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Sample records for copi coatomer complex

  1. Structure of Coatomer Cage Proteins and the Relationship among COPI, COPII, and Clathrin Vesicle Coats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Changwook; Goldberg, Jonathan (MSKCC)

    2010-09-13

    COPI-coated vesicles form at the Golgi apparatus from two cytosolic components, ARF G protein and coatomer, a heptameric complex that can polymerize into a cage to deform the membrane into a bud. Although coatomer shares a common evolutionary origin with COPII and clathrin vesicle coat proteins, the architectural relationship among the three cages is unclear. Strikingly, the {alpha}{beta}-COP core of coatomer crystallizes as a triskelion in which three copies of a {beta}-COP {beta}-propeller domain converge through their axial ends. We infer that the trimer constitutes the vertex of the COPI cage. Our model proposes that the COPI cage is intermediate in design between COPII and clathrin: COPI shares with clathrin an arrangement of three curved {alpha}-solenoid legs radiating from a common center, and COPI shares with COPII highly similar vertex interactions involving the axial ends of {beta}-propeller domains.

  2. Recombinant heptameric coatomer complexes: novel tools to study isoform-specific functions.

    NARCIS (Netherlands)

    Sahlmuller, M.C.; Strating, J.R.P.M.; Beck, R.; Eckert, P.; Popoff, V.; Haag, M.; Hellwig, A.; Berger, I.; Brugger, B.; Wieland, F.T.

    2011-01-01

    COPI (coat protein I)-coated vesicles are implicated in various transport steps within the early secretory pathway. The major structural component of the COPI coat is the heptameric complex coatomer (CM). Recently, four isoforms of CM were discovered that may help explain various transport steps in

  3. Crystal structure of truncated human coatomer protein complex subunit ζ1 (Copζ1).

    Science.gov (United States)

    Lunev, Sergey; Semmelink, Marije F W; Xian, Jia Ling; Ma, Kai Yu; Leenders, Anna J A; Dömling, Alexander S S; Shtutman, Michael; Groves, Matthew R

    2017-01-01

    The majority of modern anticancer approaches target DNA/protein targets involved in tumour-cell proliferation. Such approaches have a major drawback, as nonproliferating cancer cells remain unaffected and may cause relapse or remission. Human coatomer protein complex I (COPI) subunit ζ (Copζ), a component of the coat protein involved in cell apoptosis and intracellular trafficking, has recently been proposed as a potential anticancer drug target. Previous studies have shown that two different isoforms of the Copζ subunit exist in mammalian cells. While normal cells express both Copζ1 and Copζ2 isoforms, various types of tumour cells display a loss of Copζ2 expression and rely solely on Copζ1 for growth and survival. Subsequent knockdown of Copζ1 results in specific inhibition of both proliferating and dormant tumour-cell populations, with no adverse growth effects on normal cells. Therefore, a Copζ1-targeting therapy was proposed to bypass the problem of dormant cancer cells that are resistant to conventional antiproliferative drugs, which is the major cause of tumour relapse. In order to aid in structure-based inhibitor design, a crystal structure is required. In this article, the recombinant expression, purification, crystallization and crystal structure of Copζ1, as well as the expression and purification of Copζ2, are reported.

  4. Structural characterization of coatomer in its cytosolic state

    Directory of Open Access Journals (Sweden)

    Shengliu Wang

    2016-07-01

    Full Text Available Abstract Studies on coat protein I (COPI have contributed to a basic understanding of how coat proteins generate vesicles to initiate intracellular transport. The core component of the COPI complex is coatomer, which is a multimeric complex that needs to be recruited from the cytosol to membrane in order to function in membrane bending and cargo sorting. Previous structural studies on the clathrin adaptors have found that membrane recruitment induces a large conformational change in promoting their role in cargo sorting. Here, pursuing negative-stain electron microscopy coupled with single-particle analyses, and also performing CXMS (chemical cross-linking coupled with mass spectrometry for validation, we have reconstructed the structure of coatomer in its soluble form. When compared to the previously elucidated structure of coatomer in its membrane-bound form we do not observe a large conformational change. Thus, the result uncovers a key difference between how COPI versus clathrin coats are regulated by membrane recruitment.

  5. Sequence evidence for common ancestry of eukaryotic endomembrane coatomers

    National Research Council Canada - National Science Library

    Promponas, Vasilis J; Katsani, Katerina R; Blencowe, Benjamin J; Ouzounis, Christos A

    2016-01-01

    .... The assembly and maintenance of these complexes is facilitated by endomembrane coatomers, long suspected to be divergently related on the basis of structural and more recently phylogenomic analysis...

  6. Silkworm coatomers and their role in tube expansion of posterior silkgland.

    Directory of Open Access Journals (Sweden)

    Qiao Wang

    Full Text Available BACKGROUND: Coat protein complex I (COPI vesicles, coated by seven coatomer subunits, are mainly responsible for Golgi-to-ER transport. Silkworm posterior silkgland (PSG, a highly differentiated secretory tissue, secretes fibroin for silk production, but many physiological processes in the PSG cells await further investigation. METHODOLOGY/PRINCIPAL FINDINGS: Here, to investigate the role of silkworm COPI, we cloned six silkworm COPI subunits (α, β, β', δ, ε, and ζ-COP, determined their peak expression in day 2 in fifth-instar PSG, and visualized the localization of COPI, as a coat complex, with cis-Golgi. By dsRNA injection into silkworm larvae, we suppressed the expression of α-, β'- and γ-COP, and demonstrated that COPI subunits were required for PSG tube expansion. Knockdown of α-COP disrupted the integrity of Golgi apparatus and led to a narrower glandular lumen of the PSG, suggesting that silkworm COPI is essential for PSG tube expansion. CONCLUSIONS/SIGNIFICANCE: The initial characterization reveals the essential roles of silkworm COPI in PSG. Although silkworm COPI resembles the previously characterized coatomers in other organisms, some surprising findings require further investigation. Therefore, our results suggest the silkworm as a model for studying intracellular transport, and would facilitate the establishment of silkworm PSG as an efficient bioreactor.

  7. Coatomer and dimeric ADP ribosylation factor 1 promote distinct steps in membrane scission

    Science.gov (United States)

    Beck, Rainer; Prinz, Simone; Diestelkötter-Bachert, Petra; Röhling, Simone; Adolf, Frank; Hoehner, Kathrin; Welsch, Sonja; Ronchi, Paolo; Brügger, Britta

    2011-01-01

    Formation of coated vesicles requires two striking manipulations of the lipid bilayer. First, membrane curvature is induced to drive bud formation. Second, a scission reaction at the bud neck releases the vesicle. Using a reconstituted system for COPI vesicle formation from purified components, we find that a dimerization-deficient Arf1 mutant, which does not display the ability to modulate membrane curvature in vitro or to drive formation of coated vesicles, is able to recruit coatomer to allow formation of COPI-coated buds but does not support scission. Chemical cross-linking of this Arf1 mutant restores vesicle release. These experiments show that initial curvature of the bud is defined primarily by coatomer, whereas the membrane curvature modulating activity of dimeric Arf1 is required for membrane scission. PMID:21893600

  8. Molecular methods for genotyping complex copy number polymorphisms.

    Science.gov (United States)

    Cantsilieris, Stuart; Baird, Paul N; White, Stefan J

    2013-02-01

    Genome structural variation shows remarkable complexity with respect to copy number, sequence content and distribution. While the discovery of copy number polymorphisms (CNP) has increased exponentially in recent years, the transition from discovery to genotyping has proved challenging, particularly for CNPs embedded in complex regions of the genome. CNPs that are collectively common in the population and possess a dynamic range of copy numbers have proved the most difficult to genotype in association studies. This is in some part due to technical limitations of genotyping assays and the sequence properties of the genomic region being analyzed. Here we describe in detail the basis of a number of molecular techniques used to genotype complex CNPs, compare and contrast these approaches for determination of multi-allelic copy number, and discuss the potential application of these techniques in genetic studies.

  9. COPI complex is a regulator of lipid homeostasis.

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    Mathias Beller

    2008-11-01

    Full Text Available Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets.

  10. Human copy number variation and complex genetic disease.

    Science.gov (United States)

    Girirajan, Santhosh; Campbell, Catarina D; Eichler, Evan E

    2011-01-01

    Copy number variants (CNVs) play an important role in human disease and population diversity. Advancements in technology have allowed for the analysis of CNVs in thousands of individuals with disease in addition to thousands of controls. These studies have identified rare CNVs associated with neuropsychiatric diseases such as autism, schizophrenia, and intellectual disability. In addition, copy number polymorphisms (CNPs) are present at higher frequencies in the population, show high diversity in copy number, sequence, and structure, and have been associated with multiple phenotypes, primarily related to immune or environmental response. However, the landscape of copy number variation still remains largely unexplored, especially for smaller CNVs and those embedded within complex regions of the human genome. An integrated approach including characterization of single nucleotide variants and CNVs in a large number of individuals with disease and normal genomes holds the promise of thoroughly elucidating the genetic basis of human disease and diversity.

  11. Genetically complex epilepsies, copy number variants and syndrome constellations.

    Science.gov (United States)

    Mefford, Heather C; Mulley, John C

    2010-10-05

    Epilepsy is one of the most common neurological disorders, with a prevalence of 1% and lifetime incidence of 3%. There are numerous epilepsy syndromes, most of which are considered to be genetic epilepsies. Despite the discovery of more than 20 genes for epilepsy to date, much of the genetic contribution to epilepsy is not yet known. Copy number variants have been established as an important source of mutation in other complex brain disorders, including intellectual disability, autism and schizophrenia. Recent advances in technology now facilitate genome-wide searches for copy number variants and are beginning to be applied to epilepsy. Here, we discuss what is currently known about the contribution of copy number variants to epilepsy, and how that knowledge is redefining classification of clinical and genetic syndromes.

  12. COPI is required for enterovirus 71 replication.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Enterovirus 71 (EV71, a member of the Picornaviridae family, is found in Asian countries where it causes a wide range of human diseases. No effective therapy is available for the treatment of these infections. Picornaviruses undergo RNA replication in association with membranes of infected cells. COPI and COPII have been shown to be involved in the formation of picornavirus-induced vesicles. Replication of several picornaviruses, including poliovirus and Echovirus 11 (EV11, is dependent on COPI or COPII. Here, we report that COPI, but not COPII, is required for EV71 replication. Replication of EV71 was inhibited by brefeldin A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down assay, indicating that COPI coatomer might be directed to the viral replication complex through viral 2C protein. Additionally, because the pathway is conserved among different species of enteroviruses, it may represent a novel target for antiviral therapies.

  13. Expression of COPI components during development of Drosophila melanogaster.

    Science.gov (United States)

    Grieder, Nicole C; Kloter, Urs; Gehring, Walter J

    2005-12-01

    In a P{lArB} enhancer detector collection, a line was found that showed upregulated expression within centrally to posteriorly located germarial cysts. It was inserted in the gammaCOP locus on chromosome 3R. GammaCOP is a component of the COPI coatomer involved in membrane traffic. Most of the other known components of the COPI coatomer also showed higher expression in the posterior half of the germarium. Not only meiotic germline cysts but also migrating follicle cells upregulate the COPI subunits. During embryonic and larval development, the COPI subunits are expressed ubiquitously as expected for genes required for cell viability. In addition, they are strongly expressed in the salivary glands and the proventriculus. Whether tissue-specific transcriptional upregulation of COPI subunits is required for the reorganization of membranous compartments that are needed for the developmental processes that confer cyst polarity and follicle maturation will have to be addressed in a genetic study.

  14. Field dependence and stimulus complexity in a figure copying task.

    Science.gov (United States)

    Coté, Carol A; O'Donnell, Angela M

    2007-12-01

    Field dependence is often associated with studies of cognitive style from Witkin's laboratory but Piaget also considered the concept a fundamental factor in the development of visuoperceptual analysis. Assessment has traditionally relied on two measures, the Rod-and-Frame Test and the Embedded Figures Test. A new task was developed, based on the Rod-and-Frame Test, in which a target stimulus is drawn within a misleading frame. Misleading frames significantly influenced the orientation of drawings created by 36 kindergartners in Exp. 1, and the drawing of more complex stimulus figures was influenced by the frames for a group of 65 adults in Exp. 2. Field-dependent behavior is related to the complexity of the task and to age. The correlation of scores on the Embedded Figures Test with performance on this task was low for both groups.

  15. Specific cpb copies within the Leishmania donovani complex: evolutionary interpretations and potential clinical implications in humans.

    Science.gov (United States)

    Hide, M; Bras-Gonçalves, R; Bañuls, A L

    2007-03-01

    Leishmania infantum and Leishmania donovani both pertain to the L. (L.) donovani complex and are responsible for visceral leishmaniasis. To explore the L. donovani complex, we focused our study on cysteine protease B (cpb) and especially on 2 cpb copies: cpbE and cpbF. We selected cpb genes because of their phylogenetic interest and host-parasite interaction involvement. Sequencing these 2 copies revealed (i) that cpbE is specific to L. infantum and cpbF is specific to L. donovani and (ii) that these 2 copies are different in length and sequence. Phylogenetic analysis and protein predictions were carried out in order to compare these copies (i) with other trypanosomatid cpb, especially L. mexicana, and (ii) within the L. donovani complex. Our results revealed patterns specific to the L. donovani complex such as the COOH-terminal extension, potential epitopes and N-glycosylation sites. Moreover, phylogenetic analysis revealed different levels of polymorphism between L. infantum and L. donovani and confirmed the ancestral status of the latter. L. infantum has a shorter sequence and a deleted sequence responsible for modifications in protein conformation and catalytic triad. Considering the clinical aspect, L. infantum dermotropic strains appeared more polymorphic than L. infantum viscerotropic strains.

  16. Copy number gain at Xp22.31 includes complex duplication rearrangements and recurrent triplications.

    Science.gov (United States)

    Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C Sreenath; Bi, Weimin; Carvalho, Claudia M B; Simmons, Alexandra D; Wiszniewska, Joanna; Fang, Ping; Eng, Patricia A; Cooper, M Lance; Sutton, V Reid; Roeder, Elizabeth R; Bodensteiner, John B; Delgado, Mauricio R; Prakash, Siddharth K; Belmont, John W; Stankiewicz, Pawel; Berg, Jonathan S; Shinawi, Marwan; Patel, Ankita; Cheung, Sau Wai; Lupski, James R

    2011-05-15

    Genomic instability is a feature of the human Xp22.31 region wherein deletions are associated with X-linked ichthyosis, mental retardation and attention deficit hyperactivity disorder. A putative homologous recombination hotspot motif is enriched in low copy repeats that mediate recurrent deletion at this locus. To date, few efforts have focused on copy number gain at Xp22.31. However, clinical testing revealed a high incidence of duplication of Xp22.31 in subjects ascertained and referred with neurobehavioral phenotypes. We systematically studied 61 unrelated subjects with rearrangements revealing gain in copy number, using multiple molecular assays. We detected not only the anticipated recurrent and simple nonrecurrent duplications, but also unexpectedly identified recurrent triplications and other complex rearrangements. Breakpoint analyses enabled us to surmise the mechanisms for many of these rearrangements. The clinical significance of the recurrent duplications and triplications were assessed using different approaches. We cannot find any evidence to support pathogenicity of the Xp22.31 duplication. However, our data suggest that the Xp22.31 duplication may serve as a risk factor for abnormal phenotypes. Our findings highlight the need for more robust Xp22.31 triplication detection in that such further gain may be more penetrant than the duplications. Our findings reveal the distribution of different mechanisms for genomic duplication rearrangements at a given locus, and provide insights into aspects of strand exchange events between paralogous sequences in the human genome.

  17. Association of coatomer proteins with the beta-receptor for platelet-derived growth factor

    DEFF Research Database (Denmark)

    Hansen, Klaus; Rönnstrand, L; Rorsman, C

    1997-01-01

    of intracellular vesicle transport. In order to explore the functional significance of the interaction between alpha- and beta'-COP and the PDGF receptor, a receptor mutant was made in which the conserved histidine residue 928 was mutated to an alanine residue. The mutant receptor, which was unable to bind alpha......The nonreceptor tyrosine kinase Src binds to and is activated by the beta-receptor for platelet-derived growth factor (PDGF). The interaction leads to Src phosphorylation of Tyr934 in the kinase domain of the receptor. In the course of the functional characterization of this phosphorylation, we...... noticed that components of 136 and 97 kDa bound to a peptide from this region of the receptor in a phosphorylation-independent manner. These components have now been purified and identified as alpha- and beta'-coatomer proteins (COPs), respectively. COPs are a family of proteins involved in the regulation...

