accordingly, for inbreds, mutated traits ranged from changes in morphological traits, yield, maturity, grain quality, nutritional traits, abiotic resistance such as heat, salinity, and drought tolerance, biotic resistance such as bacterial

  14. Biotechnological approach in crop improvement by mutation breeding in Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Soeranto, H.; Sobrizal; Sutarto, Ismiyati; Manurung, Simon; Mastrizal [National Nuclear Energy Agency, Center for Research and Development of Isotope and Radiation Technology, Jakarta (Indonesia)

    2002-02-01

    Mutation breeding has become a proven method of improving crop varieties. Most research on plant mutation breeding in Indonesia is carried out at the Center for Research and Development of Isotope and Radiation Technology, National Nuclear Energy Agency (BATAN). Nowadays, a biotechnological approach has been incorporated in some mutation breeding researches in order to improve crop cultivars. This approach is simply based on cellular totipotency, or the ability to regenerate whole, flowering plants from isolated organs, pieces of tissue, individual cells, and protoplasts. Tissue culture technique has bee extensively used for micro propagation of disease-free plants. Other usage of this technique involves in various steps of the breeding process such as germplasm preservation, clonal propagation, and distant hybridization. Mutation breeding combined with tissue culture technique has made a significant contribution in inducing plant genetic variation, by improving selection technology, and by accelerating breeding time as for that by using anther or pollen culture. In Indonesia, research on mutation breeding combined with tissue culture techniques has been practiced in different crop species including rice, ginger, banana, sorghum etc. Specially in rice, a research on identification of DNA markers linked to blast disease resistance is now still progressing. A compiled report from some research activities is presented in this paper. (author)

  15. RBE-LET relationships of high-LET radiations in drosophila mutations

    International Nuclear Information System (INIS)

    Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Takada, Jun; Endo, Satoru; Hoshi, Masaharu

    1999-01-01

    The relative biological effectiveness (RBE) of 252 Cf neutrons and synchrotron-generated high-energy charged particles for mutation induction was evaluated as a function of linear energy transfer (LET), using the loss of heterozygosity for wing-hair mutations and the reversion of the mutant white-ivory eye-color in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change (2.96 kb-DNA excision) in the white locus on the X-chromosome. The measurements were performed in a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clone can be detected simultaneously in the same individual. Larvae were irradiated at the age of 3 days post oviposition with 252 Cf neutrons, carbon beam or neon beam. For the neutron irradiation, the RBE values for wing-hair mutations were larger than that for eye-color mutation by about 7 fold. The RBE of carbon ions for producing the wing-hair mutations increased with increase in LET. The estimated RBE values were found to be in the range 2 to 6.5 for the wing-hair. For neon beam irradiation, the RBE values for wing-hair mutations peak near 150 keV/μm and decrease with further increase in LET. On the other hand, the RBE values for the induction of the eye-color mutation are nearly unity in 252 Cf neutrons and both ions throughout the LET range irradiated. We discuss the relationships between the initial DNA damage and LET in considering the mechanism of somatic mutation induction. (author)

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Tomonari; Kazama, Yusuke [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Innovation Center, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Ohbu, Sumie; Shirakawa, Yuki; Liu Yang; Kambara, Tadashi; Fukunishi, Nobuhisa [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Abe, Tomoko, E-mail: tomoabe@riken.jp [Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Innovation Center, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2012-07-01

    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 {mu}m{sup -1}. In this study, we irradiated dry seeds of Arabidopsis thaliana with Ar and C ions with an LET of 290 keV {mu}m{sup -1}. We analyzed the DNA alterations caused by the higher-LET radiation. Mutants were identified from the M{sub 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 {mu}m{sup -1} radiations were higher than those of the large deletions induced by lower-LET radiations (6% for 22.5-30.0 keV {mu}m{sup -1} and 27% for 101-124 keV {mu}m{sup -1}). Therefore, the 290 keV {mu}m{sup -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.

  18. Induction of chlorophyll chimeras and chlorophyll mutations in mungbean (Vigna radiata) cv. T44

    International Nuclear Information System (INIS)

    Singh, V.P.; Yadav, R.D.S.

    1993-01-01

    Uniform and healthy seeds of mungbean (Vigna radiata) cv. T44 were exposed to varying doses of gamma rays, ethyl methane sulphonate (EMS) and combination treatment of gamma rays with EMS. The data were recorded for seed germination, plant survival, frequency and spectrum of chlorophyll chimeras in M 1 and chlorophyll mutations in M 2 generation. Among all, the combination treatments were found most effective for inducing chlorophyll chimeras and chlorophyll mutations than the gamma rays or EMS alone. Of the mutants under reference, the albino, xantha and chlorina showed monogenic recessive while viridis exhibited digenic recessive inheritance. (author). 8 refs., 2 tabs

  19. Increased production of pyruvic acid by Escherichia coli RNase G mutants in combination with cra mutations.

    Science.gov (United States)

    Sakai, Taro; Nakamura, Naoko; Umitsuki, Genryou; Nagai, Kazuo; Wachi, Masaaki

    2007-08-01

    The Escherichia coli RNase G is known as an endoribonuclease responsible for the 5'-end maturation of 16S rRNA and degradation of several specific mRNAs such as adhE and eno mRNAs. In this study, we found that an RNase G mutant derived from the MC1061 strain did not grow on a glucose minimal medium. Genetic analysis revealed that simultaneous defects of cra and ilvIH, encoding a transcriptional regulator of glycolysis/gluconeogenesis and one of isozymes of acetohydroxy acid synthase, respectively, were required for this phenomenon to occur. The results of additional experiments presented here indicate that the RNase G mutation, in combination with cra mutation, caused the increased production of pyruvic acid from glucose, which was then preferentially converted to valine due to the ilvIH mutation, resulting in depletion of isoleucine. In fact, the rng cra double mutant produced increased amount of pyruvate in the medium. These results suggest that the RNase G mutation could be applied in the breeding of producer strains of pyruvate and its derivatives such as valine.

  20. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.

    Science.gov (United States)

    Volk, Timo; Pannicke, Ulrich; Reisli, Ismail; Bulashevska, Alla; Ritter, Julia; Björkman, Andrea; Schäffer, Alejandro A; Fliegauf, Manfred; Sayar, Esra H; Salzer, Ulrich; Fisch, Paul; Pfeifer, Dietmar; Di Virgilio, Michela; Cao, Hongzhi; Yang, Fang; Zimmermann, Karin; Keles, Sevgi; Caliskaner, Zafer; Güner, S Ükrü; Schindler, Detlev; Hammarström, Lennart; Rizzi, Marta; Hummel, Michael; Pan-Hammarström, Qiang; Schwarz, Klaus; Grimbacher, Bodo

    2015-12-20

    Null mutations in genes involved in V(D)J recombination cause a block in B- and T-cell development, clinically presenting as severe combined immunodeficiency (SCID). Hypomorphic mutations in the non-homologous end-joining gene DCLRE1C (encoding ARTEMIS) have been described to cause atypical SCID, Omenn syndrome, Hyper IgM syndrome and inflammatory bowel disease-all with severely impaired T-cell immunity. By whole-exome sequencing, we investigated the molecular defect in a consanguineous family with three children clinically diagnosed with antibody deficiency. We identified perfectly segregating homozygous variants in DCLRE1C in three index patients with recurrent respiratory tract infections, very low B-cell numbers and serum IgA levels. In patients, decreased colony survival after irradiation, impaired proliferative response and reduced counts of naïve T cells were observed in addition to a restricted T-cell receptor repertoire, increased palindromic nucleotides in the complementarity determining regions 3 and long stretches of microhomology at switch junctions. Defective V(D)J recombination was complemented by wild-type ARTEMIS protein in vitro. Subsequently, homozygous or compound heterozygous DCLRE1C mutations were identified in nine patients from the same geographic region. We demonstrate that DCLRE1C mutations can cause a phenotype presenting as only antibody deficiency. This novel association broadens the clinical spectrum associated with ARTEMIS mutations. Clinicians should consider the possibility that an immunodeficiency with a clinically mild initial presentation could be a combined immunodeficiency, so as to provide appropriate care for affected patients. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Combined effects of ionizing radiation and N-ethyl-N-nitrosourea in murine T-cell lymphoma-genesis

    International Nuclear Information System (INIS)

    Shizuko, Kakinuma; Yoshiko, Amasaki; Kazumi, Yamauchi; Mayumi, Nishimura; Tatsuhiko, Imaoka; Yoshiya, Shimada

    2006-01-01

    We are living in the environment with numerous natural and man-made radiation and chemicals. Cancer development in human is considered as a result of interaction with these factors. But, the quantitative assessment and mechanistic understanding of combined effects of radiation and chemical carcinogens are still insufficient. The aim of this study is to elucidate the mode and mechanism of the combined effect of X-rays with N-ethyl-N-nitrosourea (ENU) on mouse T-cell leukemogenesis, especially at low or threshold dose range. We previously showed that the dose-response curve for X-ray- or ENU induced thymic lymphoma (TL) had threshold dose. X-ray-induced TL was characteristic for frequent inactivation of Ikaros caused by transcriptional silencing, unusual splicing, point mutation and small insertion, most of which were associated with loss of heterozygosity (LOH). In contrast, ENU-induced tumors had point mutations of Ikaros without LOH. In combination, X-irradiation followed by ENU exposure resulted in the synergistic effect at high dose, while the effect was antagonistic at low or threshold dose. When the order of exposure was reversed, i.e., ENU followed by X-rays, the mode of combined exposure was additive at any doses. Molecular analysis demonstrated that Ikaros mutation in TL after X-irradiation followed by ENLI at high doses was predominantly point mutation without LOH (ENU-type). But, after reverse treatment, mutation spectrum of Ikaros was similar to that observed in TL after X-ray exposure alone. It is concluded that the mode of combined effect is dependent upon the treatment order and the dose of carcinogens. (author)

  2. 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.

  3. Identification of coexistence of BRAF V600E mutation and EZH2 gain specifically in melanoma as a promising target for combination therapy.

    Science.gov (United States)

    Yu, Huan; Ma, Meng; Yan, Junya; Xu, Longwen; Yu, Jiayi; Dai, Jie; Xu, Tianxiao; Tang, Huan; Wu, Xiaowen; Li, Siming; Lian, Bin; Mao, Lili; Chi, Zhihong; Cui, Chuanliang; Guo, Jun; Kong, Yan

    2017-12-04

    Coexistence of enhancer of zeste homolog 2 (EZH2) and BRAF gene aberrations has been described in many cancer types. In this study, we aim to explore the coexistence status of BRAF V600E mutation and the copy number variation of EZH2 and explore the potential of this combination as a therapeutic target. A total of 138 cases of melanoma samples harboring BRAF V600E mutation were included, and EZH2 copy numbers were examined by QuantiGenePlex DNA Assays. Clinical pathological distinction between patient groups with or without EZH2 amplification (hereafter referred to as EZH2 gain) was statistically analyzed. The sensitivity of melanoma cell lines and patient-derived xenograft (PDX) models containing BRAF V600E mutation with or without EZH2 gain to vemurafenib (BRAF inhibitor), GSK2816126 (EZH2 inhibitor) and a combination of both agents was evaluated. In our cohort, the coexistence rate of BRAF V600E mutation and EZH2 gain was up to 29.0%, and significant differences in overall survival and disease-free survival were found between no EZH2 copy number gain and gain groups (P = 0.038, P = 0.030), gain and high EZH2 copy number gain groups (P = 0.006, P = 0.010). Combination with BRAF and EZH2 inhibition showed better inhibitory efficacy in melanoma prevention compared with vemurafenib monotherapy. More importantly, this improved therapeutic effect was observed especially in melanoma cell lines and PDX models containing concurrently BRAF V600E mutation and EZH2 gain. Coexistence of BRAF V600E mutation and EZH2 gain is rather prevalent in melanoma. Our findings provided evidence for the feasibility of combination therapy with EZH2 and BRAF inhibitors in melanoma with concurrent BRAF V600E mutation and EZH2 gain.

  4. Biological and genetic effects of combined treatments of sodium azide, gamma rays and EMS in barley

    International Nuclear Information System (INIS)

    Cheng, X.Y.; Gao, M.W.

    1988-01-01

    Dry seeds of diploid barley were subjected to mutagenic treatments of sodium azide, gamma rays and EMS alone or in combination. Damage (reduction in seedling height, plant height and fertility), the frequency of chimeras in the M1 generation, and the frequency of chlorophyll-deficient mutations as well as morphological mutations in the M2 generation induced by combined treatments were greater than those by either of the single treatments. Synergistic increase in the frequency of chimeras, chlorphyll-deficient mutations and morphological mutations were observed in both sodium azide post-irradiation treatments and pre-EMS treatments; interaction among the mutagens in the treatment combinations on M1 damage was generally subtractive. An 8- to 16-hr soaking period of irradiated seeds in distilled water prior to sodium azide treatment significantly increased chlorophyll mutation frequency, as compared to that from the non-soaking treatment. Damage and frequency of chimeras, chlorophyll mutations and morphological mutations were consistently reduced by the soaking treatment in sodium azide plus EMS treatments. (author)

  5. Bioleaching of Arsenic-Rich Gold Concentrates by Bacterial Flora before and after Mutation

    Directory of Open Access Journals (Sweden)

    Xuehui Xie

    2013-01-01

    Full Text Available In order to improve the bioleaching efficiency of arsenic-rich gold concentrates, a mixed bacterial flora had been developed, and the mutation breeding method was adopted to conduct the research. The original mixed bacterial flora had been enrichedin acid mine drainage of Dexing copper mine, Jiangxi Province, China. It was induced by UV (ultraviolet, ultrasonic, and microwave, and their combination mutation. The most efficient bacterial flora after mutation was collected for further bioleaching of arsenic-rich gold concentrates. Results indicated that the bacterial flora after mutation by UV 60 s combined with ultrasonic 10 min had the best oxidation rate of ferrous, the biggest density of cells, and the most activity of total protein. During bioleaching of arsenic-rich gold concentrates, the density of the mutant bacterial cells reached to 1.13×108 cells/mL at 15 days, more than 10 times compared with that of the original culture. The extraction of iron reached to 95.7% after 15 days, increased by 9.9% compared with that of the original culture. The extraction of arsenic reached to 92.6% after 12 days, which was increased by 46.1%. These results suggested that optimum combined mutation could improve leaching ability of the bacterial flora more significantly.

  6. Bioleaching of Arsenic-Rich Gold Concentrates by Bacterial Flora before and after Mutation

    Science.gov (United States)

    Xie, Xuehui; Yuan, Xuewu; Liu, Na; Chen, Xiaoguang; Abdelgadir, Awad; Liu, Jianshe

    2013-01-01

    In order to improve the bioleaching efficiency of arsenic-rich gold concentrates, a mixed bacterial flora had been developed, and the mutation breeding method was adopted to conduct the research. The original mixed bacterial flora had been enrichedin acid mine drainage of Dexing copper mine, Jiangxi Province, China. It was induced by UV (ultraviolet), ultrasonic, and microwave, and their combination mutation. The most efficient bacterial flora after mutation was collected for further bioleaching of arsenic-rich gold concentrates. Results indicated that the bacterial flora after mutation by UV 60 s combined with ultrasonic 10 min had the best oxidation rate of ferrous, the biggest density of cells, and the most activity of total protein. During bioleaching of arsenic-rich gold concentrates, the density of the mutant bacterial cells reached to 1.13 × 108 cells/mL at 15 days, more than 10 times compared with that of the original culture. The extraction of iron reached to 95.7% after 15 days, increased by 9.9% compared with that of the original culture. The extraction of arsenic reached to 92.6% after 12 days, which was increased by 46.1%. These results suggested that optimum combined mutation could improve leaching ability of the bacterial flora more significantly. PMID:24381948

  7. 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.

  8. Induced mutation and in vitro culture techniques for the genetic improvement of ornamentals

    International Nuclear Information System (INIS)

    Lapade, Avelina G.; Veluz, Ana Maria S.; Marbella, Lucia J.; Rama, Manny G.

    2001-01-01

    Mutation breeding using cobalt-60 ( 60 Co) gamma radiation coupled with tissue culture techniques is undertaken for genetic improvement of foliage ornamentals (Dracaena sp. and Murraya exotica L.) and cutflowers (Chrysanthemum morifolium and orchids; Vanda sanderiana, Dendrobium Pattaya Beauty and Phalenopsis schilleriana). Gamma radiation (10-30 Gy) induced chlorophyll mutations and several morphological changes in D. sanderiana. For D. godseffiana, irradiated cuttings resulted in reduction of leaf size and chlorophyll mutations. Reduction in height was observed in the M 2 generation of Murraya exotica L. irradiated at doses ranging from 10 to 30 Gy. The dwarf Murraya mutant was multiplied through the use of seeds and presently 116 plants are commercially available and are ''test marketed'' to the public. Tissue culture technique was used to induce mutation and as a means of micropropagation in two ornamental crops (orchids and chrysanthemum). Effects of different doses of gamma radiation on callus induction from nodal sections of chrysanthemum grown in Murashige and Skoog's (MS) with naphthalene acetic acid (NAA) and benzyl adenine (BA) were studied. Micropropagation of irradiated and unirradiated chrysanthemum using MS basal medium is presently being studied. Whorling and changes in leaf color were observed at 10 Gy and doubling of leaf growth at the node at 20 Gy for vegetatively generated V 3 plant. In orchids, irradiation of immature embryo with gamma rays ranging from 5 to 10 Gy increased the percentage of germination in Dendrobium Pattaya Beauty and P. schilleriana. Protocorms of Vanda sanderiana irradiated at 10 Gy and grown in Knudson C medium developed into plantlets that are bigger and more vigorous than those irradiated at 20 GY and from the control plant. A decrease in seedling height was observed with increasing dose of gamma radiation. (Author)

  9. 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

  10. Induced mutagenesis as a source of new mutations in maize (Zea mays L.)

    Energy Technology Data Exchange (ETDEWEB)

    Mashnenkov, A S [Krasnodar Research Institute of Agriculture, Krasnodar (USSR)

    1990-01-01

    Full text: Seed samples of 9 inbreds were treated with MNU. Mutant individuals were visually selected in M{sub 2} and M{sub 3}. Mutability was determined in 100 loci by crossing induced mutants with some well-known natural mutants obtained from the U.S. Association of Corn Geneticists. Only viable mutants characterised with distinct stable traits connected with kernel texture and mature plant were taken for tests. Mapping of the expected new mutants was realised through A-B translocations and marker lines. Evaluation of the mutant alleles' effect on yield and quality of biomass in inbreds and heterotic hybrids was done by the standard methods. The results show the ability of artificial mutagens to induce mutations in previously known loci. The genotype of the inbreds greatly affects the probability of mutation occurrence in a new locus. Due to the mutagen effect, independently inherited complexes of traits or naturally polygenic traits may become monogenic. This results in simplified inheritance, in an increase in heritability and thus in high effectiveness of selection. (author)

  11. Induced mutagenesis as a source of new mutations in maize (Zea mays L.)

    International Nuclear Information System (INIS)

    Mashnenkov, A.S.

    1990-01-01

    Full text: Seed samples of 9 inbreds were treated with MNU. Mutant individuals were visually selected in M 2 and M 3 . Mutability was determined in 100 loci by crossing induced mutants with some well-known natural mutants obtained from the U.S. Association of Corn Geneticists. Only viable mutants characterised with distinct stable traits connected with kernel texture and mature plant were taken for tests. Mapping of the expected new mutants was realised through A-B translocations and marker lines. Evaluation of the mutant alleles' effect on yield and quality of biomass in inbreds and heterotic hybrids was done by the standard methods. The results show the ability of artificial mutagens to induce mutations in previously known loci. The genotype of the inbreds greatly affects the probability of mutation occurrence in a new locus. Due to the mutagen effect, independently inherited complexes of traits or naturally polygenic traits may become monogenic. This results in simplified inheritance, in an increase in heritability and thus in high effectiveness of selection. (author)

  12. Mutations induced by X-rays and UV radiation during the nuclear cycle in the yeast Schizosarccharomyces pombe

    International Nuclear Information System (INIS)

    Barale, R.; Rusciano, D.; Loprieno, N.

