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Sample records for chromatid deletions

  1. Identification of protein complexes required for efficient sister chromatid cohesion

    NARCIS (Netherlands)

    Mayer, Melanie L; Pot, Isabelle; Chang, Michael; Xu, Hong; Aneliunas, Victoria; Kwok, Teresa; Newitt, Rick; Aebersold, Ruedi; Boone, Charles; Brown, Grant W; Hieter, Philip

    2004-01-01

    Ctf8p is a component of Ctf18-RFC, an alternative replication factor C-like complex required for efficient sister chromatid cohesion in Saccharomyces cerevisiae. We performed synthetic genetic array (SGA) analysis with a ctf8 deletion strain as a primary screen to identify other nonessential genes r

  2. Sister chromatid cohesion and recombination in meiosis

    NARCIS (Netherlands)

    Heemst, van D.; Heyting, C.

    2000-01-01

    Sister chromatids are associated from their formation until their disjunction. Cohesion between sister chromatids is provided by protein complexes, of which some components are conserved across the kingdoms and between the mitotic and meiotic cell cycles. Sister chromatid cohesion is intimately link

  3. Mechanisms of sister chromatid recombination

    International Nuclear Information System (INIS)

    Studies using T948 as a model system have been carried out aimed at elucidating the mechanism of sister chromatid recombination (SCR). Characterization of U.V. light- and x-ray-induced SCR, the relationiship between SCR induction and DNA repair using rad mutations, and the relationship between SCR induction and the time of cell division using cdc mutations are presented. It has been supposed that SCR is induced at the phase of S-G2 following DNA replication, that postreplication break of DNA strands is strongly involved in the induction of SCR, and that induction type of SCR, i.e., conversion type or recombination type, is dependent upon the type of molecular damage of DNA. (Namekawa, K.)

  4. Chromatid interchanges at intrachromosomal telomeric DNA sequences

    International Nuclear Information System (INIS)

    Chinese hamster Don cells were exposed to X-rays, mitomycin C and teniposide (VM-26) to induce chromatid exchanges (quadriradials and triradials). After fluorescence in situ hybridization (FISH) of telomere sequences it was found that interstitial telomere-like DNA sequence arrays presented around five times more breakage-rearrangements than the genome overall. This high recombinogenic capacity was independent of the clastogen, suggesting that this susceptibility is not related to the initial mechanisms of DNA damage. (author)

  5. A matter of choice: the establishment of sister chromatid cohesion

    OpenAIRE

    Uhlmann, Frank

    2009-01-01

    Sister chromatid cohesion is the basis for the recognition of chromosomal DNA replication products for their bipolar segregation in mitosis. Fundamental to sister chromatid cohesion is the ring-shaped cohesin complex, which is loaded onto chromosomes long before the initiation of DNA replication and is thought to hold replicated sister chromatids together by topological embrace. What happens to cohesin when the replication fork approaches, and how cohesin recognizes newly synthesized sister c...

  6. Mechanics of Sister Chromatids studied with a Polymer Model

    Directory of Open Access Journals (Sweden)

    Yang eZhang

    2013-10-01

    Full Text Available Sister chromatid cohesion denotes the phenomenon that sister chromatids are initially attached to each other in mitosis to guarantee the error-free distribution into the daughter cells. Cohesion is mediated by binding proteins and only resolved after mitotic chromosome condensation is completed. However, the amount of attachement points required to maintain sister chromatid cohesion while still allowing proper chromosome condensation is not known yet. Additionally the impact of cohesion on the mechanical properties of chromosomes also poses an interesting problem. In this work we study the conformational and mechanical properties of sister chromatids by means of computer simulations. We model both protein-mediated cohesion between sister chromatids and chromosome condensation with a dynamic binding mechanisms. We show in a phase diagram that only specific link concentrations lead to connected and fully condensed chromatids that do not intermingle with each other nor separate due to entropic forces. Furthermore we show that dynamic bonding between chromatids decrease the Young's modulus compared to non-bonded chromatids.

  7. PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis.

    Science.gov (United States)

    Nielsen, Christian F; Huttner, Diana; Bizard, Anna H; Hirano, Seiki; Li, Tian-Neng; Palmai-Pallag, Timea; Bjerregaard, Victoria A; Liu, Ying; Nigg, Erich A; Wang, Lily Hui-Ching; Hickson, Ian D

    2015-01-01

    PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH(-/-) cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localizes with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH. Purified PICH protein strongly stimulates the catalytic activity of Topo II in vitro. Consistent with this, a human PICH(-/-) cell line exhibits chromosome instability and chromosome condensation and decatenation defects similar to those of ICRF-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis.

  8. Meiotic sister chromatid cohesion and recombination in two filamentous fungi

    NARCIS (Netherlands)

    Heemst, van D.

    2000-01-01

    Homologous recombination and sister chromatid cohesion play important roles in the maintenance of genome integrity and the fidelity of chromosome segregation in mitosis and meiosis. Within the living cell, the integrity of the DNA is threatened by various factors that cause DNA-lesions, of which DNA

  9. Is chromatin remodeling required to build sister-chromatid cohesion?

    NARCIS (Netherlands)

    Riedel, Christian G; Gregan, Juraj; Gruber, Stephan; Nasmyth, Kim

    2004-01-01

    Chromosome segregation during mitosis and meiosis depends on the linkage of sister DNA molecules after replication. These links, known as sister-chromatid cohesion, are provided by a multi-subunit complex called cohesin. Recent papers suggest that chromatin-remodeling complexes also have a role in t

  10. Meiotic sister chromatid cohesion and recombination in two filamentous fungi

    OpenAIRE

    Heemst, van, D.

    2000-01-01

    Homologous recombination and sister chromatid cohesion play important roles in the maintenance of genome integrity and the fidelity of chromosome segregation in mitosis and meiosis. Within the living cell, the integrity of the DNA is threatened by various factors that cause DNA-lesions, of which DNA double-strand breaks (DSBs) are considered particularly deleterious. The causative agents can be of endogenous origin, such as metabolically produced free radicals, and of exogenous origin, such a...

  11. Investigating the Interplay between Sister Chromatid Cohesion and Homolog Pairing in Drosophila Nuclei.

    Science.gov (United States)

    Senaratne, T Niroshini; Joyce, Eric F; Nguyen, Son C; Wu, C-Ting

    2016-08-01

    Following DNA replication, sister chromatids must stay connected for the remainder of the cell cycle in order to ensure accurate segregation in the subsequent cell division. This important function involves an evolutionarily conserved protein complex known as cohesin; any loss of cohesin causes premature sister chromatid separation in mitosis. Here, we examined the role of cohesin in sister chromatid cohesion prior to mitosis, using fluorescence in situ hybridization (FISH) to assay the alignment of sister chromatids in interphase Drosophila cells. Surprisingly, we found that sister chromatid cohesion can be maintained in G2 with little to no cohesin. This capacity to maintain cohesion is widespread in Drosophila, unlike in other systems where a reduced dependence on cohesin for sister chromatid segregation has been observed only at specific chromosomal regions, such as the rDNA locus in budding yeast. Additionally, we show that condensin II antagonizes the alignment of sister chromatids in interphase, supporting a model wherein cohesin and condensin II oppose each other's functions in the alignment of sister chromatids. Finally, because the maternal and paternal homologs are paired in the somatic cells of Drosophila, and because condensin II has been shown to antagonize this pairing, we consider the possibility that condensin II-regulated mechanisms for aligning homologous chromosomes may also contribute to sister chromatid cohesion. PMID:27541002

  12. Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination

    NARCIS (Netherlands)

    Revenkova, E.; Eijpe, M.; Heyting, C.; Hodges, C.A.; Hunt, P.A.; Liebe, B.; Scherthan, H.; Jessberger, R.

    2004-01-01

    Sister chromatid cohesion ensures the faithful segregation of chromosomes in mitosis and in both meiotic divisions1, 2, 3, 4. Meiosis-specific components of the cohesin complex, including the recently described SMC1 isoform SMC15, were suggested to be required for meiotic sister chromatid cohesion a

  13. Frequent and efficient use of the sister chromatid for DNA double-strand break repair during budding yeast meiosis.

    Directory of Open Access Journals (Sweden)

    Tamara Goldfarb

    Full Text Available Recombination between homologous chromosomes of different parental origin (homologs is necessary for their accurate segregation during meiosis. It has been suggested that meiotic inter-homolog recombination is promoted by a barrier to inter-sister-chromatid recombination, imposed by meiosis-specific components of the chromosome axis. Consistent with this, measures of Holliday junction-containing recombination intermediates (joint molecules [JMs] show a strong bias towards inter-homolog and against inter-sister JMs. However, recombination between sister chromatids also has an important role in meiosis. The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions, and meiotic double-strand breaks (DSBs that form within such polymorphic regions must be repaired by inter-sister recombination. Efforts to study inter-sister recombination during meiosis, in particular to determine recombination frequencies and mechanisms, have been constrained by the inability to monitor the products of inter-sister recombination. We present here molecular-level studies of inter-sister recombination during budding yeast meiosis. We examined events initiated by DSBs in regions that lack corresponding sequences on the homolog, and show that these DSBs are efficiently repaired by inter-sister recombination. This occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold yields of JMs. Loss of the meiotic-chromosome-axis-associated kinase Mek1 accelerates inter-sister DSB repair and markedly increases inter-sister JM frequencies. Furthermore, inter-sister JMs formed in mek1Δ mutants are preferentially lost, while inter-homolog JMs are maintained. These findings indicate that inter-sister recombination occurs frequently during budding yeast meiosis, with the possibility that up to one-third of all recombination events occur between sister chromatids. We suggest that a Mek1-dependent reduction in

  14. DNA-mediated transfer of a human DNA repair gene that controls sister chromatid exchange.

    OpenAIRE

    Thompson, L H; Brookman, K W; Minkler, J L; Fuscoe, J C; Henning, K A; Carrano, A V

    1985-01-01

    The Chinese hamster cell line mutant EM9, which has a reduced ability to repair DNA strand breaks, is noted for its highly elevated frequency of sister chromatid exchange, a property shared with cells from individuals with Bloom's syndrome. The defect in EM9 cells was corrected by fusion hybridization with normal human fibroblasts and by transfection with DNA from hybrid cells. The transformants showed normalization of sister chromatid exchange frequency but incomplete correction of the repai...

  15. Solution Radioactivated by Hadron Radiation Can Increase Sister Chromatid Exchanges.

    Science.gov (United States)

    Maeda, Junko; Yurkon, Charles R; Fujii, Yoshihiro; Fujisawa, Hiroshi; Kato, Sayaka; Brents, Colleen A; Uesaka, Mitsuru; Fujimori, Akira; Kitamura, Hisashi; Kato, Takamitsu A

    2015-01-01

    When energetic particles irradiate matter, it becomes activated by nuclear reactions. Radioactivation induced cellular effects are not clearly understood, but it could be a part of bystander effects. This investigation is aimed at understanding the biological effects from radioactivation in solution induced by hadron radiation. Water or phosphate buffered saline was activated by being exposed to hadron radiation including protons, carbon- and iron-ions. 1 mL of radioactivated solution was transferred to flasks with Chinese hamster ovary (CHO) cells cultured in 5 mL of complete media. The induction of sister chromatid exchanges (SCE) was used to observe any increase in DNA damage responses. The energy spectrum and the half-lives of the radioactivation were analyzed by NaI scintillation detector in order to identify generated radionuclides. In the radioactivated solution, 511 keV gamma-rays were observed, and their half-lives were approximately 2 min, 10 min, and 20 min. They respectively correspond to the beta+ decay of 15O, 13N, and 11C. The SCE frequencies in CHO cells increased depending on the amount of radioactivation in the solution. These were suppressed with a 2-hour delayed solution transfer or pretreatment with dimethyl sulfoxide (DMSO). Our results suggest that the SCE induction by radioactivated solution was mediated by free radicals produced by the annihilated gamma-rays. Since the SCE induction and DMSO modulation are also reported in radiation-induced bystander effects, our results imply that radioactivation of the solution may have some contribution to the bystander effects from hadron radiation. Further investigations are required to assess if radioactivation effects would attribute an additional level of cancer risk of the hadron radiation therapy itself. PMID:26657140

  16. Cell biology of cancer: BRCA1 and sister chromatid pairing reactions?

    Science.gov (United States)

    Skibbens, Robert V

    2008-02-15

    A significant portion of familial breast/ovarian cancer patients harbors a mutation in Breast Cancer Associated gene 1 (BRCA1). Cells deficient for BRCA1 exhibit chromosome aberrations such as whole chromosome duplications, translocations, inter-sister gaps and gene mis-regulation. Here, new evidence is reviewed that defects in sister chromatid cohesion may contribute directly to cancer cell phenotypes-especially those of BRCA1 mutant cells. Linking cohesion to BRCA1-dependent tumorigenesis are reports that BRCA1-associated components (DNA helicase, RFC, PCNA and genome surveillance factors) are required for efficient sister chromatid cohesion. Other cohesion factors (WAPL, EFO2/ESCO2 and hSecurin) are tightly correlated with various cell-type specific carcinogenesis, in support of a generalized model for cohesion in cancer. Recent findings further reveal that a reciprocal relationship exists in that DNA damage induces new Ctf7/Eco1-dependent sister chromatid pairing reactions that, in turn, are required for efficient DNA repair. Future research into sister chromatid pairing mechanisms are likely to provide critical new insights into the underlying causes of cancer.

  17. 3p deletion syndrome.

    Science.gov (United States)

    Kaur, Anupam; Khetarpal, S

    2013-08-01

    3p deletion is a rare cytogenetic finding. Here we describe a 3 months old male with congenital malformations. His karyotype revealed 3p deletion 46,XY,del(3)(p25-pter). The child had flexion deformity of wrist and elbow which has never been reported before. PMID:24036645

  18. Partial deletion 11q

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Tommerup, N; Sørensen, F B;

    1995-01-01

    We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most...

  19. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others

    1995-06-01

    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  20. INDUCTION, ACCUMULATION, AND PERSISTENCE OF SISTER CHROMATID EXCHANGES IN WOMEN WITH BREAST CANCER RECEIVING CYCLOPHOSPHAMIDE, ANDRIAMYCIN, AND 5-FLUOROACIL CHEMOTHERAPY

    Science.gov (United States)

    The induction, stimulation, and persistence of sister chromatid exchanges (SCE's) and high SCE frequency cells (HFC's) was measured in peripheral lymphocytes of women with breast cancer before chemotherapy and on multiple occasions during and after therapy. Chemotherapy consisted...

  1. Shugoshin1 May Play Important Roles in Separation of Homologous Chromosomes and Sister Chromatids during Mouse Oocyte Meiosis

    OpenAIRE

    Shen Yin; Jun-Shu Ai; Li-Hong Shi; Liang Wei; Ju Yuan; Ying-Chun Ouyang; Yi Hou; Da-Yuan Chen; Heide Schatten; Qing-Yuan Sun

    2008-01-01

    BACKGROUND: Homologous chromosomes separate in meiosis I and sister chromatids separate in meiosis II, generating haploid gametes. To address the question why sister chromatids do not separate in meiosis I, we explored the roles of Shogoshin1 (Sgo1) in chromosome separation during oocyte meiosis. METHODOLOGY/PRINCIPAL FINDINGS: Sgo1 function was evaluated by exogenous overexpression to enhance its roles and RNAi to suppress its roles during two meioses of mouse oocytes. Immunocytochemistry an...

  2. A study of sister chromatid exchange in patients with dental amalgam restorations

    OpenAIRE

    E Lakshmi Priya; K Ranganathan; Uma Devi K Rao; Elizabeth Joshua; Deepu George Mathew; Kavitha Wilson

    2014-01-01

    Study Background: Dental amalgam is still widely used as a restorative material in developing countries due to its low cost and ease of manipulation. The health risks associated with the components of this restorative material has always been a matter of concern. Our study was designed to address this question regarding dental amalgam. Objective: To study sister chromatid exchange (SCE) as an indicator of systemic genotoxicity, due to the exposure from the components of amalgam restoratio...

  3. Sister Chromatid Exchange Frequency in Lymphocytes Cultured from Cotton Gin Workers

    OpenAIRE

    ATMACA, Münevver; BAĞCI, Hüseyin; AÇIKBAŞ, İbrahim; GÜMÜŞ, Dilihan; DÜZCAN, Füsun

    2004-01-01

    Genetic biomonitoring of human populations exposed to potential mutagens/carcinogens can be performed using different genetic markers. Sister chromatid exchange (SCE) is one of the most extensively used markers of the early biological effects of DNA damaging agents. In order to assess the genotoxicity associated with exposure to cotton dust, we determined SCE frequency in peripheral blood lymphocytes cultured from 20 cotton gin workers and 20 controls. Student’s-t test indicated an ...

  4. "Sister Chromatid Exchanges and Micronuclei in Lymphocyte of Nurses Handling Antineoplastic Drugs"

    OpenAIRE

    Ansari-Lari, M; M.Saadat; Shahryari, M.; DD Farhud

    2001-01-01

    Individuals handling antineoplastic drugs or their wastes may absorb these potent genotoxic agents. The effects of handling antineoplastic drugs were examined in a group of 24 nurses working in the hematology and oncology departments of two different university hospitals in Shiraz (Iran) and in a group of 18 unexposed nurses as control group. The cytogenetic repercussions of exposure were assessed by examining sister chromatid exchanges (SCEs) and micronuclei (Mn) in circulating lymphocytes. ...

  5. Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.

    OpenAIRE

    Fatma, N; Jain, A. K.; Rahman, Q

    1991-01-01

    Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and...

  6. Sister chromatid exchange analysis in lymphocytes of workers exposed to hexavalent chromium.

    OpenAIRE

    Nagaya, T.; Ishikawa, N.; Hata, H.

    1989-01-01

    To investigate the usefulness of sister chromatid exchange (SCE) analysis in lymphocytes as an indicator for mutagenic effects after in vivo exposure to hexavalent chromium (Cr), SCE frequency was analysed in lymphocytes of 44 Cr platers occupationally exposed to hexavalent Cr and 47 controls. Although urinary Cr analysis confirmed that the Cr platers were exposed to Cr, no effects of the exposure on SCE frequency were found. Smokers, both Cr platers and controls, had a significantly higher S...

  7. An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres

    OpenAIRE

    Wang, Yisong; Erdmann, Natalie; Giannone, Richard J.; Wu, Jun; Gomez, Marla; Liu, Yie

    2005-01-01

    Telomerase deficiency leads to a progressive loss of telomeric DNA that eventually triggers cell apoptosis in human primary cells during prolonged growth in culture. Rare survivors can maintain telomere length through either activation of telomerase or recombination-based telomere lengthening, and thus proliferate indefinitely. We have explored the possibility that telomeres may be maintained through telomere sister chromatid exchange (T-SCE) in murine telomere reverse transcriptase-deficient...

  8. "Sister Chromatid Exchanges and Micronuclei in Lymphocyte of Nurses Handling Antineoplastic Drugs"

    Directory of Open Access Journals (Sweden)

    M Ansari-Lari

    2001-07-01

    Full Text Available Individuals handling antineoplastic drugs or their wastes may absorb these potent genotoxic agents. The effects of handling antineoplastic drugs were examined in a group of 24 nurses working in the hematology and oncology departments of two different university hospitals in Shiraz (Iran and in a group of 18 unexposed nurses as control group. The cytogenetic repercussions of exposure were assessed by examining sister chromatid exchanges (SCEs and micronuclei (Mn in circulating lymphocytes. A significant increased frequencies of SCE and Mn is observed in circulating lymphocytes. A significant increased frequencies of SCE and Mn is observed in nurses in daily contact with antineoplastic drugs as compared to control group.

  9. Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function

    OpenAIRE

    De Lange, Job; Faramarz, Atiq; Oostra, Anneke B.; Menezes, Renee X.; van der Meulen, Ida H.; Rooimans, Martin A.; Rockx, Davy A.; Brakenhoff, Ruud H.; van Beusechem, Victor W; King, Randall W; Winter, Johan P. de; Wolthuis, Rob M. F.

    2015-01-01

    Warsaw breakage syndrome (WABS) is caused by defective DDX11, a DNA helicase that is essential for chromatid cohesion. Here, a paired genome-wide siRNA screen in patient-derived cell lines reveals that WABS cells do not tolerate partial depletion of individual APC/C subunits or the spindle checkpoint inhibitor p31comet. A combination of reduced cohesion and impaired APC/C function also leads to fatal mitotic arrest in diploid RPE1 cells. Moreover, WABS cell lines, and several cancer cell line...

  10. Chromosome aberrations and sister chromatid exchanges in Swedish paint industry workers

    Energy Technology Data Exchange (ETDEWEB)

    Haglund, U.; Lundberg, I.; Zech, L.

    1980-12-01

    Workers in the Swedish paint industry exposed to a mixture of organic solvents, mainly containing xylene or toluene, were investigated for genotoxic effects. No difference in the frequency of sister chromatid exchanges (SCE), 0.192 and 0.193 per chromosome, respectively, was noted in the peripheral lymphocytes of the exposed group of 17 workers and their matched reference group. No correlation was found between xylene or toluene exposure and SCE frequency nor between total solvent exposure and SCE frequency. The frequency of chromosome aberrations was also investigated for the five most exposed workers and their matched referents, and no difference was found. There was no correlation between SCE and chromosome breaks.

  11. UBL5 is essential for pre-mRNA splicing and sister chromatid cohesion in human cells

    DEFF Research Database (Denmark)

    Oka, Yasuyoshi; Varmark, Hanne; Vitting-Seerup, Kristoffer;

    2014-01-01

    UBL5 is an atypical ubiquitin-like protein, whose function in metazoans remains largely unexplored. We show that UBL5 is required for sister chromatid cohesion maintenance in human cells. UBL5 primarily associates with spliceosomal proteins, and UBL5 depletion decreases pre-mRNA splicing efficiency......, leading to globally enhanced intron retention. Defective sister chromatid cohesion is a general consequence of dysfunctional pre-mRNA splicing, resulting from the selective downregulation of the cohesion protection factor Sororin. As the UBL5 yeast orthologue, Hub1, also promotes spliceosome functions...

  12. Chromatids segregate without centrosomes during Caenorhabditis elegans mitosis in a Ran- and CLASP-dependent manner.

    Science.gov (United States)

    Nahaboo, Wallis; Zouak, Melissa; Askjaer, Peter; Delattre, Marie

    2015-06-01

    During mitosis, chromosomes are connected to a microtubule-based spindle. Current models propose that displacement of the spindle poles and/or the activity of kinetochore microtubules generate mechanical forces that segregate sister chromatids. Using laser destruction of the centrosomes during Caenorhabditis elegans mitosis, we show that neither of these mechanisms is necessary to achieve proper chromatid segregation. Our results strongly suggest that an outward force generated by the spindle midzone, independently of centrosomes, is sufficient to segregate chromosomes in mitotic cells. Using mutant and RNAi analysis, we show that the microtubule-bundling protein SPD-1/MAP-65 and BMK-1/kinesin-5 act as a brake opposing the force generated by the spindle midzone. Conversely, we identify a novel role for two microtubule-growth and nucleation agents, Ran and CLASP, in the establishment of the centrosome-independent force during anaphase. Their involvement raises the interesting possibility that microtubule polymerization of midzone microtubules is continuously required to sustain chromosome segregation during mitosis.

  13. KINETICS OF IN VIVO SISTER CHROMATID EXCHANGE INDUCTION IN MOUSE BONE MARROW CELLS BY ALKYLATING AGENTS: CYCLOPHOSPHAMIDE

    Science.gov (United States)

    Administration of cyclophosphamide (5, 10, 20 and 25 mg/kg body weight) to male CD-1 mice 2 hours after subcutaneous implantation of a 5-bromo-2'-deoxyuridine (BrdU) pellet (55 mg) resulted in a dose-dependent increase in sister chromatid exchanges (SCE) in bone marrow cells. Tre...

  14. Sister chromatid exchange in human populations: the effect of smoking, drug treatment, and occupational exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, B.; Bredberg, A.; McKenzie, W.; Sten, M.

    1982-01-01

    Increased rate of sister chromatid exchange (SCE) in peripheral lymphocytes has been observed in smokers as compared to nonsmokers and in patients receiving certain cytostatic drugs. The increased SCE frequency in smokers was shown to depend on the number of cigarettes smoked per day, as well as on the duration of smoking. DNA cross-links caused by photochemotherapy against psoriasis, 8-methoxypsoralen plus UVA irradiation (PUVA), as well as by the anti-cancer chemotherapeutic agent CCNU, were shown to be more effective at inducing SCE's than other types of DNA damage caused by these treatments. These observations suggest that SCE analysis may be used as an indicator of genotoxic exposure in vivo, provided that the various types of DNA damage caused by genotoxic agents and the dose, as well as the time of exposure in relation to the time of sampling, are considered.

  15. An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yisong [ORNL; Giannone, Richard J [ORNL; Wu, Jun [ORNL; Gomez, Marla V [ORNL; Liu, Yie [ORNL

    2005-01-01

    Telomerase deficiency leads to a progressive loss of telomeric DNA that eventually triggers cell apoptosis in human primary cells during prolonged growth in culture. Rare survivors can maintain telomere length through either activation of telomerase or recombination-based telomere lengthening, and thus proliferate indefinitely. We have explored the possibility that telomeres may be maintained through telomere sister chromatid exchange (T-SCE) in murine telomere reverse transcriptase-deficient (mTert -/-) splenocytes and ES cells. Because telomerase deficiency leads to gradual loss of telomeric DNA in mTert -/- splenocytes and ES cells and eventually to chromosomes with telomere signal-free ends (SFEs), we examined these cell types for evidence of sister chromatid exchange at telomeres, and observed an increase in T-SCEs only in a subset of mTert -/- splenocytes or ES cells that possessed multiple SFEs. Furthermore, T-SCEs were more often detected in ES cells than in splenocytes that harbored a similar frequency of SFEs. In mTert heterozygous (mTert +/-) ES cells or splenocytes, which are known to exhibit a decrease in average telomere length but no SFEs, no increase in T-SCE was observed. In addition to T-SCE, other genomic rearrangements (i.e., SCE) were also significantly increased in mTert -/- ES cells possessing critically short telomeres, but not in splenocytes. Our results suggest that animals and cell culture differ in their ability to carry out genomic rearrangements as a means of maintaining telomere integrity when telomeres become critically shortened.

  16. Edit Distance with Block Deletions

    OpenAIRE

    Dana Shapira; Storer, James A.

    2011-01-01

    Several variants of the edit distance problem with block deletions are considered. Polynomial time optimal algorithms are presented for the edit distance with block deletions allowing character insertions and character moves, but without block moves. We show that the edit distance with block moves and block deletions is NP-complete (Nondeterministic Polynomial time problems in which any given solution to such problem can be verified in polynomial time, and any NP problem can be converted into...

  17. Variation of the symmetrical/asymmetrical ratio in chromatid interchanges during the various phases of the cell cycle of human lymphocytes 'in vitro'

    International Nuclear Information System (INIS)

    Experiments have been performed to verify whether in a human euploid cell system, such as lymphocyte cultures in vitro, there is a differential pattern of induction of chromatid exchanges in the various phases of the cycle. (Auth.)

  18. Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

    Directory of Open Access Journals (Sweden)

    Mihailo Mirkovic

    2015-10-01

    Full Text Available Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC, is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response resulting in abnormal mitotic exit after a short delay. Quantitative live-cell imaging approaches combined with mathematical modeling indicate that weak SAC activation upon cohesion loss is caused by weak signal generation. This is further attenuated by several feedback loops in the mitotic signaling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1 gradually impair error-correction efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.

  19. Cell killing and chromatid damage in primary human bronchial epithelial cells irradiated with accelerated 56Fe ions

    Science.gov (United States)

    Suzuki, M.; Piao, C.; Hall, E. J.; Hei, T. K.

    2001-01-01

    We examined cell killing and chromatid damage in primary human bronchial epithelial cells irradiated with high-energy 56Fe ions. Cells were irradiated with graded doses of 56Fe ions (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at Brookhaven National Laboratory. The survival curves for cells plated 1 h after irradiation (immediate plating) showed little or no shoulder. However, the survival curves for cells plated 24 h after irradiation (delayed plating) had a small initial shoulder. The RBE for 56Fe ions compared to 137Cs gamma rays was 1.99 for immediate plating and 2.73 for delayed plating at the D10. The repair ratio (delayed plating/immediate plating) was 1.67 for 137Cs gamma rays and 1.22 for 56Fe ions. The dose-response curves for initially measured and residual chromatid fragments detected by the Calyculin A-mediated premature chromosome condensation technique showed a linear response. The results indicated that the induction frequency for initially measured fragments was the same for 137Cs gamma rays and 56Fe ions. On the other hand, approximately 85% of the fragments induced by 137Cs gamma rays had rejoined after 24 h of postirradiation incubation; the corresponding amount for 56Fe ions was 37%. Furthermore, the frequency of chromatid exchanges induced by gamma rays measured 24 h after irradiation was higher than that induced by 56Fe ions. No difference in the amount of chromatid damage induced by the two types of radiations was detected when assayed 1 h after irradiation. The results suggest that high-energy 56Fe ions induce a higher frequency of complex, unrepairable damage at both the cellular and chromosomal levels than 137Cs gamma rays in the target cells for radiation-induced lung cancers.

  20. Variations in dysfunction of sister chromatid cohesion in esco2 mutant zebrafish reflect the phenotypic diversity of Roberts syndrome

    Directory of Open Access Journals (Sweden)

    Stefanie M. Percival

    2015-08-01

    Full Text Available Mutations in ESCO2, one of two establishment of cohesion factors necessary for proper sister chromatid cohesion (SCC, cause a spectrum of developmental defects in the autosomal-recessive disorder Roberts syndrome (RBS, warranting in vivo analysis of the consequence of cohesion dysfunction. Through a genetic screen in zebrafish targeting embryonic-lethal mutants that have increased genomic instability, we have identified an esco2 mutant zebrafish. Utilizing the natural transparency of zebrafish embryos, we have developed a novel technique to observe chromosome dynamics within a single cell during mitosis in a live vertebrate embryo. Within esco2 mutant embryos, we observed premature chromatid separation, a unique chromosome scattering, prolonged mitotic delay, and genomic instability in the form of anaphase bridges and micronuclei formation. Cytogenetic studies indicated complete chromatid separation and high levels of aneuploidy within mutant embryos. Amongst aneuploid spreads, we predominantly observed decreases in chromosome number, suggesting that either cells with micronuclei or micronuclei themselves are eliminated. We also demonstrated that the genomic instability leads to p53-dependent neural tube apoptosis. Surprisingly, although many cells required Esco2 to establish cohesion, 10-20% of cells had only weakened cohesion in the absence of Esco2, suggesting that compensatory cohesion mechanisms exist in these cells that undergo a normal mitotic division. These studies provide a unique in vivo vertebrate view of the mitotic defects and consequences of cohesion establishment loss, and they provide a compensation-based model to explain the RBS phenotypes.

  1. Securin and not CDK1/cyclin B1 regulates sister chromatid disjunction during meiosis II in mouse eggs.

    Science.gov (United States)

    Nabti, Ibtissem; Reis, Alexandra; Levasseur, Mark; Stemmann, Olaf; Jones, Keith T

    2008-09-15

    Mammalian eggs remain arrested at metaphase of the second meiotic division (metII) for an indeterminate time before fertilization. During this period, which can last several hours, the continued attachment of sister chromatids is thought to be achieved by inhibition of the protease separase. Separase is known to be inhibited by binding either securin or Maturation (M-Phase)-Promoting Factor, a heterodimer of CDK1/cyclin B1. However, the relative contribution of securin and CDK/cyclin B1 to sister chromatid attachment during metII arrest has not been assessed. Although there are conditions in which either CDK1/cyclinB1 activity or securin can prevent sister chromatid disjunction, principally by overexpression of non-degradable cyclin B1 or securin, we find here that separase activity is primarily regulated by securin and not CDK1/cyclin B1. Thus the CDK1 inhibitor roscovitine and an antibody we designed to block the interaction of CDK1/cyclin B1 with separase, both failed to induce sister disjunction. In contrast, securin morpholino knockdown specifically induced loss of sister attachment, that could be restored by securin cRNA rescue. During metII arrest separase appears primarily regulated by securin binding, not CDK1/cyclin B1. PMID:18639540

  2. Variations in dysfunction of sister chromatid cohesion in esco2 mutant zebrafish reflect the phenotypic diversity of Roberts syndrome.

    Science.gov (United States)

    Percival, Stefanie M; Thomas, Holly R; Amsterdam, Adam; Carroll, Andrew J; Lees, Jacqueline A; Yost, H Joseph; Parant, John M

    2015-08-01

    Mutations in ESCO2, one of two establishment of cohesion factors necessary for proper sister chromatid cohesion (SCC), cause a spectrum of developmental defects in the autosomal-recessive disorder Roberts syndrome (RBS), warranting in vivo analysis of the consequence of cohesion dysfunction. Through a genetic screen in zebrafish targeting embryonic-lethal mutants that have increased genomic instability, we have identified an esco2 mutant zebrafish. Utilizing the natural transparency of zebrafish embryos, we have developed a novel technique to observe chromosome dynamics within a single cell during mitosis in a live vertebrate embryo. Within esco2 mutant embryos, we observed premature chromatid separation, a unique chromosome scattering, prolonged mitotic delay, and genomic instability in the form of anaphase bridges and micronuclei formation. Cytogenetic studies indicated complete chromatid separation and high levels of aneuploidy within mutant embryos. Amongst aneuploid spreads, we predominantly observed decreases in chromosome number, suggesting that either cells with micronuclei or micronuclei themselves are eliminated. We also demonstrated that the genomic instability leads to p53-dependent neural tube apoptosis. Surprisingly, although many cells required Esco2 to establish cohesion, 10-20% of cells had only weakened cohesion in the absence of Esco2, suggesting that compensatory cohesion mechanisms exist in these cells that undergo a normal mitotic division. These studies provide a unique in vivo vertebrate view of the mitotic defects and consequences of cohesion establishment loss, and they provide a compensation-based model to explain the RBS phenotypes.

  3. RSC facilitates Rad59-dependent homologous recombination between sister chromatids by promoting cohesin loading at DNA double-strand breaks.

    Science.gov (United States)

    Oum, Ji-Hyun; Seong, Changhyun; Kwon, Youngho; Ji, Jae-Hoon; Sid, Amy; Ramakrishnan, Sreejith; Ira, Grzegorz; Malkova, Anna; Sung, Patrick; Lee, Sang Eun; Shim, Eun Yong

    2011-10-01

    Homologous recombination repairs DNA double-strand breaks by searching for, invading, and copying information from a homologous template, typically the homologous chromosome or sister chromatid. Tight wrapping of DNA around histone octamers, however, impedes access of repair proteins to DNA damage. To facilitate DNA repair, modifications of histones and energy-dependent remodeling of chromatin are required, but the precise mechanisms by which chromatin modification and remodeling enzymes contribute to homologous DNA repair are unknown. Here we have systematically assessed the role of budding yeast RSC (remodel structure of chromatin), an abundant, ATP-dependent chromatin-remodeling complex, in the cellular response to spontaneous and induced DNA damage. RSC physically interacts with the recombination protein Rad59 and functions in homologous recombination. Multiple recombination assays revealed that RSC is uniquely required for recombination between sister chromatids by virtue of its ability to recruit cohesin at DNA breaks and thereby promoting sister chromatid cohesion. This study provides molecular insights into how chromatin remodeling contributes to DNA repair and maintenance of chromatin fidelity in the face of DNA damage.

  4. Induction of sister chromatid exchanges in xeroderma pigmentosum cells after exposure to ultraviolet light

    International Nuclear Information System (INIS)

    The role of DNA repair mechanisms in the induction of sister chromatid exchanges (SCE) after exposure to ultraviolet radiation was investigated in xeroderma pigmentosum cells. Cells from different excision-deficient XP strains, representing the 5 complementation groups in XP, A, B, C, D and E, and from excision-proficient XP variant strains were irradiated with low doses of UVR (0-3.5 J/m2). The number of SCE was counted after two cycles in the presence of BUdR. In cells of the complementation groups A, B, C and D the number of SCE was significantly higher than in UV-exposed control cells. The frequencies of SCE in group E cells and in XP variant cells were not different from those in control cells. Treatment with caffeine (0-200 μg/ml) did not result in a different response of variant cells compared with normal cells. A simple correlation between SCE frequency and residual excision-repair activity was not observed. The response of the excision-repair deficient cells suggests that unrepaired damage, produced by UVR is involved in the production of SCE

  5. Mutagen sensitivity as measured by induced chromatid breakage as a marker of cancer risk.

    Science.gov (United States)

    Wu, Xifeng; Zheng, Yun-Ling; Hsu, T C

    2014-01-01

    Risk assessment is now recognized as a multidisciplinary process, extending beyond the scope of traditional epidemiologic methodology to include biological evaluation of interindividual differences in carcinogenic susceptibility. Modulation of environmental exposures by host genetic factors may explain much of the observed interindividual variation in susceptibility to carcinogenesis. These genetic factors include, but are not limited to, carcinogen metabolism and DNA repair capacity. This chapter describes a standardized method for the functional assessment of mutagen sensitivity. This in vitro assay measures the frequency of mutagen-induced breaks in the chromosomes of peripheral blood lymphocytes. Mutagen sensitivity assessed by this method has been shown to be a significant risk factor for tobacco-related maladies, especially those of the upper aerodigestive tract. Mutagen sensitivity may therefore be a useful member of a panel of susceptibility markers for defining high-risk subgroups for chemoprevention trials. This chapter describes methods for and discusses results from studies of mutagen sensitivity as measured by quantifying chromatid breaks induced by clastogenic agents, such as the γ-radiation mimetic DNA cross-linking agent bleomycin and chemicals that form so-called bulky DNA adducts, such as 4-nitroquinoline and the tobacco smoke constituent benzo[a]pyrene, in short-term cultured peripheral blood lymphocytes.

  6. Role of the Saccharomyces cerevisiae Rad51 paralogs in sister chromatid recombination.

    Science.gov (United States)

    Mozlin, Amy M; Fung, Cindy W; Symington, Lorraine S

    2008-01-01

    Rad51 requires a number of other proteins, including the Rad51 paralogs, for efficient recombination in vivo. Current evidence suggests that the yeast Rad51 paralogs, Rad55 and Rad57, are important in formation or stabilization of the Rad51 nucleoprotein filament. To gain further insights into the function of the Rad51 paralogs, reporters were designed to measure spontaneous or double-strand break (DSB)-induced sister or nonsister recombination. Spontaneous sister chromatid recombination (SCR) was reduced 6000-fold in the rad57 mutant, significantly more than in the rad51 mutant. Although the DSB-induced recombination defect of rad57 was suppressed by overexpression of Rad51, elevated temperature, or expression of both mating-type alleles, the rad57 defect in spontaneous SCR was not strongly suppressed by these same factors. In addition, the UV sensitivity of the rad57 mutant was not strongly suppressed by MAT heterozygosity, even though Rad51 foci were restored under these conditions. This lack of suppression suggests that Rad55 and Rad57 have different roles in the recombinational repair of stalled replication forks compared with DSB repair. Furthermore, these data suggest that most spontaneous SCR initiates from single-stranded gaps formed at stalled replication forks rather than DSBs.

  7. Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function.

    Science.gov (United States)

    de Lange, Job; Faramarz, Atiq; Oostra, Anneke B; de Menezes, Renee X; van der Meulen, Ida H; Rooimans, Martin A; Rockx, Davy A; Brakenhoff, Ruud H; van Beusechem, Victor W; King, Randall W; de Winter, Johan P; Wolthuis, Rob M F

    2015-01-01

    Warsaw breakage syndrome (WABS) is caused by defective DDX11, a DNA helicase that is essential for chromatid cohesion. Here, a paired genome-wide siRNA screen in patient-derived cell lines reveals that WABS cells do not tolerate partial depletion of individual APC/C subunits or the spindle checkpoint inhibitor p31(comet). A combination of reduced cohesion and impaired APC/C function also leads to fatal mitotic arrest in diploid RPE1 cells. Moreover, WABS cell lines, and several cancer cell lines with cohesion defects, display a highly increased response to a new cell-permeable APC/C inhibitor, apcin, but not to the spindle poison paclitaxel. Synthetic lethality of APC/C inhibition and cohesion defects strictly depends on a functional mitotic spindle checkpoint as well as on intact microtubule pulling forces. This indicates that the underlying mechanism involves cohesion fatigue in response to mitotic delay, leading to spindle checkpoint re-activation and lethal mitotic arrest. Our results point to APC/C inhibitors as promising therapeutic agents targeting cohesion-defective cancers. PMID:26423134

  8. Sister chromatid exchange in human lymphocytes induced by propoxur following plant activation by Vicia faba.

    Science.gov (United States)

    Gómez-Arroyo, S; Calderón-Segura, M E; Villalobos-Pietrini, R

    1995-01-01

    Because the carbamate insecticide propoxur induced sister chromatid exchanges (SCE) in Vicia faba but was ineffective in producing SCE in lymphocytes in culture, it was hardly suspected that plant metabolism was involved. Experiments were conducted in which metabolic activation was afforded by Vicia faba roots, and SCE in human lymphocytes in vitro was used to assess cytogenetic damage. Several concentrations of propoxur (250, 500, 1,000, 1,500, and 2,000 ppm) were applied for 4 hr to the roots of Vicia faba. Extracts prepared from these treatments were added to the lymphocyte cultures and a significant increase of SCE frequencies with a concentration-response relationship could be detected. The lymphocyte proliferation kinetics and the proliferation rate index (PRI) were not affected (except in the highest concentration, of 2,000 ppm). This general behavior was in agreement with the presence of an enzymatic system (S10 fraction) in Vicia roots capable of metabolizing or activating the propoxur. With 2,000 ppm, cell necrosis was produced in Vicia; therefore, this extract did not induce SCE in lymphocytes. However, lymphocyte proliferation kinetics were delayed and PRI was significantly decreased. Ethanol, a promutagen activated by this plant, was applied directly to the lymphocyte cultures as a positive control, and the response was negative. On the other hand, the extracts of roots treated with ethanol increased the SCE to more than twice that of the negative control, but the lymphocyte proliferation kinetics and PRI were not affected.

  9. Correlation of drug-induced sister chromatid exchanges in vitro with in vivo tumor response

    International Nuclear Information System (INIS)

    A spontaneous hepatocarcinoma (HCa) grown in C/sub 3/Hf/Kam mice was used to investigate the ability of the in vitro sister chromatid exchange (SCE) assay to predict in vivo tumor sensitivity to 3 chemotherapeutic agents: melphalan, cis-Platinum, and BCNU. For HCa cells grown in monolayer culture, melphalan was the most efficient at inducing SCEs, followed by cis-Platinum, with BCNU inducing the least. According to in vitro cell survival curves, HCa was most sensitive to melphalan, less sensitive to cis-Platinum, and essentially resistant to BCNU. The relative antineoplastic effects of melphalan, cis-Platinum, and BCNU in vivo were compared by the response of artificial and spontaneous pulmonary metastases and solid tumors to these agents. BCNU had no effect on the number of artificial metastases, while there was a dose-dependent decrease in the number of lung nodules in mice treated with melphalan or cis-Platinum, with melphalan being the more effective. Spontaneous pulmonary metastases generated from HCa leg tumors were reduced in those mice treated with melphalan, unaffected by cis-Platinum, and increased by BCNU. In HCa leg tumors (5 to 6 mm in diameter), melphalan induced the longest growth delay, with cis-Platinum inducing less, and BCNU the least. Thus, the relative effects produced by these 3 drugs in vivo were the same as predicted by SCE assay in vitro

  10. A high rate of telomeric sister chromatid exchange occurs in chronic lymphocytic leukaemia B-cells.

    Science.gov (United States)

    Medves, Sandrine; Auchter, Morgan; Chambeau, Laetitia; Gazzo, Sophie; Poncet, Delphine; Grangier, Blandine; Verney, Aurélie; Moussay, Etienne; Ammerlaan, Wim; Brisou, Gabriel; Morjani, Hamid; Géli, Vincent; Palissot, Valérie; Berchem, Guy; Salles, Gilles; Wenner, Thomas

    2016-07-01

    Cancer cells protect their telomere ends from erosion through reactivation of telomerase or by using the Alternative Lengthening of Telomere (ALT) mechanism that depends on homologous recombination. Chronic lymphocytic leukaemia (CLL) B cells are characterized by almost no telomerase activity, shelterin deregulation and telomere fusions. To characterize telomeric maintenance mechanisms in B-CLL patients, we measured their telomere length, telomerase expression and the main hallmarks of the ALT activity i.e. C-circle concentration, an extra-chromosomal telomere repeat (ECTR), and the level of telomeric sister chromatid exchange (T-SCE) rate. Patients showed relative homogenous telomere length although almost no TERT transcript and nearly no C-circle were evidenced. Nevertheless, compared with normal B cells, B-CLL cells showed an increase in T-SCE rate that was correlated with a strong down-regulation of the topoisomerase III alpha (TOP3A) expression, involved in the dissolution of Holliday Junctions (HJ), together with an increased expression of SLX1A, SLX4, MUS81 and GEN1, involved in the resolution of HJ. Altogether, our results suggest that the telomere maintenance mechanism of B-CLL cells do not preferentially use telomerase or ALT. Rather, the rupture of the dissolvasome/resolvasome balance may increase telomere shuffling that could homogenize telomere length, slowing telomere erosion in this disease. PMID:26970083

  11. Induction of sister chromatid exchanges by coal dust and tobacco snuff extracts in human peripheral lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J.D.; Ong, T.

    1985-01-01

    The organic solvent extracts of sub-bituminous coal dust and tobacco snuff, both together and separately, were tested for the induction of sister chromatid exchanges (SCEs) in human peripheral lymphocytes. The results indicate that these extracts induced SCEs, and that when tested together synergistically induced SCEs in two of three donors. Studies with the organic solvent extracts of all five ranks of coal indicate that the extracts of bituminous, lignite, and peat, but not anthracite, induced SCEs. Similar experiments conducted with water extracts, induced SCEs, and that anthracite was equivocal. To determine whether individuals differed in their SCE responses to coal dust extracts, lymphocytes from five donors were tested with organic solvent extracts of bituminous and sub-bituminous coal. An analysis of variance indicates that the SCE response was significantly influenced by the donor and each of the two coal extracts. The findings presented here suggest that coal dust, with or without tobacco snuff, may play a role in the elevated incidence of gastric cancer in coal miners. Because water extracts of some ranks of coal induced SCEs, there exists the possibility of adverse environmental effects due to coal leachates.

  12. DNA crosslinking, sister-chromatid exchange and specific-locus mutations.

    Science.gov (United States)

    Carrano, A V; Thompson, L H; Stetka, D G; Minkler, J L; Mazrimas, J A; Fong, S

    1979-11-01

    Chinese hamster ovary cells were treated with the DNA-crosslinking chemicals, mitomycin C (MMC) and porfiromycin (POR), and their monofunctional derivative decarbamoyl mitomycin C (DCMMC). After exposure, the cells were studied for the induction of sister-chromatid exchanges (SCEs) and mutations at the hypoxanthine phosphoribosyltransferase and adenine phosphoribosyltransferase loci. The frequency of SCEs varied significantly in successive sampling intervals, requiring the weighting of each interval by the percentage of second-division mitosis in that interval to obtain the mean SCE frequency for each dose. All 3 compounds were potent inducers of SCEs but weakly mutagenic. All 3 chemicals by concentration were approximately equally effective in inducing SCEs or mutations. When the induced SCEs and mutations were compared at equal levels of survival, DCMMC was slightly more effective than MMC or POR in inducing SCEs and somewhat less mutagenic. These results indicate that the DNA interstrand crosslink is not the major lesion responsible for the induction of SCE or mutation by these compounds. PMID:522865

  13. DNA crosslinking, sister-chromatid exchange and specific-locus mutations

    Energy Technology Data Exchange (ETDEWEB)

    Carrano, A.V.; Thompson, L.H.; Stetka, D.G.; Minkler, J.L.; Mazrimas, J.A.; Fong, S.

    1979-01-01

    Chinese hamster ovary cells were treated with the DNA-crosslinking chemicals, mitomycin C (MMC) and porfiromycin (POR), and their monofunctional derivative decarbamoyl mitomycin C (DCMMC). After exposure, the cells were studied for the induction of sister-chromatid exchanges (SCEs) and mutations at the hypoxanthine phosphoribosyltransferase and adenine phosphoribosyltransferase loci. The frequency of SCEs varied significantly in successive sampling intervals, requiring the weighting of each interval by the percentage of second-division mitosis in that interval to obtain the mean SCE frequency for each dose. All 3 compounds were potent inducers of SCEs but weakly mutagenic. All 3 chemicals by concentration were approximately equally effective in inducing SCEs or mutations. When the induced SCEs and mutations were compared at equal levels of survival, DCMMC was slightly more effective than MMC or POR in inducing SCEs and somewhat less mutagenic. These results indicate that the DNA interstrand crosslink is not the major lesion responsible for the induction of SCE or mutation by these compounds.

  14. Health assessment of gasoline and fuel oxygenate vapors: micronucleus and sister chromatid exchange evaluations.

    Science.gov (United States)

    Schreiner, Ceinwen A; Hoffman, Gary M; Gudi, Ramadevi; Clark, Charles R

    2014-11-01

    Micronucleus and sister chromatid exchange (SCE) tests were performed for vapor condensate of baseline gasoline (BGVC), or gasoline with oxygenates, methyl tert-butyl ether (G/MTBE), ethyl tert butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), t-butyl alcohol (TBA), or ethanol (G/EtOH). Sprague Dawley rats (the same 5/sex/group for both endpoints) were exposed to 0, 2000, 10,000, or 20,000mg/m(3) of each condensate, 6h/day, 5days/week over 4weeks. Positive controls (5/sex/test) were given cyclophosphamide IP, 24h prior to sacrifice at 5mg/kg (SCE test) and 40mg/kg (micronucleus test). Blood was collected from the abdominal aorta for the SCE test and femurs removed for the micronucleus test. Blood cell cultures were treated with 5μg/ml bromodeoxyuridine (BrdU) for SCE evaluation. No significant increases in micronucleated immature erythrocytes were observed for any test material. Statistically significant increases in SCE were observed in rats given BGVC alone or in female rats given G/MTBE. G/TAME induced increased SCE in both sexes at the highest dose only. Although DNA perturbation was observed for several samples, DNA damage was not expressed as increased micronuclei in bone marrow cells. Inclusion of oxygenates in gasoline did not increase the effects of gasoline alone or produce a cytogenetic hazard. PMID:24852491

  15. In vitro genotoxicity of fipronil sister chromatid exchange, cytokinesis block micronucleus test, and comet assay.

    Science.gov (United States)

    Çelik, Ayla; Ekinci, Seda Yaprak; Güler, Gizem; Yildirim, Seda

    2014-03-01

    Fipronil (FP) is a phenylpyrazole pesticide developed by the transnational company Rhône-Poulenc Agro in 1987. Data on the genotoxicity and toxicity of FP are rather inadequate. In this study, we aimed to evaluate the potential genotoxic activity of FP using the single-cell microgel electrophoresis or comet assay, sister chromatid exchanges (SCEs), and micronuclei (MN) in human peripheral blood lymphocytes. In addition, the cytokinesis block proliferation index (CBPI) and proliferation index (PRI) were measured for cytotoxicity. In this study, three different doses of FP were used (0.7, 0.3, 0.1 μg/mL). Mitomycin C (2 μg/mL) and hydrogen peroxide were used as positive controls for SCE MN test systems, and comet assay, respectively. FP induced a statistically significant increase in the MN and SCE frequency and DNA damage in a dose-dependent manner in human peripheral blood lymphocytes (pcomet assay, we showed that all the doses of the FP induced DNA damage in human peripheral blood lymphocytes in vitro (p<0.05).

  16. ATLAS DQ2 DELETION SERVICE

    CERN Document Server

    Oleynik, D; The ATLAS collaboration; Garonne, V; Campana, S

    2012-01-01

    ATLAS DQ2 Deletion service is a sub system of the ATLAS Distributed Data Management (DDM) project DQ2. DDM DQ2 responsible for the replication, access and bookkeeping of ATLAS data across more than 130 distributed grid sites. It also enforces data management policies decided on by the collaboration and defined in the ATLAS computing model. Responsibility of ATLAS DQ2 Deletion service is serving deletion requests on the grid by interacting with grid middleware and the DQ2 catalogues. Furthermore, it also takes care of retry strategies, check-pointing transactions, load management and fault tolerance. In this talk special attention is paid to the technical details, which are used to achieve the high performance of service, accomplished without overloading either site storage, catalogues or other DQ2 components. Also specialty of database backend implementation will be described. Special section will be devote to the deletion monitoring service that allows operators a detailed view of the working system.

  17. ATLAS DQ2 Deletion Service

    CERN Document Server

    OLEYNIK, D; The ATLAS collaboration; GARONNE, V; CAMPANA, S

    2012-01-01

    The ATLAS Distributed Data Management project DQ2 is responsible for the replication, access and bookkeeping of ATLAS data across more than 100 distributed grid sites. It also enforces data management policies decided on by the collaboration and defined in the ATLAS computing model. The DQ2 deletion service is one of the most important DDM services. This distributed service interacts with 3rd party grid middleware and the DQ2 catalogs to serve data deletion requests on the grid. Furthermore, it also takes care of retry strategies, check-pointing transactions, load management and fault tolerance. In this paper special attention is paid to the technical details which are used to achieve the high performance of service (peaking at more than 4 millions files deleted per day), accomplished without overloading either site storage, catalogs or other DQ2 components. Special attention is also paid to the deletion monitoring service that allows operators a detailed view of the working system.

  18. The Relationship between Dioxin Congeners in the Breast Milk of Vietnamese Women and Sister Chromatid Exchange

    Directory of Open Access Journals (Sweden)

    Hiroyuki Suzuki

    2014-04-01

    Full Text Available The aim of this study was to clarify the relationship between dioxin concentrations in breast milk and the sister chromatid exchange (SCE frequency in women from herbicide-sprayed and non sprayed areas. Blood samples were taken from 21 women with high TCDD (tetrachlorodibenzo-p-dioxin levels from sprayed areas, 23 women with moderate TCDD levels from sprayed areas, and 19 women from non sprayed areas to determine their SCE frequency. The SCE frequencies for the high and moderate TCDD groups from the sprayed area and for the non sprayed area group were 2.40, 2.19, and 1.48 per cell, respectively. Multiple regression analysis showed that the standardized β values for 1,2,3,6,7,8-hexaCDD (β = 0.60, 1,2,3,4,6,7,8-heptaCDD (β = 0.64, and octaCDD (β = 0.65 were higher than those for TCDD (β = 0.34 and 1,2,3,7,8-pentaCDD (β = 0.42. The adjusted R2 value for polyCDDs (R2 = 0.38 was higher than that for polyCDD toxic equivalents (TEQ (toxic equivalents; R2 = 0.23. This study therefore shows that levels of hexa-, hepta-, and octaCDD, which were previously regarded as being less toxic than TCDD, are closely related to SCE frequency and that the level of dioxin (pg/g lipid is potentially more useful as an indicator than TEQ value for explaining SCE frequency.

  19. Chiasmata promote monopolar attachment of sister chromatids and their co-segregation toward the proper pole during meiosis I.

    Directory of Open Access Journals (Sweden)

    Yukinobu Hirose

    2011-03-01

    Full Text Available The chiasma is a structure that forms between a pair of homologous chromosomes by crossover recombination and physically links the homologous chromosomes during meiosis. Chiasmata are essential for the attachment of the homologous chromosomes to opposite spindle poles (bipolar attachment and their subsequent segregation to the opposite poles during meiosis I. However, the overall function of chiasmata during meiosis is not fully understood. Here, we show that chiasmata also play a crucial role in the attachment of sister chromatids to the same spindle pole and in their co-segregation during meiosis I in fission yeast. Analysis of cells lacking chiasmata and the cohesin protector Sgo1 showed that loss of chiasmata causes frequent bipolar attachment of sister chromatids during anaphase. Furthermore, high time-resolution analysis of centromere dynamics in various types of chiasmate and achiasmate cells, including those lacking the DNA replication checkpoint factor Mrc1 or the meiotic centromere protein Moa1, showed the following three outcomes: (i during the pre-anaphase stage, the bipolar attachment of sister chromatids occurs irrespective of chiasma formation; (ii the chiasma contributes to the elimination of the pre-anaphase bipolar attachment; and (iii when the bipolar attachment remains during anaphase, the chiasmata generate a bias toward the proper pole during poleward chromosome pulling that results in appropriate chromosome segregation. Based on these results, we propose that chiasmata play a pivotal role in the selection of proper attachments and provide a backup mechanism that promotes correct chromosome segregation when improper attachments remain during anaphase I.

  20. PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis

    DEFF Research Database (Denmark)

    Nielsen, Christian Thomas Friberg; Huttner, Diana; Bizard, Anna H;

    2015-01-01

    PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural......-193-treated cells. We propose that PICH and Topo II cooperate to prevent chromosome missegregation events in mitosis....

  1. Inhibition of protein synthesis does not antagonize induction of UV-induced sister-chromatid exchange in xeroderma pigmentosum cells

    International Nuclear Information System (INIS)

    Cycloheximide strongly antagonizes the induction of sisterchromatid exchanges by ethyl methanesulfonate or mitomycin C in human skin fibroblast and xeroderma pigmentosum cells (group A). Analogous behavior has been observed in several other species including Chinese hamster and plant cells. This report documents an exception to that pattern: cycloheximide fails to antagonize UV-induced sister chromatid exchange in xeroderma pigmentosum cells, whereas it does in normal human skin fibroblast cells. A genetic defect in these cells is postulated to alter the UV-mediated DNA recombination process. (author)

  2. Chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with sodium metabisulfite, a food preservative.

    Science.gov (United States)

    Rencüzogullari, E; Ila, H B; Kayraldiz, A; Topaktaş, M

    2001-02-20

    The aim of this study was to investigate the ability of sodium metabisulfite (SMB) which is used as an antimicrobial substance in food, to induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in human lymphocytes. SMB-induced CAs and SCEs at all concentrations (75, 150 and 300 microg/ml) and treatment periods (24 and 48h) dose-dependently. However, SMB decreased the replication index (RI) and the mitotic index (MI) at the concentrations of 150 and 300 microg/ml for 24 and 48h treatment periods. This decrease was dose-dependent as well.