  18. Polycomb repressive complex 1 provides a molecular explanation for repeat copy number dependency in FSHD muscular dystrophy.

    Science.gov (United States)

    Casa, Valentina; Runfola, Valeria; Micheloni, Stefano; Aziz, Arif; Dilworth, F Jeffrey; Gabellini, Davide

    2017-02-15

    Repression of repetitive elements is crucial to preserve genome integrity and has been traditionally ascribed to constitutive heterochromatin pathways. FacioScapuloHumeral Muscular Dystrophy (FSHD), one of the most common myopathies, is characterized by a complex interplay of genetic and epigenetic events. The main FSHD form is linked to a reduced copy number of the D4Z4 macrosatellite repeat on 4q35, causing loss of silencing and aberrant expression of the D4Z4-embedded DUX4 gene leading to disease. By an unknown mechanism, D4Z4 copy-number correlates with FSHD phenotype. Here we show that the DUX4 proximal promoter (DUX4p) is sufficient to nucleate the enrichment of both constitutive and facultative heterochromatin components and to mediate a copy-number dependent gene silencing. We found that both the CpG/GC dense DNA content and the repetitive nature of DUX4p arrays are important for their repressive ability. We showed that DUX4p mediates a copy number-dependent Polycomb Repressive Complex 1 (PRC1) recruitment, which is responsible for the copy-number dependent gene repression. Overall, we directly link genetic and epigenetic defects in FSHD by proposing a novel molecular explanation for the copy number-dependency in FSHD pathogenesis, and offer insight into the molecular functions of repeats in chromatin regulation. © The Author 2016. Published by Oxford University Press.

  19. Discovering Recurrent Copy Number Aberrations in Complex Patterns via Non-Negative Sparse Singular Value Decomposition.

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    Xi, Jianing; Li, Ao

    2016-01-01

    Recurrent copy number aberrations (RCNAs) in multiple cancer samples are strongly associated with tumorigenesis, and RCNA discovery is helpful to cancer research and treatment. Despite the emergence of numerous RCNA discovering methods, most of them are unable to detect RCNAs in complex patterns that are influenced by complicating factors including aberration in partial samples, co-existing of gains and losses and normal-like tumor samples. Here, we propose a novel computational method, called non-negative sparse singular value decomposition (NN-SSVD), to address the RCNA discovering problem in complex patterns. In NN-SSVD, the measurement of RCNA is based on the aberration frequency in a part of samples rather than all samples, which can circumvent the complexity of different RCNA patterns. We evaluate NN-SSVD on synthetic dataset by comparison on detection scores and Receiver Operating Characteristics curves, and the results show that NN-SSVD outperforms existing methods in RCNA discovery and demonstrate more robustness to RCNA complicating factors. Applying our approach on a breast cancer dataset, we successfully identify a number of genomic regions that are strongly correlated with previous studies, which harbor a bunch of known breast cancer associated genes.

  20. Complex and multi-allelic copy number variation in human disease.

    Science.gov (United States)

    Usher, Christina L; McCarroll, Steven A

    2015-09-01

    Hundreds of copy number variants are complex and multi-allelic, in that they have many structural alleles and have rearranged multiple times in the ancestors who contributed chromosomes to current humans. Not only are the relationships of these multi-allelic CNVs (mCNVs) to phenotypes generally unknown, but many mCNVs have not yet been described at the basic levels-alleles, allele frequencies, structural features-that support genetic investigation. To date, most reported disease associations to these variants have been ascertained through candidate gene studies. However, only a few associations have reached the level of acceptance defined by durable replications in many cohorts. This likely stems from longstanding challenges in making precise molecular measurements of the alleles individuals have at these loci. However, approaches for mCNV analysis are improving quickly, and some of the unique characteristics of mCNVs may assist future association studies. Their various structural alleles are likely to have different magnitudes of effect, creating a natural allelic series of growing phenotypic impact and giving investigators a set of natural predictions and testable hypotheses about the extent to which each allele of an mCNV predisposes to a phenotype. Also, mCNVs' low-to-modest correlation to individual single-nucleotide polymorphisms (SNPs) may make it easier to distinguish between mCNVs and nearby SNPs as the drivers of an association signal, and perhaps, make it possible to preliminarily screen candidate loci, or the entire genome, for the many mCNV-disease relationships that remain to be discovered.

  1. Complex Copy Number Variation of AMY1 does not Associate with Obesity in two East Asian Cohorts.

    Science.gov (United States)

    Yong, Rita Y Y; Mustaffa, Su'Aidah B; Wasan, Pavandip S; Sheng, Liang; Marshall, Christian R; Scherer, Stephen W; Teo, Yik-Ying; Yap, Eric P H

    2016-07-01

    The human amylase gene locus at chromosome 1p21.1 is structurally complex. This region contains two pancreatic amylase genes, AMY2B, AMY2A, and a salivary gene AMY1. The AMY1 gene harbors extensive copy number variation (CNV), and recent studies have implicated this variation in adaptation to starch-rich diets and in association to obesity for European and Asian populations. In this study, we showed that by combining quantitative PCR and digital PCR, coupled with careful experimental design and calibration, we can improve the resolution of genotyping CNV with high copy numbers (CNs). In two East Asian populations of Chinese and Malay ethnicity studied, we observed a unique non-normal distribution of AMY1 diploid CN genotypes with even:odd CNs ratio of 4.5 (3.3-4.7), and an association between the common AMY2A CN = 2 genotype and odd CNs of AMY1, that could be explained by the underlying haplotypic structure. In two further case-control cohorts (n = 932 and 145, for Chinese and Malays, respectively), we did not observe the previously reported association between AMY1 and obesity or body mass index. Improved methods for accurately genotyping multiallelic CNV loci and understanding the haplotype complexity at the AMY1 locus are necessary for population genetics and association studies.

  2. Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Xavier Estivill

    2007-10-01

    Full Text Available Genome-wide association scans (GWASs using single nucleotide polymorphisms (SNPs have been completed successfully for several common disorders and have detected over 30 new associations. Considering the large sample sizes and genome-wide SNP coverage of the scans, one might have expected many of the common variants underpinning the genetic component of various disorders to have been identified by now. However, these studies have not evaluated the contribution of other forms of genetic variation, such as structural variation, mainly in the form of copy number variants (CNVs. Known CNVs account for over 15% of the assembled human genome sequence. Since CNVs are not easily tagged by SNPs, might have a wide range of copy number variability, and often fall in genomic regions not well covered by whole-genome arrays or not genotyped by the HapMap project, current GWASs have largely missed the contribution of CNVs to complex disorders. In fact, some CNVs have already been reported to show association with several complex disorders using candidate gene/region approaches, underpinning the importance of regions not investigated in current GWASs. This reveals the need for new generation arrays (some already in the market and the use of tailored approaches to explore the full dimension of genome variability beyond the single nucleotide scale.

  3. Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

    Science.gov (United States)

    Rowbotham, David A.; Enfield, Katey S. S.; Martinez, Victor D.; Thu, Kelsie L.; Vucic, Emily A.; Stewart, Greg L.; Bennewith, Kevin L.; Lam, Wan L.

    2014-01-01

    Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation. PMID:25298778

  4. Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma

    Directory of Open Access Journals (Sweden)

    David A. Rowbotham

    2014-01-01

    Full Text Available Pheochromocytomas (PCC are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described <10% VHL mutation rate cannot account for the high frequency of hypoxic response observed. Indeed, little is known about genetic mechanisms disrupting other complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation.

  5. Multiple Components of the VHL Tumor Suppressor Complex Are Frequently Affected by DNA Copy Number Loss in Pheochromocytoma.

    Science.gov (United States)

    Rowbotham, David A; Enfield, Katey S S; Martinez, Victor D; Thu, Kelsie L; Vucic, Emily A; Stewart, Greg L; Bennewith, Kevin L; Lam, Wan L

    2014-01-01

    Pheochromocytomas (PCC) are rare tumors that arise in chromaffin tissue of the adrenal gland. PCC are frequently inherited through predisposing mutations in genes such as the von Hippel-Lindau (VHL) tumor suppressor. VHL is part of the VHL elongin BC protein complex that also includes CUL2/5, TCEB1, TCEB2, and RBX1; in normoxic conditions this complex targets hypoxia-inducible factor 1 alpha (HIF1A) for degradation, thus preventing a hypoxic response. VHL inactivation by genetic mechanisms, such as mutation and loss of heterozygosity, inhibits HIF1A degradation, even in the presence of oxygen, and induces a pseudohypoxic response. However, the described complex component genes. Here, we show that, in a panel of 171 PCC tumors, 59.6% harbored gene copy number loss (CNL) of at least one complex component. CNL significantly reduced gene expression and was associated with enrichment of gene targets controlled by HIF1. Interestingly, we show that VHL-related renal clear cell carcinoma harbored disruption of VHL alone. Our results indicate that VHL elongin BC protein complex components other than VHL could be important for PCC tumorigenesis and merit further investigation.

  6. Alu-mediated diverse and complex pathogenic copy-number variants within human chromosome 17 at p13.3.

    Science.gov (United States)

    Gu, Shen; Yuan, Bo; Campbell, Ian M; Beck, Christine R; Carvalho, Claudia M B; Nagamani, Sandesh C S; Erez, Ayelet; Patel, Ankita; Bacino, Carlos A; Shaw, Chad A; Stankiewicz, Paweł; Cheung, Sau Wai; Bi, Weimin; Lupski, James R

    2015-07-15

    Alu repetitive elements are known to be major contributors to genome instability by generating Alu-mediated copy-number variants (CNVs). Most of the reported Alu-mediated CNVs are simple deletions and duplications, and the mechanism underlying Alu-Alu-mediated rearrangement has been attributed to non-allelic homologous recombination (NAHR). Chromosome 17 at the p13.3 genomic region lacks extensive low-copy repeat architecture; however, it is highly enriched for Alu repetitive elements, with a fraction of 30% of total sequence annotated in the human reference genome, compared with the 10% genome-wide and 18% on chromosome 17. We conducted mechanistic studies of the 17p13.3 CNVs by performing high-density oligonucleotide array comparative genomic hybridization, specifically interrogating the 17p13.3 region with ∼150 bp per probe density; CNV breakpoint junctions were mapped to nucleotide resolution by polymerase chain reaction and Sanger sequencing. Studied rearrangements include 5 interstitial deletions, 14 tandem duplications, 7 terminal deletions and 13 complex genomic rearrangements (CGRs). Within the 17p13.3 region, Alu-Alu-mediated rearrangements were identified in 80% of the interstitial deletions, 46% of the tandem duplications and 50% of the CGRs, indicating that this mechanism was a major contributor for formation of breakpoint junctions. Our studies suggest that Alu repetitive elements facilitate formation of non-recurrent CNVs, CGRs and other structural aberrations of chromosome 17 at p13.3. The common observation of Alu-mediated rearrangement in CGRs and breakpoint junction sequences analysis further demonstrates that this type of mechanism is unlikely attributed to NAHR, but rather may be due to a recombination-coupled DNA replicative repair process.

  7. Family based genome-wide copy number scan identifies complex rearrangements at 17q21.31 in dyslexics.

    Science.gov (United States)

    Veerappa, Avinash M; Saldanha, Marita; Padakannaya, Prakash; Ramachandra, Nallur B

    2014-10-01

    Developmental dyslexia (DD) is a complex heritable disorder with unexpected difficulty in learning to read and spell despite adequate intelligence, education, environment, and normal senses. We performed genome-wide screening for copy number variations (CNVs) in 10 large Indian dyslexic families using Affymetrix Genome-Wide Human SNP Array 6.0. Results revealed the complex genomic rearrangements due to one non-contiguous deletion and five contiguous micro duplications and micro deletions at 17q21.31 region in three dyslexic families. CNVs in this region harbor the genes KIAA1267, LRRC37A, ARL17A/B, NSFP1, and NSF. The CNVs in case 1 and case 2 at this locus were found to be in homozygous state and case 3 was a de novo CNV. These CNVs were found with at least one CNV having a common break and end points in the parents. This cluster of genes containing NSF is implicated in learning, cognition, and memory, though not formally associated with dyslexia. Molecular network analysis of these and other dyslexia related module genes suggests NSF and other genes to be associated with cellular/vesicular membrane fusion and synaptic transmission. Thus, we suggest that NSF in this cluster would be the nearest gene responsible for the learning disability phenotype.

  8. Cognitive predictors of copying and drawing from memory of the Rey-Osterrieth complex figure in 7- to 10-year-old children.

    Science.gov (United States)

    Senese, Vincenzo Paolo; De Lucia, Natascia; Conson, Massimiliano

    2015-01-01

    Cognitive models of drawing are mainly based on assessment of copying performance of adults, whereas only a few studies have verified these models in young children. Moreover, developmental investigations have only rarely performed a systematic examination of the contribution of perceptual and representational visuo-spatial processes to copying and drawing from memory. In this study we investigated the role of visual perception and mental representation in both copying and drawing from memory skills in a sample of 227 typically developing children (53% females) aged 7-10 years. Participants underwent a neuropsychological assessment and the Rey-Osterrieth Complex Figure (ROCF). The fit and invariance of the predictive model considering visuo-spatial abilities, working memory, and executive functions were tested by means of hierarchical regressions and path analysis. Results showed that, in a gender invariant way, visual perception abilities and spatial mental representation had a direct effect on copying performance, whereas copying performance was the only specific predictor for drawing from memory. These effects were independent from age and socioeconomic status, and showed that cognitive models of drawing built up for adults could be considered for predicting copying and drawing from memory in children.

  9. Original Copies

    DEFF Research Database (Denmark)

    Sørensen, Tim Flohr

    2013-01-01

    of similarity by looking at artefactual similarity as the results of prototyping and as a production of simulacra. In this light, the concept of copying turns out to be more than simply a matter of trying to imitate an exotic or prestigious original, and it fundamentally raises the question how different a copy...

  10. The CNVrd2 package: measurement of copy number at complex loci using high-throughput sequencing data.

    Science.gov (United States)

    Nguyen, Hoang T; Merriman, Tony R; Black, Michael A

    2014-01-01

    Recent advances in high-throughout sequencing technologies have made it possible to accurately assign copy number (CN) at CN variable loci. However, current analytic methods often perform poorly in regions in which complex CN variation is observed. Here we report the development of a read depth-based approach, CNVrd2, for investigation of CN variation using high-throughput sequencing data. This methodology was developed using data from the 1000 Genomes Project from the CCL3L1 locus, and tested using data from the DEFB103A locus. In both cases, samples were selected for which paralog ratio test data were also available for comparison. The CNVrd2 method first uses observed read-count ratios to refine segmentation results in one population. Then a linear regression model is applied to adjust the results across multiple populations, in combination with a Bayesian normal mixture model to cluster segmentation scores into groups for individual CN counts. The performance of CNVrd2 was compared to that of two other read depth-based methods (CNVnator, cn.mops) at the CCL3L1 and DEFB103A loci. The highest concordance with the paralog ratio test method was observed for CNVrd2 (77.8/90.4% for CNVrd2, 36.7/4.8% for cn.mops and 7.2/1% for CNVnator at CCL3L1 and DEF103A). CNVrd2 is available as an R package as part of the Bioconductor project: http://www.bioconductor.org/packages/release/bioc/html/CNVrd2.html.

  11. Clinically significant copy number alterations and complex rearrangements of MYB and NFIB in head and neck adenoid cystic carcinoma.