    1982-01-01

    The availability of a cell-division-cycle (cdc) mutant in the fission yeast S. pombe, wee 1-50, has made possible the production of a large population of G 1 nuclear-stage synchronized cells. During their development, yeast cells from the G 1 into the G 2 nuclear stages were treated with X-rays and UV radiation at various doses. The DNA pre-replicative and replicative phases were the most sensitive to both cell lethality and mutant induction with either X-rays or UV radiation. The trends of induced biological effects that were observed suggest that the induction of mutations is dependent on the number of unrepaired DNA lesions that reach the replicating fork or of those that occur at that time. The X-ray-induced mutations were earlier saturated, possibly because of the higher number of lethal lesions so induced. (orig.)

  13. One adenosine deaminase allele in a patient with severe combined immunodeficiency contains a point mutation abolishing enzyme activity.

    OpenAIRE

    Valerio, D; Dekker, B M; Duyvesteyn, M G; van der Voorn, L; Berkvens, T M; van Ormondt, H; van der Eb, A J

    1986-01-01

    We have cloned and sequenced an adenosine deaminase (ADA) gene from a patient with severe combined immunodeficiency (SCID) caused by inherited ADA deficiency. Two point mutations were found, resulting in amino acid substitutions at positions 80 (Lys to Arg) and 304 (Leu to Arg) of the protein. Hybridization experiments with synthetic oligonucleotide probes showed that the determined mutations are present in both DNA and RNA from the ADA-SCID patient. In addition, wild-type sequences could be ...

  14. Mutation Analysis of Consanguineous Moroccan Patients with Parkinson’s Disease Combining Microarray and Gene Panel

    Directory of Open Access Journals (Sweden)

    Ahmed Bouhouche

    2017-10-01

    Full Text Available During the last two decades, 15 different genes have been reported to be responsible for the monogenic form of Parkinson’s disease (PD, representing a worldwide frequency of 5–10%. Among them, 10 genes have been associated with autosomal recessive PD, with PRKN and PINK1 being the most frequent. In a cohort of 145 unrelated Moroccan PD patients enrolled since 2013, 19 patients were born from a consanguineous marriage, of which 15 were isolated cases and 4 familial. One patient was homozygous for the common LRRK2 G2019S mutation and the 18 others who did not carry this mutation were screened for exon rearrangements in the PRKN gene using Affymetrix Cytoscan HD microarray. Two patients were determined homozygous for PRKN exon-deletions, while another patient presented with compound heterozygous inheritance (3/18, 17%. Two other patients showed a region of homozygosity covering the 1p36.12 locus and were sequenced for the candidate PINK1 gene, which revealed two homozygous point mutations: the known Q456X mutation in exon 7 and a novel L539F variation in exon 8. The 13 remaining patients were subjected to next-generation sequencing (NGS that targeted a panel of 22 PD-causing genes and overlapping phenotypes. NGS data showed that two unrelated consanguineous patients with juvenile-onset PD (12 and 13 years carried the same homozygous stop mutation W258X in the ATP13A2 gene, possibly resulting from a founder effect; and one patient with late onset (76 years carried a novel heterozygous frameshift mutation in SYNJ1. Clinical analysis showed that patients with the ATP13A2 mutation developed juvenile-onset PD with a severe phenotype, whereas patients having either PRKN or PINK1 mutations displayed early-onset PD with a relatively mild phenotype. By identifying pathogenic mutations in 45% (8/18 of our consanguineous Moroccan PD series, we demonstrate that the combination of chromosomal microarray analysis and NGS is a powerful approach to

  15. A novel radiation-induced p53 mutation is not implicated in radiation resistance via a dominant-negative effect.

    Directory of Open Access Journals (Sweden)

    Yunguang Sun

    Full Text Available Understanding the mutations that confer radiation resistance is crucial to developing mechanisms to subvert this resistance. Here we describe the creation of a radiation resistant cell line and characterization of a novel p53 mutation. Treatment with 20 Gy radiation was used to induce mutations in the H460 lung cancer cell line; radiation resistance was confirmed by clonogenic assay. Limited sequencing was performed on the resistant cells created and compared to the parent cell line, leading to the identification of a novel mutation (del at the end of the DNA binding domain of p53. Levels of p53, phospho-p53, p21, total caspase 3 and cleaved caspase 3 in radiation resistant cells and the radiation susceptible (parent line were compared, all of which were found to be similar. These patterns held true after analysis of p53 overexpression in H460 cells; however, H1299 cells transfected with mutant p53 did not express p21, whereas those given WT p53 produced a significant amount, as expected. A luciferase assay demonstrated the inability of mutant p53 to bind its consensus elements. An MTS assay using H460 and H1299 cells transfected with WT or mutant p53 showed that the novel mutation did not improve cell survival. In summary, functional characterization of a radiation-induced p53 mutation in the H460 lung cancer cell line does not implicate it in the development of radiation resistance.

  16. Sequencing analysis of mutations induced by N-ethyl-N-nitrosourea at different sampling times in mouse bone marrow.

    Science.gov (United States)

    Wang, Jianyong; Chen, Tao

    2010-03-01

    In our previous study (Wang et al., 2004, Toxicol. Sci. 82: 124-128), we observed that the cII gene mutant frequency (MF) in the bone marrow of Big Blue mice showed significant increase as early as day 1, reached the maximum at day 3 and then decreased to a plateau by day 15 after a single dose of carcinogen N-ethyl-N-nitrosourea (ENU) treatment, which is different from the longer mutation manifestation time and the constancy of MFs after reaching their maximum in some other tissues. To determine the mechanism underlying the quick increase in MF and the peak formation in the mutant manifestation, we examined the mutation frequencies and spectra of the ENU-induced mutants collected from different sampling times in this study. The cII mutants from days 1, 3 and 120 after ENU treatment were randomly selected from different animals. The mutation frequencies were 33, 217, 305 and 144 x 10(-6) for control, days 1, 3, and 120, respectively. The mutation spectra at days 1 and 3 were significantly different from that at day 120. Considering that stem cells are responsible for the ultimate MF plateau (day 120) and transit cells are accountable for the earlier MF induction (days 1 or 3) in mouse bone marrow, we conclude that transit cells are much more sensitive to mutation induction than stem cells in mouse bone marrow, which resulted in the specific mutation manifestation induced by ENU.

  17. Comparative studies of dose-response curves for recessive lethal mutations induced by ethylnitrosourea in spermatogonia and in spermatozoa of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, I.; Ayaki, T.; Ohshima, K.

    1984-01-01

    Induction of recessive lethal mutation by N-ethyl-N-nitrosourea (ENU) was studied for the second chromosome of spermatogonia and spermatozoa in Drosophila melanogaster. ENU (0.03, 0.3, and 1.0 mM) was given to flies by dissolving it in feeding sucrose solution. When plotted against absorbed doses of ENU, the observed frequencies to recessive lethals showed a linear relationship for induction in spermatozoa but a sigmoidal relationship for induction in spermatogonia. These results suggest that in spermatogonia ENU-induced mutational damage is more repairable in a lower dose range of ENU. Mosaic lethal mutations were induced by ENU but not in spermatogonia.

  18. Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas.

    Science.gov (United States)

    Jen, Kuang-Yu; Song, Ihn Young; Banta, Karl Luke; Wu, Di; Mao, Jian-Hua; Balmain, Allan

    2012-01-19

    T-cell acute lymphoblastic lymphomas commonly demonstrate activating Notch1 mutations as well as mutations or deletions in Fbxw7. However, because Fbxw7 targets Notch1 for degradation, genetic alterations in these genes are expected to be mutually exclusive events in lymphomagenesis. Previously, by using a radiation-induced Tp53-deficient mouse model for T-cell acute lymphoblastic lymphoma, we reported that loss of heterozygosity at the Fbxw7 locus occurs frequently in a Tp53-dependent manner. In the current study, we show that these thymic lymphomas also commonly exhibit activating Notch1 mutations in the proline-glutamic acid-serine-threonine (PEST) domain. Moreover, concurrent activating Notch1 PEST domain mutations and single-copy deletions at the Fbxw7 locus occur with high frequency in the same individual tumors, indicating that these changes are not mutually exclusive events. We further demonstrate that although Notch1 PEST domain mutations are independent of Tp53 status, they are completely abolished in mice with germline Fbxw7 haploinsufficiency. Therefore, Notch1 PEST domain mutations only occur when Fbxw7 expression levels are intact. These data suggest a temporal sequence of mutational events involving these important cancer-related genes, with Notch1 PEST domain mutations occurring first, followed by Fbxw7 deletion, and eventually by complete loss of Tp53.

  19. Mutation breedings in ornamental plants

    International Nuclear Information System (INIS)

    Matsubara, Hisao

    1984-01-01

    Several methods of obtaining somatic mutant plants by γ-ray irradiation on pieces of tissues as in vitro adventitious bud technique or small cutting methods with repeated pruning are described. 1) The irradiation to the adventitious buds in the small pieces of organ cultured in vitro and to the small cuttings are employed. Culture beds of agar or of Japanese Kanuma soil were used in vitro culture. In these experiments, Japanese Kanuma soil bed in in vitro culture worked well for root development and transplant of the induced mutants. 2) Combination with in vitro culture and repeated pruning technique were used for isolation and fixation of solid somatic mutant from small sectorial mutation induced by irradiation. This method was successful for begonia, chrysanthemum, aberia and winter daphne. 3) These data indicates that most of the induced mutant plants were non-chimeric, while a few others were chimeric. Among the new varieties, ''Gin-Sei'', ''Ryoku-Ha'', ''Big-Cross'', ''Kaede-Iron'', ''Mei-Fu-Hana-Tsukubane-Utsugi'' and ''Daphne-γ-3'' are non-chimeric, and ''Mini-Mini-Iron'' and ''Orange-Iron'' are chimeric. Moreover, these new varieties have remarkably differed in size and in color pattern from original variety. From the experimental results of somatic mutation, it is indicated that plant tissue culture have enormous potential in radiation breeding and in rapid propagation of the somatic mutant. (author)

  20. 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)

  1. Over-additive increase of bacterial mutations by combined action of ultraviolet light and alkylation

    International Nuclear Information System (INIS)

    Herrmann, S.; Hotz, G.; Herrlich, P.

    1982-05-01

    Mutagenic agents added in combination may contribute to an overall biological effect in proportion to the effect they would have if given individually. The combined effect may, however, not just be additive but rather result in a response above or below expectation if the two mutagenic pathways interacted at some level. We report here on one such example. Ultraviolet light and subsequent treatment with the alkylating agent ethylmethane-sulfonate (EMS) led to an over-additive increase of bacterial mutations. This is interesting with respect to unravelling the level mutagens interact. In addition such data may relate to the human situation which is only in the process of being assessed. (orig.) [de

  2. The induction of somatic mutations by high-LET radiation observed using the Drosophila assay system

    International Nuclear Information System (INIS)

    Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Hoshi, Masaharu; Takada, Jun; Endo, Satoru

    1999-01-01

    To evaluate the mutagenic potential of high-LET radiation, an analysis was made on the production of somatic mutations by 252 Cf fission neutron s and heavy particle ions accelerated by a synchrotron. A Drosophila strain that allows simultaneous detection of two types of mutations in an identical fly was constructed. One was a wing-hair mutation and the other was an eye-color mosaic spot mutation. Measurements were made using a combined assay system of both mutation assays. Larvae were exposed to radiation at the age of post-ovipositional day-3. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots was very high, the relative biological effectiveness (RBE) = 8.5, but the efficiency for eye-color mosaic spot was nearly equal (RBE = 1.2) to that of 137 Cs γ-rays. The RBE of carbon ions for inducing wing-hair mosaic spots increased as an increase in LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damages such as non-rejoinable strand break or clustered double strand break, which increase with LET may be responsible for the induction of wing-hair mutation, while simpler forms of molecular damage may induce a reversion in the white-ivory allele. (M.N.)

  3. Significance of combined detection of JAK2V617F, MPL and CALR gene mutations in patients with essential thrombocythemia.

    Science.gov (United States)

    Ji, Liying; Qian, Mengyao; Wu, Nana; Wu, Jianmin

    2017-03-01

    The aim of this study was to analyze the mutation rate of JAK2V617F, MPLW515L/K and CALR genes in adult patients with essential thrombocythemia (ET) and the accuracy of the combined detection by the receiver operating curve. Three hundred and forty-two cases with high-platelets (≥300×10 9 /l) were consecutively selected. The patients were analyzed for routine blood examination, bone marrow biopsy and genetic testing. One hundred and fifty-four cases (45.03%) were diagnosed with ET and 188 cases of secondary thrombocythemia according to the hematopoietic and lymphoid tissue tumor classification standards of 2008. It was found that the mutant type of three genes showed three bands, whereas only one band for wild-type. The JAK2V617F and MPL mutations did not cause a change in the open reading frame and the CALR mutation resulted in its change. The mutation rate of JAK2V617F and CALR in ET group was significantly higher than that in the secondary thrombocythemia group (p<0.05). The positive mutation rate of MPL was only 4.55%. JAK2V617F-positive mutation alone was used to diagnose with ET. The area under the curve (AUC) was 0.721. The sensitivity was 72.4%, the specificity was 79.5% and the cut-off value was 0.25. When CALR-positive mutation alone was used to diagnose ET, the AUC, sensitivity, specificity and cut-off value were 0.664, 68.4, 82.4 and 0.09%, respectively. JAK2V617F combined with CALR mutation were used for diagnosis of ET. The AUC was 0.862, the sensitivity was 85.9%, the specificity was 87.8%, and the cut-off values were 0.21 and 0.07. In conclusion, the positive mutation rate of JAK2V617F and CALR in ET was higher, and the sensitivity, specificity and accuracy of the diagnosis of ET were significantly improved using the detection of JAK2V617F and CALR.

  4. Site-specific analysis of UV-induced cyclobutane pyrimidine dimers in nucleotide excision repair-proficient and -deficient hamster cells: Lack of correlation with mutational spectra

    International Nuclear Information System (INIS)

    Vreeswijk, Maaike P.G.; Meijers, Caro M.; Giphart-Gassler, Micheline; Vrieling, Harry; Zeeland, Albert A. van; Mullenders, Leon H.F.; Loenen, Wil A.M.

    2009-01-01

    Irradiation of cells with UVC light induces two types of mutagenic DNA photoproducts, i.e. cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP). To investigate the relationship between the frequency of UV-induced photolesions at specific sites and their ability to induce mutations, we quantified CPD formation at the nucleotide level along exons 3 and 8 of the hprt gene using ligation-mediated PCR, and determined the mutational spectrum of 132 UV-induced hprt mutants in the AA8 hamster cell line and of 165 mutants in its nucleotide excision repair-defective derivative UV5. In AA8 cells, transversions predominated with a strong strand bias towards thymine-containing photolesions in the non-transcribed strand. As hamster AA8 cells are proficient in global genome repair of 6-4PP but selectively repair CPD from the transcribed strand of active genes, most mutations probably resulted from erroneous bypass of CPD in the non-transcribed strand. However, the relative incidence of CPD and the positions where mutations most frequently arose do not correlate. In fact some major damage sites hardly gave rise to the formation of mutations. In the repair-defective UV5 cells, mutations were almost exclusively C > T transitions caused by photoproducts at PyC sites in the transcribed strand. Even though CPD were formed at high frequencies at some TT sites in UV5, these photoproducts did not contribute to mutation induction at all. We conclude that, even in the absence of repair, large variations in the level of induction of CPD at different sites throughout the two exons do not correspond to frequencies of mutation induction.

  5. Hezu 8, a new wheat variety developed with in vitro mutation technique

    International Nuclear Information System (INIS)

    Gao Mingwei

    1992-01-01

    A new wheat variety named Hezu 8 was developed by in vitro mutation techniques combining the somatic tissue culture with the radiation-induced mutation. This is the first one in the world for breeding wheat variety in such a way, that the nuclear technology was successfully applied to biotechnology. Hezu 8 is featured by high yield potential, early maturity, disease resistance, tolerance to moisture as well as good grain quality. In vitro mutation technique has proved to be helpful in increment of the frequency of somaclonal variation, promotion of the variation stability, acceleration of breeding process, reduction of the population size for variant selection, and finally, improvement of the breeding efficiency. In vitro mutation technique can be also widely applied to other crops and will open up a brilliant prospect for crop improvement

  6. 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

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

    International Nuclear Information System (INIS)

    Serres, F.J. de

    1989-01-01

    More extensive genetic tests have been preformed on a series of 832 X-ray-induced specific-locus mutations in the ad-3 region of a 2-component heterokaryon of Neurospora crassa, reported earlier. Using new tester strains and techniques for performing large-scale genetic tests to characterize ad-3 mutants induced in 2-component heterokaryons, new data have been obtained on this sample of X-ray-induced mutants. These new data show that unexpectedly high frequencies of both single-locus mutations and multilocus deletions in the ad-3 region have addition, but separate, sites of recessive lethal damage in the imeediately adjacent genetic regions. The frequencies of these X-ray-induced multiple-locus mutants in the ad-3 region are orders of magnitude higher than expected on the basis of target theory and classical models of chromosome structure during interphase. Current models of interphase chromosome structure in higher eukaryotes as revealed by chromosome 'painting' offer a possible explanation of the Neurospora data. (author). 25 refs.; 5 figs

  8. Modifying effect of 5-fluoro-2-deoxiuridine on the frequency of x-ray-induced visible mutations in wheat

    International Nuclear Information System (INIS)

    Azatyan, R.A.; Avakyan, V.A.

    1985-01-01

    A modifying effect of FUDR on the output of visible mutations induced by X-ray radiation has been studied at soft fall wheat (Tr. aestivum var. turcicum). It is shown that at X-ray radiation of dry seeds with subsequent treatment of FUDR increased is the mutant percent in M 3 which has constituted 0.61% at irradiation in dose of 100 Gy ad 1.03% at irradiation by the same dose and FUDR influence during 10 hours. In analogous variants at irradiation by 150 Gi dose the mutation frequency reached 1.47 and 2.07% respectively. It is shown that FUDR postradiation treatment promotes not only the increase of frequency but consderablly widens the spectrum of induced mutations. A supposition is made that FUDR modyfying effect is caused by DNA synthesis inhibition. A problem is discussed on a possible realization of potential DNA changes caused by irradiation, at additional influence of inhibitor

  9. Mutational specificity of γ-rays

    International Nuclear Information System (INIS)

    Hoebee, Barbara.

    1990-01-01

    The aim of the study described in this thesis was to get more information on the mutagenic properties of radiation-induced DNA modifications and the possible mechanisms involved in radiation-induced mutagenesis, principally by investigating the kinds of mutations by DNA sequence analysis. The mutations were analyzed after γ-irradiation of recombinant bacteriophage M13 and plasmide pUC DNA in diluted aqueous solutions, followed by transfection or transformation to E. coli cells, in which the damaged DNA molecules are repaired and replicated. Error-prone repair, misrepair or bypass of lesions during replication may lead to the introduction of mutations. Both the M13 and the plasmid DNA used in our mutation studies contain a mutation target sequence, which makes an easy selection and sequence analysis of mutant DNA molecules possible. Under the radiation conditions used, e.g. irradiation of diluted aqueous DNA solutions, only DNA damage occurs introduced by the water derived OH* and H* radicals and the hydrated electrons. By using different gas conditions during irradiation the relative yields of these reaction species can be manipulated, which opens up the opportunity to determine their effects separately. The mutation spectrum obtained in double-stranded (ds) M13DNA after irradiation under oxic conditions and the mutation spectrum obtained under the same conditions and in the same mutation target but cloned in plasmid DNA, are described. The mutation specificity under anoxic conditions in ds M13DNA is given. Results obtained after irradiation of ds M13DNA under N 2 conditions are discussed together with experiments with single-stranded DNA. Similarities and differences between radiation-induced mutation spectra obtained by other groups and those presented in this thesis are discussed. (author). 155 refs.; 134 figs.; 16 tabs

  10. Induced mutation breeding in fruit trees

    International Nuclear Information System (INIS)

    Sanada, Tetsuro

    1988-01-01

    The black spot disease of Japanese pear is the most serious disease, and Nijusseiki which is one of the leading cultivars of Japanese pear is known to be susceptible to the disease. One branch of a tree planted at the distance of 53 m from a Co-60 source (15 R/day) was selected as a mutant resistant to the disease in 1981, as the spraying of fungicide was reduced when the pathogen was naturally inoculated. The symptom of black spot disease on the mutant observed under field conditions for the period of 5 years after the selection was minimal. The characteristics and the resistance of this mutant were examined. The development of a simple and reliable selection method is essential for mutation breeding. A selection method using a phytotoxin solution was developed. The induced mutant was obviously different from the original Nijusseiki in the susceptibility to the disease, but its resistance was medium. The faint brown spots observed on the leaves and fruit skins of the mutant were due to the aggregation of cytoplasm only in epidermal cells. By the selection method developed, about 500 shoots can be screened in a day. (Kako, I.)