  3. Erythrocytes modulate cell cycle progression but not the baseline frequency of sister chromatid exchanges in pig lymphocytes

    OpenAIRE

    Miguel A. Reigosa; Sonia Soloneski; Garcia, Carlos F.; Larramendy, Marcelo L.

    1997-01-01

    The effect of co-culturing varying concentrations of pig and human red blood cells (RBCs) on the baseline frequency of sister chromatid exchanges (SCEs) and cell-cycle progression in pig plasma (PLCs) and whole blood leukocyte cultures (WBCs) was studied. No variation in SCE frequency was observed between pig control WBC and PLC. Addition of pig and human RBCs to pig PLCs did not modify the baseline frequency of SCEs. On the other hand, cell proliferation was slower in PLCs than in WBCs. The ...

  4. SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs

    OpenAIRE

    van der Lelij, Petra; Stocsits, Roman R; Ladurner, Rene; Petzold, Georg; Kreidl, Emanuel; Koch, Birgit; Schmitz, Julia; Neumann, Beate; Ellenberg, Jan; Peters, Jan-Michael

    2014-01-01

    Although splicing is essential for the expression of most eukaryotic genes, inactivation of splicing factors causes specific defects in mitosis. The molecular cause of this defect is unknown. Here, we show that the spliceosome subunits SNW1 and PRPF8 are essential for sister chromatid cohesion in human cells. A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein s...

  5. ATLAS DQ2 Deletion Service

    CERN Document Server

    OLEYNIK, D; The ATLAS collaboration; GARONNE, V; CAMPANA, S

    2012-01-01

    The ATLAS Distributed Data Management project DQ2 is responsible for the replication, access and bookkeeping of ATLAS data across more than 100 distributed grid sites. It also enforces data management policies decided on by the collaboration and defined in the ATLAS computing model. The DQ2 Deletion Service is one of the most important DDM services. This distributed service interacts with 3rd party grid middleware and the DQ2 catalogues to serve data deletion requests on the grid. Furthermore, it also takes care of retry strategies, check-pointing transactions, load management and fault tolerance. In this paper special attention is paid to the technical details which are used to achieve the high performance of service, accomplished without overloading either site storage, catalogues or other DQ2 components. Special attention is also paid to the deletion monitoring service that allows operators a detailed view of the working system.

  6. In vivo study on the replicative model validity of sister chromatid exchanges production

    International Nuclear Information System (INIS)

    The sister chromatid exchanges (SCE) frequency determination has been used as index of damage to DNA, however the biological meaning of this event is still ignored. Different models in order to explain the mechanism of their formation have been proposed and they could be contained in two categories: a) those that consider that the SCE is produced by means of discreet lesions to the DNA and that they occur in the place of the lesion, and b) those that propose that the SCE is caused by a group of lesions and that therefore the place in which they occur could not be associated with a lesion in particular. The model of Painter (1980) belongs to this last group. It suggests that the region of the DNA where the clusters are united, is the only place in which the exchange of double chain could happen during the synthesis of the DNA and makes the prediction that since the x rays retard the beginning of the duplication, the pretreatment with ionizing radiation would reduce the frequency of SCE induced by agents capable to block the lengthening of the chain of DNA, that are the most efficient SCE inducers. The objective of the present work was to establish the validity of this replicative model for the SCE formation, based in its prediction. The effect of the unilateral preexposition of mouse to gamma radiation was determined on the SCE induction by Mitomycin C (MMC), in cells of the femoral bone marrow In vivo. This strategy allows to determine the effect of the pretreatment in the same organism, minimizing the variability of the response between individuals. There was not a significant variability between the frequencies of SCE, basal and induced by gamma radiation or MMC in the same organism. The animals that received the gamma radiation pretreatment, showed a reduction of approximately the 30 % in the frequency of SCE, assuming an additive effect of the radiation with the MMC. These results coincide with the prediction of the model of Painter, however it is not

  7. The MCM-binding protein ETG1 aids sister chromatid cohesion required for postreplicative homologous recombination repair.

    Directory of Open Access Journals (Sweden)

    Naoki Takahashi

    2010-01-01

    Full Text Available The DNA replication process represents a source of DNA stress that causes potentially spontaneous genome damage. This effect might be strengthened by mutations in crucial replication factors, requiring the activation of DNA damage checkpoints to enable DNA repair before anaphase onset. Here, we demonstrate that depletion of the evolutionarily conserved minichromosome maintenance helicase-binding protein ETG1 of Arabidopsis thaliana resulted in a stringent late G2 cell cycle arrest. This arrest correlated with a partial loss of sister chromatid cohesion. The lack-of-cohesion phenotype was intensified in plants without functional CTF18, a replication fork factor needed for cohesion establishment. The synergistic effect of the etg1 and ctf18 mutants on sister chromatid cohesion strengthened the impact on plant growth of the replication stress caused by ETG1 deficiency because of inefficient DNA repair. We conclude that the ETG1 replication factor is required for efficient cohesion and that cohesion establishment is essential for proper development of plants suffering from endogenous DNA stress. Cohesion defects observed upon knockdown of its human counterpart suggest an equally important developmental role for the orthologous mammalian ETG1 protein.

  8. Rtt107 phosphorylation promotes localisation to DNA double-stranded breaks (DSBs and recombinational repair between sister chromatids.

    Directory of Open Access Journals (Sweden)

    Pranav Ullal

    Full Text Available Efficient repair of DNA double-stranded breaks (DSB requires a coordinated response at the site of lesion. Nucleolytic resection commits repair towards homologous recombination, which preferentially occurs between sister chromatids. DSB resection promotes recruitment of the Mec1 checkpoint kinase to the break. Rtt107 is a target of Mec1 and serves as a scaffold during repair. Rtt107 plays an important role during rescue of damaged replication forks, however whether Rtt107 contributes to the repair of DSBs is unknown. Here we show that Rtt107 is recruited to DSBs induced by the HO endonuclease. Rtt107 phosphorylation by Mec1 and its interaction with the Smc5-Smc6 complex are both required for Rtt107 loading to breaks, while Rtt107 regulators Slx4 and Rtt101 are not. We demonstrate that Rtt107 has an effect on the efficiency of sister chromatid recombination (SCR and propose that its recruitment to DSBs, together with the Smc5-Smc6 complex is important for repair through the SCR pathway.

  9. In Vitro genotoxic and antigenotoxic studies of Thai Noni fruit juice by chromosomal aberration and sister chromatid exchange assays in human lymphocytes

    OpenAIRE

    Treetip Ratanavalachai; Sumon Thitiorul; Pranee Nandhasri

    2008-01-01

    The genotoxic and antigenotoxic effects of Noni fruit juice produced in Thailand have been studied in human lymphocytes for chromosome aberration assay and sister chromatid exchange (SCE) assay in vitro. Treatment of Noni fruit juice(3.1-50 mg/ml) alone for 3 h did not significantly induce chromosomal aberration or SCE (p

  10. Rec8p, a meiotic recombination and sister chromatid cohesion phosphoprotein of the Rad21p family conserved from fision yeast to humans.

    NARCIS (Netherlands)

    S. Parisi; M.J. McKay (Michael); M. Molnar; M.A. Thompson (Anne); P.J. van der Spek (Peter); E. van Drunen-Schoenmaker; R. Kanaar (Roland); E. Lehmann; J.H.J. Hoeijmakers (Jan); J. Kohli

    1999-01-01

    textabstractOur work and that of others defined mitosis-specific (Rad21 subfamily) and meiosis-specific (Rec8 subfamily) proteins involved in sister chromatid cohesion in several eukaryotes, including humans. Mutation of the fission yeast Schizosaccharomyces pombe rec8 gene was previously shown to c

  11. 76 FR 22680 - Procurement List; Deletions

    Science.gov (United States)

    2011-04-22

    ... INFORMATION: Deletions On 2/25/2011 (76 FR 10571), the Committee for Purchase From People Who Are Blind or... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Deletions from the Procurement List. SUMMARY:...

  12. Induction of sister-chromatid exchanges in ICR 2A frog cells exposed to 254 nm UV wavelengths

    International Nuclear Information System (INIS)

    Exposure of ICR 2A frog cells to 254 nm UV induced the formation of sister-chromatid exchanges (SCEs) in a fluence-dependent manner. Cells were also exposed to the UV produced by a fluorescent sunlamp that was filtered through 8C Mylar in order to simulate the mid-UV (290-320 nm) portion of sunlight reaching the earth's surface. In this instance, SCEs were induced in a linear fashion at low fluences but reached a plateau at a low level of induced SCEs. In addition, pretreatment of cells with the solar UV followed by exposure to 254 nm UV resulted in a significantly lower level of SCEs than in cells exposed to 254 nm UV alone. (author)

  13. Early mouse embryos exhibit strain variation in radiation-induced sister-chromatid exchange: relationship with DNA repair.

    Science.gov (United States)

    Bennett, J; Pedersen, R A

    1984-04-01

    Although mature mammalian sperm are incapable of DNA repair, repair of damaged sperm DNA can occur after fertilization, as the sperm head decondenses and forms the male pronucleus. To quantify the cytogenetic effects of damage to sperm DNA we adapted the sister-chromatid exchange (SCE) test for use in early mouse embryos. After ultraviolet (UV) irradiation of sperm, eggs were fertilized in vitro and cultured for 2 cell cycles in medium containing fluorodeoxyuridine and bromodeoxyuridine; chromosomes were then prepared for SCE analysis. We found that UV-induced SCEs could be detected at the second cleavage division, and that eggs of different strains showed different frequencies of SCEs when fertilized by damaged sperm of a single strain. These results may indicate strain-specific differences in DNA repair of UV-induced DNA lesions by the early mouse embryo.

  14. Early mouse embryos exhibit strain variation in radiation-induced sister-chromatid exchange: relationship with DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, J. (California Univ., San Francisco (USA). Lab. of Radiobiology); Pedersen, R.A. (California Univ., San Francisco (USA). Dept. of Anatomy)

    1984-04-01

    Although mature mammalian sperm are incapable of DNA repair, repair of damaged sperm DNA can occur after fertilization, as the sperm head decondenses and forms the male pronucleus. To quantify the cytogenetic effects of damage to sperm DNA we adapted the sister-chromatid exchange (SCE) test for use in early mouse embryos. After ultraviolet (UV) irradiation of sperm, eggs were fertilized in vitro and cultured for 2 cell cycles in medium containing fluorodeoxyuridine and bromodeoxyuridine; chromosomes were then prepared for SCE analysis. We found that UV-induced SCEs could be detected at the second cleavage division, and that eggs of different strains showed different frequencies of SCEs when fertilized by damaged sperm of a single strain. These results may indicate strain-specific differences in DNA repair of UV-induced DNA lesions by the early mouse embryo.

  15. Recombinant chromosome 9 possibly derived from breakage and reunion of sister chromatids within a paracentric inversion loop.

    Science.gov (United States)

    Phelan, M C; Stevenson, R E; Anderson, E V

    1993-05-15

    Chromosomally unbalanced offspring resulting from the recombination of parental paracentric inversions are uncommon. We report on a 20-month-old boy with a partial duplication of 9p due to the recombination of a paternal paracentric inversion. The patient's recombinant chromosome was designated rec(9)(p13-->p24::p12-->p24::p12-->qter). The patient's father and paternal aunt have a paracentric inversion of chromosome 9:inv(9)(p13p24). Although several mechanisms have been proposed to explain the chromosome imbalance generated from paracentric inversions, none of the previously described mechanisms can account for the structure of the recombinant chromosome observed in the propositus. We propose an unusual mechanism of formation involving breakage and unequal reunion of sister chromatids within the inversion loop to explain the structure of the patient's recombinant chromosome. PMID:8488876

  16. Test of radiation damage enhancement due to incorporation of BrUdR into DNA using chromatid aberrations

    International Nuclear Information System (INIS)

    Monte Carlo track structure calculations, leading to an estimation of the magnitude of enhancement of radiation damage due to the incorporation of the halogenated pyrimidine, bromodeoxyuridine (BrUdR) a thymine analog, into DNA have been made. The increase in the yield of double strand breaks for various degrees of substitution in one (monofilarly) or both strands (bifilarly) have been calculated. To test these calculations, quantitative selected radiation-induced aberrations have been obtained in Chinese hamster (V79) fibroblast chromosomes having various patterns of BrUdR substitution following irradiation with 250 kV X rays. Free ''breaks'' and achromatic lesions ''gaps'' show no appreciable sensitizations, but breaks involved in chromatid interchanges show significant enhancement though of lower magnitude than theoretical predictions

  17. SGO1 maintains bovine meiotic and mitotic centromeric cohesions of sister chromatids and directly affects embryo development.

    Directory of Open Access Journals (Sweden)

    Feng-Xia Yin

    Full Text Available Shugoshin (SGO is a critical factor that enforces cohesion from segregation of paired sister chromatids during mitosis and meiosis. It has been studied mainly in invertebrates. Knowledge of SGO(s in a mammalian system has only been reported in the mouse and Hela cells. In this study, the functions of SGO1 in bovine oocytes during meiotic maturation, early embryonic development and somatic cell mitosis were investigated. The results showed that SGO1 was expressed from germinal vesicle (GV to the metaphase II stage. SGO1 accumulated on condensed and scattered chromosomes from pre-metaphase I to metaphase II. The over-expression of SGO1 did not interfere with the process of homologous chromosome separation, although once separated they were unable to move to the opposing spindle poles. This often resulted in the formation of oocytes with 60 replicated chromosomes. Depletion of SGO1 in GV oocytes affected chromosomal separation resulting in abnormal chromosome alignment at a significantly higher proportion than in control oocytes. Knockdown of SGO1 expression significantly decreased the embryonic developmental rate and quality. To further confirm the function(s of SGO1 during mitosis, bovine embryonic fibroblast cells were transfected with SGO1 siRNAs. SGO1 depletion induced the premature dissociation of chromosomal cohesion at the centromere and along the chromosome arm giving rise to abnormal appearing mitotic patterns. The results of this study infer that SGO1 is involved in the centromeric cohesion of sister chromatids and chromosomal movement towards the spindle poles. Depletion of SGO1 causes arrestment of cell division in meiosis and mitosis.

  18. Deletion 22q13.3 syndrome

    OpenAIRE

    Phelan Mary C

    2008-01-01

    Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndr...

  19. Gene Deletion by Synthesis in Yeast.

    Science.gov (United States)

    Kim, Jinsil; Kim, Dong-Uk; Hoe, Kwang-Lae

    2017-01-01

    Targeted gene deletion is a useful tool for understanding the function of a gene and its protein product. We have developed an efficient and robust gene deletion approach in yeast that employs oligonucleotide-based gene synthesis. This approach requires a deletion cassette composed of three modules: a central 1397-bp KanMX4 selection marker module and two 366-bp gene-specific flanking modules. The invariable KanMX4 module can be used in combination with different pairs of flanking modules targeting different genes. The two flanking modules consist of both sequences unique to each cassette (chromosomal homologous regions and barcodes) and those common to all deletion constructs (artificial linkers and restriction enzyme sites). Oligonucleotides for each module and junction regions are designed using the BatchBlock2Oligo program and are synthesized on a 96-well basis. The oligonucleotides are ligated into a single deletion cassette by ligase chain reaction, which is then amplified through two rounds of nested PCR to obtain sufficient quantities for yeast transformation. After removal of the artificial linkers, the deletion cassettes are transformed into wild-type diploid fission yeast SP286 cells. Verification of correct clone and gene deletion is achieved by performing check PCR and tetrad analysis. This method with proven effectiveness, as evidenced by a high success rate of gene deletion, can be potentially applicable to create systematic gene deletion libraries in a variety of yeast species. PMID:27671940

  20. RSC Facilitates Rad59-Dependent Homologous Recombination between Sister Chromatids by Promoting Cohesin Loading at DNA Double-Strand Breaks ▿

    OpenAIRE

    Oum, Ji-Hyun; Seong, Changhyun; Kwon, YoungHo; Ji, Jae-Hoon; Sid, Amy; Ramakrishnan, Sreejith; Ira, Grzegorz; Malkova, Anna; Sung, Patrick; Lee, Sang Eun; Shim, Eun Yong

    2011-01-01

    Homologous recombination repairs DNA double-strand breaks by searching for, invading, and copying information from a homologous template, typically the homologous chromosome or sister chromatid. Tight wrapping of DNA around histone octamers, however, impedes access of repair proteins to DNA damage. To facilitate DNA repair, modifications of histones and energy-dependent remodeling of chromatin are required, but the precise mechanisms by which chromatin modification and remodeling enzymes cont...

  1. Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

    Directory of Open Access Journals (Sweden)

    Stephan eSauer

    2012-11-01

    Full Text Available Ever since cloning the classic iv mutation identified the ‘left-right dynein’ (lrd gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old ‘Watson’ vs. old ‘Crick’ strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical ‘left-right axis development 1’ (‘lra1’ gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

  2. DNA single strand breakage, DNA adducts, and sister chromatid exchange in lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven workers.

    OpenAIRE

    W. Popp; Vahrenholz, C.; Schell, C; Grimmer, G.; Dettbarn, G; Kraus, R.; Brauksiepe, A; Schmeling, B; Gutzeit, T; von Bülow, J; Norpoth, K

    1997-01-01

    OBJECTIVES: To investigate the specificity of biological monitoring variables (excretion of phenanthrene and pyrene metabolites in urine) and the usefulness of some biomarkers of effect (alkaline filter elution, 32P postlabelling assay, measurement of sister chromatid exchange) in workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: 29 coke oven workers and a standardised control group were investigated for frequencies of DNA single strand breakage, DNA protein cross links (al...

  3. 1p36 deletion syndrome: an update

    Directory of Open Access Journals (Sweden)

    Jordan VK

    2015-08-01

    Full Text Available Valerie K Jordan,1 Hitisha P Zaveri,2 Daryl A Scott1,2 1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA; 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA Abstract: Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are the most common terminal deletions in humans. Medical problems commonly caused by terminal deletions of 1p36 include developmental delay, intellectual disability, seizures, vision problems, hearing loss, short stature, distinctive facial features, brain anomalies, orofacial clefting, congenital heart defects, cardiomyopathy, and renal anomalies. Although 1p36 deletion syndrome is considered clinically recognizable, there is significant phenotypic variation among affected individuals. This variation is due, at least in part, to the genetic heterogeneity seen in 1p36 deletions which include terminal and interstitial deletions of varying lengths located throughout the 30 Mb of DNA that comprise chromosome 1p36. Array-based copy number variant analysis can easily identify genomic regions of 1p36 that are deleted in an affected individual. However, predicting the phenotype of an individual based solely on the location and extent of their 1p36 deletion remains a challenge since most of the genes that contribute to 1p36-related phenotypes have yet to be identified. In addition, haploinsufficiency of more than one gene may contribute to some phenotypes. In this article, we review recent successes in the effort to map and identify the genes and genomic regions that contribute to specific 1p36-related phenotypes. In particular, we highlight evidence implicating MMP23B, GABRD, SKI, PRDM16, KCNAB2, RERE, UBE4B, CASZ1, PDPN, SPEN, ECE1, HSPG2, and LUZP1 in various 1p36 deletion phenotypes. Keywords: chromosome 1p36, chromosome deletion, 1p36 deletion syndrome, monosomy 1p36

  4. Inhibition of UV-induced sister chromatid exchanges in ICR 2A frog cells by pretreatment with γ-rays

    International Nuclear Information System (INIS)

    Exposure of ICR 2A frog cells to UV induced the formation of sister chromatid exchanges (SCEs). However, pretreatment of UV-irradiated cells with γ-rays resulted in a reduction in the level of SCEs, confirming the prediction made by the replication model for SCE induction. This effect was observed over a range of UV fluences (1-5 J/m/sup 2/) and γ-ray doses (50-500 rad). The depression in the yield of SCEs was greatest when the cells were UV-irradiated either immediately or 3 h after γ-irradiation. Following a 6 h incubation, the reduction was much less pronounced while at 48 h the level of SCEs was nearly identical to that of cells exposed to UV alone. This corresponds roughly to the kinetics of depression and recovery in DNA synthesis after γ-irradiation of ICR 2A cells. Hence, these results support the hypothesis that the depression of UV-induced SCEs was the result of a delay in replicon initiation caused by //i/-irradiation

  5. Effect of chlorophyllin on induction of exchanges in sister chromatids by gamma irradiation in mice spermatogonia in vivo

    International Nuclear Information System (INIS)

    Mouse were exposed to different doses of gamma radiation and the effect on Sister Chromatid Exchange (SCE) frequency in spermatogonias was evaluated. The effect was analyzed before and after Bromodeoxyuridine (BrdU) incorporation to determine the interference of such agent with the cellular response induced by radiation. The capacity of chlorophyllin (sodium and Copper salt derivative from chlorophyll) to reduce SCE induction by radiation in normal and BrdU radio sensitized spermatogonia was also determined. The results indicate that there was a significant increase in SCE frequency by gamma radiation exposure in these cells, such effect was higher irradiating after BrdU incorporation than before. This fact confirms previous observations that BrdU sensitizes some cells to SCE induction. With regard to the chlorophyllin effect, it was determined that this salt acts as a radioprotector reducing gamma-rays induced SCE before or after BrdU incorporation Total protection was obtained with 200 μg of chlorophyllin per g of body weight in both protocols. Under the experimental conditions this study there was no evidence of genotoxicity induced by chlorophyllin itself. The results suggest that this agent may act as a radioprotector by scavenging free radicals produced by gamma-radiation which cause DNA lesions that are involved in SCE formation. (Author)

  6. SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs

    Science.gov (United States)

    van der Lelij, Petra; Stocsits, Roman R; Ladurner, Rene; Petzold, Georg; Kreidl, Emanuel; Koch, Birgit; Schmitz, Julia; Neumann, Beate; Ellenberg, Jan; Peters, Jan-Michael

    2014-01-01

    Although splicing is essential for the expression of most eukaryotic genes, inactivation of splicing factors causes specific defects in mitosis. The molecular cause of this defect is unknown. Here, we show that the spliceosome subunits SNW1 and PRPF8 are essential for sister chromatid cohesion in human cells. A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein sororin and the APC/C subunit APC2. SNW1 depletion causes cohesion defects predominantly by reducing sororin levels, which causes destabilisation of cohesin on DNA. SNW1 depletion also reduces APC/C activity and contributes to cohesion defects indirectly by delaying mitosis and causing “cohesion fatigue”. Simultaneous expression of sororin and APC2 from intron-less cDNAs restores cohesion in SNW1-depleted cells. These results indicate that the spliceosome is required for mitosis because it enables expression of genes essential for cohesion. Our transcriptome-wide identification of retained introns in SNW1- and PRPF8-depleted cells may help to understand the aetiology of diseases associated with splicing defects, such as retinosa pigmentosum and cancer. PMID:25257309

  7. Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins.

    Directory of Open Access Journals (Sweden)

    Cheri A Schaaf

    Full Text Available The cohesin protein complex was first recognized for holding sister chromatids together and ensuring proper chromosome segregation. Cohesin also regulates gene expression, but the mechanisms are unknown. Cohesin associates preferentially with active genes, and is generally absent from regions in which histone H3 is methylated by the Enhancer of zeste [E(z] Polycomb group silencing protein. Here we show that transcription is hypersensitive to cohesin levels in two exceptional cases where cohesin and the E(z-mediated histone methylation simultaneously coat the entire Enhancer of split and invected-engrailed gene complexes in cells derived from Drosophila central nervous system. These gene complexes are modestly transcribed, and produce seven of the twelve transcripts that increase the most with cohesin knockdown genome-wide. Cohesin mutations alter eye development in the same manner as increased Enhancer of split activity, suggesting that similar regulation occurs in vivo. We propose that cohesin helps restrain transcription of these gene complexes, and that deregulation of similarly cohesin-hypersensitive genes may underlie developmental deficits in Cornelia de Lange syndrome.

  8. The use of the differential staining of sister chromatids in the study of the cytogenetic radiation effects in human lymphocytes

    International Nuclear Information System (INIS)

    Differential staining of sister chromatides is performed, cells of the 1-st and the following mitoses are identified, chromosome aberrations are accounted, and statistic processing of data is performed. Venous blood of healthy donors is used as material for analysis. It is irradiated in flasks by 60Co gamma-quanta in the doses of 1, 1.5, 2, 3, 4, 5, 6, and 8 Gy. Lymphocytes of the peripheral blood are cultivated at 37 deg C in the medium containing antibiotics, phytohemaggluninin and 5-bromiurnedeoxyidine (BDU). The observed distributions of dicentrics in cells are compared with theoretic Poisson distribution. The dependence of frequency of dicentrics on radiation dose is studied by the method of regressive analysis. The importance of applying this technique in radiation cytogenetic investigations to increase the accuracy of chromosome aberration account in stimulated phytohemagglutinin cultures of lymphocytes of human peripheral blood and to study regularities of their elimination after cells pass the 1-st and the second mitoses, is shown

  9. Hypersensitivity to mutation and sister-chromatid-exchange induction in CHO cell mutants defective in incising DNA containing UV lesions

    International Nuclear Information System (INIS)

    Five UV-sensitive mutant strains of CHO cells representing different genetic complementation groups were analyzed for their ability to perform the incision step of nucleotide excision repair after UV exposure. The assay utilized inhibitors of DNA synthesis to accumulate the short-lived strand breaks resulting from repair incisions. After 6 J/m2, each of the mutants showed 2, the rate in AA8 was similar to that at 6 J/m2, but the rates in the mutants were significantly higher (approx. 20% of the rate of AA8). Thus by this incision assay the mutants were phenotypically indistinguishable. Each of the mutants were hypersensitive to mutation induction at both the hprt and aprt loci by a factor of 10, and in the one strain tested ouabain resistance was induced sevenfold more efficiently than in AA8 cells. Sister chromatid exchange was also induced with sevenfold increased efficiency in the two mutant strains examined. Thus, here CHO mutants resemble xeroderma pigmentosum cells in terms of their incision defects and their hypersensitivity to DNA damage by UV

  10. Sister chromatid exchanges and micronuclei in lymphocytes of operating room personnel occupationally exposed to enfluorane and nitrous oxide.

    Science.gov (United States)

    Pasquini, R; Scassellati-Sforzolini, G; Fatigoni, C; Marcarelli, M; Monarca, S; Donato, F; Cencetti, S; Cerami, F M

    2001-01-01

    The objective of this article is to assess whether occupational exposure to anesthetics increases genotoxic risk. We investigated two cytogenetic biomarkers, sister chromatid exchanges (SCE) and micronuclei (MN), in the peripheral blood lymphocytes of 46 anesthesiologists (24 men), working in operating rooms and mostly exposed to enfluorane and nitrous oxide, and 66 controls (35 men), not exposed to chemicals and living in the same area. Contrary to what was expected, a lower frequency of SCE was found in male anesthesiologists than in controls. Smoking status was found to be positively associated with SCE frequency in each group, while no relation to age was evident. On the contrary, MN frequency was significantly higher in female, but not male, anesthesiologists than in controls. Age and smoking status did not modify the association. No relationship between MN frequency and duration of employment was found in anesthesiologists. Smoking status and mean number of cigarettes smoked per day in smokers were not associated with MN frequency in either anesthesiologists or in controls. MN analysis seems to be a sensitive index of possible genotoxic effects of occupational exposure to anesthesiologists, and women appear to be more susceptible to these effects than men. PMID:11394710

  11. The chromosome damage induced by x-ray radiation doses. Comparison between dicentric chromosomes, micronuclei and Sister Chromatid Exchanges analyses

    International Nuclear Information System (INIS)

    Exposure to ionizing radiations is a well-known source of chromosome damage. Here we present a comparison among three different methodologies employed to recognize cytogenetic damage, after an acute exposure of human lymphocytes to 3 Gy of X-rays (100kVp). Scoring of dicentric chromosomes, present in first mitosis ''in vitro'', was the method of preference as dicentrics increased 937.5 times with respect to background. Micronucleus scoring in binucleated-cytokinesis blocked cells showed an increase of 32.5 times, while it was only of 1.46 times when Sister Chromatid Exchanges (SCEs) were analyzed. The estimated probability of an acentric fragment becoming a micronucleus was around 0.25. Intercellular distribution of dicentrics agree with Poisson, while micronucleus were overdispersed. When analyzed at second cycle after damage induction, the dicentrics yield as well as the level of cells with unstable cromosome aberrations, decreased around a half. Finally, SCEs level was similar in cells with or without unstable structural chromosome aberrations. (Author)

  12. The chromosome 9q subtelomere deletion syndrome

    NARCIS (Netherlands)

    Stewart, D.R.; Kleefstra, T.

    2007-01-01

    The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invar

  13. 13Q DELETIONS IN LYMPHOID MALIGNANCIES

    NARCIS (Netherlands)

    HERMANSON, M; GRANDER, D; MERUP, M; WU, XS; HEYMAN, M; RASOOL, O; JULIUSSON, G; GAHRTON, G; DETLOFSSON, R; NIKIFOROVA, N; BUYS, C; SODERHALL, S; YANKOVSKY, N; ZABAROVSKY, E; EINHORN, S

    1995-01-01

    Previous studies have indicated that a candidate tumor suppressor gene resides telomeric of the RB1 gene at 13q14, a region that is commonly deleted in B-cell chronic lymphocytic leukemia (B-CLL). In this study, we have evaluated the frequency and minimal region of overlap for 13q deletions in malig

  14. 78 FR 56679 - Procurement List; Deletions

    Science.gov (United States)

    2013-09-13

    ... 8/2/2013 (78 FR 46927-46928), the Committee for Purchase From People Who Are Blind or Severely... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Deletions from the Procurement List. SUMMARY:...

  15. Seven gene deletions in seven days

    DEFF Research Database (Denmark)

    Ingemann Jensen, Sheila; Lennen, Rebecca; Herrgard, Markus;

    2015-01-01

    enables growth at 37 °C, thereby facilitating removal of integrated antibiotic cassettes and deletion of additional genes in the same day. Phosphorothioated primers were demonstrated to enable simultaneous deletions during one round of electroporation. Utilizing these methods, we constructed strains...

  16. Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo

    International Nuclear Information System (INIS)

    The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

  17. Sister chromatid exchanges in the bone marrow cells of in vivo rats induced by gamma radiation and chemical mutagens

    International Nuclear Information System (INIS)

    Sister chromatid exchanges (SCE) in the bone marrow of in vivo rats induced by gamma radiation doses and by the chemical mutagens, mitomycin C (MMC), cyclophosphamide (CP), and sulphonate-methylmethane (SMM), were studied. The purpose was to evaluate the sensitivity and reproducibility of a simplified SCE in vivo detecting system developed in our laboratory and to compare the results obtained with those reported elsewhere. Simplification consisted in administering the amounts of 5-bromo-2'-deoxyuridine (BrdU) necessary to observe the SCE, after first adsorbing the BrdU in activated carbon and then injecting it interperitoneally, into the rats. The results were a longer time in vivo ADN incorporation without convulsions in the rats, and a reduction in the time course as compared to other methods. We observed a basal rate of 3.6+-0.37 SCE/cell and that: 0.44 Gy of gamma radiation induced 7.7+-0.73 SCE/cell; 1.6 μg/g of MMC induced 8.1+-1.20 SCE/cell; 5 μg/g of CP induced 8.25+-1.5 SCE/cell, 40 μg/g of SMM induced 22.0+-5 SCE/cell and 380 μg/g of sulphonate-ethylmethane induced 8.6+-1.2 SCE/cell. This showed that all the agents were capable of inducing SCE in the bone marrow cells of rats in vivo under our conditions. We noted a greater induced efficiency for gamma radiation than the obtained by other investigators and a relatively similar efficiency in the case of chemical mutagens as reported in other studies. (author)

  18. Chaetophractus villosus as a sentinel organism: Baseline values of mitotic index, chromosome aberrations and sister chromatid exchanges.

    Science.gov (United States)

    Rossi, Luis Francisco; Luaces, Juan Pablo; Browne, Melanie; Chirino, Mónica Gabriela; Merani, María Susana; Mudry, Marta Dolores

    2016-01-15

    Sentinel species are useful tools for studying the deleterious effects of xenobiotics on wildlife. The large hairy armadillo (Chaetophractus villosus) is the most abundant and widely distributed mammal in Argentina. It is a long-lived, omnivorous, burrowing species, with fairly restricted home ranges. To evaluate the level of spontaneous genetic damage in this mammal, we determined the baseline values of several genotoxicity biomarkers. The study included 20 C. villosus adults of both sexes from eight pristine localities within its geographic distribution range. Genotoxicity analysis was performed on 72-h lymphocyte cultures, using mitomycin C as positive control. We obtained the baseline values of mitotic index (MI=10.52±0.30 metaphases/total cells, n=20), chromosome aberrations (CA=0.13±0.22, n=20), sister chromatid exchanges (SCE)=6.55±0.26, n=6) and replication index (RI=1.66, n=6). MI and CA did not show significant differences (P>0.05) among localities or between sexes. No significant differences in MI, CA, SCE, and RI (P>0.05) were found between values from the pristine localities and historical data. There were significant differences in CA, SCE, and RI (Parmadillo as a sentinel organism for environmental biomonitoring of genotoxic chemicals due to its abundance, easy manipulation, well-known biology, the fact that it is usually exposed to different mixtures and concentrations of environmental contaminants, and the baseline values of genetic damage characterized by MI, CA, SCE and RI as biomarkers. PMID:26778508

  19. A novel frameshift mutation in BLM gene associated with high sister chromatid exchanges (SCE) in heterozygous family members.

    Science.gov (United States)

    Ben Salah, Ghada; Hadj Salem, Ikhlas; Masmoudi, Abderrahmen; Kallabi, Fakhri; Turki, Hamida; Fakhfakh, Faiza; Ayadi, Hamadi; Kamoun, Hassen

    2014-11-01

    The Bloom syndrome (BS) is an autosomic recessive disorder comprising a wide range of abnormalities, including stunted growth, immunodeficiency, sun sensitivity and increased frequency of various types of cancer. Bloom syndrome cells display a high level of genetic instability, including a 10-fold increase in the sister chromatid exchanges (SCE) level. Bloom syndrome arises through mutations in both alleles of the BLM gene, which was identified as a member of the RecQ helicase family. In this study, we screened a Tunisian family with three BS patients. Cytogenetic analysis showed several chromosomal aberrations, and an approximately 14-fold elevated SCE frequency in BS cells. A significant increase in SCE frequency was observed in some family members but not reaching the BS patients values, leading to suggest that this could be due to the heterozygous profile. Microsatellite genotyping using four fluorescent dye-labeled microsatellite markers revealed evidence of linkage to BLM locus and the healthy members, sharing higher SCE frequency, showed heterozygous haplotypes as expected. Additionally, the direct BLM gene sequencing identified a novel homozygous frameshift mutation c.3617-3619delAA (p.K1207fsX9) in BS patients and a heterozygous BLM mutation in the family members with higher SCE frequency. Our findings suggest that this latter mutation likely leads to a reduced BLM activity explaining the homologous recombination repair defect and, therefore, the increase in SCE. Based on the present data, the screening of this mutation could contribute to the rapid diagnosis of BS. The genetic confirmation of the mutation in BLM gene provides crucial information for genetic counseling and prenatal diagnosis.

  20. Evaluation of radioprotection properties of propolis by chromosomal alterations, cell proliferation kinetics, mitotic index and sister chromatid exchange

    International Nuclear Information System (INIS)

    A consequence of ionizing radiation is the induction of chromosomal alterations. This causality relation involves that chromosomal alterations can be considered a good indicator of the radiological damage. Some chemical agents can modulate the tissue response to radiation. These compounds are useful because they show certain selectivity, protecting the healthy tissues (radioprotectors) or increasing the sensibility of tissues to radiations (radiosensibilizators). Propolis substance has showed radioprotection properties which are performed in the following study. Propolis is a product of extraordinary interest for both medicine and pharmaceutical industry, since it is assumed to show diverse beneficial health effects. Among many other attributes of EEP (propolis ethanolic extract), it exhibits antioxidant and radical free scavenger properties. In a previous study, human peripheral blood lymphocytes were exposed to 2 Gy of γ rays in presence and absence of EEP, and the analysis showed a reduction in the frequency of dicentrics and rings, with a maximum protection of 50%. The proposed concentration for radioprotection would be between 120-500 μg.ml-1. The cytotoxic effect has been evaluated analyzing the EEP effect in the cellular division cycle. Propolis ethanolic extract (EEP) has been obtained and samples of peripheral blood have been cultured in the presence of increasing concentrations of EEP. In order to quantify it, two indexes have been used, the mitotic index and cell proliferation index. For both indexes the cytotoxic effect takes place from 750 μg.ml-1 concentrations onwards. Similar results were obtained for the analysis of chromosomal aberrations. Finally, propolis effect in lymphocytes by sister chromatid exchange test has been presented for higher concentrations of EEP. (author)

  1. Variation in sister chromatid exchange frequencies between human and pig whole blood, plasma leukocyte, and mononuclear leukocyte cultures

    International Nuclear Information System (INIS)

    Sister chromatid exchange (SCE) induction by ultraviolet (UV) light was studied in both human and pig whole blood cultures (WBC) and plasma leukocyte cultures (PLC). No variation in SCE frequency was observed between pig WBC and PLC in control as well as in treated cells. Conversely, SCE frequencies of human PLC were consistently higher than those of WBC in control and UV-exposed cells. Thus, red blood cells (RBCs) do not influence the sensitivity of lymphocytes to UV LIGHT exposure, and there must be some different culture condition(s) in the inducation of SCEs between human WBC and PLC but not in swine lymphocyte cultures. Since the BrdUrd/lymphocyte ratio of WBC was halved in PLC, the effect of BrdUrd concentration in inducing the SCE baseline frequency of PLC may be ruled out. Neither the cell separation technique nor polymorphonuclear leukocytes had a significant role in the elevated SCE frequency of human PLC or MLC. Experiments where human RBCs were titrated into human PLC showed that the induction of an elevated SCE frequency of PLC was suppressed in a dose-dependent manner by the presence of RBCs in the culture medium. Since the incorporation of pig or human RBCs into human PLC as well as into MLC reduced the SCE frequency to that of WBC, a common component and/or function existing in these cells is suggested. Analysis of different RBC components showed that RBCs, specifically RBC ghosts, release a diffusible but not dialyzable corrective factor into culture medium that is able to reduce the SCE frequencies of PLC

  2. Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Nagasawa, H; Wilson, P F; Chen, D J; Thompson, L H; Bedford, J S; Little, J B

    2007-10-26

    We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells (Nagasawa et al., Radiat. Res. 164, 141-147, 2005). In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23-0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after {alpha}-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.

  3. Gene deletion analysis of a Chinese boy with Xp21 contiguous gene deletion syndrome

    Institute of Scientific and Technical Information of China (English)

    麻宏伟; 姜俊; 王岳平; 王志超; 陈丽英; 松尾雅文

    2004-01-01

    @@ Xp21 contiguous gene deletion syndrome, sometimes called complex glycerol kinase deficiency, is associated with variable size Xp21 deletions that usually include the glycerol kinase gene and span multiple Xp21 disease gene loci in the region. The order of the potentially affected loci are as follows:

  4. In Vitro genotoxic and antigenotoxic studies of Thai Noni fruit juice by chromosomal aberration and sister chromatid exchange assays in human lymphocytes

    Directory of Open Access Journals (Sweden)

    Treetip Ratanavalachai

    2008-09-01

    Full Text Available The genotoxic and antigenotoxic effects of Noni fruit juice produced in Thailand have been studied in human lymphocytes for chromosome aberration assay and sister chromatid exchange (SCE assay in vitro. Treatment of Noni fruit juice(3.1-50 mg/ml alone for 3 h did not significantly induce chromosomal aberration or SCE (p<0.05. Noni fruit juice at 6.2 mg/ml is the optimum dose for cell survival and cell replication as demonstrated by the highest value of mitotic index and proliferation index (P.I.. Interestingly, pretreatment of Noni fruit juice at the same concentration of 6.2 mg/ml for 2 hfollowed by mitomycin C treatment at 3 μg/ml for 2 h significantly reduced SCE level induced by mitomycin C (p<0.05. However, these treatments did not show significant decrease in chromatid-type aberrations. Our data indicate that Thai Noni fruit juice is not genotoxic against human lymphocytes in vitro. In addition, pretreatment of Noni fruit juice at 6.2 mg/ml demonstrated no anticlastogenic effect while had some antigenotoxic effects as demonstrated by significant decrease in the SCE level induced by mitomycin C (p<0.05. Therefore, the optimum dose of Noni fruit juice used as a traditional medicine is required and needs to be studied further for the benefit of human health.

  5. Increased sister chromatid cohesion and DNA damage response factor localization at an enzyme-induced DNA double-strand break in vertebrate cells.

    LENUS (Irish Health Repository)

    Dodson, Helen

    2009-10-01

    The response to DNA damage in vertebrate cells involves successive recruitment of DNA signalling and repair factors. We used light microscopy to monitor the genetic dependencies of such localization to a single, induced DNA double strand break (DSB) in vertebrate cells. We used an inducible version of the rare-cutting I-SceI endonuclease to cut a chromosomally integrated I-SceI site beside a Tet operator array that was visualized by binding a Tet repressor-GFP fusion. Formation of gamma-H2AX foci at a single DSB was independent of ATM or Ku70. ATM-deficient cells showed normal kinetics of 53Bp1 recruitment to DSBs, but Rad51 localization was retarded. 53Bp1 and Rad51 foci formation at a single DSB was greatly reduced in H2AX-null DT40 cells. We also observed decreased inter-sister chromatid distances after DSB induction, suggesting that cohesin loading at DSBs causes elevated sister chromatid cohesion. Loss of ATM reduced DSB-induced cohesion, consistent with cohesin being an ATM target in the DSB response. These data show that the same genetic pathways control how cells respond to single DSBs and to multiple lesions induced by whole-cell DNA damage.

  6. 77 FR 68737 - Procurement List, Proposed Deletions

    Science.gov (United States)

    2012-11-16

    ... From the Federal Register Online via the Government Publishing Office COMMITTEE FOR PURCHASE FROM... Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Deletions from the Procurement... Must Be Received On or Before: 12/17/2012. ADDRESSES: Committee for Purchase From People Who Are...

  7. 78 FR 65618 - Procurement List; Proposed Deletions

    Science.gov (United States)

    2013-11-01

    ... From the Federal Register Online via the Government Publishing Office COMMITTEE FOR PURCHASE FROM... Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Deletions from the Procurement... Received on or Before: 12/2/2013. ADDRESSES: Committee for Purchase From People Who Are Blind or...

  8. Union-Find with Constant Time Deletions

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Thorup, Mikkel; Gørtz, Inge Li;

    2014-01-01

    operations performed, and α_M/N_(n) is a functional inverse of Ackermann’s function. They left open the question whether delete operations can be implemented more efficiently than find operations, for example, in o(log n) worst-case time. We resolve this open problem by presenting a relatively simple...

  9. Familial deletion 18p syndrome: case report

    Directory of Open Access Journals (Sweden)

    Lemyre Emmanuelle

    2006-07-01

    Full Text Available Abstract Background Deletion 18p is a frequent deletion syndrome characterized by dysmorphic features, growth deficiencies, and mental retardation with a poorer verbal performance. Until now, five families have been described with limited clinical description. We report transmission of deletion 18p from a mother to her two daughters and review the previous cases. Case presentation The proband is 12 years old and has short stature, dysmorphic features and moderate mental retardation. Her sister is 9 years old and also has short stature and similar dysmorphic features. Her cognitive performance is within the borderline to mild mental retardation range. The mother also presents short stature. Psychological evaluation showed moderate mental retardation. Chromosome analysis from the sisters and their mother revealed the same chromosomal deletion: 46, XX, del(18(p11.2. Previous familial cases were consistent regarding the transmission of mental retardation. Our family differs in this regard with variable cognitive impairment and does not display poorer verbal than non-verbal abilities. An exclusive maternal transmission is observed throughout those families. Women with del(18p are fertile and seem to have a normal miscarriage rate. Conclusion Genetic counseling for these patients should take into account a greater range of cognitive outcome than previously reported.

  10. Deletion of GPIHBP1 causing severe chylomicronemia.

    Science.gov (United States)

    Rios, Jonathan J; Shastry, Savitha; Jasso, Juan; Hauser, Natalie; Garg, Abhimanyu; Bensadoun, André; Cohen, Jonathan C; Hobbs, Helen H

    2012-05-01

    Lipoprotein lipase (LPL) is a hydrolase that cleaves circulating triglycerides to release fatty acids to the surrounding tissues. The enzyme is synthesized in parenchymal cells and is transported to its site of action on the capillary endothelium by glycophosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). Inactivating mutations in LPL; in its cofactor, apolipoprotein (Apo) C2; or in GPIHBP1 cause severe hypertriglyceridemia. Here we describe an individual with complete deficiency of GPIHBP1. The proband was an Asian Indian boy who had severe chylomicronemia at 2 months of age. Array-based copy-number analysis of his genomic DNA revealed homozygosity for a 17.5-kb deletion that included GPIHBP1. A 44-year-old aunt with a history of hypertriglyceridemia and pancreatitis was also homozygous for the deletion. A bolus of intravenously administered heparin caused a rapid increase in circulating LPL and decreased plasma triglyceride levels in control individuals but not in two GPIHBP1-deficient patients. Thus, short-term treatment with heparin failed to attenuate the hypertriglyceridemia in patients with GPIHBP1 deficiency. The increasing resolution of copy number microarrays and their widespread adoption for routine cytogenetic analysis is likely to reveal a greater role for submicroscopic deletions in Mendelian conditions. We describe the first neonate with complete GPIHBP1 deficiency due to homozygosity for a deletion of GPIHBP1. PMID:22008945

  11. Insertion and deletion processes in recent human history.

    Directory of Open Access Journals (Sweden)

    Per Sjödin

    Full Text Available BACKGROUND: Although insertions and deletions (indels account for a sizable portion of genetic changes within and among species, they have received little attention because they are difficult to type, are alignment dependent and their underlying mutational process is poorly understood. A fundamental question in this respect is whether insertions and deletions are governed by similar or different processes and, if so, what these differences are. METHODOLOGY/PRINCIPAL FINDINGS: We use published resequencing data from Seattle SNPs and NIEHS human polymorphism databases to construct a genomewide data set of short polymorphic insertions and deletions in the human genome (n = 6228. We contrast these patterns of polymorphism with insertions and deletions fixed in the same regions since the divergence of human and chimpanzee (n = 10,546. The macaque genome is used to resolve all indels into insertions and deletions. We find that the ratio of deletions to insertions is greater within humans than between human and chimpanzee. Deletions segregate at lower frequency in humans, providing evidence for deletions being under stronger purifying selection than insertions. The insertion and deletion rates correlate with several genomic features and we find evidence that both insertions and deletions are associated with point mutations. Finally, we find no evidence for a direct effect of the local recombination rate on the insertion and deletion rate. CONCLUSIONS/SIGNIFICANCE: Our data strongly suggest that deletions are more deleterious than insertions but that insertions and deletions are otherwise generally governed by the same genomic factors.

  12. Sister-chromatid exchanges and cell-cycle kinetics in the lymphocytes of workers occupationally exposed to a chemical mixture in the tyre industry.

    Science.gov (United States)

    Sasiadek, M

    1993-08-01

    Cytogenetic studies of clinically healthy workers employed in the rubber industry showed an increase in chromosome aberrations (CAs), sister-chromatid exchanges (SCEs) and a decrease in proliferation indices (PIs). The aim of the present study was to establish, using the SCE and PI tests, genotoxic effects of hazardous chemicals in the rubber industry. An increase in mean SCEs in the lymphocytes of vulcanizers as compared to controls was observed. Since the PI in the exposed group was insignificantly decreased as compared to the controls, it could be concluded that the SCE test is the most sensitive cytogenetic test for the detection of a genotoxic effect of chemicals in the rubber industry. There was no evidence in the present study that the genotoxic effect of chemicals in the rubber industry was enhanced by cigarette smoking. PMID:7688857

  13. Effect of chlorophyllin on frequency radiation-induced of sister chromatid exchanges (SCE) and other cytogenetic events in mice bone marrow cells In Vivo

    International Nuclear Information System (INIS)

    The effect of chlorophyllin on gamma radiation induced Sister chromatid exchanges (SCE) and on the mitotic index (IM) and average generation time was determined. Groups of mice were treated in one of the following regimens: (1) untreated, (2) treated with chlorophyllin only, (3) irradiated and (4) treated with chlorophyllin and irradiated intraperitoneal administration of chlorophyllin preceding gamma radiation exposure protected again SCE induction and diminution of IM. However, radioprotection was not reflected in the average generation time for the chlorophyllin per se acceleration the average generation time. The results suggest that, under the experimental conditions of the study the SCE and IM are caused by free radicals produced by radiation and wat the action mechanics of chlorophyllin is scavenger free radicals. (Author)

  14. Sister chromatid exchanges, hyperdiploidy and chromosomal rearrangements studied in cells from melanoma-prone individuals belonging to families with the dysplastic nevus syndrome.

    Science.gov (United States)

    Jaspers, N G; Roza-de Jongh, E J; Donselaar, I G; Van Velzen-Tillemans, J T; van Hemel, J O; Rümke, P; van der Kamp, A W

    1987-01-01

    Cytogenetic investigations were performed on 25 individuals belonging to six melanoma-prone families with multiple melanocytic lesions (the dysplastic nevus syndrome, DNS). Patients having DNS with or without a history of melanoma were compared with clinically normal relatives and unrelated normal controls. The results indicate normal frequencies of hyperdiploidy and spontaneous sister chromatid exchanges in the fibroblasts of all individuals studied. Karyotypic analyses were carried out on the members of one family. The patients with DNS had a normal constitutional karyotype. In lymphocytes or fibroblasts from five patients, however, increased frequencies of cells with random chromosomal rearrangements were observed. These abnormalities, mainly translocations and inversions, were not found in two of the patients' spouses and in six clinically normal relatives. In the fibroblast cultures considerable clonal selection of cytogenetically abnormal cells occurred. PMID:3791172

  15. A comparative investigation of DNA strand breaks, sister chromatid exchanges and K-ras gene mutations induced by cadmium salts in cultured human cells

    International Nuclear Information System (INIS)

    Cadmium (Cd) is a toxic heavy metal of continuing occupational and environmental concern with a wide variety of adverse effects. Several studies have shown that cadmium produces DNA strand breaks, DNA-protein cross-links, oxidative DNA damage, chromosomal aberrations, dysregulation of gene expression resulting in enhanced proliferation, depressed apoptosis and/or altered DNA repair. This study was undertaken to investigate the ability of cadmium chloride (CdCl2) and cadmium sulphate (CdSO4) to induce point mutations in codon 12 of the K-ras protooncogene assessed by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and RFLP-enriched PCR methods. Also their genotoxic effects were analyzed by the comet assay and sister chromatid exchanges test. The human lung fibroblast cell line MRC-5 was used for the experiments. Sister chromatid exchanges assay (SCEs) frequencies were significantly increased in cells exposed to cadmium salts in relation to controls (p < 0.001). Despite the slow increment observed in the three comet parameters considered when cells were treated with cadmium chloride, significant differences between groups were only found in the variable comet moment (CM) (p < 0.005). On the other hand, when cells were exposed to cadmium sulphate, the Kruskal-Wallis test showed highly significant differences between groups for migration, tail moment and comet moment parameters (p < 0.001). Nevertheless, a null or weak point mutation induction in K-ras protooncogene was detected using polymerase chain reaction-low ionic strength-single strand conformation polymorphisms (PCR-LIS-SSCP) and RFLP-enriched PCR methods when cells were treated with cadmium salts. Thus, inorganic cadmium produces genotoxicity in human lung fibroblast MRC-5 cells, in the absence of significant point mutation of the K-ras gene

  16. Fetal ventriculomegaly due to familial submicroscopic terminal 6q deletions

    DEFF Research Database (Denmark)

    Wadt, Karin; Jensen, Lisa Neerup; Bjerglund, Lise;

    2012-01-01

    Submicroscopic terminal 6q deletions are rare. We report on two familial submicroscopic terminal 6q deletions ascertained because of prenatally detected isolated ventriculomegaly and further delineate the variable prenatal and postnatal phenotype. We review published cases of......Submicroscopic terminal 6q deletions are rare. We report on two familial submicroscopic terminal 6q deletions ascertained because of prenatally detected isolated ventriculomegaly and further delineate the variable prenatal and postnatal phenotype. We review published cases of...

  17. Orbital deletion procedure and its applications

    Institute of Scientific and Technical Information of China (English)

    莫亦荣; 林梦海; 吴玮; 张乾二

    1999-01-01

    The orbital deletion procedure is introduced, which is suited to quantitatively investigating the electronic delocalization effiect in earboeations and boranes. While the routine, ab initio molecular orbital methods can generate wavefunetions for real systems where all electrons are delocalized, the present orbital deletion procedure can generate wavefunctions for hypothetical reference molecules where electronic delocalization effect is deactivated. The latter wavefunetion normlly corresponds In the most stable resonance structure in terms of the resonance theory. By comparing and analyzing the delocalized and the localized wavefunetions, one can obtain a quantitative and instinct pieture to show how electronic deloealizalion inside a molecule affects the molecular structure, energy as well as other physical properties. Two examples are detailedly discussed. The first is related to the hypercoujugation of alkyl groups in carbocations and a comparison of the order of stability of carbocations is made, T

  18. An environment-mediated quantum deleter

    CERN Document Server

    Srikanth, R; Banerjee, Subhashish

    2006-01-01

    Environment-induced decoherence presents a great challenge to realizing a quantum computer. We point out the somewhat surprising fact that decoherence can be useful, indeed necessary, for practical quantum computation, in particular, for the effective erasure of quantum memory in order to initialize the state of the quantum computer. The essential point behind the deleter is that the environment, by means of a dissipative interaction, furnishes a contractive map towards a pure state. We present a specific example of an amplitude damping channel provided by a two-level system's interaction with its environment in the weak Born-Markov approximation. This is contrasted with a purely dephasing, non-dissipative channel provided by a two-level system's interaction with its environment by means of a quantum nondemolition interaction. We point out that currently used state preparation techniques, for example using optical pumping, essentially perform as quantum deleters.

  19. Rac1 deletion causes thymic atrophy.

    Science.gov (United States)

    Hunziker, Lukas; Benitah, Salvador Aznar; Aznar Benitah, Salvador; Braun, Kristin M; Jensen, Kim; McNulty, Katrina; Butler, Colin; Potton, Elspeth; Nye, Emma; Boyd, Richard; Laurent, Geoff; Glogauer, Michael; Wright, Nick A; Watt, Fiona M; Janes, Sam M

    2011-04-29

    The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

  20. Rac1 deletion causes thymic atrophy.

    Directory of Open Access Journals (Sweden)

    Lukas Hunziker

    Full Text Available The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

  1. Secure Deletion of Data from SSD

    Directory of Open Access Journals (Sweden)

    Akli Fundo

    2014-08-01

    Full Text Available The deletion of data from storage is an important component on data security. The deletion of entire disc or special files is well-known on hard drives, but this is quite different on SSDs, because they have a different architecture inside, and the main problem is if they serve the same methods like hard drives for data deletion or erasing. The built-in operations are used to do this on SSDs. The purpose of this review is to analyses some methods which are proposed to erase data form SSDs and their results too, to see which of them offers the best choice. In general we will see that the techniques of erasing data from entire disc from hard drives can be used also on SSDs, but there’s a problem with bugs. On the other hand, we cannot use the same techniques of erasing a file from hard drives and SSDs. To make this possible, there are required changes in FTL layer, which is responsible for mapping between logic addresses and physical addresses.

  2. FLCN intragenic deletions in Chinese familial primary spontaneous pneumothorax.

    Science.gov (United States)

    Ding, Yibing; Zhu, Chengchu; Zou, Wei; Ma, Dehua; Min, Haiyan; Chen, Baofu; Ye, Minhua; Pan, Yanqing; Cao, Lei; Wan, Yueming; Zhang, Wenwen; Meng, Lulu; Mei, Yuna; Yang, Chi; Chen, Shilin; Gao, Qian; Yi, Long

    2015-05-01

    Primary spontaneous pneumothorax (PSP) is a significant clinical problem, affecting tens of thousands patients annually. Germline mutations in the FLCN gene have been implicated in etiology of familial PSP (FPSP). Most of the currently identified FLCN mutations are small indels or point mutations that detected by Sanger sequencing. The aim of this study was to determine large FLCN deletions in PSP families that having no FLCN sequence-mutations. Multiplex ligation-dependent probe amplification (MLPA) assays and breakpoint analyses were used to detect and characterize the deletions. Three heterozygous FLCN intragenic deletions were identified in nine unrelated Chinese families including the exons 1-3 deletion in two families, the exons 9-14 deletion in five families and the exon 14 deletion in two families. All deletion breakpoints are located in Alu repeats. A 5.5 Mb disease haplotype shared in the five families with exons 9-14 deletion may date the appearance of this deletion back to approximately 16 generations ago. Evidences for founder effects of the other two deletions were also observed. This report documents the first identification of founder mutations in FLCN, as well as expands mutation spectrum of the gene. Our findings strengthen the view that MLPA analysis for intragenic deletions/duplications, as an important genetic testing complementary to DNA sequencing, should be used for clinical molecular diagnosis in FPSP.

  3. Automatic Airway Deletion in Pulmonary Segmentation

    Institute of Scientific and Technical Information of China (English)

    WANG Ping; ZHUANG Tian-ge

    2005-01-01

    A method of removing the airway from pulmonary segmentation image was proposed. This method firstly segments the image into several separate regions based on the optimum threshold and morphological operator,and then each region is labeled and noted with its mean grayscale. Therefore, most of the non-lung regions can be removed according to the tissue's Hounsfield units (HU) and the imaging modality. Finally, the airway region is recognized and deleted automatically through using the priori information of its HU and size. This proposed method is tested using several clinical images, yielding satisfying results.