    Science.gov (United States)

    Persson, Marta; Andrén, Ywonne; Moskaluk, Christopher A; Frierson, Henry F; Cooke, Susanna L; Futreal, Philip Andrew; Kling, Teresia; Nelander, Sven; Nordkvist, Anders; Persson, Fredrik; Stenman, Göran

    2012-08-01

    Adenoid cystic carcinoma (ACC) of the head and neck is a malignant tumor with poor long-term prognosis. Besides the recently identified MYB-NFIB fusion oncogene generated by a t(6;9) translocation, little is known about other genetic alterations in ACC. Using high-resolution, array-based comparative genomic hybridization, and massively paired-end sequencing, we explored genomic alterations in 40 frozen ACCs. Eighty-six percent of the tumors expressed MYB-NFIB fusion transcripts and 97% overexpressed MYB mRNA, indicating that MYB activation is a hallmark of ACC. Thirty-five recurrent copy number alterations (CNAs) were detected, including losses involving 12q, 6q, 9p, 11q, 14q, 1p, and 5q and gains involving 1q, 9p, and 22q. Grade III tumors had on average a significantly higher number of CNAs/tumor compared to Grade I and II tumors (P = 0.007). Losses of 1p, 6q, and 15q were associated with high-grade tumors, whereas losses of 14q were exclusively seen in Grade I tumors. The t(6;9) rearrangements were associated with a complex pattern of breakpoints, deletions, insertions, inversions, and for 9p also gains. Analyses of fusion-negative ACCs using high-resolution arrays and massively paired-end sequencing revealed that MYB may also be deregulated by other mechanisms in addition to gene fusion. Our studies also identified several down-regulated candidate tumor suppressor genes (CTNNBIP1, CASP9, PRDM2, and SFN) in 1p36.33-p35.3 that may be of clinical significance in high-grade tumors. Further, studies of these and other potential target genes may lead to the identification of novel driver genes in ACC.

  12. The CNVrd2 package: measurement of copy number at complex loci using high-throughput sequencing data

    Directory of Open Access Journals (Sweden)

    Hoang eNguyen

    2014-08-01

    Full Text Available Recent advances in high-throughout sequencing technologies have made it possible to accurately assign copy number (CN at CN variable loci. However, current analytic methods often perform poorly in regions in which complex CN variation is observed. Here we report the development of a read depth-based approach, CNVrd2, for investigation of CN variation using high-throughput sequencing data. This methodology was developed using data from the 1000 Genomes Project from the CCL3L1 locus, and tested using data from the DEFB103A locus. In both cases, samples were selected for which paralogue ratio test data were also available for comparison. The CNVrd2 method first uses observed read-count ratios to refine segmentation results in one population. Then a linear regression model is applied to adjust the results across multiple populations, in combination with a Bayesian normal mixture model to cluster segmentation scores into groups for individual CN counts. The performance of CNVrd2 was compared to that of two other read depth-based methods (CNVnator, cn.mops at the CCL3L1 and DEFB103A loci, and the highest concordance with the paralog ratio test method was observed for CNVrd2 (77.8%/90.4% for CNVrd2, 36.7%/4.8% for cn.mops and 7.2%/1% for CNVnator at CCL3L1 and DEF103A. CNVrd2 is available as an R package as part of the Bioconductor project: http://www.bioconductor.org/packages/release/bioc/html/CNVrd2.html.

  13. Contribution of the Visual Perception and Graphic Production Systems to the Copying of Complex Geometrical Drawings: A Developmental Study

    Science.gov (United States)

    Bouaziz, Serge; Magnan, Annie

    2007-01-01

    The aim of this study was to determine the contribution of the visual perception and graphic production systems [Van Sommers, P. (1989). "A system for drawing and drawing-related neuropsychology." "Cognitive Neuropsychology," 6, 117-164] to the manifestation of the "Centripetal Execution Principle" (CEP), a graphic rule for the copying of drawings…

  14. Copy number variation in chemokine superfamily: the complex scene of CCL3L-CCL4L genes in health and disease.

    Science.gov (United States)

    Colobran, R; Pedrosa, E; Carretero-Iglesia, L; Juan, M

    2010-10-01

    Genome copy number changes (copy number variations: CNVs) include inherited, de novo and somatically acquired deviations from a diploid state within a particular chromosomal segment. CNVs are frequent in higher eukaryotes and associated with a substantial portion of inherited and acquired risk for various human diseases. CNVs are distributed widely in the genomes of apparently healthy individuals and thus constitute significant amounts of population-based genomic variation. Human CNV loci are enriched for immune genes and one of the most striking examples of CNV in humans involves a genomic region containing the chemokine genes CCL3L and CCL4L. The CCL3L-CCL4L copy number variable region (CNVR) shows extensive architectural complexity, with smaller CNVs within the larger ones and with interindividual variation in breakpoints. Furthermore, the individual genes embedded in this CNVR account for an additional level of genetic and mRNA complexity: CCL4L1 and CCL4L2 have identical exonic sequences but produce a different pattern of mRNAs. CCL3L2 was considered previously as a CCL3L1 pseudogene, but is actually transcribed. Since 2005, CCL3L-CCL4L CNV has been associated extensively with various human immunodeficiency virus-related outcomes, but some recent studies called these associations into question. This controversy may be due in part to the differences in alternative methods for quantifying gene copy number and differentiating the individual genes. This review summarizes and discusses the current knowledge about CCL3L-CCL4L CNV and points out that elucidating their complete phenotypic impact requires dissecting the combinatorial genomic complexity posed by various proportions of distinct CCL3L and CCL4L genes among individuals.

  15. A role of genomic copy number variation in the complex behavioral phenotype of alcohol dependence: a commentary.

    Science.gov (United States)

    Urban, Alexander E

    2012-09-01

    In their paper "Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence" Lin and colleagues report on the association between alcohol dependence and 2 duplication CNVs in the genome sequence, one containing 8 genes within its boundaries and another that contains no genes. In this commentary, I point out some of the opportunities and challenges that arise from such a finding.

  16. Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity

    Directory of Open Access Journals (Sweden)

    Zadeh Soheila

    2010-07-01

    Full Text Available Abstract Background HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin, remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC and fluorescence in situ hybridization (FISH are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods. Methods In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms. Results Array-based comparative genomic hybridization (array CGH analysis of chromosome 17 resolved HER2 gene status in [20/20] (100% of cases and revealed additional chromosome 17 copy number changes in [18/20] (90% of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to "ratio skewing" caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability. Conclusions These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17

  17. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.

    Science.gov (United States)

    Svobodova, Karla; Zemanova, Zuzana; Lhotska, Halka; Novakova, Milena; Podskalska, Lucie; Belickova, Monika; Brezinova, Jana; Sarova, Iveta; Izakova, Silvia; Lizcova, Libuse; Berkova, Adela; Siskova, Magda; Jonasova, Anna; Cermak, Jaroslav; Michalova, Kyra

    2016-03-01

    Complex karyotypes are seen in approximately 20% of patients with myelodysplastic syndromes (MDS) and are associated with a high risk of transformation to acute myeloid leukemia and poor outcomes in patients. Copy number neutral loss of heterozygosity (CN-LOH, i.e., both copies of a chromosomal pair or their parts originate from one parent) might contribute to increased genomic instability in the bone-marrow cells of patients with MDS. The pathological potential of CN-LOH, which arises as a clonal aberration in a proportion of somatic cells, consists of tumor suppressor gene and oncogene homozygous mutations. The aim of our study was to evaluate the frequency of CN-LOH at 17p in bone-marrow cells of newly diagnosed MDS patients with complex chromosomal aberrations and to assess its correlation with mutations in the TP53 gene (17p13.1). CN-LOH was detected in 40 chromosomal regions in 21 (29%) of 72 patients analyzed. The changes in 27 of the 40 regions identified were sporadic. The most common finding was CN-LOH of the short arm of chromosome 17, which was detected in 13 (18%) of 72 patients. A mutational analysis confirmed the homozygous mutation of TP53 in all CN-LOH 17p patients, among which two frameshift mutations are not registered in the International Agency for Research on Cancer TP53 Database. CN-LOH 17p correlated with aggressive disease (median overall survival 4 months) and was strongly associated with a complex karyotype in the cohort studied, which might cause rapid disease progression in high-risk MDS. No other CN-LOH region previously recorded in MDS or AML patients (1p, 4q, 7q, 11q, 13q, 19q, 21q) was detected in our cohort of patients with complex karyotype examined at the diagnosis of MDS. The LOH region appeared to be balanced (i.e., with no DNA copy number change) when examined with conventional and molecular cytogenetic methods. Therefore, a microarray that detects single-nucleotide polymorphisms is an ideal method with which to identify and

  18. Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies.

    NARCIS (Netherlands)

    Vissers, L.E.L.M.; Stankiewicz, P.; Yatsenko, S.A.; Crawford, E.; Creswick, H.; Proud, V.K.; Vries, B. de; Pfundt, R.; Marcelis, C.L.M.; Zackowski, J.; Bi, W.; Geurts van Kessel, A.H.M.; Lupski, J.R.; Veltman, J.A.

    2007-01-01

    Recent molecular cytogenetic data have shown that the constitution of complex chromosome rearrangements (CCRs) may be more complicated than previously thought. The complicated nature of these rearrangements challenges the accurate delineation of the chromosomal breakpoints and mechanisms involved. H

  19. Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake.

    Science.gov (United States)

    Willcocks, Lisa C; Lyons, Paul A; Clatworthy, Menna R; Robinson, James I; Yang, Wanling; Newland, Stephen A; Plagnol, Vincent; McGovern, Naomi N; Condliffe, Alison M; Chilvers, Edwin R; Adu, Dwomoa; Jolly, Elaine C; Watts, Richard; Lau, Yu Lung; Morgan, Ann W; Nash, Gerard; Smith, Kenneth G C

    2008-07-07

    Copy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcgammaRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcgammaRIIIb-deficiency and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcgammaRIIIb. Reduced FcgammaRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes, which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus, we define a role for FCGR3B CNV in immune complex clearance, a function that may explain why low FCGR3B CNV is associated with SLE, but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility.

  20. Allopolyploid speciation and ongoing backcrossing between diploid progenitor and tetraploid progeny lineages in the Achillea millefolium species complex: analyses of single-copy nuclear genes and genomic AFLP

    Directory of Open Access Journals (Sweden)

    Ehrendorfer Friedrich

    2010-04-01

    Full Text Available Abstract Background In the flowering plants, many polyploid species complexes display evolutionary radiation. This could be facilitated by gene flow between otherwise separate evolutionary lineages in contact zones. Achillea collina is a widespread tetraploid species within the Achillea millefolium polyploid complex (Asteraceae-Anthemideae. It is morphologically intermediate between the relic diploids, A. setacea-2x in xeric and A. asplenifolia-2x in humid habitats, and often grows in close contact with either of them. By analyzing DNA sequences of two single-copy nuclear genes and the genomic AFLP data, we assess the allopolyploid origin of A. collina-4x from ancestors corresponding to A. setacea-2x and A. asplenifolia-2x, and the ongoing backcross introgression between these diploid progenitor and tetraploid progeny lineages. Results In both the ncpGS and the PgiC gene tree, haplotype sequences of the diploid A. setacea-2x and A. asplenifolia-2x group into two clades corresponding to the two species, though lineage sorting seems incomplete for the PgiC gene. In contrast, A. collina-4x and its suspected backcross plants show homeologous gene copies: sequences from the same tetraploid individual plant are placed in both diploid clades. Semi-congruent splits of an AFLP Neighbor Net link not only A. collina-4x to both diploid species, but some 4x individuals in a polymorphic population with mixed ploidy levels to A. setacea-2x on one hand and to A. collina-4x on the other, indicating allopolyploid speciation as well as hybridization across ploidal levels. Conclusions The findings of this study clearly demonstrate the hybrid origin of Achillea collina-4x, the ongoing backcrossing between the diploid progenitor and their tetraploid progeny lineages. Such repeated hybridizations are likely the cause of the great genetic and phenotypic variation and ecological differentiation of the polyploid taxa in Achillea millefolium agg.

  1. ANS complex of St John’s wort PR-10 protein with 28 copies in the asymmetric unit: a fiendish combination of pseudosymmetry with tetartohedral twinning

    Energy Technology Data Exchange (ETDEWEB)

    Sliwiak, Joanna [Polish Academy of Sciences, Poznan (Poland); Dauter, Zbigniew [National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); Kowiel, Marcin [Poznan University of Medical Sciences, Poznan (Poland); McCoy, Airlie J.; Read, Randy J. [University of Cambridge, Cambridge CB2 0XY (United Kingdom); Jaskolski, Mariusz, E-mail: mariuszj@amu.edu.pl [Polish Academy of Sciences, Poznan (Poland); A. Mickiewicz University, Poznan (Poland)

    2015-04-01

    Hyp-1, a pathogenesis-related class 10 (PR-10) protein from H. perforatum, was crystallized in complex with the fluorescent probe 8-anilino-1-naphthalene sulfonate (ANS). The asymmetric unit of the tetartohedrally twinned crystal contains 28 copies of the protein arranged in columns with noncrystallographic sevenfold translational symmetry and with additional pseudotetragonal rotational NCS. Hyp-1, a pathogenesis-related class 10 (PR-10) protein from St John’s wort (Hypericum perforatum), was crystallized in complex with the fluorescent probe 8-anilino-1-naphthalene sulfonate (ANS). The highly pseudosymmetric crystal has 28 unique protein molecules arranged in columns with sevenfold translational noncrystallographic symmetry (tNCS) along c and modulated X-ray diffraction with intensity crests at l = 7n and l = 7n ± 3. The translational NCS is combined with pseudotetragonal rotational NCS. The crystal was a perfect tetartohedral twin, although detection of twinning was severely hindered by the pseudosymmetry. The structure determined at 2.4 Å resolution reveals that the Hyp-1 molecules (packed as β-sheet dimers) have three novel ligand-binding sites (two internal and one in a surface pocket), which was confirmed by solution studies. In addition to 60 Hyp-1-docked ligands, there are 29 interstitial ANS molecules distributed in a pattern that violates the arrangement of the protein molecules and is likely to be the generator of the structural modulation. In particular, whenever the stacked Hyp-1 molecules are found closer together there is an ANS molecule bridging them.

  2. Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody.

    Science.gov (United States)

    Park, Young-Jun; Pardon, Els; Wu, Meiting; Steyaert, Jan; Hol, Wim G J

    2012-02-01

    The parasite Trypanosoma brucei, the causative agent of sleeping sickness across sub-Saharan Africa, depends on a remarkable U-insertion/deletion RNA editing process in its mitochondrion. A approximately 20 S multi-protein complex, called the editosome, is an essential machinery for editing pre-mRNA molecules encoding the majority of mitochondrial proteins. Editosomes contain a common core of twelve proteins where six OB-fold interaction proteins, called A1-A6, play a crucial role. Here, we report the structure of two single-strand nucleic acid-binding OB-folds from interaction proteins A3 and A6 that surprisingly, form a heterodimer. Crystal growth required the assistance of an anti-A3 nanobody as a crystallization chaperone. Unexpectedly, this anti-A3 nanobody binds to both A3(OB) and A6, despite only ~40% amino acid sequence identity between the OB-folds of A3 and A6. The A3(OB)-A6 heterodimer buries 35% more surface area than the A6 homodimer. This is attributed mainly to the presence of a conserved Pro-rich loop in A3(OB). The implications of the A3(OB)-A6 heterodimer, and of a dimer of heterodimers observed in the crystals, for the architecture of the editosome are profound, resulting in a proposal of a 'five OB-fold center' in the core of the editosome.

  3. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome.

    Science.gov (United States)

    Rücker, Frank G; Schlenk, Richard F; Bullinger, Lars; Kayser, Sabine; Teleanu, Veronica; Kett, Helena; Habdank, Marianne; Kugler, Carla-Maria; Holzmann, Karlheinz; Gaidzik, Verena I; Paschka, Peter; Held, Gerhard; von Lilienfeld-Toal, Marie; Lübbert, Michael; Fröhling, Stefan; Zenz, Thorsten; Krauter, Jürgen; Schlegelberger, Brigitte; Ganser, Arnold; Lichter, Peter; Döhner, Konstanze; Döhner, Hartmut

    2012-03-01

    To assess the frequency of TP53 alterations and their correlation with other genetic changes and outcome in acute myeloid leukemia with complex karyotype (CK-AML), we performed integrative analysis using TP53 mutational screening and array-based genomic profiling in 234 CK-AMLs. TP53 mutations were found in 141 of 234 (60%) and TP53 losses were identified in 94 of 234 (40%) CK-AMLs; in total, 164 of 234 (70%) cases had TP53 alterations. TP53-altered CK-AML were characterized by a higher degree of genomic complexity (aberrations per case, 14.30 vs 6.16; P number alterations, such as -5/5q-, -7/7q-, -16/16q-, -18/18q-, +1/+1p, and +11/+11q/amp11q13∼25; among CK-AMLs, TP53-altered more frequently exhibited a monosomal karyotype (MK). Patients with TP53 alterations were older and had significantly lower complete remission rates, inferior event-free, relapse-free, and overall survival. In multivariable analysis for overall survival, TP53 alterations, white blood cell counts, and age were the only significant factors. In conclusion, TP53 is the most frequently known altered gene in CK-AML. TP53 alterations are associated with older age, genomic complexity, specific DNA copy number alterations, MK, and dismal outcome. In multivariable analysis, TP53 alteration is the most important prognostic factor in CK-AML, outweighing all other variables, including the MK category.