  11. 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 )

  12. Study on cellular genotoxicities induced by alpha particles irradiation in combination with NNK treatment

    International Nuclear Information System (INIS)

    Li Ping; Yang Zhihua; Pan Xiujie; Cao Zhenshan; Mi Na; Chen Zhongmin; Liu Gang; Wei Han; Li Huiying; Zhu Maoxiang

    2006-01-01

    Objective: To investigate cellular genotoxicities of aplha particles irradiation in combination with NNK treatment. Methods: Exponentially growing immortalized human bronchial epithelial cells were divided into the normal control group (NC), alpha particles irradiation (α), NNK administration group (NNK), NNK administration (100 μg/ml) followed by alpha particles irradiation group (NNK + α), and alpha particles irradiation followed by NNK administration (100 μg/ml) group (μ + NNK). DNA damage were detected by single cell gel electrophoresis (SCGE); multinuclear cell assay was used to detect the frequency of the HPRT gene mutation; cell micronucleus frequency were detected by cytogenetic methods. Results: In the group exposed to both alpha particles irradiation and NNK, DNA damage, HPRT gene mutation frequency, and cell micronucleus frequency were significantly higher than those in the same dose groups irradiated with alpha particles or NNK administration alone. Subtracted the NNK effect, DNA damage, HPRT gene mutation frequency and cell micronucleus frequency in the group irradiated by alpha particles in combination with NNK administration were significantly higher than those of alpha particles irradiation alone. Conclusion: The genotoxicity of alpha particles irradiation in combination with NNK administration had synergistic effect. (authors)

  13. A/α-specific effect of the mms3 mutation on ultraviolet mutagenesis in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Martin, P.; Prakash, L.; Prakash, S.

    1981-01-01

    A new gene involved in error-prone repair of ultraviolet (uv) damage has been identified in Saccharomyces cerevisiae by the mms3-1 mutation. Uv-induced reversion is reduced in diploids that are homozygous for mms3-1, only if they are also heterozygous (MATa/MATα) at the mating type locus. The mms3-1 mutation has no effect on uv-induced reversion either in haploids or MATa/MATα or MATα/MATα diploids. The mutation confers sensitivity to uv and methyl methane sulfonate in both haploids and diploids. Even though mutation induction by uv is restored to wild-type levels in MATa/MATa mms3-1/mms3-1 or MATα/MATα mms3-1/mms3-1 diploids, such strains still retain sensitivity to the lethal effects of uv. Survival after uv irradiation in mms3-1 rad double mutant combinations indicates that mms3-1 is epistatic to rad6-1 whereas non-epistatic interactions are observed with rad3 and rad52 mutants. When present in the homozygous state in MATa/MATα his1-1/his1-315 heteroallelic diploids, mms3-1 was found to lower uv-induced mitotic recombination

  14. MT-CYB mutations in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole

    2013-01-01

    Mitochondrial dysfunction is a characteristic of heart failure. Mutations in mitochondrial DNA, particularly in MT-CYB coding for cytochrome B in complex III (CIII), have been associated with isolated hypertrophic cardiomyopathy (HCM). We hypothesized that MT-CYB mutations might play an important...... and m.15482T>C; p.S246P were identified. Modeling showed that the p.C93Y mutation leads to disruption of the tertiary structure of Cytb by helix displacement, interfering with protein-heme interaction. The p.S246P mutation induces a diproline structure, which alters local secondary structure and induces...... of HCM patients. We propose that further patients with HCM should be examined for mutations in MT-CYB in order to clarify the role of these variants....

  15. 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

  16. 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

  17. Mutation breeding newsletter. No. 33

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  18. 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

  19. Crop improvement through mutation techniques in Chinese agriculture

    International Nuclear Information System (INIS)

    Wen, X.; Qu, L.

    1996-01-01

    Induced mutations for crop improvement is the most developed field in China's nuclear-agricultural sciences. It is well known that China has supported 22% of the world's population with only 7% of its cultivated land. The continued rise in population stresses the importance of increasing food production. Although developing crop varieties is efficient in increasing food production, plant breeders are approaching the outer limits of existing and useful genetic variability. As nuclear techniques provide an efficient route to inducing genetic mutations, more and more efforts have been focused on induced genetic variability. Induced mutations have become an effective way of improving cultivars and supplementing existing germplasm. Since 1981 two nationwide co-operation programs for mutation breeding, organized by the IAEA, have been carried out. 3 tabs

  20. 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

  1. A synthetic combination of mutations, including fs(1)pyrSu(b), rSu(b) and b, causes female sterility and reduces embryonic viability in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Piskur, Jure; Gojkovic, Zoran; Bahn, E.

    1999-01-01

    A Drosophila melangaster mutant, fs(1)pyr(Su(b)), carrying a mutation that maps to the tip of the X chromosome, has been isolated. The mutation, when present alone, does not confer a detectable phenotype. However, this mutation causes female sterility and reduces embryonic viability when combined...

  2. 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)

  3. The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis.

    Science.gov (United States)

    Wang, Lulu; Li, Yan; Li, Luchun; Wu, Zhijuan; Yang, Dan; Ma, Huiwen; Wang, Donglin

    2018-01-01

    This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation) in a real-life setting. One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS). Longer PFS and overall survival (OS), and better objective response rate (ORR) were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS, especially in those who harbored the EGFR exon 19 deletion.

  4. A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome).

    Science.gov (United States)

    Hofstra, R M; Osinga, J; Tan-Sindhunata, G; Wu, Y; Kamsteeg, E J; Stulp, R P; van Ravenswaaij-Arts, C; Majoor-Krakauer, D; Angrist, M; Chakravarti, A; Meijers, C; Buys, C H

    1996-04-01

    Hirschsprung disease (HSCR) or colonic aganglionosis is a congenital disorder characterized by an absence of intramural ganglia along variable lengths of the colon resulting in intestinal obstruction. The incidence of HSCR is 1 in 5,000 live births. Mutations in the RET gene, which codes for a receptor tyrosine kinase, and in EDNRB which codes for the endothelin-B receptor, have been shown to be associated with HSCR in humans. The lethal-spotted mouse which has pigment abnormalities, but also colonic aganglionosis, carries a mutation in the gene coding for endothelin 3 (Edn3), the ligand for the receptor protein encoded by EDNRB. Here, we describe a mutation of the human gene for endothelin 3 (EDN3), homozygously present in a patient with a combined Waardenburg syndrome type 2 (WS2) and HSCR phenotype (Shah-Waardenburg syndrome). The mutation, Cys159Phe, in exon 3 in the ET-3 like domain of EDN3, presumably affects the proteolytic processing of the preproendothelin to the mature peptide EDN3. The patient's parents were first cousins. A previous child in this family had been diagnosed with a similar combination of HSCR, depigmentation and deafness. Depigmentation and deafness were present in other relatives. Moreover, we present a further indication for the involvement of EDNRB in HSCR by reporting a novel mutation detected in one of 40 unselected HSCR patients.

  5. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa.

    Science.gov (United States)

    Hartel, Bas P; Löfgren, Maria; Huygen, Patrick L M; Guchelaar, Iris; Lo-A-Njoe Kort, Nicole; Sadeghi, Andre M; van Wijk, Erwin; Tranebjærg, Lisbeth; Kremer, Hannie; Kimberling, William J; Cremers, Cor W R J; Möller, Claes; Pennings, Ronald J E

    2016-09-01

    Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups. Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations. The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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...... Lambert (SJL) strain. Here we identify a SJL-specific mutation in the Tbc1d1 gene that results in a truncated protein lacking the TBC Rab-GTPase-activating protein domain. TBC1D1, which has been recently linked to human obesity, is related to the insulin signaling protein AS160 and is predominantly...... and reduced glucose uptake in isolated skeletal muscle. Our data strongly suggest that mutation of Tbc1d1 suppresses high-fat diet-induced obesity by increasing lipid use in skeletal muscle....

  7. Mutation induction by ion beams in arabidopsis

    International Nuclear Information System (INIS)

    Tanaka, Atsushi

    1999-01-01

    An investigation was made on characteristics of ion beams for the biological effects and the induction of mutation using Arabidopsis plant as a model plant for the molecular genetics. Here, the characteristics of mutation at the molecular level as well as new mutants induced by ion beams were described. The ast and sep1 were obtained from the offspring of 1488 carbon ion-irradiated seeds respectively. The uvi1-uvi4 mutants were also induced from 1280 M 1 lines. Thus, ion beams can induce not only known mutants such as tt, gl and hy but also novel mutants with high frequency. Even in the tt phenotype, two new mutant loci other than known loci were found. In chrysanthemum, several kinds of single, complex or stripped flower-color mutants that have been never induced by γirradiation, indicating that ion beams could produce a variety of mutants with the same phenotype. In conclusion, ion beams for the mutation induction are characterized by 1) to induce mutants with high frequency, 2) to show broad mutation spectrum and 3) to produce novel mutants. For these reasons, chemical mutagens such as EMS and low LET ionizing radiation such as X-rays and γ-rays will predominantly induce many but small modifications or DNA damages on the DNA strands. As the result, several point mutations will be produced on the genome. On the contrary, ion beams as a high LET ionizing radiation will not cause so many but large and irreparable DNA damage locally, resulting in production of limited number of null mutation. (M.N.)

  8. Mutation induction by ion beams in arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1999-07-01

    An investigation was made on characteristics of ion beams for the biological effects and the induction of mutation using Arabidopsis plant as a model plant for the molecular genetics. Here, the characteristics of mutation at the molecular level as well as new mutants induced by ion beams were described. The ast and sep1 were obtained from the offspring of 1488 carbon ion-irradiated seeds respectively. The uvi1-uvi4 mutants were also induced from 1280 M{sub 1} lines. Thus, ion beams can induce not only known mutants such as tt, gl and hy but also novel mutants with high frequency. Even in the tt phenotype, two new mutant loci other than known loci were found. In chrysanthemum, several kinds of single, complex or stripped flower-color mutants that have been never induced by {gamma}irradiation, indicating that ion beams could produce a variety of mutants with the same phenotype. In conclusion, ion beams for the mutation induction are characterized by 1) to induce mutants with high frequency, 2) to show broad mutation spectrum and 3) to produce novel mutants. For these reasons, chemical mutagens such as EMS and low LET ionizing radiation such as X-rays and {gamma}-rays will predominantly induce many but small modifications or DNA damages on the DNA strands. As the result, several point mutations will be produced on the genome. On the contrary, ion beams as a high LET ionizing radiation will not cause so many but large and irreparable DNA damage locally, resulting in production of limited number of null mutation. (M.N.)

  9. 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

  10. 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)

  11. In silico analysis of conformational changes induced by mutation of aromatic binding residues: consequences for drug binding in the hERG K+ channel.

    Directory of Open Access Journals (Sweden)

    Kirsten Knape

    Full Text Available Pharmacological inhibition of cardiac hERG K(+ channels is associated with increased risk of lethal arrhythmias. Many drugs reduce hERG current by directly binding to the channel, thereby blocking ion conduction. Mutation of two aromatic residues (F656 and Y652 substantially decreases the potency of numerous structurally diverse compounds. Nevertheless, some drugs are only weakly affected by mutation Y652A. In this study we utilize molecular dynamics simulations and docking studies to analyze the different effects of mutation Y652A on a selected number of hERG blockers. MD simulations reveal conformational changes in the binding site induced by mutation Y652A. Loss of π-π-stacking between the two aromatic residues induces a conformational change of the F656 side chain from a cavity facing to cavity lining orientation. Docking studies and MD simulations qualitatively reproduce the diverse experimentally observed modulatory effects of mutation Y652A and provide a new structural interpretation for the sensitivity differences.

  12. 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

  13. Mutagenic effects of gamma rays and EMS on frequency and spectrum of chlorophyll mutations in urdbean (Vigna mungo (L.) Hepper)

    International Nuclear Information System (INIS)

    Usharani, K.S.; Ananda Kumar, C.R.

    2015-01-01

    Chlorophyll mutations act as a significant index in the judgment of induced genetic variations in mutagen treated populations. Different types of chlorophyll mutation have been observed in various crop plants. In the current study, the effect of different concentrations (40 kR, 50 kR and 60 kR) of gamma rays, Ethyl Methane Sulphonate (50 mM, 60 mM and 70 mM) in single and combination dose/concentration on the frequency and spectrum of chlorophyll mutation and the effect of VBN 4 urdbean variety to such irradiation dose was observed. Results showed induction of broad spectrum of chlorophyll mutations which included albina, xantha, chlorina and viridis. Among these chlorina type was predominant in all the mutagenic treatments. The albina type of chlorophyll mutants occurred very rarely and was found only at 60 mM of EMS treatment and at 40 kR + 50 mM, 60 kR + 70 mM of combination treatments. Based on the chlorophyll mutation frequency, gamma rays were most effective followed by EMS and combination of treatments. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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

  15. 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

  16. Morphological mutations induced by gamma rays, ethylene imine and N-nitroso-N-ethyl urea in lentil (Lens culinaris medik.)

    International Nuclear Information System (INIS)

    Solanki, I.S.; Sharma, B.

    2003-01-01

    Dry and healthy seeds of a large seeded lentil cv, 'Precoz Selection', were treated with three doses each of gamma rays, ethylene imine (EI) and N-nitroso-N-ethyl urea (NEU). Based on the frequency of morphological mutations, the mutagens were arranged in the order: NEU > EI >. Gamma rays and dose-dependent relationship was observed in the case of gamma rays (5 kR 1 damage groups induced morphological mutations in the order: HH > HL > LH > LL. The morphological mutations included changes for growth habit, foliage, plant height and maturity and flowering behaviour. A mild relative mutagenic specificity and differences in mutability of genes for different traits were observed, In general the spectrum of morphological mutations was not influenced by the groups of M 1 damage, except that some mutation types occurred more frequently, than others in certain groups. (author)

  17. Apoptosis-inducing signal sequence mutation in carbonic anhydrase IV identified in patients with the RP17 form of retinitis pigmentosa

    Science.gov (United States)

    Rebello, George; Ramesar, Rajkumar; Vorster, Alvera; Roberts, Lisa; Ehrenreich, Liezle; Oppon, Ekow; Gama, Dumisani; Bardien, Soraya; Greenberg, Jacquie; Bonapace, Giuseppe; Waheed, Abdul; Shah, Gul N.; Sly, William S.

    2004-01-01

    Genetic and physical mapping of the RP17 locus on 17q identified a 3.6-megabase candidate region that includes the gene encoding carbonic anhydrase IV (CA4), a glycosylphosphatidylinositol-anchored protein that is highly expressed in the choriocapillaris of the human eye. By sequencing candidate genes in this region, we identified a mutation that causes replacement of an arginine with a tryptophan (R14W) in the signal sequence of the CA4 gene at position -5 relative to the signal sequence cleavage site. This mutation was found to cosegregate with the disease phenotype in two large families and was not found in 36 unaffected family members or 100 controls. Expression of the mutant cDNA in COS-7 cells produced several findings, suggesting a mechanism by which the mutation can explain the autosomal dominant disease. In transfected COS-7 cells, the R14W mutation (i) reduced the steady-state level of carbonic anhydrase IV activity expressed by 28% due to a combination of decreased synthesis and accelerated turnover; (ii) led to up-regulation of immunoglobulin-binding protein, double-stranded RNA-regulated protein kinase-like ER kinase, and CCAAT/enhancer-binding protein homologous protein, markers of the unfolded protein response and endoplasmic reticulum stress; and (iii) induced apoptosis, as evidenced by annexin V binding and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining, in most cells expressing the mutant, but not the WT, protein. We suggest that a high level of expression of the mutant allele in the endothelial cells of the choriocapillaris leads to apoptosis, leading in turn to ischemia in the overlying retina and producing autosomal dominant retinitis pigmentosa. PMID:15090652

  18. Combined mutation and rearrangement screening by quantitative PCR high-resolution melting: is it relevant for hereditary recurrent Fever genes?

    Directory of Open Access Journals (Sweden)

    Nathalie Pallares-Ruiz

    2010-11-01

    Full Text Available The recent identification of genes implicated in hereditary recurrent fevers has allowed their specific diagnosis. So far however, only punctual mutations have been identified and a significant number of patients remain with no genetic confirmation of their disease after routine molecular approaches such as sequencing. The possible involvement of sequence rearrangements in these patients has only been examined in familial Mediterranean fever and was found to be unlikely. To assess the existence of larger genetic alterations in 3 other concerned genes, MVK (Mevalonate kinase, NLRP3 (Nod like receptor family, pyrin domain containing 3 and TNFRSF1A (TNF receptor superfamily 1A, we adapted the qPCR-HRM method to study possible intragenic deletions and duplications. This single-tube approach, combining both qualitative (mutations and quantitative (rearrangement screening, has proven effective in Lynch syndrome diagnosis. Using this approach, we studied 113 unselected (prospective group and 88 selected (retrospective group patients and identified no intragenic rearrangements in the 3 genes. Only qualitative alterations were found with a sensitivity similar to that obtained using classical molecular techniques for screening punctual mutations. Our results support that deleterious copy number alterations in MVK, NLRP3 and TNFRSF1A are rare or absent from the mutational spectrum of hereditary recurrent fevers, and demonstrate that a routine combined method such as qPCR-HRM provides no further help in genetic diagnosis. However, quantitative approaches such as qPCR or SQF-PCR did prove to be quick and effective and could still be useful after non contributory punctual mutation screening in the presence of clinically evocative signs.

  19. Multi-walled carbon nanotubes (NM401) induce ROS-mediated HPRT mutations in Chinese hamster lung fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Rubio, Laura [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra (Spain); El Yamani, Naouale [Health Effects Laboratory-MILK, NILU-Norwegian Institute for Air Research, Kjeller (Norway); Kazimirova, Alena [Department of Biology, Slovak Medical University, Bratislava (Slovakia); Dusinska, Maria, E-mail: maria.dusinska@nilu.no [Health Effects Laboratory-MILK, NILU-Norwegian Institute for Air Research, Kjeller (Norway); Marcos, Ricard, E-mail: ricard.marcos@uab.es [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra (Spain); CIBER Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid (Spain)

    2016-04-15

    Although there is an important set of data showing potential genotoxic effects of nanomaterials (NMs) at the DNA (comet assay) and chromosome (micronucleus test) levels, few studies have been conducted to analyze their potential mutagenic effects at gene level. We have determined the ability of multi-walled carbon nanotubes (MWCNT, NM401), to induce mutations in the HPRT gene in Chinese hamster lung (V79) fibroblasts. NM401, characterized in the EU NanoGenotox project, were further studied within the EU Framework Programme Seven (FP7) project NANoREG. From the proliferation assay data we selected a dose-range of 0.12 to 12 µg/cm{sup 2} At these range we have been able to observe significant cellular uptake of MWCNT by using transmission electron microscopy (TEM), as well as a concentration-dependent induction of intracellular reactive oxygen species. In addition, a clear concentration-dependent increase in the induction of HPRT mutations was also observed. Data support a potential genotoxic/ carcinogenic risk associated with MWCNT exposure. - Highlights: • MWCNT were tested in V79 cells. • Cellular uptake of MWCNT was detected using TEM. • Intracellular ROS induction was observed after MWCNT exposure. • MWCNT induced a concentration-dependent increase of HPRT mutations.