  4. Secure Deletion on Log-structured File Systems

    CERN Document Server

    Reardon, Joel; Capkun, Srdjan; Basin, David

    2011-01-01

    We address the problem of secure data deletion on log-structured file systems. We focus on the YAFFS file system, widely used on Android smartphones. We show that these systems provide no temporal guarantees on data deletion and that deleted data still persists for nearly 44 hours with average phone use and indefinitely if the phone is not used after the deletion. Furthermore, we show that file overwriting and encryption, methods commonly used for secure deletion on block-structured file systems, do not ensure data deletion in log-structured file systems. We propose three mechanisms for secure deletion on log-structured file systems. Purging is a user-level mechanism that guarantees secure deletion at the cost of negligible device wear. Ballooning is a user-level mechanism that runs continuously and gives probabilistic improvements to secure deletion. Zero overwriting is a kernel-level mechanism that guarantees immediate secure deletion without device wear. We implement these mechanisms on Nexus One smartphon...

  5. Detection of mitochondrial DNA deletion by a modified PCR method

    Institute of Scientific and Technical Information of China (English)

    汪振诚; 王学敏; 缪明永; 章卫平; 焦炳华; 倪庆桂

    2003-01-01

    Objective: To develop a simple and efficient method for detecting small populations of mitochondrial DNA deletion. Methods: Peripheral blood cell DNA was obtained from a victim who was accidently exposed to a 60Co radiation source 11 years ago. Using the DNA as template, PCR was performed to generate multiple products including true deletions and artifacts. The full length product was recovered and used as template of secondary PCR. The suspicious deletion product of mtDNA could be confirmed if it was only yielded by first PCR. Using either original primers or their nested primers, the suspicious deletion product was amplified and authenticated as true deletion product. The template was recovered and determined to be a deletion by sequencing directly. Results: A new mtDNA deletion, spanning 889 bp from nt11688 to nt12576, was detected in the peripheral blood cells of the victim. Conclusion: The new PCR-based method is more efficient in detecting small populations of mtDNA deletion than other routine methods. MtDNA deletion is found in the victim, suggesting there is relationship between the deletion and phenotypes of the disease.

  6. Deletion of ultraconserved elements yields viable mice

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Zhu, Yiwen; Visel, Axel; Holt, Amy; Afzal, Veena; Pennacchio, Len A.; Rubin, Edward M.

    2007-07-15

    Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities when assayed for a variety of phenotypes including growth,longevity, pathology and metabolism. In addition more targeted screens,informed by the abnormalities observed in mice where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.

  7. Rare human diseases: 9p deletion syndrome

    Directory of Open Access Journals (Sweden)

    Galagan V.O.

    2014-09-01

    Full Text Available Objective of the study was to review the anamnesis, pheno - and genotype in patients with rare chromosome disorders such as 9p deletion syndrome. Genetic methods of investigation (clinical and genealogical, cytogenetic, FISH- method, paraclinical and instrumental methods of examination were used. Karyotyping was performed by the G-method of differential staining of chromosomes. Only three cases of pathology were diagnosed in the Medical Genetics Center over the last 10 years. By anamnesis data nobody in the probands’ families had bad habits, was exposed to occupational hazards, took part in the elimination of the Chernobyl accident or lived in contaminated areas. Clinical signs of diseases have not been identified in probands’ parents. All probands had trigonocephaly, bilateral epicanthal folds, ocular hypertelorism, downslanting palpebral fissures, long philtrum, flat face and nasal bridge, low set ears with malformed auricles. Two patients of three ones had exophthalmos, contracture of the second and third fingers, abnormal external genitalia. In all three cases there was monosomy of chromosome 9 of critical segment p 24. Normal karyotypes were seen in all parents, so there were three cases of new mutations of 9p deletion syndrome. Retardation of physical, psycho-spech, mental development in proband with or without congenital anomalies requires medical genetic counseling in a specialized institution. Cases of reproductive loss in anamnesis require cytogenetic investigation of fetal membranes and amniotic fluid.

  8. Are there ethnic differences in deletions in the dystrophin gene?

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, M.; Verma, I.C. [All India Inst. of Medical Sciences, New Delhi (India)

    1997-01-20

    We studied 160 cases of Duchenne muscular dystrophy (DMD) drawn from all parts of India, using multiplex PCR of 27 exons. Of these, 103 (64.4%) showed intragenic deletions. Most (69.7%) of the deletions involved exons 45-51. The phenotype of cases with deletion of single exons did not differ significantly from those with deletion of multiple exons. The distribution of deletions in studies from different countries was variable, but this was accounted for either by the small number of cases studied, or by fewer exons analyzed. It is concluded that there is likely to be no ethnic difference with respect to deletions in the DMD gene. 38 refs., 2 figs., 3 tabs.

  9. Analysis of partial AZFc deletions in Malaysian infertile male subjects.

    Science.gov (United States)

    Almeamar, Hussein Ali; Ramachandran, Vasudevan; Ismail, Patimah; Nadkarni, Prashan; Fawzi, Nora

    2013-04-01

    Complete deletions in the AZF (a, b, and c) sub-regions of the Y-chromosome have been shown to contribute to unexplained male infertility. However, the role of partial AZFc deletions in male infertility remains to be verified. Three types of partial AZFc deletions have been identified. They are gr/gr, b1/b3, and b2/b3 deletions. A recent meta-analysis showed that ethnic and geographical factors might contribute to the association of partial AZFc deletions with male infertility. This study analyzed the association of partial AZFc deletions in Malaysian infertile males. Fifty two oligozoospermic infertile males and 63 fertile controls were recruited to this study. Screening for partial AZFc deletions was done using the two sequence-tagged sites approach (SY1291 and SY1191) which were analyzed using both the conventional PCR gel-electrophoresis and the high resolution melt, HRM method. Gr/gr deletions were found in 11.53% of the cases and 9.52% of the controls (p = 0.725). A B2/b3 deletion was found in one of the cases (p = 0.269). No B1/b3 deletions were identified in this study. The results of HRM analysis were consistent with those obtained using the conventional PCR gel-electrophoresis method. The HRM analysis was highly repeatable (95% limit of agreement was -0.0879 to 0.0871 for SY1191 melting temperature readings). In conclusion, our study showed that partial AZFc deletions were not associated with male infertility in Malaysian subjects. HRM analysis was a reliable, repeatable, fast, cost-effective, and semi-automated method which can be used for screening of partial AZFc deletions. PMID:23231020

  10. A deletion map of the WAGR region on chromosome 11.

    OpenAIRE

    Gessler, M; Thomas, G H; Couillin, P; Junien, C; McGillivray, B C; Hayden, M; Jaschek, G.; Bruns, G. A.

    1989-01-01

    The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual ...

  11. Characterization of the enhancing effect of caffeine on sister-chromatid exchanges induced by ultraviolet radiation in excision-proficient xeroderma pigmentosum lymphoblastoid cells

    International Nuclear Information System (INIS)

    Cells of some excision-proficient xeroderma pigmentosum (XP) cell lines are highly sensitive to post-UV caffeine treatment in terms of sister-chromatid exchange (SCE) induction as well as cell lethality. In the present study, the authors conducted a detailed investigation of the enhancing effect of caffeine on SCE frequency induced by UV in excision-proficient XP cells, and obtained the following results. (1). Continuous post-UV treatment with 1mM caffeine markedly enhances UV-induced SCEs and such enhanced SCEs occur with similar frequency during either the 1st or the 2nd cell cycle in the presence of caffeine and 5-bromodeoxyuridine (BrdUrd). (2) The high sensitivity of the cells to post-UV caffeine treatment persists for at least 2 days after UV when irradiated cells are held in either the proliferating of the nonproliferating state prior to the addition of BrdUrd. (3) Caffeine exerts its effect on cells in S phase. The most likely explanation for our findings is as follows. In excision-proficient XP cells, the cause of SCE formation such as UV-induced lesions or resulting perturbations of DNA replication persists untill the 2nd round or more of post-UV DNA replication. If caffeine is given as post-UV treatment, such abnormalities may be amplified, resulting in a synergistic increase in SCE frequency. (author). 21 refs.; 4 figs.; 4 tabs

  12. The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1.

    Science.gov (United States)

    Voets, Erik; Marsman, Judith; Demmers, Jeroen; Beijersbergen, Roderick; Wolthuis, Rob

    2015-01-01

    Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and is early embryonic lethal in mice. Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cdk1 inhibitors, is also detrimental for proliferating cells, but has been associated with defects in mitotic progression, and the formation of aneuploid daughter cells. Here, we used a large-scale RNAi screen to identify the human genes that critically determine the cellular toxicity of Cdk1 inhibition. We show that Cdk1 inhibition leads to fatal sister chromatid alignment errors and mitotic arrest in the spindle checkpoint. These problems start early in mitosis and are alleviated by depletion of isoform 1 of PRC1 (PRC1-1), by gene ablation of its binding partner KIF4, or by abrogation of KIF4 motor activity. Our results show that, normally, Cdk1 activity must rise above the level required for mitotic entry. This prevents KIF4-dependent PRC1-1 translocation to astral microtubule tips and safeguards proper chromosome congression. We conclude that cell death in response to Cdk1 inhibitors directly relates to chromosome alignment defects generated by insufficient repression of PRC1-1 and KIF4 during prometaphase. PMID:26423135

  13. Repairability during G 1 phase of inducting lesions of sister chromatid exchange produced by mitomycin C in salivary gland cells of mice In Vivo

    International Nuclear Information System (INIS)

    The repairability of the injuries that lead to the formation of sister chromatid exchange (SCE) produced by mitomycin C (MMC) with a dose of 2.1 mg/g in vivo, during the G 1 phase in the first cycle of cellular division (before the incorporation of BrdU [5-bromo-2 deoxyurine] to the DNA), as well as during the G 1 phase of the second cycle of cellular division (after the incorporation of BrdU) were analyzed. A 35.1% decrease in the frequency of SCE produced by Mitomycin C was observed, in the early G 1 phase of the first division, with respect to the frequency of SCE induced in the later G 1 phase. When Mitomycin C is given to cells whose DNA is substituted with BrdU in only one of the chain's filaments such decrease is not observed. The results suggest that the injuries caused by MMC, which give place to the SCE, in cells of the salivary glands of the mouse in vivo, are partially repaired only when induced in DNA which has not been substituted with BrdU. (Author)

  14. Relationship of enhanced survival during confluent holding recovery in ultraviolet-irradiated human and mouse cells to chromosome aberrations, sister chromatid exchanges, and DNA repair

    International Nuclear Information System (INIS)

    The relationship among cellular recovery from ultraviolet light (UVL) damage, cytogenetic changes, and DNA repair was studied in density-inhibited cultures of mouse 10T1/2 cells and human diploid fibroblasts. Both cell types showed similar UVL sensitivites to cell killing and a similar enhancement in survival when subculture to a low density was delayed for 24-48 hr after irradiation (potential lethal damage repair). However, excision repair as measured by the loss of endonuclease-sensitive sites was biphasic and much slower in the mouse cells: 30% were removed in the first 24 hr compared with 60% removed in the first 5 hr in the human cells. More than five times as many excision-induced DNA strand breaks as measured by alkaline elution were detected in the human as compared with the mouse cells. DNA-protein crosslinks were removed with a T 1/2 of 30 hr after 10 J/m2 UVL. UVL induced few chromosomal aberrations in the human cells as compared with mouse cells. The frequency of induced sister chromatid exchanges and the pattern of their decline during recovery were similar in both cell types; the kinetics of this decline was similar to that observed for the removal of DNA-protein crosslinks, and slowly removed endonuclease-sensitive sites. Chromosome aberrations, however, correlated with rapidly removed endo sites and DNA strand breaks and appeared to reflect the number of residual pyrimidine dimers in DNA at the time of its replication

  15. On fixed-parameter algorithms for Split Vertex Deletion

    OpenAIRE

    CYGAN, Marek; Pilipczuk, Marcin

    2012-01-01

    In the Split Vertex Deletion problem, given a graph G and an integer k, we ask whether one can delete k vertices from the graph G to obtain a split graph (i.e., a graph, whose vertex set can be partitioned into two sets: one inducing a clique and the second one inducing an independent set). In this paper we study fixed-parameter algorithms for Split Vertex Deletion parameterized by k: we show that, up to a factor quasipolynomial in k and polynomial in n, the Split Vertex Deletion problem can ...

  16. Mitochondrial DNA deletions in patients with chronic suppurative otitis media.

    Science.gov (United States)

    Tatar, Arzu; Tasdemir, Sener; Sahin, Ibrahim; Bozoglu, Ceyda; Erdem, Haktan Bagis; Yoruk, Ozgur; Tatar, Abdulgani

    2016-09-01

    The aim of this study was to investigate the 4977 and 7400 bp deletions of mitochondrial DNA in patients with chronic suppurative otitis media and to indicate the possible association of mitochondrial DNA deletions with chronic suppurative otitis media. Thirty-six patients with chronic suppurative otitis media were randomly selected to assess the mitochondrial DNA deletions. Tympanomastoidectomy was applied for the treatment of chronic suppurative otitis media, and the curettage materials including middle ear tissues were collected. The 4977 and 7400 bp deletion regions and two control regions of mitochondrial DNA were assessed by using the four pair primers. DNA was extracted from middle ear tissues and peripheral blood samples of the patients, and then polymerase chain reactions (PCRs) were performed. PCR products were separated in 2 % agarose gel. Seventeen of 36 patients had the heterozygote 4977 bp deletion in the middle ear tissue but not in peripheral blood. There wasn't any patient who had the 7400 bp deletion in mtDNA of their middle ear tissue or peripheral blood tissue. The patients with the 4977 bp deletion had a longer duration of chronic suppurative otitis media and a higher level of hearing loss than the others (p media and the reactive oxygen species can cause the mitochondrial DNA deletions and this may be a predisposing factor to sensorineural hearing loss in chronic suppurative otitis media. An antioxidant drug as a scavenger agent may be used in long-term chronic suppurative otitis media.

  17. 44 CFR 5.27 - Deletion of identifying details.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Deletion of identifying details. 5.27 Section 5.27 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY..., FEMA may delete identifying details when making available or publishing an opinion, statement of...

  18. Recurrence and Variability of Germline EPCAM Deletions in Lynch Syndrome

    NARCIS (Netherlands)

    Kuiper, Roland P.; Vissers, Lisenka E. L. M.; Venkatachalam, Ramprasath; Bodmer, Danielle; Hoenselaar, Eveline; Goossens, Monique; Haufe, Aline; Kamping, Eveline; Niessen, Renee C.; Hogervorst, Frans B. L.; Gille, Johan J. P.; Redeker, Bert; Tops, Carli M. J.; van Gijn, Marielle E.; van den Ouweland, Ans M. W.; Rahner, Nils; Steinke, Verena; Kahl, Philip; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Stemmler, Susanne; Betz, Beate; Hutter, Pierre; Bunyan, David J.; Syngal, Sapna; Culver, Julie O.; Graham, Tracy; Chan, Tsun L.; Nagtegaal, Iris D.; van Krieken, J. Han J. M.; Schackert, Hans K.; Hoogerbrugge, Nicoline; van Kessel, Ad Geurts; Ligtenberg, Marjolijn J. L.

    2011-01-01

    Recently, we identified 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome. These truncating EPCAM deletions cause allele-specific epigenetic silencing of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM. Here we screened a cohort of unexplained Lynch-like

  19. Linguistic and Psychomotor Development in Children with Chromosome 14 Deletions

    Science.gov (United States)

    Zampini, Laura; D'Odorico, Laura; Zanchi, Paola; Zollino, Marcella; Neri, Giovanni

    2012-01-01

    The present study focussed on a specific type of rare genetic condition: chromosome 14 deletions. Children with this genetic condition often show developmental delays and brain and neurological problems, although the type and severity of symptoms varies depending on the size and location of the deleted genetic material. The specific aim of the…

  20. Molecular mimicry and clonal deletion: A fresh look.

    Science.gov (United States)

    Rose, Noel R

    2015-06-21

    In this article, I trace the historic background of clonal deletion and molecular mimicry, two major pillars underlying our present understanding of autoimmunity and autoimmune disease. Clonal deletion originated as a critical element of the clonal selection theory of antibody formation in order to explain tolerance of self. If we did have complete clonal deletion, there would be major voids, the infamous "black holes", in our immune repertoire. For comprehensive, protective adaptive immunity, full deletion is necessarily a rare event. Molecular mimicry, the sharing of epitopes among self and non-self antigens, is extraordinary common and provides the evidence that complete deletion of self-reactive clones is rare. If molecular mimicry were not common, protective adaptive immunity could not be all-encompassing. By taking a fresh look at these two processes together we can envision their evolutionary basis and understand the need for regulatory devices to prevent molecular mimicry from progressing to autoimmune disease. PMID:25172771

  1. Ku80-deleted cells are defective at base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)

    2013-05-15

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

  2. Analysis of chromosomal aberrations, sister-chromatid exchanges and micronuclei in peripheral lymphocytes of pharmacists before and after working with cytostatic drugs.

    Science.gov (United States)

    Roth, S; Norppa, H; Järventaus, H; Kyyrönen, P; Ahonen, M; Lehtomäki, J; Sainio, H; Sorsa, M

    1994-12-01

    The frequencies of chromosome aberrations, SCEs and micronuclei (cytokinesis-block method) in blood lymphocytes were compared among six nonsmoking female pharmacists before and after 1 year of working with cytostatic drugs. All possible precautions were taken to avoid exposure to cytostatics, including proper protective clothing and a monitored, negative-pressured working environment with vertical laminar flow cabinet. As referents, an age-matched group of six nonsmoking female hospital workers not dealing with cytostatics was simultaneously sampled twice with the same time interval. The pharmacists showed a marginally higher mean frequency of SCEs/cell (6.3; P = 0.049) after the working period than 1 year earlier (5.8). On the other hand, the referents, with no obvious exposure, had a higher mean number of cells with chromatid-type aberrations, gaps excluded, in the second sampling (2.0%; P = 0.048) than in the first one (0.5%). In addition, a slight (P = 0.055) trend towards a higher frequency of micronucleated binucleate cells was observed in the second sampling for both the exposed and control subjects. As such findings suggest technical variation in the cytogenetic parameters, the small difference observed in SCEs for the pharmacists between the two samplings was probably not related to the cytostatics exposure. No statistically significant differences were observed for any of the cytogenetic parameters in comparisons between the pharmacists and the referents. The findings suggest that caution should be exercised in comparing results obtained from two different samplings in prospective cytogenetic studies. PMID:7527908

  3. Genotoxic effects of a particular mixture of acetamiprid and alpha-cypermethrin on chromosome aberration, sister chromatid exchange, and micronucleus formation in human peripheral blood lymphocytes.

    Science.gov (United States)

    Kocaman, Ayşe Yavuz; Topaktaş, Mehmet

    2010-04-01

    The genotoxic effects of a particular mixture of acetamiprid (Acm, neonicotinoid insecticide) and alpha-cypermethrin (alpha-cyp, pyrethroid insecticide) on human peripheral lymphocytes were examined in vitro by chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronucleus (MN) tests. The human peripheral lymphocytes were treated with 12.5 + 2.5, 15 + 5, 17.5 + 7.5, and 20 + 10 microg/mL of Acm+alpha-cyp, respectively, for 24 and 48 h. The mixture of Acm+alpha-cyp induced the CAs and SCEs at all concentrations and treatment times when compared with both the control and solvent control and these increases were concentration-dependent in both treatment times. MN formation was significantly induced at 12.5 + 2.5, 15 + 5, 17.5 + 7.5, microg/mL of Acm+alpha-cyp when compared with both controls although these increases were not concentration-dependent. Binuclear cells could not be detected sufficiently in the highest concentration of the mixture (20 + 10 microg/mL) for both the 24- and 48-h treatment times. Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) significantly decreased because of the cytotoxic and cytostatic effects of the mixture, at all concentrations for two treatment periods. Significant decreases in MI and PI were concentration dependent at both treatment times. The decrease in NDI was also concentration-dependent at 48-h treatment period. In general, Acm+alpha-cyp inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC. Furthermore, in this article, the results of combined effects of Acm+alpha-cyp were compared with the results of single effects of Acm or alpha-cyp (Kocaman and Topaktas,2007,2009, respectively). In conclusion, the particular mixture of Acm+alpha-cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes.

  4. Fungal ABC transporter deletion and localization analysis.

    Science.gov (United States)

    Kovalchuk, Andriy; Weber, Stefan S; Nijland, Jeroen G; Bovenberg, Roel A L; Driessen, Arnold J M

    2012-01-01

    Fungal cells are highly complex as their metabolism is compartmentalized harboring various types of subcellular organelles that are bordered by one or more membranes. Knowledge about the intracellular localization of transporter proteins is often required for the understanding of their biological function. Among different approaches available, the localization analysis based on the expression of GFP fusions is commonly used as a relatively fast and cost-efficient method that allows visualization of proteins of interest in both live and fixed cells. In addition, inactivation of transporter genes is an important tool to resolve their specific function. Here we provide a detailed protocol for the deletion and localization analysis of ABC transporters in the filamentous fungus Penicillium chrysogenum. It includes construction of expression plasmids, their transformation into fungal strains, cultivation of transformants, microscopy analysis, as well as additional protocols on staining of fungal cells with organelle-specific dyes like Hoechst 33342, MitoTracker DeepRed, and FM4-64. PMID:22183644

  5. Ectrodactyly and proximal/intermediate interstitial deletion 7q

    Energy Technology Data Exchange (ETDEWEB)

    McElveen, C.; Carvajal, M.V.; Moscatello, D. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)] [and others

    1995-03-13

    We report on an individual with severe mental retardation, seizures, microcephaly, unusual face, scoliosis, and cleft feet and cleft right hand. The chromosomal study showed a proximal interstitial deletion 7q (q11.23q22). From our review of the literature, 11 patients have been reported with ectrodactyly (split hand/split foot malformation) and proximal/intermediate interstitial deletions or rearrangements of 7q. The critical segment for ectrodactyly seems to be located between 7q21.2 and 7q22.1. This malformation is present in 41% of the patients whose deletion involves the critical segment. 37 refs., 3 figs., 1 tab.

  6. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available BACKGROUND: Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1 deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis. METHODOLOGY/PRINCIPAL FINDINGS: We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/- or hmox(+/+ bone marrow cells, we evaluated (i the erythrocyte parameters in the peripheral blood; (ii the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii the patterns of histological iron staining; and (iv the number of Mac-1(+-cells expressing TNF-α. In the spleens of mice that received hmox(+/- cells, we show (i decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii increases in the insoluble iron levels and decreases in the soluble iron levels; (iii increased numbers of Mac-1(+-cells expressing TNF-α; and (iv decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations. CONCLUSIONS/SIGNIFICANCE: As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

  7. Evaluation of the persistence in the induction of Sister Chromatid Exchanges (SCE) by alkylating agents; Evaluacion de la persistencia en la induccion de Intercambio en las Cromatidas Hermanas (ICH) por agentes alquilantes

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez R, R.; Huerta V, C.; MOrales R, P.R. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2006-07-01

    The persistence in the induction of sister chromatid exchanges (SCE) by the alkylating agents methyl and ethyl-methanesulfonates (MMS and EMS) was evaluated. For it, to groups of mice its were administered a dose of these agents and later its were analyzed the induced SCE's in two periods: early and late. Both agents caused high increments of SCE in the early period and small in the late one; however, the caused lately by EMS was significantly bigger. This late induction of SCE by EMS possibly is associated with an epigenetic change or with the presence of etiladucts in the phosphodiester bonds of the DNA. (Author)

  8. 78 FR 63967 - Procurement List; Proposed Addition and Deletions

    Science.gov (United States)

    2013-10-25

    ...: Social Vocational Services, Inc.--Deleted, San Jose, CA Contracting Activity: DEPT OF THE ARMY, W40M NATL... Sustainment Systems, Natick, MA NPA: ReadyOne Industries (ROI), Inc., El Paso, TX Contracting Activity:...

  9. Characterization of a lymphoblastoid line deleted for lambda immunoglobulin genes

    Energy Technology Data Exchange (ETDEWEB)

    Hough, C.A., White, B.N., Holden, J.A. [Queen`s Univ., Ontario (Canada)

    1995-04-01

    While characterizing the cat eye syndrome (CES) supernumerary chromosome for the presence of {lambda} immunoglobulin gene region sequences, a lymphoblastoid cell line from one CES patient was identified in which there was selection of cells deleted from some IGLC and IGLV genes. Two distinct deletions, one on each chromosome 22, were identified, presumably arising from independent somatic recombination events occurring during B-lymphocyte differentiation. The extent of the deleted regions was determined using probes from the various IGLV subgroups and they each covered at least 82 kilobases. The precise definition of the deletions was not possible because of conservation of some restriction sites in the IGLV region. The cell line was used to map putative IGLV genes within the recombinant phage {lambda}V{lambda}135 to the distal part of the IGLV gene region. 35 refs., 4 figs.

  10. Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

    OpenAIRE

    de Rooij, Jasmijn D.E.; Beuling, Eva; Marry M van den Heuvel-Eibrink; Obulkasim, Askar; Baruchel, André; Trka, Jan; Reinhardt, Dirk; Sonneveld, Edwin; Gibson, Brenda E.S.; Pieters, Rob; Zimmermann, Martin; Zwaan, C. Michel; Fornerod, Maarten

    2015-01-01

    IKAROS family zinc finger 1/IKZF1 is a transcription factor important in lymphoid differentiation, and a known tumor suppressor in acute lymphoid leukemia. Recent studies suggest that IKZF1 is also involved in myeloid differentiation. To investigate whether IKZF1 deletions also play a role in pediatric acute myeloid leukemia, we screened a panel of pediatric acute myeloid leukemia samples for deletions of the IKZF1 locus using multiplex ligation-dependent probe amplification and for mutations...

  11. Construction of Deletion-knockout Mutant Fowlpox Virus (FWPV)

    OpenAIRE

    Laidlaw, Stephen M.; Skinner, Michael A.

    2014-01-01

    The construction of deletion-knockout poxviruses is a useful approach to determining the function of specific virus genes. This protocol is an adaptation of the transient dominant knockout selection protocol published by Falkner and Moss (1990) for use with vaccinia virus. The protocol makes use of the dominant selectable marker Escherichia coli guanine phosphoribosyltransferase (gpt) gene (Mulligan and Berg, 1981), under the control of an early/late poxvirus promoter. The deletion viruses th...

  12. Bilateral hand amyotrophy with PMP-22 gene deletion.

    Science.gov (United States)

    Gochard, A; Guennoc, A M; Praline, J; Malinge, M C; de Toffol, B; Corcia, P

    2007-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) phenotypes are heterogeneous. We report the case of a 52-year-old woman without medical history, who complained of bilateral hand weakness suggestive first of a motor neuron disorder. The presence of a diffuse predominant distal demyelinating neuropathy suggested a deletion of PMP-22 gene, which was confirmed by genetic analysis. This case report underlines a novel phenotype related to the deletion of PMP-22 gene.

  13. Insertion and Deletion Processes in Recent Human History

    OpenAIRE

    Per Sjödin; Thomas Bataillon; Schierup, Mikkel H.

    2010-01-01

    BACKGROUND: Although insertions and deletions (indels) account for a sizable portion of genetic changes within and among species, they have received little attention because they are difficult to type, are alignment dependent and their underlying mutational process is poorly understood. A fundamental question in this respect is whether insertions and deletions are governed by similar or different processes and, if so, what these differences are. METHODOLOGY/PRINCIPAL FINDINGS: We use publishe...

  14. Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes.

    Directory of Open Access Journals (Sweden)

    Jessica Hopkins

    2014-07-01

    Full Text Available Cohesins are important for chromosome structure and chromosome segregation during mitosis and meiosis. Cohesins are composed of two structural maintenance of chromosomes (SMC1-SMC3 proteins that form a V-shaped heterodimer structure, which is bridged by a α-kleisin protein and a stromal antigen (STAG protein. Previous studies in mouse have shown that there is one SMC1 protein (SMC1β, two α-kleisins (RAD21L and REC8 and one STAG protein (STAG3 that are meiosis-specific. During meiosis, homologous chromosomes must recombine with one another in the context of a tripartite structure known as the synaptonemal complex (SC. From interaction studies, it has been shown that there are at least four meiosis-specific forms of cohesin, which together with the mitotic cohesin complex, are lateral components of the SC. STAG3 is the only meiosis-specific subunit that is represented within all four meiosis-specific cohesin complexes. In Stag3 mutant germ cells, the protein level of other meiosis-specific cohesin subunits (SMC1β, RAD21L and REC8 is reduced, and their localization to chromosome axes is disrupted. In contrast, the mitotic cohesin complex remains intact and localizes robustly to the meiotic chromosome axes. The instability of meiosis-specific cohesins observed in Stag3 mutants results in aberrant DNA repair processes, and disruption of synapsis between homologous chromosomes. Furthermore, mutation of Stag3 results in perturbation of pericentromeric heterochromatin clustering, and disruption of centromere cohesion between sister chromatids during meiotic prophase. These defects result in early prophase I arrest and apoptosis in both male and female germ cells. The meiotic defects observed in Stag3 mutants are more severe when compared to single mutants for Smc1β, Rec8 and Rad21l, however they are not as severe as the Rec8, Rad21l double mutants. Taken together, our study demonstrates that STAG3 is required for the stability of all meiosis

  15. Fast detection of deletion breakpoints using quantitative PCR

    Directory of Open Access Journals (Sweden)

    Gulshara Abildinova

    2016-01-01

    Full Text Available Abstract The routine detection of large and medium copy number variants (CNVs is well established. Hemizygotic deletions or duplications in the large Duchenne muscular dystrophy DMD gene responsible for Duchenne and Becker muscular dystrophies are routinely identified using multiple ligation probe amplification and array-based comparative genomic hybridization. These methods only map deleted or duplicated exons, without providing the exact location of breakpoints. Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. Here, we present a strategy for detecting the breakpoints of medium and large CNVs regardless of their size. The hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. The strategy is fast, reliable and cost-efficient, making it amenable to widespread use in genetic laboratories.

  16. Fast detection of deletion breakpoints using quantitative PCR.

    Science.gov (United States)

    Abildinova, Gulshara; Abdrakhmanova, Zhanara; Tuchinsky, Helena; Nesher, Elimelech; Pinhasov, Albert; Raskin, Leon

    2016-06-16

    The routine detection of large and medium copy number variants (CNVs) is well established. Hemizygotic deletions or duplications in the large Duchenne muscular dystrophy DMD gene responsible for Duchenne and Becker muscular dystrophies are routinely identified using multiple ligation probe amplification and array-based comparative genomic hybridization. These methods only map deleted or duplicated exons, without providing the exact location of breakpoints. Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. Here, we present a strategy for detecting the breakpoints of medium and large CNVs regardless of their size. The hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. The strategy is fast, reliable and cost-efficient, making it amenable to widespread use in genetic laboratories. PMID:27333265

  17. Exon Deletions of Parkin Gene in Patients with Parkinson Disease

    Institute of Scientific and Technical Information of China (English)

    王涛; 梁直厚; 孙圣刚; 曹学兵; 彭海; 刘红进; 童萼塘

    2004-01-01

    Summary: Mutations in the parkin gene have recently been identified in familial and isolated patients with early-onset Parkinson disease (PD) and that subregions between exon 2 and 4 of the parkin gene are hot spots of deletive mutations. To study the distribution of deletions in the parkin gene among variant subset patients with PD in China, and to explore the role of parkin gene in the pathogenesis of PD, 63 patients were divided into early onset and later onset groups. Exons 1-12 were amplified by PCR, templated by the genomic DNA of patients, and then the deletion distribution detected by agarose electrophoresis. Four patients were found to be carrier of exon deletions in 63 patients with PD. The location of the deletion was on exon 2 (1 case), exon 3 (2 cases) and exon 4 (1 case). All patients were belong to the group of early onset PD. The results showed that parkin gene deletion on exon 2, exon 3 and exon 4 found in Chinese population contributes partly to early onset PD.

  18. Similarity of DMD gene deletion and duplication in the Chinese patients compared to global populations

    Directory of Open Access Journals (Sweden)

    Yan Ming

    2008-04-01

    Full Text Available Abstract Background DNA deletion and duplication were determined as the major mutation underlying Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD. Method Applying multiplex ligation-dependent probe amplification (MLPA, we have analyzed 179 unrelated DMD/BMD subjects from northern China. Results Seventy-three percent of the subjects were found having a deletion (66.25% or duplication (6.25%. Exons 51–52 were detected as the most common fragment deleted in single-exon deletion, and the region of exons 45–50 was the most common exons deleted in multi-exon deletions. About 90% of DMD/BMD cases carry a small size deletion that involves 10 exons or less, 26.67% of which carry a single-exon deletion. Most of the smaller deletions resulted in an out-of-frame mutation. The most common exons deleted were determined to be between exon 48 and exon 52, with exon 50 was the model allele. Verifying single-exon deletion, one sample with a deletion of exon 53 that was initially observed from MLPA showed that there was a single base deletion that abolished the ligation site in MLPA. Confirmation of single-exon deletion is recommended to exclude single base deletion or mutation at the MLPA ligation site. Conclusion The frequency of deletion and duplication in northern China is similar to global ethnic populations.

  19. Functional Genomics Using the Saccharomyces cerevisiae Yeast Deletion Collections.

    Science.gov (United States)

    Nislow, Corey; Wong, Lai Hong; Lee, Amy Huei-Yi; Giaever, Guri

    2016-01-01

    Constructed by a consortium of 16 laboratories, the Saccharomyces genome-wide deletion collections have, for the past decade, provided a powerful, rapid, and inexpensive approach for functional profiling of the yeast genome. Loss-of-function deletion mutants were systematically created using a polymerase chain reaction (PCR)-based gene deletion strategy to generate a start-to-stop codon replacement of each open reading frame by homologous recombination. Each strain carries two molecular barcodes that serve as unique strain identifiers, enabling their growth to be analyzed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays or through the use of next-generation sequencing technologies. Functional profiling of the deletion collections, using either strain-by-strain or parallel assays, provides an unbiased approach to systematically survey the yeast genome. The Saccharomyces yeast deletion collections have proved immensely powerful in contributing to the understanding of gene function, including functional relationships between genes and genetic pathways in response to diverse genetic and environmental perturbations. PMID:27587784

  20. Deletion analysis of spinal muscular atrophy in southern Indian population

    Directory of Open Access Journals (Sweden)

    Swaminathan Bhairavi

    2008-01-01

    Full Text Available Background: Proximal spinal muscular atrophy (SMA is a genetically heterogeneous disease with paresis and muscle atrophy due to loss of anterior horn cell function. The survival of motor neuron gene (SMN and neuronal apoptosis inhibitory protein (NAIP play a primary role. Both the gene homologues exist as inverted duplications on Chromosome 5q. The telomeric/functional (SMN1 and the centromeric (SMN2 copies differ from each other in eight nucleotides. The C→T transition (at Codon 280 within Exon 7 of SMN2 causes disruption of an exonic splicing enhancer (ESE and/or creates an exonic splicing silencer (ESS leading to abnormal splicing and a truncated protein. Objective: To determine the molecular genetics of SMN1 and NAIP genes in SMA from southern India. Materials and Methods: In the present study, 37 patients from the neuromuscular disorders clinic of National Institute of Mental Health and Neurosciences were assayed for the deletions in the SMN1 and NAIP genes using PCR-RFLP methods. Results: Among the SMA Type I patients, 43% showed deletions of SMN1 and NAIP. In patients Type II SMA, 57% showed deletions of the SMN1 exons. Conclusion: Thus, deletions were found to occur in 47.8% of the Type I and II patients. Lower sensitivity of gene deletion study in clinically suspected SMA needs further study as clinical diagnosis of SMA is not gold standard. However, the results do correlate with other studies conducted in India.

  1. Functional Profiling Using the Saccharomyces Genome Deletion Project Collections.

    Science.gov (United States)

    Nislow, Corey; Wong, Lai Hong; Lee, Amy Huei-Yi; Giaever, Guri

    2016-01-01

    The ability to measure and quantify the fitness of an entire organism requires considerably more complex approaches than simply using traditional "omic" methods that examine, for example, the abundance of RNA transcripts, proteins, or metabolites. The yeast deletion collections represent the only systematic, comprehensive set of null alleles for any organism in which such fitness measurements can be assayed. Generated by the Saccharomyces Genome Deletion Project, these collections allow the systematic and parallel analysis of gene functions using any measurable phenotype. The unique 20-bp molecular barcodes engineered into the genome of each deletion strain facilitate the massively parallel analysis of individual fitness. Here, we present functional genomic protocols for use with the yeast deletion collections. We describe how to maintain, propagate, and store the deletion collections and how to perform growth fitness assays on single and parallel screening platforms. Phenotypic fitness analyses of the yeast mutants, described in brief here, provide important insights into biological functions, mechanisms of drug action, and response to environmental stresses. It is important to bear in mind that the specific assays described in this protocol represent some of the many ways in which these collections can be assayed, and in this description particular attention is paid to maximizing throughput using growth as the phenotypic measure. PMID:27587776

  2. Deletion 2q37 syndrome: Cognitive-behavioral trajectories and autistic features related to breakpoint and deletion size.

    Science.gov (United States)

    Fisch, Gene S; Falk, Rena E; Carey, John C; Imitola, Jaime; Sederberg, Maria; Caravalho, Karen S; South, Sarah

    2016-09-01

    Subtelomeric deletions have been reported in ∼2.5% of individuals with developmental disabilities. Subtelomeric deletion 2q37 has been detected in many individuals diagnosed with intellectual disabilities (ID) and autism spectrum disorders (ASD). Previously, genotype-phenotype correspondences were examined for their relationship to breakpoints 37.1, 37.2, or 37.3. Our purpose was to ascertain whether there were phenotypic differences at these breakpoints, elucidate the cognitive-behavioral phenotype in del2q37, and examine the genotype-phenotype association in the deletion with respect to cognitive-behavioral profiles and ASD. We administered a comprehensive cognitive-behavioral battery to nine children diagnosed with del 2q37, ages 3.9-17.75 years. ID for five tested with the Stanford-Binet (4th Edition) (SBFE) ranged from severe to mild [IQ Range: 36-59]. Adaptive behavior scores from the Vineland Adaptive Behavior Scale (VABS) were much below adequate levels (DQ Range: floor value ["19"] to 55). Autism scores from the Child Autism Rating Scale (CARS) ranged from 22 [non-autistic] to 56 [extremely autistic]; 5/8 [63%] children received scores on the autism spectrum. Participants with the largest deletions, 10.1 and 9.5 Mb, attained the highest IQ and DQ scores while those with the smallest deletions, 7.9 and 6.6 Mb, made the lowest IQ and DQ scores. No association between deletion breakpoint and phenotype were found. Assessment of the various deleted regions suggested histone deacetylase 4 gene (HDAC4) was a likely candidate gene for ASD in our sample. However, two earlier reports found no association between HDAC4 haploinsufficiency and ASD. © 2016 Wiley Periodicals, Inc.

  3. Reliable communication over non-binary insertion/deletion channels

    CERN Document Server

    Yazdani, Raman

    2012-01-01

    We consider the problem of reliable communication over non-binary insertion/deletion channels where symbols are randomly deleted from or inserted in the transmitted sequence and all symbols are corrupted by additive white Gaussian noise. To this end, we utilize the inherent redundancy achievable in non-binary symbol sets by first expanding the symbol set and then allocating part of the bits associated with each symbol to watermark symbols. The watermark sequence, known at the receiver, is then used by a forward-backward algorithm to provide soft information for an outer code which decodes the transmitted sequence. Through numerical results and discussions, we evaluate the performance of the proposed solution and show that it leads to significant system ability to detect and correct insertions/deletions. We also provide estimates of the maximum achievable information rates of the system, compare them with the available bounds, and construct practical codes capable of approaching these limits.

  4. A local-world node deleting evolving network model

    Energy Technology Data Exchange (ETDEWEB)

    Gu Yuying [Department of Mathematics, Tongji University, Shanghai 200092 (China); Sun Jitao [Department of Mathematics, Tongji University, Shanghai 200092 (China)], E-mail: sunjt@sh163.net

    2008-06-16

    A new type network growth rule which comprises node addition with the concept of local-world connectivity and node deleting is studied. A series of theoretical analysis and numerical simulation to the LWD network are conducted in this Letter. Firstly, the degree distribution p(k) of this network changes no longer pure scale free but truncates by an exponential tail and the truncation in p(k) increases as p{sub a} decreases. Secondly, the connectivity is tighter, as the local-world size M increases. Thirdly, the average path length L increases and the clustering coefficient decreases as generally node deleting increases. Finally, trends up when the local-world size M increases, so as to k{sub max}. Hence, the expanding local-world can compensate the infection of the node deleting.

  5. Effects of crp deletion in Salmonella enterica serotype Gallinarum

    Directory of Open Access Journals (Sweden)

    Rubino Salvatore

    2007-05-01

    Full Text Available Abstract Background Salmonella enterica serotype Gallinarum (S. Gallinarum remains an important pathogen of poultry, especially in developing countries. There is a need to develop effective and safe vaccines. In the current study, the effect of crp deletion was investigated with respect to virulence and biochemical properties and the possible use of a deletion mutant as vaccine candidate was preliminarily tested. Methods Mutants were constructed in S. Gallinarum by P22 transduction from Salmonella Typhimurium (S. Typhimurium with deletion of the crp gene. The effect was characterized by measuring biochemical properties and by testing of invasion in a chicken loop model and by challenge of six-day-old chickens. Further, birds were immunized with the deleted strain and challenged with the wild type isolate. Results The crp deletions caused complete attenuation of S. Gallinarum. This was shown by ileal loop experiments not to be due to significantly reduced invasion. Strains with such deletions may have vaccine potential, since oral inoculatoin with S. Gallinarum Δcrp completely protected against challenge with the same dose of wild type S. Gallinarum ten days post immunization. Interestingly, the mutations did not cause the same biochemical and growth changes to the two biotypes of S. Gallinarum. All biochemical effects but not virulence could be complemented by providing an intact crp-gene from S. Typhimurium on the plasmid pSD110. Conclusion Transduction of a Tn10 disrupted crp gene from S. Typhimurium caused attenuation in S. Gallinarum and mutated strains are possible candidates for live vaccines against fowl typhoid.

  6. Dissecting the phenotypes of Dravet syndrome by gene deletion.

    Science.gov (United States)

    Rubinstein, Moran; Han, Sung; Tai, Chao; Westenbroek, Ruth E; Hunker, Avery; Scheuer, Todd; Catterall, William A

    2015-08-01

    Neurological and psychiatric syndromes often have multiple disease traits, yet it is unknown how such multi-faceted deficits arise from single mutations. Haploinsufficiency of the voltage-gated sodium channel Nav1.1 causes Dravet syndrome, an intractable childhood-onset epilepsy with hyperactivity, cognitive deficit, autistic-like behaviours, and premature death. Deletion of Nav1.1 channels selectively impairs excitability of GABAergic interneurons. We studied mice having selective deletion of Nav1.1 in parvalbumin- or somatostatin-expressing interneurons. In brain slices, these deletions cause increased threshold for action potential generation, impaired action potential firing in trains, and reduced amplification of postsynaptic potentials in those interneurons. Selective deletion of Nav1.1 in parvalbumin- or somatostatin-expressing interneurons increases susceptibility to thermally-induced seizures, which are strikingly prolonged when Nav1.1 is deleted in both interneuron types. Mice with global haploinsufficiency of Nav1.1 display autistic-like behaviours, hyperactivity and cognitive impairment. Haploinsufficiency of Nav1.1 in parvalbumin-expressing interneurons causes autistic-like behaviours, but not hyperactivity, whereas haploinsufficiency in somatostatin-expressing interneurons causes hyperactivity without autistic-like behaviours. Heterozygous deletion in both interneuron types is required to impair long-term spatial memory in context-dependent fear conditioning, without affecting short-term spatial learning or memory. Thus, the multi-faceted phenotypes of Dravet syndrome can be genetically dissected, revealing synergy in causing epilepsy, premature death and deficits in long-term spatial memory, but interneuron-specific effects on hyperactivity and autistic-like behaviours. These results show that multiple disease traits can arise from similar functional deficits in specific interneuron types. PMID:26017580

  7. Ku80-Deleted Cells are Defective at Base Excision Repair

    OpenAIRE

    Li, Han; Marple, Teresa; Hasty, Paul

    2013-01-01

    Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repa...

  8. Binding numbers of fractional k-deleted graphs

    OpenAIRE

    KOTANI, Keiko

    2010-01-01

    Let k be an integer with $k \\ge 2$. We show that if G be a graph such that $|G| > 4k+1 -4\\sqrt {k-1}$ and $bind(G)> {(2k-1)(n-1) \\over k(n-2)},$ then G is a fractional k-deleted graph. We also show that in the case where k is even, if G be a graph such that $|G| > 4k+1 -4\\sqrt {k}$ and $bind(G)> {(2k-1)(n-1) \\over k(n-2)+1},$ then G is a fractional k-deleted graph.

  9. Functional analysis of hepatitis B virus pre-s deletion variants associated with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Lin Chih-Ming

    2012-02-01

    Full Text Available Abstract Background Naturally occurring pre-S deletion mutants have been identified in hepatitis B carriers and shown to be associated with the development of hepatocellular carcinoma. The phenotypes of these pre-S deletion genomes remain unclear, and they were investigated in this study. Methods The pre-S deletion genomes: (1 pre-S1 deletion, (2 deletion spanning pre-S1 and pre-S2, (3 pre-S2 N-terminal deletion, and (4 pre-S2 internal deletion were constructed and analyzed by transfection into Huh-7 cells. Results Functional analyses reveal that these mutants were divided into two groups: S promoter deletion and non-S promoter deletion variants. Compared with the wild-type genome, S promoter deletion variants led to an inverse ratio of pre-S1 mRNA and pre-S2/S mRNA, and intracellular accumulation of surface proteins. An interesting finding is that a small amount of L proteins was detected in the medium from S promoter deletion variant-transfected cells. Non-S promoter deletion variants conversely displayed a wild-type like mRNA and protein pattern. The secretion of surface proteins from non-S promoter deletion variants was inhibited less than from S promoter deletion variant. Immunofluorescence analysis showed mutant surface proteins colocalized with ER and exhibited an atypical distribution: granular staining pattern in the S-promoter deletion variants and perinuclear staining pattern in the non-S promoter deletion variants. Conclusion This study shows that these pre-S deletion genomes exhibit two different phenotypes in mRNA transcription, surface protein expression and secretion. This diversity seems to result from the deletion of S promoter rather than result from the deletion of pre-S1 or pre-S2.

  10. 77 FR 22288 - Procurement List; Additions and Deletions

    Science.gov (United States)

    2012-04-13

    ... . SUPPLEMENTARY INFORMATION: Additions On 2/17/2012 (77 FR 9631), the Committee for Purchase From People Who Are..., Office of Acquisitions, Alexandria, VA. Deletions On 2/17/2012 (77 FR 9631), the Committee for Purchase... From the Federal Register Online via the Government Publishing Office COMMITTEE FOR PURCHASE...

  11. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  12. Behavioral Phenotype in the 9q Subtelomeric Deletion Syndrome

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Kleefstra, T.; Egger, J.I.M.

    2010-01-01

    The 9q Subtelomeric Deletion Syndrome (9qSTDS) is clinically characterized by mental retardation, childhood hypotonia, and facial dysmorphisms. Haploinsufficiency of the EHMT1 gene has been demonstrated to be responsible for its core phenotype. In a significant number of patients behavioral abnormal

  13. Distinct effects of tafazzin deletion in differentiated and undifferentiated mitochondria

    NARCIS (Netherlands)

    D. Acehan; Z. Khuchua; R.H. Houtkooper; A. Malhotra; J. Kaufman; F.M. Vaz; M. Ren; H.A. Rockman; D.L. Stokes; M. Schlame

    2009-01-01

    Tafazzin is a conserved mitochondrial protein that is required to maintain normal content and composition of cardiolipin. We used electron tomography to investigate the effect of tafazzin deletion on mitochondrial structure and found that cellular differentiation plays a crucial role in the manifest

  14. Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Joseph Tripodi

    2010-09-01

    Full Text Available Joseph Tripodi1, Ronald Hoffman1, Vesna Najfeld2, Rona Weinberg31The Myeloproliferative Disorders Program, Tisch Cancer Institute, Department of Medicine and 2Department of Medicine and Pathology, Mount Sinai School of Medicine, 3The Myeloproliferative Disorders Program, Cellular Therapy Laboratory, The New York Blood Center, New York, NY, USAAbstract: The Philadelphia chromosome (Ph-negative myeloproliferative neoplasms (MPNs, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a group of clonal hematopoietic stem cell disorders with overlapping clinical and cytogenetic features and a variable tendency to evolve into acute leukemia. These diseases not only share overlapping chromosomal abnormalities but also a number of acquired somatic mutations. Recently, mutations in a putative tumor suppressor gene, ten-eleven translocation 2 (TET2 on chromosome 4q24 have been identified in 12% of patients with MPN. Additionally 4q24 chromosomal rearrangements in MPN, including TET2 deletions, have also been observed using conventional cytogenetics. The goal of this study was to investigate the frequency of genomic TET2 rearrangements in MPN using fluorescence in situ hybridization as a more sensitive method for screening and identifying genomic deletions. Among 146 MPN patients, we identified two patients (1.4% who showed a common 4q24 deletion, including TET2. Our observations also indicated that the frequency of TET2 deletion is increased in patients with an abnormal karyotype (5%.Keywords: TET2, myeloproliferative neoplasms, fluorescence in situ hybridization, cytogenetics

  15. Efficient Generation of Unmarked Deletions in Legionella pneumophila▿ †

    OpenAIRE

    Bryan, Andrew; Harada, Kaoru; Michele S Swanson

    2011-01-01

    Unmarked gene deletions facilitate studies of Legionella pneumophila multicomponent processes, such as motility and exonuclease activity. For this purpose, FRT-flanked alleles constructed in Escherichia coli using λ-Red recombinase were transferred to L. pneumophila by natural transformation. Resistance cassettes were then efficiently excised using the Flp site-specific recombinase encoded on a plasmid that is readily lost.

  16. 76 FR 14942 - Procurement List; Additions and Deletions

    Science.gov (United States)

    2011-03-18

    ..., XRAW7M8 USPFO Activity IA ARNG, Johnston, IA. ] Deletions On 1/21/2011 (76 FR 3879-3880), the Committee... constructed and will be under the control and military management of the 2D Engineer Battalion when it... replace absent military food service personnel. The Contracting Officer stated that the military...

  17. Expanding Our Understanding of mtDNA Deletions.

    Science.gov (United States)

    Picard, Martin; Vincent, Amy E; Turnbull, Doug M

    2016-07-12

    Clonal expansion of mtDNA deletions compromises mitochondrial function in human disease and aging, but how deleterious mtDNA genomes propagate has remained unclear. In this issue (Gitschlag et al., 2016) and in a recent Nature publication, C. elegans studies implicate the mitochondrial unfolded protein response (UPR(mt)) and offer mechanistic insights into this process. PMID:27411002

  18. 76 FR 21336 - Procurement List; Proposed Additions and Deletions

    Science.gov (United States)

    2011-04-15

    ..., W6QK RDECOM CONTR CTR NATICK, MA. Coverage: C-List for 100% of the requirement of the U.S Army, as... SERVICES ADMINISTRATION, NEW YORK, NY. Slacks, Woman's, Navy--Tropical Blue NSN: 8410-01-377-9373. NPAs... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletions...

  19. 78 FR 20620 - Procurement List; Additions to and Deletions

    Science.gov (United States)

    2013-04-05

    ...-00-NIB-0004--Mouse, Optical Sensor, Black and Grey, Ergonomic shaped NPA: L.C. Industries for the... . SUPPLEMENTARY INFORMATION: Additions On 2/1/2013 (78 FR 7412-7413) and 2/8/2013 (78 FR 9386-9387), the Committee... SERVICE, GSA/PBS/R03 SOUTH SERVICE CENTER, PHILADELPHIA, PA Deletions On 3/23/2012 (77 FR 17035),...

  20. Genetics Home Reference: 22q11.2 deletion syndrome

    Science.gov (United States)

    ... Seattle, Washington Children's Hospital of Philadelphia Cincinnati Children's Hospital Medical Center Disease InfoSearch: 22q11.2 Deletion Syndrome Emory University School of Medicine Genetics Education Materials for School Success (GEMSS) MalaCards: chromosome 22q11. ...

  1. Deletion affecting band 7q36 not associated with holoprosencephaly

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahim, S.A.D.; Krivchenia, E.; Mohamed, A.N. [Wayne State Univ., Detroit, MI (United States)] [and others

    1994-09-01

    Although the appearance of 7q36 aberrations have been postulated to be responsible for holoprosencephaly (HPE), the presence of a de novo 7q36 deletion in fetus without HPE has not been reported. We report the first case of a fetus with 7q36 deletion but lacking HPE. Ultrasound examination of a 25-year-old G3P1 Caucasian female showed small head circumference with microcephaly at 28 weeks. Decreased amniotic fluid volume, bilateral renal dilatation and abnormal facial features were also noted. Chromosome analysis after cordocentesis showed an abnormal female karyotype with a deletion involving the chromosome band 7q36, 46,XX,del(7)(q36). Chromosome studies on the biological parents were normal. In view of the chromosome finding and after extensive counseling, the couple elected to terminate the pregnancy. The chromosome findings were confirmed by fetal blood chromosome analysis at termination. Post-mortem examination confirmed dysmorphic features including a depressed nasal bridge and large flat ears with no lobules, but no cleft lip or palate was noted. Internal abnormalities included a bicuspid pulmonary valve and abnormally located lungs. The brain weighed 190g (249 {plus_minus} 64g expected) and had symmetric cerebral hemispheres without evidence of HPE or other gross or microscopic malformation, except focal cerebellar cortical dysplasia. In summary, our patient showed a deletion of the same chromosomal band implicated in HPE but lacked HPE. This finding indicates that 7q36 deletion may be seen in the absence of HPE and suggests that other genetic mechanisms may be responsible for HPE in this setting.

  2. Rare copy number deletions predict individual variation in intelligence.

    Directory of Open Access Journals (Sweden)

    Ronald A Yeo

    Full Text Available Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in "mutation load" emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent copy number variations (CNVs, and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77 had been administered the Wechsler Abbreviated Scale of Intelligence (WASI. After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = -.30, p = .01. As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES, we also examined the impact of ethnicity (Anglo/White vs. Other, as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed.

  3. Screening for clinically significant non-deletional alpha thalassaemia mutations by pyrosequencing

    OpenAIRE

    Haywood, Anna; Dreau, Helene; Timbs, Adele; Schuh, Anna; Old, John; Henderson, Shirley

    2010-01-01

    Abstract Non-deletional ?+-thalassaemia is associated with a higher degree of morbidity and mortality than deletional forms of ?+-thalassaemia. Screening for the common deletional forms of ?-thalassaemia by Gap-PCR is widely practiced; however, the detection of non-deletional ?-thalassaemia mutations is technically more labour-intensive and expensive, as it requires DNA sequencing. In addition, the presence of four very closely homologous alpha globin genes and the frequent co-exis...

  4. Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes.

    Directory of Open Access Journals (Sweden)

    Bekim Sadikovic

    Full Text Available Mitochondrial DNA (mtDNA deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM, progressive external ophthalmoplegia (PEO, and Kearns-Sayre syndrome (KSS, to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (<6 years old showed a diffused pattern of deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41. Only 15% (3/20 of the young patients (<6 years old carry the 5 kb common deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17 exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier

  5. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    Energy Technology Data Exchange (ETDEWEB)

    Lushaj, Entela B., E-mail: lushaj@surgery.wisc.edu [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States); Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States)

    2012-06-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  6. Common Deletion (CD) in mitochondrial DNA of irradiated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Raquel Gomes; Ferreira-Machado, Samara C.; Almeida, Carlos E.V. de, E-mail: raquelgsiqueira@gmail.com [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Ciencias Radiologicas; Silva, Dayse A. da; Carvalho, Elizeu F. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Diagnosticos por DNA; Melo, Luiz D.B. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biofisica Carlos Chagas Filho. Lab. de Parasitologia Molecular

    2014-05-15

    The purpose of this study was to map the common deletion (CD) area in mtDNA and investigate the levels of this deletion in irradiated heart. The assays were developed in male Wistar rats that were irradiated with three different single doses (5, 10 or 15 Gy) delivered directly to the heart and the analyses were performed at various times post-irradiation (3, 15 or 120 days). The CDs area were sequenced and the CD quantified by real-time PCR. Our study demonstrated that the CD levels progressively decreased from the 3rd until the 15th day after irradiation, and then increased thereafter. Additionally, it was observed that the levels of CD are modulated differently according to the different categories of doses (moderate and high). This study demonstrated an immediate response to ionizing radiation, measured by the presence of mutations in the CD area and a decrease in the CD levels. (author)

  7. Optimizing Gateway™ technology (Invitrogen) to construct Rhizobium leguminosarum deletion mutants

    OpenAIRE

    Lanza Lucio, Monica; Alborno, Marcelo; Rey Navarro, Luis; Imperial Ródenas, Juan

    2010-01-01

    The study of the role of different genes in Rhizobium leguminosarum requires the generation of mutants by homologous recombination. In this communication we describe a novel approach to obtain deletion mutants of genes in Rhizobium using Gateway TM Cloning technology (Invitrogen) and a new vector (pK18-attR), both conjugative and Rhizobium specific, that carries the recombination tails of Gateway system. This tool is a new alternative to the classic approach based on cloning using rest...

  8. Research Progress on Pseudorabies Gene-deleted Vaccine

    Institute of Scientific and Technical Information of China (English)

    JIN Sheng-zao; CHEN Huang-chun; XIONG Fu

    2002-01-01

    Pseudorabies is caused by pseudorabies virus (PrV), which is a member of family Herpesviridae, subfamily Alphaherpesvirinae and is the agent of acute infectious disease in many domestic and wild animals. Swine was the natural host and reservior of PRV, which inflicts major economic loss in pig industries world wide. Immunization with safe, effective vaccine is main measurements to prevent the disease.In this assay, research progress on PRV gene-deleted vaccine used extensively today was discussed.

  9. Delete-free Reachability Analysis for Temporal and Hierarchical Planning

    OpenAIRE

    Bit-Monnot, Arthur; Smith, David E.; Do, Minh

    2016-01-01

    Reachability analysis is a crucial part of the heuristic computation for many state of the art classical and temporal planners. In this paper, we study the difficulty that arises in assessing the reachability of actions in planning problems containing sets of interdependent actions, notably including problems with required concurrency as well as hierarchical planning problems. In temporal planners, this complication has been addressed by augmenting a delete-free relaxation with additional rel...