  4. Scaling up Copy Detection

    OpenAIRE

    Li, Xian; Dong, Xin Luna; Lyons, Kenneth B.; Meng, Weiyi; Srivastava, Divesh

    2015-01-01

    Recent research shows that copying is prevalent for Deep-Web data and considering copying can significantly improve truth finding from conflicting values. However, existing copy detection techniques do not scale for large sizes and numbers of data sources, so truth finding can be slowed down by one to two orders of magnitude compared with the corresponding techniques that do not consider copying. In this paper, we study {\\em how to improve scalability of copy detection on structured data}. Ou...

  5. Quantum copying: A review

    Directory of Open Access Journals (Sweden)

    Mark Hillery

    2000-07-01

    Full Text Available Quantum information is stored in two-level quantum systems known as qubits. The no-cloning theorem states that the state of an unknown qubit cannot be copied. This is in contrast to classical information which can be copied. If one drops the requirement that the copies be perfect it is possible to design quantum copiers. This paper presents a short review of the theory of quantum copying.

  6. Global repeat discovery and estimation of genomic copy number in a large, complex genome using a high-throughput 454 sequence survey

    Directory of Open Access Journals (Sweden)

    Varala Kranthi

    2007-05-01

    Full Text Available Abstract Background Extensive computational and database tools are available to mine genomic and genetic databases for model organisms, but little genomic data is available for many species of ecological or agricultural significance, especially those with large genomes. Genome surveys using conventional sequencing techniques are powerful, particularly for detecting sequences present in many copies per genome. However these methods are time-consuming and have potential drawbacks. High throughput 454 sequencing provides an alternative method by which much information can be gained quickly and cheaply from high-coverage surveys of genomic DNA. Results We sequenced 78 million base-pairs of randomly sheared soybean DNA which passed our quality criteria. Computational analysis of the survey sequences provided global information on the abundant repetitive sequences in soybean. The sequence was used to determine the copy number across regions of large genomic clones or contigs and discover higher-order structures within satellite repeats. We have created an annotated, online database of sequences present in multiple copies in the soybean genome. The low bias of pyrosequencing against repeat sequences is demonstrated by the overall composition of the survey data, which matches well with past estimates of repetitive DNA content obtained by DNA re-association kinetics (Cot analysis. Conclusion This approach provides a potential aid to conventional or shotgun genome assembly, by allowing rapid assessment of copy number in any clone or clone-end sequence. In addition, we show that partial sequencing can provide access to partial protein-coding sequences.

  7. The Art of Copying

    DEFF Research Database (Denmark)

    Christensen, Hans Dam

    2017-01-01

    This article discusses copies within the field of art museums by way of mapping strategies for copy practices. This mapping leans heavily towards parts of the writings of Jacques Derrida (1930–2004). Against the backdrop of this theoretical premise, the article distinguishes five main strategies....... An informational copy is just as unique as an original object of art, and at the same time, it defines the original and is itself defined by this opposition. Lastly, the strategy for the imagined relation between original and copy follows. This strategy is dependent upon several of the previous approaches, and...

  8. The Art of Copying

    DEFF Research Database (Denmark)

    Christensen, Hans Dam

    2017-01-01

    This article discusses copies within the field of art museums by way of mapping strategies for copy practices. This mapping leans heavily towards parts of the writings of Jacques Derrida (1930–2004). Against the backdrop of this theoretical premise, the article distinguishes five main strategies...... for the informational originalcopy will be discussed as it has a vital function in terms of talking about museum originals and copies. This is the strategy which grants the original artifacts their status as museum objects. An informational originalcopy is just as unique as an original object of art, and at the same...

  9. Watermark copy attack

    OpenAIRE

    Kutter, Martin; Voloshynovskyy, Svyatoslav; Herrigel, Alexander

    2000-01-01

    Research in digital watermarking has progressed along two paths. While new watermarking technologies are being developed, some researchers are also investigating di erent ways of attacking digital watermarks. Common attacks to watermarks usually aim to destroy theembedded watermark or to impair its detection. In this paper we propose a conceptually new attack for digitally watermarked images. The proposed attack doesnot destroy anembedded watermark, but copies it from one image to a di erent ...

  10. Robust Adaptable Video Copy Detection

    DEFF Research Database (Denmark)

    Assent, Ira; Kremer, Hardy

    2009-01-01

    Video copy detection should be capable of identifying video copies subject to alterations e.g. in video contrast or frame rates. We propose a video copy detection scheme that allows for adaptable detection of videos that are altered temporally (e.g. frame rate change) and/or visually (e.g. change...... in contrast). Our query processing combines filtering and indexing structures for efficient multistep computation of video copies under this model. We show that our model successfully identifies altered video copies and does so more reliably than existing models....

  11. Robust Adaptable Video Copy Detection

    DEFF Research Database (Denmark)

    Assent, Ira; Kremer, Hardy

    2009-01-01

    Video copy detection should be capable of identifying video copies subject to alterations e.g. in video contrast or frame rates. We propose a video copy detection scheme that allows for adaptable detection of videos that are altered temporally (e.g. frame rate change) and/or visually (e.g. change...... in contrast). Our query processing combines filtering and indexing structures for efficient multistep computation of video copies under this model. We show that our model successfully identifies altered video copies and does so more reliably than existing models....

  12. Copy number analysis of the low-copy repeats at the primate NPHP1 locus by array comparative genomic hybridization.

    Science.gov (United States)

    Yuan, Bo; Liu, Pengfei; Rogers, Jeffrey; Lupski, James R

    2016-06-01

    Array comparative genomic hybridization (aCGH) has been widely used to detect copy number variants (CNVs) in both research and clinical settings. A customizable aCGH platform may greatly facilitate copy number analyses in genomic regions with higher-order complexity, such as low-copy repeats (LCRs). Here we present the aCGH analyses focusing on the 45 kb LCRs [1] at the NPHP1 region with diverse copy numbers in humans. Also, the interspecies aCGH analysis comparing human and nonhuman primates revealed dynamic copy number transitions of the human 45 kb LCR orthologues during primate evolution and therefore shed light on the origin of complexity at this locus. The original aCGH data are available at GEO under GSE73962.

  13. Local repeat sequence organization of an intergenic spacer in the chloroplast genome of Chlamydomonas reinhardtii leads to DNA expansion and sequence scrambling: a complex mode of “copy-choice replication”?

    Indian Academy of Sciences (India)

    Mahendra D Wagle; Subhojit Sen; Basuthkar J Rao

    2001-12-01

    Parent-specific, randomly amplified polymorphic DNA (RAPD) markers were obtained from total genomic DNA of Chlamydomonas reinhardtii. Such parent-specific RAPD bands (genomic fingerprints) segregated uniparentally (through mt+) in a cross between a pair of polymorphic interfertile strains of Chlamydomonas (C. reinhardtii and C. minnesotti), suggesting that they originated from the chloroplast genome. Southern analysis mapped the RAPD-markers to the chloroplast genome. One of the RAPD-markers, ``P2” (1.6 kb) was cloned, sequenced and was fine mapped to the 3 kb region encompassing 3′ end of 23S, full 5S and intergenic region between 5S and psbA. This region seems divergent enough between the two parents, such that a specific PCR designed for a parental specific chloroplast sequence within this region, amplified a marker in that parent only and not in the other, indicating the utility of RAPD-scan for locating the genomic regions of sequence divergence. Remarkably, the RAPD-product, ``P2” seems to have originated from a PCR-amplification of a much smaller (about 600 bp), but highly repeat-rich (direct and inverted) domain of the 3 kb region in a manner that yielded no linear sequence alignment with its own template sequence. The amplification yielded the same uniquely ``sequence-scrambled” product, whether the template used for PCR was total cellular DNA, chloroplast DNA or a plasmid clone DNA corresponding to that region. The PCR product, a ``unique” new sequence, had lost the repetitive organization of the template genome where it had originated from and perhaps represented a ``complex path” of copy-choice replication.

  14. Protocols for Copying and Proofreading in Template-Assisted Polymerization

    Science.gov (United States)

    Pigolotti, Simone; Sartori, Pablo

    2016-03-01

    We discuss how information encoded in a template polymer can be stochastically copied into a copy polymer. We consider four different stochastic copy protocols of increasing complexity, inspired by building blocks of the mRNA translation pathway. In the first protocol, monomer incorporation occurs in a single stochastic transition. We then move to a more elaborate protocol in which an intermediate step can be used for error correction. Finally, we discuss the operating regimes of two kinetic proofreading protocols: one in which proofreading acts from the final copying step, and one in which it acts from an intermediate step. We review known results for these models and, in some cases, extend them to analyze all possible combinations of energetic and kinetic discrimination. We show that, in each of these protocols, only a limited number of these combinations leads to an improvement of the overall copying accuracy.

  15. Vocal copying of individually distinctive signature whistles in bottlenose dolphins

    Science.gov (United States)

    King, Stephanie L.; Sayigh, Laela S.; Wells, Randall S.; Fellner, Wendi; Janik, Vincent M.

    2013-01-01

    Vocal learning is relatively common in birds but less so in mammals. Sexual selection and individual or group recognition have been identified as major forces in its evolution. While important in the development of vocal displays, vocal learning also allows signal copying in social interactions. Such copying can function in addressing or labelling selected conspecifics. Most examples of addressing in non-humans come from bird song, where matching occurs in an aggressive context. However, in other animals, addressing with learned signals is very much an affiliative signal. We studied the function of vocal copying in a mammal that shows vocal learning as well as complex cognitive and social behaviour, the bottlenose dolphin (Tursiops truncatus). Copying occurred almost exclusively between close associates such as mother–calf pairs and male alliances during separation and was not followed by aggression. All copies were clearly recognizable as such because copiers consistently modified some acoustic parameters of a signal when copying it. We found no evidence for the use of copying in aggression or deception. This use of vocal copying is similar to its use in human language, where the maintenance of social bonds appears to be more important than the immediate defence of resources. PMID:23427174

  16. Mate Choice Copying in Humans.

    Science.gov (United States)

    Waynforth, D

    2007-09-01

    There is substantial evidence that in human mate choice, females directly select males based on male display of both physical and behavioral traits. In non-humans, there is additionally a growing literature on indirect mate choice, such as choice through observing and subsequently copying the mating preferences of conspecifics (mate choice copying). Given that humans are a social species with a high degree of sharing information, long-term pair bonds, and high parental care, it is likely that human females could avoid substantial costs associated with directly searching for information about potential males by mate choice copying. The present study was a test of whether women perceived men to be more attractive when men were presented with a female date or consort than when they were presented alone, and whether the physical attractiveness of the female consort affected women's copying decisions. The results suggested that women's mate choice decision rule is to copy only if a man's female consort is physically attractive. Further analyses implied that copying may be a conditional female mating tactic aimed at solving the problem of informational constraints on assessing male suitability for long-term sexual relationships, and that lack of mate choice experience, measured as reported lifetime number of sex partners, is also an important determinant of copying.

  17. Zero-Copy Objects System

    Science.gov (United States)

    Burleigh, Scott C.

    2011-01-01

    Zero-Copy Objects System software enables application data to be encapsulated in layers of communication protocol without being copied. Indirect referencing enables application source data, either in memory or in a file, to be encapsulated in place within an unlimited number of protocol headers and/or trailers. Zero-copy objects (ZCOs) are abstract data access representations designed to minimize I/O (input/output) in the encapsulation of application source data within one or more layers of communication protocol structure. They are constructed within the heap space of a Simple Data Recorder (SDR) data store to which all participating layers of the stack must have access. Each ZCO contains general information enabling access to the core source data object (an item of application data), together with (a) a linked list of zero or more specific extents that reference portions of this source data object, and (b) linked lists of protocol header and trailer capsules. The concatenation of the headers (in ascending stack sequence), the source data object extents, and the trailers (in descending stack sequence) constitute the transmitted data object constructed from the ZCO. This scheme enables a source data object to be encapsulated in a succession of protocol layers without ever having to be copied from a buffer at one layer of the protocol stack to an encapsulating buffer at a lower layer of the stack. For large source data objects, the savings in copy time and reduction in memory consumption may be considerable.

  18. Quantum Copy-Protection and Quantum Money

    CERN Document Server

    Aaronson, Scott

    2011-01-01

    Forty years ago, Wiesner proposed using quantum states to create money that is physically impossible to counterfeit, something that cannot be done in the classical world. However, Wiesner's scheme required a central bank to verify the money, and the question of whether there can be unclonable quantum money that anyone can verify has remained open since. One can also ask a related question, which seems to be new: can quantum states be used as copy-protected programs, which let the user evaluate some function f, but not create more programs for f? This paper tackles both questions using the arsenal of modern computational complexity. Our main result is that there exist quantum oracles relative to which publicly-verifiable quantum money is possible, and any family of functions that cannot be efficiently learned from its input-output behavior can be quantumly copy-protected. This provides the first formal evidence that these tasks are achievable. The technical core of our result is a "Complexity-Theoretic No-Clon...

  19. Some bounds for quantum copying

    CERN Document Server

    Rastegin, A E

    2001-01-01

    We derive lower bounds on the absolute error and the relative error of an abstract copying of two-state set. We do not specify a copying transformation and a dimension of state space. Only the unitarity of quantum mechanical transformations is used. Our approach is based on the notion of angle between two states. We first prove several useful statements, simply expressed in terms of angles. We then examine a lower bound on the absolute error, that was first considered by Hillery and Buzek. Our reasonings supplement and reinforce the results, obtained by them. So, we derive more strong bounds on the absolute error, and we also consider a tradeoff between size of error and corresponding probability distributions. After that we examine a lower bound on the relative error.

  20. First and last ancestors: reconstructing evolution of the endomembrane system with ESCRTs, vesicle coat proteins, and nuclear pore complexes.

    Science.gov (United States)

    Field, Mark C; Dacks, Joel B

    2009-02-01

    The eukaryotic endomembrane system is responsible for the biosynthesis and transport of proteins and lipids, and for the definition of the major subcellular compartments. Recent work indicates that the endomembrane system is ancient, with near modern complexity predating the radiation of the major eukaryotic lineages. The challenge is to look beyond the last eukaryotic common ancestor and to attempt to deduce the evolutionary steps in the rise of membrane-trafficking complexity. Relationships between the endomembrane coatomer complexes and their evolutionary connection to the nuclear pore complex are emerging. These studies, plus the realization of a role for the ESCRT complex as an alternate, but equally ancient, system for membrane deformation are providing insight into the earliest stages of endomembrane evolution.

  1. Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.

    Science.gov (United States)

    Paolella, Brenton R; Gibson, William J; Urbanski, Laura M; Alberta, John A; Zack, Travis I; Bandopadhayay, Pratiti; Nichols, Caitlin A; Agarwalla, Pankaj K; Brown, Meredith S; Lamothe, Rebecca; Yu, Yong; Choi, Peter S; Obeng, Esther A; Heckl, Dirk; Wei, Guo; Wang, Belinda; Tsherniak, Aviad; Vazquez, Francisca; Weir, Barbara A; Root, David E; Cowley, Glenn S; Buhrlage, Sara J; Stiles, Charles D; Ebert, Benjamin L; Hahn, William C; Reed, Robin; Beroukhim, Rameen

    2017-02-08

    Genomic instability is a hallmark of human cancer, and results in widespread somatic copy number alterations. We used a genome-scale shRNA viability screen in human cancer cell lines to systematically identify genes that are essential in the context of particular copy-number alterations (copy-number associated gene dependencies). The most enriched class of copy-number associated gene dependencies was CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) genes, and spliceosome components were the most prevalent. One of these, the pre-mRNA splicing factor SF3B1, is also frequently mutated in cancer. We validated SF3B1 as a CYCLOPS gene and found that human cancer cells harboring partial SF3B1 copy-loss lack a reservoir of SF3b complex that protects cells with normal SF3B1 copy number from cell death upon partial SF3B1 suppression. These data provide a catalog of copy-number associated gene dependencies and identify partial copy-loss of wild-type SF3B1 as a novel, non-driver cancer gene dependency.