  20. Multi-walled carbon nanotubes (NM401) induce ROS-mediated HPRT mutations in Chinese hamster lung fibroblasts

    International Nuclear Information System (INIS)

    Rubio, Laura; El Yamani, Naouale; Kazimirova, Alena; Dusinska, Maria; Marcos, Ricard

    2016-01-01

    Although there is an important set of data showing potential genotoxic effects of nanomaterials (NMs) at the DNA (comet assay) and chromosome (micronucleus test) levels, few studies have been conducted to analyze their potential mutagenic effects at gene level. We have determined the ability of multi-walled carbon nanotubes (MWCNT, NM401), to induce mutations in the HPRT gene in Chinese hamster lung (V79) fibroblasts. NM401, characterized in the EU NanoGenotox project, were further studied within the EU Framework Programme Seven (FP7) project NANoREG. From the proliferation assay data we selected a dose-range of 0.12 to 12 µg/cm 2 At these range we have been able to observe significant cellular uptake of MWCNT by using transmission electron microscopy (TEM), as well as a concentration-dependent induction of intracellular reactive oxygen species. In addition, a clear concentration-dependent increase in the induction of HPRT mutations was also observed. Data support a potential genotoxic/ carcinogenic risk associated with MWCNT exposure. - Highlights: • MWCNT were tested in V79 cells. • Cellular uptake of MWCNT was detected using TEM. • Intracellular ROS induction was observed after MWCNT exposure. • MWCNT induced a concentration-dependent increase of HPRT mutations.

  1. Predictable Phenotypes of Antibiotic Resistance Mutations.

    Science.gov (United States)

    Knopp, M; Andersson, D I

    2018-05-15

    Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations. IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain

  2. Combined Effects of Medicinal Plants on Induced Upper ...

    African Journals Online (AJOL)

    Combined Effects of Medicinal Plants on Induced Upper Gastrointestinal Tract Injury ... treated in different doses of single and combined extracts of Allium sativum, ... was no visible sign of ulceration or perforation observed on the stomach and ...

  3. Molecular nature of forvard gene mutations induced by γ- and UV-irradiation ip the yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Ivanov, E.L.; Koval'tsova, S.V.; Korolev, V.G.

    1983-01-01

    Gamma and UV-radiation induce the following mutation spectra in the ADE2 gene of Saccharomyces cerevisial yeast respectively: 27 and 41% of GTs→AT transitions, 8 and 11% of AT→GTs transitions, 59 and 40% transversions, 6 and 8% mutations of the reading fame shift type. The results obtained prove the presence of specific nature of UV rays in respect to induction of GTs→AT transitions. The experimental data are discussed from the point of view of studying molecular mechanisms of radiation mutagenesis

  4. Mutation studies on garden roses: a review

    International Nuclear Information System (INIS)

    Datta, S.K.

    1997-01-01

    Most of the modern roses are the result of hybridization, selection and spontaneous mutation. For floriculture trade, there is always demand and necessity for new varieties due to change in taste and fashion. Mutation breeding is an established method for crop improvement. Induced somatic mutation breeding holds promise for effective improvement and have high potential for bringing about genetic improvement and it has led to a great burst of flower colour, form, pattern and other variations in rose by using ionizing radiations. The details of prospects and utilization of induced mutation breeding technique for developing new rose varieties have been compiled. (author)

  5. 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

  6. 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

  7. 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

  8. Modification of mutation frequency in Saccharomyces Cerevisiae

    International Nuclear Information System (INIS)

    Vashishat, R.K.; Kakar, S.N.

    1976-01-01

    In a reverse mutation system, using haploid, histidine-requirinq strain of Saccharomyces cerevisiae, the frequency of uv-induced prototrophs increased if the post-irradiation minimal medium was supplemented with limited amounts of histidine. Addition of natural amino acids or RNA bases in the post-irradiation minimal medium, with or without histidine, also increased the uv-induced mutation frequency. Thus, post-irradiation conditions favouring protein and RNA synthesis, are effective in increasing uv-induced mutations in yeast. As compared to uv light, nitrous acid was more effective in inducing reversions in this strain and the frequency increased if the treated cells were plated on minimal medium supplemented with limited amounts of histidine. However, the addition of amino acids or RNA bases decreased the number of revertants. An additional inclusion of histidine reversed the suppressive effect of these metabolites. The mutation induction processes are thus different or differently modifiable in uv and nitrous acid. (author)

  9. 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

  10. Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

    Science.gov (United States)

    Xia, Pinghui; Cao, Jinlin; Lv, Xiayi; Wang, Luming; Lv, Wang; Hu, Jian

    2018-05-01

    Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wessendorf, Petra [Institute of Medical and Human Genetics, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin (Germany); Vijg, Jan [Albert Einstein College of Medicine, Michael F. Price Center, 1301 Morris Park Avenue, Bronx, NY 10461 (United States); Nussenzweig, André [Laboratory of Genome Integrity, National Cancer Institute, National Institute of Health, 37 Convent Drive, Room 1106, Bethesda, MD 20892 (United States); Digweed, Martin, E-mail: martin.digweed@charite.de [Institute of Medical and Human Genetics, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin (Germany)

    2014-11-15

    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.

  13. Stamina pistilloida: a new mutation induced in pea.

    Science.gov (United States)

    Monti, L M; Devreux, M

    1969-01-01

    After diethylsulphate treatment of seeds of the pea variety 'Parvus', a new floral mutation was isolated in the second generation. This mutation, named stamina pistilloida, is characterized by a partial fusion of the androecium with the gynoecium; the two marginal stamens of the staminal column are transformed in rudimentary carpels more or less differentiated according to ecoclimatic conditions. The genetic analysis has shown the monogenic and recessive behaviour of the mutation (gene proposed stp) and its linkage with the gene oh in the chromosome II.

  14. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection.

    Science.gov (United States)

    Ye, Lin; Wang, Jiaming; Beyer, Ashley I; Teque, Fernando; Cradick, Thomas J; Qi, Zhongxia; Chang, Judy C; Bao, Gang; Muench, Marcus O; Yu, Jingwei; Levy, Jay A; Kan, Yuet Wai

    2014-07-01

    Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination of transcription activator-like effector nucleases (TALENs) or RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 together with the piggyBac technology. Remarkably, TALENs or CRISPR-Cas9-mediated double-strand DNA breaks resulted in up to 100% targeting of the colonies on one allele of which biallelic targeting occurred at an average of 14% with TALENs and 33% with CRISPR. Excision of the piggyBac using transposase seamlessly reproduced exactly the naturally occurring CCR5Δ32 mutation without detectable exogenous sequences. We differentiated these modified iPSCs into monocytes/macrophages and demonstrated their resistance to HIV-1 challenge. We propose that this strategy may provide an approach toward a functional cure of HIV-1 infection.

  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. 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

  17. Study on the abnormalities in sperm and gene mutation induced by retention of 147Pm in testis

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Lun Mingyue; Yang Shuqin

    1990-05-01

    The purpose of the present study is to ascertain 147 Pm retention in testis and its radiogenotoxicological effects of gene mutation through varying radioactivities of internal exposure. Especially the accumulation of 147 Pm in testis induces the dominant lethal, dominant skeletal mutation and abnormalities in sperm. Studies indicated that the cumulative absorption dose in testis increases as the internal exposure of 147 Pm increases. The internal exposure of 147 Pm can destroy the genetic materials and raise the rates of dominant lethal and dominant mutation of skeletal abnormalities in the offspring. The relationship between the rate of dominant skeletal mutation (B) and accumulated radioactivities of 147 Pm (D) in testis can be described by a linear equation that is B 20.68 + 35.48 D. The relationship between abnormalities of the sperm and the cumulative dose from 147 Pm in testis can be expressed by the following equation: S = 10.8705 D 0.5224 + 3.1768

  18. Some aspects of the combined mutagenic utilization of ionizing radiation and chemical mutagens in the experimental mutagenesis with Chlorella vulgaris B

    International Nuclear Information System (INIS)

    Mekhandzhiev, A.D.; Chankova, S.G.; Petkova, S.D.

    1979-01-01

    The influence of mutagen dose and cell cycle phase in combined mutagenic effects of ionizing radiation and EMS was experimentally studied on Chlorella vulgaris B. The duration of the cell cycle phases was determined from autoradiographic data on the kinetics of the incorporated labelled precursor ( 3 H-thymidine). The mutagenic effect was evaluated on the 10th or 11th day by the induced pigment mutations on a total of 450,105 colonies. It was found that the combining of 2, 6 or 15 krad gamma rays with EMC in doses 0.002, 0.125 or 0.5 M on the 4th, 12th, 11th, 16th or 18th hour of the cell cycle has a different effect, depending on mutagen dose and cell cycle phase. In this way, combining three different doses of gamma rays with 0.5 M EMC(LDsub(90-99)) at the onset of G 1 induces a distinct rise in the percentage of pigment mutations, as compared to the theoretically expected. The superadditive effect in this case however was associated with limitation of the mutation spectrum. Treatment with average lethal combination (6 krad gamma rays + 0.002 M EMC or 6 krad gamma rays + 0.125 M EMC) was not very effective, but the induced mutations had a rather broader spectrum (8-9 types). A comparison of the theoretically expected yield of pigment mutations with the actually obtained one shows a superadditibility only in cells treated in G 1 (LD 60 ) and in the mid S-phase (LD 40 ). (A.B.)

  19. 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)

  20. 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.

  1. 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 ...

  2. 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

  3. TAL effector nucleases induce mutations at a pre-selected location in the genome of primary barley transformants

    DEFF Research Database (Denmark)

    Wendt, Toni; Holm, Preben Bach; Starker, Colby G

    2013-01-01

    , and their broad targeting range. Here we report the assembly of several TALENs for a specific genomic locus in barley. The cleavage activity of individual TALENs was first tested in vivo using a yeast-based, single-strand annealing assay. The most efficient TALEN was then selected for barley transformation....... Analysis of the resulting transformants showed that TALEN-induced double strand breaks led to the introduction of short deletions at the target site. Additional analysis revealed that each barley transformant contained a range of different mutations, indicating that mutations occurred independently...

  4. Epistatic participation of REV1 and REV3 in the formation of UV-induced frameshift mutations in cell cycle-arrested yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Heidenreich, Erich [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)]. E-mail: erich.heidenreich@meduniwien.ac.at; Eisler, Herfried [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Steinboeck, Ferdinand [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)

    2006-01-29

    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 {zeta}). Employing the same two conditions, we now examined the effect of deletions of the genes coding for polymerase eta (Pol {eta}) (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 {eta} 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 rad30{delta} strains, but substantially reduced in a rev1{delta} as well as a rev3{delta} strain. The similarity of the rev1{delta} and the rev3{delta} 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

  5. Retigabine, a Kv7.2/Kv7.3-Channel Opener, Attenuates Drug-Induced Seizures in Knock-In Mice Harboring Kcnq2 Mutations.

    Science.gov (United States)

    Ihara, Yukiko; Tomonoh, Yuko; Deshimaru, Masanobu; Zhang, Bo; Uchida, Taku; Ishii, Atsushi; Hirose, Shinichi

    2016-01-01

    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.

  6. Involvement of p53 Mutation and Mismatch Repair Proteins Dysregulation in NNK-Induced Malignant Transformation of Human Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Ying Shen

    2014-01-01

    Full Text Available Genome integrity is essential for normal cellular functions and cell survival. Its instability can cause genetic aberrations and is considered as a hallmark of most cancers. To investigate the carcinogenesis process induced by tobacco-specific carcinogen NNK, we studied the dynamic changes of two important protectors of genome integrity, p53 and MMR system, in malignant transformation of human bronchial epithelial cells after NNK exposure. Our results showed that the expression of MLH1, one of the important MMR proteins, was decreased early and maintained the downregulation during the transformation in a histone modification involved and DNA methylation-independent manner. Another MMR protein PMS2 also displayed a declined expression while being in a later stage of transformation. Moreover, we conducted p53 mutation analysis and revealed a mutation at codon 273 which led to the replacement of arginine by histidine. With the mutation, DNA damage-induced activation of p53 was significantly impaired. We further reintroduced the wild-type p53 into the transformed cells, and the malignant proliferation can be abrogated by inducing cell cycle arrest and apoptosis. These findings indicate that p53 and MMR system play an important role in the initiation and progression of NNK-induced transformation, and p53 could be a potential therapeutic target for tobacco-related cancers.

  7. 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)

  8. Newly identified CHO ERCC3/XPB mutations and phenotype characterization

    Science.gov (United States)

    Rybanská, Ivana; Gurský, Ján; Fašková, Miriam; Salazar, Edmund P.; Kimlíčková-Polakovičová, Erika; Kleibl, Karol; Thompson, Larry H.; Piršel, Miroslav

    2010-01-01

    Nucleotide excision repair (NER) is a complex multistage process involving many interacting gene products to repair a wide range of DNA lesions. Genetic defects in NER cause human hereditary diseases including xeroderma pigmentosum (XP), Cockayne syndrome (CS), trichothiodystrophy and a combined XP/CS overlapping symptom. One key gene product associated with all these disorders is the excision repair cross-complementing 3/xeroderma pigmentosum B (ERCC3/XPB) DNA helicase, a subunit of the transcription factor IIH complex. ERCC3 is involved in initiation of basal transcription and global genome repair as well as in transcription-coupled repair (TCR). The hamster ERCC3 gene shows high degree of homology with the human ERCC3/XPB gene. We identified new mutations in the Chinese hamster ovary cell ERCC3 gene and characterized the role of hamster ERCC3 protein in DNA repair of ultraviolet (UV)-induced and oxidative DNA damage. All but one newly described mutations are located in the protein C-terminal region around the last intron–exon boundary. Due to protein truncations or frameshifts, they lack amino acid Ser751, phosphorylation of which prevents the 5′ incision of the UV-induced lesion during NER. Thus, despite the various locations of the mutations, their phenotypes are similar. All ercc3 mutants are extremely sensitive to UV-C light and lack recovery of RNA synthesis (RRS), confirming a defect in TCR of UV-induced damage. Their limited global genome NER capacity averages ∼8%. We detected modest sensitivity of ercc3 mutants to the photosensitizer Ro19-8022, which primarily introduces 8-oxoguanine lesions into DNA. Ro19-8022-induced damage interfered with RRS, and some of the ercc3 mutants had delayed kinetics. All ercc3 mutants showed efficient base excision repair (BER). Thus, the positions of the mutations have no effect on the sensitivity to, and repair of, Ro19-8022-induced DNA damage, suggesting that the ERCC3 protein is not involved in BER. PMID:19942596

  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. 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.

  11. Combinations of mutations in envZ, ftsI, mrdA, acrB and acrR can cause high-level carbapenem resistance in Escherichia coli

    DEFF Research Database (Denmark)

    Adler, Marlen; Anjum, Mehreen; Andersson, Dan I.

    2016-01-01

    of meropenem or ertapenem for similar to 60 generations. Isolated clones were whole-genome sequenced, and the order in which the identified mutations arose was determined in the passaged populations. Key mutations were reconstructed, and bacterial growth rates of populations and isolated clones and resistance...... levels to 23 antibiotics were measured. High-level resistance to carbapenems resulted from a combination of downstream effects of envZ mutation and target mutations in AcrAB-TolC-mediated drug export, together with PBP genes [mrdA (PBP2) after meropenem exposure or ftsI (PBP3) after ertapenem exposure...

  12. 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.)

  13. 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.)

  14. Early presentation of cystic kidneys in a family with a homozygous INVS mutation.

    Science.gov (United States)

    Oud, Machteld M; van Bon, Bregje W; Bongers, Ernie M H F; Hoischen, Alexander; Marcelis, Carlo L; de Leeuw, Nicole; Mol, Suzanne J J; Mortier, Geert; Knoers, Nine V A M; Brunner, Han G; Roepman, Ronald; Arts, Heleen H

    2014-07-01

    Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is the most frequent monogenic cause of end-stage renal disease in children. Infantile NPHP, often in combination with other features like situs inversus, are commonly caused by mutations in the INVS gene. INVS encodes the ciliary protein inversin, and mutations induce dysfunction of the primary cilia. In this article, we present a family with two severely affected fetuses that were aborted after discovery of grossly enlarged cystic kidneys by ultrasonography before 22 weeks gestation. Exome sequencing showed that the fetuses were homozygous for a previously unreported nonsense mutation, resulting in a truncation in the IQ1 domain of inversin. This mutation induces nonsense-mediated RNA decay, as suggested by a reduced RNA level in fibroblasts derived from the fetus. However, a significant amount of mutant INVS RNA was present in these fibroblasts, yielding mutant inversin protein that was mislocalized. In control fibroblasts, inversin was present in the ciliary axoneme as well as at the basal body, whereas in the fibroblasts from the fetus, inversin could only be detected at the basal body. The phenotype of both fetuses is partly characteristic of infantile NPHP and Potter sequence. We also identified that the fetuses had mild skeletal abnormalities, including shortening and bowing of long bones, which may expand the phenotypic spectrum associated with INVS mutations. © 2014 Wiley Periodicals, Inc.

  15. Assessment of anti-mutagenic effects of stobadine dihydro-chloride on MNNG-induced mutations in Chinese hamster cells V79

    International Nuclear Information System (INIS)

    Horvathova, E.; Slamenova, D.; Chorvatovicova, D.; Wsolova, L.

    1995-01-01

    Mutagenicity of N-methyl-n'-nitro-N-nitrosoguanidine (MNNG) and anti-mutagenic effect of antioxidant stobadine (STB) were investigated by so called HGPRT/V79 system. Cells were treated by STB before, during and after MNNG-treatment. Our results showed that the highest anti-mutagenic effect of STB was observed if the drug was given as a pretreatment before exposure of cells to MNNG. This effect was not concentration dependent within the framework of 1.5 - 9 mmol. All other combinations of MNNG- and STB-treatment led to the weaker but statistically significant decrease of 6-TG r mutations. Inhibition of proteosynthesis induced by methylxanthine pentoxifylline in the time of pre-MNNG-treatment removed completely anti-mutagenic effects of STB. In addition of mutagenicity assays, cytotoxicity of STB and combined effects of MNNG and STB were studied. Trypan blue exclusion and growth activity of influenced cells showed that application of STB (1.5 mmol) before or after MNNG (0.5 μg/cm 3 ) treatment had a similar toxic effects as MNNG alone. Application of STB during MNNG-treatment or pretreatment of cells with STB followed by combined treatment of cells by STB + MNNG statistically significantly decreased viability of cells. There are probably no relationship between the anti-mutagenic and the toxic effects of combined influence of STB and MNNG on V79 cells. (author)

  16. Adaptive mutation: has the unicorn landed?

    Science.gov (United States)

    Foster, P L

    1998-04-01

    Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution.

  17. Adaptive mutation: has the unicorn landed?

    Science.gov (United States)

    Foster, P L

    1998-01-01

    Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution. PMID:9560365

  18. Mutation breeding in malting barley

    Energy Technology Data Exchange (ETDEWEB)

    Hiraki, Makoto; Sanada, Matsuyoshi

    1984-03-01

    The released varieties of malting barley through mutation breeding is more than ten in number, including foreign varieties. In Japan four varieties has been released so far. We started mutation breeding in 1956 together with cross breeding that we employed before. Until now, Gamma 4, Amagi Nijo 1 and Fuji Nijo 2 have been produced from the direct use of induced mutations and Nirasaki Nijo 8 from the indirect use of them. Mutation breeding has been used mainly in the partial improvement of agronomic characteristics since the selection for malting quality was very complicated. As the variety bred by induced mutation is usually equivalent to the original variety in malting quality, both this new variety and the original one could be cultivated in the same area without any problem on later malt production. Particularly when one farmer cultivates barley in an extensive acreage, he can harvest at the best time according to the different maturing time of each variety. From these points of view, mutation breeding is an efficient tool in malting barley breeding. Mutagens we have used so far are X-rays, ..gamma..-rays, neutron and chemicals such as dES. From our experience in selection, the low dose of radiation and chemical mutagens are more effective in selection of point mutation than the high dose of radiation which tends to produce many abnormal but few practical mutants. (author).