  10. Multidrug Resistance of a Porin Deletion Mutant of Mycobacterium smegmatis

    OpenAIRE

    Stephan, Joachim; Mailaender, Claudia; Etienne, Gilles; Daffé, Mamadou; Niederweis, Michael

    2004-01-01

    Mycobacteria contain an outer membrane of unusually low permeability which contributes to their intrinsic resistance to many agents. It is assumed that small and hydrophilic antibiotics cross the outer membrane via porins, whereas hydrophobic antibiotics may diffuse through the membrane directly. A mutant of Mycobacterium smegmatis lacking the major porin MspA was used to examine the role of the porin pathway in antibiotic sensitivity. Deletion of the mspA gene caused high-level resistance of...

  11. 78 FR 71582 - Procurement List; Proposed Additions and Deletions

    Science.gov (United States)

    2013-11-29

    ...-583-9479--SS NSN: 8415-01-583-9480--SR NSN: 8415-01-583-9483--SL NSN: 8415-01-583-9485--MS NSN: 8415...: 8415-01-584-1640--SS NSN: 8415-01-584-1641--SR NSN: 8415-01-584-1642--SL NSN: 8415-01-584-1643--MS NSN... for deletion from the Procurement List: Products Stamp Pad Ink NSN: 7510-01-316-7516--Refill...

  12. Molecular basis of human growth hormone gene deletions

    International Nuclear Information System (INIS)

    Crossover sites resulting from unequal recombination within the human growth hormone (GH) gene cluster that cause GH1 gene deletions and isolated GH deficiency type 1A were localized in nine patients. In eight unrelated subjects homozygous for 6.7-kilobase (kb) deletions, the breakpoints are within two blocks of highly homologous DNA sequences that lie 5' and 3' to the GH1 gene. In seven of these eight cases, the breakpoints map within a 1,250-base-pair (bp) region composed of 300-bp Alu sequences of 86% homology and flanking non-Alu sequences that are 600 and 300 bp in length and are of 96% and 88% homology, respectively. In the eighth patient, the breakpoints are 5' to these Alu repeats and are most likely within a 700-bp-region of 96% homologous DNA sequences. In the ninth patient homozygous for a 7.6-kb deletion, the breakpoints are contained with a 29-bp perfect repeat lying 5' to GH1 and the human chorionic somatomammotropin pseudogene (CSHP1). Together, these results indicate that the presence of highly homologous DNA sequences flanking GH1 predispose to recurrent unequal recombinational events presumably through chromosomal misalignment

  13. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.

    Science.gov (United States)

    Poulter, James A; Murillo, Gina; Brookes, Steven J; Smith, Claire E L; Parry, David A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-10-15

    Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid.

  14. Novel features of 3q29 deletion syndrome: Results from the 3q29 registry

    OpenAIRE

    Glassford, Megan R.; Jill A. Rosenfeld; Freedman, Alexa A.; Michael E Zwick; ,; Mulle, Jennifer G.

    2016-01-01

    3q29 deletion syndrome is caused by a recurrent, typically de novo heterozygous 1.6 Mb deletion, but because incidence of the deletion is rare (1 in 30,000 births) the phenotype is not well described. To characterize the range of phenotypic manifestations associated with 3q29 deletion syndrome, we have developed an online registry (3q29deletion.org) for ascertainment of study subjects and phenotypic data collection via Internet‐based survey instruments. We report here on data collected during...

  15. In vitro deletions in the partition locus of plasmid pSC101.

    OpenAIRE

    Kalla, S R; Gustafsson, P

    1984-01-01

    Deletion mutants in the 375-base-pair EcoRI-AvaI fragment carrying the partition locus of plasmid pSC101 were formed by the combined action of exonuclease III and nuclease S1. Six deletion mutants were isolated, and the endpoints of the deletions were sequenced. One of the deletions extended 69 base pairs from the EcoRI site without impairing plasmid stability. The other five deletions caused the plasmid to be unstable and extended 199 to 251 base pairs from the EcoRI site.

  16. Interstitial deletion 5p accompanied by dicentric ring formation of the deleted segment resulting in trisomy 5p13-cen

    Energy Technology Data Exchange (ETDEWEB)

    Schuffenhauer, S.; Daumer-Haas, C.; Murken, J. [Ludwig-Maximilians-Universitaet Muenchen (Germany)] [and others

    1996-10-02

    Karyotypes with an interstitial deletion and a marker chromosome formed from the deleted segment are rare. We identified such a rearrangement in a newborn infant, who presented with macrocephaly, asymmetric square skull, minor facial anomalies, omphalocele, inguinal hernias, hypospadias, and club feet. The karyotype 46,XY,del(5)(pter{r_arrow}p13::cen{r_arrow}qter)/47,XY,+dicr(5)(:p13{r_arrow}cen::p13{r_arrow}cen),del(5)(pter{r_arrow}p13::cen{r_arrow}qter) was identified by banding studies and FISH analysis in the peripheral lymphocytes. One breakpoint on the del(5) maps distal to GDNF, and FISH analysis using an {alpha}-satellite probe suggests that the proximal breakpoint maps within the centromere. The dicentric r(5) consists of two copies of the segment deleted in the del(5), resulting in trisomy of proximal 5p (5p13-cen). The phenotype of the propositus is compared with other trisomy 5p cases and possible mechanisms for the generation of this unique chromosomal rearrangement are discussed. 27 refs., 3 figs.

  17. Characterization of genetic deletions in Becker muscular dystrophy using monoclonal antibodies against a deletion-prone region of dystrophin

    Energy Technology Data Exchange (ETDEWEB)

    Thanh, L.T.; Man, Nguyen Thi; Morris, G.E. [Wales Institute, Clwyd (United Kingdom)] [and others

    1995-08-28

    We have produced a new panel of 20 monoclonal antibodies (mAbs) against a region of the dystrophin protein corresponding to a deletion-prone region of the Duchenne muscular dystrophy gene (exons 45-50). We show that immunohistochemistry or Western blotting with these {open_quotes}exon-specific{close_quotes} mAbs can provide a valuable addition to Southern blotting or PCR methods for the accurate identification of genetic deletions in Becker muscular dystrophy patients. The antibodies were mapped to the following exons: exon 45 (2 mAbs), exon 46 (6), exon 47 (1), exons 47/48 (4), exons 48-50 (6), and exon 50 (1). PCR amplification of single exons or groups of exons was used both to produce specific dystrophin immunogens and to map the mAbs obtained. PCR-mediated mutagenesis was also used to identify regions of dystrophin important for mAb binding. Because the mAbs can be used to characterize the dystrophin produced by individual muscle fibres, they will also be useful for studying {open_quotes}revertant{close_quotes} fibres in Duchenne muscle and for monitoring the results of myoblast therapy trials in MD patients with deletions in this region of the dystrophin gene. 27 refs., 7 figs., 3 tabs.

  18. Deletion breakpoint mapping on chromosome 9p21 in breast cancer cell line MCF-7

    Directory of Open Access Journals (Sweden)

    Hua-ping XIE

    2012-05-01

    Full Text Available Objective  To map the deletion breakpoint of chromosome 9p21 in breast cancer cell line MCF-7. Methods  The deletion of chromosome 9p21 was checked by Multiplex Ligation-dependent Probe Amplification (MLPA in MCF-7. Subsequently, the deletion breakpoint was amplified by long range PCR and the deletion region was narrowed by primer walking. Finally, the deletion position was confirmed by sequencing. Results  The deletion was found starting within the MTAP gene and ending within CDKN2A gene by MLPA. Based on long range PCR and primer walking, the deletion was confirmed to cover the region from chr9:21819532 to chr9:21989622 by sequencing, with a deletion size of 170kb, starting within the intron 4 of MTAP and ending within the intron 1 near exon 1β of CDKN2A. Conclusions  Long range PCR is an efficient way to detect deletion breakpoints. In MCF-7, the deletion has been confirmed to be 170kb, starting within the MTAP gene and ending within the CDKN2A gene. The significance of the deletion warrants further research.

  19. DNA-based detection of chromosome deletion and amplification: diagnostic and mechanistic significance

    International Nuclear Information System (INIS)

    This paper describes a few of the many possible examples in which application of a molecular cytogenetic approach can ultimately lead to a new, important understanding about the statics and dynamics of human chromosome structure. In the case of retinoblastoma, cytological observations of deletions and linkage analysis have positioned the retinoblastoma locus to bank 13q14. This locus is grossly deleted in some spontaneous tumors. It is still necessary to locate more precisely and characterize the nature of the retinoblastoma locus, as well as the basis for the heterogeneity in deletions removing one copy of this locus. One is left with the possibility that those deletions that may be observed cytologically reflect but the tip of the iceberg of deletions; detection of others may require molecular probes. A related question is the nature of the DNA sequences at the deletion boundaries and the role they play in promoting these deletions

  20. Deletion of chromosomal region 13q14.3 in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Cavé, H; Avet-Loiseau, H; Devaux, I; Rondeau, G; Boutard, P; Lebrun, E; Méchinaud, F; Vilmer, E; Grandchamp, B

    2001-03-01

    Deletion of the 13q14 chromosomal region is frequent in B cell chronic lymphocytic leukemia (B-CLL) and is believed to inactivate a tumor supressor gene (TSG) next to RB1. We studied microsatellite markers spanning the 13q14 chromosomal region in 138 children with acute lymphoblastic leukemia (ALL). Allelic loss was demonstrated in six cases (4.3%). Deletion did not include RB1 in two cases. In five patients, the deleted region overlapped that described in B-CLL. A sixth patient harbored a smaller deletion, slightly more telomeric than minimal deleted regions reported in B-CLL. Apparent differences in the delineation of the minimal deleted region could be due to the fact that the putative TSG is a very large gene, with some deletions affecting only a part of it. Our present findings suggest that at least some of its exons lie within a region of less than 100 kb more telomeric that previously thought.

  1. Molecular cytogenetic detection of chromosome 15 deletions in patients with Prader-Willi and Angelman syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Chadwick, D.E.; Weksberg, R.; Shuman, C. [Hospital for Sick Children, Toronto (Canada)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct genetic disorders involving alterations of chromosome 15q11-q13. Approximately 75% of individuals with PWS and AS have deletions within 15q11-q13 by molecular analysis. We have evaluated fluorescence in situ hybridization (FISH) for the clinical laboratory detection of del(15)(q11q13) using the cosmid probes D15S11 and GABRB3 (ONCOR, Gaithersburg, NY). 4/4 PWS and 1/1 AS patients previously identified as having cytogenetic deletions were deleted for both probes. In a prospectively ascertained series of 54 patient samples referred to rule out either PWS or AS, 8 were deleted for D15S11 and GABRB3. In addition, an atypical deletion patient with PWS was also identified who was found to be deleted for GABRB3 but not D15S11. The SNRPN locus was also deleted in this patient. Only 4 of the 9 patient samples having molecular cytogenetic deletions were clearly deleted by high resolution banding (HRB) analysis. The microscopic and submicroscopic deletions have been confirmed by dinucleotide (CA) repeat analysis. Microsatellite polymorphism analysis was also used to demonstrate that five non-deletion patients in this series had biparental inheritance of chromosome 15, including region q11-q13. Deletions were not detected by either HRB, FISH or microsatellite polymorphism analysis in samples obtained from parents of the deletion patients. Methylation studies of chromosome 15q11-q13 are in progress for this series of PWS and AS families. FISH analysis of chromosome 15q11-q13 in patients with PWS and AS is a rapid, sensitive and reliable method for deletion detection.

  2. Deletion involving D15S113 in a mother and son without Angelman syndrome: Refinement of the Angelman syndrome critical deletion region

    Energy Technology Data Exchange (ETDEWEB)

    Michaelis, R.C.; Skinner, S.A.; Lethco, B.A. [Greenwood Genetic Center, SC (United States)] [and others

    1995-01-02

    Deletions of 15q11-q13 typically result in Angelman syndrome when inherited from the mother and Prader-Willi syndrome when inherited from the father. The critical deletion region for Angelman syndrome has recently been restricted by a report of an Angelman syndrome patient with a deletion spanning less than 200 kb around the D15S113 locus. We report here on a mother and son with a deletion of chromosome 15 that includes the D15S113 locus. The son has mild to moderate mental retardation and minor anomalies, while the mother has a borderline intellectual deficit and slightly downslanting palpebral fissures. Neither patient has the seizures, excessive laughter and hand clapping, ataxia or the facial anomalies which are characteristic of Angelman syndrome. The proximal boundary of the deletion in our patients lies between the D15S10 and The D15S113 loci. Our patients do not have Angelman syndrome, despite the deletion of the D15S113 marker. This suggests that the Angelman syndrome critical deletion region is now defined as the overlap between the deletion found in the previously reported Angelman syndrome patient and the region that is intact in our patients. 28 refs., 6 figs.

  3. 5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

    Science.gov (United States)

    Ilari, Rita; Agosta, Guillermo; Bacino, Carlos

    2016-03-01

    We report the case of a young girl who was presented with complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin disorder and vascular malformations involving central nervous system is consistent with a RASopathy. The child's neurological manifestations are observed in most patients suffering from 5q14.3 by deletion or mutation of the MEF2C gene. A review of the literature allowed us to conclude that the contiguous deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the penetrance of RASA1 and clinical manifestations of MEF2C according to the type of deletion. This child described presents the complete symptomatology of both deleted genes. We would also like to highlight the progression of the disorder.

  4. Radial aplasia and chromosome 22q11 deletion.

    Science.gov (United States)

    Digilio, M C; Giannotti, A; Marino, B; Guadagni, A M; Orzalesi, M; Dallapiccola, B

    1997-01-01

    We report on a neonate with deletion 22q11 (del22q11) presenting with facial dysmorphism, ocular coloboma, congenital heart defect, urogenital malformations, and unilateral radial aplasia. This malformation complex includes features frequently occurring in velocardiofacial syndrome as well as findings described in the CHARGE and VACTERL associations. To our knowledge, the present case is the first report of radial aplasia in del22q11. This observation further supports and extends the clinical variability of del22q11. Images PMID:9391893

  5. Targeted deletions of cyclooxygenase-2 and atherogenesis in mice

    DEFF Research Database (Denmark)

    Hui, Yiqun; Ricciotti, Emanuela; Crichton, Irene;

    2010-01-01

    -2 in macrophages and T cells (TCs) to atherogenesis. METHODS AND RESULTS: Deletion of macrophage-COX-2 (Mac-COX-2KOs) was attained with LysMCre mice and completely suppressed lipopolysaccharide-stimulated macrophage prostaglandin (PG) formation and lipopolysaccharide-evoked systemic PG biosynthesis...... by approximately 30%. Lipopolysaccharide-stimulated COX-2 expression was suppressed in polymorphonuclear leukocytes isolated from MacKOs, but PG formation was not even detected in polymorphonuclear leukocyte supernatants from control mice. Atherogenesis was attenuated when MacKOs were crossed into hyperlipidemic...

  6. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Martinelli, Diego [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Dionisi-Vici, Carlo [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Nobili, Valerio [Gastroenterology and Liver Unit, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Francalanci, Paola; Boldrini, Renata; Callea, Francesco [Dept. Pathology, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Santorelli, Filippo Maria [UOC Neurogenetica e Malattie Neuromuscolari, Fondazione Stella Maris, Pisa (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); and others

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  7. Geometric figure-ground cues override standard depth from accretion-deletion.

    Science.gov (United States)

    Tanrikulu, Ömer Daglar; Froyen, Vicky; Feldman, Jacob; Singh, Manish

    2016-01-01

    Accretion-deletion is widely considered a decisive cue to surface depth ordering, with the accreting or deleting surface interpreted as behind an adjoining surface. However, Froyen, Feldman, and Singh (2013) have shown that when accretion-deletion occurs on both sides of a contour, accreting-deleting regions can also be perceived as in front and as self-occluding due to rotation in three dimensions. In this study we ask whether geometric figure-ground cues can override the traditional "depth from accretion-deletion" interpretation even when accretion-deletion takes place only on one side of a contour. We used two tasks: a relative-depth task (front/back), and a motion-classification task (translation/rotation). We conducted two experiments, in which texture in only one set of alternating regions was moving; the other set was static. Contrary to the traditional interpretation of accretion-deletion, the moving convex and symmetric regions were perceived as figural and rotating in three dimensions in roughly half of the trials. In the second experiment, giving different motion directions to the moving regions (thereby weakening motion-based grouping) further weakened the traditional accretion-deletion interpretation. Our results show that the standard "depth from accretion-deletion" interpretation is overridden by static geometric cues to figure-ground. Overall, the results demonstrate a rich interaction between accretion-deletion, figure-ground, and structure from motion that is not captured by existing models of depth from motion.

  8. Evidence that cyclophosphamide can to induce exchanges in the sister chromatids (ICH) through secondary injuries; Evidencia de que la ciclofosfamida puede inducir intercambios en las cromatidas hermanas (ICH) a traves de lesiones secundarias

    Energy Technology Data Exchange (ETDEWEB)

    Morales R, P.; Rodriguez R, R. [Instituto Nacional de Investigaciones nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    By means of the use of destination protocol of ICH inductive injuries (DLI-ICH), it was studied if interchanges in the sister chromatids (ICH) induced by cyclophosphamide (CP), in the second post-treatment division (ICH-2) are produced by secondary injuries or by fresh injuries. For discard between these possibilities it was administered CP at different periods before of the first post-treatment division, taking as reference the administered time for high dose of bromodeoxyuridine (BrdU ) which was approximately at the beginning of this division. The ICH frequencies that occur in the first, the second and the third synthesis stages (S) were determined. It was observed that when the administered CP was four hours before BrdU , the ICH frequencies of the second and the third S were reduced. The frequency of the first ICH increased lightly in relation to those of the normal protocol (0.5 h before BrdU ) and that the supplying of CP six hours before caused almost a total reduction of ICH of second and third S and an important increment of ICH of first S.This was interpreted as evidence that the ICH-2 are product of secondary injuries. (Author)

  9. Angelman syndrome: Validation of molecular cytogenetic analysis of chromosome 15q11-q13 for deletion detection

    Energy Technology Data Exchange (ETDEWEB)

    White, L.; Knoll, J.H.M. [Harvard Medical School, Boston, MA (United States)

    1995-03-13

    In a series of 18 individuals comprising parents of Angelman syndrome (AS) patients and AS patients with large deletions, microdeletions, and no deletions, we utilized fluorescence in situ hybridization (FISH) with genomic phage clones for loci D15S63 and GABRB3 for deletion detection of chromosome 15q11-q13. Utilization of probes at these loci allows detection of common large deletions and permits discrimination of less common small deletions. In all individuals the molecular cytogenetic data were concordant with the DNA deletion analyses. FISH provides an accurate method of deletion detection for chromosome 15q11-q13. 23 refs., 2 figs., 1 tab.

  10. Dystrophin in frameshift deletion patients with Becker Muscular Dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Gangopadhyay, S.B.; Ray, P.N.; Worton, R.G.; Sherratt, T.G.; Heckmatt, J.Z.; Dubowitz, V.; Strong, P.N.; Miller, G. (Penn State College of Medicine, Hershey, PA (United States)); Shokeir, M. (Univ. Hospital, Saskatchewan (Canada))

    1992-09-01

    In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases they detected slightly lower-molecular-weight dystrophin in 12%-15% abundance relative to the normal. By sequencing amplified mRNA they have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternate splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. 34 refs., 5 figs. 1 tab.

  11. Mucopolysaccharidosis type IVA: Common double deletion in the N-Acetylgalactosamine-6-sulfatase gene (GALNS)

    Energy Technology Data Exchange (ETDEWEB)

    Hori, Toshinori; Tomatsu, Shunji; Fukuda, Seiji [Gifu Univ. School of Medicine, Gifu (Japan)] [and others

    1995-04-10

    Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency in N-acetylgalactosamine-6-sulfatase (GALNS). We found two separate deletions of nearly 8.0 and 6.0 kb in the GALNS gene, including some exons. There are Alu repetitive elements near the breakpoints of the 8.0-kb deletion, and this deletion resulted from an Alu-Alu recombination. The other 6.0-kb deletion involved illegitimate recombinational events between incomplete short direct repeats of 8 bp at deletion breakpoints. The same rearrangement has been observed in a heteroallelic state in four unrelated patients. This is the first documentation of a common double deletion a gene that is not a member of a gene cluster. 39 refs., 5 figs.

  12. STUDY OF DELETION OF P16 GENE IN THE PROGRESSION OF BRAIN ASTROCYTOMAS

    Institute of Scientific and Technical Information of China (English)

    Zhai Guang; Yuan Xianhou

    1998-01-01

    Objective:To study the relationship between deletion of P16 gene and occurrence and progression of astrocytomas. Methods: The techniques of polymerase chain reaction (PCR) and immunohistochemistry were used to detect the deletion of exon2 of P16 gene and expression of P16 gene in 52 cases of Brain astrocytoma.Results: The deletion rate of exon2 of P16 gene in the tumors analyzed was 34.6%. Most of them with deletion of exon2 of p16 gene were high grade astrocytomas (grade Ⅲ 42%, grade Ⅳ 50%). 61.5% of the tumors were absent from expression of p16 and the deletion rate of p16 protein increased with the grade of astrocytoma (X2=10.83, P<0.005). Conclusion: Deletion of p16 gene and protein may correlate with the malignant progression of astrocytoma.

  13. Deletion mapping indicates that MTS1 is the target of frequent deletions at chromosome 9p21 in paediatric acute lymphoblastic leukaemias.

    Science.gov (United States)

    Guidal-Giroux, C; Gérard, B; Cavé, H; Duval, M; Rohrlich, P; Elion, J; Vilmer, E; Grandchamp, B

    1996-02-01

    Recent reports have indicated a high frequency of deletions of MTS1 (CDKN2, p16ink4, CDKI4) in acute lymphoblastic leukaemias (ALLs). This gene is located at chromosome 9p21 and encodes an inhibitor of cyclin D-dependent kinases. In contrast with the observations in some other malignancies, no inactivation of MTS1 by intragenic mutation was demonstrated in leukaemias. A contribution of MTS1 alterations to leukaemogenesis therefore remains questionable. In order to test for the implication of MTS1 as a tumour suppressor gene in paediatric ALLs we have explored the 9p21 chromosomal region of 46 children with this disease. The copy number of the MTS1 gene in blasts from the patients was determined using a quantitative PCR assay enabling us to precisely detect mono- and bi-allelic deletions. Rearrangements of the gene were sought by Southern blot analysis. The extent of the deletions was studied using microsatellite markers spanning the 9p21 chromosomal region. Point mutations were sought in exon 1 and exon 2 of the MTS1 gene in patients with a mono-allelic deletion in addition, exon 2 of MTS1, which contains two-thirds of the coding region, was sequenced in all patients who had no deletion of the gene. Altogether, our data are consistent with the view that MTS1 is the target of 9p21 deletions. Either one or two alleles of the gene were deleted in 36% of non-selected children with B-lineage ALL and both alleles were deleted in all seven patients we studied with T-lineage ALL. The absence of any point mutation implies that the major mechanism of inactivation of MTS1 in ALLs is deletional.

  14. A Chinese familial growth hormone deficiency with a deletion of 7.1 kb of DNA.

    OpenAIRE

    He, Y A; Chen, S S; Wang, Y. X; Lin, X. Y.; D. F. Wang

    1990-01-01

    Using restriction endonuclease analysis and a human growth hormone cDNA probe, we have found a Chinese family with a human growth hormone gene deletion. Two affected sibs are homozygous for a deletion of approximately 7.1 kb of DNA, which contains the normal human growth hormone gene. The patients' parents and grandmothers are heterozygous for the deleted gene. Their grandfathers are normal and homozygous for the hGH-N gene. All of them have normal stature.

  15. The rates and patterns of deletions in the human factor IX gene

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.L.; Lind, T.J.; Thorland, E.C.; Sommer S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    1994-02-01

    Deletions are commonly observed in genes with either segments of highly homologous sequences or excessive gene length. However, in the factor IX gene and in most genes, deletions (of [ge]21 bp) are uncommon. The authors have analyzed DNA from 290 families with hemophilia B (203 independent mutations) and have found 12 deletions >20 bp. Eleven of these are >2 kb (range >3-163 kb), and one is 1.1 kb. The junctions of the four deletions that are completely contained within the factor IX gene have been determined. A novel mutation occurred in patient HB128: the data suggest that a 26.8-kb deletion occurred between two segments of alternating purines and pyrimidines and that a 2.3-kb sense strand segment derived from the deleted region was inserted. For a sample of 203 independent mutations, the authors estimate the [open quotes]baseline[close quotes] rates of deletional mutation per base pair per generation as a function of size. The rate for large (>2 kb)I deletions is exceedingly low. For every mutational event in which a given base is at the junction of a large deletion, there are an estimated 58 microdeletions (<20 bp) and 985 single-base substitutions at that base. Analysis of the nine reported deletion junctions in the factor IX gene literature reveals that (i) five are associated with inversion, orphan sequences, or sense strand insertions; (ii) four are simple deletions that display an excess of short direct repeats at their junctions; (iii) there is no dramatic clustering of junctions within the gene; and (iv) with the exception of alternating purines and pyrimidines, deletion junctions are not preferentially associated with repetitive DNA. 58 refs., 5 figs., 5 tabs.

  16. Frequency of the mtDNA 9-bp deletion in Chinese ethnic groups

    Institute of Scientific and Technical Information of China (English)

    姚永刚; 袁志刚; 周曾娣; 耿排力; 李庆伟; 张亚平

    2001-01-01

    The 9-bp deletion in the COIl/tRNALys intergenic region (region V) of human mitochondrial DNA was screened in 1521 Chinese from 16 ethnic groups and 9 Han geographic groups. The highest frequency was found in populations of Miao (32.4%) and Bouyei (30.8%) from Guizhou Province, whereas no deletion was found in Kazak population in Xinjiang. In the populations of Wa and Lahu from Yunnan Province, Uygur and Mongolian from Xinjiang,the deletion frequency was relatively low ( ≤ 4 % ), while in the remaining 18 groups, the frequency was moderate (6 % ~ 24% ). Except those Hans in Xinjiang, Guizhou and that reported in Taiwan, the deletion frequency in the Han geo graphic groups did not show a substantial difference. However, the deletion frequency in some ethnic groups from the same geographic region or with similar ethnohistory did not show similarity. A general decrease tendency in the deletion frequency was found from south to north and from coastal to inland. The frequency of the 9-bp deletion was approximate ly 17.20% in all Chinese we studied and reported elsewhere. Additionally, 4 individuals were found to carry the tripli cation of 9-bp segment in region V; one individual had X. II type of 9-bp deletion; and no other length polymorphisms were detected in this region in 27 randomly selected individuals with or without the deletion.

  17. Induction of Mitochondrial DNA Deletion by Ionizing Radiation in Human Lung Fibroblast IMR-90 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-06-15

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with {sup 137}Cs -rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and H{sub 2}O{sub 2}-treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and H{sub 2}O{sub 2}-treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells.

  18. One-dimensional Array Grammars and P Systems with Array Insertion and Deletion Rules

    Directory of Open Access Journals (Sweden)

    Rudolf Freund

    2013-09-01

    Full Text Available We consider the (one-dimensional array counterpart of contextual as well as insertion and deletion string grammars and consider the operations of array insertion and deletion in array grammars. First we show that the emptiness problem for P systems with (one-dimensional insertion rules is undecidable. Then we show computational completeness of P systems using (one-dimensional array insertion and deletion rules even of norm one only. The main result of the paper exhibits computational completeness of one-dimensional array grammars using array insertion and deletion rules of norm at most two.

  19. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, H.B.; Timm, S.; Wang, A.G.;

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  20. Cognitive and structural neuroimaging characteristics of schizophrenia patients with large, rare copy number deletions.

    Science.gov (United States)

    Kenneth Martin, Andrew; Robinson, Gail; Reutens, David; Mowry, Bryan

    2014-12-30

    Large (>500 Kb), rare (frequency <1%) deletions are associated with risk for schizophrenia. The aim of the study was to characterise patients with these deletions using measures of cognition, grey-matter volume and white-matter integrity. Patients with schizophrenia and large, rare deletions (SZ-del) (n=17) were assessed on a test of intelligence, the Wechsler Abbreviated Scale of Intelligence (WASI), and compared with age- and sex-matched schizophrenia patients without large, rare deletions (SZ-nodel) (n=65), and healthy controls (HCs) (n=50). Regional grey-matter differences were investigated using voxel-based morphometry (SZ-del=9; SZ-nodel=26; HC=19). White-matter integrity was assessed using fractional anisotropy (SZ-del=9; SZ-nodel=24; HC=15). Compared with schizophrenia patients without large, rare deletions, those with large, rare deletions had lower IQ; greater grey-matter volume in clusters with peaks in the left and right cerebellum, left hippocampus, and right rectal gyrus; and increased white-matter anisotropy in the body and genu of the corpus callosum. Compared with healthy controls, patients with large, rare deletions had reduced grey matter volume in the right calcarine gyrus. In sum, patients with large, rare deletions had structural profiles intermediate to those observed in healthy controls and schizophrenia patients without large, rare deletions, but had greater impairment in intelligence. PMID:25453991

  1. Effect of aquaporin-q deletion on pleural fluid transport

    Institute of Scientific and Technical Information of China (English)

    JIANGJin-Jun; HONGQun-Ying; 等

    2003-01-01

    AIM:To investigate the role of aquaporin-1(AQP1)and sodium channel on pleural fluid transport.METHODS:Wild-type and AQP1 null mice were used in this study.After the mice were briefly anesthetized,0.25mL of hyperosmolar or isosmolar solution(containing terbutaline,amiloride or saline only)was infused into the pleural space.Then mice were sacrificed at scheduled times for measurement of pleural fluid osmolality or volume,RESULTS:After instillation of hyperosmolar fluid into the pleural space,the osmolality of pleural fluid in wild-type mice was higher than that in AQP1 null mice killed at the same time(1,2,5min).There was no difference in the isosmolar clearance between the wild-type and AQP1 null mice after injection of 0.25mL isosmolar fluid into the pleural space.Terbutaline increased the osmotic and isosmolar fluid transport across pleura,but these effects were not influenced by AQP1 dfeletion.In contrast,amiloride reduced osmotic and isosmolar pleural fluid transport and these effects were not influenced by AQP1 deletion.CONCLUSION;AQP1 water channels facilitated osmotic fluid transport across the pleural surface,However,AQP1 did not play an important role in pleural isosmolar fluid clearance.Sodium channel may play a role in osmotic and isosmolar pleural fluid transport.The effects of sodium channel on fluid transport across pleural space were not influenced by aquaporin-1 deletion.

  2. Deletion of 7q33-q35 in a Patient with Intellectual Disability and Dysmorphic Features: Further Characterization of 7q Interstitial Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Kristen Dilzell

    2015-01-01

    Full Text Available This case report concerns a 16-year-old girl with a 9.92 Mb, heterozygous interstitial chromosome deletion at 7q33-q35, identified using array comparative genomic hybridization. The patient has dysmorphic facial features, intellectual disability, recurrent infections, self-injurious behavior, obesity, and recent onset of hemihypertrophy. This patient has overlapping features with previously reported individuals who have similar deletions spanning the 7q32-q36 region. It has been difficult to describe an interstitial 7q deletion syndrome due to variations in the sizes and regions in the few patients reported in the literature. This case contributes to the further characterization of an interstitial distal 7q deletion syndrome.

  3. Third case of 8q23.3-q24.13 deletion in a patient with Langer-Giedion syndrome phenotype without TRPS1 gene deletion.

    Science.gov (United States)

    Pereza, Nina; Severinski, Srećko; Ostojić, Saša; Volk, Marija; Maver, Aleš; Dekanić, Kristina Baraba; Kapović, Miljenko; Peterlin, Borut

    2012-03-01

    Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases.

  4. Third case of 8q23.3-q24.13 deletion in a patient with Langer-Giedion syndrome phenotype without TRPS1 gene deletion.

    Science.gov (United States)

    Pereza, Nina; Severinski, Srećko; Ostojić, Saša; Volk, Marija; Maver, Aleš; Dekanić, Kristina Baraba; Kapović, Miljenko; Peterlin, Borut

    2012-03-01

    Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases. PMID:22315192

  5. Increased mitochondrial DNA deletions in substantia nigra dopamine neurons of the aged rat.

    Science.gov (United States)

    Parkinson, Gemma M; Dayas, Christopher V; Smith, Doug W

    2014-01-01

    The dopaminergic neurons of the substantia nigra (SN), which constitute the origin of the nigrostriatal system, are vulnerable to age-related degenerative processes. For example, in humans there is a relatively small age-related loss of neurons but a marked decline of the dopaminergic phenotype associated with impaired voluntary motor control. However, the mechanisms responsible for the dysfunction and degeneration of SN dopamine neurons remain poorly understood. One potential contributor is mitochondrial dysfunction, resulting from an increased abundance of mitochondrial DNA (mtDNA) mutations such as deletions. Human studies have identified relatively high levels of mtDNA deletions in these cells in both aging and Parkinson's disease (>35%), with a higher abundance of deletions (>60%) in individual neurons with mitochondrial dysfunction. However, it is unknown whether similar mtDNA mutations occur in other species such as the rat. In the present study, we quantified mtDNA deletion abundance in laser microdissected SN dopaminergic neurons from young and old F344 rats. Our results indicate that mtDNA deletions accumulated with age, with approximately 20% more mtDNA deletions in SN dopaminergic neurons from old compared to young animals. Thus, while rat SN dopaminergic neurons do accumulate mtDNA deletions with aging, this does not reflect the deletion burden in humans, and other mechanisms may be operating to compensate for age-related mtDNA damage in the rat SN dopaminergic neurons. PMID:25612740

  6. Deletion in sigB in Bacillus cereus affects spore properties

    NARCIS (Netherlands)

    Vries, de Y.P.; Hornstra, L.M.; Atmadja, R.D.; Schaik, van W.; Vos, de W.M.; Abee, T.

    2005-01-01

    In Bacillus cereus and other gram-positive bacteria the alternative sigma factor ¿B is an important regulator of the stress response. Deletion of the sigB gene generally leads to a stress-sensitive phenotype of vegetative cells. In this study, we describe the effect of the deletion of the sigB gene

  7. Multiple Patterns of FHIT Gene Homozygous Deletion in Egyptian Breast Cancer Patients

    International Nuclear Information System (INIS)

    Fragile histidine triad (FHIT) gene encodes a putative tumour suppressor protein. Loss of Fhit protein in cancer is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in at least one FHIT exon. The incidence of homozygous deletion was not associated with patients clinico pathological parameters including patients age, tumour grade, tumour type, and lymph node involvement. Using correlation analysis, we have observed a strong correlation between homozygous deletions of exon 3 and exon 4 (P<0.0001). Deletions in exon 5 were positively correlated with deletions in exon 7 (P<0.0001), Exon 8 (P<0.027), and exon 9 (P=0.04). Additionally, a strong correlation was observed between exons 8 and exon 9 (P<0.0001).We conclude that FHIT gene exons are homozygously deleted at high frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene genomic structure.

  8. 10 CFR 9.19 - Segregation of exempt information and deletion of identifying details.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Segregation of exempt information and deletion of identifying details. 9.19 Section 9.19 Energy NUCLEAR REGULATORY COMMISSION PUBLIC RECORDS Freedom of Information Act Regulations § 9.19 Segregation of exempt information and deletion of identifying details....

  9. A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW)).

    NARCIS (Netherlands)

    Phylipsen, M.; Vogelaar, I.P.; Schaap, R.A.; Arkesteijn, S.G.; Boxma, G.L.; Helden, W.C. van; Wildschut, I.C.; Bruin-Roest, A.C. de; Giordano, P.C.; Harteveld, C.L.

    2010-01-01

    Alpha-thalassemia is an inherited hemoglobin disorder characterized by a microcytic hypochromic anemia caused by a quantitative reduction of the alpha-globin chain. The majority of the alpha-thalassemias is caused by deletions in the alpha-globin gene cluster. A deletion in the alpha-globin gene clu

  10. Rapid deletion plasmid construction methods for protoplast and Agrobacterium based fungal transformation systems

    Science.gov (United States)

    Increasing availability of genomic data and sophistication of analytical methodology in fungi has elevated the need for functional genomics tools in these organisms. Gene deletion is a critical tool for functional analysis. The targeted deletion of genes requires both a suitable method for the trans...

  11. Detection of Homozygous Deletions and Mutations in the CDKN2A Gene in Hydatidiform Moles

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Shuying Wu; Ying Gu; Yan Zhu; Xiaowei Zhang

    2008-01-01

    OBJECTIVE To investigate homozygous deletions and mutations in the CDKN2A gene (p16INK4a and p14ARF gene) in hydatidiform moles.METHODS A total of 38 hydatidiform mole samples and 30 villi samples were examined for homozygous deletions in the CDKN2A gene by PCR and for mutations by DHPLC.RESULTS I) Among 38 hydatidiform mole samples,homozygous deletions in the p16INK4a exon 1 were identified in 5 cases (13.2%), while no homozygous deletions were found in the p16INK4a exon 1 of 30 early-pregnancy samples. The rates of those deletions in hydatidiform compared to early-pregnancy villi samples was statistically significant (P = 0.036). Ii) No homozygous deletions in the p14ARF exon 1 or p16INK4a exon 2 were found in any of the hydatidiform moles or early-preganancy samples, iii)In all hydatidiform moles and early-pregnancy villi samples, no mutations were detected by DHPLC.CONCLUSION We suggest there may be a close correlation between homozygous deletions in the CDKN2A gene and occurrence of hydatidiform moles variation in the CDKN2A gene is mainly caused by homozygous deletions, while mutations may be not a major cause.

  12. The smt-0 mutation which abolishes mating-type switching in fission yeast is a deletion

    DEFF Research Database (Denmark)

    Styrkársdóttir, U; Egel, R; Nielsen, O;

    1993-01-01

    Mating-type switching in the fission yeast, S. pombe, is initiated by a DNA double-strand break (DSB) between the mat1 cassette and the H1 homology box. The mat1-cis-acting mutant, smt-0, abolishes mating-type switching and is shown here to be a 263-bp deletion. This deletion starts in the middle...

  13. L1CAM whole gene deletion in a child with L1 syndrome.

    Science.gov (United States)

    Chidsey, Brandalyn A; Baldwin, Erin E; Toydemir, Reha; Ahles, Lauren; Hanson, Heather; Stevenson, David A

    2014-06-01

    L1 syndrome is a group of overlapping, X-linked disorders caused by mutations in L1CAM. Clinical phenotypes within L1 syndrome include X-linked hydrocephalus with stenosis of the aqueduct of sylvius (HSAS); mental retardation, adducted thumbs, shuffling gait, and aphasia (MASA) syndrome; spastic paraplegia type 1; and agenesis of the corpus callosum. Over 200 mutations in L1CAM have been reported; however, only a few large gene deletions have been observed. We report on a 4-month-old male with a de novo whole gene deletion of L1CAM presenting with congenital hydrocephalus, aqueductal stenosis, and adducted thumbs. Initial failure of L1CAM gene sequencing suggested the possibility of a whole gene deletion of L1CAM. Further investigation through chromosome microarray analysis showed a 62Kb deletion encompassing the first exon of the PDZD4 gene and the entire L1CAM gene. Investigations into genotype-phenotype correlations have suggested that mutations leading to truncated or absent L1 protein cause more severe forms of L1 syndrome. Based on the presentation of the proband and other reported patients with whole gene deletions, we provide further evidence that L1CAM whole gene deletions result in L1 syndrome with a severe phenotype, deletions of PDZD4 do not cause additional manifestations, and that X-linked nephrogenic diabetes insipidus reported in a subset of patients with large L1CAM deletions results from the loss of AVPR2. PMID:24668863

  14. How To Recover Delete photos from iPhone 5/4S/4

    OpenAIRE

    James, MR

    2015-01-01

    Lost photos from iPhone can be recovered with the iPhone photo recovery, which provides three ways to recover deleted photos from iPhone recover photos from iphone directly restore photos from iTunes backup recover photos from iCloud backup http://www.smart-iphone-recovery.com/how-to-recover-deleted-photos-from-iphone.html

  15. Yod Deletion in Fiji English: Phonological Shibboleth or L2 English?

    Science.gov (United States)

    Tent, Jan

    2001-01-01

    Discusses one pronunciation feature shared by the vast majority of speakers of English in Fiji: the deletion of yod in non-primary stressed /Cju/ syllables. Considers variation in yod pronunciation according to ethnicity, age, gender, and education and examines whether yod deletion is a phonological shibboleth of Fiji English or merely a feature…

  16. A case of 3p deletion syndrome associated with cerebellar hemangioblastoma.

    Science.gov (United States)

    Suzuki-Muromoto, Sato; Hino-Fukuyo, Naomi; Haginoya, Kazuhiro; Kikuchi, Atsuo; Sato, Hiroki; Sato, Yuko; Nakayama, Tojo; Kubota, Yuki; Kakisaka, Yosuke; Uematsu, Mitsugu; Kumabe, Toshihiro; Md, Shigeo Kure

    2016-02-01

    We described clinical course of a 24-year-old woman with 3p deletion syndrome associated with cerebellar hemangioblastoma at the age of 16 years old. She presented dysmorphic facial features, growth retardation and severe psychomotor retardation associated with 3p deletion syndrome. We identified de novo 3p deletion encompassing p25 by using array-based comparative genomic hybridization, where causative gene of von Hippel-Lindau (VHL) disease located. Surgical therapy for cerebellar hemangioblastoma was performed, and histological examination was consistent in cerebellar hemangioblastoma. She showed no other tumors associated VHL disease till 24 years old. This is the first case report of a patient with 3p deletion syndrome whose cerebellar hemangioblastoma may be associated with VHL disease. Repeat imaging studies were recommended for the patients with 3p deletion syndrome. PMID:26365017

  17. Deletion Analysis Of The Duchenne/Becker Muscular Dystrophy Gene Using Multiplex Polymerase Chain Reaction

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    Dastur P

    2004-01-01

    Full Text Available The diagnosis of Duchenna Muscular Dystrophy (DMD and Becker Muscular Dystorphy (BMD is mainly based on clinical profile, serum CPK values, muscle biopsy and immunostaining for dystrophin. This was done in 100 unrelated patients using 19 exons including the promoter region in two sets of multiplex polymerase chain reaction (PCR. These primers amplify most of the exons in the deletion prone ′hot spot′ regions allowing determinations of deletion end points. Intragenic deletions were detected in 74 patients indicating that the use of PCR- based assays will allow deletion detection help in prenatal diagnosis for most of the DMD/BMD patients. The frequency of deletions observed in the present study was 74%.

  18. Relatively low proportion of dystrophin gene deletions in Israeili Duchenne and Becker muscular dystrophy patients

    Energy Technology Data Exchange (ETDEWEB)

    Shomrat, R.; Gluck, E.; Legum, C.; Shiloh, Y. [Tel Aviv Univ. (Israel)

    1994-02-15

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55-65%). Seventy-eight percent of the deletions were confined to exons 44-52, half of these exons 44-45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes. 43 refs., 1 fig., 1 tab.

  19. Analysis of dystrophin gene deletions by multiplex PCR in eastern India

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    Basak Jayasri

    2006-01-01

    Full Text Available The most common genetic neuromuscular disease of childhood, Duchenne and Becker muscular dystrophy (DMD/BMD is caused by deletion, duplication or point mutation of the dystrophin gene located at Xp 21.2. In the present study DNA from seventy unrelated patients clinically diagnosed as having DMD/BMD referred from different parts of West Bengal, a few other states and Bangladesh are analyzed using the multiplex polymerase chain reaction (m-PCR to screen for exon deletions and its distribution within the dystrophin gene. Out of seventy patients forty six (63% showed large intragenic deletion in the dystrophin gene. About 79% of these deletions are located in the hot spot region i.e., between exon 42 to 53. This is the first report of frequency and distribution of deletion in dystrophin gene in eastern Indian DMD/BMD population.

  20. Deletion Analysis Of The Duchenne/Becker Muscular Dystrophy Gene Using Multiplex Polymerase Chain Reaction

    Directory of Open Access Journals (Sweden)

    Dastur R

    2003-01-01

    Full Text Available The diagnosis of Duchenne Muscular Dystrophy (DMD and Becker Muscular Dystrophy (BMD is mainly based on clinical profile, serum CPK values, muscle biopsy and immunostaining for dystrophin. Most recent and accurate method for diagnosing DMD/BMD is by detection of mutations in the DMD gene. This was done in 100 unrelated patients using 19 exons including the promoter region in two sets of multiplex polymerase chain reaction (PCR. These primers amplify most of the exons in the deletion prone ′hotspot′ regions allowing determination of deletion end point. Intragenic deletions were detected in 74 patients indicating that the use of PCR-based assays will allow deletion detection help in prenatal diagnosis for most of the DMD/BMD patients. The frequency of deletions observed in the present study was 74%.

  1. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G;

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  2. Id2 deletion attenuates Apc-deficient ileal tumor formation

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    Kyoko Biyajima

    2015-08-01

    Full Text Available The expression level of inhibitor of DNA binding 2 (Id2 is increased in colorectal carcinomas and is positively correlated with poor prognosis. However, the functional significance of Id2 in intestinal tumorigenesis has not been fully defined using genetic approaches. Here, we show that Id2 promotes ileal tumor initiation in Apc-deficient mice. Expression of Id2 was stimulated by Wnt signaling through the enhancer region of the Id2 promoter at the early stage of tumorigenesis in Apc+/Δ716 (ApcΔ716 mice. Genetic depletion of Id2 in ApcΔ716 mice caused ∼80% reduction in the number of ileal polyps, but had little effect on tumor size. Notably, the lack of Id2 increased the number of apoptotic cells in the normal crypt epithelium of the mice. Furthermore, DNA microarray analysis revealed that the expression level of Max dimerization protein 1 (Mxd1, known as a c-Myc antagonist, was specifically increased by Id2 deletion in the ileal intestinal epithelium of ApcΔ716 mice. In contrast, the protein level of c-Myc, but not the mRNA level, was decreased by loss of Id2 in these mice. These results indicate that loss of Id2 inhibits tumor initiation by up-regulation of Mxd1 and down-regulation of c-Myc in ApcΔ716 mice.

  3. INDEPENDENT-SET-DELETABLE FACTOR-CRITICAL POWER GRAPHS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    It is said that a graph G is independent-set-deletable factor-critical (in short,ID-factor-critical), if, for every independent set I which has the same parity as |V(G)|,G - I has a perfect matching. A graph G is strongly IM-extendable, if for every spanning supergraph H of G, every induced matching of H is included in a perfect matching of H.The k-th power of G, denoted by Gk, is the graph with vertex set V(G) in which two vertices are adjacent if and only if they have distance at most k in G. ID-factor-criticality and IM-extendability of power graphs are discussed in this article. The author shows that,if G is a connected graph, then G3 and T(G) (the total graph of G) are ID-factor-critical,and G4 (when |V(G)| is even) is strongly IM-extendable; if G is 2-connected, then D2 is ID-factor-critical.

  4. Azoospermia factor deletions in varicocele cases with severe oligozoospermia

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    Dada Rima

    2007-09-01

    Full Text Available Background : Varicocele is the most common cause of male infertility. The etiology and pathophysiology of varicocele are multifactorial. When low sperm counts are associated with varicocele, varicocelectomy can partially restore spermatogenesis and fertility. Few recent studies have reported that in some varicocele cases, there may be an associated genetic etiology. Presence of a genetic factor like azoospermia factor microdeletions may lead to irreversible spermatogenic arrest in these cases, but very few reports support these findings. However, it is still not understood why some cases improve after varicocelectomy and why some cases show no improvement in semen parameters postoperatively. Aim: It is important to distinguish varicocele cases from Yq microdeletions as these cases have irreversible testicular damage and thus carry a poor prognosis after varicocelectomy. Settings : Research and Referral tertiary care hospital. Design : Prospective study. Materials and Methods: Seventy-two infertile men with varicocele were referred for Yq microdeletion analysis from the infertility clinic of AIIMS and Army Research and Referral Hospital. Genomic DNA was isolated from blood and polymerase chain reaction microdeletion screening was done in these cases to determine the presence or deletion of AZF loci. Results: In this study 7 (9.7% varicocele cases harbored Yq microdeletion. The sperm count in cases which harbored Yq microdeletion was significantly lower than in cases without Yq microdeletion. Conclusion : Varicocele cases with Yq microdeletion do not show improvement in semen parameters post-varicocelectomy. Detection of Yq microdeletion determines prognosis and future management in such cases.

  5. A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity.

    Science.gov (United States)

    Biamino, Elisa; Di Gregorio, Eleonora; Belligni, Elga Fabia; Keller, Roberto; Riberi, Evelise; Gandione, Marina; Calcia, Alessandro; Mancini, Cecilia; Giorgio, Elisa; Cavalieri, Simona; Pappi, Patrizia; Talarico, Flavia; Fea, Antonio M; De Rubeis, Silvia; Cirillo Silengo, Margherita; Ferrero, Giovanni Battista; Brusco, Alfredo

    2016-03-01

    Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity. PMID:26620927

  6. Molecular investigations of mitochondrial deletions: evaluating the usefulness of different genetic tests.

    Science.gov (United States)

    Tońska, Katarzyna; Piekutowska-Abramczuk, Dorota; Kaliszewska, Magdalena; Kowalski, Paweł; Tańska, Anna; Bartnik, Ewa; Pronicka, Ewa; Krajewska-Walasek, Małgorzata

    2012-09-10

    Deletions in mitochondrial DNA are a common cause of mitochondrial disorders. The molecular diagnosis of mtDNA deletions for years was based on Southern hybridization later replaced by PCR methods such as PCR with primers specific for a particular deletion (mainly the so-called common deletion of 4977 bp) and long PCR. In order to evaluate the usefulness of MLPA (Multiplex Ligation-dependent Probe Amplification) in molecular diagnosis of large scale mtDNA deletions we compare four diagnostic methods: Southern hybridization, PCR, long-PCR and MLPA in a group of 16 patients with suspected deletions. Analysis was performed on blood, muscle and in one case hepatic tissue DNA. The MLPA was not able to confirm all the deletions detected by PCR methods, but due to its relative ease of processing, minimal equipment, low costs and the additional possibility to detect frequent point mtDNA mutations in one assay it is worth considering as a screening method. We recommend to always confirm MLPA results by PCR methods.

  7. Clinical and molecuar characterization of Brazilian patients with growth hormone gene deletions

    Directory of Open Access Journals (Sweden)

    I.J.P. Arnhold

    1998-04-01

    Full Text Available Genomic DNA from 23 patients with isolated growth hormone (GH deficiency (12 males and 11 females: heights -4.9 ± 1.4 SDS was screened for GH gene deletions by restriction endonuclease analysis of polymerase chain reaction amplification products. Three unrelated patients had typical features of severe GH deficiency and deletions (6.7 kb in two and 7.6 kb in one of the GH gene. The two patients with 6.7-kb deletions developed growth-attenuating anti-GH antibodies whereas the patient with the 7.6-kb deletion continued to grow with GH replacement therapy. Our finding that 3/23 (~13% Brazilian subjects had GH gene deletions agrees with previous studies of severe isolated GH deficiency subjects in other populations. Two of three subjects (67% with deletions developed blocking antibodies despite administration of exogenous GH at low doses. Interestingly, only 1/10 of cases with affected relatives or parental consanguinity had GH-1 gene deletions

  8. A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion.

    Science.gov (United States)

    Viñas-Jornet, Marina; Esteba-Castillo, Susanna; Gabau, Elisabeth; Ribas-Vidal, Núria; Baena, Neus; San, Joan; Ruiz, Anna; Coll, Maria Dolors; Novell, Ramon; Guitart, Miriam

    2014-11-01

    Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are associated with intellectual disability and various psychiatric disorders, in particular, autism and schizophrenia. We present three unrelated patients, two adults and one child, in whom we identified an intragenic 2p16.3 deletion within the NRXN1 gene using an oligonucleotide comparative genomic hybridization array. The three patients presented dual diagnosis that consisted of mild intellectual disability and autism and bipolar disorder. Also, they all shared a dysmorphic phenotype characterized by a long face, deep set eyes, and prominent premaxilla. Genetic analysis of family members showed two inherited deletions. A comprehensive neuropsychological examination of the 2p16.3 deletion carriers revealed the same phenotype, characterized by anxiety disorder, borderline intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive syndrome with poor working memory and reduced attention switching, mental flexibility, and verbal fluency was the same than those of the adult probands. We suggest that in addition to intellectual disability and psychiatric disease, NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic profile. The new cognitive phenotype found in the 2p16.3 deletion carriers suggests that 2p16.3 deletions might have a wide variable expressivity instead of incomplete penetrance.

  9. Analysis of Dystrophin Gene Deletions by Multiplex PCR in Moroccan Patients

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    Aziza Sbiti

    2002-01-01

    Full Text Available Duchenne and Becker muscular dystrophy (DMD and BMD are X-linked diseases resulting from a defect in the dystrophin gene located on Xp21. DMD is the most frequent neuromuscular disease in humans (1/3500 male newborn. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. We have analyzed DNA from 72 Moroccan patients with DMD/BMD using the multiplex polymerase chain reaction (PCR to screen for exon deletions within the dystrophin gene, and to estimate the frequency of these abnormalities. We found dystrophin gene deletions in 37 cases. Therefore the frequency in Moroccan DMD/BMD patients is about 51.3%. All deletions were clustered in the two known hot-spots regions, and in 81% of cases deletions were detected in the region from exon 43 to exon 52. These findings are comparable to those reported in other studies. It is important to note that in our population, we can first search for deletions of DMD gene in the most frequently deleted exons determined by this study. This may facilitate the molecular diagnosis of DMD and BMD in our country.

  10. Molecular Diagnosis of Duchenne/Becker Muscular Dystrophy: Analysis of Exons Deletion and Carrier Detection

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Akbari

    2010-01-01

    Full Text Available Objective: Duchenne and Becker Muscular Dystrophy (DMD and BMD are X-linked conditionsresulting from a defect in the dystrophin gene located at Xp21.2. DMD is the mostfrequent neuromuscular disease in humans (1/3500 male newborns. In approximately65% of DMD and BMD patients, deletions in the dystrophin gene have been identified asthe molecular determinant. The frequency and distribution of dystrophin gene deletions inDMD/BMD patients from different populations are different.The aim of this study was to delineate various types of deleted exons and their frequencyin affected male patients and identification of carrier females by linkage analysis.Materials and Methods: In this study 100 unrelated patients with DMD/BMD were studiedfor intragenic deletions in 28 exons and the promoter region of the dystrophin geneusing multiplex PCR. We also performed linkage analysis within the dystrophin gene utilizing8 short tandem repeat markers.Results: Fifty-two (52% patients showed intragenic deletions. A total of 81% of the deletionswere located at the distal hot spot region (44-55 exons and 19% of the deletionswere located at the proximal region (exon 2-19. The most frequent deleted exons were47(16%, 48 and 46 (11%.Most of the STR markers showed heterozygosity in the families studied. The linkageanalysis was useful for detecting carrier status.Conclusion: The present study suggests that intragenic dystrophin gene deletions occurwith the same frequency in Iranian patients compared with other ethnic groups.

  11. FISH detection of chromosome 15 deletions in Prader-Willi and Angelman syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Teshima, I.; Chadwick, D.; Chitayat, D. [Hospital for Sick Children and Univ. of Toronto, Ontario (Canada)

    1996-03-29

    We have evaluated fluorescence in situ hybridization (FISH) analysis for the clinical laboratory detection of the 15q11-q13 deletion seen in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) using probes for loci D15S11, SNRPN, D15S10, and GABRB3. In a series of 118 samples from patients referred for PWS or AS, 29 had deletions by FISH analysis. These included two brothers with a paternally transmitted deletion detectable with the probe for SNRPN only. G-banding analysis was less sensitive for deletion detection but useful in demonstrating other cytogenetic alterations in four cases. Methylation and CA-repeat analyses of 15q11-q13 were used to validate the FISH results. Clinical findings of patients with deletions were variable, ranging from newborns with hypotonia as the only presenting feature to children who were classically affected. We conclude that FISH analysis is a rapid and reliable method for detection of deletions within 15q11-q13 and whenever a deletion is found, FISH analysis of parental chromosomes should also be considered. 41 refs., 4 figs., 2 tabs.

  12. Polypeptone induces dramatic cell lysis in ura4 deletion mutants of fission yeast.

    Directory of Open Access Journals (Sweden)

    Yuzy Matsuo

    Full Text Available Polypeptone is widely excluded from Schizosaccharomyces pombe growth medium. However, the reasons why polypeptone should be avoided have not been documented. Polypeptone dramatically induced cell lysis in the ura4 deletion mutant when cells approached the stationary growth phase, and this phenotype was suppressed by supplementation of uracil. To determine the specificity of this cell lysis phenotype, we created deletion mutants of other genes involved in de novo biosynthesis of uridine monophosphate (ura1, ura2, ura3, and ura5. Cell lysis was not observed in these gene deletion mutants. In addition, concomitant disruption of ura1, ura2, ura3, or ura5 in the ura4 deletion mutant suppressed cell lysis, indicating that cell lysis induced by polypeptone is specific to the ura4 deletion mutant. Furthermore, cell lysis was also suppressed when the gene involved in coenzyme Q biosynthesis was deleted. This is likely because Ura3 requires coenzyme Q for its activity. The ura4 deletion mutant was sensitive to zymolyase, which mainly degrades (1,3-beta-D glucan, when grown in the presence of polypeptone, and cell lysis was suppressed by the osmotic stabiliser, sorbitol. Finally, the induction of cell lysis in the ura4 deletion mutant was due to the accumulation of orotidine-5-monophosphate. Cell wall integrity was dramatically impaired in the ura4 deletion mutant when grown in the presence of polypeptone. Because ura4 is widely used as a selection marker in S. pombe, caution needs to be taken when evaluating phenotypes of ura4 mutants.