  2. Candidate gene copy number analysis by PCR and multicapillary electrophoresis.

    Science.gov (United States)

    Szantai, Eszter; Elek, Zsuzsanna; Guttman, András; Sasvari-Szekely, Maria

    2009-04-01

    Genetic polymorphisms are often considered as risk factors of complex diseases serving as valuable and easily detectable biomarkers, also stable during the whole lifespan. A novel type of genetic polymorphism has been identified just recently, referred to as gene copy number variation (CNV) or copy number polymorphism. CNV of glycogen synthase kinase 3 beta and its adjacent gene, Nr1i2 (pregnane X receptor isoform), has been reported to associate with bipolar depression. In our study we introduced multicapillary electrophoresis for gene copy number analysis as an affordable alternative to real-time PCR quantification with TaqMan gene probes. Our results show the reliability of the developed method based on conventional PCR followed by separation of products by multicapillary electrophoresis with quantitative evaluation. This method can be readily implemented for the analysis of candidate gene CNVs in high throughput clinical laboratories and also in personalized medicine care of depression-related risk factors.

  3. Complexity

    CERN Document Server

    Gershenson, Carlos

    2011-01-01

    The term complexity derives etymologically from the Latin plexus, which means interwoven. Intuitively, this implies that something complex is composed by elements that are difficult to separate. This difficulty arises from the relevant interactions that take place between components. This lack of separability is at odds with the classical scientific method - which has been used since the times of Galileo, Newton, Descartes, and Laplace - and has also influenced philosophy and engineering. In recent decades, the scientific study of complexity and complex systems has proposed a paradigm shift in science and philosophy, proposing novel methods that take into account relevant interactions.

  4. Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats.

    Science.gov (United States)

    Stankiewicz, Paweł; Kulkarni, Shashikant; Dharmadhikari, Avinash V; Sampath, Srirangan; Bhatt, Samarth S; Shaikh, Tamim H; Xia, Zhilian; Pursley, Amber N; Cooper, M Lance; Shinawi, Marwan; Paciorkowski, Alex R; Grange, Dorothy K; Noetzel, Michael J; Saunders, Scott; Simons, Paul; Summar, Marshall; Lee, Brendan; Scaglia, Fernando; Fellmann, Florence; Martinet, Danielle; Beckmann, Jacques S; Asamoah, Alexander; Platky, Kathryn; Sparks, Susan; Martin, Ann S; Madan-Khetarpal, Suneeta; Hoover, Jacqueline; Medne, Livija; Bonnemann, Carsten G; Moeschler, John B; Vallee, Stephanie E; Parikh, Sumit; Irwin, Polly; Dalzell, Victoria P; Smith, Wendy E; Banks, Valerie C; Flannery, David B; Lovell, Carolyn M; Bellus, Gary A; Golden-Grant, Kathryn; Gorski, Jerome L; Kussmann, Jennifer L; McGregor, Tracy L; Hamid, Rizwan; Pfotenhauer, Jean; Ballif, Blake C; Shaw, Chad A; Kang, Sung-Hae L; Bacino, Carlos A; Patel, Ankita; Rosenfeld, Jill A; Cheung, Sau Wai; Shaffer, Lisa G

    2012-01-01

    We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers.

  5. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles

    Science.gov (United States)

    Karanasios, Eleftherios; Walker, Simon A.; Okkenhaug, Hanneke; Manifava, Maria; Hummel, Eric; Zimmermann, Hans; Ahmed, Qashif; Domart, Marie-Charlotte; Collinson, Lucy; Ktistakis, Nicholas T.

    2016-01-01

    Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment. PMID:27510922

  6. Complex

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    Schiff bases and their complex compounds have been studied for their .... establishing coordination of the N–(2 – hydroxybenzyl) - L - α - valine Schiff base ..... (1967); “Spectrophotometric Identification of Organic Compounds”, Willey, New.

  7. Patterns, correlates, and reduction of homework copying

    Science.gov (United States)

    Palazzo, David J.; Lee, Young-Jin; Warnakulasooriya, Rasil; Pritchard, David E.

    2010-06-01

    Submissions to an online homework tutor were analyzed to determine whether they were copied. The fraction of copied submissions increased rapidly over the semester, as each weekly deadline approached and for problems later in each assignment. The majority of students, who copied less than 10% of their problems, worked steadily over the three days prior to the deadline, whereas repetitive copiers (those who copied >30% of their submitted problems) exerted little effort early. Importantly, copying homework problems that require an analytic answer correlates with a 2(σ) decline over the semester in relative score for similar problems on exams but does not significantly correlate with the amount of conceptual learning as measured by pretesting and post-testing. An anonymous survey containing questions used in many previous studies of self-reported academic dishonesty showed ˜1/3 less copying than actually was detected. The observed patterns of copying, free response questions on the survey, and interview data suggest that time pressure on students who do not start their homework in a timely fashion is the proximate cause of copying. Several measures of initial ability in math or physics correlated with copying weakly or not at all. Changes in course format and instructional practices that previous self-reported academic dishonesty surveys and/or the observed copying patterns suggested would reduce copying have been accompanied by more than a factor of 4 reduction of copying from ˜11% of all electronic problems to less than 3%. As expected (since repetitive copiers have approximately three times the chance of failing), this was accompanied by a reduction in the overall course failure rate. Survey results indicate that students copy almost twice as much written homework as online homework and show that students nationally admit to more academic dishonesty than MIT students.

  8. Patterns, correlates, and reduction of homework copying

    Directory of Open Access Journals (Sweden)

    David J. Palazzo

    2010-03-01

    Full Text Available Submissions to an online homework tutor were analyzed to determine whether they were copied. The fraction of copied submissions increased rapidly over the semester, as each weekly deadline approached and for problems later in each assignment. The majority of students, who copied less than 10% of their problems, worked steadily over the three days prior to the deadline, whereas repetitive copiers (those who copied >30% of their submitted problems exerted little effort early. Importantly, copying homework problems that require an analytic answer correlates with a 2(σ decline over the semester in relative score for similar problems on exams but does not significantly correlate with the amount of conceptual learning as measured by pretesting and post-testing. An anonymous survey containing questions used in many previous studies of self-reported academic dishonesty showed ∼1/3 less copying than actually was detected. The observed patterns of copying, free response questions on the survey, and interview data suggest that time pressure on students who do not start their homework in a timely fashion is the proximate cause of copying. Several measures of initial ability in math or physics correlated with copying weakly or not at all. Changes in course format and instructional practices that previous self-reported academic dishonesty surveys and/or the observed copying patterns suggested would reduce copying have been accompanied by more than a factor of 4 reduction of copying from ∼11% of all electronic problems to less than 3%. As expected (since repetitive copiers have approximately three times the chance of failing, this was accompanied by a reduction in the overall course failure rate. Survey results indicate that students copy almost twice as much written homework as online homework and show that students nationally admit to more academic dishonesty than MIT students.

  9. Breaking the COPI monopoly on Golgi recycling.

    Science.gov (United States)

    Storrie, B; Pepperkok, R; Nilsson, T

    2000-09-01

    The unexpected discovery of a transport pathway from the Golgi to the endoplasmic reticulum (ER) independent of COPI coat proteins sheds light on how Golgi resident enzymes and protein toxins gain access to the ER from as far as the trans Golgi network. This new pathway provides an explanation for how membrane is recycled to allow for an apparent concentration of anterograde cargo at distinct stages of the secretory pathway. As signal-mediated COPI-dependent recycling also involves the concentration of resident proteins into retrograde COPI vesicles, the main bulk of lipids must be recycled, possibly through a COPI-independent pathway.

  10. Why Can We Copy Classical Information?

    Institute of Scientific and Technical Information of China (English)

    SHEN Yao; HAO Liang; LONG Gui-Lu

    2011-01-01

    It is pointed out that the noncloning theorem in quantum mechanics also holds for unknown state in linear classical physics. The apparent capability of copying of a classical state is essentially the capability of perfect measurement in classical physics. The difference in copying between quantum and classical physics is the difference in measurement between the two theories. A classical copying process is the combined action of measurement of an unknown state and the preparation of this state onto another system. Hence perfect measurability in classical physics enables the copying of a classical state.

  11. Private Copying and Downloading from Unlawful Sources

    NARCIS (Netherlands)

    Quintais, J.P.

    2015-01-01

    Private copying is one of the most contested areas of EU copyright law. This paper surveys that nebulous area and examines the issue of copies made from unlawful sources in light of the ECJ’s ACI Adam decision. After describing the legal background of copyright levies and the facts of the

  12. Private Copying and Downloading from Unlawful Sources

    NARCIS (Netherlands)

    J.P. Quintais

    2015-01-01

    Private copying is one of the most contested areas of EU copyright law. This paper surveys that nebulous area and examines the issue of copies made from unlawful sources in light of the ECJ’s ACI Adam decision. After describing the legal background of copyright levies and the facts of the litigation

  13. Hacking DNA copy number for circuit engineering.

    Science.gov (United States)

    Wu, Feilun; You, Lingchong

    2017-07-27

    DNA copy number represents an essential parameter in the dynamics of synthetic gene circuits but typically is not explicitly considered. A new study demonstrates how dynamic control of DNA copy number can serve as an effective strategy to program robust oscillations in gene expression circuits.

  14. 14 CFR 249.4 - Photographic copies.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Photographic copies. 249.4 Section 249.4 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS PRESERVATION OF AIR CARRIER RECORDS General Instructions § 249.4 Photographic copies. (a)...

  15. Copy-number changes in evolution: rates, fitness effects and adaptive significance

    Directory of Open Access Journals (Sweden)

    Vaishali eKatju

    2013-12-01

    Full Text Available Gene copy-number differences due to gene duplications and deletions are rampant in natural populations and play a crucial role in the evolution of genome complexity. Per-locus analyses of gene duplication rates in the pre-genomic era revealed that gene duplication rates are much higher than the per nucleotide substitution rate. Analyses of gene duplication and deletion rates in mutation accumulation lines of model organisms have revealed that these high rates of copy-number mutations occur at a genome-wide scale. Furthermore, comparisons of the spontaneous duplication and deletion rates to copy-number polymorphism data and bioinformatic-based estimates of duplication rates from sequenced genomes suggest that the vast majority of gene duplications are detrimental and removed by natural selection. The rate at which new gene copies appear in populations greatly influences their evolutionary dynamics and standing gene copy-number variation in populations. The opportunity for mutations that result in the maintenance of duplicate copies, either through neofunctionalization or subfunctionalization, also depends on the equilibrium frequency of additional gene copies in the population, and hence on the spontaneous gene duplication (and loss rate. The duplication rate may therefore have profound effects on the role of adaptation in the evolution of duplicated genes as well as important consequences for the evolutionary potential of organisms. We further discuss the broad ramifications of this standing gene copy-number variation on fitness and adaptive potential from a population-genetic and genome-wide perspective.

  16. High-resolution copy number arrays in cancer and the problem of normal genome copy number variation.

    Science.gov (United States)

    Gorringe, Kylie L; Campbell, Ian G

    2008-11-01

    High-resolution techniques for analysis of genome copy number (CN) enable the analysis of complex cancer somatic genetics. However, the analysis of these data is difficult, and failure to consider a number of issues in depth may result in false leads or unnecessary rejection of true positives. First, segmental duplications may falsely generate CN breakpoints in aneuploid samples. Second, even when tumor data were each normalized to matching lymphocyte DNA, we still observed copy number polymorphisms masquerading as somatic alterations due to allelic imbalance. We investigated a number of different solutions and determined that evaluating matching normal DNA, or at least using locally derived normal baseline data, were preferable to relying on current online databases because of poor cross-platform compatibility and the likelihood of excluding genuine small somatic alterations.

  17. Estimating Copy Number and Allelic Variation at the Immunoglobulin Heavy Chain Locus Using Short Reads.

    Directory of Open Access Journals (Sweden)

    Shishi Luo

    2016-09-01

    Full Text Available The study of genomic regions that contain gene copies and structural variation is a major challenge in modern genomics. Unlike variation involving single nucleotide changes, data on the variation of copy number is difficult to collect and few tools exist for analyzing the variation between individuals. The immunoglobulin heavy variable (IGHV locus, which plays an integral role in the adaptive immune response, is an example of a complex genomic region that varies in gene copy number. Lack of standard methods to genotype this region prevents it from being included in association studies and is holding back the growing field of antibody repertoire analysis. Here we develop a method that takes short reads from high-throughput sequencing and outputs a genetic profile of the IGHV locus with the read coverage depth and a putative nucleotide sequence for each operationally defined gene cluster. Our operationally defined gene clusters aim to address a major challenge in studying the IGHV locus: the high sequence similarity between gene segments in different genomic locations. Tests on simulated data demonstrate that our approach can accurately determine the presence or absence of a gene cluster from reads as short as 70 bp. More detailed resolution on the copy number of gene clusters can be obtained from read coverage depth using longer reads (e.g., ≥ 100 bp. Detail at the nucleotide resolution of single copy genes (genes present in one copy per haplotype can be determined with 250 bp reads. For IGHV genes with more than one copy, accurate nucleotide-resolution reconstruction is currently beyond the means of our approach. When applied to a family of European ancestry, our pipeline outputs genotypes that are consistent with the family pedigree, confirms existing multigene variants and suggests new copy number variants. This study paves the way for analyzing population-level patterns of variation in IGHV gene clusters in larger diverse datasets and for

  18. ACTA Technology Presents EPA with Patent Copy

    Science.gov (United States)

    US EPA SBIR awardee, ACTA Technology, presented James H. Johnson, Director of the US EPA National Center for Environmental Research, and April Richards, Program Manager of the US EPA's SBIR Program, with a copy of their Red Ribbon patent.

  19. Preservation Copying Endangered Historic Negative Collections

    DEFF Research Database (Denmark)

    Kejser, Ulla Bøgvad

    2008-01-01

    This article discusses preservation copying of unstable B&W nitrate and acetate still photographic negatives. It focuses on evaluating two different strategies for preserving the copies from a point of view of quality and cost-effectiveness. The evaluated strategies are preservation of the master...... by describing essential characteristics of negatives, which must be passed on to the copies, and the required metadata and technical imaging specifications. Next the paper discusses strategies for preservation and makes an analysis with the LIFE2 Costing Model. The paper concludes that the most beneficial...... and cost-effective preservation solution for large format negatives is to keep the preservation copies as digital files. However, it also acknowledges that it is important to revisit such strategies regularly to monitor changes in user expectations, technologies and costs....

  20. Copy number variation across European populations.

    Directory of Open Access Journals (Sweden)

    Wanting Chen

    Full Text Available Genome analysis provides a powerful approach to test for evidence of genetic variation within and between geographical regions and local populations. Copy number variants which comprise insertions, deletions and duplications of genomic sequence provide one such convenient and informative source. Here, we investigate copy number variants from genome wide scans of single nucleotide polymorphisms in three European population isolates, the island of Vis in Croatia, the islands of Orkney in Scotland and the South Tyrol in Italy. We show that whereas the overall copy number variant frequencies are similar between populations, their distribution is highly specific to the population of origin, a finding which is supported by evidence for increased kinship correlation for specific copy number variants within populations.

  1. Line copy presentation slides with Kodalith.

    Science.gov (United States)

    Kraushar, M F; Bailey, B A

    1978-08-01

    Line copy presentation slides with white letters on a blue background can be produced with a two-step process. The slides are more permanent than diazo slides, and the process is faster and less expensive.

  2. Preservation Copying Endangered Historic Negative Collections

    DEFF Research Database (Denmark)

    Kejser, Ulla Bøgvad

    2008-01-01

    This article discusses preservation copying of unstable B&W nitrate and acetate still photographic negatives. It focuses on evaluating two different strategies for preserving the copies from a point of view of quality and cost-effectiveness. The evaluated strategies are preservation of the master...... files in a digital repository and outputting the copies on film, which is preserved in a traditional storage facility. The issues are put into perspective by a case study completed at the Royal Library, where endangered nitrate negatives of unique national value have been digitized. The paper starts...... by describing essential characteristics of negatives, which must be passed on to the copies, and the required metadata and technical imaging specifications. Next the paper discusses strategies for preservation and makes an analysis with the LIFE2 Costing Model. The paper concludes that the most beneficial...