  19. 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

  20. Induction of mutation on mulberry (morus alba L.) by using in vitro techniques in combination with gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen Van Vinh [Nuclear Research Institute, Department of Biotechnology, Dalat (Viet Nam)

    2001-03-01

    Mutation induction and selection of desired characters on mulberry will contribute to industrialization and modernization in agricultural development in Vietnam. The objectives are to conduct biochemical and physiological analyses of collected mulberry varieties and to improve techniques for boosting yield and better quality in some mulberry genotypes by using in vitro technique combined with gamma irradiation. Two mulberry varieties named BauDen and VA 186 were used. Cuts of them were treated with gamma rays of Co-60, cultivated in experimental field with use of vitro technique to rapidly isolate mutants in irradiated population and investigated for plantlets, color of leaves, etc 30 days after cultivation. The results on the mutation frequency and spectrum of variation as well as the results of selection and isolation are presented. Eleven mutated clones from the two starting varieties were obtained during 1993-99. Three of them are now being cultivated in LamDong province fields. (S. Ohno)

  1. Induction of mutation on mulberry (morus alba L.) by using in vitro techniques in combination with gamma irradiation

    International Nuclear Information System (INIS)

    Nguyen Van Vinh

    2001-01-01

    Mutation induction and selection of desired characters on mulberry will contribute to industrialization and modernization in agricultural development in Vietnam. The objectives are to conduct biochemical and physiological analyses of collected mulberry varieties and to improve techniques for boosting yield and better quality in some mulberry genotypes by using in vitro technique combined with gamma irradiation. Two mulberry varieties named BauDen and VA 186 were used. Cuts of them were treated with gamma rays of Co-60, cultivated in experimental field with use of vitro technique to rapidly isolate mutants in irradiated population and investigated for plantlets, color of leaves, etc 30 days after cultivation. The results on the mutation frequency and spectrum of variation as well as the results of selection and isolation are presented. Eleven mutated clones from the two starting varieties were obtained during 1993-99. Three of them are now being cultivated in LamDong province fields. (S. Ohno)

  2. Antitumor bystander effect induced by radiation-inducible target gene therapy combined with α particle irradiation

    International Nuclear Information System (INIS)

    Liu Hui; Jin Chufeng; Wu Yican; Ge Shenfang; Wu Lijun; FDS Team

    2012-01-01

    In this work, we investigated the bystander effect of the tumor and normal cells surrounding the target region caused by radiation-inducible target gene therapy combined with α-particle irradiation. The receptor tumor cell A549 and normal cell MRC-5 were co-cultured with the donor cells irradiated to 0.5 Gy or the non-irradiated donor cells, and their survival and apoptosis fractions were evaluated. The results showed that the combined treatment of Ad-ET and particle irradiation could induce synergistic antitumor effect on A549 tumor cell, and the survival fraction of receptor cells co-cultured with the irradiated cells decreased by 6%, compared with receptor cells co-cultured with non-irradiated cells, and the apoptosis fraction increased in the same circumstance, but no difference was observed with the normal cells. This study demonstrates that Ad-ET combined with α-particle irradiation can significantly cause the bystander effect on neighboring tumor cells by inhibiting cell growth and inducing apoptosis, without obvious toxicity to normal cells. This suggests that combining radiation-inducible TRAIL gene therapy and irradiation may improve tumor treatment efficacy by specifically targeting tumor cells and even involving the neighboring tumor cells. (authors)

  3. 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)

  4. Deletion mutations of bacteriophage

    International Nuclear Information System (INIS)

    Ryo, Yeikou

    1975-01-01

    Resolution of mutation mechanism with structural changes of DNA was discussed through the studies using bacteriophage lambda. One of deletion mutations inductions of phage lambda is the irradiation of ultraviolet ray. It is not clear if the inductions are caused by errors in reparation of ultraviolet-induced damage or by the activation of int gene. Because the effective site of int gene lies within the regions unnecessary for existing, it is considered that int gene is connected to deletion mutations induction. A certain system using prophage complementarity enables to detect deletion mutations at essential hereditary sites and to solve the relations of deletion mutations with other recombination system, DNA reproduction and repairment system. Duplication and multiplication of hereditary elements were discussed. If lambda deletion mutations of the system, which can control recombination, reproduction and repairment of added DNA, are constructed, mutations mechanism with great changes of DNA structure can be solved by phage lambda. (Ichikawa, K.)

  5. 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)

  6. 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)

  7. 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.)

  8. 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

  9. A Somatic HIF2α Mutation-Induced Multiple and Recurrent Pheochromocytoma/Paraganglioma with Polycythemia: Clinical Study with Literature Review.

    Science.gov (United States)

    Liu, Qiuli; Wang, Yan; Tong, Dali; Liu, Gaolei; Yuan, Wenqiang; Zhang, Jun; Ye, Jin; Zhang, Yao; Yuan, Gang; Feng, Qingxing; Zhang, Dianzheng; Jiang, Jun

    2017-03-01

    A syndrome known as pheochromocytomas (PCC)/paragangliomas (PGL) and polycythemia resulted from gain-of-function mutation of hypoxia-inducible factor 2α (HIF2α) has been reported recently. However, clinical features of this syndrome vary from patient to patient. In our study, we described the clinical features of the patient within 15-year follow-up with a literature review. The patient presented with "red face" since childhood and was diagnosed with polycythemia and pheochromocytoma in 2000, and then, tumor was removed at his age of 27 (year 2000). However, 13 years later (2013), he was diagnosed with multiple paragangliomas. Moreover, 2 years later (2015), another two paragangaliomas were also confirmed. Genetic analysis of hereditary PCC/PGL-related genes was conducted. A somatic heterozygous missense mutation of HIF2α (c.1589C>T) was identified at exon 12, which is responsible for the elevated levels of HIF2α and erythropoietin (EPO) and subsequent development of paragangaliomas. However, this mutation was only found in the tumors from three different areas, not in the blood. So far, 13 cases of PCC/PGL with polycythemia have been reported. Among them, somatic mutations of HIF2α at exon 12 are responsible for 12 cases, and only 1 case was caused by germline mutation of HIF2α at exon 9. The HIF2α mutation-induced polycythemia with PCC/PGL is a rare syndrome with no treatment for cure. Comprehensive therapies for this disease include removal of the tumors and intermittent phlebotomies; administration of medications to control blood pressure and to prevent complications or death resulted from high concentration of red blood cell (RBC). Genetic test is strongly recommended for patients with early onset of polycythemia and multiple/recurrent PCC/PGL.

  10. 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.

  11. Study on the abnormalities in sperm and gene mutation induced by retention of {sup 147}Pm in testis

    Energy Technology Data Exchange (ETDEWEB)

    Shoupeng, Zhu; Mingyue, Lun; Shuqin, Yang [Suzhou Medical Coll., JS (China)

    1990-05-01

    The purpose of the present study is to ascertain {sup 147}Pm retention in testis and its radiogenotoxicological effects of gene mutation through varying radioactivities of internal exposure. Especially the accumulation of {sup 147}Pm in testis induces the dominant lethal, dominant skeletal mutation and abnormalities in sperm. Studies indicated that the cumulative absorption dose in testis increases as the internal exposure of {sup 147}Pm increases. The internal exposure of {sup 147}Pm can destroy the genetic materials and raise the rates of dominant lethal and dominant mutation of skeletal abnormalities in the offspring. The relationship between the rate of dominant skeletal mutation (B) and accumulated radioactivities of {sup 147}Pm (D) in testis can be described by a linear equation that is B 20.68 + 35.48 D. The relationship between abnormalities of the sperm and the cumulative dose from {sup 147}Pm in testis can be expressed by the following equation: S = 10.8705 D{sup 0.5224} + 3.1768.

  12. Was Muller's 1946 Nobel Prize research for radiation-induced gene mutations peer-reviewed?

    Science.gov (United States)

    Calabrese, Edward J

    2018-06-06

    This historical analysis indicates that it is highly unlikely that the Nobel Prize winning research of Hermann J. Muller was peer-reviewed. The published paper of Muller lacked a research methods section, cited no references, and failed to acknowledge and discuss the work of Gager and Blakeslee (PNAS 13:75-79, 1927) that claimed to have induced gene mutation via ionizing radiation six months prior to Muller's non-data Science paper (Muller, Science 66(1699):84-87, 1927a). Despite being well acclimated into the scientific world of peer-review, Muller choose to avoid the peer-review process on his most significant publication. It appears that Muller's actions were strongly influenced by his desire to claim primacy for the discovery of gene mutation. The actions of Muller have important ethical lessons and implications today, when self-interest trumps one's obligations to society and the scientific culture that supports the quest for new knowledge and discovery.

  13. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice

    Science.gov (United States)

    Safdar, Adeel; Bourgeois, Jacqueline M.; Ogborn, Daniel I.; Little, Jonathan P.; Hettinga, Bart P.; Akhtar, Mahmood; Thompson, James E.; Melov, Simon; Mocellin, Nicholas J.; Kujoth, Gregory C.; Prolla, Tomas A.; Tarnopolsky, Mark A.

    2011-01-01

    A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities. PMID:21368114

  14. Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches.

    Science.gov (United States)

    Gobin-Limballe, Stéphanie; McAndrew, Ryan P; Djouadi, Fatima; Kim, Jung-Ja; Bastin, Jean

    2010-05-01

    Very-Long-Chain Acyl-CoA Dehydrogenase deficiency (VLCADD) is an autosomal recessive disorder considered as one of the more common ss-oxidation defects, possibly associated with neonatal cardiomyopathy, infantile hepatic coma, or adult-onset myopathy. Numerous gene missense mutations have been described in these VLCADD phenotypes, but only few of them have been structurally and functionally analyzed, and the molecular basis of disease variability is still poorly understood. To address this question, we first analyzed fourteen disease-causing amino acid changes using the recently described crystal structure of VLCAD. The predicted effects varied from the replacement of amino acid residues lining the substrate binding cavity, involved in holoenzyme-FAD interactions or in enzyme dimerisation, predicted to have severe functional consequences, up to amino acid substitutions outside key enzyme domains or lying on near enzyme surface, with predicted milder consequences. These data were combined with functional analysis of residual fatty acid oxidation (FAO) and VLCAD protein levels in patient cells harboring these mutations, before and after pharmacological stimulation by bezafibrate. Mutations identified as detrimental to the protein structure in the 3-D model were generally associated to profound FAO and VLCAD protein deficiencies in the patient cells, however, some mutations affecting FAD binding or monomer-monomer interactions allowed a partial response to bezafibrate. On the other hand, bezafibrate restored near-normal FAO rates in some mutations predicted to have milder consequences on enzyme structure. Overall, combination of structural, biochemical, and pharmacological analysis allowed assessment of the relative severity of individual mutations, with possible applications for disease management and therapeutic approach. Copyright 2010 Elsevier B.V. All rights reserved.

  15. The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Wang LL

    2018-04-01

    Full Text Available Lulu Wang, Yan Li, Luchun Li, Zhijuan Wu, Dan Yang, Huiwen Ma, Donglin Wang Oncology Department, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Shapingba District, Chongqing, China Purpose: This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC patients harboring epidermal growth factor receptor (EGFR-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation in a real-life setting. Patients and methods: One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS. Results: Longer PFS and overall survival (OS, and better objective response rate (ORR were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. Conclusion: The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS,especially in those who harbored the EGFR exon 19 deletion. Keywords: non-small-cell lung cancer, EGFR-TKI, icotinib, chemotherapy, first-line treatment

  16. Non-homologous end joining dependency of {gamma}-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Heidenreich, Erich [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)]. E-mail: erich.heidenreich@meduniwien.ac.at; Eisler, Herfried [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)

    2004-11-22

    There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by {gamma}-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the {gamma}-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development.

  17. Non-homologous end joining dependency of γ-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

    International Nuclear Information System (INIS)

    Heidenreich, Erich; Eisler, Herfried

    2004-01-01

    There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by γ-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the γ-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development

  18. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

    Science.gov (United States)

    Braun, Daniela A; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A; Schanze, Denny; Ashraf, Shazia; Ullmann, Jeremy F P; Hoogstraten, Charlotte A; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I Chiara; Sanchez-Ferras, Oraly; Hu, Jennifer F; Boschat, Anne-Claire; Sanquer, Sylvia; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E; Pabst, Werner L; Warejko, Jillian K; Daga, Ankana; Basta, Tamara; Matejas, Verena; Scharmann, Karin; Kienast, Sandra D; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T; Gaffney, Patrick M; Gipson, Patrick E; Hsu, Chyong-Hsin; Kari, Jameela A; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-Ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okashah; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Ozaltin, Fatih; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth R; Rump, Patrick; Schnur, Rhonda E; Shiihara, Takashi; Sinha, Manish D; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A; Tsai, Wen-Hui; Tsai, Jeng-Daw; Topaloglu, Rezan; Vester, Udo; Viskochil, David H; Vatanavicharn, Nithiwat; Waxler, Jessica L; Wierenga, Klaas J; Wolf, Matthias T F; Wong, Sik-Nin; Leidel, Sebastian A; Truglio, Gessica; Dedon, Peter C; Poduri, Annapurna; Mane, Shrikant; Lifton, Richard P; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Callewaert, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

    2017-10-01

    Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.

  19. Study on creation and utilization of induced mutation rice materials

    International Nuclear Information System (INIS)

    Pang Aijun; Peng Weizheng; Pang Boliang; Peng Xuanming; Yang Zhen; Zhang Xianxin; Zhang Yuanhai

    2011-01-01

    60 Co γ-ray, spaceflight, laser were respectively or combinedly used to treat rice lines or hybrid materials. Many special type of seed breed lines, including high yielding ones, top quality ones, stunt stem ones, disease/pest resistent ones, colourful rices, big size of grain ones etc. were selected from the mutation materials, some were directly used as new varieties and some were indirectly used to breed hybrid varieties. All the new varieties such as 'xiangzaonuo No.1', 'xiangzaoxian No.20', 'xiangzaoxian No.21', 'xiangfu 994', 'peiliangyou 721', 'zhuliangyou 124' were popularly planted and great social and economical benefit was obtained. (authors)

  20. Combination therapy with vemurafenib (PLX4032/RG7204 and metformin in melanoma cell lines with distinct driver mutations

    Directory of Open Access Journals (Sweden)

    Recio Juan A

    2011-05-01

    Full Text Available Abstract Background A molecular linkage between the MAPK and the LKB1-AMPK energy sensor pathways suggests that combined MAPK oncogene inhibition and metabolic modulation of AMPK would be more effective than either manipulation alone in melanoma cell lines. Materials and methods The combination of the BRAF inhibitor vemurafenib (formerly PLX4032 and metformin were tested against a panel of human melanoma cell lines with defined BRAF and NRAS mutations for effects on viability, cell cycle and apoptosis. Signaling molecules in the MAPK, PI3K-AKT and LKB1-AMPK pathways were studied by Western blot. Results Single agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status, but in one NRASQ61K mutant cell line it powerfully stimulated cell growth. Synergistic anti-proliferative effects of the combination of metformin with vemurafenib were observed in 6 out of 11 BRAFV600E mutants, including highly synergistic effects in two BRAFV600E mutant melanoma cell lines. Antagonistic effects were noted in some cell lines, in particular in BRAFV600E mutant cell lines resistant to single agent vemurafenib. Seven out of 8 BRAF wild type cell lines showed marginally synergistic anti-proliferative effects with the combination, and one cell line had highly antagonistic effects with the combination. The differential effects were not dependent on the sensitivity to each drug alone, effects on cell cycle or signaling pathways. Conclusions The combination of vemurafenib and metformin tended to have stronger anti-proliferative effects on BRAFV600E mutant cell lines. However, determinants of vemurafenib and metformin synergism or antagonism need to be understood with greater detail before any potential clinical utility of this combination.

  1. Environmental modulation of somatic mutations: nature of interactions. Final report, 1 June 1974--31 May 1977

    International Nuclear Information System (INIS)

    Mericle, L.W.

    1977-05-01

    Research on this project has had as a major goal a combined ecologic-genetic investigation of somatic mutations in order to evaluate the impacts of certain changing environmental parameters. The ultimate aim, to better understand how such environmental-mutation interactions operate and to assure the information obtained be extrapolatable to conditions and events in nature. Higher plants delineate reproductive tissues late in development from meristematic, somatic tissues. Moreover, the prevailing method of reproduction may be without sexual fusion of gametes and/or wholly asexual (vegetative). Therefore, somatic mutations can have as far-reaching genetic significance for a plant population as when germ cells, themselves, are directly affected. Our data show diurnal temperature differences (DTD) of greater than or equal to 22.2 C-degrees to be very effective mutagenic agents in the Tradescantia somatic mutation system. Further, these ranges of DTD were found to occur often in important seed production areas. A DTD of 22.2 in magnitude can increase mutations 10-fold. And, durations short as 1-day can induce significant increases in mutation rate. Whether interaction of 22.2 DTD with low-level radiation (800 mR/day) is synergistic or attenuative is still debatable. We believe, however, that spontaneous, and 22.2 DTD induced, mutations occur mainly via the genetic mechanism of somatic crossing-over; mutations from acute ionizing radiation (e.g., 30-60 R γ) via chromosome breakage, producing micronuclei. Requirements for maximizing the Discriminatory Response Capability (DRC) in the Tradescantia somatic mutation system are set forth

  2. Induced mutations for disease resistance in wheat

    International Nuclear Information System (INIS)

    Cerny, J.; Hanis, M.; Hanisova, A.; Knytl, V.; Sasek, A.

    1983-01-01

    Mutation induction has been used over a period of 20 years to obtain mutants of wheat with improved disease resistance. 34 wheat cultivars have been treated with X-rays, gamma rays, thermal neutrons or EMS. A great number of mutants were selected. Their mutational origin was verified by electrophoretic analysis of gliadin spectra. Resistances have been confirmed over several generations. None of the mutants have been released yet for commercial cultivation because of shortcomings in yield or susceptibility to other diseases. The use of mutants in cross-breeding is considered. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1970-03-01

    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.

  4. 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.

  5. Mutational specificity of SOS mutagenesis

    International Nuclear Information System (INIS)

    Kato, Takeshi

    1986-01-01

    In an approach to the isolation of mutants of E. coli unable to produce mutations by ultraviolet light, the author has found new umuC-mutants. Their properties could be explained by ''SOS hypothesis of Radman and Witkin'', which has now been justified by many investigators. Analysis of the umuC region of E. coli chromosome cloned in pSK 100 has led to the conclusion that two genes, umuD and umuC, having the capacity of mutation induction express in the same mechanism as that of SOS genes, which is known to be inhibited by LexA protein bonding to ''SOS box'' found at promotor region. Suppressor analysis for mutational specificity has revealed: (i) umuDC-independent mutagens, such as EMS and (oh) 4 Cy, induce selected base substitution alone; and (ii) umuDC-dependent mutagens, such as X-rays and gamma-rays, induce various types of base substitution simultaneously, although they have mutational specificity. In the umuDC-dependent processes of basechange mutagenesis, the spectra of base substitution were a mixture of base substitution reflecting the specific base damages induced by individual mutagens and nonspecific base substitution. In conclusion, base substitution plays the most important role in umuDC-dependent mutagenesis, although mutagenesis of umuDC proteins remains uncertain. (Namekawa, K.)