  13. A persistent mitochondrial deletion reduces fitness and sperm performance in heteroplasmic populations of C. elegans

    Directory of Open Access Journals (Sweden)

    Chin Kara

    2007-03-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA mutations are of increasing interest due to their involvement in aging, disease, fertility, and their role in the evolution of the mitochondrial genome. The presence of reactive oxygen species and the near lack of repair mechanisms cause mtDNA to mutate at a faster rate than nuclear DNA, and mtDNA deletions are not uncommon in the tissues of individuals, although germ-line mtDNA is largely lesion-free. Large-scale deletions in mtDNA may disrupt multiple genes, and curiously, some large-scale deletions persist over many generations in a heteroplasmic state. Here we examine the phenotypic effects of one such deletion, uaDf5, in Caenorhabditis elegans (C. elegans. Our study investigates the phenotypic effects of this 3 kbp deletion. Results The proportion of uaDf5 chromosomes in worms was highly heritable, although uaDf5 content varied from worm to worm and within tissues of individual worms. We also found an impact of the uaDf5 deletion on metabolism. The deletion significantly reduced egg laying rate, defecation rate, and lifespan. Examination of sperm bearing the uaDf5 deletion revealed that sperm crawled more slowly, both in vitro and in vivo. Conclusion Worms harboring uaDf5 are at a selective disadvantage compared to worms with wild-type mtDNA. These effects should lead to the rapid extinction of the deleted chromosome, but it persists indefinitely. We discuss both the implications of this phenomenon and the possible causes of a shortened lifespan for uaDf5 mutant worms.

  14. Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

    Directory of Open Access Journals (Sweden)

    Ritch Robert

    2004-06-01

    Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

  15. A 3-base pair deletion, c.9711_9713del, in DMD results in intellectual disability without muscular dystrophy

    NARCIS (Netherlands)

    de Brouwer, Arjan P. M.; Nabuurs, Sander B.; Verhaart, Ingrid E. C.; Oudakker, Astrid R.; Hordijk, Roel; Yntema, Helger G.; Hordijk-Hos, Jannet M.; Voesenek, Krysta; de Vries, Bert B. A.; van Essen, Ton; Chen, Wei; Hu, Hao; Chelly, Jamel; den Dunnen, Johan T.; Kalscheuer, Vera M.; Aartsma-Rus, Annemieke M.; Hamel, Ben C. J.; van Bokhoven, Hans; Kleefstra, Tjitske

    2014-01-01

    We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3

  16. Novel 31.2 kb α0 Deletion in a Palestinian Family with α-Thalassemia

    DEFF Research Database (Denmark)

    Brieghel, Christian; Birgens, Henrik; Frederiksen, Henrik;

    2015-01-01

    A previously unknown α(0) deletion, designated - -(DANE), was found in three generations of a Danish family of Palestinian origin. Six patients were heterozygous and three patients had deletional Hb H (β4) disease with a compound heterozygosity for the common -α(3.7) (rightward) deletion. Multiplex...

  17. Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    M' Bemba-Meka, Prosper [Universite de Montreal, Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Main Station, P.O. Box 6128, Montreal, QC (Canada); University of Louisville, Department of Pharmacology and Toxicology, Center for Genetics and Molecular Medicine, Louisville, KY (United States); Lemieux, Nicole [Universite de Montreal, Department of Pathology and Cellular Biology, Faculty of Medicine, Main Station, P.O. Box 6128, Montreal, QC (Canada); Chakrabarti, Saroj K. [Universite de Montreal, Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Main Station, P.O. Box 6128, Montreal, QC (Canada)

    2007-02-15

    Human peripheral lymphocytes from whole blood cultures were exposed to either soluble form of nickel carbonate hydroxide (NiCH) (0-60 {mu}M), or of nickel subsulfide (Ni{sub 3}S{sub 2}) (0-120 {mu}M), or of nickel oxide (NiO) (0-120 {mu}M), or nickel sulfate (NiSO{sub 4}) (0-120 {mu}M) for a short duration of 2 h. The treatments occurred 46 h after the beginning of the cultures. The cultures were harvested after a total incubation of 72 h, and sister-chromatid exchange (SCE), replication index (RI), and mitotic index (MI) were measured for each nickel compound. The soluble form of NiCH at 30 {mu}M but those of Ni{sub 3}S{sub 2} and NiO at 120 {mu}M produced significant increase in the SCE per cell compared to the control value, whereas NiSO{sub 4} failed to produce any such significant increase. Except NiSO{sub 4}, the soluble forms of NiCH, Ni{sub 3}S{sub 2}, and NiO produced significant cell-cycle delay (as measured by the inhibition of RI) as well as significant inhibition of the MI at respective similar concentrations as mentioned above. Pretreatment of human blood lymphocytes with catalase (H{sub 2}O{sub 2} scavenger), or superoxide dismutase (superoxide anion scavenger), or dimethylthiourea (hydroxyl radical scavenger), or deferoxamine (iron chelator), or N-acetylcysteine (general antioxidant) inhibited NiCH-induced SCE, and changes in RI and MI. This suggests the participation of oxidative stress involving H{sub 2}O{sub 2}, the superoxide anion radical, the hydroxyl radical, and iron in the NiCH-induced genotoxic responses. Cotreatment of NiCH with either verapamil (inhibitor of intracellular calcium ion ([Ca{sup 2+}]{sub i}) movement through plasma membranes), or dantrolene (inhibitor of [Ca{sup 2+}]{sub i} release from sarcoplasmic reticulum), or BAPTA (Ca{sup 2+} chelator) also inhibited the NiCH-induced responses. These results suggest that [Ca{sup 2+}]{sub i} is also implicated in the genotoxicity of NiCH. Overall these data indicate that various types

  18. Relationship of the demethylation of the DNA with the induction of the sister chromatid exchanges (SCE) In vivo; Relacion de la desmetilacion del ADN con la induccion de intercambios en las cromatidas hermanas (ICH) In vivo

    Energy Technology Data Exchange (ETDEWEB)

    Toribio E, E

    2005-07-01

    The methylation of the DNA is an epigenetic modification that has an important paper in the regulation of the functionality of the genome of the organisms. It can be altered by demethylation processes, either natural or experimentally induced. The 5-azacytidine (Aza) is a compound that causes the demethylation of the DNA (dm-DNA), inducing with it, expression genic and increase in the frequency of the Sister Chromatid Exchange (SCE). The SCE is a genotoxicity indicator, caused by diverse mutagens and carcinogen. Since the biological meaning and the formation mechanism of this phenomenon has not been totally illustrious, the exploration of the relation between the dm-DNA and the induction of SCE, it could offer new knowledge to explain those queries. The purpose of this work was to study in cells of the mouse bone marrow In vivo, the effect of the Aza on the induction of SCE, based on two aspects: 1) dose answer and 2) the effectiveness of multiple exhibition. To six groups of three to five animals, they are administered Aza to dose of 5, 10, 15 or 20 mg/Kg of weight; in sharp or multiple form, previously to the bromodeoxyuridine supply and 24 h was sacrificed after this; 2 h after an injection with colchicine. Preparations of those metaphases were made, those which were dyed by means of a technique of fluorescence more Giemsa. It was observed that to sharp low dose, the Aza produced an increment in the frequency of SCE that although small it was proportional and statistically significant. To sharp and multiple high doses, the Aza doesn't cause additional increments of SCE, but if toxicity at cellular level and of individuals. It is concluded that a relationship exists between the dm-DNA and the induction of SCE. It is suggested that the total demethylation of the DNA causes 2 SCE/Cell in cells of the mouse bone marrow, or that the cytotoxicity prevents to evidence a bigger induction. (Author)

  19. Occurrence of two different intragenic deletions in two male relatives affected with Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Mostacciuolo, M.L.; Miorin, M.; Vitiello, L.; Rampazzo, A.; Fanin, M.; Angelini, C.; Danieli, G.A. [Univ. of Padua (Italy)

    1994-03-01

    The occurrence of 2 different intragenic deletions (exons 10-44 and exon 45, respectively) is reported in 2 male relatives affected with Duchenne muscular dystrophy, both showing the same haplotype for DNA markers not included in the deleted segment. The 2 different deletions seem to have occurred independently in the same X chromosome. This finding, together with other reports, suggests possibly an increased predisposition to mutations within the DMD locus in some families. Therefore, when dealing with prenatal diagnosis, the investigation on fetal DNA cannot be restricted only to the region in which a mutation was previously identified in the family. 14 refs., 1 fig.

  20. Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage

    OpenAIRE

    Darshan, Deepak; Vanoaica, Liviu; Richman, Larry; Beermann, Friedrich; Kühn, Lukas C.

    2009-01-01

    Ferritin plays a central role in iron metabolism by acting both as iron storage and detoxifying protein. We have generated a ferritin H allele with loxP sites and studied the conditional ferritin H deletion in adult mice. Ten days after Mx-Cre induced deletion, ferritin H mRNA was below 5% in the liver, spleen and bone marrow of deleted mice compared to control littermates. Mice lost their cellular iron stores indicating the requirement of ferritin H in iron deposition. Serum iron and...

  1. Deletion pattern of the STS gene in X-linked ichthyosis in a Mexican population.

    OpenAIRE

    Jimenez Vaca, A. L.; Valdes-Flores, M. del R.; Rivera-Vega, M. R.; González-Huerta, L. M.; Kofman-Alfaro, S. H.; Cuevas-Covarrubias, S. A.

    2001-01-01

    BACKGROUND: X-linked ichthyosis (XLI) is an inherited disorder due to steroid sulfatase deficiency (STS). Most XLI patients (>90%) have complete deletion of the STS gene and flanking sequences. The presence of low copy number repeats (G1.3 and CRI-S232) on either side of the STS gene seems to play a role in the high frequency of these interstitial deletions. In the present study, we analyzed 80 Mexican patients with XLI and complete deletion of the STS gene. MATERIALS AND METHODS: STS activit...

  2. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Deng, Kathy; Nanda, Deepak

    2016-01-01

    Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia. PMID:27366335

  3. Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors

    OpenAIRE

    Silvia Hennecke; Julia Beck; Kirsten Bornemann-Kolatzki; Stephan Neumann; Hugo Murua Escobar; Ingo Nolte; Susanne Conradine Hammer; Marion Hewicker-Trautwein; Johannes Junginger; Franz-Josef Kaup; Bertram Brenig; Ekkehard Schütz

    2015-01-01

    Background A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. Me...

  4. Mitochondrial Genome Deletion for Detection of Prostate Cancer — EDRN Public Portal

    Science.gov (United States)

    The Prostate Core Mitomic Test™ is based upon a 3.4 kb mitochondrial genome deletion (3.4 mtdelta) that was identified through PCR analysis of frozen prostate cancer samples. In cancer research it has been found that deletions in mitochondrial DNA can correlate with cellular changes that indicate development of cancer. This deletion includes the terminal 22 bases of MT-ND4L, all of MT-ND4, 3 tRNAs (histidine, serine 2, and leucine 2), and all except the terminal 24 bases of MT-ND5.

  5. Acute Myelogenous Leukemia without Maturation with a Retinoic Alpha-Receptor Deletion: A Case Report

    Directory of Open Access Journals (Sweden)

    Christopher Trosclair

    2014-06-01

    Full Text Available Acute promyelocytic leukemia (APL is characterized by a t(15;17 which fuses the 17q retinoic acid alpha-receptor sequence to the 15q PML gene sequence. The resulting fusion product plays a role in the development and maintenance of APL, and is very rarely found in other acute myeloid leukemia (AML subtypes. Rare complex APL genomic rearrangements have retinoic acid alpha-receptor sequence deletions. Here we report a retinoic acid alpha-receptor sequence deletion in a case of AML without differentiation. To our knowledge, this is the first example of a retinoic acid alpha-receptor sequence deletion in this AML subtype.

  6. Microcephaly/lymphedema and terminal deletion of the long arm of chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Fryns, J.P. [Univ. of Leuven (Belgium)

    1995-07-03

    Recently, we examined a 2-year-old boy with the association of microcephaly and significant pedal edema that extended to the distal parts of the legs. Prometaphase chromosome studies showed a small terminal deletion in the long arm of chromosome 13 of band 13q34, karyotype 46,XY,del(13)(q34{yields}qter). The present finding of a small terminal 13q34 deletion in this young boy with microcephaly/lymphedema is a first indication that the lymphedema/microcephaly association can be due to a small terminal 13q deletion. 2 refs.

  7. Receptor binding site-deleted foot-and-mouth disease (FMD) virus protects cattle from FMD.

    OpenAIRE

    McKenna, T S; Lubroth, J; Rieder, E; Baxt, B; Mason, P W

    1995-01-01

    Binding of foot-and-mouth disease virus (FMDV) to cells requires an arginine-glycine-aspartic acid (RGD) sequence in the capsid protein VP1. We have genetically engineered an FMDV in which these three amino acids have been deleted, producing a virus particle which is unable to bind to cells. Cattle vaccinated with these receptor binding site-deleted virions were protected from disease when challenged with a virulent virus, demonstrating that these RGD-deleted viruses could serve as the basis ...

  8. A child with mosaicism for deletion (14(q11.2q13

    Directory of Open Access Journals (Sweden)

    Thilini H Gamage

    2012-01-01

    Full Text Available In this case report we describe a child with a de novo deletion in the (q11.2q13 region of chromosome 14. The child presented with dysmorphic features - anophthalmia, microcephaly, and growth retardation. Cytogenetic studies showed mosaicism. The karyotype was 46,XX,del(14(q11.2;q13 [16] /46,XX [9]. We compared the features observed in this child with that of others with the same deletion reported in scientific literature and found that this is the first report of a child mosaic for this deletion. It is also the first time it has been reported in association with anophthalmia.

  9. A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Atwal, Paldeep S; Macmurdo, C

    2015-12-01

    Features of Miller-Dieker syndrome (MDS, 17p13.3 deletion syndrome, LIS1-associated lissencephaly) include classic lissencephaly, microcephaly, cardiac malformations, growth restriction, and characteristic facial changes. Individuals with 22q11.2 deletion syndrome (DiGeorge syndrome or velocardiofacial syndrome) are known to have congenital cardiac malformations (in particular conotruncal defects), palatal abnormalities (especially velopharyngeal insufficiency), hypocalcemia, immune deficiency, learning disabilities, and characteristic facial features. This case report describes phenotypic characteristics of a patient with extremely rare instance of having both MDS and 22q11.2 deletion syndrome that is unique in the medical literature. Prognosis in this concurrent phenotype is poor with our patient suffering from several malformations seen in both conditions and expiring in the neonatal period. PMID:27617133

  10. Discovering sequence motifs with arbitrary insertions and deletions.

    Directory of Open Access Journals (Sweden)

    Martin C Frith

    2008-04-01

    Full Text Available BIOLOGY IS ENCODED IN MOLECULAR SEQUENCES: deciphering this encoding remains a grand scientific challenge. Functional regions of DNA, RNA, and protein sequences often exhibit characteristic but subtle motifs; thus, computational discovery of motifs in sequences is a fundamental and much-studied problem. However, most current algorithms do not allow for insertions or deletions (indels within motifs, and the few that do have other limitations. We present a method, GLAM2 (Gapped Local Alignment of Motifs, for discovering motifs allowing indels in a fully general manner, and a companion method GLAM2SCAN for searching sequence databases using such motifs. glam2 is a generalization of the gapless Gibbs sampling algorithm. It re-discovers variable-width protein motifs from the PROSITE database significantly more accurately than the alternative methods PRATT and SAM-T2K. Furthermore, it usefully refines protein motifs from the ELM database: in some cases, the refined motifs make orders of magnitude fewer overpredictions than the original ELM regular expressions. GLAM2 performs respectably on the BAliBASE multiple alignment benchmark, and may be superior to leading multiple alignment methods for "motif-like" alignments with N- and C-terminal extensions. Finally, we demonstrate the use of GLAM2 to discover protein kinase substrate motifs and a gapped DNA motif for the LIM-only transcriptional regulatory complex: using GLAM2SCAN, we identify promising targets for the latter. GLAM2 is especially promising for short protein motifs, and it should improve our ability to identify the protein cleavage sites, interaction sites, post-translational modification attachment sites, etc., that underlie much of biology. It may be equally useful for arbitrarily gapped motifs in DNA and RNA, although fewer examples of such motifs are known at present. GLAM2 is public domain software, available for download at http://bioinformatics.org.au/glam2.

  11. Proton magnetic resonance spectroscopy in 22q11 deletion syndrome.

    Directory of Open Access Journals (Sweden)

    Fabiana da Silva Alves

    Full Text Available OBJECTIVE: People with velo-cardio-facial syndrome or 22q11 deletion syndrome (22q11DS have behavioral, cognitive and psychiatric problems. Approximately 30% of affected individuals develop schizophrenia-like psychosis. Glutamate dysfunction is thought to play a crucial role in schizophrenia. However, it is unknown if and how the glutamate system is altered in 22q11DS. People with 22q11DS are vulnerable for haploinsufficiency of PRODH, a gene that codes for an enzyme converting proline into glutamate. Therefore, it can be hypothesized that glutamatergic abnormalities may be present in 22q11DS. METHOD: We employed proton magnetic resonance spectroscopy ((1H-MRS to quantify glutamate and other neurometabolites in the dorsolateral prefrontal cortex (DLPFC and hippocampus of 22 adults with 22q11DS (22q11DS SCZ+ and without (22q11DS SCZ- schizophrenia and 23 age-matched healthy controls. Also, plasma proline levels were determined in the 22q11DS group. RESULTS: We found significantly increased concentrations of glutamate and myo-inositol in the hippocampal region of 22q11DS SCZ+ compared to 22q11DS SCZ-. There were no significant differences in levels of plasma proline between 22q11DS SCZ+ and 22q11DS SCZ-. There was no relationship between plasma proline and cerebral glutamate in 22q11DS. CONCLUSION: This is the first in vivo(1H-MRS study in 22q11DS. Our results suggest vulnerability of the hippocampus in the psychopathology of 22q11DS SCZ+. Altered hippocampal glutamate and myo-inositol metabolism may partially explain the psychotic symptoms and cognitive impairments seen in this group of patients.

  12. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the continued development of a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and...

  13. Chromatid Painting for Chromosomal Inversion Detection Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  14. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

    Directory of Open Access Journals (Sweden)

    Colovati Mileny ES

    2012-01-01

    Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

  15. Identifying and calling insertions, deletions, and single-base mutations efficiently from sequence data

    Science.gov (United States)

    Whole genome sequencing studies can directly identify causative mutations for subsequent use in genomic evaluations, but sequence variant identification is a lengthy and sometimes inaccurate process. The speed and accuracy of identifying small insertions and deletions of sequence, collectively terme...

  16. Study on 4977-bp deletion mutation of mitochondrial DNA in lung cancer

    Institute of Scientific and Technical Information of China (English)

    DAI Ji-gang; XIAO Ying-bin; MIN Jia-xin; ZHANG Guo-qiang; YAO Ke; ZHOU Ren-jie

    2005-01-01

    Objective: To study the 4977-bp deletion of mitochondiral DNA in lung cancer, adjacent normal tissue and health lung and its significance in the development of cancer. Methods: Thirty-seven matched lung cancer/adjacent histologically normal and 20 "true" normal lung tissue samples from patients without lung cancer were analyzed by long PCR technique. Results: Mitochondrial DNA 4977-bp deletion was detected in 54. 1% (20/37) of lung cancers, 59.5% (22/37) of adjacent normal and 30.0% (6/30) of"true" normal lung tissues. The correlation of 4977-bp deletion with age and smoking factors was present in our data. Conclusion: Mitochondrial DNA 4977-bp deletion is not specific to lung cancer and unlikely to play an important role in carcinogenesis, and may only reflect the environmental and genetic influences during tumor progression.

  17. DELETION AND 5'CPG ISLAND METHYLATION OF p15 GENE IN BRAIN GLIOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the abnormality of p15 gene in brain glioma and the correlation of it with occurrence or malignant progression of brain glioma. Methods: Deletion and 5'CPG island methylation of p15 gene were detected by the methods of PCR and PCR-based methylation in 56 cases of brain glioma. Results: Out of 43 cases of high grade glioma, 14 cases were found to have homozygous deletion of p15E1, while none of the 13 cases of low grade glioma was found to have deletion of p15E1 (P<0.05). Methylation of 5'CPG Island of p15 gene was found only in four cases of glioma. Conclusion: Abnormality of p15 gene may involved in the occurrence and malignant progression of brain glioma. Homozygous deletion of gene is the major mechanism of inactivation for p15 gene in brain glioma.

  18. Association of GSTM1 and GSTT1 deletion with lung cancer development in Pakistani population

    Directory of Open Access Journals (Sweden)

    Nosheen Masood

    2016-01-01

    Conclusion: Results revealed that certain environmental factors may be considered as a risk factor but deletion of GSTM1 and GSTT1 are not associated with the development of lung cancer; however, studies including >500 patient samples is suggested.

  19. Using Fluorescence in situ Hybridization to Identify DMD/BMD Deletion Carriers

    Institute of Scientific and Technical Information of China (English)

    Ren-li WANG; Yan-ping XIAO; Xiu-rong JIANG

    2003-01-01

    Objective To identify the deletions in Duchenne/Becker muscular dystrophy (DMD/BMD) by using fluorescence in situ hybridization (FISH) Methods The exon-specific cosmid DNA probes (representing 18 exons) were used to perform one-color FISH on metaphase and interphase preparations. The peripheral blood samples from 9 normal people (4 males and 5 females) and 5 females from independent deletion DMD/BMD families, as well as 2 amniotic fluid specimens and 2 chorionic villus samples (CVS) from normal pregnant females were analyzed.Results 72%~100% of peripheral blood lymphocyte metaphases or interphases, 60%~70% of amniocyte interphases, and 95~99% of chorionic villus cell interphases showed expected signals. One suspected female was identified as deletion carriers and two were excluded.Conclusion FISH in combination with other available techniques allows efficient screening of DMD/BMD deletion carriers, which also lay the ground work for prenatal diagnosis for potential fetal carriers.

  20. A method for the analysis of 32 X chromosome insertion deletion polymorphisms in a single PCR

    DEFF Research Database (Denmark)

    Pereira, Rui; Pereira, Vania; Gomes, Iva;

    2012-01-01

    Studies of human genetic variation predominantly use short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) but Insertion deletion polymorphisms (Indels) are being increasingly explored. They combine desirable characteristics of other genetic markers, especially the possibility of...

  1. Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation

    DEFF Research Database (Denmark)

    Lugtenberg, Dorien; Zangrande-Vieira, Luiz; Kirchhoff, Maria;

    2010-01-01

    ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected...... 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating...... that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P...

  2. Delete-group Jackknife Estimate in Partially Linear Regression Models with Heteroscedasticity

    Institute of Scientific and Technical Information of China (English)

    Jin-hong You; Gemai Chen

    2003-01-01

    Consider a partially linear regression model with an unknown vector parameter β, an unknown function g(.), and unknown heteroscedastic error variances. Chen, You[23] proposed a semiparametric generalized least squares estimator (SGLSE) for β, which takes the heteroscedasticity into account to increase efficiency. For inference based on this SGLSE, it is necessary to construct a consistent estimator for its asymptotic covariance matrix. However, when there exists within-group correlation, the traditional delta method and the delete-1 jackknife estimation fail to offer such a consistent estimator. In this paper, by deleting grouped partial residuals a delete-group jackknife method is examined. It is shown that the delete-group jackknife method indeed can provide a consistent estimator for the asymptotic covariance matrix in the presence of within-group correlations.This result is an extension of that in [21].

  3. An improved Flp deleter mouse in C57Bl/6 based on Flpo recombinase.

    Science.gov (United States)

    Kranz, Andrea; Fu, Jun; Duerschke, Kristin; Weidlich, Stefanie; Naumann, Ronald; Stewart, A Francis; Anastassiadis, Konstantinos

    2010-08-01

    Recently, a codon improved version of the Flpe site specific recombinase, termed Flpo, was reported as having greatly improved performance in mammalian cell applications. However, the degree of improvement could not be estimated because essentially no Flpe activity was observed. Here, we compare Flpe and Flpo accurately in a mammalian cell assay to estimate that Flpo is about five times more active than Flpe and similar to Cre and Dre. Consequently, we generated a Flpo deleter mouse line from the JM8 C57Bl/6 ES cells used in the EUCOMM and KOMP systematic knock-out programs. In breeding experiments, we show that the Flpo deleter delivers complete recombination using alleles that are incompletely recombined by a commonly used Flpe deleter. This indicates that the Flpo deleter is more efficient. PMID:20506501

  4. Retention or deletion of personality disorder diagnoses for DSM-5: an expert consensus approach.

    Science.gov (United States)

    Mullins-Sweatt, Stephanie N; Bernstein, David P; Widiger, Thomas A

    2012-10-01

    One of the official proposals for the fifth edition of the American Psychiatric Association's (APA) diagnostic manual (DSM-5) is to delete half of the existing personality disorders (i.e., dependent, histrionic, narcissistic, paranoid, and schizoid). Within the APA guidelines for DSM-5 decisions, it is stated that there should be expert consensus agreement for the deletion of a diagnostic category. Additionally, categories to be deleted should have low clinical utility and/or minimal evidence for validity. The current study surveyed members of two personality disorder associations (n = 146) with respect to the utility, validity, and status of each DSM-IV-TR personality disorder diagnosis. Findings indicated that the proposal to delete five of the personality disorders lacks consensus support within the personality disorder community.

  5. Accumulation of mitochondrial DNA deletions within dopaminergic neurons triggers neuroprotective mechanisms.

    Science.gov (United States)

    Perier, Celine; Bender, Andreas; García-Arumí, Elena; Melià, Ma Jesus; Bové, Jordi; Laub, Christoph; Klopstock, Thomas; Elstner, Matthias; Mounsey, Ross B; Teismann, Peter; Prolla, Tomas; Andreu, Antoni L; Vila, Miquel

    2013-08-01

    Acquired alterations in mitochondrial DNA are believed to play a pathogenic role in Parkinson's disease. In particular, accumulation of mitochondrial DNA deletions has been observed in substantia nigra pars compacta dopaminergic neurons from patients with Parkinson's disease and aged individuals. Also, mutations in mitochondrial DNA polymerase gamma result in multiple mitochondrial DNA deletions that can be associated with levodopa-responsive parkinsonism and severe substantia nigra pars compacta dopaminergic neurodegeneration. However, whether mitochondrial DNA deletions play a causative role in the demise of dopaminergic neurons remains unknown. Here we assessed the potential pathogenic effects of mitochondrial DNA deletions on the dopaminergic nigrostriatal system by using mutant mice possessing a proofreading-deficient form of mitochondrial DNA polymerase gamma (POLGD257A), which results in a time-dependent accumulation of mitochondrial DNA deletions in several tissues, including the brain. In these animals, we assessed the occurrence of mitochondrial DNA deletions within individual substantia nigra pars compacta dopaminergic neurons, by laser capture microdissection and quantitative real-time polymerase chain reaction, and determined the potential deleterious effects of such mitochondrial DNA alterations on mitochondrial function and dopaminergic neuronal integrity, by cytochrome c oxidase histochemistry and quantitative morphology. Nigral dopaminergic neurons from POLGD257A mice accumulate mitochondrial DNA deletions to a similar extent (∼40-60%) as patients with Parkinson's disease and aged individuals. Despite such high levels of mitochondrial DNA deletions, the majority of substantia nigra pars compacta dopaminergic neurons from these animals did not exhibit mitochondrial dysfunction or degeneration. Only a few individual substantia nigra pars compacta neurons appeared as cytochrome c oxidase-negative, which exhibited higher levels of mitochondrial DNA

  6. Accumulation of mitochondrial DNA deletions within dopaminergic neurons triggers neuroprotective mechanisms.

    Science.gov (United States)

    Perier, Celine; Bender, Andreas; García-Arumí, Elena; Melià, Ma Jesus; Bové, Jordi; Laub, Christoph; Klopstock, Thomas; Elstner, Matthias; Mounsey, Ross B; Teismann, Peter; Prolla, Tomas; Andreu, Antoni L; Vila, Miquel

    2013-08-01

    Acquired alterations in mitochondrial DNA are believed to play a pathogenic role in Parkinson's disease. In particular, accumulation of mitochondrial DNA deletions has been observed in substantia nigra pars compacta dopaminergic neurons from patients with Parkinson's disease and aged individuals. Also, mutations in mitochondrial DNA polymerase gamma result in multiple mitochondrial DNA deletions that can be associated with levodopa-responsive parkinsonism and severe substantia nigra pars compacta dopaminergic neurodegeneration. However, whether mitochondrial DNA deletions play a causative role in the demise of dopaminergic neurons remains unknown. Here we assessed the potential pathogenic effects of mitochondrial DNA deletions on the dopaminergic nigrostriatal system by using mutant mice possessing a proofreading-deficient form of mitochondrial DNA polymerase gamma (POLGD257A), which results in a time-dependent accumulation of mitochondrial DNA deletions in several tissues, including the brain. In these animals, we assessed the occurrence of mitochondrial DNA deletions within individual substantia nigra pars compacta dopaminergic neurons, by laser capture microdissection and quantitative real-time polymerase chain reaction, and determined the potential deleterious effects of such mitochondrial DNA alterations on mitochondrial function and dopaminergic neuronal integrity, by cytochrome c oxidase histochemistry and quantitative morphology. Nigral dopaminergic neurons from POLGD257A mice accumulate mitochondrial DNA deletions to a similar extent (∼40-60%) as patients with Parkinson's disease and aged individuals. Despite such high levels of mitochondrial DNA deletions, the majority of substantia nigra pars compacta dopaminergic neurons from these animals did not exhibit mitochondrial dysfunction or degeneration. Only a few individual substantia nigra pars compacta neurons appeared as cytochrome c oxidase-negative, which exhibited higher levels of mitochondrial DNA

  7. Simple Method for Markerless Gene Deletion in Multidrug-Resistant Acinetobacter baumannii

    OpenAIRE

    Oh, Man Hwan; Lee, Je Chul; Kim, Jungmin; Choi, Chul Hee; Han, Kyudong

    2015-01-01

    The traditional markerless gene deletion technique based on overlap extension PCR has been used for generating gene deletions in multidrug-resistant Acinetobacter baumannii. However, the method is time-consuming because it requires restriction digestion of the PCR products in DNA cloning and the construction of new vectors containing a suitable antibiotic resistance cassette for the selection of A. baumannii merodiploids. Moreover, the availability of restriction sites and the selection of re...

  8. Microarray Analysis of 8p23.1 Deletion in New Patients with Atypical Phenotypical Traits.

    Science.gov (United States)

    Khelifa, Hela Ben; Kammoun, Molka; Hannachi, Hanene; Soyah, Najla; Hammami, Saber; Elghezal, Hatem; Sanlaville, Damien; Saad, Ali; Mougou-Zerelli, Soumaya

    2015-12-01

    We describe two patients carrying deletions of chromosome 8p23.1 with a commonly critical region identified by means of oligonucleotide array comparative genomic hybridization (array CGH). They didn't present congenital heart defects or behavioral problems. Only one patient presented with intellectual disability and carrying deletion of TNKS gene. We presumed the inclusion of TNKS gene in the mental impairment. PMID:27617130

  9. Identification of three critical regions within mouse interleukin 2 by fine structural deletion analysis.

    OpenAIRE

    Zurawski, S M; Zurawski, G

    1988-01-01

    We have analyzed structure--function relationships of the protein hormone murine interleukin 2 by fine structural deletion mapping. A total of 130 deletion mutant proteins, together with some substitution and insertion mutant proteins, was expressed in Escherichia coli and analyzed for their ability to sustain the proliferation of a cloned murine T cell line. This analysis has permitted a functional map of the protein to be drawn and classifies five segments of the protein, which together con...

  10. Restriction enzyme mapping of the DNA of Streptomyces bacteriophage B alpha and its deletion derivatives.

    Science.gov (United States)

    Ishihara, H; Nakano, M M; Ogawara, H

    1982-12-01

    Cleavage analysis of actinophage B alpha DNA was done with several restriction enzymes, and a restriction map of the DNA was determined. The DNA appeared to carry cohesive ends. Deletion mutants of actinophage B alpha were isolated by five cycles of treatment with 15 mM PPi. Both mutants had deletions of 2.5 of 1.8 megadaltons near one end of the genome, and one of them lost the single EcoRI cleavage site.

  11. Prevalence and Nature of Hearing Loss in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Van Eynde, Charlotte; Swillen, Ann; Lambeens, Elien; Verhaert, Nicolas; Desloovere, Christian; Luts, Heleen; Vander Poorten, Vincent; Devriendt, Koenraad; Hens, Greet

    2016-01-01

    Purpose: The purpose of this study was to clarify the prevalence, type, severity, and age-dependency of hearing loss in 22q11.2 deletion syndrome. Method: Extensive audiological measurements were conducted in 40 persons with proven 22q11.2 deletion (aged 6-36 years). Besides air and bone conduction thresholds in the frequency range between 0.125…

  12. Hepatic Mttp deletion reverses gallstone susceptibility in L-Fabp knockout mice

    OpenAIRE

    Xie, Yan; Fung, Ho Yee Joyce; Newberry, Elizabeth P.; Kennedy, Susan,; Luo, Jianyang; Crooke, Rosanne M.; Graham, Mark J.; Davidson, Nicholas O.

    2014-01-01

    Previous studies demonstrated that L-Fabp KO mice are more susceptible to lithogenic diet (LD)-induced gallstones because of altered hepatic cholesterol metabolism and increased canalicular cholesterol secretion. Other studies demonstrated that liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) reduced LD-induced gallstone formation by increasing biliary phospholipid secretion. Here we show that mice with combined deletion (i.e., DKO mice) are protected from LD-ind...

  13. Age-and gender-dependent obesity in individuals with 16p11.2 deletion

    Institute of Scientific and Technical Information of China (English)

    Yongguo Yu; Haitao Zhu; David T. Miller; James F. Gusella; Orah S. Platt; Bai-Lin Wu; Yiping Shen

    2011-01-01

    Recurrent genomic imbalances at 16p11.2 are genetic risk factors of variable penetrance for developmental delay and autism.Recently,16p11.2 (chr16:29.5 Mb-30.1 Mb) deletion has also been detected in individuals with early-onset severe obesity.The penetrance of 16p11.2deletion as a genetic risk factor for obesity is unknown.We evaluated the growth and body mass characteristics of 28 individuals with 16p11.2(chr16:29.5 Mb-30.1 Mb) deletion originally ascertained for their developmental disorders by reviewing their medical records.We found that nine individuals could be classilied as obese and six as overweight.These individuals generally had early feeding and growth difficulties,and started to gain excessive weight around 5-6 years of age.Thirteen out of the 18 deletion carriers aged 5 years and older (72%) were overweight or obese,whereas only two of 10 deletion carriers (20%) younger than five were overweight or obese.Males exhibited more severe obesity than females.Thus,the obesity phenotype of 16p11.2 deletion carriers is of juvenile onset,exhibited an age.and gender-dependent penetrance.16p11.2 deletion appears to predispose individuals to juvenile onset obesity and in this case are similar to the well-described Prader-Willi syndrome (PWS).Early detection of this deletion will provide opportunity to prevent obesity.

  14. Deletion analysis of SMN1 and NAIP genes in southern Chinese children with spinal muscular atrophy

    Institute of Scientific and Technical Information of China (English)

    Yu-hua LIANG; Xiao-ling CHEN; Zhong-sheng YU; Chun-yue CHEN; Sheng BI; Lian-gen MAO; Bo-lin ZHOU; Xian-ning ZHANG

    2009-01-01

    Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are rec-ognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: SMA1, SMA2, and SMA3. The survival of motor neuron (SMN) gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was performed to detect the deletion of both exon 7 and exon 8 of SMNI and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMAI patients and 76% (13/17) of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMN1 exon 7 along with 24% (4/17) of SMA2 patients. Eleven out of 32 (34%) SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NAIP deletion. The findings of homozygous deletions of exon 7 and/or exon 8 of SMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion of SMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NA1P gene may be a modifying factor for disease severity of SMA 1. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA.

  15. Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Juyal, R.C.; Figuera, L.E.; Hauge, X. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1996-05-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable, multiple congenital anomalies/mental retardation syndrome caused by an interstitial deletion involving band p11.2 of chromosome 17. Toward the molecular definition of the interval defining this microdeletion syndrome, 62 unrelated SMS patients in conjunction with 70 available unaffected parents were molecularly analyzed with respect to the presence or absence of 14 loci in the proximal region of the short arm of chromosome 17. A multifaceted approach was used to determine deletion status at the various loci that combined (1) FISH analysis, (2) PCR and Southern analysis of somatic cell hybrids retaining the deleted chromosome 17 from selected patients, and (3) genotype determination of patients for whom a parent(s) was available at four microsatellite marker loci and at four loci with associated RFLPs. The relative order of two novel anonymous markers and a new microsatellite marker was determined in 17p11.2. The results confirmed that the proximal deletion breakpoint in the majority of SMS patients is located between markers D17S58 (EW301) and D17S446 (FG1) within the 17p11.1-17p11.2 region. The common distal breakpoint was mapped between markers cCI17-638, which lies distal to D17S71, and cCI17-498, which lies proximal to the Charcot Marie-Tooth disease type 1A locus. The locus D17S258 was found to be deleted in all 62 patients, and probes from this region can be used for diagnosis of the SMS deletion by FISH. Ten patients demonstrated molecularly distinct deletions; of these, two patients had smaller deletions and will enable the definition of the critical interval for SMS. 49 refs.

  16. Geometric figure–ground cues override standard depth from accretion-deletion

    Science.gov (United States)

    Tanrıkulu, Ömer Dağlar; Froyen, Vicky; Feldman, Jacob; Singh, Manish

    2016-01-01

    Accretion-deletion is widely considered a decisive cue to surface depth ordering, with the accreting or deleting surface interpreted as behind an adjoining surface. However, Froyen, Feldman, and Singh (2013) have shown that when accretion-deletion occurs on both sides of a contour, accreting-deleting regions can also be perceived as in front and as self-occluding due to rotation in three dimensions. In this study we ask whether geometric figure–ground cues can override the traditional “depth from accretion-deletion” interpretation even when accretion-deletion takes place only on one side of a contour. We used two tasks: a relative-depth task (front/back), and a motion-classification task (translation/rotation). We conducted two experiments, in which texture in only one set of alternating regions was moving; the other set was static. Contrary to the traditional interpretation of accretion-deletion, the moving convex and symmetric regions were perceived as figural and rotating in three dimensions in roughly half of the trials. In the second experiment, giving different motion directions to the moving regions (thereby weakening motion-based grouping) further weakened the traditional accretion-deletion interpretation. Our results show that the standard “depth from accretion-deletion” interpretation is overridden by static geometric cues to figure–ground. Overall, the results demonstrate a rich interaction between accretion-deletion, figure–ground, and structure from motion that is not captured by existing models of depth from motion. PMID:26982528

  17. Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification.

    OpenAIRE

    Chamberlain, J S; Gibbs, R A; Ranier, J E; Nguyen, P N; Caskey, C. T.

    1988-01-01

    The application of recombinant DNA technology to prenatal diagnosis of many recessively inherited X-linked diseases is complicated by a high frequency of heterogeneous, new mutations (1). Partial gene deletions account for more than 50% of Duchenne muscular dystrophy (DMD) lesions, and approximately one-third of all cases result from a new mutation (2-5). We report the isolation and DNA sequence of several deletion prone exons from the human DMD gene. We also describe a rapid method capable o...

  18. Genomic deletions and precise removal of transposable elements mediated by short identical DNA segments in primates

    OpenAIRE

    Louie N van de Lagemaat; Gagnier, Liane; Medstrand, Patrik; Mager, Dixie L.

    2005-01-01

    Insertion of transposable elements is a major cause of genomic expansion in eukaryotes. Less is understood, however, about mechanisms underlying contraction of genomes. In this study, we show that retroelements can, in rare cases, be precisely deleted from primate genomes, most likely via recombination between 10- to 20-bp target site duplications (TSDs) flanking the retroelement. The deleted loci are indistinguishable from pre-integration sites, effectively reversing the insertion. Through h...

  19. Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy

    DEFF Research Database (Denmark)

    Møller, Rikke S; Weber, Yvonne G; Klitten, Laura L;

    2013-01-01

    Neurexins are neuronal adhesion molecules located in the presynaptic terminal, where they interact with postsynaptic neuroligins to form a transsynaptic complex required for efficient neurotransmission in the brain. Recently, deletions and point mutations of the neurexin 1 (NRXN1) gene have been ...... associated with a broad spectrum of neuropsychiatric disorders. This study aimed to investigate if NRXN1 deletions also increase the risk of idiopathic generalized epilepsies (IGEs)....

  20. In vitro assembly of apophytochrome and apophytochrome deletion mutants expressed in yeast with phycocyanobilin.

    OpenAIRE

    Deforce, L; Tomizawa, K; Ito, N; Farrens, D; Song, P S; Furuya, M.

    1991-01-01

    Recombinant pea type I phytochrome apoprotein expressed in yeast is shown to assemble in vitro with phycocyanobilin to produce a photoreversible phytochrome-like adduct. As an initial investigation of the amino acid sequence requirements for chromophore incorporation, three phyA gene product deletion mutants were produced in yeast. Truncation of the N-terminal tail to residue 46 demonstrates that this region is not critical to bilin attachment, but a deletion mutant lacking 222 amino acids fr...

  1. Candidate Genes and the Behavioral Phenotype in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Prasad, Sarah E.; Howley, Sarah; Murphy, Kieran C.

    2008-01-01

    There is an overwhelming evidence that children and adults with 22q11.2 deletion syndrome (22q11.2DS) have a characteristic behavioral phenotype. In particular, there is a growing body of evidence that indicates an unequivocal association between 22q11.2DS and schizophrenia, especially in adulthood. Deletion of 22q11.2 is the third highest risk…

  2. Catecholamine metabolism drives generation of mitochondrial DNA deletions in dopaminergic neurons.

    Science.gov (United States)

    Neuhaus, Johannes F G; Baris, Olivier R; Hess, Simon; Moser, Natasha; Schröder, Hannsjörg; Chinta, Shankar J; Andersen, Julie K; Kloppenburg, Peter; Wiesner, Rudolf J

    2014-02-01

    Accumulation of mitochondrial DNA deletions is observed especially in dopaminergic neurons of the substantia nigra during ageing and even more in Parkinson's disease. The resulting mitochondrial dysfunction is suspected to play an important role in neurodegeneration. However, the molecular mechanisms involved in the preferential generation of mitochondrial DNA deletions in dopaminergic neurons are still unknown. To study this phenomenon, we developed novel polymerase chain reaction strategies to detect distinct mitochondrial DNA deletions and monitor their accumulation patterns. Applying these approaches in in vitro and in vivo models, we show that catecholamine metabolism drives the generation and accumulation of these mitochondrial DNA mutations. As in humans, age-related accumulation of mitochondrial DNA deletions is most prominent in dopaminergic areas of mouse brain and even higher in the catecholaminergic adrenal medulla. Dopamine treatment of terminally differentiated neuroblastoma cells, as well as stimulation of dopamine turnover in mice over-expressing monoamine oxidase B both induce multiple mitochondrial DNA deletions. Our results thus identify catecholamine metabolism as the driving force behind mitochondrial DNA deletions, probably being an important factor in the ageing-associated degeneration of dopaminergic neurons.

  3. Genotype-phenotype correlation in 13q13.3-q21.3 deletion.

    Science.gov (United States)

    Tosca, Lucie; Brisset, Sophie; Petit, François M; Metay, Corinne; Latour, Stéphanie; Lautier, Benoît; Lebas, Axel; Druart, Luc; Picone, Olivier; Mas, Anne-Elisabeth; Prévot, Sophie; Tardieu, Marc; Goossens, Michel; Tachdjian, Gérard

    2011-01-01

    Pure interstitial deletions of the long arm of chromosome 13 are correlated with variable phenotypes according to the size and the location of the deleted region. Deletions involving the 13q13q21 region are rare. In order to establish interstitial 13q genotype-phenotype correlation, we used high resolution 244K oligonucleotide array in addition to conventional karyotype and molecular (fluorescent in situ hybridization, microsatellite markers analysis) techniques in two independent probands carrying a deletion 13q13 to 13q21. First patient was a 3-year-old girl with mental retardation and dysmorphy carrying a 13q13.3q21.31 de novo deletion diagnosed post-natally. The second one was a fetus with de novo del(13)(q14q21.2) associated with first trimester increased nuchal translucency. We showed that specific dysmorphic features (macrocephaly, high forehead, hypertelorism, large nose, large and malformed ears and retrognathia) were correlated to the common 13q14q21 chromosomal segment. Physical examination revealed overgrowth with global measurement up to the 95th percentile in both probands. This is the second description of overgrowth in patients carrying a 13q deletion. Haploinsufficiency of common candidates genes such as CKAP2, SUGT1, LECT1, DCLK1 and SMAD9, involved in cell division and bone development, is a possible mechanism that could explain overgrowth in both patients. This study underlines also that cytogenetic analysis could be performed in patients with overgrowth.

  4. Unambiguous molecular detections with multiple genetic approach for the complicated chromosome 22q11 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Lin Lung-Huang

    2009-02-01

    Full Text Available Abstract Background Chromosome 22q11 deletion syndrome (22q11DS causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions. Methods We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH, quantitative real-time polymerase chain reaction (qPCR and multiplex ligation-dependent probe amplification (MLPA. Results Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (p Conclusion Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.

  5. Deletion of chromosome 2q24-q31 causes characteristic digital anomalies: Case report and review

    Energy Technology Data Exchange (ETDEWEB)

    Boles, R.G. [Univ. of Southern California School of Medicine, Los Angeles, CA (United States); Pober, B.R.; Gibson, L.H. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1995-01-16

    We describe a newborn boy with multiple anomalies, including bilateral split foot and an interstitial deletion of chromosome 2 (q24.2-q31.1). Four additional cases in 2 families involving similar deletions have been reported. Bilateral digital anomalies of hands and feet were seen in all 5 cases, including a wide cleft between the first and second toes, wide halluces, brachsyndactyly of the toes, and camptodactyly of the fingers. Other common manifestations have included postnatal growth and mental retardation, microcephaly, down-slanting palpebral fissures, micrognathia, and apparently low-set ears. Bilateral digital anomalies were reported in 22 of 24 cases with deletions including at least part of region 2q24-q31. Digital anomalies were not prevalent in 18 patients with deletions of chromosome 2q not overlapping 2q24-q31. 2q31.1 appears to be the common deleted segment in all cases with significant digital anomalies, which implies the existence of one or more genes involved in distal limb morphogenesis in this region. HOXD13 and EVX2, located in the proximity of 2q31, were not deleted in our patient by Southern analysis. Bilateral digital malformations of the hands and feet associated with other anomalies should be evaluated by chromosome analysis focused at the 2q24-q31 region. 42 refs., 5 figs., 2 tabs.

  6. Mosaic 18q21.2 deletions including the TCF4 gene: a clinical report.

    Science.gov (United States)

    Rossi, Massimiliano; Labalme, Audrey; Cordier, Marie-Pierre; Till, Marianne; Blanchard, Gaëlle; Dubois, Remi; Guibaud, Laurent; Heissat, Sophie; Javouhey, Etienne; Lachaux, Alain; Mure, Pierre-Yves; Ville, Dorothée; Edery, Patrick; Sanlaville, Damien

    2012-12-01

    Pitt-Hopkins syndrome (PTHS) is characterized by distinctive facial dysmorphism, profound intellectual disability, and the possible occurrence of epilepsy and breathing anomalies. It is caused by haploinsufficiency of the TCF4 gene. No significant difference in clinical severity has been reported to date between PTHS patients carrying 18q21 deletions including the TCF4 gene, and those harboring TCF4 point mutations, suggesting a lack of genotype/phenotype correlation. Moreover, the size of 18q21 deletions including the TCF4 gene does not appear to have a significant effect on the phenotypic severity, suggesting that TCF4 haploinsufficiency is the most important prognostic factor in 18q deletions. We describe two unrelated patients presenting with clinical features reminiscent of PTHS and carrying mosaic interstitial 18q21 deletions characterized by array comparative genomic hybridization. One of the patients presented the lowest level of mosaic 18q21 deletion reported to date (5-10%). Our report and a review of the literature show that the mosaic status does not appear to have a significant effect on the clinical severity of 18q21 deletions, which are associated with a poor neurological outcome, whereas a mosaic TCF4 point mutation can result in a significantly milder phenotype. Malformations of internal organs are currently considered to be rare in PTHS. The patients described here had visceral anomalies, suggesting that a full morphological assessment, including heart and abdominal ultrasound scans, should be performed systematically in PTHS patients. PMID:23165966

  7. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-05-01

    From 1971--1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF{sub 1} mice irradiated with {sup 60}Co {gamma}-rays or JANUS fission-spectrum neutrons. Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice were analyzed for mRb deletions. In all normal mouse tissues studies all six mRb exon fragments were present on Southern blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, 1 of 6 tumors from {gamma}-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5{prime} region of the mRb gene.

  8. Deletion of chromosome 21 in a girl with congenital hypothyroidism and mild mental retardation

    Energy Technology Data Exchange (ETDEWEB)

    Ahlbom, B.E.; Anneren, G. [Univ. Hospital, Uppsala (Sweden); Sidenvall, R. [Central Hospital of Hudiksvall (Sweden)

    1996-08-23

    We report on a girl with a large interstitial deletion of the long arm of chromosome 21 and with mild mental retardation, congenital hypothyroidism, and hyperopia. The deletion [del(21)(q11.1-q22.1)] extends molecularly from marker D21S215 to D21S213. The distal breakpoint is not clearly defined but is situated between markers D21S213 and IFNAR. This patient has the largest deletion of chromosome 21 known without having severe mental retardation or malformations. The deletion does not involve the {open_quotes}Down syndrome chromosome{close_quotes} region, the region of chromosome 21 which in trisomy causes most of the manifestations of Down syndrome. Apparently, the proximal part of the long arm of chromosome 21 does not include genes that are responsible for severe clinical effects in the event of either deletion or duplication, since several reported patients with either trisomy or deletion of this region have mild phenotypic abnormalities. Congenital hypothyroidism is much more common in Down syndrome than in the average population. Thus, the congenital hypothyroidism of the present patient might indicate that there is one or several genes on the proximal part of chromosome 21, which might be of importance for the thyroid function. 24 refs., 4 figs., 2 tabs.

  9. Grin1 receptor deletion within CRF neurons enhances fear memory.

    Directory of Open Access Journals (Sweden)

    Georgette Gafford

    Full Text Available Corticotropin releasing factor (CRF dysregulation is implicated in mood and anxiety disorders such as posttraumatic stress disorder (PTSD. CRF is expressed in areas engaged in fear and anxiety processing including the central amygdala (CeA. Complicating our ability to study the contribution of CRF-containing neurons to fear and anxiety behavior is the wide variety of cell types in which CRF is expressed. To manipulate specific subpopulations of CRF containing neurons, our lab has developed a mouse with a Cre recombinase gene driven by a CRF promoter (CRFp3.0Cre (Martin et al., 2010. In these studies, mice that have the gene that encodes NR1 (Grin1 flanked by loxP sites (floxed were crossed with our previously developed CRFp3.0Cre mouse to selectively disrupt Grin1 within CRF containing neurons (Cre+/fGrin1+. We find that disruption of Grin1 in CRF neurons did not affect baseline levels of anxiety, locomotion, pain sensitivity or exploration of a novel object. However, baseline expression of Grin1 was decreased in Cre+/fGrin1+ mice as measured by RTPCR. Cre+/fGrin1+ mice showed enhanced auditory fear acquisition and retention without showing any significant effect on fear extinction. We measured Gria1, the gene that encodes AMPAR1 and the CREB activator Creb1 in the amygdala of Cre+/fGrin1+ mice after fear conditioning. Both Gria1 and Creb1 were enhanced in the amygdala after training. To determine if the Grin1-expressing CRF neurons within the CeA are responsible for the enhancement of fear memory in adults, we infused a lentivirus with Cre driven by a CRF promoter (LV pCRF-Cre/fGrin1+ into the CeA of floxed Grin1 mice. Cre driven deletion of Grin1 specifically within CRF expressing cells in the CeA also resulted in enhanced fear memory acquisition and retention. Altogether, these findings suggest that selective disruption of Grin1 within CeA CRF neurons strongly enhances fear memory.

  10. Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors.

    Directory of Open Access Journals (Sweden)

    Silvia Hennecke

    Full Text Available A somatic deletion at the proximal end of canine chromosome 27 (CFA27 was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5 and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors.Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32. Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry.The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9 showed the highest frequency of the deletion (67% and those malignomas without microscopical high fraction of benign tissue (n = 71 had a 32% frequency (p<0.01 vs. benign samples. The Ki-67 score was found to be significantly higher (p<0.05 in the PFDN5-deleted group compared to malignant tumors without the deletion.A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer

  11. Different pre-S deletion patterns and their association with hepatitis B virus genotypes

    Science.gov (United States)

    Chen, Bing-Fang

    2016-01-01

    AIM To investigate the associations of different types of pre-S deletions with hepatitis B virus (HBV) genotypes. METHODS The sequences of the pre-S region, basal core promoter (BCP) mutation, and precore (PC) mutation were examined through direct DNA sequencing or clonal analysis and sequencing in 273 HBV carriers, namely 55 asymptomatic carriers, 55 carriers with chronic hepatitis (CH), 55 with liver cirrhosis (LC), 53 with liver cirrhotic hepatocellular carcinoma (LC-HCC), and 55 with noncirrhotic HCC. A total of 126 HBV carriers (46.2%) harbored pre-S deletions. The DNA sequences of pre-S deletion mutants from 43 age-matched genotype B (HBV/B)-infected carriers and 43 age-matched genotype C (HBV/C)-infected carriers were further examined, aligned, and compared. RESULTS No significant difference was observed in the mean age distribution (P = 0.464), male sex (P = 0.805), viral load (P = 0.635), or BCP mutation (P = 0.117) between the HBV/B and HBV/C groups. However, the rate of PC mutation was significantly higher in the HBV/B-infected carriers than in the HBV/C-infected carriers (P = 0.003). Both genotypes exhibited a high rate of deletion in the C-terminal half of the pre-S1 region and N-terminus of the pre-S2 region (86.0% and 79.1% in the HBV/B group; 69.8% and 72.1% in the HBV/C group, respectively). Epitope mapping showed that deletion in several epitope sites was frequent in both genotypes, particularly pS1-BT and pS2-B2. Conversely, the rate of pS2-B1 deletion was significantly higher in the HBV/B group (72.1% vs 37.2%, P = 0.002), and the rate of pS2-T deletion was significantly higher in the HBV/C group (48.8% vs 25.6%, P = 0.044). Functional mapping showed that the rate of deletion in three functional sites (the nucleocapsid binding site, start codon of M, and site for viral secretion) located in the N-terminus of the pre-S2 region was significantly higher in the HBV/B group (P < 0.05). One type of N-terminus pre-S1 deletion mutant with deletion of

  12. Genotype/phenotype correlation in women with nonmosaic X chromosome deletions and Turner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Zinn, A.R. [Univ. of Texas Southwestern Medical School, Dallas, TX (United States)

    1994-09-01

    Turner syndrome is a complex human developmental disorder associated with the absence of the second sex chromosome (monosomy X). Cardinal features of the Turner phenotype include high intrauterine lethality, growth retardation, gonadal failure, and the variable presence of specific somatic abnormalities such as webbed neck, lymphedema, and skeletal abnormalities. Recent observations support the hypothesis that the phenotype associated with monosomy X results from haploid dosage of genes common the X and Y chromosomes that escape X-inactivation ({open_quotes}Turner genes{close_quotes}). Apart from a locus causing short stature that maps to the pseudoautosomal region on the distal short arm, the location of X-linked Turner genes is not known. Karyotype/phenotype correlations in women with partial X deletions have been inconsistent. However, previous studies have focused on sporadic sex chromosome aberrations and may have been confounded by occult mosaicism. In addition, mapping of deletions was limited by the resolution of cytogenetic techniques. I am reexamining genotype/phenotype correlations in partial X monosomy, focusing on a subset of cases in which mosaicism is highly unlikely (e.g., unbalanced X-autosome translocations, familial X deletions), and using molecular techniques to map deletions. I have collected eight cases of nonmosaic X deletions in women with varied manifestations of Turner syndrome. Cytogenetic data suggests that genes responsible for Turner anatomic abnormalities may lie within a critical region of the very proximal portion of the short arm (Xp11). Molecular characterization of the deletions is in progress. Methods include (1) fluorescence in situ hybridization of metaphase spreads from patient-derived cell lines, using cosmid probes that map to known locations on Xp, and (2) sequence tagged site (STS) content mapping of somatic cell hybrids retaining the deleted X chromosomes derived from these cell lines.

  13. Multi-exon deletions of the FBN1 gene in Marfan syndrome

    Directory of Open Access Journals (Sweden)

    Schrijver Iris

    2001-10-01

    Full Text Available Abstract Background Mutations in the fibrillin -1 gene (FBN1 cause Marfan syndrome (MFS, an autosomal dominant multi-system connective tissue disorder. The 200 different mutations reported in the 235 kb, 65 exon-containing gene include only one family with a genomic multi-exon deletion. Methods We used long-range RT-PCR for mutation detection and long-range genomic PCR and DNA sequencing for identification of deletion breakpoints, allele-specific transcript analyses to determine stability of the mutant RNA, and pulse-chase studies to quantitate fibrillin synthesis and extracellular matrix deposition in cultured fibroblasts. Southern blots of genomic DNA were probed with three overlapping fragments covering the FBN1 coding exons Results Two novel multi-exon FBN1 deletions were discovered. Identical nucleotide pentamers were found at or near the intronic breakpoints. In a Case with classic MFS, an in-frame deletion of exons 42 and 43 removed the C-terminal 24 amino acids of the 5th LTBP (8-cysteine domain and the adjacent 25th calcium-binding EGF-like (6-cysteine domain. The mutant mRNA was stable, but fibrillin synthesis and matrix deposition were significantly reduced. A Case with severe childhood-onset MFS has a de novo deletion of exons 44–46 that removed three EGF-like domains. Fibrillin protein synthesis was normal, but matrix deposition was strikingly reduced. No genomic rearrangements were detected by Southern analysis of 18 unrelated MFS samples negative for FBN1 mutation screening. Conclusions Two novel deletion cases expand knowledge of mutational mechanisms and genotype/phenotype correlations of fibrillinopathies. Deletions or mutations affecting an LTBP domain may result in unstable mutant protein cleavage products that interfere with microfibril assembly.

  14. The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

    Directory of Open Access Journals (Sweden)

    Devilee Peter

    2009-04-01

    Full Text Available Abstract Background Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH, the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. Methods We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. Results A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. Conclusion The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL.