  3. Local Reasoning about a Copying Garbage Collector

    DEFF Research Database (Denmark)

    Torp-Smith, Noah; Birkedal, Lars; Reynolds, John C.

    2008-01-01

    We present a programming language, model, and logic appropriate for implementing and reasoning about a memory management system. We state semantically what is meant by correctness of a copying garbage collector, and employ a variant of the novel separation logics to formally specify partial...... correctness of Cheney’s copying garbage collector in our program logic. Finally, we prove that our implementation of Cheney’s algorithm meets its specification using the logic we have given and auxiliary variables. Udgivelsesdato: 2008...

  4. Interactive Data Integration through Smart Copy & Paste

    CERN Document Server

    Ives, Zachary; Minton, Steve; Jacob, Marie; Talukdar, Partha; Tuchinda, Rattapoom; Ambite, Jose Luis; Muslea, Maria; Gazen, Cenk

    2009-01-01

    In many scenarios, such as emergency response or ad hoc collaboration, it is critical to reduce the overhead in integrating data. Ideally, one could perform the entire process interactively under one unified interface: defining extractors and wrappers for sources, creating a mediated schema, and adding schema mappings ? while seeing how these impact the integrated view of the data, and refining the design accordingly. We propose a novel smart copy and paste (SCP) model and architecture for seamlessly combining the design-time and run-time aspects of data integration, and we describe an initial prototype, the CopyCat system. In CopyCat, the user does not need special tools for the different stages of integration: instead, the system watches as the user copies data from applications (including the Web browser) and pastes them into CopyCat?s spreadsheet-like workspace. CopyCat generalizes these actions and presents proposed auto-completions, each with an explanation in the form of provenance. The user provides f...

  5. How best practices are copied, transferred, or translated between health care facilities: A conceptual framework.

    Science.gov (United States)

    Guzman, Gustavo; Fitzgerald, Janna Anneke; Fulop, Liz; Hayes, Kathryn; Poropat, Arthur; Avery, Mark; Campbell, Steve; Fisher, Ron; Gapp, Rod; Herington, Carmel; McPhail, Ruth; Vecchio, Nerina

    2015-01-01

    In spite of significant investment in quality programs and activities, there is a persistent struggle to achieve quality outcomes and performance improvements within the constraints and support of sociopolitical parsimonies. Equally, such constraints have intensified the need to better understand the best practice methods for achieving quality improvements in health care organizations over time.This study proposes a conceptual framework to assist with strategies for the copying, transferring, and/or translation of best practice between different health care facilities. Applying a deductive logic, the conceptual framework was developed by blending selected theoretical lenses drawn from the knowledge management and organizational learning literatures. The proposed framework highlighted that (a) major constraints need to be addressed to turn best practices into everyday practices and (b) double-loop learning is an adequate learning mode to copy and to transfer best practices and deuteron learning mode is a more suitable learning mode for translating best practice. We also found that, in complex organizations, copying, transferring, and translating new knowledge is more difficult than in smaller, less complex organizations. We also posit that knowledge translation cannot happen without transfer and copy, and transfer cannot happen without copy of best practices. Hence, an integration of all three learning processes is required for knowledge translation (copy best practice-transfer knowledge about best practice-translation of best practice into new context). In addition, the higher the level of complexity of the organization, the more best practice is tacit oriented and, in this case, the higher the level of K&L capabilities are required to successfully copy, transfer, and/or translate best practices between organizations. The approach provides a framework for assessing organizational context and capabilities to guide copy/transfer/translation of best practices. A

  6. Identifying single copy orthologs in Metazoa.

    Directory of Open Access Journals (Sweden)

    Christopher J Creevey

    2011-12-01

    Full Text Available The identification of single copy (1-to-1 orthologs in any group of organisms is important for functional classification and phylogenetic studies. The Metazoa are no exception, but only recently has there been a wide-enough distribution of taxa with sufficiently high quality sequenced genomes to gain confidence in the wide-spread single copy status of a gene.Here, we present a phylogenetic approach for identifying overlooked single copy orthologs from multigene families and apply it to the Metazoa. Using 18 sequenced metazoan genomes of high quality we identified a robust set of 1,126 orthologous groups that have been retained in single copy since the last common ancestor of Metazoa. We found that the use of the phylogenetic procedure increased the number of single copy orthologs found by over a third more than standard taxon-count approaches. The orthologs represented a wide range of functional categories, expression profiles and levels of divergence.To demonstrate the value of our set of single copy orthologs, we used them to assess the completeness of 24 currently published metazoan genomes and 62 EST datasets. We found that the annotated genes in published genomes vary in coverage from 79% (Ciona intestinalis to 99.8% (human with an average of 92%, suggesting a value for the underlying error rate in genome annotation, and a strategy for identifying single copy orthologs in larger datasets. In contrast, the vast majority of EST datasets with no corresponding genome sequence available are largely under-sampled and probably do not accurately represent the actual genomic complement of the organisms from which they are derived.

  7. Decomposition of Parallel Copies with Duplication

    Directory of Open Access Journals (Sweden)

    G. N. Purohit

    2012-05-01

    Full Text Available SSA form is becoming more popular in the context of JIT compilation since it allows the compiler to perform important optimizations like common sub-expression elimination or constant propagation without the drawbacks of keeping huge data structures in memory or requiring a lot of computing power. The recent approach of SSA-based register allocation performs SSA elimination after register allocation. F. Bouchez et al. proposed parallel copy motion to prevent the splitting of edges when going out of colored SSA by moving the code that should be assigned to the edges to a more convenient place. Duplications in parallel copies pose some problems when moving them. In this paper an approach has been developed to decompose parallel copies so that duplications can be handled separately and parallel copies can be easily moved away without duplication. A simple and elegant application is moving duplicated copies out of critical edges. This is often beneficial compared to the alternative splitting the edge.

  8. The Energy of COPI for Budding Membranes

    Science.gov (United States)

    Thiam, Abdou Rachid; Pincet, Frédéric

    2015-01-01

    As a major actor of cellular trafficking, COPI coat proteins assemble on membranes and locally bend them to bud 60 nm-size coated particles. Budding requires the energy of the coat assembly to overcome the one necessary to deform the membrane which primarily depends on the bending modulus and surface tension, γ. Using a COPI-induced oil nanodroplet formation approach, we modulated the budding of nanodroplets using various amounts and types of surfactant. We found a Heaviside-like dependence between the budding efficiency and γ: budding was only dependent on γ and occurred beneath 1.3 mN/m. With the sole contribution of γ to the membrane deformation energy, we assessed that COPI supplies ~1500 kBT for budding particles from membranes, which is consistent with common membrane deformation energies. Our results highlight how a simple remodeling of the composition of membranes could mechanically modulate budding in cells. PMID:26218078

  9. Black holes and the double copy

    CERN Document Server

    Monteiro, Ricardo; White, Chris D

    2014-01-01

    Recently, a perturbative duality between gauge and gravity theories (the double copy) has been discovered, that is believed to hold to all loop orders. In this paper, we examine the relationship between classical solutions of non-Abelian gauge theory and gravity. We propose a general class of gauge theory solutions that double copy to gravity, namely those involving stationary Kerr-Schild metrics. The Schwarzschild and Kerr black holes (plus their higher-dimensional equivalents) emerge as special cases. We also discuss plane wave solutions. Furthermore, a recently examined double copy between the self-dual sectors of Yang-Mills theory and gravity can be reinterpreted using a momentum-space generalisation of the Kerr-Schild framework.

  10. Teaching Ad Copy--I and II.

    Science.gov (United States)

    Welty, Ward; Vanden Bergh, Bruce G.

    1981-01-01

    Ward Welty notes that the standard advertising course could be improved by including a unit of study in rhetoric, especially Aristotelian rhetoric. Bruce Vanden Bergh reports on research on the differences in creating advertising copy for radio versus the visual media of magazines, newspapers, and television. (RL)

  11. 48 CFR 1401.105-3 - Copies.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Copies. 1401.105-3 Section... of the Interior, 1849 C Street (MS 2607-MIB), NW., Washington, DC 20240. Additional information on DOI may be obtained on the Internet at http://www.doi.gov/pam....

  12. 48 CFR 2901.105-3 - Copies.

    Science.gov (United States)

    2010-10-01

    ... information on DOL may be obtained on the Internet at www.dol.gov. Other DOL procurement policy documents... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Copies. 2901.105-3 Section 2901.105-3 Federal Acquisition Regulations System DEPARTMENT OF LABOR GENERAL DEPARTMENT OF...

  13. Teaching Ad Copy--I and II.

    Science.gov (United States)

    Welty, Ward; Vanden Bergh, Bruce G.

    1981-01-01

    Ward Welty notes that the standard advertising course could be improved by including a unit of study in rhetoric, especially Aristotelian rhetoric. Bruce Vanden Bergh reports on research on the differences in creating advertising copy for radio versus the visual media of magazines, newspapers, and television. (RL)

  14. Genomic copy number alterations of primary and secondary metastasizing pleomorphic adenomas.

    Science.gov (United States)

    Mariano, Fernanda Viviane; Gondak, Rogério de Oliveira; Martins, Antonio Santos; Coletta, Ricardo Della; Paes de Almeida, Oslei; Kowalski, Luiz Paulo; Krepischi, Ana Cristina Victorino; Altemani, Albina

    2015-09-01

    Metastasizing pleomorphic adenoma (MPA) is a rare tumour, and its mechanism of metastasis still is unknown. To date, there has been no study on MPA genomics. We analysed primary and secondary MPAs with array comparative genomic hybridization to identify somatic copy number alterations and affected genes. Tumour DNA samples from primary (parotid salivary gland) and secondary (scalp skin) MPAs were subjected to array comparative genomic hybridization investigation, and the data were analysed with NEXUS COPY NUMBER DISCOVERY. The primary MPA showed copy number losses affecting 3p22.2p14.3 and 19p13.3p123, and a complex pattern of four different deletions at chromosome 6. The 3p deletion encompassed several genes: CTNNB1, SETD2, BAP1, and PBRM1, among others. The secondary MPA showed a genomic profile similar to that of the primary MPA, with acquisition of additional copy number changes affecting 9p24.3p13.1 (loss), 19q11q13.43 (gain), and 22q11.1q13.33 (gain). Our findings indicated a clonal origin of the secondary MPA, as both tumours shared a common profile of genomic copy number alterations. Furthermore, we were able to detect in the primary tumour a specific pattern of copy number alterations that could explain the metastasizing characteristic, whereas the secondary MPA showed a more unbalanced genome. © 2015 John Wiley & Sons Ltd.

  15. An Essential Role for COPI in mRNA Localization to Mitochondria and Mitochondrial Function.

    Science.gov (United States)

    Zabezhinsky, Dmitry; Slobodin, Boris; Rapaport, Doron; Gerst, Jeffrey E

    2016-04-19

    Nuclear-encoded mRNAs encoding mitochondrial proteins (mMPs) can localize directly to the mitochondrial surface, yet how mMPs target mitochondria and whether RNA targeting contributes to protein import into mitochondria and cellular metabolism are unknown. Here, we show that the COPI vesicle coat complex is necessary for mMP localization to mitochondria and mitochondrial function. COPI inactivation leads to reduced mMP binding to COPI itself, resulting in the dissociation of mMPs from mitochondria, a reduction in mitochondrial membrane potential, a decrease in protein import in vivo and in vitro, and severe deficiencies in mitochondrial respiration. Using a model mMP (OXA1), we observed that COPI inactivation (or mutation of the potential COPI-interaction site) led to altered mRNA localization and impaired cellular respiration. Overall, COPI-mediated mMP targeting is critical for mitochondrial protein import and function, and transcript delivery to the mitochondria or endoplasmic reticulum is regulated by cis-acting RNA sequences and trans-acting proteins.

  16. Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.

    Science.gov (United States)

    Ramakrishna, Manasa; Williams, Louise H; Boyle, Samantha E; Bearfoot, Jennifer L; Sridhar, Anita; Speed, Terence P; Gorringe, Kylie L; Campbell, Ian G

    2010-04-08

    Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (> 40% of samples). Within these regions, 703/1370 (51%) unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r > or =0.6) between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2.

  17. Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.

    Directory of Open Access Journals (Sweden)

    Manasa Ramakrishna

    Full Text Available Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (> 40% of samples. Within these regions, 703/1370 (51% unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r > or =0.6 between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2.

  18. Adaptive copy number evolution in malaria parasites.

    Directory of Open Access Journals (Sweden)

    Shalini Nair

    2008-10-01

    Full Text Available Copy number polymorphism (CNP is ubiquitous in eukaryotic genomes, but the degree to which this reflects the action of positive selection is poorly understood. The first gene in the Plasmodium folate biosynthesis pathway, GTP-cyclohydrolase I (gch1, shows extensive CNP. We provide compelling evidence that gch1 CNP is an adaptive consequence of selection by antifolate drugs, which target enzymes downstream in this pathway. (1 We compared gch1 CNP in parasites from Thailand (strong historical antifolate selection with those from neighboring Laos (weak antifolate selection. Two percent of chromosomes had amplified copy number in Laos, while 72% carried multiple (2-11 copies in Thailand, and differentiation exceeded that observed at 73 synonymous SNPs. (2 We found five amplicon types containing one to greater than six genes and spanning 1 to >11 kb, consistent with parallel evolution and strong selection for this gene amplification. gch1 was the only gene occurring in all amplicons suggesting that this locus is the target of selection. (3 We observed reduced microsatellite variation and increased linkage disequilibrium (LD in a 900-kb region flanking gch1 in parasites from Thailand, consistent with rapid recent spread of chromosomes carrying multiple copies of gch1. (4 We found that parasites bearing dhfr-164L, which causes high-level resistance to antifolate drugs, carry significantly (p = 0.00003 higher copy numbers of gch1 than parasites bearing 164I, indicating functional association between genes located on different chromosomes but linked in the same biochemical pathway. These results demonstrate that CNP at gch1 is adaptive and the associations with dhfr-164L strongly suggest a compensatory function. More generally, these data demonstrate how selection affects multiple enzymes in a single biochemical pathway, and suggest that investigation of structural variation may provide a fast-track to locating genes underlying adaptation.

  19. Copy number variation associates with mortality in long-lived individuals

    DEFF Research Database (Denmark)

    Nygaard, Marianne; Debrabant, Birgit; Tan, Qihua

    2016-01-01

    Copy number variants (CNVs) represent a significant source of genetic variation in the human genome and have been implicated in numerous diseases and complex traits. To date, only a few studies have investigated the role of CNVs in human lifespan. To investigate the impact of CNVs on prospective...

  20. Chimpanzees copy dominant and knowledgeable individuals

    DEFF Research Database (Denmark)

    Kendal, Rachel; Hopper, Lydia M.; Whiten, Andrew

    2015-01-01

    Evolutionary theory predicts that natural selection will fashion cognitive biases to guide when, and from whom, individuals acquire social information, but the precise nature of these biases, especially in ecologically valid group contexts, remains unknown. We exposed four captive groups...... of chimpanzees (Pan troglodytes) to a novel extractive foraging device and, by fitting statistical models, isolated four simultaneously operating transmission biases. These include biases to copy (i) higher-ranking and (ii) expert individuals, and to copy others when (iii) uncertain or (iv) of low rank. High......-ranking individuals were relatively un-strategic in their use of acquired knowledge, which, combined with the bias for others to observe them, may explain reports that high innovation rates (in juveniles and subordinates) do not generate a correspondingly high frequency of traditions in chimpanzees. Given...

  1. Laser thermographic technologies for hard copy recording

    Science.gov (United States)

    Bessmel'tsev, Viktor P.; Baev, Sergej G.

    1995-04-01

    Methods of hard copies recording based on thermal interaction of the beam from CO2 or YAG lasers with various kinds of films on any substrates have been developed. The recording processes are single-step and require no additional development. Among them are: (1) Laser thermodestruction of thin mask layers or of a material surface on any kinds of substrates. (2) Laser thermochemical reactions of thermal decomposition of metal salts in solid state phase on a surface of various hygroscopic substrates. The laser recording devices using the methods, described above have been developed and are manufactured now; they allow one to record hard copies with a size of up to 27 X 31 inches, a resolution of 4000 dpi.

  2. [Create or copy... Which is the difference?].