  6. DNA replication error-induced extinction of diploid yeast.

    Science.gov (United States)

    Herr, Alan J; Kennedy, Scott R; Knowels, Gary M; Schultz, Eric M; Preston, Bradley D

    2014-03-01

    Genetic defects in DNA polymerase accuracy, proofreading, or mismatch repair (MMR) induce mutator phenotypes that accelerate adaptation of microbes and tumor cells. Certain combinations of mutator alleles synergistically increase mutation rates to levels that drive extinction of haploid cells. The maximum tolerated mutation rate of diploid cells is unknown. Here, we define the threshold for replication error-induced extinction (EEX) of diploid Saccharomyces cerevisiae. Double-mutant pol3 alleles that carry mutations for defective DNA polymerase-δ proofreading (pol3-01) and accuracy (pol3-L612M or pol3-L612G) induce strong mutator phenotypes in heterozygous diploids (POL3/pol3-01,L612M or POL3/pol3-01,L612G). Both pol3-01,L612M and pol3-01,L612G alleles are lethal in the homozygous state; cells with pol3-01,L612M divide up to 10 times before arresting at random stages in the cell cycle. Antimutator eex mutations in the pol3 alleles suppress this lethality (pol3-01,L612M,eex or pol3-01,L612G,eex). MMR defects synergize with pol3-01,L612M,eex and pol3-01,L612G,eex alleles, increasing mutation rates and impairing growth. Conversely, inactivation of the Dun1 S-phase checkpoint kinase suppresses strong pol3-01,L612M,eex and pol3-01,L612G,eex mutator phenotypes as well as the lethal pol3-01,L612M phenotype. Our results reveal that the lethal error threshold in diploids is 10 times higher than in haploids and likely determined by homozygous inactivation of essential genes. Pronounced loss of fitness occurs at mutation rates well below the lethal threshold, suggesting that mutator-driven cancers may be susceptible to drugs that exacerbate replication errors.

  7. Combination of diffusion tensor imaging and conventional MRI correlates with isocitrate dehydrogenase 1/2 mutations but not 1p/19q genotyping in oligodendroglial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Ji [Huashan Hospital of Fudan University, Department of Radiology, Shanghai (China); Huashan Hospital of Fudan University, Department of Neuropathology, Shanghai (China); Tan, Wenli [Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Department of Radiology, Shanghai (China); Wen, Jianbo; Pan, Jiawei; Zhang, Jun; Geng, Daoying [Huashan Hospital of Fudan University, Department of Radiology, Shanghai (China); Wang, Yin [Huashan Hospital of Fudan University, Department of Neuropathology, Shanghai (China)

    2016-06-15

    To explore the correlations of conventional MRI (cMRI) and diffusion tensor imaging (DTI) values with the 1p/19 codeletion and IDH mutations in oligodendroglial tumours (OTs). Eighty-four patients with OTs who underwent cMRI and DTI were retrospectively reviewed. The maximal fractional anisotropy and minimal apparent diffusion coefficient (ADC) were measured and compared using the Mann-Whitney U test. Receiver operating characteristic curves, logistic regression analysis and four-table statistics analysis were performed to predict genotypings. OTs with 1p/19q codeletion or IDH mutations were prone to locate in frontal (P = 0.106 and 0.005, respectively) and insular lobes and were associated with absent or blurry contrast enhancement (P = 0.040 and 0.013, respectively). DTI values showed significant differences between OTs with and without IDH mutations (P < 0.05) but not in OTs with and without 1p/19q loss. The Ki-67 index significantly correlated with IDH mutations (P = 0.002) but not with 1p/19q codeletion. A combination of DTI and cMRI for the identification of IDH mutations resulted in sensitivity, specificity, positive and negative predictive values of 92.2 %, 75.8 %, 93.8 % and 71.1 %, respectively. Combination of DTI and cMRI correlates with isocitrate dehydrogenase 1/2 mutations but not 1p/19q genotyping in OTs. (orig.)

  8. CRISPR Correction of a Homozygous Low-Density Lipoprotein Receptor Mutation in Familial Hypercholesterolemia Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Omer, Linda; Hudson, Elizabeth A; Zheng, Shirong; Hoying, James B; Shan, Yuan; Boyd, Nolan L

    2017-11-01

    Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans. However, demand for donated livers and high-quality hepatocytes overwhelm the supply. Human pluripotent stem cells can differentiate to hepatocyte-like cells (HLCs) with the potential for experimental and clinical use. To be of future clinical use as autologous cells, LDLR genetic mutations in derived FH-HLCs need to be corrected. Genome editing technology clustered-regularly-interspaced-short-palindromic-repeats/CRISPR-associated 9 (CRISPR/Cas9) can repair pathologic genetic mutations in human induced pluripotent stem cells. We used CRISPR/Cas9 genome editing to permanently correct a 3-base pair homozygous deletion in LDLR exon 4 of patient-derived HoFH induced pluripotent stem cells. The genetic correction restored LDLR-mediated endocytosis in FH-HLCs and demonstrates the proof-of-principle that CRISPR-mediated genetic modification can be successfully used to normalize HoFH cholesterol metabolism deficiency at the cellular level.

  9. 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

  10. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Saamin, S [Cocoa and Coconut Research Division, Malaysian Agricultural Research and Development Institute (Malaysia); Thompson, M M [Department of Horticulture, Oregon State University, Corvallis, OR (United States)

    1989-01-01

    Full text: Dormant scions of 'Bing' were exposed to 1-2.5 kR gamma radiation. The main buds were excised and the scions grafted to allow the growth of accessory buds into primary shoots. The frequency and types of mutations were described in a population of 3307 M{sub 1}V{sub 2} shoot. The overall mutation frequency was 2.7% incl. 0.15% growth-reduced mutants. The experiment was repeated using 3kR and 4kR fractionated doses in water. Differences in mutation frequency at 3kR and 4kR were not significant. Of 2765 surviving M{sub 1}V{sub 2} shoots derived from irradiation of accessory buds of both standard and V{sub 1} shoots, the overall mutation frequency was 3.3% incl. 1.7% partial leaf mutants, 1.0% leaf mutants, and 0.54% growth-reduced mutants. For maximum mutation rate with adequate survival we suggest acute irradiation of accessory buds in air at dosages approximating LD50. Mutant sectors in M{sub 1}V{sub 1} shoots derived from accessory buds are larger than those from main buds, as revealed by the higher number of mutant repeats. (author)

  12. 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 o...

  13. Induction of different types of mutations in yeast Saccharomyces serevisiae by γ-radiation

    International Nuclear Information System (INIS)

    Lyubimova, K.A.; Shvaneva, N.V.; Koltovaya, N.A.

    2005-01-01

    Several tester systems were used to study a wide spectrum of genetic changes induced by γ-radiation in the yeast Saccharomyces cerevisiae. The tester systems allow one to identify a loss of chromosomes, recombination (crossing over) and point mutations (frame shifts and base-pair substitutions.) Large genome changes were induced by γ-rays more efficiently than the point mutations. The dose dependence of the point mutations frequency was linear. Spontaneous and induced mutation rates per base pair corresponded with the known literature data for the same tester systems. Our finding shows that the used tester systems are not specific. They are useful for further study of mutations induced by ionizing radiation with various physical characteristics

  14. Somatic mutation in larvae of the silkworm, Bombyx mori, induced by heavy ion irradiation to diapause eggs

    Energy Technology Data Exchange (ETDEWEB)

    Kotani, Eiji; Furusawa, Toshiharu [Kyoto Inst. of Tech. (Japan). Faculty of Textile Science; Nagaoka, Shunji [Fujita Health Univ., Toyoake, Aichi (Japan). School of Health Sciences] [and others

    2002-12-01

    In order to investigate whether eggs of the black-striped strain (P{sup S}) of the silkworm, Bombyx mori, represent an appropriate model for estimating the biological effect of cosmic radiation, radiosensitivity of the eggs against X-rays and heavy ion particles was examined as ground-based experiments. The exposure of diapause eggs to X-rays or heavy ion particles resulted in somatic mutations appearing as a white spot on the black integument during larval stage. Irradiation of non-diapause eggs with X-rays demonstrated a significant difference in frequency of the mutation between fractionated and single administration doses, but no difference was observed in diapause eggs. Incidence of the mutation as induced by carbon ion beams for 15-day old eggs was higher for eggs that had been kept at 15 deg C than those kept at 25 deg C. Neon beam irradiation of diapause eggs displayed dose- and linear energy transfer (LET)-dependent effects, causing a maximal rate of the mutation at 150 keV/{mu}m. These results confirm that B. mori eggs represent valid models for estimating the biological effects of cosmic radiation. (author)

  15. Induced mutations for disease resistance in wheat and barley

    International Nuclear Information System (INIS)

    Hanis, M.; Hanisova, A.; Knytl, V.; Cerny, J.; Benc, S.

    1977-01-01

    The induction of mutations in cultivars of wheat (Triticum aestivum), barley (Hordeum vulgare), and field beans (Phaseolus vulgaris) has been part of the breeding programme at the Plant Breeding Station at Stupice since 1960. A total of 26 cultivars or selections of winter wheat, 4 cultivars or selections of spring wheat, 2 cultivars of field beans, and 43 selections of spring barley have been treated since 1960. A total of 140 mutant lines of wheat and 37 mutant lines of barley with improved disease resistance of a race-specific type have been obtained. Several mutation programme derived cultivars have been registered in Czechoslovakia (''Diamant'', ''Ametyst'', ''Favorit'', ''Hana'', ''Rapid'', and ''Atlas'' in barley, and ''Alfa'' in field beans), but none of them is a mutation for disease resistance. A series of mutants have been used in crossing programmes. Approaches to improve the efficiency of mutation breeding for disease resistance are suggested. (author)

  16. Biological effects of space-induced mutation on robinia pseudoacacia

    International Nuclear Information System (INIS)

    Yuan Cunquan; Li Yun; Lu Chao; Yang Min; Zhang Yuyao

    2010-01-01

    Dry seeds of Robinia pseudoacacia were carried by Shijian No.8 breeding satellite for mutagenesis and the biological effect of space-induced mutation was studied. The parameters of Robinia pseudoacacia such as plant height, stem base, branch number, knot spacing, length of thorn and chlorophyll content were analyzed, and, at the same time, the genetic diversity was tested by SSR marker. The results showed that the plant height and stem base of 2-year-old seedlings which derived from space mutagenesis were 22.0% and 24.1% lower than those of control, and 3-year-old seedlings were 13.1% and 22.4% lower than those of control, respectively. While the inhibiting effect of plant height became undermined in the following growth years. However, the inhibiting effect in stem base existed all the time,the length of thorn of branch and stem were 15.6% and 28.6% shorter than the control,respectively. Compared with the control,the variation of the length of thorn from stem was extremely significant. The variation of chlorophyll a content from space mutagenesis compared with control was not remarkable, while the total chlorophyll and chlorophyll b contents were 18.7% and 9.7% lower than those of control, respectively, and the difference between space mutagenesis and control was significant. While the chlorophyll a/b was 25.6% higher than that of control, but the difference was not significant. The coefficient of variation of the relative traits was increased by the space mutagenesis. The extensively population genome mutation after space-induction were not detected by SSR (Simple Sequence Repeats). (authors)

  17. PINK1 heterozygous mutations induce subtle alterations in dopamine-dependent synaptic plasticity

    Science.gov (United States)

    Madeo, G.; Schirinzi, T.; Martella, G.; Latagliata, E.C.; Puglisi, F.; Shen, J.; Valente, E.M.; Federici, M.; Mercuri, N.B.; Puglisi-Allegra, S.; Bonsi, P.; Pisani, A.

    2014-01-01

    Background Homozygous or compound heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene are causative of autosomal recessive, early onset PD. Single heterozygous mutations have been repeatedly detected in a subset of patients as well as in non-affected subjects, and their significance has long been debated. Several neurophysiological studies from non-manifesting PINK1 heterozygotes have shown the existence of neural plasticity abnormalities, indicating the presence of specific endophenotypic traits in the heterozygous state. Methods In the present study, we performed a functional analysis of corticostriatal synaptic plasticity in heterozygous PINK1 knock-out (PINK1+/−) mice by a multidisciplinary approach. Results We found that, despite a normal motor behavior, repetitive activation of cortical inputs to striatal neurons failed to induce long-term potentiation (LTP), whereas long-term depression (LTD) was normal. Although nigral dopaminergic neurons exhibited normal morphological and electrophysiological properties with normal responses to dopamine receptor activation, we measured a significantly lower dopamine release in the striatum of PINK1+/−, compared to control mice, suggesting that a decrease in stimulus-evoked dopamine overflow acts as a major determinant for the LTP deficit. Accordingly, pharmacological agents capable of increasing the availability of dopamine in the synaptic cleft restored a normal LTP in heterozygous mice. Moreover, MAO-B inhibitors rescued a physiological LTP and a normal dopamine release. Conclusions Our results provide novel evidence for striatal plasticity abnormalities even in the heterozygous disease state. These alterations might be considered an endophenotype to this monogenic form of PD, and a valid tool to characterize early disease stage and design possible disease-modifying therapies. PMID:24167038

  18. 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

  19. Plant mutation reports, Vol. 2, No. 1, December 2008

    International Nuclear Information System (INIS)

    2008-12-01

    The International Symposium on Induced Mutations in Plants (ISIMP) was successfully held in Vienna, Austria 12-15 August 2008. It attracted more almost 500 participants, demonstrating a broad interest in induced mutations in the plant breeding and research community. The titles of oral presentations are included in this issue. Some papers submitted to the Symposium by authors who were unable to attend the Symposium are included in this issue. In this issue, you will learn that mutations can be induced in uncommon plants using various means and utilized for various purposes. For example, Kacholam, guar and cocoyam are not widely cultivated crop species and there is very limited genetic variability, Kanakamanay, Arora et al. and Ndzana et al. reported the induction of mutations as a valuable source of genetic variability in these crops. Rice is a staple food crop and has a history of successful application of mutation techniques for its improvement; however, the virus resistant mutant varieties released in the United Republic of Tanzania, the cold tolerant mutant lines developed in Madagascar and the use of proton radiation for mutation induction in this field. The use of mutation techniques for improving tomato productivity in low water supply area, for increasing crossability and progeny fertility of mungbean crossed with its wild relative species and for investigating leaf structure in mungbean are convincing examples of the usefulness of mutation techniques

  20. Mutation Processes in 293-Based Clones Overexpressing the DNA Cytosine Deaminase APOBEC3B.

    Directory of Open Access Journals (Sweden)

    Monica K Akre

    Full Text Available Molecular, cellular, and clinical studies have combined to demonstrate a contribution from the DNA cytosine deaminase APOBEC3B (A3B to the overall mutation load in breast, head/neck, lung, bladder, cervical, ovarian, and other cancer types. However, the complete landscape of mutations attributable to this enzyme has yet to be determined in a controlled human cell system. We report a conditional and isogenic system for A3B induction, genomic DNA deamination, and mutagenesis. Human 293-derived cells were engineered to express doxycycline-inducible A3B-eGFP or eGFP constructs. Cells were subjected to 10 rounds of A3B-eGFP exposure that each caused 80-90% cell death. Control pools were subjected to parallel rounds of non-toxic eGFP exposure, and dilutions were done each round to mimic A3B-eGFP induced population fluctuations. Targeted sequencing of portions of TP53 and MYC demonstrated greater mutation accumulation in the A3B-eGFP exposed pools. Clones were generated and microarray analyses were used to identify those with the greatest number of SNP alterations for whole genome sequencing. A3B-eGFP exposed clones showed global increases in C-to-T transition mutations, enrichments for cytosine mutations within A3B-preferred trinucleotide motifs, and more copy number aberrations. Surprisingly, both control and A3B-eGFP clones also elicited strong mutator phenotypes characteristic of defective mismatch repair. Despite this additional mutational process, the 293-based system characterized here still yielded a genome-wide view of A3B-catalyzed mutagenesis in human cells and a system for additional studies on the compounded effects of simultaneous mutation mechanisms in cancer cells.

  1. Induced mutation aiming at obtaining lodging resistance in wheat C V.Omid(Triticum Aestivum)

    International Nuclear Information System (INIS)

    Majd, F.; Rezazadeh, M.; Ghohari, A.

    1993-01-01

    Mutation breeding has been an important part breeding research for solving some of the existing problems related to wheat. A locally adopted wheat cultivar 'Omid' which is a traditionally tall wheat mostly cultivated in regions with a continental climate and is susceptible to lodging was chosen as research material. The nuclear research department for agriculture of Atomic Energy Organization of Iran initiated a mutation breeding program for creating genetic variability in wheat using this local cultivar. Seeds of this variety was irradiated with gamma radiation (50-150 Gy) to induce short straw mutants with greater lodging resistance and yield potential. from a total of about 20000 irradiated seeds 1500 plants showing promising agronomic character were isolated as potential mutants. Following progeny tests and selection 18 mutants lines entered preliminary yield trail. Further field trails at different locations gave two promising lines which are characterized by higher yield, lodging resistance and early maturity. (author). 3 tabs

  2. Dedicator of cytokinesis 8 mutation related combined immune deficiency: A single centre experience from India

    Directory of Open Access Journals (Sweden)

    Dhwanee Thakkar

    2017-10-01

    Full Text Available The Dedicator of cytokinesis 8 (DOCK8 related combined immune deficiency is a recently discovered entity which differs from the classic STAT3 associated autosomal dominant hyper-IgE syndrome with respect to the genetic origin and the clinical manifestations. It is characterised by increased risk of autoimmunity, malignancy and neurological complications in addition to increased risk of recurrent cutaneous, sinopulmonary and gastrointestinal infections. We report a series 11 children from three families suffering from DOCK8 related combined immunodeficiency. Out of 11 children only 5 were alive at diagnosis and rest 6 were siblings who had died of similar complaints. Among the 5 children only one underwent allogeneic haploidentical stem cell transplant (SCT from his mother but died before engraftment due to infection. Other 4 are alive without SCT but have multiple co-morbidities. A constellation of cutaneous lesions, recurrent sinopulmonary & gastro intestinal infections and allergic manifestations in a child who may have a similar family history should arouse a suspicion of combined immunodeficiency associated with DOCK8 mutation. Early diagnosis in such children can expedite the appropriate management with SCT. Keywords: Combined immunodeficiency, DOCK8, Children

  3. 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)

  4. Methylmethane-sulphonate and X-ray-induced mutations in the Chinese hamster hprt gene: mRNA phenotyping using polymerase chain reactions

    International Nuclear Information System (INIS)

    Chaudhry, M.A.; Fox, Margaret

    1990-01-01

    Alterations in the hprt gene of Chinese hamster cells were determined in 71 spontaneous, methylmethane sulphonate (MMS)-and X-ray induced mutants, using the Southern blot hybridization technique. To investigate the possibility of small deletions, MMS-induced mutants were studied with proves derived from exons 3 and 9 but no evidence of specific deletion of these two exons was found. The polymerase chain reaction (PCR) was used to phenotype hprt transcripts in 48 MMS, X-ray and spontaneous Chinese hamster mutants by amplifying the coding region of their cDNA. Among 22 MMS-induced mutants the message was present in 16 instances. An analysis of 20 X-ray-induced mutants showed the presence of hprt mRNA in 11 of them with five having low levels of transcription. Among six spontaneous mutants, four were negative for mRNA on standard Northern blots and in one the message was only detected after PCR amplification. Direct DNA sequencing of 10 mutants revealed the presence of base substitutions in five of them while a 7 bp deletion was found in another. No mutations were found in another four mutants, suggesting the presence of mutation outside the coding region. (author)

  5. A challenge to mutation theory of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Watanabe, Masami

    2006-01-01

    This paper presents an objection against the commonly accepted mutation theory in radiation carcinogenesis. First, author's studies of X-ray irradiated syrian hamster embryo (SHE) cells on malignant morphological changes and mutational change of HGPRT gene showed that the changing patterns were quite different, and as well, other studies in mice gave the essentially similar results. Thus radiation-induced carcinogenesis in cells does not simply occur by an accumulation of radiation-induced mutation. Second, as cultured cells usually used for oncogenesis studies already have the infinitively proliferative ability, the author used the primary cell culture obtained from the rodent embryo. Even those cells became immortal to be cancerous after repeated culture passage with the higher frequency of 10 3 -10 4 relative to somatic cell mutation. Cells thus seem to be easily changeable to cancerous ones. Bystander effect can cause transformation in non-irradiated cells and genetic instability by radiation can form the potentially unstable chromatin region, which induces telomere instability. The author has found that, while short-lived radicals yielded by X-ray irradiation attack DNA to induce cell death and chromosome aberration, long-lived radicals in biomolecules do not, but can cause mutation and carcinogenesis, which are reduced by vitamine C supplementation. The author concludes that the primary target in the radiation carcinogenesis in cells and even in the whole individuals is conceivably protein and not DNA. (T.I.)