  15. Clinical comparison of 10q26 overlapping deletions: delineating the critical region for urogenital anomalies.

    Science.gov (United States)

    Vera-Carbonell, Ascensión; López-González, Vanesa; Bafalliu, Juan Antonio; Ballesta-Martínez, María J; Fernández, Asunción; Guillén-Navarro, Encarna; López-Expósito, Isabel

    2015-04-01

    The 10q26 deletion syndrome is a clinically heterogeneous disorder. The most common phenotypic characteristics include pre- and/or postnatal growth retardation, microcephaly, developmental delay/intellectual disability and a facial appearance consisting of a broad nasal bridge with a prominent nose, low-set malformed ears, strabismus, and a thin vermilion of the upper lip. In addition, limb and cardiac anomalies as well as urogenital anomalies are occasionally observed. In this report, we describe three unrelated females with 10q26 terminal deletions who shared clinical features of the syndrome, including urogenital defects. Cytogenetic studies showed an apparently de novo isolated deletion of the long arm of chromosome 10, with breakpoints in 10q26.1, and subsequent oligo array-CGH analysis confirmed the terminal location and defined the size of the overlapping deletions as ∼ 13.46, ∼ 9.31 and ∼ 9.17 Mb. We compared the phenotypic characteristics of the present patients with others reported to have isolated deletions and we suggest that small 10q26.2 terminal deletions may be associated with growth retardation, developmental delay/intellectual disability, craniofacial features and external genital anomalies whereas longer terminal deletions affecting the 10q26.12 and/or 10q26.13 regions may be responsible for renal/urinary tract anomalies. We propose that the haploinsufficiency of one or several genes located in the 10q26.12-q26.13 region may contribute to the renal or urinary tract pathogenesis and we highlight the importance of FGFR2 and probably of CTBP2 as candidate genes. PMID:25655674

  16. Becker muscular dystrophy in Indian patients: Analysis of dystrophin gene deletion patterns

    Directory of Open Access Journals (Sweden)

    Dastur Rashna

    2008-01-01

    Full Text Available Background: Becker muscular dystrophy (BMD is caused by mutations in the dystrophin gene with variable phenotypes. Becker muscular dystrophy patients have low levels of nearly full-length dystrophin and carry in-frame mutations, which allow partial functioning of the protein. Aim: To study the deletion patterns of BMD and to correlate the same with reading frame rule and different phenotypes. Setting: A tertiary care teaching hospital. Design: This is a prospective hospital-based study. Materials and Methods: Thirty-two exons spanning different "hot spot" regions using Multiplex PCR techniques were studied in 347 patients. Two hundred and twenty-two showed deletions in one or more of the 32 exons. Out of these, 46 diagnosed as BMD patients were analyzed. Results: Forty-six BMD patients showed deletions in both regions of the dystrophin gene. Out of these 89.1% (41/46 were in-frame deletions. Deletions starting with Exon 45 were found in 76.1% (35/46 of the cases. Mutations in the majority of cases i.e. 39/46 (84.8% were seen in 3′ downstream region (Exon 45-55, distal rod domain. Few, i.e. 5/46 (10.8% showed deletions in 5′ upstream region (Exons 3-20, N-terminus and proximal rod domain of the gene, while in 2/46 (4.4% large mutations (>40 bp spanning both regions (Exons 3-55 were detected. Conclusion: This significant gene deletion analysis has been carried out for BMD patients particularly from Western India using 32 exons.

  17. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

    Directory of Open Access Journals (Sweden)

    Wen Ying

    2010-07-01

    Full Text Available Abstract Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs, and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously

  18. Type I oculocutaneous albinism (OCA1) associated with a large deletion of the tyrosinase (TYR) gene

    Energy Technology Data Exchange (ETDEWEB)

    Spritz, R.A.; Wick, P.A.; Holmes, S.A.; Schnur, R.E. [Univ. of Wisconsin, Madison, WI (United States)]|[Children`s Hospital of Philadelphia, PA (United States)

    1994-09-01

    OCA1 is an autosomal recessive disorder in which the biosynthesis of melanin is reduced or absent in skin, hair, and eyes, due to deficient enzymatic activity of tyrosinase. TYR consists of 5 exons spanning over 65 kb at 11q14-q21. Analyses of TYR in >400 unrelated patients with OCA1 have identified more than 50 different point mutations; however, no large deletions have been detected. Here we report a large deletion of TYR in a Caucasian boy with OCA1B. Simultaneous SSCP/heteroduplex screening and DNA sequence analysis indicated that the patient was apparently homozygous for a previously described TYR mutation, adjacent to the 3` splice site of IVS2 (-7, t{r_arrow}a). To distinguish between possible gene deletion vs. maternal uniparental isodisomy, we characterized several chromosome 11 polymorphisms. Maternal uniparental isodisomy was excluded by the patient`s heterozygosity for alleles at D11S35 (11q21-122) and HBG2 (11p15.5). In addition, the patient failed to inherit paternal alleles at an MboI RFLP in exon 1 of TYR and at a TaqI RFLP in the promoter region of the gene. To detect a possible submicroscopic deletion, we performed quantitative Southern blot hybridization using a full length TYR cDNA. Compared with controls, both the patient and his father appeared deleted for two or three TYR-derived PstI fragments; the two TYRL-derived fragments appeared normal. These data indicate that the patient and his father have a partial TYR deletion, including at least exons 1, 2, and IVS2. Based on the organization of the gene, this deletion is at least 50 kb in size. The patient is thus hemizygous for the maternally-inherited mutation in IVS2, accounting for his OCA1B phenotype.

  19. Structural and dynamic changes associated with beneficial engineered single-amino-acid deletion mutations in enhanced green fluorescent protein

    International Nuclear Information System (INIS)

    The beneficial engineered single-amino-acid deletion variants EGFPD190Δ and EGFPA227Δ have been studied. Single-amino-acid deletions are a common part of the natural evolutionary landscape but are rarely sampled during protein engineering owing to limited and prejudiced molecular understanding of mutations that shorten the protein backbone. Single-amino-acid deletion variants of enhanced green fluorescent protein (EGFP) have been identified by directed evolution with the beneficial effect of imparting increased cellular fluorescence. Biophysical characterization revealed that increased functional protein production and not changes to the fluorescence parameters was the mechanism that was likely to be responsible. The structure EGFPD190Δ containing a deletion within a loop revealed propagated changes only after the deleted residue. The structure of EGFPA227Δ revealed that a ‘flipping’ mechanism was used to adjust for residue deletion at the end of a β-strand, with amino acids C-terminal to the deletion site repositioning to take the place of the deleted amino acid. In both variants new networks of short-range and long-range interactions are generated while maintaining the integrity of the hydrophobic core. Both deletion variants also displayed significant local and long-range changes in dynamics, as evident by changes in B factors compared with EGFP. Rather than being detrimental, deletion mutations can introduce beneficial structural effects through altering core protein properties, folding and dynamics, as well as function

  20. Structural and dynamic changes associated with beneficial engineered single-amino-acid deletion mutations in enhanced green fluorescent protein

    Energy Technology Data Exchange (ETDEWEB)

    Arpino, James A. J. [Cardiff University, Park Place, Cardiff CF10 3AT Wales (United Kingdom); Rizkallah, Pierre J., E-mail: rizkallahp@cardiff.ac.uk [Cardiff University, Heath Park, Cardiff CF14 4XN Wales (United Kingdom); Jones, D. Dafydd, E-mail: rizkallahp@cardiff.ac.uk [Cardiff University, Park Place, Cardiff CF10 3AT Wales (United Kingdom)

    2014-08-01

    The beneficial engineered single-amino-acid deletion variants EGFP{sup D190Δ} and EGFP{sup A227Δ} have been studied. Single-amino-acid deletions are a common part of the natural evolutionary landscape but are rarely sampled during protein engineering owing to limited and prejudiced molecular understanding of mutations that shorten the protein backbone. Single-amino-acid deletion variants of enhanced green fluorescent protein (EGFP) have been identified by directed evolution with the beneficial effect of imparting increased cellular fluorescence. Biophysical characterization revealed that increased functional protein production and not changes to the fluorescence parameters was the mechanism that was likely to be responsible. The structure EGFP{sup D190Δ} containing a deletion within a loop revealed propagated changes only after the deleted residue. The structure of EGFP{sup A227Δ} revealed that a ‘flipping’ mechanism was used to adjust for residue deletion at the end of a β-strand, with amino acids C-terminal to the deletion site repositioning to take the place of the deleted amino acid. In both variants new networks of short-range and long-range interactions are generated while maintaining the integrity of the hydrophobic core. Both deletion variants also displayed significant local and long-range changes in dynamics, as evident by changes in B factors compared with EGFP. Rather than being detrimental, deletion mutations can introduce beneficial structural effects through altering core protein properties, folding and dynamics, as well as function.

  1. Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number

    DEFF Research Database (Denmark)

    Mau Kai, Claudia; Juul, A; McElreavey, K;

    2008-01-01

    Deletions in the azoospermia factor (AZF) region of the Y chromosome are frequent in infertile men. The clinical consequences and the mode of inheritance of these deletions are not yet clear.......Deletions in the azoospermia factor (AZF) region of the Y chromosome are frequent in infertile men. The clinical consequences and the mode of inheritance of these deletions are not yet clear....

  2. Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?

    Directory of Open Access Journals (Sweden)

    Erin A Gutilla

    2016-01-01

    Full Text Available The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown ofPTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.

  3. Molecular and clinical characterization of patients with overlapping 10p deletions.

    Science.gov (United States)

    Lindstrand, Anna; Malmgren, Helena; Verri, Annapia; Benetti, Elisa; Eriksson, Maud; Nordgren, Ann; Anderlid, Britt-Marie; Golovleva, Irina; Schoumans, Jacqueline; Blennow, Elisabeth

    2010-05-01

    Chromosome 10p terminal deletions have been associated with DiGeorge phenotype, and within the same genomic region haploinsufficiency of GATA3 causes the HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia). We have performed detailed molecular analysis of four patients with partial overlapping 10p deletions by using FISH-mapping, array-CGH, and custom-designed high-resolution oligonucleotide array. All four patients had mental retardation and speech impairment and three of them showed variable signs of HDR syndrome. In addition, two patients had autistic behaviors and had similar dysmorphic features giving them a striking physical resemblance. A review of the literature identified 10 previously published cases with similar 10p deletions and reliable molecular or molecular cytogenetic mapping data. The combined information of present and previous cases suggests that partial deletions of 10p14-p15 represent a syndrome with a distinct and more severe phenotype than previously assumed. The main characteristics include severe mental retardation, language impairment, autistic behavior, and characteristic clinical features. A critical region involved in mental retardation and speech impairment is defined within 1.6 Mb in 10p15.3. In addition, deletion of 4.3 Mb within 10p14 is associated with autism and characteristic clinical findings. PMID:20425828

  4. A case report of 22q11 deletion syndrome confirmed by array-CGH method

    Directory of Open Access Journals (Sweden)

    Maryam Sedghi

    2012-01-01

    Full Text Available Velo-cardio-facial syndrome (VCFS is caused by a submicroscopic deletion on the long arm of chromosome 22 and affects approximately 1 in 4000 persons, making it the second most prevalent genetic syndrome after Down syndrome and the most common genetic syndrome associated with cleft palate. Most of the 22q11.2 deletion cases are new occurrences or sporadic; however, in about 10 % of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children. This report describes a 1.5 years-old male child with clinical signs of velo-cardio-facial syndrome (VCFS presented with heart defect, soft cleft palate, developmental delay, acrocephaly, seizure, MRI abnormalities and descriptive facial feature, such as hypertelorism. Array-CGH test was done to confirm the diagnosis; the result revealed a 2.6 Mbp deletion in 22q11.2 chromosome that containing TBX1 and COMT genes. Our data suggest that haploinsufficiency of TBX1 gene is probably a major contributor to some of the syndrome characteristic signs, such as heart defect. Because of developmental delay and dysmorphic facial feature were observed in the index′s mother and relatives, inherited autosomal dominant form of VCF is probable, and MLPA (multiplex ligation-dependent probe amplification test should be performed for parents to estimate the recurrent risk in next pregnancy.

  5. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    International Nuclear Information System (INIS)

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

  6. Abnormal auditory and language pathways in children with 16p11.2 deletion

    Directory of Open Access Journals (Sweden)

    Jeffrey I. Berman

    2015-01-01

    Full Text Available Copy number variations at chromosome 16p11.2 contribute to neurodevelopmental disorders, including autism spectrum disorder (ASD. This study seeks to improve our understanding of the biological basis of behavioral phenotypes common in ASD, in particular the prominent and prevalent disruption of spoken language seen in children with the 16p11.2 BP4–BP5 deletion. We examined the auditory and language white matter pathways with diffusion MRI in a cohort of 36 pediatric deletion carriers and 45 age-matched controls. Diffusion MR tractography of the auditory radiations and the arcuate fasciculus was performed to generate tract specific measures of white matter microstructure. In both tracts, deletion carriers exhibited significantly higher diffusivity than that of controls. Cross-sectional diffusion parameters in these tracts changed with age with no group difference in the rate of maturation. Within deletion carriers, the left-hemisphere arcuate fasciculus mean and radial diffusivities were significantly negatively correlated with clinical language ability, but not non-verbal cognitive ability. Diffusion metrics in the right-hemisphere arcuate fasciculus were not predictive of language ability. These results provide insight into the link between the 16p11.2 deletion, abnormal auditory and language pathway structures, and the specific behavioral deficits that may contribute to neurodevelopmental disorders such as ASD.

  7. Neuronal Deletion of Ghrelin Receptor Almost Completely Prevents Diet-Induced Obesity.

    Science.gov (United States)

    Lee, Jong Han; Lin, Ligen; Xu, Pingwen; Saito, Kenji; Wei, Qiong; Meadows, Adelina G; Bongmba, Odelia Y N; Pradhan, Geetali; Zheng, Hui; Xu, Yong; Sun, Yuxiang

    2016-08-01

    Ghrelin signaling has major effects on energy and glucose homeostasis, but it is unknown whether ghrelin's functions are centrally and/or peripherally mediated. The ghrelin receptor, growth hormone secretagogue receptor (GHS-R), is highly expressed in the brain and detectable in some peripheral tissues. To understand the roles of neuronal GHS-R, we generated a mouse line where Ghsr gene is deleted in all neurons using synapsin 1 (Syn1)-Cre driver. Our data showed that neuronal Ghsr deletion abolishes ghrelin-induced spontaneous food intake but has no effect on total energy intake. Remarkably, neuronal Ghsr deletion almost completely prevented diet-induced obesity (DIO) and significantly improved insulin sensitivity. The neuronal Ghsr-deleted mice also showed improved metabolic flexibility, indicative of better adaption to different fuels. In addition, gene expression analysis suggested that hypothalamus and/or midbrain might be the sites that mediate the effects of GHS-R in thermogenesis and physical activity, respectively. Collectively, our results indicate that neuronal GHS-R is a crucial regulator of energy metabolism and a key mediator of DIO. Neuronal Ghsr deletion protects against DIO by regulating energy expenditure, not by energy intake. These novel findings suggest that suppressing central ghrelin signaling may serve as a unique antiobesity strategy. PMID:27207529

  8. [A Simple and Efficient Method of Inducing Targeted Deletions in the Drosophila Genome].

    Science.gov (United States)

    Kravchuk, O I; Mikhailov, V S; Savitsky, M Yu

    2015-11-01

    Deletion mutagenesis is one of the most efficient approaches to studying gene function. However, conventional methods of inducing targeted mutations in the drosophila genome are time- and labor-consuming. This work proposes a new, simple, and effective method of producing drosophila mutants with gene deletions. The method involves the insertion of I-Scel and I-CreI recognition sites and a fragment homologous to the target sequence into the chromosome region of interest by means of an attB-containing construct, the induction of double-strand DNA breaks by the appropriate meganuclease, and their repair by homologous recombination. The procedure results in a deletion extending from the attP-site to the target locus. A cassette was designed to enable single-step construct production for the deletion of any given genomic region. A set of markers facilitates the selection of recombination events. The efficacy of the proposed technique was confirmed by the induction of a 47-kb deletion containing the qtc gene.

  9. Screening of Dystrophin Gene Deletions in Egyptian Patients with DMD/BMD Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Laila K. Effat

    2000-01-01

    Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are allelic disorders caused by mutations within the dystrophin gene. Our study has identified 100 Egyptian families collected from the Human Genetics Clinic, National Research Center, Cairo. All cases were subjected to complete clinical evaluation pedigree analysis, electromyography studies, estimation of serum creatine phosphokinase enzyme (CPK levels and DNA analysis. Multiplex PCR using 18 pairs of specific primers were used for screening of deletion mutations within the dystrophin gene. A frequency of 55% among the families. Sixty per cent of detected deletions involved multiple exons spanning the major or the minor hot spot of the dystrophin gene. The remainder 40% which mainly involved exon 45. Comparing these findings with frequencies of other countries it was found that our figures fall within the reported range of 40%– for deletions. The distribution of deletions in our study and other different studies was variable and specific ethnic differences do not apparently account for specific deletions. In addition this study concluded that employment of the 18 exon analysis is a cost effective and a highly accurate (97% to launch a nationwide program.

  10. First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome.

    Science.gov (United States)

    Beygo, J; Buiting, K; Seland, S; Lüdecke, H-J; Hehr, U; Lich, C; Prager, B; Lohmann, D R; Wieczorek, D

    2012-01-01

    Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by facial anomalies and ear defects. TCS is caused by mutations in the TCOF1 gene and follows autosomal dominant inheritance. Recently, mutations in the POLR1D and POLR1C genes have also been identified to cause TCS. However, in a subset of patients no causative mutation could be found yet. Inter- and intrafamilial phenotypic variability is high as is the variety of mainly family-specific mutations identified throughout TCOF1. No obvious correlation between pheno- and genotype could be observed. The majority of described point mutations, small insertions and deletions comprising only a few nucleotides within TCOF1 lead to a premature termination codon. We investigated a cohort of 112 patients with a tentative clinical diagnosis of TCS by multiplex ligation-dependent probe amplification (MLPA) to search for larger deletions not detectable with other methods used. All patients were selected after negative screening for mutations in TCOF1, POLR1D and POLR1C. In 1 patient with an unequivocal clinical diagnosis of TCS, we identified a 3.367 kb deletion. This deletion abolishes exon 3 and is the first described single exon deletion within TCOF1. On RNA level we observed loss of this exon which supposedly leads to haploinsufficiency of TREACLE, the nucleolar phosphoprotein encoded by TCOF1.

  11. Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis.

    Science.gov (United States)

    Rachinger, Michael; Bauch, Melanie; Strittmatter, Axel; Bongaerts, Johannes; Evers, Stefan; Maurer, Karl-Heinz; Daniel, Rolf; Liebl, Wolfgang; Liesegang, Heiko; Ehrenreich, Armin

    2013-09-20

    Conjugative shuttle vectors of the pKVM series, based on an IncP transfer origin and the pMAD vector with a temperature sensitive replication were constructed to establish a markerless gene deletion protocol for Bacilli without natural competence such as the exoenzyme producer Bacillus licheniformis. The pKVM plasmids can be conjugated to strains of B. licheniformis and B. subtilis. For chromosomal gene deletion, regions flanking the target gene are fused and cloned in a pKVM vector prior to conjugative transfer from Escherichia coli to B. licheniformis. Appropriate markers on the vector backbone allow for the identification of the integration at the target locus and thereafter the vector excision, both events taking place via homologous recombination. The functionality of the deletion system was demonstrated with B. licheniformis by a markerless 939 bp in-frame deletion of the yqfD gene and the deletion of a 31 kbp genomic segment carrying a PBSX-like prophage. PMID:23916947

  12. Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation.

    Science.gov (United States)

    Lugtenberg, Dorien; Zangrande-Vieira, Luiz; Kirchhoff, Maria; Whibley, Annabel C; Oudakker, Astrid R; Kjaergaard, Susanne; Vianna-Morgante, Angela M; Kleefstra, Tjitske; Ruiter, Mariken; Jehee, Fernanda S; Ullmann, Reinhard; Schwartz, Charles E; Stratton, Michael; Raymond, F Lucy; Veltman, Joris A; Vrijenhoek, Terry; Pfundt, Rolph; Schuurs-Hoeijmakers, Janneke H M; Hehir-Kwa, Jayne Y; Froyen, Guy; Chelly, Jamel; Ropers, Hans Hilger; Moraine, Claude; Gècz, Jozef; Knijnenburg, Jeroen; Kant, Sarina G; Hamel, Ben C J; Rosenberg, Carla; van Bokhoven, Hans; de Brouwer, Arjan P M

    2010-03-01

    ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P-value = 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value = 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation.

  13. Antibodies with higher bactericidal activity induced by a Neisseria gonorrhoeae Rmp deletion mutant strain.

    Directory of Open Access Journals (Sweden)

    Guocai Li

    Full Text Available Neisseria gonorrhoeae (N. gonorrhoeae outer membrane protein reduction modifiable protein (Rmp has strong immunogenicity. However, anti-Rmp antibodies block rather than preserve the antibacterial effects of protective antibodies, which hampers the development of vaccines for gonococcal infections. We herein constructed an Rmp deletion mutant strain of N. gonorrhoeae by gene homologous recombination. The 261-460 nucleotide residues of Rmp gene amplified from N. gonorrhoeae WHO-A strain were replaced with a kanamycin-resistant Kan gene amplified from pET-28a. The resultant hybridized DNA was transformed into N. gonorrhoeae WHO-A strain. PCR was used to screen the colonies in which wild-type Rmp gene was replaced with a mutant gene fragment. Western blotting revealed that the Rmp deletion mutant strain did not express Rmp protein. Rmp deletion did not alter the morphological and Gram staining properties of the mutant strain that grew slightly more slowly than the wild-type one. Rmp gene mutated stably throughout 25 generations of passage. Antibody-mediated complement-dependent cytotoxicity assay indicated that the antibodies induced by the mutant strain had evidently higher bactericidal activities than those induced by the wild-type strain. Further modification of the Rmp deletion mutant strain is still required in the development of novel live attenuated vaccines for gonorrhea by Opa genes deletion or screening of phenotypic variant strains that do not express Opa proteins.

  14. Deletions in the fifth alpha helix of HIV-1 matrix block virus release

    International Nuclear Information System (INIS)

    The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1–α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release. - Highlights: • Deletions were identified in the C-terminus of matrix that block virus release. • These deletion mutants still multimerized and associated with membranes. • TEM showed the mutant particles were tethered to the cell surface. • Amino acid mutagenesis of the region did not affect release. • The data suggests that disruption of matrix structure blocks virus release

  15. The deletion of YLR042c improves ethanolic xylose fermentation by recombinant Saccharomyces cerevisiae.

    Science.gov (United States)

    Parachin, Nádia S; Bengtsson, Oskar; Hahn-Hägerdal, Bärbel; Gorwa-Grauslund, Marie-F

    2010-09-01

    In a recent study combining transcriptome analyses of a number of recombinant laboratory and industrial S. cerevisiae strains with improved xylose utilization and their respective control strains, the ORF YLR042c was identified as a downregulated gene and it was shown that the gene deletion improved aerobic growth on xylose in the tested strain background. In the present study, the influence of deleting YLR042c on xylose fermentation was investigated in two different xylose-fermenting strains: TMB3001, which expresses genes from the initial xylose catabolizing pathway, including heterologous xylose reductase (XR) and xylitol dehydrogenase (XDH) and endogenous xylulokinase (XK); and TMB3057, which, in addition to the initial xylose catabolizing pathway, overexpresses the endogenous genes encoding the non-oxidative pentose phosphate pathway enzymes. The deletion of YLR042c led to improved aerobic growth on xylose in both strain backgrounds. However, the effect was more significant in the strain with the poorer growth rate on xylose (TMB3001). Under anaerobic conditions, the deletion of YLR042c increased the specific xylose consumption rate and the ethanol and xylitol yields. In strain TMB3057, xylose consumption was also improved at low concentrations and during co-fermentation of xylose and glucose. The effect of the gene deletion and overexpression was also tested for different carbon sources. Altogether, these results suggest that YLR042c influences xylose and the assimilation of carbon sources other than glucose, and that the effect could be at the level of sugar transport or sugar signalling. PMID:20641017

  16. Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Woloschak, G.E. [Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology

    1997-08-01

    This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF{sub 1} male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P < 0.05) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed.

  17. A macaque's-eye view of human insertions and deletions: differences in mechanisms.

    Directory of Open Access Journals (Sweden)

    Erika M Kvikstad

    2007-09-01

    Full Text Available Insertions and deletions (indels cause numerous genetic diseases and lead to pronounced evolutionary differences among genomes. The macaque sequences provide an opportunity to gain insights into the mechanisms generating these mutations on a genome-wide scale by establishing the polarity of indels occurring in the human lineage since its divergence from the chimpanzee. Here we apply novel regression techniques and multiscale analyses to demonstrate an extensive regional indel rate variation stemming from local fluctuations in divergence, GC content, male and female recombination rates, proximity to telomeres, and other genomic factors. We find that both replication and, surprisingly, recombination are significantly associated with the occurrence of small indels. Intriguingly, the relative inputs of replication versus recombination differ between insertions and deletions, thus the two types of mutations are likely guided in part by distinct mechanisms. Namely, insertions are more strongly associated with factors linked to recombination, while deletions are mostly associated with replication-related features. Indel as a term misleadingly groups the two types of mutations together by their effect on a sequence alignment. However, here we establish that the correct identification of a small gap as an insertion or a deletion (by use of an outgroup is crucial to determining its mechanism of origin. In addition to providing novel insights into insertion and deletion mutagenesis, these results will assist in gap penalty modeling and eventually lead to more reliable genomic alignments.

  18. Exon Deletion Pattern in Duchene Muscular Dystrophy in North West of Iran

    Directory of Open Access Journals (Sweden)

    Mohammad BARZEGAR

    2015-01-01

    Full Text Available How to Cite This Article: Barzegar M, Habibi P, Bonyady M, Topchizadeh V, Shiva Sh. Exon Deletion Pattern in Duchene Muscular Dystrophy in North West of Iran. Iran J Child Neurol. 2015 Winter; 9(1: 42-48.AbstractObjectiveDuchene and Becker Muscular Dystrophy (DMD/ BMD are x-linked disorders that both are the result of heterogeneous mutations in the dystrophin gene. The frequency and distribution of dystrophin gene deletions in DMD/ BMD patients show different patterns among different populations. This study investigates the deletion rate, type, and distribution of this gene in the Azeri Turk population of North West Iran.Materials &MethodsIn this study, 110 patients with DMD/ BMD were studied for intragenic deletions in 24 exons and promoter regions of dystrophin genes by using multiplex PCR.ResultsDeletions were detected in 63 (57.3% patients, and around 83% localized in the mid-distal hotspot of the gene (on exons 44–52, 21 cases (33.3 % with singleexon deletions, and 42 cases (66.6% with multi-exonic deletions. The most frequent deleted exons were exon 50 (15 % and exon 49 (14%. No deletion was detected in exon 3.ConclusionThis study suggests that the frequency and pattern of dystrophin gene deletions in DMD/ BMD in the Azeri Turk population of North West Iran occur in the same pattern when compared with other ethnic groups.ReferencesEmery AE. Clinical and molecular studies in Duchenne muscular dystrophy. Prog Clin Biol Res 1989; 306:15-28.Moser H. Duchenne muscular dystrophy: pathogenic aspects and genetic prevention. Hum Genet 1984; 66(1:17-40.Emery AE. Population Frequencies of inherited neuromuscular diseases: a world survey Neuromuscul Disord 1991; I (I:19-29.Bushby KM, Thmabyayah M, Gardner M D. Prevalence and incidence of Becker muscular dystrophy. Lancet 1991; 337(8748:1022-1024.Koenig M, Hoffman EP, Bertelosn CJ, Monaco AP, Feener C, Kunkel LM. Complete cloning of the Duchenne muscular dystrophy (DMD DNA and

  19. High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome

    DEFF Research Database (Denmark)

    Aretz, S; Stienen, D; Uhlhaas, S;

    2007-01-01

    suspected to have JPS. RESULTS: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis...... polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted. Udgivelsesdato: 2007-Nov...

  20. The Role of Inhibition in Age-related Off-Topic Verbosity: Not Access but Deletion and Restraint Functions

    OpenAIRE

    Yin, Shufei; Peng, Huamao

    2016-01-01

    The speech of older adults is commonly described as verbose and off-topic, which is thought to influence their social communication. This study investigated the role of inhibition in age-related off-topic verbosity (OTV). Inhibition consists of three functions: access, deletion, and restraint. The access function is responsible for preventing irrelevant information from accessing the attention center (pre-mechanism of inhibition); The deletion function is responsible for deleting previously r...

  1. An If-Item-Deleted Sensitive Analysis of Cronbach’s Alpha Technique using Simulated Anneling Algorithm

    OpenAIRE

    Valdecy Pereira; Henrique Rego Monteiro da Hora; Helder Gomes Costa; Lívia Dias de Oliveira Nepomuceno

    2014-01-01

    This work proposes a nonlinear model and also a solution method to improve the overall Cronbach’s alpha coefficient technique, by grouping items of an instrument (questionnaire) that should be considered to deletion. The classical method called if-item-deleted Alpha also improves the overall reliability, however it considerers the deletion of only one item per time. Due to the combinatorial nature of the proposed model, a simulated annealing algorithm was implemented in order to achieve optim...

  2. Deletion of the secretory vesicle proteins IA-2 and IA-2β disrupts circadian rhythms of cardiovascular and physical activity

    OpenAIRE

    Kim, Soo Mi; Power, Andrea; Brown, Timothy M.; Constance, Cara M.; Coon, Steven L.; Nishimura, Takuya; Hirai, Hiroki; Cai, Tao; Eisner, Christoph; David R Weaver; Piggins, Hugh D.; Klein, David C.; Schnermann, Jürgen; Notkins, Abner L.

    2009-01-01

    Targeted deletion of IA-2 and IA-2β, major autoantigens in type 1 diabetes and transmembrane secretory vesicle proteins, results in impaired secretion of hormones and neurotransmitters. In the present study, we evaluated the effect of these deletions on daily rhythms in blood pressure, heart rate, core body temperature, and spontaneous physical and neuronal activity. We found that deletion of both IA-2 and IA-2β profoundly disrupts the usual diurnal variation of each of these parameters, wher...

  3. Uterine deletion of Trp53 compromises antioxidant responses in mouse decidua

    Energy Technology Data Exchange (ETDEWEB)

    Burnum, Kristin E.; Hirota, Yasushi; Baker, Erin Shammel; Yoshie, Mikihiro; Ibrahim, Yehia M.; Monroe, Matthew E.; Anderson, Gordon A.; Smith, Richard D.; Daikoku, Takiko; Dey, Sudhansu K.

    2012-09-01

    Preterm birth is a global health issue impacting both mothers and children. However, the etiology of preterm birth is not clearly understood. From our recent finding that premature decidual senescence with terminal differentiation is a cause of preterm birth in mice with uterine Trp53 deletion, encoding p53 protein, led us to explore other potential factors that are related to preterm birth. Utilizing proteomics approaches, here we show that 183 candidate proteins cause significant changes in decidua with Trp53 deletion as compared to normal decidua. Functional categorization of these proteins unveiled new pathways that are influenced by p53. In particular, downregulation of a cluster of antioxidant proteins in p53 deficient decidua suggests that increased oxidative stress could be one cause of preterm birth in mice with uterine deletion of Trp53.

  4. Neuropsychological profiles of patients with 2q37.3 deletion associated with developmental dyspraxia.

    Science.gov (United States)

    Ogura, Kaeko; Takeshita, Kenzo; Arakawa, Chikako; Shimojima, Keiko; Yamamoto, Toshiyuki

    2014-12-01

    Patients with 2q37 deletions manifest brachydactyly mental retardation syndrome (BDMR). Recent advances in human molecular research have revealed that alterations in the histone deacetylase 4 gene (HDAC4) are responsible for the clinical manifestations of BDMR. Here, we report two male patients with 2q37.3 deletions. One of the patients showed a typical BDMR phenotype, and HDAC4 was included in the deletion region. HDAC4 was preserved in the other patient, and he showed a normal intelligence level with the delayed learning of complex motor skills. Detailed neuropsychological examinations revealed similar neuropsychological profiles in these two patients (visuo-spatial dyspraxia) that suggested developmental dyspraxia. These observations suggested that some other candidate genes for neuronal development exist in the telomeric region of HDAC4. PMID:25329715

  5. Double gene deletion reveals the lack of cooperation between PPARα and PPARβ in skeletal muscle

    International Nuclear Information System (INIS)

    The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of most of the pathways linked to lipid metabolism. PPARα and PPARβ isotypes are known to regulate muscle fatty acid oxidation and a reciprocal compensation of their function has been proposed. Herein, we investigated muscle contractile and metabolic phenotypes in PPARα-/-, PPARβ-/-, and double PPARα-/- β-/- mice. Heart and soleus muscle analyses show that the deletion of PPARα induces a decrease of the HAD activity (β-oxidation) while soleus contractile phenotype remains unchanged. A PPARβ deletion alone has no effect. However, these mild phenotypes are not due to a reciprocal compensation of PPARβ and PPARα functions since double gene deletion PPARα-PPARβ mostly reproduces the null PPARα-mediated reduced β-oxidation, in addition to a shift from fast to slow fibers. In conclusion, PPARβ is not required for maintaining skeletal muscle metabolic activity and does not compensate the lack of PPARα in PPARα null mice

  6. Exonal deletion of SLC24A4 causes hypomaturation amelogenesis imperfecta.

    Science.gov (United States)

    Seymen, F; Lee, K-E; Tran Le, C G; Yildirim, M; Gencay, K; Lee, Z H; Kim, J-W

    2014-04-01

    Amelogenesis imperfecta is a heterogeneous group of genetic conditions affecting enamel formation. Recently, mutations in solute carrier family 24 member 4 (SLC24A4) have been identified to cause autosomal recessive hypomaturation amelogenesis imperfecta. We recruited a consanguineous family with hypomaturation amelogenesis imperfecta with generalized brown discoloration. Sequencing of the candidate genes identified a 10-kb deletion, including exons 15, 16, and most of the last exon of the SLC24A4 gene. Interestingly, this deletion was caused by homologous recombination between two 354-bp-long homologous sequences located in intron 14 and the 3' UTR. This is the first report of exonal deletion in SLC24A4 providing confirmatory evidence that the function of SLC24A4 in calcium transport has a crucial role in the maturation stage of amelogenesis.

  7. Partial Gene Deletions of PMP22 Causing Hereditary Neuropathy with Liability to Pressure Palsies

    Directory of Open Access Journals (Sweden)

    Sun-Mi Cho

    2014-01-01

    Full Text Available Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22 gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.

  8. Molecular analysis of the Duchenne muscular dystrophy gene in Spanish individuals: Deletion detection and familial diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Patino, A.; Garcia-Delgado, M.; Narbona, J. [Univ. of Navarra, Pamplona (Spain)

    1995-11-06

    Deletion studies were performed in 26 Duchenne muscular dystrophy (DMD) patients through amplification of nine different exons by multiplex polymerase chain reaction (PCR). DNA from paraffin-embedded muscle biopsies was analyzed in 12 of the 26 patients studied. Optimization of this technique is of great utility because it enables analysis of material stored in pathology archives. PCR deletion detection, useful in DMD-affected boys, is problematic in determining the carrier state in female relatives. For this reason, to perform familial linkage diagnosis, we made use of a dinucleotide repeat polymorphism (STRP, or short tandem repeat polymorphism) located in intron 49 of the gene. We designed a new pair of primers that enabled the detection of 22 different alleles in relatives in the 14 DMD families studied. The use of this marker allowed familial diagnosis in 11 of the 14 DMD families and detection of de novo deletions in 3 of the probands. 8 refs., 5 figs., 2 tabs.

  9. Targeted Large-Scale Deletion of Bacterial Genomes Using CRISPR-Nickases.

    Science.gov (United States)

    Standage-Beier, Kylie; Zhang, Qi; Wang, Xiao

    2015-11-20

    Programmable CRISPR-Cas systems have augmented our ability to produce precise genome manipulations. Here we demonstrate and characterize the ability of CRISPR-Cas derived nickases to direct targeted recombination of both small and large genomic regions flanked by repetitive elements in Escherichia coli. While CRISPR directed double-stranded DNA breaks are highly lethal in many bacteria, we show that CRISPR-guided nickase systems can be programmed to make precise, nonlethal, single-stranded incisions in targeted genomic regions. This induces recombination events and leads to targeted deletion. We demonstrate that dual-targeted nicking enables deletion of 36 and 97 Kb of the genome. Furthermore, multiplex targeting enables deletion of 133 Kb, accounting for approximately 3% of the entire E. coli genome. This technology provides a framework for methods to manipulate bacterial genomes using CRISPR-nickase systems. We envision this system working synergistically with preexisting bacterial genome engineering methods.

  10. An efficient gene replacement and deletion system for an extreme thermophile, Thermus thermophilus.

    Science.gov (United States)

    Tamakoshi, M; Yaoi, T; Oshima, T; Yamagishi, A

    1999-04-15

    A Thermus thermophilus host strain of which the leuB gene was totally deleted was constructed from a delta pyrE strain by a two step method. First, the leuB gene was replaced with the pyrE gene. Second, the inserted pyrE gene was deleted by using 5-fluoroorotic acid. A plasmid vector with the leuB marker was constructed and the plasmid complemented the leuB deficiency of the host. When the leuB gene from Escherichia coli and its derivative encoding a stabilized enzyme were expressed with the host-vector system, their growth temperature reflected the stability of the enzyme. These results suggest that the gene replacement deletion method using the pyrE gene is useful for the construction of a reliable plasmid vector system and it can be applied to the selection of stabilized enzymes. PMID:10227171

  11. Karect: accurate correction of substitution, insertion and deletion errors for next-generation sequencing data

    KAUST Repository

    Allam, Amin

    2015-07-14

    Motivation: Next-generation sequencing generates large amounts of data affected by errors in the form of substitutions, insertions or deletions of bases. Error correction based on the high-coverage information, typically improves de novo assembly. Most existing tools can correct substitution errors only; some support insertions and deletions, but accuracy in many cases is low. Results: We present Karect, a novel error correction technique based on multiple alignment. Our approach supports substitution, insertion and deletion errors. It can handle non-uniform coverage as well as moderately covered areas of the sequenced genome. Experiments with data from Illumina, 454 FLX and Ion Torrent sequencing machines demonstrate that Karect is more accurate than previous methods, both in terms of correcting individual-bases errors (up to 10% increase in accuracy gain) and post de novo assembly quality (up to 10% increase in NGA50). We also introduce an improved framework for evaluating the quality of error correction.

  12. Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger

    DEFF Research Database (Denmark)

    Meijer, Susan Lisette; Nielsen, Michael Lynge; Olsson, Lisbeth;

    2009-01-01

    With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell...... factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which...... the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger....

  13. The relationship of the factor V Leiden mutation or the deletion-deletion polymorphism of the angiotensin converting enzyme to postoperative thromboembolic events following total joint arthroplasty

    Directory of Open Access Journals (Sweden)

    Fang Carrie

    2001-04-01

    Full Text Available Abstract Background Although all patients undergoing total joint arthroplasty are subjected to similar risk factors that predispose to thromboembolism, only a subset of patients develop this complication. The objective of this study was to determine whether a specific genetic profile is associated with a higher risk of developing a postoperative thromboembolic complication. Specifically, we examined if the Factor V Leiden (FVL mutation or the deletion polymorphism of the angiotensin-converting enzyme (ACE gene increased a patient's risk for postoperative thromboembolic events. The FVL mutation has been associated with an increased risk of idiopathic thromboembolism and the deletion polymorphism of the ACE gene has been associated with increased vascular tone, attenuated fibrinolysis and increased platelet aggregation. Methods The presence of these genetic profiles was determined for 38 patients who had a postoperative symptomatic pulmonary embolus or proximal deep venous thrombosis and 241 control patients without thrombosis using molecular biological techniques. Results The Factor V Leiden mutation was present in none of the 38 experimental patients and in 3% or 8 of the 241 controls (p = 0.26. Similarly there was no difference detected in the distribution of polymorphisms for the ACE gene with the deletion-deletion genotype present in 36% or 13 of the 38 experimental patients and in 31% or 74 of the 241 controls (p = 0.32. Conclusions Our results suggest that neither of these potentially hypercoaguable states are associated with an increased risk of symptomatic thromboembolic events following total hip or knee arthroplasty in patients receiving pharmacological thromboprophylaxis.

  14. Genomics meets induced mutations in citrus: identification of deleted genes through comparative genomic hybridization

    International Nuclear Information System (INIS)

    We report on the use of genomic approaches to identify pivotal genes in induced citrus mutants. Citrus is the most economically important fruit crop in the world while Spain is the first fresh citrus producer. The survival of the Citrus industry is critically dependent on genetically superior cultivars but improvements in fruit quality traits through traditional techniques are extremely difficult due to the unusual combination of biological characteristics of citrus. Genomic science, however, holds promise of improvements in breeding. In this work, we reported the successful identification of genes included in hemizygous deletions induced by fast neutron irradiation on Citrus clementina. Microarray-based CGH was used to identify underrepresented genes in a citrus mutant that shows color break delay. Subsequent confirmation of gene doses through quantitative PCR and comparison of best hits of putative deleted citrus genes against annotated genomes from other eudicots, specially poplar, enabled the prediction that these genes were clustered into a 700 kb fragment. The availability of Citrus BAC end sequences helped to draw a partial physical map of the deletion. Furthermore, gene content and order in the deleted segment was established by PCR location of gene hits on the physical map. Finally, a lower chlorophyll a/b ratio was found in green tissues from the mutant, an observation that can be related to the hemizygous deletion of a ClpC-like gene, coding a putative subunit of a multifunctional protease complex located into the chloroplast. Analysis of gene content and order inside this Citrus deletion led to the conclusion that microsynteny and local gene colinearity with Populus trichocarpa were higher than with the phylogenetically closer Arabidopsis thaliana genome. In conclusion, a combined strategy including genomics tools and induced citrus mutations has been proved to be a successful approach to identify genes with major roles in citrus fruit development

  15. Genomics Meets Induced Mutations in Citrus: Identification of Deleted Genes Through Comparative Genomic Hybridization

    International Nuclear Information System (INIS)

    We report on the use of genomic approaches to identify pivotal genes in induced citrus mutants. Citrus is the most economically important fruit crop in the world and Spain is the first fresh citrus producer. The survival of the citrus industry is critically dependent on genetically superior cultivars but improvements in fruit quality traits through traditional techniques are extremely difficult due to the unusual combination of biological characteristics of citrus. Genomic science, however, holds promise of improvements in breeding. In this work, we reported the successful identification of genes included in hemizygous deletions induced by fast neutron irradiation on Citrus clementina. Microarray-based CGH was used to identify underrepresented genes in a citrus mutant that shows color break delay. Subsequent confirmation of gene doses through quantitative PCR and comparison of best hits of putative deleted citrus genes against annotated genomes from other eudicots, specially poplar, enabled the prediction that these genes were clustered into a 700 kb fragment. The availability of Citrus BAC end sequences helped to draw a partial physical map of the deletion. Furthermore, gene content and order in the deleted segment was established by PCR location of gene hits on the physical map. Finally, a lower chlorophyll a/b ratio was found in green tissues from the mutant, an observation that can be related to the hemizygous deletion of a ClpC-like gene, coding a putative subunit of a multifunctional protease complex located into the chloroplast. Analysis of gene content and order inside this Citrus deletion led to the conclusion that microsynteny and local gene colinearity with Populus trichocarpa were higher than with the phylogenetically closer Arabidopsis thaliana genome. In conclusion, a combined strategy including genomics tools and induced citrus mutations has been proved to be a successful approach to identify genes with major roles in citrus fruit development

  16. SNP genotyping to screen for a common deletion in CHARGE Syndrome

    Directory of Open Access Journals (Sweden)

    Molinari Laura M

    2005-02-01

    Full Text Available Abstract Background CHARGE syndrome is a complex of birth defects including coloboma, choanal atresia, ear malformations and deafness, cardiac defects, and growth delay. We have previously hypothesized that CHARGE syndrome could be caused by unidentified genomic microdeletion, but no such deletion was detected using short tandem repeat (STR markers spaced an average of 5 cM apart. Recently, microdeletion at 8q12 locus was reported in two patients with CHARGE, although point mutation in CHD7 on chromosome 8 was the underlying etiology in most of the affected patients. Methods We have extended our previous study by employing a much higher density of SNP markers (3258 with an average spacing of approximately 800 kb. These SNP markers are diallelic and, therefore, have much different properties for detection of deletions than STRs. Results A global error rate estimate was produced based on Mendelian inconsistency. One marker, rs431722 exceeded the expected frequency of inconsistencies, but no deletion could be demonstrated after retesting the 4 inconsistent pedigrees with local flanking markers or by FISH with the corresponding BAC clone. Expected deletion detection (EDD was used to assess the coverage of specific intervals over the genome by deriving the probability of detecting a common loss of heterozygosity event over each genomic interval. This analysis estimated the fraction of unobserved deletions, taking into account the allele frequencies at the SNPs, the known marker spacing and sample size. Conclusions The results of our genotyping indicate that more than 35% of the genome is included in regions with very low probability of a deletion of at least 2 Mb.

  17. Large Genomic Deletions in CACNA1A Cause Episodic Ataxia Type 2

    Directory of Open Access Journals (Sweden)

    Jijun eWan

    2011-09-01

    Full Text Available Episodic ataxia (EA syndromes are heritable diseases characterized by dramatic episodes of imbalance and incoordination. Episodic ataxia type 2 (EA2, the most common and the best characterized subtype, is caused by mostly nonsense, splice site, small indel and sometimes missense mutations in CACNA1A. Direct sequencing of CACNA1A fails to identify mutations in some patients with EA2-like features, possibly due to incomplete interrogation of CACNA1A or defects in other EA genes not yet defined. Previous reports described genomic deletions between 4-40kb in EA2. In 47 subjects with EA (26 with EA2-like features who tested negative for mutations in the known EA genes, we used Multiplex Ligation-dependent Probe Amplification (MLPA to analyze CACNA1A for exonic copy number variations. Breakpoints were further defined by long-range PCR. We identified distinct multi-exonic deletions in three probands with classic EA2-like features: episodes of prolonged vertigo and ataxia triggered by stress and fatigue, interictal nystagmus, with onset during infancy or early childhood. The breakpoints in all three probands are located in Alu sequences, indicating errors in homologous recombination of Alu sequences as the underlying mechanism. The smallest deletion spanned exons 39 and 40, while the largest deletion spanned 200kb, missing all but the first three exons. One deletion involving exons 39 through 47 arose spontaneously. The search for mutations in CACNA1A appears most fruitful in EA patients with interictal nystagmus and onset early in life. The finding of large heterozygous deletions suggests haploinsufficiency as a possible pathomechanism of EA2.

  18. Deletions in the genomes of fifteen inbred mouse lines and their possible implications for fat accumulation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Copy number variants (CNVs) are pieces of genomic DNA of 1000 base pairs or longer which occur in a given genome at a different frequency than in a reference genome. Their importance as a source for phenotypic variability has been recognized only in the last couple of years. Chromosomal deletions can be seen as a special case of CNVs where stretches of DNA are missing in certain lines when compared to the reference genome of the mouse line C57BL/6, for example. Based upon more than 8 million single nucleotide polymorphisms (SNPs) in the fifteen inbred mouse lines which were determined in a whole genome chip based resequencing project by Perlegen Sciences, we detected 20166 such long chromosomal deletions. They cover altogether between 4.4 million and 8.8 million base pairs, depending on the mouse line. Thus, their extent is comparable to that of SNPs. The chromosomal deletions were found by searching for clusters of missing values in the genotyping data by applying bioinformatics and biostatistical methods. In contrast to isolated missing values, clusters are likely the consequence of missing DNA probe rather than of a failed hybridization or deficient oligos. We analyzed these deletion sites in various ways. Twenty-two percent of these deletion sites overlap with exons; they could therefore affect a gene's functioning. The corresponding genes seem to exist in alternative forms, a phenomenon that reminds of the altemative forms of mRNA generated during gene splicing. We furthermore detected statistically significant association between hundreds of deletion sites and fat weight at the age of eight weeks.

  19. Neuropathological signs of inflammation correlate with mitochondrial DNA deletions in mesial temporal lobe epilepsy.

    Science.gov (United States)

    Volmering, Elisa; Niehusmann, Pitt; Peeva, Viktoriya; Grote, Alexander; Zsurka, Gábor; Altmüller, Janine; Nürnberg, Peter; Becker, Albert J; Schoch, Susanne; Elger, Christian E; Kunz, Wolfram S

    2016-08-01

    Accumulation of mitochondrial DNA (mtDNA) deletions has been proposed to be responsible for the presence of respiratory-deficient neurons in several CNS diseases. Deletions are thought to originate from double-strand breaks due to attack of reactive oxygen species (ROS) of putative inflammatory origin. In epileptogenesis, emerging evidence points to chronic inflammation as an important feature. Here we aimed to analyze the potential association of inflammation and mtDNA deletions in the hippocampal tissue of patients with mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS). Hippocampal and parahippocampal tissue samples from 74 patients with drug-refractory mTLE served for mtDNA analysis by multiplex PCR as well as long-range PCR, single-molecule PCR and ultra-deep sequencing of mtDNA in selected samples. Patients were sub-classified according to neuropathological findings. Semi-quantitative assessment of neuronal cell loss was performed in the hippocampal regions CA1-CA4. Inflammatory infiltrates were quantified by cell counts in the CA1, CA3 and CA4 regions from well preserved hippocampal samples (n = 33). Samples with HS showed a significantly increased frequency of a 7436-bp mtDNA deletion (p T transversions compared to mTLE patients with different histopathology. Interestingly, the number of T-lymphocytes in the hippocampal CA1, CA3 and CA4 regions was, similar to the 7436-bp mtDNA deletion, significantly increased in samples with HS compared to other subgroups. Our findings show a coincidence of HS, increased somatic G>T transversions, the presence of a specific mtDNA deletion, and increased inflammatory infiltrates. These results support the hypothesis that chronic inflammation leads to mitochondrial dysfunction by ROS-mediated mtDNA mutagenesis which promotes epileptogenesis and neuronal cell loss in patients with mTLE and HS. PMID:26993140

  20. Large genomic fragment deletions and insertions in mouse using CRISPR/Cas9.

    Directory of Open Access Journals (Sweden)

    Luqing Zhang

    Full Text Available ZFN, TALENs and CRISPR/Cas9 system have been used to generate point mutations and large fragment deletions and insertions in genomic modifications. CRISPR/Cas9 system is the most flexible and fast developing technology that has been extensively used to make mutations in all kinds of organisms. However, the most mutations reported up to date are small insertions and deletions. In this report, CRISPR/Cas9 system was used to make large DNA fragment deletions and insertions, including entire Dip2a gene deletion, about 65kb in size, and β-galactosidase (lacZ reporter gene insertion of larger than 5kb in mouse. About 11.8% (11/93 are positive for 65kb deletion from transfected and diluted ES clones. High targeting efficiencies in ES cells were also achieved with G418 selection, 46.2% (12/26 and 73.1% (19/26 for left and right arms respectively. Targeted large fragment deletion efficiency is about 21.4% of live pups or 6.0% of injected embryos. Targeted insertion of lacZ reporter with NEO cassette showed 27.1% (13/48 of targeting rate by ES cell transfection and 11.1% (2/18 by direct zygote injection. The procedures have bypassed in vitro transcription by directly co-injection of zygotes or co-transfection of embryonic stem cells with circular plasmid DNA. The methods are technically easy, time saving, and cost effective in generating mouse models and will certainly facilitate gene function studies.

  1. 1p/14q co-deletion: A determinant of recurrence in histologically benign meningiomas

    Directory of Open Access Journals (Sweden)

    Aanchal Kakkar

    2015-01-01

    Full Text Available Background: Meningiomas are the most common benign central nervous system tumors. However, a sizeable fraction recurs, irrespective of histological grade. No molecular marker is available for prediction of recurrence in these tumors. Materials and Methods: We analyzed recurrent meningiomas with paired parent and recurrent tumors by fluorescence in situ hybridization for 1p36 and 14q32 deletion, AKT and SMO mutations by sequencing, and immunohistochemistry for GAB1, progesterone receptor (PR, p53, and MIB-1. Results: 18 recurrent meningiomas (11 grade I, 3 grade II, 4 grade III with their parent tumors (14 grade I, 2 grade II and 2 grade III were identified. Overall, 61% of parent and 78% of recurrent meningiomas showed 1p/14q co-deletion. Notably, grade I parent tumors showed 1p/14q co-deletion in 64% cases while 82% of grade I recurrent tumors were co-deleted. AKT mutation was seen in two cases, in both parent and recurrent tumors. SMO mutations were absent. GAB1 was immunopositive in 80% parent and 56.3% recurrent tumors. MIB-1 labeling index (LI, PR and p53 expression did not appear to have any significant contribution in possible prediction of recurrence. Conclusion: Identification of 1p/14q co-deletion in a significant proportion of histologically benign (grade I meningiomas that recurred suggests its utility as a marker for prediction of recurrence. It appears to be a better predictive marker than MIB1-LI, PR and p53 expression. Recognition of AKT mutation in a subset of meningiomas may help identify patients that may benefit from PI3K/AKT pathway inhibitors, particularly among those at risk for development of recurrence, as determined by presence of 1p/14q co-deletion.

  2. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1993-04-01

    From 1971 to 1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF{sub 1} mice irradiated with {sup 60}Co {gamma} rays or JANUS fission-spectrum neutrons; normal and tumor tissues from mice in these studies were preserved in paraffin blocks. A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma (mRb) gene in the paraffin-embedded tissues. Microtomed sections were used as the DNA source in PCR reaction mixtures. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments (relative to control PCR products) on a Southern blot indicated a deletion of that portion of the mRb gene. The tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice (569 cGy of {sup 60}Co {gamma} rays or 60 cGy of JANUS neutrons, doses that have been found to have approximately equal biological effectiveness in the BCF, mouse) were analyzed for mRb deletions. In all normal mouse tissues studies, all six mRb exon fragments were present on Southem blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, I of 6 tumors from {gamma}-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice had a deletion in one or both mRb alleles. All deletions detected were in the 5{prime} region of the mRb gene.

  3. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1993-01-01

    From 1971 to 1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF[sub 1] mice irradiated with [sup 60]Co [gamma] rays or JANUS fission-spectrum neutrons; normal and tumor tissues from mice in these studies were preserved in paraffin blocks. A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma (mRb) gene in the paraffin-embedded tissues. Microtomed sections were used as the DNA source in PCR reaction mixtures. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments (relative to control PCR products) on a Southern blot indicated a deletion of that portion of the mRb gene. The tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice (569 cGy of [sup 60]Co [gamma] rays or 60 cGy of JANUS neutrons, doses that have been found to have approximately equal biological effectiveness in the BCF, mouse) were analyzed for mRb deletions. In all normal mouse tissues studies, all six mRb exon fragments were present on Southem blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, I of 6 tumors from [gamma]-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice had a deletion in one or both mRb alleles. All deletions detected were in the 5[prime] region of the mRb gene.

  4. Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies.

    Science.gov (United States)

    Puda, Ana; Milosevic, Jelena D; Berg, Tiina; Klampfl, Thorsten; Harutyunyan, Ashot S; Gisslinger, Bettina; Rumi, Elisa; Pietra, Daniela; Malcovati, Luca; Elena, Chiara; Doubek, Michael; Steurer, Michael; Tosic, Natasa; Pavlovic, Sonja; Guglielmelli, Paola; Pieri, Lisa; Vannucchi, Alessandro M; Gisslinger, Heinz; Cazzola, Mario; Kralovics, Robert

    2012-03-01

    Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have an inherent tendency to progress to acute myeloid leukemia (AML). Using high-resolution SNP microarrays, we studied a total of 517 MPN and MDS patients in different disease stages, including 77 AML cases with previous history of MPN (N = 46) or MDS (N = 31). Frequent chromosomal deletions of variable sizes were detected, allowing the mapping of putative tumor suppressor genes involved in the leukemic transformation process. We detected frequent deletions on the short arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1-Mb region and contained only the JARID2 gene--member of the polycomb repressive complex 2 (PRC2). When we compared the frequency of del6p between chronic and leukemic phase, we observed a strong association of del6p with leukemic transformation (P = 0.0033). Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1. Using next generation exome sequencing of 40 patients, we identified only one somatic mutation in the PRC2 complex member SUZ12. As the frequency of point mutations in PRC2 members was found to be low, deletions were the main type of lesions targeting PRC2 complex members. Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders. PMID:22190018

  5. PAX3 gene deletion detected by microarray analysis in a girl with hearing loss

    OpenAIRE

    Drozniewska, Malgorzata; Haus, Olga

    2014-01-01

    Deletions of the PAX3 gene have been rarely reported in the literature. Mutations of this gene are a common cause of Waardenburg syndrome type 1 and 3. We report a 16 year old female presenting hearing loss and normal intellectual development, without major features of Waardenburg syndrome type 1, and without family history of the syndrome. Her phenotype, however, overlaps with features of craniofacial-deafness-hand syndrome. Microarray analysis showed ~862 kb de novo deletion at 2q36.1 inclu...

  6. 21q21 deletion involving NCAM2: report of 3 cases with neurodevelopmental disorders.

    Science.gov (United States)

    Petit, Florence; Plessis, Ghislaine; Decamp, Matthieu; Cuisset, Jean-Marie; Blyth, Moira; Pendlebury, Maria; Andrieux, Joris

    2015-01-01

    Here we report three patients affected with neurodevelopmental disorders and harbouring 21q21 deletions involving NCAM2 gene. NCAM (Neural Cell Adhesion Molecule) proteins are involved in axonal migration, synaptic formation and plasticity. Poor axonal growth and fasciculation is observed in animal models deficient for NCAM2. Moreover, this gene has been proposed as a candidate for autism, based on genome-wide association studies. In this report, we provide a comprehensive molecular and phenotypical characterisation of three deletion cases giving additional clues for the involvement of NCAM2 in neurodevelopment.