    Science.gov (United States)

    López P, Ricardo

    2009-01-01

    Creating and copying are two different processes; we must not confuse creativity with plagiarism. However, this distinction is problematic, because there is no possibility of creating from scratch, this implies that any creative act necessarily arises from accumulative experience, inevitably producing a continuity between old and new. Even so it is necessary to establish clearly the difference between creating and copying. It is not desirable that a matter of such importance remains in the nebula or that the relationship between creativity and ethics is kept unaware. There are many cases of plagiarism, but this cannot be a consolation. There is no gain when the existence of a plagiarism is ignored or concealed and less when it is unjustified.

  3. Watermarking scar as an ultimate copy protection

    Energy Technology Data Exchange (ETDEWEB)

    Braci, Sofiane; Miraoui, Abdelkader; Delpha, Claude; Boyer, Remy, E-mail: sofiane.braci@lss.supelec.f, E-mail: Abdelkader.Miraoui@lss.supelec.f, E-mail: claude.delpha@lss.supelec.f, E-mail: remy.boyer@lss.supelec.f [University Paris-Sud 11, Laboratory of Signals and Systems, Supelec, 3 rue Joliot-Curie, 91192 Gif-sur-Yvette cedex (France)

    2010-02-01

    Strong and powerful attacks are able to make the watermark extraction impossible even if there is some watermarking. In this work, we call this residual information the scar and we use it to prove the existence of an attacked watermark. We evaluate the Scar by the mutual information between the embedded watermark and the attacked copies. It is well known that the mutual information between two random variables gives an evaluation of the shared information between the two variables. Thus, the attack can compromise the correct decoding by removing partially the watermarking information. However, it is possible to make the watermarking existence proof possible when the mutual information between the embedded message and the attacked copies is above a certain threshold. We propose a practical way to use the scar by measuring the correlation between the attacked watermark and the original one.

  4. Colour hard-copy from workstation screens

    Science.gov (United States)

    Clayton, C. A.

    It is possible to produce a colour print on the DEC LJ250 inkjet printer of either the entire screen or a portion of the screen from VAXstations, DECstations, SUN workstations and the IKON image display. This document describes how to achieve this with each of the above workstations. The IKONPAINT software which is used to produce colour hard-copy from the IKON screen on the inkjet printer is fully documented in SUN/71 and is not described here.

  5. Confirmed rare copy number variants implicate novel genes in schizophrenia.

    Science.gov (United States)

    Tam, Gloria W C; van de Lagemaat, Louie N; Redon, Richard; Strathdee, Karen E; Croning, Mike D R; Malloy, Mary P; Muir, Walter J; Pickard, Ben S; Deary, Ian J; Blackwood, Douglas H R; Carter, Nigel P; Grant, Seth G N

    2010-04-01

    Understanding how cognitive processes including learning, memory, decision making and ideation are encoded by the genome is a key question in biology. Identification of sets of genes underlying human mental disorders is a path towards this objective. Schizophrenia is a common disease with cognitive symptoms, high heritability and complex genetics. We have identified genes involved with schizophrenia by measuring differences in DNA copy number across the entire genome in 91 schizophrenia cases and 92 controls in the Scottish population. Our data reproduce rare and common variants observed in public domain data from >3000 schizophrenia cases, confirming known disease loci as well as identifying novel loci. We found copy number variants in PDE10A (phosphodiesterase 10A), CYFIP1 [cytoplasmic FMR1 (Fragile X mental retardation 1)-interacting protein 1], K(+) channel genes KCNE1 and KCNE2, the Down's syndrome critical region 1 gene RCAN1 (regulator of calcineurin 1), cell-recognition protein CHL1 (cell adhesion molecule with homology with L1CAM), the transcription factor SP4 (specificity protein 4) and histone deacetylase HDAC9, among others (see http://www.genes2cognition.org/SCZ-CNV). Integrating the function of these many genes into a coherent model of schizophrenia and cognition is a major unanswered challenge.

  6. Why copy others? Insights from the social learning strategies tournament.

    Science.gov (United States)

    Rendell, L; Boyd, R; Cownden, D; Enquist, M; Eriksson, K; Feldman, M W; Fogarty, L; Ghirlanda, S; Lillicrap, T; Laland, K N

    2010-04-09

    Social learning (learning through observation or interaction with other individuals) is widespread in nature and is central to the remarkable success of humanity, yet it remains unclear why copying is profitable and how to copy most effectively. To address these questions, we organized a computer tournament in which entrants submitted strategies specifying how to use social learning and its asocial alternative (for example, trial-and-error learning) to acquire adaptive behavior in a complex environment. Most current theory predicts the emergence of mixed strategies that rely on some combination of the two types of learning. In the tournament, however, strategies that relied heavily on social learning were found to be remarkably successful, even when asocial information was no more costly than social information. Social learning proved advantageous because individuals frequently demonstrated the highest-payoff behavior in their repertoire, inadvertently filtering information for copiers. The winning strategy (discountmachine) relied nearly exclusively on social learning and weighted information according to the time since acquisition.

  7. Digital authentication with copy-detection patterns

    Science.gov (United States)

    Picard, Justin

    2004-06-01

    Technologies for making high-quality copies of documents are getting more available, cheaper, and more efficient. As a result, the counterfeiting business engenders huge losses, ranging to 5% to 8% of worldwide sales of brand products, and endangers the reputation and value of the brands themselves. Moreover, the growth of the Internet drives the business of counterfeited documents (fake IDs, university diplomas, checks, and so on), which can be bought easily and anonymously from hundreds of companies on the Web. The incredible progress of digital imaging equipment has put in question the very possibility of verifying the authenticity of documents: how can we discern genuine documents from seemingly "perfect" copies? This paper proposes a solution based on creating digital images with specific properties, called a Copy-detection patterns (CDP), that is printed on arbitrary documents, packages, etc. CDPs make an optimal use of an "information loss principle": every time an imae is printed or scanned, some information is lost about the original digital image. That principle applies even for the highest quality scanning, digital imaging, printing or photocopying equipment today, and will likely remain true for tomorrow. By measuring the amount of information contained in a scanned CDP, the CDP detector can take a decision on the authenticity of the document.

  8. 42 CFR 456.612 - Copies of reports.

    Science.gov (United States)

    2010-10-01

    ... Institutions for Mental Diseases § 456.612 Copies of reports. The agency must send a copy of each inspection... function, including, if inspection reports concern IMD's, the appropriate State mental health authorities....

  9. 19 CFR 133.42 - Infringing copies or phonorecords.

    Science.gov (United States)

    2010-04-01

    ...) Referral to the U.S. Attorney. In the event that phonorecords or copies of motion pictures arrive in the U... trafficking in counterfeit labels for phonorecords or copies of motion pictures or other audiovisual works...

  10. Conditionally amplifiable BACs: switching from single-copy to high-copy vectors and genomic clones.

    Science.gov (United States)

    Wild, Jadwiga; Hradecna, Zdenka; Szybalski, Waclaw

    2002-09-01

    The widely used, very-low-copy BAC (bacterial artificial chromosome) vectors are the mainstay of present genomic research. The principal advantage of BACs is the high stability of inserted clones, but an important disadvantage is the low yield of DNA, both for vectors alone and when carrying genomic inserts. We describe here a novel class of single-copy/high-copy (SC/HC) pBAC/oriV vectors that retain all the advantages of low-copy BAC vectors, but are endowed with a conditional and tightly controlled oriV/TrfA amplification system that allows: (1) a yield of ~100 copies of the vector per host cell when conditionally induced with L-arabinose, and (2) analogous DNA amplification (only upon induction and with copy number depending on the insert size) of pBAC/oriV clones carrying >100-kb inserts. Amplifiable clones and libraries facilitate high-throughput DNA sequencing and other applications requiring HC plasmid DNA. To turn on DNA amplification, which is driven by the oriV origin of replication, we used copy-up mutations in the gene trfA whose expression was very tightly controlled by the araC-P(araBAD) promoter/regulator system. This system is inducible by L-arabinose, and could be further regulated by glucose and fucose. Amplification of DNA upon induction with L-arabinose and its modulation by glucose are robust and reliable. Furthermore, we discovered that addition of 0.2% D-glucose to the growth medium helped toward the objective of obtaining a real SC state for all BAC systems, thus enhancing the stability of their maintenance, which became equivalent to cloning into the host chromosome

  11. Prevalence and pathogen load estimates for the fungus Batrachochytrium dendrobatidis are impacted by ITS DNA copy number variation

    DEFF Research Database (Denmark)

    Rebollar, Eria A.; Woodhams, Douglas C.; LaBumbard, Brandon

    2017-01-01

    The ribosomal gene complex is a multi-copy region that is widely used for phylogenetic analyses of organisms from all 3 domains of life. In fungi, the copy number of the internal transcribed spacer (ITS) is used to detect abundance of pathogens causing diseases such as chytridiomycosis in amphibi...

  12. 33 CFR 88.05 - Copy of rules.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Copy of rules. 88.05 Section 88... RULES ANNEX V: PILOT RULES § 88.05 Copy of rules. The operator of each self-propelled vessel 12 meters or more in length shall carry on board and maintain for ready reference a copy of the Inland...

  13. 27 CFR 478.95 - Certified copy of license.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Certified copy of license... Conduct of Business § 478.95 Certified copy of license. The license furnished to each person licensed... the licensee desires an additional copy of the license for certification (instead of making a...

  14. 47 CFR 95.673 - Copy of rules.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Copy of rules. 95.673 Section 95.673... SERVICES Technical Regulations Additional Certification Requirements for Cb Transmitters § 95.673 Copy of rules. A copy of part 95, subpart D, of the FCC Rules, current at the time of packing of the transmitter...

  15. 40 CFR 374.5 - Copy of complaint.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Copy of complaint. 374.5 Section 374.5... COMMUNITY RIGHT-TO-KNOW PROGRAMS PRIOR NOTICE OF CITIZEN SUITS § 374.5 Copy of complaint. At the time of filing an action under this Act, the plaintiff must provide a copy of the complaint to the Attorney...

  16. Optimal copying of entangled two-qubit states

    CERN Document Server

    Novotny, J; Jex, I

    2004-01-01

    We investigate the problem of copying pure two-qubit states of a given degree of entanglement in an optimal way. Completely positive covariant quantum operations are constructed which maximize the fidelity of the output states with respect to two separable copies. These optimal copying processes hint at the intricate relationship between fundamental laws of quantum theory and entanglement.

  17. 27 CFR 22.165 - Photographic copies of records.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Photographic copies of records. 22.165 Section 22.165 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Transactions § 22.165 Photographic copies of records. (a) General. Permittees may record, copy, or...

  18. 27 CFR 19.725 - Photographic copies of records.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Photographic copies of records. 19.725 Section 19.725 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Photographic copies of records. (a) Application. Proprietors who desire to record, copy or reproduce...

  19. 27 CFR 31.192 - Photographic copies of records.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Photographic copies of records. 31.192 Section 31.192 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Records and Files § 31.192 Photographic copies of records. (a) General. Dealers may record, copy,...

  20. 27 CFR 18.64 - Photographic copies of records.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Photographic copies of records. 18.64 Section 18.64 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Reports § 18.64 Photographic copies of records. Proprietors may record, copy, or reproduce...

  1. 27 CFR 20.268 - Photographic copies of records.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Photographic copies of records. 20.268 Section 20.268 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Reports § 20.268 Photographic copies of records. (a) General. Permittees may record, copy, or...

  2. Deletion of a single-copy DAAM1 gene in congenital heart defect: a case report

    Directory of Open Access Journals (Sweden)

    Bao Bihui

    2012-08-01

    Full Text Available Abstract Background With an increasing incidence of congenital heart defects (CHDs in recent years, genotype-phenotype correlation and array-based methods have contributed to the genome-wide analysis and understanding of genetic variations in the CHD population. Here, we report a copy number deletion of chromosomal 14q23.1 in a female fetus with complex congenital heart defects. This is the first description of DAAM1 gene deletion associated with congenital heart anomalies. Case Presentation Compared with the control population, one CHD fetus showed a unique copy number deletion of 14q23.1, a region that harbored DAAM1 and KIAA0666 genes. Conclusions Results suggest that the copy number deletion on chromosome 14q23.1 may be critical for cardiogenesis. However, the exact relationship and mechanism of how DAAM1 and KIAA0666 deletion contributes to the onset of CHD is yet to be determined.

  3. Conserved genetic regions across angiosperms as tools to develop single-copy nuclear markers in gymnosperms: an example using cycads

    Science.gov (United States)

    Several individuals of the Caribbean Zamia clade (Zamia pumila complex) and other cycads were used to identify potential low copy nuclear genes for further studies of the phylogeographic relationships within the Caribbean Z. pumila complex and also among genera of Cycadales. Two strategies were used...

  4. Stolen and lost copies of Vesalius's Fabrica.

    Science.gov (United States)

    Steeno, Omer; Biesbrouck, Maurits

    2012-01-01

    Thefts and losses of precious books are not rare. Here we report several incidents concerning vesalius's Fabrica: the fire of the University Library of Leuven in Belgium, the fate of the collection of the Leopoldina Library of Halle in Germany, the thefts from the Crerar Library in Chicago and in Christ Church College in Oxford, the disappearance of an exceptionally beautiful 'royal' copy from the Castle of Argenteuil (Belgium), and other Fabrica's missing at the Franeker Library in the Netherlands and at the Library of oradea in West Romania. Finally the means of protecting precious book collections are discussed in short as well as the importance of book identification.

  5. Getting DNA copy numbers without control samples

    Directory of Open Access Journals (Sweden)

    Ortiz-Estevez Maria

    2012-08-01

    Full Text Available Abstract Background The selection of the reference to scale the data in a copy number analysis has paramount importance to achieve accurate estimates. Usually this reference is generated using control samples included in the study. However, these control samples are not always available and in these cases, an artificial reference must be created. A proper generation of this signal is crucial in terms of both noise and bias. We propose NSA (Normality Search Algorithm, a scaling method that works with and without control samples. It is based on the assumption that genomic regions enriched in SNPs with identical copy numbers in both alleles are likely to be normal. These normal regions are predicted for each sample individually and used to calculate the final reference signal. NSA can be applied to any CN data regardless the microarray technology and preprocessing method. It also finds an optimal weighting of the samples minimizing possible batch effects. Results Five human datasets (a subset of HapMap samples, Glioblastoma Multiforme (GBM, Ovarian, Prostate and Lung Cancer experiments have been analyzed. It is shown that using only tumoral samples, NSA is able to remove the bias in the copy number estimation, to reduce the noise and therefore, to increase the ability to detect copy number aberrations (CNAs. These improvements allow NSA to also detect recurrent aberrations more accurately than other state of the art methods. Conclusions NSA provides a robust and accurate reference for scaling probe signals data to CN values without the need of control samples. It minimizes the problems of bias, noise and batch effects in the estimation of CNs. Therefore, NSA scaling approach helps to better detect recurrent CNAs than current methods. The automatic selection of references makes it useful to perform bulk analysis of many GEO or ArrayExpress experiments without the need of developing a parser to find the normal samples or possible batches within the

  6. Ribosomal DNA copy number loss and sequence variation in cancer.

    Science.gov (United States)

    Xu, Baoshan; Li, Hua; Perry, John M; Singh, Vijay Pratap; Unruh, Jay; Yu, Zulin; Zakari, Musinu; McDowell, William; Li, Linheng; Gerton, Jennifer L

    2017-06-01

    Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with mapping and analysis. We applied computational and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes. Counterintuitively, human cancer genomes show a loss of copies, accompanied by global copy number co-variation. The sequence can also be more variable in the cancer genome. Cancer genomes with lower copies have mutational evidence of mTOR hyperactivity. The PTEN phosphatase is a tumor suppressor that is critical for genome stability and a negative regulator of the mTOR kinase pathway. Surprisingly, but consistent with the human cancer genomes, hematopoietic cancer stem cells from a Pten-/- mouse model for leukemia have lower rDNA copy number than normal tissue, despite increased proliferation, rRNA production, and protein synthesis. Loss of copies occurs early and is associated with hypersensitivity to DNA damage. Therefore, copy loss is a recurrent feature in cancers associated with mTOR activation. Ribosomal DNA copy number may be a simple and useful indicator of whether a cancer will be sensitive to DNA damaging treatments.

  7. Identification of copy number variants in horses

    KAUST Repository

    Doan, R.

    2012-03-01

    Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds.