  6. Combination of traditional mutation and metabolic engineering to enhance ansamitocin P-3 production in Actinosynnema pretiosum.

    Science.gov (United States)

    Du, Zhi-Qiang; Zhang, Yuan; Qian, Zhi-Gang; Xiao, Han; Zhong, Jian-Jiang

    2017-12-01

    Ansamitocin P-3 (AP-3) is a maytansinoid with its most compelling antitumor activity, however, the low production titer of AP-3 greatly restricts its wide commercial application. In this work, a combinatorial approach including random mutation and metabolic engineering was conducted to enhance AP-3 biosynthesis in Actinosynnema pretiosum. First, a mutant strain M was isolated by N-methyl-N'-nitro-N-nitrosoguanidine mutation, which could produce AP-3 almost threefold that of wild type (WT) in 48 deep-well plates. Then, by overexpressing key biosynthetic genes asmUdpg and asm13-17 in the M strain, a further 60% increase of AP-3 production in 250-ml shake flasks was achieved in the engineered strain M-asmUdpg:asm13-17 compared to the M strain, and its maximum AP-3 production reached 582.7 mg/L, which is the highest as ever reported. Both the gene transcription levels and intracellular intermediate concentrations in AP-3 biosynthesis pathway were significantly increased in the M and M-asmUdpg:asm13-17 during fermentation compared to the WT. The good fermentation performance of the engineered strain was also confirmed in a lab-scale bioreactor. This work demonstrated that combination of random mutation and metabolic engineering could promote AP-3 biosynthesis and might be helpful for increasing the production of other industrially important secondary metabolites. © 2017 Wiley Periodicals, Inc.

  7. 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)

  8. Mutation breeding in Philippine fruits

    International Nuclear Information System (INIS)

    Espino, R.R.C.

    1987-09-01

    Studies were made to establish standard conditions for mutation induction by gamma-irradiation to be performed in combination with in-vitro culture for banana and citrus spp. Besides this, radio-sensitivity of seeds and/or plantlets of mango, sugar apple, soursop, lanzones and Jack fruit was investigated and primary observation on the occurrence of mutation was made. For the mutagenesis of banana shoot tip cultures, radio-sensitivity of plantlets derived from the culture as well as fresh-cultured shoots was examined and phenotypes indicative of mutation, such as chlorophyl streaking, slow growth, pigmentation and varied bunch orientation were recorded. Isozyme analysis for mutated protein structure was not conclusive. In the in-vitro culture of Citrus spp., seeds placed on fresh media as well as germinating seeds and two-leaf stage seedlings in test tubes were examined for their radio-sensitivity. Irradiated materials were propagated for further observation. In these two crops, basic methodology for mutation induction with combined use of in-vitro culture and gamma-irradiation was established. In mango, sugar apple, soursop, lanzones and Jack fruit, basic data on radiosensitivity were obtained. In mango, leaf abnormalities were observed after the treatment of scions

  9. A study of dose effect response and the interrelationship between cell survival, mutation and chromosomal aberration

    International Nuclear Information System (INIS)

    Chadwick, K.H.; Leenhouts, H.P.; Werry, P.A.Th.J.; Ramulu, K.S.

    1980-01-01

    Research was carried out on four topics: generation of cell reproductive death and mutation induction in cell cultures of Haplopappus gracilis by ionizing radiation; radiation induced repair in Saintpaulia epidermis cells; analysis of the combined effect of radiation with other mutagens; and the effect of very low doses of radiation on the Oenothera model system. (Auth.)

  10. 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

  11. Spontaneous mutation by mutagenic repair of spontaneous lesions in DNA

    International Nuclear Information System (INIS)

    Hastings, P.J.; Quah, S.-K.; Borstel, R.C. von

    1976-01-01

    It is stated that strains of yeast carrying mutations in many of the steps in pathways repairing radiation-induced damage to DNA have enhanced spontaneous mutation rates. Most strains isolated because they have enhanced spontaneous mutation carry mutations in DNA repair systems. This suggests that much spontaneous mutation arises by mutagenic repair of spontaneous lesions. (author)

  12. 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

  13. A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells.

    Science.gov (United States)

    Kuijpers, Taco W; van Leeuwen, Ester M M; Barendregt, Barbara H; Klarenbeek, Paul; aan de Kerk, Daan J; Baars, Paul A; Jansen, Machiel H; de Vries, Niek; van Lier, René A W; van der Burg, Mirjam

    2013-07-01

    Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined immunodeficiencies with a variety of clinical presentations. We analyzed peripheral blood mononuclear cells of a 6-year-old boy with normal lymphocyte counts, who suffered from recurrent pneumonia and disseminated mollusca contagiosa. Since proliferative responses of T cells and NK cells to γc -cytokines were severely impaired, we performed IL2RG gene analysis, showing a heterozygous mutation in the presence of a single X-chromosome. Interestingly, an IL2RG reversion to normal predominated in both naïve and antigen-primed CD8(+) T cells and increased over time. Only the revertant CD8(+) T cells showed normal expression of CD132 and the various CD8(+) T cell populations had a different T-cell receptor repertoire. Finally, a fraction of γδ(+) T cells and differentiated CD4(+)CD27(-) effector-memory T cells carried the reversion, whereas NK or B cells were repeatedly negative. In conclusion, in a patient with a novel IL2RG mutation, gene-reverted CD8(+) T cells accumulated over time. Our data indicate that selective outgrowth of particular T-cell subsets may occur following reversion at the level of committed T progenitor cells.

  14. Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia.

    Science.gov (United States)

    Beam, Teresa A; Loudermilk, Emily F; Kisor, David F

    2017-02-01

    A review of the pharmacogenetics (PGt) and pathophysiology of calcium voltage-gated channel subunit alpha1 S (CACNA1S) mutations in malignant hyperthermia susceptibility type 5 (MHS5; MIM #60188) is presented. Malignant hyperthermia (MH) is a life-threatening hypermetabolic state of skeletal muscle usually induced by volatile, halogenated anesthetics and/or the depolarizing neuromuscular blocker succinylcholine. In addition to ryanodine receptor 1 (RYR1) mutations, several CACNA1S mutations are known to be risk factors for increased susceptibility to MH (MHS). However, the presence of these pathogenic CACNA1S gene variations cannot be used to positively predict MH since the condition is genetically heterogeneous with variable expression and incomplete penetrance. At present, one or at most six CACNA1S mutations display significant linkage or association either to clinically diagnosed MH or to MHS as determined by contracture testing. Additional pathogenic variants in CACNA1S, either alone or in combination with genes affecting Ca 2+ homeostasis, are likely to be discovered in association to MH as whole exome sequencing becomes more commonplace. Copyright © 2017 the American Physiological Society.

  15. Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome.

    Science.gov (United States)

    Neuhaus, Christine; Eisenberger, Tobias; Decker, Christian; Nagl, Sandra; Blank, Cornelia; Pfister, Markus; Kennerknecht, Ingo; Müller-Hofstede, Cornelie; Charbel Issa, Peter; Heller, Raoul; Beck, Bodo; Rüther, Klaus; Mitter, Diana; Rohrschneider, Klaus; Steinhauer, Ute; Korbmacher, Heike M; Huhle, Dagmar; Elsayed, Solaf M; Taha, Hesham M; Baig, Shahid M; Stöhr, Heidi; Preising, Markus; Markus, Susanne; Moeller, Fabian; Lorenz, Birgit; Nagel-Wolfrum, Kerstin; Khan, Arif O; Bolz, Hanno J

    2017-09-01

    Combined retinal degeneration and sensorineural hearing impairment is mostly due to autosomal recessive Usher syndrome (USH1: congenital deafness, early retinitis pigmentosa (RP); USH2: progressive hearing impairment, RP). Sanger sequencing and NGS of 112 genes (Usher syndrome, nonsyndromic deafness, overlapping conditions), MLPA, and array-CGH were conducted in 138 patients clinically diagnosed with Usher syndrome. A molecular diagnosis was achieved in 97% of both USH1 and USH2 patients, with biallelic mutations in 97% (USH1) and 90% (USH2), respectively. Quantitative readout reliably detected CNVs (confirmed by MLPA or array-CGH), qualifying targeted NGS as one tool for detecting point mutations and CNVs. CNVs accounted for 10% of identified USH2A alleles, often in trans to seemingly monoallelic point mutations. We demonstrate PTC124-induced read-through of the common p.Trp3955* nonsense mutation (13% of detected USH2A alleles), a potential therapy target. Usher gene mutations were found in most patients with atypical Usher syndrome, but the diagnosis was adjusted in case of double homozygosity for mutations in OTOA and NR2E3 , genes implicated in isolated deafness and RP. Two patients with additional enamel dysplasia had biallelic PEX26 mutations, for the first time linking this gene to Heimler syndrome. Targeted NGS not restricted to Usher genes proved beneficial in uncovering conditions mimicking Usher syndrome.

  16. 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)

  17. 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.

  18. Mutation breeding in jute

    International Nuclear Information System (INIS)

    Joshua, D.C.

    1980-01-01

    Mutagenic studies in jute in general dealt with the morphological abnormalities of the M 1 generation in great detail. Of late, induction of a wide spectrum of viable mutations have been reported in different varieties of both the species. Mutations affecting several traits of agronomic importance such as, plant height, time of flowering, fibre yield and quality, resistance to pests and diseases are also available. Cytological analysis of a large collection of induced mutants resulted in the isolation of seven trisomics in an olitorius variety. Several anatomical parameters which are the components of fibre yield, have also received attention. Some mutants with completely altered morphology were used for interpreting the evolution of leaf shape in Tiliaceas and related families. A capsularis variety developed using mutation breeding technique has been released for cultivation. Several others, including derivatives of inter-mutant hybridization have been found to perform well at different locations in the All India Coordinated Trials. Presently, chemical mutagenesis and induction of mutants of physiological significance are receiving considerable attention. The induced variability is being used in genetic and linkage studies. (author)

  19. Transfection with extracellularly UV-damaged DNA induces human and rat cells to express a mutator phenotype towards parvovirus H-1

    International Nuclear Information System (INIS)

    Dinsart, C.; Cornelis, J.J.; Klein, B.; van der Eb, A.J.; Rommelaere, J.

    1984-01-01

    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

  20. Experimental mutations in soybean and their selection value

    International Nuclear Information System (INIS)

    Sichkar', V.I.

    1979-01-01

    Efficiency of widely used chemical mutagens and gamma irradiation in inducing chlorophyll changes in some soya varieties has been compared in order to further specify the relationship between this type of mutations and other morphological changes. The most active mutations found were NMU, NEU, EI and gamma radiation. The frequency of chrolophyll changes depended on the mutagen concentration and soya variety and varied from 1.58% to 19.04%. EO, NDMM and DMS produced 4-5 times lower yield of chlorophyll mutations. The following mutagen concentrations for the varieties studied were found optimum (in per cent): NMU - 0.0125, NEU - 0.025, EI - 0.03, EO - 0.05, NDMM - 0.0O625, DMS - 0.02. No relationship between the dose of gamma radiation and the mutation frequency was found. Varieties of VNIIMK 9186 and Lanka were the most mutable, 89-10 hybrid showed very low mutability. Mutagens that induced high frequency of mutations also gave the broadest spectrum of changes. Most frequent changes were xantha, lutescens and xanthaterminalis. Very few mutations from green color to white one were isolated

  1. Mutation induction by ion beams in higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2003-04-01

    This review mainly describes study results obtained in the Takasaki ion-beam (IB) irradiation facility (TIARA) on the mutation induction in higher plants. Biological effects like lethality and on budding of IBs (carbon, Ne and Ar) are discussed in relation with their linear energy transfer (LET), relative biological effectiveness and the developmental states in shepherd's-purse and tobacco. Induced mutation by IB are characterized by those findings that the mutation rate by C beam is 1.9 x 10{sup -6}, being 17 times higher than the electron beam, in the shepherd's-purse, that C beam induces larger structural changes than electron beam when examined by molecular mechanism of tt and gl gene mutations, and that mutation spectrum of IB is different from that of {gamma}-ray and is wider. Novel mutants are described on shepherd's-purse (pigment mutants, ultraviolet (UV)-resistant and sensitive ones, and flowering ones), disease-resistant rice, barley and tobacco plants, and flowering plants. IB mutation is possibly useful for solving the problems of environment and foods in future. (N.I.)

  2. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa

    DEFF Research Database (Denmark)

    Hartel, Bas P.; Lofgren, Maria; Huygen, Patrick L. M.

    2016-01-01

    Objectives Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates...... the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. Design...... A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA...

  3. Genetic Correction of Induced Pluripotent Stem Cells From a Deaf Patient With MYO7A Mutation Results in Morphologic and Functional Recovery of the Derived Hair Cell-Like Cells.

    Science.gov (United States)

    Tang, Zi-Hua; Chen, Jia-Rong; Zheng, Jing; Shi, Hao-Song; Ding, Jie; Qian, Xiao-Dan; Zhang, Cui; Chen, Jian-Ling; Wang, Cui-Cui; Li, Liang; Chen, Jun-Zhen; Yin, Shan-Kai; Huang, Tao-Sheng; Chen, Ping; Guan, Min-Xin; Wang, Jin-Fu

    2016-05-01

    The genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation. In the present study, iPSCs were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T; P-iPSCs), the asymptomatic father of the patient (MYO7A c.1184G>A mutation; CF-iPSCs), and a normal donor (MYO7A(WT/WT); C-iPSCs). One of MYO7A mutation sites (c.4118C>T) in the P-iPSCs was corrected using CRISPR/Cas9. The corrected iPSCs (CP-iPSCs) retained cell pluripotency and normal karyotypes. Hair cell-like cells induced from CP-iPSCs showed restored organization of stereocilia-like protrusions; moreover, the electrophysiological function of these cells was similar to that of cells induced from C-iPSCs and CF-iPSCs. These results might facilitate the development of iPSC-based gene therapy for genetic disorders. Induced pluripotent stem cells (iPSCs) were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T). One of the MYO7A mutation sites (c.4118C>T) in the iPSCs was corrected using CRISPR/Cas9. The genetic correction of MYO7A mutation resulted in morphologic and functional recovery of hair cell-like cells derived from iPSCs. These findings confirm the hypothesis that MYO7A plays an important role in the assembly of stereocilia into stereociliary bundles. Thus, the present study might provide further insight into the pathogenesis of sensorineural hearing loss and facilitate the development of therapeutic strategies against monogenic disease through the genetic repair of patient-specific iPSCs. ©AlphaMed Press.

  4. The Oenothera plastome mutator: effect of UV irradiation and nitroso-methyl urea on mutation frequencies

    International Nuclear Information System (INIS)

    Sears, B.B.; Sokalski, M.B.

    1991-01-01

    Oenothera plants homozygous for a recessive plastome mutator allele (pm) showed spontaneous mutation frequencies for plastome genes that are 200-fold higher than spontaneous levels. Mutations occurred at high frequencies in plants grown in the field, in a glasshouse, or as leaf tip cultures under fluorescent light, indicating that the plastome mutator activity is UV-independent. However, the chlorotic sectors became visible at an earlier stage of development when seedlings were irradiated, compared to seedlings that were not exposed to UV. These results imply that the rate of sorting-out was increased by the irradiation treatment, possibly due to a decrease in the effective number of multiplication-competent plastids, or a reduction in the extent of cytoplasmic mixing. Nitroso-methyl urea treatment of seeds had a dramatic effect on mutation frequency in both wild-type and plastome mutator samples. When the background mutation rates were low, the combination of the plastome mutator nucleus and the chemical mutagenesis treatment resulted in a synergistic effect, suggesting that the plastome mutator may involve a cpDNA repair pathway. (author)

  5. 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)

  6. Mutation induction by heavy ions

    Science.gov (United States)

    Kiefer, J.; Stoll, U.; Schneider, E.

    1994-10-01

    Mutation induction by heavy ions is compared in yeast and mammalian cells. Since mutants can only be recovered in survivors the influence of inactivation cross sections has to be taken into account. It is shown that both the size of the sensitive cellular site as well as track structure play an important role. Another parameter which influences the probability of mutation induction is repair: Contrary to naive assumptions primary radiation damage does not directly lead to mutations but requires modification to reconstitute the genetic machinery so that mutants can survive. The molecular structure of mutations was analyzed after exposure to deuterons by amplification with the aid of polymerase chain reaction. The results-although preliminary-demonstrate that even with densely ionizing particles a large fraction does not carry big deletions which suggests that point mutations may also be induced by heavy ions.

  7. 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

  8. Mutation directional selection sheds light on prion pathogenesis

    International Nuclear Information System (INIS)

    Shen, Liang; Ji, Hong-Fang

    2011-01-01

    Highlights: → Most pathogenic mutations possess strong directional selection, i.e., enhancing hydrophobicity or decreasing negative and increasing positive charge. → Mutation-induced changes may strengthen the interactions between PrP and facilitating factors. → The findings also have significant implications for exploring potential regions involved in the conformational transition from PrP C to PrP Sc . -- Abstract: As mutations in the PRNP gene account for human hereditary prion diseases (PrDs), it is crucial to elucidating how these mutations affect the central pathogenic conformational transition of normal cellular prion protein (PrP C ) to abnormal scrapie isoform (PrP Sc ). Many studies proposed that these pathogenic mutations may make PrP more susceptible to conformational change through altering its structure stability. By evaluating the most recent observations regarding pathogenic mutations, it was found that the pathogenic mutations do not exert a uniform effect on the thermodynamic stability of the human PrP's structure. Through analyzing the reported PrDs-related mutations, we found that 25 out of 27 mutations possess strong directional selection, i.e., enhancing hydrophobicity or decreasing negative and increasing positive charge. Based on the triggering role reported by previous studies of facilitating factors in PrP C conversion, e.g., lipid and polyanion, we proposed that the mutation-induced changes may strengthen the interaction between PrP and facilitating factors, which will accelerate PrP conversion and cause PrDs.

  9. Mutation directional selection sheds light on prion pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Liang [Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo 255049 (China); Ji, Hong-Fang, E-mail: jhf@sdut.edu.cn [Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo 255049 (China)

    2011-07-01

    Highlights: {yields} Most pathogenic mutations possess strong directional selection, i.e., enhancing hydrophobicity or decreasing negative and increasing positive charge. {yields} Mutation-induced changes may strengthen the interactions between PrP and facilitating factors. {yields} The findings also have significant implications for exploring potential regions involved in the conformational transition from PrP{sup C} to PrP{sup Sc}. -- Abstract: As mutations in the PRNP gene account for human hereditary prion diseases (PrDs), it is crucial to elucidating how these mutations affect the central pathogenic conformational transition of normal cellular prion protein (PrP{sup C}) to abnormal scrapie isoform (PrP{sup Sc}). Many studies proposed that these pathogenic mutations may make PrP more susceptible to conformational change through altering its structure stability. By evaluating the most recent observations regarding pathogenic mutations, it was found that the pathogenic mutations do not exert a uniform effect on the thermodynamic stability of the human PrP's structure. Through analyzing the reported PrDs-related mutations, we found that 25 out of 27 mutations possess strong directional selection, i.e., enhancing hydrophobicity or decreasing negative and increasing positive charge. Based on the triggering role reported by previous studies of facilitating factors in PrP{sup C} conversion, e.g., lipid and polyanion, we proposed that the mutation-induced changes may strengthen the interaction between PrP and facilitating factors, which will accelerate PrP conversion and cause PrDs.