  7. Deletion analysis of the cloned replication origin region from bacteriophage M13.

    OpenAIRE

    Cleary, J M; Ray, D S

    1981-01-01

    A cloned 270-nucleotide fragment from the origin region of the M13 duplex replicative form DNA confers an M13-dependent replication mechanism upon the plasmid vector pBR322. This M13 insert permits M13 helper-dependent replication of the hybrid plasmid in polA cells which are unable to replicate the pBR322 replicon alone. Using in vitro techniques, we have constructed several plasmids containing deletions in the M13 DNa insert. The endpoints of these deletions have been determined by DNA sequ...

  8. Exon Deletion Pattern in Duchene Muscular Dystrophy in North West of Iran

    OpenAIRE

    Barzegar, Mohammad; Parinaz HABIBI; Mortaza Mortaza BONYADY; TOPCHIZADEH, Vahideh; Shadi SHIVA

    2015-01-01

    How to Cite This Article: Barzegar M, Habibi P, Bonyady M, Topchizadeh V, Shiva Sh. Exon Deletion Pattern in Duchene Muscular Dystrophy in North West of Iran. Iran J Child Neurol. 2015 Winter; 9(1): 42-48.AbstractObjectiveDuchene and Becker Muscular Dystrophy (DMD/ BMD) are x-linked disorders that both are the result of heterogeneous mutations in the dystrophin gene. The frequency and distribution of dystrophin gene deletions in DMD/ BMD patients show different patterns among different popula...

  9. Whole Xp Deletion in a Girl with Mental Retardation, Epilepsy, and Biochemical Features of OTC Deficiency

    OpenAIRE

    Joost, K.; Tammur, P.; Teek, R.; Žilina, O.; Peters, M; Kreile, M.; Lace, B.; Žordania, R.; Talvik, I.; Õunap, K.

    2011-01-01

    Background: Females with a total or partial deletion of the short arm of the X chromosome have variable features of Turner syndrome, but mental retardation (MR) rarely occurs. The haploinsufficiency of deleted genes that escape X-inactivation may explain the occurrence of MR and autism. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is inherited in an X-linked semi-dominant trait, and the OTC gene maps to Xp21. Methods: We report on a girl with MR, epil...

  10. Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA-1/ICAM interactions.

    Science.gov (United States)

    Carlow, D A; van Oers, N S; Teh, S J; Teh, H S

    1992-03-15

    An in vitro assay was used for assessing the participation of various cell surface molecules and the efficacy of various cell types in the deletion of Ag-specific immature thymocytes. Thymocytes from mice expressing a transgenic TCR specific for the male Ag presented by the H-2Db class I MHC molecule were used as a target for deletion. In H-2d transgenic mice, cells bearing the transgenic TCR are not subjected to thymic selection as a consequence of the absence of the restricting H-2Db molecule but, nevertheless, express this TCR on the vast majority of immature CD4+8+ thymocytes. In this report we show that CD4+8+ thymocytes from H-2d TCR-transgenic mice are preferentially killed upon in vitro culture with male APC; DC were particularly effective in mediating in vitro deletion when compared with either B cells or T cells. Deletion of CD4+8+ thymocytes by DC was H-2b restricted and could be inhibited by mAb to either LFA-1 alpha or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb to CD4 and LFA-1 beta were without effect. These results are the first direct evidence of LFA-1 involvement in negative selection and provide further direct support for the participation of CD8/class I MHC interactions in this process. Like the requirements for deletion, activation of mature male-specific CD4-8+ T cells from female H-2b TCR-transgenic mice was also largely dependent on Ag presentation by DC and required both LFA-1/ICAM and CD8/class I MHC interactions; these results support the view that activation and deletion may represent maturation stage-dependent consequences of T cells encountering the same APC. Finally, our results also support the hypothesis that negative selection (deletion) does not require previous positive selection because deletion was observed under conditions where positive selection had not occurred.

  11. Prenatal detection of short arm deletion and isochromosome 18 formation investigated by molecular techniques.

    OpenAIRE

    Qumsiyeh, M B; Tomasi, A; Taslimi, M

    1995-01-01

    A patient was referred for amniocentesis because of advanced maternal age and polyhydramnios. The fetal karyotype was a mosaic 46,XX,del(18)(p11.1)/46,XX,-18,+i(18q)de novo. The deletion appeared to encompass the whole short arm as evidenced by G banding and in situ hybridisation. However, telomere sequences were found on both ends of the deleted chromosome as well as the isochromosome. The normal 18 and the isochromosome showed more alphoid sequences than the del(18). Subsequent passages of ...

  12. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes

    Science.gov (United States)

    Doco-Fenzy, Martine; Leroy, Camille; Schneider, Anouck; Petit, Florence; Delrue, Marie-Ange; Andrieux, Joris; Perrin-Sabourin, Laurence; Landais, Emilie; Aboura, Azzedine; Puechberty, Jacques; Girard, Manon; Tournaire, Magali; Sanchez, Elodie; Rooryck, Caroline; Ameil, Agnès; Goossens, Michel; Jonveaux, Philippe; Lefort, Geneviève; Taine, Laurence; Cailley, Dorothée; Gaillard, Dominique; Leheup, Bruno; Sarda, Pierre; Geneviève, David

    2014-01-01

    Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader–Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion. PMID:24129437

  13. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes.

    Science.gov (United States)

    Doco-Fenzy, Martine; Leroy, Camille; Schneider, Anouck; Petit, Florence; Delrue, Marie-Ange; Andrieux, Joris; Perrin-Sabourin, Laurence; Landais, Emilie; Aboura, Azzedine; Puechberty, Jacques; Girard, Manon; Tournaire, Magali; Sanchez, Elodie; Rooryck, Caroline; Ameil, Agnès; Goossens, Michel; Jonveaux, Philippe; Lefort, Geneviève; Taine, Laurence; Cailley, Dorothée; Gaillard, Dominique; Leheup, Bruno; Sarda, Pierre; Geneviève, David

    2014-04-01

    Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader-Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion.

  14. An improved method for rapid generation of unmarked Pseudomonas aeruginosa deletion mutants

    Directory of Open Access Journals (Sweden)

    Schweizer Herbert P

    2005-05-01

    Full Text Available Abstract Background Traditional gene replacement procedures are still time-consuming. They usually necessitate cloning of the gene to be mutated, insertional inactivation of the gene with an antibiotic resistance cassette and exchange of the plasmid-borne mutant allele with the bacterial chromosome. PCR and recombinational technologies can be exploited to substantially accelerate virtually all steps involved in the gene replacement process. Results We describe a method for rapid generation of unmarked P. aeruginosa deletion mutants. Three partially overlapping DNA fragments are amplified and then spliced together in vitro by overlap extension PCR. The resulting DNA fragment is cloned in vitro into the Gateway vector pDONR221 and then recombined into the Gateway-compatible gene replacement vector pEX18ApGW. The plasmid-borne deletions are next transferred to the P. aeruginosa chromosome by homologous recombination. Unmarked deletion mutants are finally obtained by Flp-mediated excision of the antibiotic resistance marker. The method was applied to deletion of 25 P. aeruginosa genes encoding transcriptional regulators of the GntR family. Conclusion While maintaining the key features of traditional gene replacement procedures, for example, suicide delivery vectors, antibiotic resistance selection and sucrose counterselection, the method described here is considerably faster due to streamlining of some of the key steps involved in the process, especially plasmid-borne mutant allele construction and its transfer into the target host. With appropriate modifications, the method should be applicable to other bacteria.

  15. Large scale deletions of the mitochondrial DNA in astheno, asthenoterato and oligoasthenoterato-spermic men.

    Science.gov (United States)

    Hosseinzadeh Colagar, Abasalt; Karimi, Fatemeh

    2014-08-01

    The purpose of this study was to investigate the association of large-scale deletions of mtDNA between idiopathic astheno, asthenoterato and oligoasthenoterato-spermic as patient group and normospermic as control group. Forty semen samples including: 10 asthenospermic (A), 10 asthenoteratospermic (AT), 10 oligoasthenoteratospermic (OAT) and 10 normospermic samples as control group, were collected from IVF center. Our analysis of long-range polymerase chain reaction were shown multiple deletions; 4977-bp, 7599-bp and 7491-bp of mtDNA in spermatozoa of patients (A, AT and OAT) and control groups. However, the frequency of multiple mtDNA deletions in astheno (60%), asthenoterato (60%), oligoasthenoterato (70%) spermic groups were significantly higher than normal (40%) group. These results suggest that mtDNA mutations cause infertility through an effect on sperm motility. Therefore, identification of mtDNA mutations and large scale deletions in the pathophysiology of human spermatozoa dysfunction is considered to be important to better understanding of the etiology of idiopathic infertility.

  16. Behavioral phenotype in the 9q subtelomeric deletion syndrome: a report about two adult patients.

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Kleefstra, T.; Egger, J.I.

    2010-01-01

    The 9q Subtelomeric Deletion Syndrome (9qSTDS) is clinically characterized by mental retardation, childhood hypotonia, and facial dysmorphisms. Haploinsufficiency of the EHMT1 gene has been demonstrated to be responsible for its core phenotype. In a significant number of patients behavioral abnormal

  17. A natural extension for the greedy beta-transformation with three deleted digits

    OpenAIRE

    Dajani, Karma; Kalle, Charlene

    2008-01-01

    We give an explicit expression for the invariant measure, absolutely continuous with respect to the Lebesgue measure, of the greedy beta-transformation with three deleted digits. We define a version of the natural extension of the transformation to obtain this expression. We get that the transformation is exact and weakly Bernoulli.

  18. Insertion/deletion polymorphism of the ACE gene and adherence to ACE inhibitors

    NARCIS (Netherlands)

    H. Schelleman (Hedi); O.H. Klungel (Olaf); C.M. van Duijn (Cock); J.C.M. Witteman (Jacqueline); A. Hofman (Albert); A. de Boer (Anthonius); B.H.Ch. Stricker (Bruno)

    2005-01-01

    textabstractAims: We investigated whether the insertion/deletion (I/D) polymorphism of the ACE gene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug. Methods: This was a cohort study among 239 subjects who s

  19. Insertion/deletion polymorphism of the ACE gene and adherence to ACE inhibitors

    NARCIS (Netherlands)

    Schelleman, H; Klungel, O H; van Duijn, C M; Witteman, J C M; Hofman, A; de Boer, A; Stricker, B H Ch

    2005-01-01

    AIMS: We investigated whether the insertion/deletion (I/D) polymorphism of the ACE gene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug. METHODS: This was a cohort study among 239 subjects who started ACE i

  20. Submicroscopic Deletions at 13q32.1 Cause Congenital Microcoria

    Science.gov (United States)

    Fares-Taie, Lucas; Gerber, Sylvie; Tawara, Akihiko; Ramirez-Miranda, Arturo; Douet, Jean-Yves; Verdin, Hannah; Guilloux, Antoine; Zenteno, Juan C.; Kondo, Hiroyuki; Moisset, Hugo; Passet, Bruno; Yamamoto, Ken; Iwai, Masaru; Tanaka, Toshihiro; Nakamura, Yusuke; Kimura, Wataru; Bole-Feysot, Christine; Vilotte, Marthe; Odent, Sylvie; Vilotte, Jean-Luc; Munnich, Arnold; Regnier, Alain; Chassaing, Nicolas; De Baere, Elfride; Raymond-Letron, Isabelle; Kaplan, Josseline; Calvas, Patrick; Roche, Olivier; Rozet, Jean-Michel

    2015-01-01

    Congenital microcoria (MCOR) is a rare autosomal-dominant disorder characterized by inability of the iris to dilate owing to absence of dilator pupillae muscle. So far, a dozen MCOR-affected families have been reported worldwide. By using whole-genome oligonucleotide array CGH, we have identified deletions at 13q32.1 segregating with MCOR in six families originating from France, Japan, and Mexico. Breakpoint sequence analyses showed nonrecurrent deletions in 5/6 families. The deletions varied from 35 kbp to 80 kbp in size, but invariably encompassed or interrupted only two genes: TGDS encoding the TDP-glucose 4,6-dehydratase and GPR180 encoding the G protein-coupled receptor 180, also known as intimal thickness-related receptor (ITR). Unlike TGDS which has no known function in muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth. The identification of a null GPR180 mutation segregating over two generations with iridocorneal angle dysgenesis, which can be regarded as a MCOR endophenotype, is consistent with the view that deletions of this gene, with or without the loss of elements regulating the expression of neighboring genes, are the cause of MCOR. PMID:25772937

  1. 78 FR 2363 - Notification of Deletion of a System of Records; Automated Trust Funds Database

    Science.gov (United States)

    2013-01-11

    ... Agriculture (USDA) published in the Federal Register (73 FR 23414- 23416, Docket No. APHIS-2008-0026) a system of records notice establishing the Automated Trust Funds (ATF) database system of records. The...; ] DEPARTMENT OF AGRICULTURE Office of the Secretary Notification of Deletion of a System of Records;...

  2. Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome.

    NARCIS (Netherlands)

    Reeuwijk, J. van; Grewal, P.K.; Salih, M.A.; Beltran Valero de Bernabe, D.; McLaughlan, J.M.; Michielse, C.B.; Herrmann, R.; Hewitt, J.E.; Steinbrecher, A.; Seidahmed, M.Z.; Shaheed, M.M.; Abomelha, A.; Brunner, H.G.; Bokhoven, J.H.L.M. van; Voit, T.

    2007-01-01

    Intragenic homozygous deletions in the Large gene are associated with a severe neuromuscular phenotype in the myodystrophy (myd) mouse. These mutations result in a virtual lack of glycosylation of alpha-dystroglycan. Compound heterozygous LARGE mutations have been reported in a single human patient,

  3. CHILD: a new tool for detecting low-abundance insertions and deletions in standard sequence traces.

    Science.gov (United States)

    Zhidkov, Ilia; Cohen, Raphael; Geifman, Nophar; Mishmar, Dan; Rubin, Eitan

    2011-04-01

    Several methods have been proposed for detecting insertion/deletions (indels) from chromatograms generated by Sanger sequencing. However, most such methods are unsuitable when the mutated and normal variants occur at unequal ratios, such as is expected to be the case in cancer, with organellar DNA or with alternatively spliced RNAs. In addition, the current methods do not provide robust estimates of the statistical confidence of their results, and the sensitivity of this approach has not been rigorously evaluated. Here, we present CHILD, a tool specifically designed for indel detection in mixtures where one variant is rare. CHILD makes use of standard sequence alignment statistics to evaluate the significance of the results. The sensitivity of CHILD was tested by sequencing controlled mixtures of deleted and undeleted plasmids at various ratios. Our results indicate that CHILD can identify deleted molecules present as just 5% of the mixture. Notably, the results were plasmid/primer-specific; for some primers and/or plasmids, the deleted molecule was only detected when it comprised 10% or more of the mixture. The false positive rate was estimated to be lower than 0.4%. CHILD was implemented as a user-oriented web site, providing a sensitive and experimentally validated method for the detection of rare indel-carrying molecules in common Sanger sequence reads.

  4. 22q11 Deletion Syndrome and Multiple Complex Developmental Disorder: a case report

    NARCIS (Netherlands)

    V. Scandurra; M.R. Scordo; R. Canitano; E.I. de Bruin

    2013-01-01

    22q11.2 Deletion Syndrome (22q11 DS) is a multisystemic condition that may also include neuropsychiatric disorders. We present a case of a 15-year-old boy that was evaluated for social difficulties, and anxiety with the above genetic abnormality. Clinical features were rather complex as different ne

  5. Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis

    DEFF Research Database (Denmark)

    Müller-Enbergs, Helmut; Hu, Jiong; Popp, Rüdiger;

    2012-01-01

    OBJECTIVE: Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated in innate immunity, cell polarity, and differentiation. Here we studied the role of DMBT1 in endothelial cells. METHODS AND RESULTS: DMBT1 was secreted ...

  6. Sensorineural hearing impairment in patients with Pmp22 duplication, deletion, and frameshift mutations.

    NARCIS (Netherlands)

    Verhagen, W.I.M.; Huygen, P.L.M.; Gabreëls-Festen, A.A.W.M.; Engelhart, M.J.; Mierlo, P.J. van; Engelen, B.G.M. van

    2005-01-01

    OBJECTIVE: To characterize and distinguish the types of sensorineural hearing impairment (SNHI) that occur in hereditary motor and sensory neuropathy Type 1a (HMSN-1a) and hereditary neuropathy with liability to pressure palsies (HNPP), which are caused by deletion or frameshift mutation. STUDY DESI

  7. Molecular characterization of the porcine deleted in malignant brain tumors 1 gene (DMBT1)

    DEFF Research Database (Denmark)

    Haase, Bianca; Humphray, Sean J; Lyer, Stefan;

    2006-01-01

    The human gene deleted in malignant brain tumors 1 (DMBT1) is considered to play a role in tumorigenesis and pathogen defense. It encodes a protein with multiple scavenger receptor cysteine-rich (SRCR) domains, which are involved in recognition and binding of a broad spectrum of bacterial pathoge...

  8. Is 1p36 deletion associated with anterior body wall defects?

    Science.gov (United States)

    Çöllü, Medis; Yüksel, Şirin; Şirin, Başak Kumbasar; Abbasoğlu, Latif; Alanay, Yasemin

    2016-07-01

    Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion. Here we report a second patient with 1p36 deletion who also has classic bladder exstrophy, supporting the possible role of genes in this region in the development of BEEC. The absence of omphalocele and imperforate anus in our patient places him toward classic bladder exstrophy while presence of spina bifida and the absence of coccyx suggest an overlap with OEIS complex. An additional differential diagnosis is the pentalogy of Cantrell in our patient as he also has a diaphragmatic hernia and an incomplete sternum. This is the second observation of a ventral midline birth defect in association with 1p36 deletion syndrome, following El-Hattab et al.'s report [2009]. The three genes (NOCL2, DVL1, and MMP23B) discussed as possible candidates are also among the deleted ones in our patient, supporting the possible role of these genes in BEEC spectrum. © 2016 Wiley Periodicals, Inc. PMID:27144803

  9. Deletion of the V2 vasopressin receptor gene in two Chinese patients with nephrogenic diabetes insipidus

    Directory of Open Access Journals (Sweden)

    Yin Jun

    2006-11-01

    Full Text Available Abstract Background Congenital nephrogenic diabetes insipidus (NDI is a rare X-linked inherited disorder characterized by the excretion of large volumes of diluted urine and caused by mutations in arginine vasopressin receptor 2 (AVPR2 gene. To investigate the mutation of AVPR2 gene in a Chinese family with congenital NDI, we screened AVPR2 gene in two NDI patients and eight family members by PCR amplification and direct sequencing. Results Five specific fragments, covering entire coding sequence and their flanking intronic sequences of AVPR2 gene, were not observed in both patients, while those fragments were all detected in the control subjects. Several different fragments around the AVPR2 locus were amplified step by step. It was revealed that a genomic fragment of 5,995-bp, which contained the entire AVPR2 gene and the last exon (exon 22 of the C1 gene, was deleted and a 3-bp (GAG was inserted. Examination of the other family members showed that the mothers and the grandmother were carriers for this deletion. Conclusion Our findings suggest that the two patients in a Chinese family suffering from congenital NDI had a 5,995-bp deletion and 3-bp (GAG insertion at Xq28. The deletion contained the entire AVPR2 gene and exon 22 of the C1 gene.

  10. [Para-Bombay phenotype caused by combined heterozygote of two bases deletion on fut1 alleles].

    Science.gov (United States)

    Ma, Kan-Rong; Tao, Shu-Dan; Lan, Xiao-Fei; Hong, Xiao-Zhen; Xu, Xian-Guo; Zhu, Fa-Ming; Lü, Hang-Jun; Yan, Li-Xing

    2011-02-01

    This study was purposed to investigate the molecular basis of a para-Bombay phenotype for screening and identification of rare blood group. ABO and H phenotypes of the proband were identified by serological techniques. The exon 6 to exon 7 of ABO gene and full coding region of α-1,2-fucosyltransferase (fut1) gene of the proband were analyzed by polymerase chain reaction and direct sequencing of the amplified fragments. The haplotype of compound heterozygote of fut1 was also identified by cloning sequencing. The results indicated that a rare para-Bombay phenotype was confirmed by serological techniques. Two deletion or insertion variant sites near nucleotide 547 and 880 were detected in fut1 gene. The results of cloning sequence showed that one haplotype of fut1 gene was two bases deletion at 547-552 (AGAGAG→AGAG), and another one was two bases deletion at position 880-882 (TTT→T). Both two variants caused a reading frame shift and a premature stop codon. It is concluded that a rare para-Bombay phenotype is found and confirmed in blood donor population. The molecular basis of this individual is compound heterozygote of two bases deletion on fut1 gene which weaken the activity of α-1, 2-fucosyltransferase.

  11. Domain Specific Attentional Impairments in Children with Chromosome 22Q11.2 Deletion Syndrome

    Science.gov (United States)

    Bish, Joel P.; Chiodo, Renee; Mattei, Victoria; Simon, Tony J.

    2007-01-01

    One of the defining cognitive characteristics of the chromosome 22q deletion syndrome (DS22q11.2) is visuospatial processing impairments. The purpose of this study was to investigate and extend the specific attentional profile of children with this disorder using both an object-based attention task and an inhibition of return task. A group of…

  12. Deletion of short arm of chromosome 18, Del(18p syndrome

    Directory of Open Access Journals (Sweden)

    Prashant Babaji

    2014-01-01

    Full Text Available Deletion of the short arm of chromosome 18 is a rare syndrome clinically presenting with variable mental retardation, growth retardation, low height, pectus excavatum, craniofacial malformations including long ear, ptosis, microcephaly and short neck. This case report presents with characteristic features along with rare feature of single nostril.

  13. Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

    Science.gov (United States)

    Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

    2014-01-01

    Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…

  14. Mapping of polyketide biosynthesis pathways in Aspergillus nidulans using a genome wide PKS gene deletion library

    DEFF Research Database (Denmark)

    Larsen, Thomas Ostenfeld; Rank, Christian; Klejnstrup, Marie Louise;

    In order to map new links between PKS genes and their products in Aspergillus nidulans we have systematically deleted all thirty-two individual genes predicted to encode polyketide synthases in this model organism. This number greatly exceeds the number of currently known PKs calling for new...

  15. Amplified and homozygously deleted genes in glioblastoma: impact on gene expression levels.

    Directory of Open Access Journals (Sweden)

    Inês Crespo

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. METHODOLOGY: Single-nucleotide polymorphism (SNP-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46, and to evaluate the impact of copy number alterations (CNA on mRNA levels of the genes involved. PRINCIPAL FINDINGS: Recurrent amplicons were detected for chromosomes 7 (50%, 12 (22%, 1 (11%, 4 (9%, 11 (4%, and 17 (4%, whereas homozygous deletions involved chromosomes 9p21 (52% and 10q (22%. Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2, while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively. Despite homozygous del(9p21 and del(10q23.31 included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene. CONCLUSIONS: Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.

  16. Mapping Cortical Morphology in Youth with Velocardiofacial (22q11.2 Deletion) Syndrome

    Science.gov (United States)

    Kates, Wendy R.; Bansal, Ravi; Fremont, Wanda; Antshel, Kevin M.; Hao, Xuejun; Higgins, Anne Marie; Liu, Jun; Shprintzen, Robert J.; Peterson, Bradley S.

    2011-01-01

    Objective: Velocardiofacial syndrome (VCFS; 22q11.2 deletion syndrome) represents one of the highest known risk factors for schizophrenia. Insofar as up to 30% of individuals with this genetic disorder develop schizophrenia, VCFS constitutes a unique, etiologically homogeneous model for understanding the pathogenesis of schizophrenia. Method:…

  17. FAK deletion accelerates liver regeneration after two-thirds partial hepatectomy

    Science.gov (United States)

    Shang, Na; Arteaga, Maribel; Chitsike, Lennox; Wang, Fang; Viswakarma, Navin; Breslin, Peter; Qiu, Wei

    2016-01-01

    Understanding the molecular mechanisms of liver regeneration is essential to improve the survival rate of patients after surgical resection of large amounts of liver tissue. Focal adhesion kinase (FAK) regulates different cellular functions, including cell survival, proliferation and cell migration. The role of FAK in liver regeneration remains unknown. In this study, we found that Fak is activated and induced during liver regeneration after two-thirds partial hepatectomy (PHx). We used mice with liver-specific deletion of Fak and investigated the role of Fak in liver regeneration in 2/3 PHx model (removal of 2/3 of the liver). We found that specific deletion of Fak accelerates liver regeneration. Fak deletion enhances hepatocyte proliferation prior to day 3 post-PHx but attenuates hepatocyte proliferation 3 days after PHx. Moreover, we demonstrated that the deletion of Fak in liver transiently increases EGFR activation by regulating the TNFα/HB-EGF axis during liver regeneration. Furthermore, we found more apoptosis in Fak-deficient mouse livers compared to WT mouse livers after PHx. Conclusion: Our data suggest that Fak is involved in the process of liver regeneration, and inhibition of FAK may be a promising strategy to accelerate liver regeneration in recipients after liver transplantation. PMID:27677358

  18. A New Case of an Extremely Rare 3p21.31 Interstitial Deletion.

    Science.gov (United States)

    Lovrecic, Luca; Bertok, Sara; Žerjav Tanšek, Mojca

    2016-05-01

    Interstitial 3p21.31 deletions have been very rarely reported. We describe a 7-year-old boy with global developmental delay, specific facial characteristics, hydronephrosis, and hypothyreosis with a de novo deletion of 3p21.31, encompassing 29 OMIM genes. Despite the wide use of microarrays, no similar case has been reported in the literature so far. Five overlapping cases are deposited in the DECIPHER database, 2 of which have significant overlapping chromosomal aberrations. They both share some phenotypic characteristics with our case, e.g. developmental delay, intellectual disability and facial dysmorphism (arched eyebrows, hypertelorism, low-set ears, and a large nose tip). In addition, loss-of-function mutations in the SETD2 gene (OMIM 612778) of the deleted region have been described in 3 patients, presenting with some similar clinical features, namely overgrowth, intellectual disability, speech delay, hypotonia, autism, and epilepsy. Therefore, SETD2 may explain part of the phenotype in our case. We focused on 3 other genes in the deleted region, based on their known functions, namely CSPG5 (OMIM 606775), PTH1R (OMIM 168468) and SMARCC1 (OMIM 601732), and assessed their potentially important role in describing the patient's phenotype. Additional cases with haploinsufficiency of this region are needed to elucidate further genotype-phenotype correlations. PMID:27385966

  19. 22q13.3 Deletion Syndrome : Clinical and Molecular Analysis Using Array CGH

    NARCIS (Netherlands)

    Dhar, S. U.; del Gaudio, D.; German, J. R.; Peters, S. U.; Ou, Z.; Bader, P. I.; Berg, J. S.; Blazo, M.; Brown, C. W.; Graham, B. H.; Grebe, T. A.; Lalani, S.; Irons, M.; Sparagana, S.; Williams, M.; Phillips, J. A.; Beaudet, A. L.; Stankiewicz, P.; Patel, A.; Cheung, S. W.; Sahoo, T.

    2010-01-01

    The 22q13.3 deletion syndrome results from loss of terminal segments of varying sizes at 22qter. Few genotype phenotype correlations have been found but all patients have mental retardation and severe delay, or absence of, expressive speech. We carried out clinical and molecular characterization of

  20. 78 FR 40737 - Notification of Deletion of System of Records; Office of Criminal Enforcement, Forensics...

    Science.gov (United States)

    2013-07-08

    ... AGENCY Notification of Deletion of System of Records; Office of Criminal Enforcement, Forensics... Investigations Center, Office of Criminal Enforcement, Forensics & Training at (303) 462-9051 or Tammy Stein..., Forensics & Training at (303) 462-9054, P.O. Box 25227, Denver Federal Center, 6th and Kipling, Building...

  1. Chemical analysis of a genome wide polyketide synthase gene deletion library in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Larsen, Thomas Ostenfeld; Klejnstrup, Marie Louise; Nielsen, Jakob Blæsbjerg;

    predicted to encode polyketide synthases have been individually been deleted. This presentation will highlight our recent linking of secondary metabolites in A. nidulans to genes, and in particular describe some recent work on characterization of ANID_6448 and associated genes responsible for biosynthesis...

  2. Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype and deletion size

    Directory of Open Access Journals (Sweden)

    Halder Ashutosh

    2012-03-01

    Full Text Available Abstract We report on a pair of male monozygotic twins with 22q11.2 microdeletion, discordant phenotype and discordant deletion size. The second twin had findings suggestive of DiGeorge syndrome, while the first twin had milder anomalies without any cardiac malformation. The second twin had presented with intractable convulsion, cyanosis and cardiovascular failure in the fourth week of life and expired on the sixth week of life, whereas the first twin had some characteristic facial appearance with developmental delay but no other signs of the 22q11.2 microdeletion syndrome including cardiovascular malformation. The fluorescence in situ hybridization (FISH analysis had shown a microdeletion on the chromosome 22q11.2 in both twins. The interphase FISH did not find any evidence for the mosaicism. The genomic DNA microarray analysis, using HumanCytoSNP-12 BeadChip (Illumina, was identical between the twins except different size of deletion of 22q11.2. The zygosity using HumanCytoSNP-12 BeadChip (Illumina microarray analysis suggested monozygosity. This observation indicates that altered size of the deletion may be the underlying etiology for the discordance in phenotype in monozygotic twins. We think early post zygotic events (mitotic non-allelic homologous recombination could have been played a role in the alteration of 22q11.2 deletion size and, thus phenotypic variability in the monozygotic twins.

  3. Core Neuropsychological Characteristics of Children and Adolescents with 22q11.2 Deletion

    Science.gov (United States)

    Jacobson, C.; Shearer, J.; Habel, A.; Kane, F.; Tsakanikos, E.; Kravariti, E.

    2010-01-01

    Background: The 22q11.2 deletion syndrome (22qDS) confers high risk for intellectual disability and neuropsychological/academic impairment, although a minority of patients show average intelligence. Intellectual heterogeneity and the high prevalence of psychiatric diagnoses in earlier studies may have obscured the prototypical neuropsychological…

  4. The 11q Terminal Deletion Disorder Jacobsen Syndrome is a Syndromic Primary Immunodeficiency

    NARCIS (Netherlands)

    V.A.S.H. Dalm (Virgil); G.J.A. Driessen (Gertjan); B.H. Barendregt (Barbara); P.M. van Hagen (Martin); M. van der Burg (Mirjam)

    2015-01-01

    textabstractBackground: Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case

  5. Subtypes in 22q11.2 Deletion Syndrome Associated with Behaviour and Neurofacial Morphology

    Science.gov (United States)

    Sinderberry, Brooke; Brown, Scott; Hammond, Peter; Stevens, Angela F.; Schall, Ulrich; Murphy, Declan G. M.; Murphy, Kieran C.; Campbell, Linda E.

    2013-01-01

    22q11.2 deletion syndrome (22q11DS) has a complex phenotype with more than 180 characteristics, including cardiac anomalies, cleft palate, intellectual disabilities, a typical facial morphology, and mental health problems. However, the variable phenotype makes it difficult to predict clinical outcome, such as the high prevalence of psychosis among…

  6. Penetrance and clinical consequences of a gross SDHB deletion in a large family.

    Science.gov (United States)

    Solis, D C; Burnichon, N; Timmers, H J L M; Raygada, M J; Kozupa, A; Merino, M J; Makey, D; Adams, K T; Venisse, A; Gimenez-Roqueplo, A-P; Pacak, K

    2009-04-01

    Mutations in the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) are inherited in an autosomal dominant manner and are associated with hereditary paraganglioma (PGL) and pheochromocytoma. The phenotype of patients with SDHB point mutations has been previously described. However, the phenotype and penetrance of gross SDHB deletions have not been well characterized as they are rarely described. The objective was to describe the phenotype and estimate the penetrance of an exon 1 large SDHB deletion in one kindred. A retrospective and prospective study of 41 relatives across five generations was carried out. The main outcome measures were genetic testing, clinical presentations, plasma catecholamines and their O-methylated metabolites. Of the 41 mutation carriers identified, 11 were diagnosed with PGL, 12 were found to be healthy carriers after evaluation, and 18 were reportedly healthy based on family history accounts. The penetrance of PGL related to the exon 1 large SDHB deletion in this family was estimated to be 35% by age 40. Variable expressivity of the phenotype associated with a large exon 1 SDHB deletion was observed, including low penetrance, diverse primary PGL tumor locations, and malignant potential.

  7. CCR5 Deletion Protects Against Inflammation-Associated Mortality in Dialysis Patients

    NARCIS (Netherlands)

    F.L.H. Muntinghe; M. Verduijn; M.W. Zuurman; D.C. Grootendorst; J.J. Carrero; A.R. Qureshi; K. Luttropp; L. Nordfors; B. Lindholm; V. Brandenburg; M. Schalling; P. Stenvinkel; E.W. Boeschoten; R.T. Krediet; G. Navis; F.W. Dekker

    2009-01-01

    The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR5 Delta 32) leads to deficiency of the receptor. We hypothesized that CCR5 Delta 32 modulates inflammation-driven mortality in patients with ESRD. We studied the inter

  8. MECP2 deletions and genotype-phenotype correlation in Rett syndrome.

    Science.gov (United States)

    Scala, Elisa; Longo, Ilaria; Ottimo, Federica; Speciale, Caterina; Sampieri, Katia; Katzaki, Eleni; Artuso, Rosangela; Mencarelli, Maria Antonietta; D'Ambrogio, Tatiana; Vonella, Giuseppina; Zappella, Michele; Hayek, Giuseppe; Battaglia, Agatino; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

    2007-12-01

    Rett syndrome is a neurodevelopmental disorder that represents one of the most common genetic causes of mental retardation in girls. MECP2 point mutations in exons 2-4 account for about 80% of classic Rett cases and for a lower percentage of variant patients. We investigated the genetic cause in 77 mutation-negative Rett patients (33 classic, 31 variant, and 13 Rett-like cases) by searching missed MECP2 defects. DHPLC analysis of exon 1 and MLPA analysis allowed us to identify the defect in 17 Rett patients: one exon 1 point mutation (c.47_57del) in a classic case and 16 MECP2 large deletions (15/33 classic and 1/31 variant cases). One identical intragenic MECP2 deletion, probably due to gonadal mosaicism, was found in two sisters with discordant phenotype: one classic and one "highly functioning" preserved speech variant. This result indicates that other epigenetic or genetic factors, beside MECP2, may contribute to phenotype modulation. Three out of 16 MECP2 deletions extend to the adjacent centromeric IRAK1 gene. A putative involvement of the hemizygosity of this gene in the ossification process is discussed. Finally, results reported here clearly indicate that MECP2 large deletions are a common cause of classic Rett, and MLPA analysis is mandatory in MECP2-negative patients, especially in those more severely affected (P = 0.044).

  9. Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1

    DEFF Research Database (Denmark)

    Tscharntke, Michael; Pofahl, Ruth; Chrostek-Grashoff, Anna;

    2007-01-01

    -specific deletion of Rac1. Primary epidermal keratinocytes that expressed the N17Rac1 transgene were less proliferative than control cells and showed reduced ERK1/2 phosphorylation upon growth factor stimulation. Adhesion, spreading, random migration and closure of scratch wounds in vitro were significantly...

  10. Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome : a cohort study

    NARCIS (Netherlands)

    Kempers, Marlies J. E.; Kuiper, Roland P.; Ockeloen, Charlotte W.; Chappuis, Pierre O.; Hutter, Pierre; Rahner, Nils; Schackert, Hans K.; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Buettner, Reinhard; Verwiel, Eugene T. P.; van Krieken, J. Han; Nagtegaal, Iris D.; Goossens, Monique; van der Post, Rachel S.; Niessen, Renee C.; Sijmons, Rolf H.; Kluijt, Irma; Hogervorst, Frans B. L.; Leter, Edward M.; Gille, Johan J. P.; Aalfs, Cora M.; Redeker, Egbert J. W.; Hes, Frederik J.; Tops, Carli M. J.; van Nesselrooij, Bernadette P. M.; van Gijn, Marielle E.; Garcia, Encarna B. Gomez; Eccles, Diana M.; Bunyan, David J.; Syngal, Sapna; Stoffel, Elena M.; Culver, Julie O.; Palomares, Melanie R.; Graham, Tracy; Velsher, Lea; Papp, Janos; Olah, Edith; Chan, Tsun L.; Leung, Suet Y.; van Kessel, Ad Geurts; Kiemeney, Lambertus A. L. M.; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J. L.

    2011-01-01

    Background Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH

  11. The Role of Dicentric Chromosome Formation and Secondary Centromere Deletion in the Evolution of Myeloid Malignancy

    Directory of Open Access Journals (Sweden)

    Ruth N. MacKinnon

    2011-01-01

    Full Text Available Dicentric chromosomes have been identified as instigators of the genome instability associated with cancer, but this instability is often resolved by one of a number of different secondary events. These include centromere inactivation, inversion, and intercentromeric deletion. Deletion or excision of one of the centromeres may be a significant occurrence in myeloid malignancy and other malignancies but has not previously been widely recognized, and our reports are the first describing centromere deletion in cancer cells. We review what is known about dicentric chromosomes and the mechanisms by which they can undergo stabilization in both constitutional and cancer genomes. The failure to identify centromere deletion in cancer cells until recently can be partly explained by the standard approaches to routine diagnostic cancer genome analysis, which do not identify centromeres in the context of chromosome organization. This hitherto hidden group of primary dicentric, secondary monocentric chromosomes, together with other unrecognized dicentric chromosomes, points to a greater role for dicentric chromosomes in cancer initiation and progression than is generally acknowledged. We present a model that predicts and explains a significant role for dicentric chromosomes in the formation of unbalanced translocations in malignancy.

  12. Courses to be Deleted from the Credit and Noncredit Program of the Community Colleges.

    Science.gov (United States)

    Petersen, Allan L.

    This report describes the procedures employed in the preparation of a list of courses to be deleted from the credit and noncredit programs of the California community colleges in response to a $30 million deduction from the total community college apportionments. The first section presents background on the 1982-83 budget bill, specifies three…

  13. TNF-alpha levels are not increased in inflamed patients carrying the CCR5 deletion 32

    NARCIS (Netherlands)

    Muntinghe, Friso L. H.; Carrero, Juan Jesus; Navis, Gerjan; Stenvinkel, Peter

    2011-01-01

    Background and aims: Recently we reported on a genetically predisposed protection from C-reactive protein (CRP) related mortality in dialysis patients carrying the functional CC-chemokine receptor 5 deletion 32 allele (CCR5 Delta 32) mutation. Since CCR5 Delta 32 is associated with a less pro-inflam

  14. Role of CCR5 Delta 32 bp deletion in RA and SLE

    NARCIS (Netherlands)

    Martens, H. A.; Kallenberg, C. G. M.; Bijl, M.

    2009-01-01

    CCR5 and its ligands play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A deletion of 32 bp in its gene leads to the production of a non-functional receptor. Although a protective effect of CCR5 Delta 32 for the development of RA has been suggested, future stud

  15. Genomic deletions in OPA1 in Danish patients with autosomal dominant optic atrophy

    DEFF Research Database (Denmark)

    Almind, Gitte J; Grønskov, Karen; Milea, Dan;

    2011-01-01

    Autosomal dominant optic atrophy (ADOA, Kjer disease, MIM #165500) is the most common form of hereditary optic neuropathy. Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases. Although deletions of OPA1 were recently reported...

  16. Distinctive phenotypic abnormalities associated with submicroscopic 21q22 deletion including DYRK1A

    NARCIS (Netherlands)

    R. Oegema (Renske); J.E.M.M. de Klein (Annelies); A. Verkerk; R. Schot (Rachel); B. Dumee (Belinda); H. Douben (Hannie); H.J.F.M.M. Eussen (Bert); L. Dubbel (L.); P. Poddighe (Pino); I.M.B.H. van de Laar (Ingrid); W.B. Dobyns (William); P.J. van der Spek (Peter); M.H. Lequin (Maarten); I.F.M. de Coo (René); M.C.Y. de Wit (Marie Claire); M.W. Wessels (Marja); G.M.S. Mancini (Grazia)

    2010-01-01

    textabstractPartial monosomy 21 has been reported, but the phenotypes described are variable with location and size of the deletion. We present 2 patients with a partially overlapping microdeletion of 21q22 and a striking phenotypic resemblance. They both presented with severe psychomotor delay, beh

  17. 41 CFR 51-6.8 - Deletion of items from the Procurement List.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Deletion of items from the Procurement List. 51-6.8 Section 51-6.8 Public Contracts and Property Management Other Provisions Relating to Public Contracts COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED...

  18. Deletion of host histone acetyltransferases and deacetylases strongly affects Agrobacterium-mediated transformation of Saccharomyces cerevisiae.

    Science.gov (United States)

    Soltani, Jalal; van Heusden, Gerard Paul H; Hooykaas, Paul J J

    2009-09-01

    Agrobacterium tumefaciens is a plant pathogen that genetically transforms plant cells by transferring a part of its Ti-plasmid, the T-strand, to the host cell. Under laboratory conditions, it can also transform cells from many different nonplant organisms, including the yeast Saccharomyces cerevisiae. Collections of S. cerevisiae strains have been developed with systematic deletion of all coding sequences. Here, we used these collections to identify genes involved in the Agrobacterium-mediated transformation (AMT) of S. cerevisiae. We found that deletion of genes (GCN5, NGG1, YAF9 and EAF7) encoding subunits of the SAGA, SLIK, ADA and NuA4 histone acetyltransferase complexes highly increased the efficiency of AMT, while deletion of genes (HDA2, HDA3 and HST4) encoding subunits of histone deacetylase complexes decreased AMT. These effects are specific for AMT as the efficiency of chemical (lithium acetate) transformation was not or only slightly affected by these deletions. Our data are consistent with a positive role of host histone deacetylation in AMT.

  19. White matter abnormalities in adults with 22q11 deletion syndrome with and without schizophrenia

    NARCIS (Netherlands)

    F. da Silva Alves; N. Schmitz; O. Bloemen; J. van der Meer; J. Meijer; E. Boot; A. Nederveen; L. de Haan; D. Linszen; T. van Amelsvoort

    2011-01-01

    Dysfunction of cerebral white matter (WM) is a potential factor underlying the neurobiology of schizophrenia. People with 22q11 deletion syndrome have altered brain morphology and increased risk for schizophrenia, therefore decreased WM integrity may be related to schizophrenia in 22q11DS. We measur

  20. An analysis of substitution, deletion and insertion mutations in cancer genes.

    Science.gov (United States)

    Iengar, Prathima

    2012-08-01

    Cancer-associated mutations in cancer genes constitute a diverse set of mutations associated with the disease. To gain insight into features of the set, substitution, deletion and insertion mutations were analysed at the nucleotide level, from the COSMIC database. The most frequent substitutions were c → t, g → a, g → t, and the most frequent codon changes were to termination codons. Deletions more than insertions, FS (frameshift) indels more than I-F (in-frame) ones, and single-nucleotide indels, were frequent. FS indels cause loss of significant fractions of proteins. The 5'-cut in FS deletions, and 5'-ligation in FS insertions, often occur between pairs of identical bases. Interestingly, the cut-site and 3'-ligation in insertions, and 3'-cut and join-pair in deletions, were each found to be the same significantly often (p Proto-oncogenes undergo fewer, less-disruptive mutations, in selected protein regions, to activate a single allele. Finally, catalogues, in ranked order, of genes mutated in each cancer, and cancers in which each gene is mutated, were created. The study highlights the nucleotide level preferences and disruptive nature of cancer mutations.

  1. Refinement of the critical 2p25.3 deletion region

    DEFF Research Database (Denmark)

    De Rocker, Nina; Vergult, Sarah; Koolen, David;

    2015-01-01

    PURPOSE: Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis. METHODS: In this stu...

  2. Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

    DEFF Research Database (Denmark)

    Delio, Maria; Guo, Tingwei; McDonald-McGinn, Donna M;

    2013-01-01

    Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplication...

  3. Fifteen-year follow-up of pulmonary function in individuals heterozygous for the cystic fibrosis phenylalanine-508 deletion

    DEFF Research Database (Denmark)

    Dahl, Morten; Nordestgaard, B G; Lange, P;

    2001-01-01

    In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma.......In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma....

  4. Osteopathia striata congenita with cranial sclerosis and intellectual disability due to contiguous gene deletions involving the WTX locus

    DEFF Research Database (Denmark)

    Holman, Sk; Morgan, T; Baujat, G;

    2013-01-01

    sclerosis, with a high prevalence of cleft palate and hearing loss. Intellectual disability or neurodevelopmental delay is not observed in females with point mutations in WTX leading to OSCS. One female has been described with a deletion spanning multiple neighbouring genes suggesting that deletion of some...

  5. Interstitial deletion of chromosome 4p associated with mild mental retardation, epilepsy and polymicrogyria of the left temporal lobe

    DEFF Research Database (Denmark)

    Møller, R S; Hansen, C P; Jackson, G D;

    2007-01-01

    In this study, we present a 38-year-old woman with an interstitial deletion of 4p15.1-15.3, mild mental retardation, epilepsy and polymicrogyria adjacent to an arachnoid cyst of the left temporal lobe. The deletion was ascertained through array-comparative genome hybridization screening of patien...

  6. 78 FR 70942 - Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations

    Science.gov (United States)

    2013-11-27

    ... AGENCY Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations... Insecticide, Fungicide, and Rodenticide Act (FIFRA), EPA is issuing a notice of receipt of request for amendments by registrants to delete uses in certain pesticide registrations. FIFRA provides that a...

  7. 77 FR 6562 - Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations

    Science.gov (United States)

    2012-02-08

    ... AGENCY Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations...) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, EPA is issuing a notice of receipt of request for amendments by registrants to delete uses in certain...

  8. 78 FR 44948 - Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations

    Science.gov (United States)

    2013-07-25

    ... AGENCY Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations... Insecticide, Fungicide, and Rodenticide Act (FIFRA), EPA is issuing a notice of receipt of request for amendments by registrants to delete uses in certain pesticide registrations. FIFRA provides that a...

  9. 75 FR 60114 - Notice of Receipt of Requests for Amendments to Delete Uses in Certain Pesticide Registrations

    Science.gov (United States)

    2010-09-29

    ... AGENCY Notice of Receipt of Requests for Amendments to Delete Uses in Certain Pesticide Registrations...)(1) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, EPA is issuing a notice of receipt of request for amendments by registrants to delete uses in certain...

  10. 77 FR 34042 - Notice of Receipt of Requests for Amendments to Delete Uses in Certain Pesticide Registrations

    Science.gov (United States)

    2012-06-08

    ... AGENCY Notice of Receipt of Requests for Amendments to Delete Uses in Certain Pesticide Registrations...) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, EPA is issuing a notice of receipt of request for amendments by registrants to delete uses in certain...

  11. 75 FR 24699 - Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations

    Science.gov (United States)

    2010-05-05

    ... AGENCY Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations...) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, EPA is issuing a notice of receipt of request for amendments by registrants to delete uses in certain...

  12. 76 FR 2111 - Notice of Receipt of Requests for Amendments to Delete Uses in Certain Pesticide Registrations

    Science.gov (United States)

    2011-01-12

    ... AGENCY Notice of Receipt of Requests for Amendments to Delete Uses in Certain Pesticide Registrations...) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, EPA is issuing a notice of receipt of request for amendments by Valent USA registrants to delete uses in certain...

  13. 77 FR 52331 - Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations

    Science.gov (United States)

    2012-08-29

    ... AGENCY Notice of Receipt of Requests for Amendments To Delete Uses in Certain Pesticide Registrations...) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, EPA is issuing a notice of receipt of request for amendments by registrants to delete uses in certain...

  14. Contiguous gene deletion of ELOVL7, ERCC8 and NDUFAF2 in a patient with a fatal multisystem disorder

    DEFF Research Database (Denmark)

    Janssen, Rolf J R J; Distelmaier, Felix; Smeets, Roel;

    2009-01-01

    gene deletion on chromosome 5. The deletion encompassed the NDUFAF2, ERCC8 and ELOVL7 genes, encoding complex I assembly factor 2 (also known as human B17.2L), a protein of the transcription-coupled nucleotide excision repair (TC-NER) machinery, and a putative elongase of very long-chain fatty acid...

  15. The Use of Transposons to Introduce Well-Defined Deletions in Plasmids : Possibilities for in Vivo Cloning

    NARCIS (Netherlands)

    Hille, Jacques; Schilperoort, Rob

    1981-01-01

    A method for obtaining well-defined deletions in an octopine Ti plasmid was developed. It was based on the assumption that deletions would occur between two directly repeated transposons, when both are temporarily present in one plasmid molecule. To obtain such a situation, recombination has been fo

  16. Deletion at chromosome 16p13. 3 as a cause of Rubinstein-Taybi syndrome: Clinical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Hennekam, R.C.M.; Tilanus, M.; Boogaard, M.J.H. van den (State Univ., Utrecht (Netherlands)); Hamel, B.C.J.; Voshart-van Heeren, H.; Mariman, E.C.M.; Beersum, S.E.C. van (University Hospital, Nijmegen (Netherlands)); Breuning, M.H. (Clinical Genetics Center, Rotterdam (Netherlands))

    1993-02-01

    In the accompanying paper, a chromosomal localization of the Rubinstein-Taybi syndrome by cytogenetic investigations with fluorescence in situ hybridization techniques at chromosome 16p13.3 is described. The authors investigated 19 of these patients and their parents (a) to ascertain the parental origin of the chromosome with the deletion in families where such a deletion was detected, (b) to disclose whether uniparental disomy plays a role in etiology, and (c) to compare clinical features in patients with a deletion to those in individuals in whom deletions were not detectable. Molecular studies showed a copy of chromosome 16 from each parent in all 19 patients. Uniparental disomy was also excluded for five other chromosome arms known to be imprinted in mice. None of the probes used for determining the origin of the deleted chromosome proved to be informative. The clinical features were essentially the same in patients with and without visible deletion, with a possible exception for the incidence of microcephaly, angulation of thumbs and halluces, and partial duplication of the halluces. A small deletion at 16p13.3 may be found in some patients with Rubinstein-Taybi syndrome. Cytogenetically undetectable deletions, point mutations, mosaicism, heterogeneity, or phenocopy by a nongenetic cause are the most probable explanations for the absence of cytogenetic or molecular abnormalities in other patients with Rubinstein-Taybi syndrome. 26 refs., 3 tabs., 2 figs.

  17. A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle

    Science.gov (United States)

    The role of non-structural protein 3A in foot-and-mouth disease virus (FMDV) on the virulence in cattle has received significant attention. Particularly, a characteristic 10–20 amino acid deletion has been implicated as being responsible for virus attenuation in cattle: a 10 amino acid deletion in t...

  18. Deletion mutants of region E1 a of AD12 E1 plasmids: Effect on oncogenic transformation

    NARCIS (Netherlands)

    Bos, J.L.; Jochemsen, A.G.; Bernards, R.A.; Schrier, P.I.; Ormondt, H. van; Eb, A.J. van der

    1983-01-01

    Plasmids containing the El region of Ad12 DNA can transform certain rodent cells into oncogenic cells. To study the role of the Ela subregion in the process of oncogenic transformation, Ad12 region El mutants carrying deletions in the Ela region were constructed. Deletion mutants pR7 and pR8 affect

  19. Deletional analysis of functional regions of complementary sense promoter from cotton leaf curl virus

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Complementary sense promoter from cotton leaf curl virus (CLCuV) is a novel plant promoter for genetic engineering that could drive high-level foreign gene expression in plant. To determine the optimal promoter sequence for gene expression, CLCuV promoter was deleted from its 5' end to form promoter fragments with five different lengths, and chimeric gus genes were constructed using the promoter deletion. These vectors were delivered into Agrobacterium and tobacco (Nicotiana tabacum L. cv. Xanthi) plants which were transformed by leaf discs method. GUS activity of transgenic plants was measured. The results showed that GUS activities with the promoter deleted to -287 and -271 from the translation initiation site were respectively about five and three times that of full-length promoter. There exists a cis-element which is important for the expressing activity in phloem from -271 to -176. Deletion from -176 to -141 resulted in a 20-30-fold reduction in GUS activity in leaves with weak activity in leaves and stems and losing GUS activity in roots. The functional domains of complementary sense gene promoter of CLCuV were firstly analyzed and compared. It was found that the promoter activity with the deletion of negative cis-elements was much stronger than that of full-length promoter and was about twelve times on average that of CaMV 35S promoter, suggesting that the promoter has great application potential. Results also provide novel clues for understanding the mechanisms of geminivirus gene regulation and interaction between virus and plant.

  20. Simple Method for Markerless Gene Deletion in Multidrug-Resistant Acinetobacter baumannii.

    Science.gov (United States)

    Oh, Man Hwan; Lee, Je Chul; Kim, Jungmin; Choi, Chul Hee; Han, Kyudong

    2015-05-15

    The traditional markerless gene deletion technique based on overlap extension PCR has been used for generating gene deletions in multidrug-resistant Acinetobacter baumannii. However, the method is time-consuming because it requires restriction digestion of the PCR products in DNA cloning and the construction of new vectors containing a suitable antibiotic resistance cassette for the selection of A. baumannii merodiploids. Moreover, the availability of restriction sites and the selection of recombinant bacteria harboring the desired chimeric plasmid are limited, making the construction of a chimeric plasmid more difficult. We describe a rapid and easy cloning method for markerless gene deletion in A. baumannii, which has no limitation in the availability of restriction sites and allows for easy selection of the clones carrying the desired chimeric plasmid. Notably, it is not necessary to construct new vectors in our method. This method utilizes direct cloning of blunt-end DNA fragments, in which upstream and downstream regions of the target gene are fused with an antibiotic resistance cassette via overlap extension PCR and are inserted into a blunt-end suicide vector developed for blunt-end cloning. Importantly, the antibiotic resistance cassette is placed outside the downstream region in order to enable easy selection of the recombinants carrying the desired plasmid, to eliminate the antibiotic resistance cassette via homologous recombination, and to avoid the necessity of constructing new vectors. This strategy was successfully applied to functional analysis of the genes associated with iron acquisition by A. baumannii ATCC 19606 and to ompA gene deletion in other A. baumannii strains. Consequently, the proposed method is invaluable for markerless gene deletion in multidrug-resistant A. baumannii. PMID:25746991

  1. Increased attenuation but decreased immunogenicity by deletion of multiple vaccinia virus immunomodulators.

    Science.gov (United States)

    Sumner, Rebecca P; Ren, Hongwei; Ferguson, Brian J; Smith, Geoffrey L

    2016-09-14

    Vaccinia virus (VACV)-derived vectors are popular candidates for vaccination against diseases such as HIV-1, malaria and tuberculosis. However, their genomes encode a multitude of proteins with immunomodulatory functions, several of which reduce the immunogenicity of these vectors. Hitherto only limited studies have investigated whether the removal of these immunomodulatory genes in combination can increase vaccine efficacy further. To this end we constructed viruses based on VACV strain Western Reserve (WR) lacking up to three intracellular innate immunomodulators (N1, C6 and K7). These genes were selected because the encoded proteins had known functions in innate immunity and the deletion of each gene individually had caused a decrease in virus virulence in the murine intranasal and intradermal models of infection and an increase in immunogenicity. Data presented here demonstrate that deletion of two, or three of these genes in combination attenuated the virus further in an incremental manner. However, when vaccinated mice were challenged with VACV WR the double and triple gene deletion viruses provided weaker protection against challenge. This was accompanied by inferior memory CD8(+) T cell responses and lower neutralising antibody titres. This study indicates that, at least for the three genes studied in the context of VACV WR, the single gene deletion viruses are the best vaccine vectors, and that increased attenuation induced by deletion of additional genes decreased immunogenicity. These data highlight the fine balance and complex relationship between viral attenuation and immunogenicity. Given that the proteins encoded by the genes examined in this study are known to affect specific aspects of innate immunity, the set of viruses constructed here are interesting tools to probe the role of the innate immune response in influencing immune memory and vaccine efficacy. PMID:27544585

  2. Genomic clones of bovine parvovirus: Construction and effect of deletions and terminal sequence inversions on infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Shull, B.C.; Chen, K.C.; Lederman, M.; Stout, E.R.; Bates, R.C. (Virginia Polytechnic Institute and State Univ., Blacksburg (USA))

    1988-02-01

    Genomic clones of the autonomous parvovirus bovine parvovirus (BPV) were constructed by blunt-end ligation of reannealed virion plus and minus DNA strands into the plasmid pUC8. These clones were stable during propagation in Escherichia coli JM107. All clones tested were found to be infectious by the criteria of plaque titer and progressive cytophathic effect after transfection into bovine fetal lung cells. Sequencing of the recombinant plasmids demonstrated that all of the BPV inserts had left-end (3{prime})-terminal deletions of up to 34 bases. Defective genomes could also be detected in the progeny DNA even though the infection was initiated with homogeneous, cloned DNA. Full-length genomic clones with 3{prime} flip and 3{prime} flop conformations were constructed and were found to have equal infectivity. Expression of capsid proteins from tranfected genomes was demonstrated by hemagglutination, indirect immunofluorescence, and immunoprecipitation of ({sup 35}S)methionine-labeled cell lysates. Use of appropriate antiserum for immunoprecipitation showed the synthesis of BPV capsid and noncapsid proteins after transfection. Independently, a series of genomic clones with increasingly larger 3{prime}-terminal deletions was prepared from separately subcloned 3{prime}-terminal fragments. Transfection of these clones into bovine fetal lung cells revealed that deletions of up to 34 bases at the 3{prime} end lowered but did not abolish infectivity, while deletions of greater than 52 bases were lethal. End-label analysis showed that the 34-base deletion was repaired to wild-type length in the progeny virus.