  10. 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

  11. Disease-associated mutations that alter the RNA structural ensemble.

    Directory of Open Access Journals (Sweden)

    Matthew Halvorsen

    2010-08-01

    Full Text Available Genome-wide association studies (GWAS often identify disease-associated mutations in intergenic and non-coding regions of the genome. Given the high percentage of the human genome that is transcribed, we postulate that for some observed associations the disease phenotype is caused by a structural rearrangement in a regulatory region of the RNA transcript. To identify such mutations, we have performed a genome-wide analysis of all known disease-associated Single Nucleotide Polymorphisms (SNPs from the Human Gene Mutation Database (HGMD that map to the untranslated regions (UTRs of a gene. Rather than using minimum free energy approaches (e.g. mFold, we use a partition function calculation that takes into consideration the ensemble of possible RNA conformations for a given sequence. We identified in the human genome disease-associated SNPs that significantly alter the global conformation of the UTR to which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, beta-Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive Pulmonary Disease (COPD, and Hypertension, we identified multiple SNPs in UTRs that alter the mRNA structural ensemble of the associated genes. Using a Boltzmann sampling procedure for sub-optimal RNA structures, we are able to characterize and visualize the nature of the conformational changes induced by the disease-associated mutations in the structural ensemble. We observe in several cases (specifically the 5' UTRs of FTL and RB1 SNP-induced conformational changes analogous to those observed in bacterial regulatory Riboswitches when specific ligands bind. We propose that the UTR and SNP combinations we identify constitute a "RiboSNitch," that is a regulatory RNA in which a specific SNP has a structural consequence that results in a disease phenotype. Our SNPfold algorithm can help identify RiboSNitches by leveraging GWAS data and an analysis of the mRNA structural ensemble.

  12. 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

  13. 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)

  14. 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

  15. Gain-of-Function Mutations in STAT1: A Recently Defined Cause for Chronic Mucocutaneous Candidiasis Disease Mimicking Combined Immunodeficiencies

    Directory of Open Access Journals (Sweden)

    Sanem Eren Akarcan

    2017-01-01

    Full Text Available Chronic Mucocutaneous Candidiasis (CMC is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF (c.1154 C>T, p.Thr385Met in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.

  16. Mutation breeding in peas

    Energy Technology Data Exchange (ETDEWEB)

    Jaranowski, J [Institute of Genetics and Plant Breeding, Academy of Agriculture, Poznan (Poland); Micke, A [Joint FAO/IAEA Division of Isotope and Radiation Applications of Atomic Energy for Food and Agricultural Development, International Atomic Energy Agency, Vienna (Austria)

    1985-02-01

    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)

  17. 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)

  18. 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

  19. 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.

  20. Influence of single and combination treatments of physical and chemical mutagen on chlorophyll mutations in Finger Millet

    International Nuclear Information System (INIS)

    Kumar, Binod; Mahto, Jaylal; Haider, Z.A.

    1993-01-01

    Gamma rays, ethyl methane sulfonate (EMS) and their combined treatments influenced differently in producing chlorophyll mutations. A good number of chlorophyll mutants with varied frequencies were recorded in M 2 generation. The frequency of chlorophyll mutants was higher at lower doses of gamma rays, EMS and their combination treatments. The most frequently observed mutant was Albino type. The other chlorophyll mutants isolated were Xantha, Viridis, Striata and Tigrina. The frequency of tigrina and striata was lowest in variety A-404 and Hr-374, respectively. The efficiency and effectiveness was high at the lower doses of mutagens in both the varieties. EMS (0.2%) was more effective than the corresponding lower dose of gamma rays for both the varieties. (author). 10 refs., 4 tabs

  1. Accurate calculation of mutational effects on the thermodynamics of inhibitor binding to p38α MAP kinase: a combined computational and experimental study.

    Science.gov (United States)

    Zhu, Shun; Travis, Sue M; Elcock, Adrian H

    2013-07-09

    A major current challenge for drug design efforts focused on protein kinases is the development of drug resistance caused by spontaneous mutations in the kinase catalytic domain. The ubiquity of this problem means that it would be advantageous to develop fast, effective computational methods that could be used to determine the effects of potential resistance-causing mutations before they arise in a clinical setting. With this long-term goal in mind, we have conducted a combined experimental and computational study of the thermodynamic effects of active-site mutations on a well-characterized and high-affinity interaction between a protein kinase and a small-molecule inhibitor. Specifically, we developed a fluorescence-based assay to measure the binding free energy of the small-molecule inhibitor, SB203580, to the p38α MAP kinase and used it measure the inhibitor's affinity for five different kinase mutants involving two residues (Val38 and Ala51) that contact the inhibitor in the crystal structure of the inhibitor-kinase complex. We then conducted long, explicit-solvent thermodynamic integration (TI) simulations in an attempt to reproduce the experimental relative binding affinities of the inhibitor for the five mutants; in total, a combined simulation time of 18.5 μs was obtained. Two widely used force fields - OPLS-AA/L and Amber ff99SB-ILDN - were tested in the TI simulations. Both force fields produced excellent agreement with experiment for three of the five mutants; simulations performed with the OPLS-AA/L force field, however, produced qualitatively incorrect results for the constructs that contained an A51V mutation. Interestingly, the discrepancies with the OPLS-AA/L force field could be rectified by the imposition of position restraints on the atoms of the protein backbone and the inhibitor without destroying the agreement for other mutations; the ability to reproduce experiment depended, however, upon the strength of the restraints' force constant

  2. Mutation breeding in ornamental plants

    International Nuclear Information System (INIS)

    Datta, S.K.

    1990-01-01

    Full text: Mutation induction produced a large number of new promising varieties in ornamental species. 37 new mutants of Chrysanthemum and 14 of rose have been developed by mutations and released for commercialisation. The mutations in flower colour/shape were detected as chimeras in M 1 V 1 , M 1 V 2 , M 1 V 3 generations. The mutation frequency varied with the cultivar and exposure to gamma rays. Comparative analysis of original cultivars and their respective induced mutants on cytomorphological, anatomical and biochemical characters are being carried out for better understanding of the mechanism involved in the origin and evolution of somatic flower colour/shape mutations. Cytological analysis with reference to chromosomal aberrations, chromosome number, ICV, INV and DNA content gave no differences between the original and mutant cultivars. Analysis of florets/petal pigments by TLC and spectrophotometric methods indicated both qualitative and quantitative changes. (author)

  3. Germ-line origins of mutation in families with hemophilia B: The sex ratio varies with the type of mutation

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.; Bottema, C.D.K.; Schaid, D.J.; Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States)); Cohen, M.P. (Vanderbilt Univ., Nashville, TN (United States)); Sexauer, C.L. (Children' s Hospital, Oklahoma City, OK (United States))

    1993-01-01

    Previous epidemiological and biochemical studies have generated conflicting estimates of the sex ratio of mutation. Direct genomic sequencing in combination with haplotype analysis extends previous analyses by allowing the precise mutation to be determined in a given family. From analysis of the factor IX gene of 260 consecutive families with hemophilia B, the authors report the germ-line origin of mutation in 25 families. When combined with 14 origins of mutation reported by others and with 4 origins previously reported by them, a total of 25 occur in the female germ line, and 18 occur in the male germ line. The excess of germ-line origins in females does not imply an overall excess mutation rate per base pair in the female germ line. Bayesian analysis of the data indicates that the sex ratio varies with the type of mutation. The aggregate of single-base substitutions shows a male predominance of germ-line mutations (P < .002). The maximum-likelihood estimate of the male predominance is 3.5-fold. Of the single-base substitutions, deletions display a sex ratio of unity. Analysis of the parental age at transmission of a new mutation suggests that germ-line mutations are associated with a small increase in parental age in females but little, if any, increase in males. Although direct genomic sequencing offers a general method for defining the origin of mutation in specific families, accurate estimates of the sex ratios of different mutational classes require large sample sizes and careful correction for multiple biases of ascertainment. The biases in the present data result in an underestimate of the enhancement of mutation in males. 62 refs., 1 fig., 5 tabs.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

    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 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

  5. 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.

  6. JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis.

    Science.gov (United States)

    Xia, Jun; Lu, Mi-Ze; Jiang, Yuan-Qiang; Yang, Guo-Hua; Zhuang, Yun; Sun, Hong-Li; Shen, Yun-Feng

    2012-03-01

    JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF). We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

  7. Mutation induction by ion beams in plants

    International Nuclear Information System (INIS)

    Tanaka, Atsushi

    2001-01-01

    The effect of ion beams such as C, He, and Ne ions was investigated on the mutation induction in plants with the expectation that ion beams of high linear energy transfer (LET) can frequently produce large DNA alternation such as inversion, translocation and large deletion rather than point mutation. Mutation frequency was investigated using Arabidopsis visible phenotype loci and was 8 to 33 fold higher for 220 MeV carbon ions than for electrons. Mutation spectrum was investigated on the flower color of chrysanthemum cv to find that flower mutants induced by ion beams show complex and stripe types rather than single color. Polymerase chain reaction analysis was performed to investigate DNA alteration of mutations. In conclusion, the characteristics of ion beams for the mutation induction are 1) high frequency, 2) broad mutation spectrum, and 3) novel mutants. (S. Ohno)

  8. Mutation induction by ion beams in plants

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2001-03-01

    The effect of ion beams such as C, He, and Ne ions was investigated on the mutation induction in plants with the expectation that ion beams of high linear energy transfer (LET) can frequently produce large DNA alternation such as inversion, translocation and large deletion rather than point mutation. Mutation frequency was investigated using Arabidopsis visible phenotype loci and was 8 to 33 fold higher for 220 MeV carbon ions than for electrons. Mutation spectrum was investigated on the flower color of chrysanthemum cv to find that flower mutants induced by ion beams show complex and stripe types rather than single color. Polymerase chain reaction analysis was performed to investigate DNA alteration of mutations. In conclusion, the characteristics of ion beams for the mutation induction are 1) high frequency, 2) broad mutation spectrum, and 3) novel mutants. (S. Ohno)

  9. Combined effect of Hashimoto's thyroiditis and BRAF(V600E) mutation status on aggressiveness in papillary thyroid cancer.

    Science.gov (United States)

    Kim, Su-jin; Myong, Jun Pyo; Jee, Hyeon-Gun; Chai, Young Jun; Choi, June Young; Min, Hye Sook; Lee, Kyu Eun; Youn, Yeo-Kyu

    2016-01-01

    The purpose of this study was to evaluate the association between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid cancer (PTC) and to determine their combined association with tumor aggressiveness in PTC. A total of 1780 patients with PTC who underwent surgery were enrolled in this study. Simple and multiple analyses were performed to determine the association between Hashimoto's thyroiditis and the BRAF(V600E) mutation in PTC. Hashimoto's thyroiditis was present in 11.5% of patients (204/1780) with PTC. Multiple logistic regressions showed that BRAF(V600E) (odds ratio [OR] = 0.493; 95% confidence interval [CI] = 0.360-0.678) and the female sex (OR = 7.146; 95% CI = 3.408-18.347) were independent factors associated with Hashimoto's thyroiditis in PTC. BRAF(V600E) mutation and the Hashimoto's thyroiditis-negative PTC group were associated with aggressive disease (OR = 3.069; 95% CI = 1.654-5.916). Hashimoto's thyroiditis was associated less frequently with BRAF(V600E) , and frequently with the female sex in patients with PTC. Hashimoto's thyroiditis and BRAF(V600E) status may help to predict clinical outcome of PTC. © 2015 Wiley Periodicals, Inc.

  10. 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

  11. Utilization of radiations in mutation breeding of tuber crops

    International Nuclear Information System (INIS)

    Kukimura, H.

    1981-01-01

    Most of the tuber crops are vegetatively propagated and their spontaneous mutations have been constructively utilized to practical farming. Significance of utilization of mutations to breeding should not be overlooked, since mutation can be articially induced by various mutagenic agents. In tuber crops, ionizing radiations are mostly applied to induce mutations. Radiosensitivity varies with species, genotypes and organs. For the purpose of mutation induction, 10-20 kR of gamma-rays is given to tubers and/or shoots in sweet potato and 2-10 kR in potato. It should be noted that radiation damage is more or less transmissible to later vegetative generations. A useful characters in practical agriculture, following mutations have been obtained so far: skin colour, short stemmed, changes in dry matter content, total sugars content and tuber yield, earlier maturity and sculf resistance in sweet potato. And, skin colour, changes in starch content and stolon length, day-neutral tuberization and cyst-nematode resistance in potato. Apart from mutations, radiation can be utilized for breaking down the incompatibility in sweet potato. Promising mutant clones with probable release in Japan are Kyushu 78 of sweet potato and Koniku 16 and Konkei 55 of potato. (author)

  12. Translational read-through of a nonsense mutation causing Bartter syndrome.

    Science.gov (United States)

    Cho, Hee Yeon; Lee, Beom Hee; Cheong, Hae Il

    2013-06-01

    Bartter syndrome (BS) is classified into 5 genotypes according to underlying mutant genes and BS III is caused by loss-of-function mutations in the CLCNKB gene encoding for basolateral ClC-Kb. BS III is the most common genotype in Korean patients with BS and W610X is the most common CLCNKB mutation in Korean BS III. In this study, we tested the hypothesis that the CLCNKB W610X mutation can be rescued in vitro using aminoglycoside antibiotics, which are known to induce translational read-through of a nonsense mutation. The CLCNKB cDNA was cloned into a eukaryotic expression vector and the W610X nonsense mutation was generated by site-directed mutagenesis. Cultured polarized MDCK cells were transfected with the vectors, and the read-through was induced using an aminoglycoside derivative, G418. Cellular expression of the target protein was monitored via immunohistochemistry. While cells transfected with the mutant CLCNKB failed to express ClC-Kb, G418 treatment of the cells induced the full-length protein expression, which was localized to the basolateral plasma membranes. It is demonstrated that the W610X mutation in CLCNKB can be a good candidate for trial of translational read-through induction as a therapeutic modality.

  13. Mutation breeding in crop improvement - achievements and prospects

    International Nuclear Information System (INIS)

    Kharkwal, M.C.

    2004-01-01

    Crop improvement programmes through induced mutations were initiated about seven decades ago. Majority of the mutant varieties have been released during the last two decades. In terms of the development and release of mutant varieties, China (605), India (309), Russia (204), the Netherlands (176), USA (125) and Japan (120) are the leading countries. Radiation, especially gamma radiation was the most frequently used mutagen for inducing mutations in crop plants. Out of 1072 mutant varieties of cereals, rice alone accounts for 434 varieties followed by barley (269). Mutation breeding has made significant contribution in increasing the production of rice, ground nut, castor, chickpea, mungbean and urd bean in the Indian subcontinent. The future mutation breeding programmes should be aimed at improving the root characters, nodulation in legumes, alteration of fatty acid composition in oil seeds, host pathogen interactions, photo- insensitivity and apomixix in crop plants

  14. [Cetuximab in combination with icotinib overcomes the acquired resistance caused by EGFR T790M mutation in non-small cell lung cancer].

    Science.gov (United States)

    Wang, Meng; Zhang, Lianmin; Zhao, Xiaoliang; Liu, Jun; Chen, Yulong; Wang, Changli

    2014-09-01

    The aim of this study was to investigate the effects of combination of icotinib and cetuximab on the acquired drug resistance caused by T790M mutation of EGFR in NSCLC, and provide experimental evidence for rational treatment of NSCLC. The effects of these two agents on cell proliferation, apoptosis, and EGFR-dependent signaling were evaluated using 3-(4, 5-dimethylthiazol-2-yl)- 5-diphenyltetrazolium bromide (MTT) assay, annexin V staining, and Western blotting. The expression of molecular markers of tumor proliferation PCNA and Ki-67 protein was further examined by immunohistochemistry, and the expression of EGFR-signaling-related proteins in tissue sections taken from H1975 tumor xenografts was assessed by Western blot assay. Sensitivity to EGFR inhibitors was detected in human H1975 tumor xenograft in nude mice. The in vitro experiment showed that the proliferative ability of H1975 cells was inhibited in a dose-dependent manner, along with the increasing doses of cetuximab and icotinib, and the combination of cetuximab with icotinib resulted in a more pronounced growth inhibition of the H1975 cells. The apoptosis rate of H1975 cells after treatment with 0.5 µmol/L icotinib and 1 µg/ml cetuximab was (22.03 ± 2.41)% and that after treatment with 5 µmol/L icotinib and 10 µg/ml cetuximab was (42.75 ± 2.49)%, both were significantly higher than that after treatment with the same dose of icotinib or cetuximab alone (P icotinib treatment, but (30.8 ± 2.0) mm(3) in the cetuximab treatment group and 0 mm(3) in the cetuximab combined with icotinib group. There was a significantly decreased expression of Ki-67 and PCNA proteins and down-regulation of phosphorylation of EGFR signaling-related proteins in the cetuximab combined with icotinib group. The combination of icotinib with cetuximab can exert synergistic inhibitory effect on the acquired drug resistance caused by T790M mutation of EGFR in NSCLC H1975 cells, interrupts the EGFR-downstream signaling pathway

  15. Mutation breeding in pepper

    International Nuclear Information System (INIS)

    Daskalov, S.

    1986-01-01

    Pepper (Capsicum sp.) is an important vegetable and spice crop widely grown in tropical as well as in temperate regions. Until recently the improvement programmes were based mainly on using natural sources of germ plasma, crossbreeding and exploiting the heterosis of F 1 hybrids. However, interest in using induced mutations is growing. A great number of agronomically useful mutants as well as mutants valuable for genetic, cytological and physiological studies have been induced and described. In this review information is presented about suitable mutagen treatment procedures with radiation as well as chemicals, M 1 effects, handling the treated material in M 1 , M 2 and subsequent generations, and mutant screening procedures. This is supplemented by a description of reported useful mutants and released cultivars. Finally, general advice is given on when and how to incorporate mutation induction in Capsicum improvement programmes. (author)

  16. Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor: clinical evaluation and molecular characterization of a novel mutation.

    Directory of Open Access Journals (Sweden)

    Frédéric Brioude

    Full Text Available CONTEXT: KISS1R mutations have been reported in few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH (OMIM #146110. OBJECTIVE: To describe in detail nCHH patients with biallelic KISS1R mutations belonging to 2 unrelated families, and to functionally characterize a novel KISS1R mutation. RESULTS: An original mutant, p.Tyr313His, was found in the homozygous state in 3 affected kindred (2 females and 1 male from a consanguineous Portuguese family. This mutation, located in the seventh transmembrane domain, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs MAP kinase signaling and intracellular calcium release. In the second family, a French Caucasian male patient with nCHH was found to carry two recurrent mutations in the compound heterozygous state (p.Leu102Pro/Stop399Arg. In this man, pulsatile GnRH (Gonadotropin Releasing Hormone administration restored pulsatile LH (Luteinizing Hormone secretion and testicular hormone secretion. Later, long-term combined gonadotropin therapy induced spermatogenesis, enabling 3 successive pregnancies that resulted in 2 miscarriages and the birth of a healthy boy. CONCLUSION: We show that a novel loss-of-function mutation (p.Tyr313His in the KISS1R gene can cause familial nCHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of gonadotropin secretion by exogenous GnRH administration further supports, in humans, the hypothalamic origin of the gonadotropin deficiency in this genetic form of nCHH.

  17. Mutation breeding newsletter. No. 20

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  18. Mutation breeding newsletter. No. 17

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  19. Mutation breeding newsletter. No. 16

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  20. Mutation breeding newsletter. No. 8

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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. 12

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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. 10

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  3. Mutation breeding newsletter. No. 32

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  4. Mutation breeding newsletter. No. 18

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  5. Mutation breeding newsletter. No. 9

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  6. Mutation breeding newsletter. No. 22

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  7. Mutation breeding newsletter. No. 15

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Mutation breeding newsletter. No. 11

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  20. Mutation breeding newsletter. No. 31

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.