  3. Hereditary vitamin D resistant rickets due to deletion of exon 3 of the vitamin D receptor

    Energy Technology Data Exchange (ETDEWEB)

    Rut, A.R.; O`Riordan, J.L.H.; Hughes, M.R. [Baylor College of Medicine, Houston, TX (United States)

    1994-09-01

    Hereditary vitamin D resistant rickets is an autosomal recessive disorder characterized by severe rickets, hypolcalcaemia, secondary hyperparathyroidism and occasionally, the absence of body hair. The pathological process involves resistance of target tissues to the actions of calcitriol [1,25(OH{sub 2}D{sub 3})], the hormonal form of vitamin D. Calcitriol mediates its actions through a nuclear receptor (VDR) which has been cloned and shown to be a member of the superfamily of steriod/thyroid/retinoic acid receptors. Skin fibroblasts were obtained from a Greek child with characteristic features of the condition. Total RNA was extracted from rapidly dividing cells and reverse transcribed. The coding region was amplified by PCR with primers 31a in the 5{prime} untranslated region and 31b in the 3{prime} untranslated region of the VDR cDNA sequence. The 5{prime} and 3{prime} halves of VDR were further amplified using primers tagged with M13 forward and reverse primer sequences. The whole process was carried out in duplicate starting with RNA. Sequence data was obtained using Taq dye primer cycle sequencing (ABI). Agarose gel electrophoresis revealed that the 5{prime} product was approximately 100 bp shorter than control. This was confirmed by sequencing which demonstrated a 131 bp deletion of the C-terminal part of the DNA binding domain (bases 147-277). Bases 147-277 are coded for by exon 3 and this deletion is bounded by the splice junctions. This is the first report of a deletion in VDR in any patient with vitamin D-resistant rickets. Such a deletion not only removes the second zinc finger but also results in a frameshift that corrupts the remainder of the receptor. Such a deletion may have arisen as a result of a microdeletion of genomic DNA or, more likely, as a result of defective splicing.

  4. Bethlem myopathy and engineered collagen VI triple helical deletions prevent intracellular multimer assembly and protein secretion.

    Science.gov (United States)

    Lamandé, S R; Shields, K A; Kornberg, A J; Shield, L K; Bateman, J F

    1999-07-30

    Mutations in the genes that code for collagen VI subunits, COL6A1, COL6A2, and COL6A3, are the cause of the autosomal dominant disorder, Bethlem myopathy. Although three different collagen VI structural mutations have previously been reported, the effect of these mutations on collagen VI assembly, structure, and function is currently unknown. We have characterized a new Bethlem myopathy mutation that results in skipping of COL6A1 exon 14 during pre-mRNA splicing and the deletion of 18 amino acids from the triple helical domain of the alpha1(VI) chain. Sequencing of genomic DNA identified a G to A transition in the +1 position of the splice donor site of intron 14 in one allele. The mutant alpha1(VI) chains associated intracellularly with alpha2(VI) and alpha3(VI) to form disulfide-bonded monomers, but further assembly into dimers and tetramers was prevented, and molecules containing the mutant chain were not secreted. This triple helical deletion thus resulted in production of half the normal amount of collagen VI. To further explore the biosynthetic consequences of collagen VI triple helical deletions, an alpha3(VI) cDNA expression construct containing a 202-amino acid deletion within the triple helix was produced and stably expressed in SaOS-2 cells. The transfected mutant alpha3(VI) chains associated with endogenous alpha1(VI) and alpha2(VI) to form collagen VI monomers, but dimers and tetramers did not form and the mutant-containing molecules were not secreted. Thus, deletions within the triple helical region of both the alpha1(VI) and alpha3(VI) chains can prevent intracellular dimer and tetramer assembly and secretion. These results provide the first evidence of the biosynthetic consequences of structural collagen VI mutations and suggest that functional protein haploinsufficiency may be a common pathogenic mechanism in Bethlem myopathy. PMID:10419498

  5. 22q11 deletion syndrome: a review of the neuropsychiatric features and their neurobiological basis

    Directory of Open Access Journals (Sweden)

    Squarcione C

    2013-12-01

    Full Text Available Chiara Squarcione, Maria Chiara Torti, Fabio Di Fabio, Massimo Biondi Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy Abstract: The 22q11.2 deletion syndrome (22q11DS is caused by an autosomal dominant microdeletion of chromosome 22 at the long arm (q 11.2 band. The 22q11DS is among the most clinically variable syndromes, with more than 180 features related with the deletion, and is associated with an increased risk of psychiatric disorders, accounting for up to 1%–2% of schizophrenia cases. In recent years, several genes located on chromosome 22q11 have been linked to schizophrenia, including those encoding catechol-O-methyltransferase and proline dehydrogenase, and the interaction between these and other candidate genes in the deleted region is an important area of research. It has been suggested that haploinsufficiency of some genes within the 22q11.2 region may contribute to the characteristic psychiatric phenotype and cognitive functioning of schizophrenia. Moreover, an extensive literature on neuroimaging shows reductions of the volumes of both gray and white matter, and these findings suggest that this reduction may be predictive of increased risk of prodromal psychotic symptoms in 22q11DS patients. Experimental and standardized cognitive assessments alongside neuroimaging may be important to identify one or more endophenotypes of schizophrenia, as well as a predictive prodrome that can be preventively treated during childhood and adolescence. In this review, we summarize recent data about the 22q11DS, in particular those addressing the neuropsychiatric and cognitive phenotypes associated with the deletion, underlining the recent advances in the studies about the genetic architecture of the syndrome. Keywords: 22q11 deletion syndrome, microdeletion, neuropsychiatric disorders, cognitive impairments

  6. Deletion pattern of the STS gene in X-linked ichthyosis in a Mexican population.

    Science.gov (United States)

    Jimenez Vaca, A. L.; Valdes-Flores, M. del R.; Rivera-Vega, M. R.; González-Huerta, L. M.; Kofman-Alfaro, S. H.; Cuevas-Covarrubias, S. A.

    2001-01-01

    BACKGROUND: X-linked ichthyosis (XLI) is an inherited disorder due to steroid sulfatase deficiency (STS). Most XLI patients (>90%) have complete deletion of the STS gene and flanking sequences. The presence of low copy number repeats (G1.3 and CRI-S232) on either side of the STS gene seems to play a role in the high frequency of these interstitial deletions. In the present study, we analyzed 80 Mexican patients with XLI and complete deletion of the STS gene. MATERIALS AND METHODS: STS activity was measured in the leukocytes using 7-[(3)H]-dehydroepiandrosterone sulfate as a substrate. Amplification of the regions telomeric-DXS89, DXS996, DXS1139, DXS1130, 5' STS, 3' STS, DXS1131, DXS1133, DXS237, DXS1132, DXF22S1, DXS278, DXS1134-centromeric was performed through PCR. RESULTS: No STS activity was detected in the XLI patients (0.00 pmoles/mg protein/h). We observed 3 different patterns of deletion. The first two groups included 25 and 32 patients, respectively, in which homologous sequences were involved. These subjects showed the 5' STS deletion at the sequence DXS1139, corresponding to the probe CRI-S232A2. The group of 32 patients presented the 3' STS rupture site at the sequence DXF22S1 (probe G1.3) and the remaining 25 patients had the 3' STS breakpoint at the sequence DXS278 (probe CRI-S232B2). The third group included 23 patients with the breakpoints at several regions on either side of the STS gene. No implication of the homologous sequences were observed in this group. CONCLUSION: These data indicate that more complex mechanisms, apart from homologous recombination, are occurring in the genesis of the breakpoints of the STS gene of XLI Mexican patients. PMID:11844872

  7. Identification of a novel functional deletion variant in the 5'-UTR of the DJ-1 gene

    Directory of Open Access Journals (Sweden)

    Warnich Louise

    2009-10-01

    Full Text Available Abstract Background DJ-1 forms part of the neuronal cellular defence mechanism against oxidative insults, due to its ability to undergo self-oxidation. Oxidative stress has been implicated in the pathogenesis of central nervous system damage in different neurodegenerative disorders including Alzheimer's disease and Parkinson's disease (PD. Various mutations in the DJ-1 (PARK7 gene have been shown to cause the autosomal recessive form of PD. In the present study South African PD patients were screened for mutations in DJ-1 and we aimed to investigate the functional significance of a novel 16 bp deletion variant identified in one patient. Methods The possible effect of the deletion on promoter activity was investigated using a Dual-Luciferase Reporter assay. The DJ-1 5'-UTR region containing the sequence flanking the 16 bp deletion was cloned into a pGL4.10-Basic luciferase-reporter vector and transfected into HEK293 and BE(2-M17 neuroblastoma cells. Promoter activity under hydrogen peroxide-induced oxidative stress conditions was also investigated. Computational (in silico cis-regulatory analysis of DJ-1 promoter sequence was performed using the transcription factor-binding site database, TRANSFAC via the PATCH™ and rVISTA platforms. Results A novel 16 bp deletion variant (g.-6_+10del was identified in DJ-1 which spans the transcription start site and is situated 93 bp 3' from a Sp1 site. The deletion caused a reduction in luciferase activity of approximately 47% in HEK293 cells and 60% in BE(2-M17 cells compared to the wild-type (P Conclusion This is the first report of a functional DJ-1 promoter variant, which has the potential to influence transcript stability or translation efficiency. Further work is necessary to determine the extent to which the g.-6_+10del variant affects the normal function of the DJ-1 promoter and whether this variant confers a risk for PD.

  8. Amelogenesis imperfecta in two families with defined AMELX deletions in ARHGAP6.

    Directory of Open Access Journals (Sweden)

    Jan C-C Hu

    Full Text Available Amelogenesis imperfecta (AI is a group of inherited conditions featuring isolated enamel malformations. About 5% of AI cases show an X-linked pattern of inheritance, which are caused by mutations in AMELX. In humans there are two, non-allelic amelogenin genes: AMELX (Xp22.3 and AMELY (Yp11.2. About 90% of amelogenin expression is from AMELX, which is nested within intron 1 of the gene encoding Rho GTPase activating protein 6 (ARHGAP6. We recruited two AI families and determined that their disease-causing mutations were partial deletions in ARHGAP6 that completely deleted AMELX. Affected males in both families had a distinctive enamel phenotype resembling "snow-capped" teeth. The 96,240 bp deletion in family 1 was confined to intron 1 of ARHGAP6 (g.302534_398773del96240, but removed alternative ARHGAP6 promoters 1c and 1d. Analyses of developing teeth in mice showed that ARHGAP6 is not expressed from these promoters in ameloblasts. The 52,654 bp deletion in family 2 (g.363924_416577del52654insA removed ARHGAP6 promoter 1d and exon 2, precluding normal expression of ARHGAP6. The male proband of family 2 had slightly thinner enamel with greater surface roughness, but exhibited the same pattern of enamel malformations characteristic of males in family 1, which themselves showed minor variations in their enamel phenotypes. We conclude that the enamel defects in both families were caused by amelogenin insufficiency, that deletion of AMELX results in males with a characteristic snow-capped enamel phenotype, and failed ARHGAP6 expression did not appreciably alter the severity of enamel defects when AMELX was absent.

  9. Cryptic 13q34 and 4q35.2 Deletions in an Italian Family.

    Science.gov (United States)

    Riccardi, Federica; Rivolta, Gianna F; Uliana, Vera; Grati, Francesca R; La Starza, Roberta; Marcato, Livia; Di Perna, Caterina; Quintavalle, Gabriele; Garavelli, Livia; Rosato, Simonetta; Sammarelli, Gabriella; Neri, Tauro M; Tagliaferri, Annarita; Martorana, Davide

    2015-01-01

    Variations of DNA sequences in the human genome range from large, microscopically visible chromosome anomalies to single nucleotide changes. Submicroscopic genomic copy number variations, i.e. chromosomal imbalances which are undetectable by conventional cytogenetic analysis, play an intriguing clinical role. In this study, we describe the clinical consequences of the concurrent presence of an interstitial deletion in 13q34 and a terminal deletion in 4q35.2 in an Italian family. The index patient, a 19-year-old male, as well as his 12-year-old sister are carriers of both deletions, one of maternal and the other of paternal origin. The phenotype includes language delay, multiorgan involvement and bleeding diathesis with mild deficiency of factors X and VII. In the sister, the concomitant presence of Noonan syndrome may partly explain the clinical symptoms. The deleted region on chromosome 13 involves several genes (ATP11A, MCF2L, F7, F10, PROZ, PCID2, CUL4A, and LAMP1); some of these seem to play a role in the proband's phenotype. The terminal deletion in 4q35.2 contains other OMIM genes (FRG1, FRG2 and DBET); moreover, the 4q region is reported as a susceptibility locus for Crohn's disease, diagnosed in the proband's father. To our knowledge, this is the first report of a family with these 2 submicroscopic copy number changes. We tried to relate the clinical phenotype of the proband and his family to the molecular function of the involved genes. PMID:26645620

  10. Prevalence of the 4977-bp and 4408-bp mitochondrial DNA deletions in mesenteric arteries from patients with colorectal cancer.

    Science.gov (United States)

    Li, Tao; Chen, Gui-Lan; Lan, Huan; Mao, Liang; Zeng, Bo

    2016-09-01

    Mitochondrial DNA (mtDNA) deletions are found in many diseased tissues and lead to impairment of mitochondrial functions. In this study, we found wide presence of the common 4977-bp and a novel 4408-bp deletion in the mtDNA of mesenteric arteries from patients with colorectal cancer. These two deletions were also detected in samples from healthy individuals. The content of mtDNA with the 4977-bp deletion was significantly lower in healthy controls than cancer-associated samples, and there was no significant difference for the 4408-bp deletion between the two groups. These results suggest that mtDNA in blood vessels around cancer cells may be strongly affected by oxidative stress and tend to accumulate more large-scale variations. PMID:26332461

  11. Han Chinese patients with dopa-responsive dystonia exhibit a low frequency of exonic deletion in the GCH1 gene.

    Science.gov (United States)

    Shi, W T; Cai, C Y; Li, M S; Ling, C; Li, W D

    2015-01-01

    We identified three novel mutations of the GTP cyclohydrolase 1 (GCH1) gene in patients with familial dopa-responsive dystonia (DRD), but were unable to identify meaningful sporadic mutations in patients with no obvious family DRD background. To investigate whether GCH1 regional deletions account for the etiology of DRD, we screened for heterozygous exonic deletions in DRD families and in patients with sporadic DRD. Multiple ligation-dependent probe amplification analysis and quantitative real-time polymerase chain reaction amplification was performed in all members of our DRD cohort and in controls to detect exonic deletions in GCH1, tyrosine hydroxylase, and the epsilon-sarcoglycan-encoding (SGCE) genes. Using these techniques, we detected a GCH1 exon 1 heterozygous deletion in 1 of 10 patients with sporadic DRD. Therefore, we concluded that exonic deletion in the GCH1 gene only accounted for the etiology in a small percentage of patients with sporadic DRD in our Han Chinese cohort. PMID:26400349

  12. Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome

    DEFF Research Database (Denmark)

    Vega, H; Trainer, A H; Gordillo, M;

    2010-01-01

    Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2, which codes for an acetyltransferase involved in the regulation of sister chromatid cohesion. Of 26 mutations described to date, only one missense mutation has been reported and all others are predicted to be truncating mu...

  13. Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Wittmann Christoph

    2008-03-01

    Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

  14. Physiology of deletion mutants in the anaerobic β-myrcene degradation pathway in Castellaniella defragrans

    Directory of Open Access Journals (Sweden)

    Lüddeke Frauke

    2012-09-01

    Full Text Available Abstract Background Monoterpenes present a large and versatile group of unsaturated hydrocarbons of plant origin with widespread use in the fragrance as well as food industry. The anaerobic β-myrcene degradation pathway in Castellaniella defragrans strain 65Phen differs from well known aerobic, monooxygenase-containing pathways. The initial enzyme linalool dehydratase-isomerase ldi/LDI catalyzes the hydration of β-myrcene to (S-(+-linalool and its isomerization to geraniol. A high-affinity geraniol dehydrogenase geoA/GeDH and a geranial dehydrogenase geoB/GaDH contribute to the formation of geranic acid. A genetic system was for the first time applied for the betaproteobacterium to prove in vivo the relevance of the linalool dehydratase-isomerase and the geraniol dehydrogenase. In-frame deletion cassettes were introduced by conjugation and two homologous recombination events. Results Polar effects were absent in the in-frame deletion mutants C. defragrans Δldi and C. defragrans ΔgeoA. The physiological characterization of the strains demonstrated a requirement of the linalool dehydratase-isomerase for growth on acyclic monoterpenes, but not on cyclic monoterpenes. The deletion of geoA resulted in a phenotype with hampered growth rate on monoterpenes as sole carbon and energy source as well as reduced biomass yields. Enzyme assays revealed the presence of a second geraniol dehydrogenase. The deletion mutants were in trans complemented with the broad-host range expression vector pBBR1MCS-4ldi and pBBR1MCS-2geoA, restoring in both cases the wild type phenotype. Conclusions In-frame deletion mutants of genes in the anaerobic β-myrcene degradation revealed novel insights in the in vivo function. The deletion of a high-affinity geraniol dehydrogenase hampered, but did not preclude growth on monoterpenes. A second geraniol dehydrogenase activity was present that contributes to the β-myrcene degradation pathway. Growth on cyclic monoterpenes

  15. Double helicase II (uvrD)-helicase IV (helD) deletion mutants are defective in the recombination pathways of Escherichia coli.

    OpenAIRE

    Mendonca, V M; Kaiser-Rogers, K; Matson, S W

    1993-01-01

    The Escherichia coli helD (encoding helicase IV) and uvrD (encoding helicase II) genes have been deleted, independently and in combination, from the chromosome and replaced with genes encoding antibiotic resistance. Each deletion was verified by Southern blots, and the location of each deletion was confirmed by P1-mediated transduction. Cell strains containing the single and double deletions were viable, indicating that helicases II and IV are not essential for viability. Cell strains lacking...

  16. A Japanese boy with myalgia and cramps has a novel in-frame deletion of the dystrophin gene.

    Science.gov (United States)

    Ishigaki, C; Patria, S Y; Nishio, H; Yabe, M; Matsuo, M

    1996-05-01

    We report a Japanese Becker muscular dystrophy (BMD) patient with occasional myalgia and cramps during normal activity that developed at the age of 28 months. His family history was negative for neuromuscular diseases. Muscle biopsy analyses, including dystrophin immunostaining, disclosed no clinically relevant findings. The diagnosis of BMD was initially made at the age of 10 years, when indications of persistent high serum levels of CK prompted us to screen deletions in the dystrophin gene by amplification of 19 deletion-prone exons from the genomic DNA by the polymerase chain reaction (PCR). Among the exons examined, exons 13 and 17 were deleted. To clarify the size of the deletion, the dystrophin transcript was analyzed by reverse transcription PCR. The determined nucleotide sequence of the amplified product encompassing exons 10 to 20 disclosed that the entire segment corresponding to exons 13 to 18 (810 bp) was absent, a deletion that would be expected to cause the production of a dystrophin protein lacking 270 amino acids from the rod domain. This result indicates that occasional myalgia and cramps could be early clinical manifestations of mild BMD, especially in patients who have a deletion in the rod domain, and that deletion screening of the dystrophin gene might be the only reliable method to diagnose such cases.

  17. CO-DELETION OF BOTH p15/p16 GENES CORRELATES WITH POOR PROGNOSIS NON-SMALL CELL LUNG CNACER

    Institute of Scientific and Technical Information of China (English)

    胡颖; 廖美琳; 丁嘉安; 周瑾; 许凯黎

    2002-01-01

    Objective: To investigate the relationship between co-deletion of p15/p16 genes and the prognostic significance in patients with non-small cell lung cancer (NSCLC). Methods: By using polymerase chain reaction (PCR), the loss of p15/pl6 genes was examined in DNA samples from 140 NSCLC patients. Results: The rate of co-deletion in adenocarcinoma was significantly higher than that in squamous cell carcinoma (P0.05). By a five years' follow-up survey, the survival rate of NSCLC patients with co-deletion of pl5/pl6 genes was obviously lower than that of patients without co-deletion (P<0.01). In the multivariate analysis, co-deletion of p15/p16 genes and TNM stages were identified as independent predictors for overall survival (P<0.01). Conclusion: Since the co-deletion of pl5/pl6 genes is significantly related to the prognosis of NSCLC patients, detecting co-deletion of both genes might be used as a potential marker for NSCLC prognosis.

  18. R3-R4 deletion in the PRNP gene is associated with Creutzfeldt-Jakob disease (CJD)

    Energy Technology Data Exchange (ETDEWEB)

    Cervenakova, L.; Brown, P.; Nagle, J. [and others

    1994-09-01

    There are conflicting reports on the association of deletions in the PRNP gene on chromosome 20 with CJD, a rapidly progressive fatal spongiform encephalopathy. We accumulated data suggesting that a deletion of R3-R4 type (parts of the third and fourth repeats are deleted from the area of four repeating 24 bp sequences in the 5{prime} region of the gene) is causing CJD. Screening of 129 unaffected control individuals demonstrated presence of a deletion of R2 type in four (1.55% of the studied chromosomes), but none of them had the R3-R4 type. Of 181 screened patients with spongiform encephalopathies, two had a deletion of R3-R4 type with no other mutations in the coding sequence. Both patients had a classical rapidly progressive dementing disease and diffuse spongiform degeneration, and both cases were apparently sporadic. The same R3-R4 type of deletion was detected in three additional neuropathologically confirmed spongiform encephalopathy patients, of which two had other known pathogenic mutations in the PRNP gene: at codon 178 on the methionine allele exhibiting the phenotype of fatal familial insomnia, and codon 200 causing CJD with severe dementia; the third was a patient with iatrogenic CJD who developed the disease after treatment with growth hormone extracted from cadaveric human pituitary glands. In all cases the deletion coincided with a variant sequence at position 129 coding for methionine.

  19. A Tool for Multiple Targeted Genome Deletions that Is Precise, Scar-Free, and Suitable for Automation.

    Directory of Open Access Journals (Sweden)

    Wayne Aubrey

    Full Text Available Many advances in synthetic biology require the removal of a large number of genomic elements from a genome. Most existing deletion methods leave behind markers, and as there are a limited number of markers, such methods can only be applied a fixed number of times. Deletion methods that recycle markers generally are either imprecise (remove untargeted sequences, or leave scar sequences which can cause genome instability and rearrangements. No existing marker recycling method is automation-friendly. We have developed a novel openly available deletion tool that consists of: 1 a method for deleting genomic elements that can be repeatedly used without limit, is precise, scar-free, and suitable for automation; and 2 software to design the method's primers. Our tool is sequence agnostic and could be used to delete large numbers of coding sequences, promoter regions, transcription factor binding sites, terminators, etc in a single genome. We have validated our tool on the deletion of non-essential open reading frames (ORFs from S. cerevisiae. The tool is applicable to arbitrary genomes, and we provide primer sequences for the deletion of: 90% of the ORFs from the S. cerevisiae genome, 88% of the ORFs from S. pombe genome, and 85% of the ORFs from the L. lactis genome.

  20. Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J.; Mecucci, Cristina

    2016-01-01

    Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia. PMID:27151989

  1. Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J; Mecucci, Cristina

    2016-08-01

    Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia.

  2. Clinical implications of cytosine deletion of exon 5 of P53 gene in non small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Rashid Mir

    2016-01-01

    Full Text Available Aim: Lung cancer is considered to be the most common cancer in the world. In humans, about 50% or more cancers have a mutated tumor suppressor p53 gene thereby resulting in accumulation of p53 protein and losing its function to activate the target genes that regulate the cell cycle and apoptosis. Extensive research conducted in murine cancer models with activated p53, loss of p53, or p53 missense mutations have facilitated researchers to understand the role of this key protein. Our study was aimed to evaluate the frequency of cytosine deletion in nonsmall cell lung cancer (NSCLC patients. Methods: One hundred NSCLC patients were genotyped for P53 (exon5, codon168 cytosine deletion leading to loss of its function and activate the target genes by allele-specific polymerase chain reaction. The P53 cytosine deletion was correlated with all the clinicopathological parameters of the patients. Results and Analysis: 59% cases were carrying P53 cytosine deletion. Similarly, the significantly higher incidence of cytosine deletion was reported in current smokers (75% in comparison to exsmoker and nonsmoker. Significantly higher frequency of cytosine deletion was reported in adenocarcinoma (68.08% than squamous cell carcinoma (52.83%. Also, a significant difference was reported between p53 cytosine deletion and metastasis (64.28%. Further, the majority of the cases assessed for response carrying P53 cytosine deletion were found to show faster disease progression. Conclusion: The data suggests that there is a significant association of the P53 exon 5 deletion of cytosine in codon 168 with metastasis and staging of the disease.

  3. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth

    Energy Technology Data Exchange (ETDEWEB)

    Perez Jurado, L.A.; Peoples, R.; Francke, U. [Stanford Univ. School of Medicine, CA (United States)] [and others

    1996-10-01

    Williams syndrome (WS) is a developmental disorder with variable phenotypic expression associated, in most cases, with a hemizygous deletion of part of chromosomal band 7q11.23 that includes the elastin gene (ELN). We have investigated the frequency and size of the deletions, determined the parental origin, and correlated the molecular results with the clinical findings in 65 WS patients. Hemizygosity at the ELN locus was established by typing of two intragenic polymorphisms, quantitative Southern analysis, and/or FISH. Polymorphic markers covering the deletion and flanking regions were ordered by a combination of genetic and physical mapping. Genotyping of WS patients and available parents for 13 polymorphisms revealed that of 65 clinically defined WS patients, 61 (94%) had a deletion of the ELN locus and were also hemizygous (or non-informative) at loci D7S489B, D7S2476, D7S613, D7S2472, and D7S1870. None of the four patients without ELN deletion was hemizygous at any of the polymorphic loci studied. All patients were heterozygous (or noninformative) for centromeric (D7S1816, D7S1483, and D7S653) and telomeric (D7S489A, D7S675, and D7S669) flanking loci. The genetic distance between the most-centromeric deleted locus, D7S489B, and the most-telomeric one, D7S1870, is 2 cM. The breakpoints cluster at {approximately}1 cM to either side of ELN. In 39 families informative for parental origin, all deletions were de novo, and 18 were paternally and 21 maternally derived. Comparison of clinical data, collected in a standardized quantifiable format, revealed significantly more severe growth retardation and microcephaly in the maternal deletion group. An imprinted locus, silent on the paternal chromosome and contributing to statural growth, may be affected by the deletion. 53 refs., 5 figs., 2 tabs.

  4. Emergence of porcine reproductive and respiratory syndrome virus deletion mutants: Correlation with the porcine antibody response to a hypervariable site in the ORF 3 structural glycoprotein

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Bøtner, Anette; Toft, P.;

    2000-01-01

    deletion mutants at this ORF 3/4 site. Phylogenetic analysis showed the presence of a highly accurate ORF 3 molecular clock, according to which deletion mutants and nondeleted viruses evolved at differing speeds. Furthermore, deletion mutants and nondeleted viruses evolved as separate lineages...

  5. Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Oki, Mitsuaki; Hori, Shin-ichiro; Asayama, Shinya; Wate, Reika; Kaneko, Satoshi; Kusaka, Hirofumi

    2016-01-01

    We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symptoms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was diagnosed with early-onset Parkinson's disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of (123)I-metaiodobenzylguanidine was normal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson's disease. PMID:26831029

  6. Chromosome 17p deletion in human medulloblastoma: a missing checkpoint in the Hedgehog pathway.

    Science.gov (United States)

    De Smaele, Enrico; Di Marcotullio, Lucia; Ferretti, Elisabetta; Screpanti, Isabella; Alesse, Edoardo; Gulino, Alberto

    2004-10-01

    Although deregulation of Hedgehog signalling is considered to play a crucial oncogenic role and commonly occurrs in medulloblastoma, genetic lesions in components of this pathway are observed in a minority of cases. The recent identification of a novel putative tumor suppressor (REN(KCTD11)) on chromosome 17p13.2, a region most frequently lost in human medulloblastoma, highlights the role of allelic deletion of the gene in this brain malignancy, leading to the loss of growth inhibitory activity via suppression of Gli-dependent activation of Hedgehog target genes. The presence on 17p13 of another tumor suppressor gene (p53) whose inactivation cooperates with Hedgehog pathway for medulloblastoma formation, suggests that 17p deletion unveils haploinsufficiency conditions leading to abrogation of either direct and indirect checkpoints of Hedgehog signalling in cancer. PMID:15467454

  7. PAX3 gene deletion detected by microarray analysis in a girl with hearing loss.

    Science.gov (United States)

    Drozniewska, Malgorzata; Haus, Olga

    2014-01-01

    Deletions of the PAX3 gene have been rarely reported in the literature. Mutations of this gene are a common cause of Waardenburg syndrome type 1 and 3. We report a 16 year old female presenting hearing loss and normal intellectual development, without major features of Waardenburg syndrome type 1, and without family history of the syndrome. Her phenotype, however, overlaps with features of craniofacial-deafness-hand syndrome. Microarray analysis showed ~862 kb de novo deletion at 2q36.1 including PAX3. The above findings suggest that the rearrangement found in our patient appeared de novo and with high probability is a cause of her phenotype. PMID:24839464

  8. Deletion of ABL/BCR on der(9 associated with severe basophilia

    Directory of Open Access Journals (Sweden)

    Shantashri Vaidya

    2011-01-01

    Full Text Available Chronic basophilic leukemia is a rare form in chronic myeloid leukemia patients. Only limited number of reports are available. Herein, we describe a patient who presented with fatigue, weight loss, leucocytosis, prominent basophilia, and mild eosinophilia. On biopsy, bone marrow was hypercellular with marked basophils. The immunophenotype showed abnormal expression of CD7, which is suggestive of basophilic maturation. Chromosomal analysis from GTG-banded metaphases revealed Ph positivity, and fluorescence in situ hybridization (FISH with BCR/ABL dual color, dual fusion probe showed single fusion on the der(22 chromosome and ABL/BCR fusion was deleted on the der(9 chromosome. The deletion (ABL/BCR on der(9 may be associated with basophilia which may be also indicative of the transformation of CML to acute myeloid leukemia.

  9. Barosensitivity in Saccharomyces cerevisiae is Closely Associated with a Deletion of the COX1 Gene.

    Science.gov (United States)

    Nomura, Kazuki; Iwahashi, Hitoshi; Iguchi, Akinori; Shigematsu, Toru

    2015-05-01

    High hydrostatic pressure causes physical stress to microorganisms; therefore, this technology may be applied to food pasteurization without introducing the unfavorable effects of thermal denaturation. However, its application is limited to high-value foods because the treatment requires a robust steel vessel and expensive pressurization equipment. To reduce these costs, we studied the pasteurization of Saccharomyces cerevisiae using relatively moderate high-pressure levels. A mutant strain isolated by ultraviolet mutagenesis showed significant loss of viability under high-pressure conditions. Gene expression analysis of the mutant strain revealed that it incurred a deletion of the COX1 gene. Our results suggest that the pressure-sensitivity can readily be introduced into industrial/food microorganisms by complementing a COX1 deleted mitochondria. PMID:25881710

  10. Deletion of a coordinate regulator of type 2 cytokine expression in mice

    Energy Technology Data Exchange (ETDEWEB)

    Mohrs, Markus; Blankespoor, Catherine M.; Wang, Zhi-En; Loots, Gaby G.; Hadeiba, Husein; Shinkai, Kanade; Rubin, Edward M.; Locksley, Richard M.

    2001-07-30

    Mechanisms underlying the differentiation of stable T helper subsets will be important in understanding how discrete types of immunity develop in response to different pathogens. An evolutionarily conserved {approx}400 base pair non-coding sequence in the IL-4/IL-13 intergenic region, designated CNS-1, was deleted in mice. The capacity to develop Th2 cells was compromised in vitro and in vivo in the absence of CNS-1. Despite the profound effect in T cells, mast cells from CNS-1-deleted mice maintained their capacity to produce IL-4. A T cell-specific element critical for optimal expression of type 2 cytokines may represent evolution of a regulatory sequence exploited by adaptive immunity.

  11. The Metric-FF Planning System: Translating "Ignoring Delete Lists" to Numeric State Variables

    CERN Document Server

    Hoffmann, J

    2011-01-01

    Planning with numeric state variables has been a challenge for many years, and was a part of the 3rd International Planning Competition (IPC-3). Currently one of the most popular and successful algorithmic techniques in STRIPS planning is to guide search by a heuristic function, where the heuristic is based on relaxing the planning task by ignoring the delete lists of the available actions. We present a natural extension of ``ignoring delete lists'' to numeric state variables, preserving the relevant theoretical properties of the STRIPS relaxation under the condition that the numeric task at hand is ``monotonic''. We then identify a subset of the numeric IPC-3 competition language, ``linear tasks'', where monotonicity can be achieved by pre-processing. Based on that, we extend the algorithms used in the heuristic planning system FF to linear tasks. The resulting system Metric-FF is, according to the IPC-3 results which we discuss, one of the two currently most efficient numeric planners.

  12. Detection of deletion in the dystrophin gene of a patient with quadriceps myopathy.

    Directory of Open Access Journals (Sweden)

    Kumari D

    2000-01-01

    Full Text Available A 43 year old male presented with slowly progressive weakness of limbs and hypertrophy of triceps, brachioradialis and calf muscles for four years. There was thinning of quadriceps muscles in both thighs. Histological study was compatible with Becker muscular dystrophy (BMD. Genomic DNA analysis showed a deletion of the Hind III fragments, spanning exons 45-47. A junction fragment of 11.0 kb was observed along with a deletion of a 3.4 kb PstI fragment containing exon 51 in the patient, and in one of his two sisters. The clinical and laboratory characteristics in this patient are in keeping with what has been described ′quadriceps myopathy′ and fall within the phenotypic variants of BMD as has been shown by others.

  13. Molecular basis and consequences of a deletion in the amelogenin gene, analyzed by capture PCR

    Energy Technology Data Exchange (ETDEWEB)

    Lagerstroem-Fermer, M.; Pettersson, U.; Landegren, U. (Univ. of Uppsala (Sweden))

    1993-07-01

    A mutation that disrupts the gene for one of the major proteins in tooth enamel has been investigated. The mutation is located in the amelogenin gene and causes X-linked amelogenesis imperfecta, characterized by defective mineralization of tooth enamel. The authors have isolated the breakpoints of a 5-kb deletion in the amelogenin gene on the basis of nucleotide sequence information located upstream of the lesion, using a technique termed capture PCR. The deletion removes five of the seven exons, spanning from the second intron to the last exon. Only the first two codons for the mature protein remain, consistent with the relatively severe phenotype of affected individuals in the present family. The mutation appears to have arisen as an illegitimate recombination event since of 11 nucleotide positions immediately surrounding the two breakpoints, 9 are identical. 17 refs., 3 figs., 1 tab.

  14. Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach.

    Science.gov (United States)

    Entian, K D; Schuster, T; Hegemann, J H; Becher, D; Feldmann, H; Güldener, U; Götz, R; Hansen, M; Hollenberg, C P; Jansen, G; Kramer, W; Klein, S; Kötter, P; Kricke, J; Launhardt, H; Mannhaupt, G; Maierl, A; Meyer, P; Mewes, W; Munder, T; Niedenthal, R K; Ramezani Rad, M; Röhmer, A; Römer, A; Hinnen, A

    1999-12-01

    In a systematic approach to the study of Saccharomyces cerevisiae genes of unknown function, 150 deletion mutants were constructed (1 double, 149 single mutants) and phenotypically analysed. Twenty percent of all genes examined were essential. The viable deletion mutants were subjected to 20 different test systems, ranging from high throughput to highly specific test systems. Phenotypes were obtained for two-thirds of the mutants tested. During the course of this investigation, mutants for 26 of the genes were described by others. For 18 of these the reported data were in accordance with our results. Surprisingly, for seven genes, additional, unexpected phenotypes were found in our tests. This suggests that the type of analysis presented here provides a more complete description of gene function.

  15. A pause-in-speech deletion technique of delay-allowable communication systems

    Science.gov (United States)

    Yoshida, T.; Ueda, J.

    1983-07-01

    The technique outlined here makes it possible, after the detection of a voice segment, to go backward some tens of milliseconds before the voice segment and turn on a voice switch. In a delay-allowable communication system, this allows efficient compression of the pause in speech while maintaining minimum quality degradation; it can be an effective method of reducing costs. Consideration is given to the possibility of a backward hangover process with pause deletion and to the rewriting of voice segments in pause segments in the buffering process using addressing control. Experimental results show that the backward hangover process (hangover time, approximately 32-64 ms) requires less voice deletion than the ordinary hangover process; this is especially true at word fronts, which are essential to quality reproduction. It is shown that the cost of the system can be reduced without speech quality degradation by applying the backward hangover process and addressing control at buffering.

  16. Metyrosine in psychosis associated with 22q11.2 deletion syndrome: case report.

    Science.gov (United States)

    Carandang, Carlo G; Scholten, Monique C

    2007-02-01

    This report describes the use of metyrosine (Demser) in an adolescent male with psychosis associated with the 22q11.2 deletion syndrome (velocardiofacial syndrome; VCFS), diagnosed by fluorescence in situ hybridization (FISH). He presented with multiple features of 22q11.2 deletion syndrome, including ventricular septal defect, palatal abnormalities, speech and motor delays, attention deficits, mood lability, and psychosis. After a failed trial of an atypical antipsychotic to address the psychosis, metyrosine was initiated, with significant reduction of psychotic symptoms and mood lability. Metyrosine treatment allowed this youth to live at home and to attend school, after months of recurrent psychiatric hospitalizations. The successful treatment of metyrosine for psychosis associated with VCFS represents a first in psychiatry, where a known biochemical abnormality in a psychiatric disorder was corrected by a treatment that targets the biochemical pathway, leading to reduction of psychiatric symptoms and improvement of functioning.

  17. A genome-wide screen for Schizosaccharomyces pombe deletion mutants that affect telomere length

    Institute of Scientific and Technical Information of China (English)

    Ning-Ning Liu; Tian Xu Han; Li-Lin Du; Jin-Qiu Zhou

    2010-01-01

    @@ Dear Editor, Both the fission yeast Schizosaccharomyces pombe and the budding yeast Saccharomyces cerevisiae are popular model organisms, and studies using these models have provided many informative clues for solving fundamental biological questions [1], such as DNA replication,cell cycle regulation and gene transcription. Since the completion of genome sequencing of these fungi [2, 3],systematic genetic modification, e.g. gene deletion, has become possible, and genome-wide phenotypic screening for gene function has been widely carried out. For example, Askree et al. and Gatbonton et al. examined the telomere-length change in about 4 800 non-essential gene deletion mutants of S. cerevisiae, and found that about 250 genes are involved in telomere-length regulation.

  18. Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data

    OpenAIRE

    Mok, K. Y.; Sheerin, U.; Simón-Sánchez, J.; Salaka, A.; Chester, L.; Escott-Price, V; Mantripragada, K.; Doherty, K M; Noyce, A. J.; Mencacci, N. E.; Lubbe, S. J.; International Parkinson's Disease Genomics Consortium (IPDGC); Williams-Gray, C. H.; Barker, R. A.; Dijk, K.D. van

    2016-01-01

    Summary Background Parkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2. Methods We used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on ...

  19. Chromosome 22q11.2 deletion may contain a locus for recessive early-onset Parkinson’s disease

    OpenAIRE

    Ogaki, Kotaro; Ross, Owen A.

    2014-01-01

    Recently, it has been reported that carriers of a hemizygous chromosome 22q11.2 deletion may be at increased risk of early-onset Parkinson’s disease. Herein, we propose a hypothesis that it is not the microdeletion per se that is responsible for the phenotype but rather a complete loss of function of a gene within the region due to the combination of the deletion and another mutation on the alternate allele. Thus we propose the deletion may be highlighting a novel locus for ...

  20. Phylogenetic analysis of mitochondrial DNA in a patient with Kearns-Sayre syndrome containing a novel 7629-bp deletion.

    Science.gov (United States)

    Montiel-Sosa, Jose Francisco; Herrero, María Dolores; Munoz, Maria de Lourdes; Aguirre-Campa, Luis Enrique; Pérez-Ramírez, Gerardo; García-Ramírez, Rubén; Ruiz-Pesini, Eduardo; Montoya, Julio

    2013-08-01

    Mitochondrial DNA mutations have been associated with different illnesses in humans, such as Kearns-Sayre syndrome (KSS), which is related to deletions of different sizes and positions among patients. Here, we report a Mexican patient with typical features of KSS containing a novel deletion of 7629 bp in size with 85% heteroplasmy, which has not been previously reported. Sequence analysis revealed 3-bp perfect short direct repeats flanking the deletion region, in addition to 7-bp imperfect direct repeats within 9-10 bp. Furthermore, sequencing, alignment and phylogenetic analysis of the hypervariable region revealed that the patient may belong to a founder Native American haplogroup C4c.

  1. Mitochondrial DNA deletion and impairment of mitochondrial biogenesis by reactive oxygen species in ionizing radiation-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-10-15

    The aim of this study was to determine whether an increase of ROS level in cellular senescence induced by IR could mediate mtDNA deletion via impairment of mitochondria biogenesis in IMR-90 human lung fibroblast cells. Our results showed that IR induced cellular senescence, intracellular ROS, and mtDNA deletion, and in particular, suppressed the expression of mitochondrial biogenesis genes (NRF-1, TFAM). Furthermore, these IR-induced events were abolished using a potent antioxidant, NAC, which suggests that ROS is a key cause of mtDNA deletion in IR-induced cellular senescence, and that the alteration of mitochondrial biogenesis may mediate these processes

  2. A Catalog of Genes Homozygously Deleted in Human Lung Cancer and the Candidacy of PTPRD as a Tumor Suppressor Gene

    OpenAIRE

    Kohno, Takashi; Otsuka, Ayaka; Girard, Luc; Sato, Masanori; Iwakawa, Reika; Ogiwara, Hideaki; Sanchez-Cespedes, Montse; Minna, John D.; Yokota, Jun

    2010-01-01

    A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array-based whole genome scanning of 52 lung cancer cell lines and subsequent genomic PCR in 74 cell lines, including the 52 cell lines scanned. One or more exons of these genes were homozygously deleted in one (1%) to 20 (27%) cell lines. These genes included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, and SMAD4, and candidate tumor suppressor genes whose hemizygous or homozygous deletions were rep...

  3. A nine-nucleotide deletion and splice variation in the coding region of the interferon induced ISG12 gene

    DEFF Research Database (Denmark)

    Smidt, Kamille; Hansen, Lise Lotte; Søgaard, T Max M;

    2003-01-01

    Interferons (IFNs) are a family of cytokines with growth inhibitory, and antiviral functions. IFNs exert their biological actions through the expression of more than 1000 IFN stimulated genes, ISGs. ISG12 is an IFN type I induced gene encoding a protein of Mr 12,000. We have identified a novel, IFN...... distributed between ISG12 and ISG12-S in breast carcinoma cells, in cancer cell lines and in cervical cytobrush material with neoplastic lesions. In addition, we have found a nine-nucleotide deletion situated in exon 4 of the ISG12 gene. This deletion leads to a three-amino-acid deletion (AMA) in the putative...

  4. Novel interstitial 2.6Mb deletion on 9q21 associated with multiple congenital anomalies

    OpenAIRE

    Pua, HH; Krishnamurthi, S.; Farrell, J.; Margeta, M; Ursell, PC; Powers, M.; Slavotinek, AM; Jeng, LJB

    2014-01-01

    Array comparative genomic hybridization (aCGH) is now commonly used to identify copy number changes in individuals with developmental delay, intellectual disabilities, autism spectrum disorders, and/or multiple congenital anomalies. We report on an infant with multiple congenital anomalies and a novel 2.6Mb interstitial deletion within 9q21.32q21.33 detected by aCGH. Her clinical presentation included dysmorphic craniofacial features, cleft palate, atrial septal defect, bicornuate uterus, bil...

  5. Iterative carotenogenic screens identify combinations of yeast gene deletions that enhance sclareol production

    DEFF Research Database (Denmark)

    Trikka, Fotini A; Nikolaidis, Alexandros; Athanasakoglou, Anastasia;

    2015-01-01

    advantage of existing knowledge of the sterol biosynthetic pathway, while many additional factors may affect the output of the engineered system. RESULTS: Aiming to develop a yeast strain that can support high titers of sclareol, a diterpene of great importance for the perfume industry, we sought to....... Applying the same approach using a different starting point could yield alternative sets of deletions with similar or improved outcome....

  6. Headbobber: a combined morphogenetic and cochleosaccular mouse model to study 10qter deletions in human deafness.

    Science.gov (United States)

    Buniello, Annalisa; Hardisty-Hughes, Rachel E; Pass, Johanna C; Bober, Eva; Smith, Richard J; Steel, Karen P

    2013-01-01

    The recessive mouse mutant headbobber (hb) displays the characteristic behavioural traits associated with vestibular defects including headbobbing, circling and deafness. This mutation was caused by the insertion of a transgene into distal chromosome 7 affecting expression of native genes. We show that the inner ear of hb/hb mutants lacks semicircular canals and cristae, and the saccule and utricle are fused together in a single utriculosaccular sac. Moreover, we detect severe abnormalities of the cochlear sensory hair cells, the stria vascularis looks severely disorganised, Reissner's membrane is collapsed and no endocochlear potential is detected. Myo7a and Kcnj10 expression analysis show a lack of the melanocyte-like intermediate cells in hb/hb stria vascularis, which can explain the absence of endocochlear potential. We use Trp2 as a marker of melanoblasts migrating from the neural crest at E12.5 and show that they do not interdigitate into the developing strial epithelium, associated with abnormal persistence of the basal lamina in the hb/hb cochlea. We perform array CGH, deep sequencing as well as an extensive expression analysis of candidate genes in the headbobber region of hb/hb and littermate controls, and conclude that the headbobber phenotype is caused by: 1) effect of a 648 kb deletion on distal Chr7, resulting in the loss of three protein coding genes (Gpr26, Cpmx2 and Chst15) with expression in the inner ear but unknown function; and 2) indirect, long range effect of the deletion on the expression of neighboring genes on Chr7, associated with downregulation of Hmx3, Hmx2 and Nkx1.2 homeobox transcription factors. Interestingly, deletions of the orthologous region in humans, affecting the same genes, have been reported in nineteen patients with common features including sensorineural hearing loss and vestibular problems. Therefore, we propose that headbobber is a useful model to gain insight into the mechanisms underlying deafness in human 10qter

  7. Delayed diagnosis of 22q11.2 deletion syndrome in an adult Chinese lady

    Institute of Scientific and Technical Information of China (English)

    SHEA Yat-fung; LEE Chi-ho; Harinder Gill; CHOW Wing-sun; LAM Yui-ming; LUK Ho-ming; LAM Stephen Tak-sum; CHU Leung-wing

    2012-01-01

    We report a 32 year-old Chinese lady with history of tetralogy of Fallot,presented to us with chest pain due to hypocalcemia secondary to hypoparathyroidism.With her dysmorphic facial features and intellectual disability 22q11.2 deletion was suspected and confirmed by genetic study.Clinicians should consider the diagnosis of DiGeorge syndrome in adult patient with past medical history of congenital heart disease,facial dysmorphism,intellectual disability and primary hypoparathyroidism.

  8. Functional constraint and small insertions and deletions in the ENCODE regions of the human genome.

    OpenAIRE

    Clark, TG; Andrew, T.; Cooper, GM; Margulies, EH; Mullikin, JC; Balding, DJ

    2007-01-01

    BACKGROUND: We describe the distribution of indels in the 44 Encyclopedia of DNA Elements (ENCODE) regions (about 1% of the human genome) and evaluate the potential contributions of small insertion and deletion polymorphisms (indels) to human genetic variation. We relate indels to known genomic annotation features and measures of evolutionary constraint. RESULTS: Indel rates are observed to be reduced approximately 20-fold to 60-fold in exonic regions, 5-fold to 10-fold in sequence that exhib...

  9. Association between Y-chromosome AZFc region micro-deletions with recurrent miscarriage

    OpenAIRE

    Saeede Soleimanian; Seyyed Mahdi Kalantar; Mohamad Hasan Sheikhha; Mohamad Ali Zaimy; Azam Rasti; Hossein Fazli

    2013-01-01

    Background: In human, about 25% of implanted embryos are losing 1-2 week following attachment to the uterus. A subset of this population will have three or more consecutive miscarriages which define as repeated pregnancy loss (RPL). Introducing the assisted reproductive technologies (ARTS) made a chance for infertile couples to solve their childless problem. Objective: This study was conducted to evaluate the incidence of Y-chromosome AZF region's micro-deletions in male partners of couples w...

  10. Automated Genotyping of Biobank Samples by Multiplex Amplification of Insertion/Deletion Polymorphisms

    OpenAIRE

    Lucy Mathot; Elin Falk-Sörqvist; Lotte Moens; Marie Allen; Tobias Sjöblom; Mats Nilsson

    2012-01-01

    The genomic revolution in oncology will entail mutational analyses of vast numbers of patient-matched tumor and normal tissue samples. This has meant an increased risk of patient sample mix up due to manual handling. Therefore, scalable genotyping and sample identification procedures are essential to pathology biobanks. We have developed an efficient alternative to traditional genotyping methods suited for automated analysis. By targeting 53 prevalent deletions and insertions found in human p...

  11. The Neuropsychology of 22q11 Deletion Syndrome. A Neuropsychiatric Study of 100 Individuals

    Science.gov (United States)

    Niklasson, Lena; Gillberg, Christopher

    2010-01-01

    The primary objective of this study was to study the impact of ASD/ADHD on general intellectual ability and profile, executive functions and visuo-motor skills in children and adults with 22q11 deletion syndrome (22q11DS). A secondary aim was to study if gender, age, heart disease, ASD, ADHD or ASD in combination with ADHD had an impact on general…

  12. Adenovirus mediated homozygous endometrial epithelial Pten deletion results in aggressive endometrial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Ayesha; Ellenson, Lora Hedrick, E-mail: lora.ellenson@med.cornell.edu

    2011-07-01

    Pten is the most frequently mutated gene in uterine endometriod carcinoma (UEC) and its precursor complex atypical hyperplasia (CAH). Because the mutation frequency is similar in CAH and UEC, Pten mutations are thought to occur relatively early in endometrial tumorigenesis. Previous work from our laboratory using the Pten{sup +/-} mouse model has demonstrated somatic inactivation of the wild type allele of Pten in both CAH and UEC. In the present study, we injected adenoviruses expressing Cre into the uterine lumen of adult Pten floxed mice in an attempt to somatically delete both alleles of Pten specifically in the endometrium. Our results demonstrate that biallelic inactivation of Pten results in an increased incidence of carcinoma as compared to the Pten{sup +/-} mouse model. In addition, the carcinomas were more aggressive with extension beyond the uterus into adjacent tissues and were associated with decreased expression of nuclear ER{alpha} as compared to associated CAH. Primary cultures of epithelial and stromal cells were prepared from uteri of Pten floxed mice and Pten was deleted in vitro using Cre expressing adenovirus. Pten deletion was evident in both the epithelial and stromal cells and the treatment of the primary cultures with estrogen had different effects on Akt activation as well as Cyclin D3 expression in the two purified components. This study demonstrates that somatic biallelic inactivation of Pten in endometrial epithelium in vivo results in an increased incidence and aggressiveness of endometrial carcinoma compared to mice carrying a germline deletion of one allele and provides an important in vivo and in vitro model system for understanding the genetic underpinnings of endometrial carcinoma.

  13. RENKCTD11 is a suppressor of Hedgehog signaling and is deleted in human medulloblastoma

    OpenAIRE

    Di Marcotullio, Lucia; Ferretti, Elisabetta; De Smaele, Enrico; Argenti, Beatrice; Mincione, Claudia; Zazzeroni, Francesca; Gallo, Rita; Masuelli, Laura; Napolitano, Maddalena; Maroder, Marella; Modesti, Andrea; Giangaspero, Felice; Screpanti, Isabella; Alesse, Edoardo; Gulino, Alberto

    2004-01-01

    Hedgehog signaling is suggested to be a major oncogenic pathway in medulloblastoma, which arises from aberrant development of cerebellar granule progenitors. Allelic loss of chromosome 17p has also been described as the most frequent genetic defect in this human neoplasia. This observation raises the question of a possible interplay between 17p deletion and the Hedgehog tumorigenic pathway. Here, we identify the human orthologue of mouse RENKCTD11, previously reported to be expressed in diffe...

  14. Diagnosis and fine localization of deletion region in Wolf Hirschhorn syndrome patients

    Institute of Scientific and Technical Information of China (English)

    JI Tao-yun; David CHIA; WANG Jing-min; WU Ye; LI Jie; XIAO Jing; JIANG Yu-wu

    2010-01-01

    Background Wolf-Hirschhorn syndrome (WHS) results from the partial deletion of 4p. This study aimed to identify and fine map the chromosome deletion regions of Chinese children with Wolf-Hirschhorn syndrome among the developmental delay/mental retardation (DD/MR) patients.Methods We analyzed the relationship of phenotype and genotype. Inclusion criteria were: moderate to severe DD/MR, no definite perinatal brain injury, and no trauma, toxication, hypoxia, infection of central nervous system; routine karyotyping was normal, no evidence of typical inherited metabolic disorder or specific neurodegenerative disorders from cranial neuro-imaging and blood/urinary metabolic diseases screening; no mutation of FMR1 in male patients, no typical clinical manifestation of Rett syndrome in female patients. Multiplex ligation-dependent probe amplification (MLPA) and Affymetrix genome-wide human SNP array 6.0 assays were applied to accurately define the exact size of subtelomeric aberration region of four WHS patients.Results All four WHS patients presented with severe DD, hypotonia and microcephaly, failure to thrive, 3/4 patients with typical facial features and seizures, 2/4 patients with congenital heart defects and cleft lip/palate, 1/4 patients with other malformations. The length of the deletions ranged from 3.3 Mb to 9.8 Mb. Two of four patients had "classic" WHS, 1/4 patients had "mild"-to-"classic" WHS, and 1/4 patients had "mild" WHS.Conclusions WHS patients in China appear to be consistent with those previously reported. The prevalence of signs and symptoms, distribution of cases between "mild" and "classic" WHS, and the correlation between length of deletion and severity of disease of these patients were all similar to those of the patients from other populations.

  15. High Frequency of Large Intragenic Deletions in the Fanconi Anemia Group A Gene

    OpenAIRE

    Morgan, Neil V.; Tipping, Alex J.; Joenje, Hans; Mathew, Christopher G.

    1999-01-01

    Fanconi anemia (FA) is an autosomal recessive disorder exhibiting chromosomal fragility, bone-marrow failure, congenital abnormalities, and cancer. At least eight complementation groups have been described, with group A accounting for 60%–65% of FA patients. Mutation screening of the group A gene (FANCA) is complicated by its highly interrupted genomic structure and heterogeneous mutation spectrum. Recent reports of several large deletions of FANCA, coupled with modest mutation-detection rate...

  16. EXPRESSION AND DELETION ANALYSIS OF EcoRII ENDONUCLEASE AND METHYLASE GENE

    Institute of Scientific and Technical Information of China (English)

    刘金毅; 赵晓娟; 孟雁; 沈洁; 薛越强; 史顺娣; 蔡有余

    2001-01-01

    Objective. To clone complete EcoRII restriction endonuclease gene (ecoRllR) and methyltransferase gene(ecoRllM) in one ector and to analyze the coordinating expression of this whole R-M system.Methods. Unidirectional deletion subclones were constructed with ExolII. ecoRllR/M genes were preliminari-ly located in the cloned fragment according to the enzyme activities of subclones. Exact deletion sites were deter-mined by sequencing, and transcriptional start sites were determined by S1 mapping.Results. The DNA fragment which was cloned into pBluescript SK + contained intact ecoRIlR gene andecoRllM gene, anc two transcriptional start sites of ecoRllR gene were determined. 132bp to 458bp from 3' endof ecoRllR gene ar.e indispensable to enzyme activities and deletion of 202bp from 3' end of ecoRllM gene madeenzyme lose the capability in DNA protection to resist specific cut with EcoRII endonuclease (EcoRII. R). Dele-tion of the coding ar d flanking sequences of one gene did not affect the expression of the other gene, and the recombi-nants only containing ecoRllR gene appeared to be lethal to dcm+ host.Conclusion. scoRllM gene linking closely to ecoRIIR gene is very important for the existence of the R-M sys-tem in process of evolution, but the key to control EcoRlI R-M order may not exist in transcriptional level .``Liu Jmy,Corresponding author.

  17. Deletion of conserved protein phosphatases reverses defects associated with mitochondrial DNA damage in Saccharomyces cerevisiae

    OpenAIRE

    Garipler, Görkem; Mutlu, Nebibe; Lack, Nathan; Dunn, Cory David

    2014-01-01

    Mitochondrial biogenesis is regulated by signaling pathways sensitive to extracellular conditions and to the internal environment of the cell. Therefore, treatments for disease caused by mutation of mtDNA may emerge from studies of how signal transduction pathways command mitochondrial function. We have examined the role of phosphatases under the control of the conserved alpha 4/Tap42 protein in cells lacking a mitochondrial genome. We found that deletion of protein phosphatase 2A (PP2A) or o...

  18. A generalized threading model using integer programming that allows for secondary structure element deletion.

    Science.gov (United States)

    Ellrott, Kyle; Guo, Jun-tao; Olman, Victor; Xu, Ying

    2006-01-01

    Integer programming is a combinatorial optimization method that has been successfully applied to the protein threading problem. We seek to expand the model optimized by this technique to allow for a more accurate description of protein threading. We have developed and implemented an expanded model of integer programming that has the capability to model secondary structure element deletion, which was not possible in previous version of integer programming based optimization. PMID:17503397

  19. 7q36 deletion and 9p22 duplication: effects of a double imbalance

    OpenAIRE

    Pelegrino Karla de; Sugayama Sofia; Catelani Ana; Lezirovitz Karina; Kok Fernando; Chauffaille Maria de

    2013-01-01

    Abstract The etiology of mental retardation/developmental delay (MRDD) remains a challenge to geneticists and clinicians and can be correlated to environmental and genetic factors. Chromosomal aberrations are common causes of moderate to severe mental retardation and may represent 10% of these occurrences. Here we report the case of a boy with development delay, hypoplasia of corpus callosum, microcephaly, muscular hypotonia, and facial dysmorphisms. A deletion of 7q36.1 → 36.3 and duplicatio...

  20. Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways

    OpenAIRE

    Richards, Sally; Liu, Su-ting; Majumdar, Alokes; Liu, Ji-Lan; Nairn, Rodney S.; Bernier, Michel; Maher, Veronica; Seidman, Michael M.

    2005-01-01

    We have synthesized triple helix forming oligonucleotides (TFOs) that target a psoralen (pso) interstrand crosslink to a specific chromosomal site in mammalian cells. Mutagenesis of the targeted crosslinks results in base substitutions and deletions. Identification of the gene products involved in mutation formation is important for developing practical applications of pso-TFOs, and may be informative about the metabolism of other interstrand crosslinks. We have studied mutagenesis of a pso-T...