  8. Decoding NF1 Intragenic Copy-Number Variations.

    Science.gov (United States)

    Hsiao, Meng-Chang; Piotrowski, Arkadiusz; Callens, Tom; Fu, Chuanhua; Wimmer, Katharina; Claes, Kathleen B M; Messiaen, Ludwine

    2015-08-06

    Genomic rearrangements can cause both Mendelian and complex disorders. Currently, several major mechanisms causing genomic rearrangements, such as non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), fork stalling and template switching (FoSTeS), and microhomology-mediated break-induced replication (MMBIR), have been proposed. However, to what extent these mechanisms contribute to gene-specific pathogenic copy-number variations (CNVs) remains understudied. Furthermore, few studies have resolved these pathogenic alterations at the nucleotide-level. Accordingly, our aim was to explore which mechanisms contribute to a large, unique set of locus-specific non-recurrent genomic rearrangements causing the genetic neurocutaneous disorder neurofibromatosis type 1 (NF1). Through breakpoint-spanning PCR as well as array comparative genomic hybridization, we have identified the breakpoints in 85 unrelated individuals carrying an NF1 intragenic CNV. Furthermore, we characterized the likely rearrangement mechanisms of these 85 CNVs, along with those of two additional previously published NF1 intragenic CNVs. Unlike the most typical recurrent rearrangements mediated by flanking low-copy repeats (LCRs), NF1 intragenic rearrangements vary in size, location, and rearrangement mechanisms. We propose the DNA-replication-based mechanisms comprising both FoSTeS and/or MMBIR and serial replication stalling to be the predominant mechanisms leading to NF1 intragenic CNVs. In addition to the loop within a 197-bp palindrome located in intron 40, four Alu elements located in introns 1, 2, 3, and 50 were also identified as intragenic-rearrangement hotspots within NF1.

  9. Germline copy number variation and ovarian cancer survival

    Directory of Open Access Journals (Sweden)

    Brooke L Fridley

    2012-08-01

    Full Text Available Copy number variants (CNVs have been implicated in many complex diseases. We examined whether inherited CNVs were associated with overall survival among women with invasive epithelial ovarian cancer. Germline DNA from 1,056 cases (494 deceased, average of 3.7 years follow-up was interrogated with the Illumina 610quad genome-wide array containing, after quality control exclusions, 581,903 single nucleotide polymorphisms (SNPs and 17,917 CNV probes. Comprehensive analysis capitalized upon the strengths of three complementary approaches to CNV classification. First, to identify small CNVs, single markers were evaluated and, where associated with survival, consecutive markers were combined. Two chromosomal regions were associated with survival using this approach (14q31.3 rs2274736 p=1.59x10-6, p=0.001; 22q13.31 rs2285164 p=4.01x10-5, p=0.009, but were not significant after multiple testing correction. Second, to identify large CNVs, genome-wide segmentation was conducted to characterize chromosomal gains and losses, and association with survival was evaluated by segment. Four regions were associated with survival (1q21.3 loss p=0.005, 5p14.1 loss p=0.004, 9p23 loss p=0.002, and 15q22.31 gain p=0.002; however, again, after correcting for multiple testing, no regions were statistically significant, and none were in common with the single-marker approach. Finally, to evaluate associations with general amounts of copy number changes across the genome, we estimated CNV burden based on genome-wide numbers of gains and losses; no associations with survival were observed (p>0.40. Although CNVs that were not well-covered by the Illumina 610quad array merit investigation, these data suggest no association between inherited CNVs and survival after ovarian cancer.

  10. Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Yi-Hsuan Chen

    2014-02-01

    Full Text Available Bipolar disorder is a complex psychiatric disorder with high heritability, but its genetic determinants are still largely unknown. Copy number variation (CNV is one of the sources to explain part of the heritability. However, it is a challenge to estimate discrete values of the copy numbers using continuous signals calling from a set of markers, and to simultaneously perform association testing between CNVs and phenotypic outcomes. The goal of the present study is to perform a series of data filtering and analysis procedures using a DNA pooling strategy to identify potential CNV regions that are related to bipolar disorder. A total of 200 normal controls and 200 clinically diagnosed bipolar patients were recruited in this study, and were randomly divided into eight control and eight case pools. Genome-wide genotyping was employed using Illumina Human Omni1-Quad array with approximately one million markers for CNV calling. We aimed at setting a series of criteria to filter out the signal noise of marker data and to reduce the chance of false-positive findings for CNV regions. We first defined CNV regions for each pool. Potential CNV regions were reported based on the different patterns of CNV status between cases and controls. Genes that were mapped into the potential CNV regions were examined with association testing, Gene Ontology enrichment analysis, and checked with existing literature for their associations with bipolar disorder. We reported several CNV regions that are related to bipolar disorder. Two CNV regions on chromosome 11 and 22 showed significant signal differences between cases and controls (p < 0.05. Another five CNV regions on chromosome 6, 9, and 19 were overlapped with results in previous CNV studies. Experimental validation of two CNV regions lent some support to our reported findings. Further experimental and replication studies could be designed for these selected regions.

  11. BIOFILTER AS A FUNCTIONAL ANNOTATION PIPELINE FOR COMMON AND RARE COPY NUMBER BURDEN.

    Science.gov (United States)

    Kim, Dokyoon; Lucas, Anastasia; Glessner, Joseph; Verma, Shefali S; Bradford, Yuki; Li, Ruowang; Frase, Alex T; Hakonarson, Hakon; Peissig, Peggy; Brilliant, Murray; Ritchie, Marylyn D

    2016-01-01

    Recent studies on copy number variation (CNV) have suggested that an increasing burden of CNVs is associated with susceptibility or resistance to disease. A large number of genes or genomic loci contribute to complex diseases such as autism. Thus, total genomic copy number burden, as an accumulation of copy number change, is a meaningful measure of genomic instability to identify the association between global genetic effects and phenotypes of interest. However, no systematic annotation pipeline has been developed to interpret biological meaning based on the accumulation of copy number change across the genome associated with a phenotype of interest. In this study, we develop a comprehensive and systematic pipeline for annotating copy number variants into genes/genomic regions and subsequently pathways and other gene groups using Biofilter - a bioinformatics tool that aggregates over a dozen publicly available databases of prior biological knowledge. Next we conduct enrichment tests of biologically defined groupings of CNVs including genes, pathways, Gene Ontology, or protein families. We applied the proposed pipeline to a CNV dataset from the Marshfield Clinic Personalized Medicine Research Project (PMRP) in a quantitative trait phenotype derived from the electronic health record - total cholesterol. We identified several significant pathways such as toll-like receptor signaling pathway and hepatitis C pathway, gene ontologies (GOs) of nucleoside triphosphatase activity (NTPase) and response to virus, and protein families such as cell morphogenesis that are associated with the total cholesterol phenotype based on CNV profiles (permutation p-value Biofilter can be used for CNV data from any genotyping or sequencing platform and to explore CNV enrichment for any traits or phenotypes. Biofilter continues to be a powerful bioinformatics tool for annotating, filtering, and constructing biologically informed models for association analysis - now including copy number

  12. Copy number variation in the bovine genome

    DEFF Research Database (Denmark)

    Fadista, João; Thomsen, Bo; Holm, Lars-Erik;

    2010-01-01

    to genetic variation in cattle. Results We designed and used a set of NimbleGen CGH arrays that tile across the assayable portion of the cattle genome with approximately 6.3 million probes, at a median probe spacing of 301 bp. This study reports the highest resolution map of copy number variation...... in the cattle genome, with 304 CNV regions (CNVRs) being identified among the genomes of 20 bovine samples from 4 dairy and beef breeds. The CNVRs identified covered 0.68% (22 Mb) of the genome, and ranged in size from 1.7 to 2,031 kb (median size 16.7 kb). About 20% of the CNVs co-localized with segmental...

  13. The Double Copy Structure of Soft Gravitons

    CERN Document Server

    Vera, Agustin Sabio

    2014-01-01

    The subleading corrections to factorization theorems for soft bremsstrahlung in nonabelian gauge theories and gravity are investigated. Building on recent results, we write the action of the angular momentum operators on scattering amplitudes as derivatives with respect to the Mandelstam invariants to uncover a double copy structure in the contribution of the soft graviton to the amplitude, both in the leading term and the first correction. Using our approach, we study Gribov's theorem as extended to nonabelian gauge theories and gravity by Lipatov, and find that subleading corrections can be obtained from those to Low's theorem by dropping the terms with derivatives with respect to the center-of-mass energy, which are suppressed at high energies. In this case, the emitted gravitons are not necessarily soft.

  14. Double-copy constructions and unitarity cuts

    Science.gov (United States)

    Bern, Zvi; Davies, Scott; Nohle, Josh

    2016-05-01

    The duality between color and kinematics enables the construction of multiloop gravity integrands directly from corresponding gauge-theory integrands. This has led to new nontrivial insights into the structure of gravity theories, including the discovery of enhanced ultraviolet cancellations. To continue to gain deeper understandings and probe these new properties, it is crucial to further improve techniques for constructing multiloop gravity integrands. In this paper, we show by example how one can alleviate difficulties encountered at the multiloop level by relaxing the color-kinematics duality conditions to hold manifestly only on unitarity cuts instead of globally on loop integrands. As an example, we use a minimal Ansatz to construct an integrand for the two-loop four-point nonsupersymmetric pure Yang-Mills amplitude in D dimensions that is compatible with these relaxed color-kinematics duality constraints. We then immediately obtain a corresponding gravity integrand through the double-copy procedure. Comments on ultraviolet divergences are also included.

  15. Double-Copy Constructions and Unitarity Cuts

    CERN Document Server

    Bern, Zvi; Nohle, Josh

    2016-01-01

    The duality between color and kinematics enables the construction of multiloop gravity integrands directly from corresponding gauge-theory integrands. This has led to new nontrivial insights into the structure of gravity theories, including the discovery of enhanced ultraviolet cancellations. To continue to gain deeper understandings and probe these new properties, it is crucial to further improve techniques for constructing multiloop gravity integrands. In this paper, we show by example how one can alleviate difficulties encountered at the multiloop level by relaxing the color-kinematics duality conditions to hold manifestly only on unitarity cuts instead of globally on loop integrands. As an example, we use a minimal ansatz to construct an integrand for the two-loop four-point nonsupersymmetric pure Yang-Mills amplitude in $D$ dimensions that is compatible with these relaxed color-kinematics duality constraints. We then immediately obtain a corresponding gravity integrand through the double-copy procedure. ...

  16. Comparing Android Applications to Find Copying

    Directory of Open Access Journals (Sweden)

    Larry Melling

    2012-03-01

    Full Text Available The Android smartphone operating system includes a Java mobile development platform that provides for rapid development and deployment of a wide variety of applications. The open nature of the platform means that reverse engineering of applications is relatively easy, and many developers are concerned as applications similar to their own show up in the Android marketplace and want to know if these applications are pirated. Fortunately, the same characteristics that make an Android application easy to reverse engineer and copy also provide opportunities for Android developers to compare downloaded applications to their own. This paper describes the process for comparing a developer’s application with a downloaded application and defines an identifiability metric to quantify the degree to which an application can be identified by its bytecode.

  17. Copy-move forgery detection in digital image

    Science.gov (United States)

    Alamro, Loai; Yusoff, Nooraini

    2016-08-01

    Copy-move is considered as one of the most popular kind of digital image tempering, in which one or more parts of a digital image are copied and pasted into different locations. Geometric transformation is among the major challenges in detecting copy-move forgery of a digital image. In such forgery, the copied and moved parts of a forged image are either rotated or/and re-scaled. Hence, in this study we propose a combination of Discrete Wavelet Transform (DWT) and Speeded Up Robust Features (SURF) to detect a copy-move activity. The experiments results prove that the proposed method is superior with overall accuracy 95%. The copy-move attacks in digital image has been successfully detected and the method is also can detect the fraud parts exposed to rotation and scaling issue.

  18. The standardised copy of pentagons test

    Directory of Open Access Journals (Sweden)

    Terzoglou Vassiliki A

    2011-04-01

    Full Text Available Abstract Background The 'double-diamond copy' task is a simple paper and pencil test part of the Bender-Gestalt Test and the Mini Mental State Examination (MMSE. Although it is a widely used test, its method of scoring is crude and its psychometric properties are not adequately known. The aim of the present study was to develop a sensitive and reliable method of administration and scoring. Methods The study sample included 93 normal control subjects (53 women and 40 men aged 35.87 ± 12.62 and 127 patients suffering from schizophrenia (54 women and 73 men aged 34.07 ± 9.83. Results The scoring method was based on the frequencies of responses of healthy controls and proved to be relatively reliable with Cronbach's α equal to 0.61, test-retest correlation coefficient equal to 0.41 and inter-rater reliability equal to 0.52. The factor analysis produced two indices and six subscales of the Standardised Copy of Pentagons Test (SCPT. The total score as well as most of the individual items and subscales distinguished between controls and patients. The discriminant function correctly classified 63.44% of controls and 75.59% of patients. Discussion The SCPT seems to be a satisfactory, reliable and valid instrument, which is easy to administer, suitable for use in non-organic psychiatric patients and demands minimal time. Further research is necessary to test its psychometric properties and its usefulness and applications as a neuropsychological test.

  19. 38 CFR 1.526 - Copies of records and papers.

    Science.gov (United States)

    2010-07-01

    ... papers. 1.526 Section 1.526 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Copies of records and papers. (a) Any person desiring a copy of any record or document in the custody of... plain one-sided paper copies of a standard size (81/2″ × 11″; 81/2″ × 14″; 11″ × 14″) $0.15 per...

  20. Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability.

    Science.gov (United States)

    Beckmann, Jacques S; Estivill, Xavier; Antonarakis, Stylianos E

    2007-08-01

    A considerable and unanticipated plasticity of the human genome, manifested as inter-individual copy number variation, has been discovered. These structural changes constitute a major source of inter-individual genetic variation that could explain variable penetrance of inherited (Mendelian and polygenic) diseases and variation in the phenotypic expression of aneuploidies and sporadic traits, and might represent a major factor in the aetiology of complex, multifactorial traits. For these reasons, an effort should be made to discover all common and rare copy number variants (CNVs) in the human population. This will also enable systematic exploration of both SNPs and CNVs in association studies to identify the genomic contributors to the common disorders and complex traits.

  1. Quantum Copying Beyond the No-Cloning Theorem

    CERN Document Server

    Buzek, V; Buzek, Vladimir; Hillery, Mark

    1996-01-01

    We analyze to what extent it is possible to copy arbitrary states of a two-level quantum system. We show that there exists a "universal quantum copying machine", which approximately copies quantum mechanical states in such a way that the quality of its output does not depend on the input. We also examine a machine which combines a unitary transformation with a selective measurement to produce good copies of states in a neighborhood of a particular state. We discuss the problem of measurement of the output states.

  2. Rsp5 ubiquitin ligase is required for protein trafficking in Saccharomyces cerevisiae COPI mutants.

    Directory of Open Access Journals (Sweden)

    Katarzyna Jarmoszewicz

    Full Text Available Retrograde trafficking from the Golgi to the endoplasmic reticulum (ER depends on the formation of vesicles coated with the multiprotein complex COPI. In Saccharomyces cerevisiae ubiquitinated derivatives of several COPI subunits have been identified. The importance of this modification of COPI proteins is unknown. With the exception of the Sec27 protein (β'COP neither the ubiquitin ligase responsible for ubiquitination of COPI subunits nor the importance of this modification are known. Here we find that the ubiquitin ligase mutation, rsp5-1, has a negative effect that is additive with ret1-1 and sec28Δ mutations, in genes encoding α- and ε-COP, respectively. The double ret1-1 rsp5-1 mutant is also more severely defective in the Golgi-to-ER trafficking compared to the single ret1-1, secreting more of the ER chaperone Kar2p, localizing Rer1p mostly to the vacuole, and increasing sensitivity to neomycin. Overexpression of ubiquitin in ret1-1 rsp5-1 mutant suppresses vacuolar accumulation of Rer1p. We found that the effect of rsp5 mutation on the Golgi-to-ER trafficking is similar to that of sla1Δ mutation in a gene encoding actin cytoskeleton proteins, an Rsp5p substrate. Additionally, Rsp5 and Sla1 proteins were found by co-immunoprecipitation in a complex containing COPI subunits. Together, our results show that Rsp5 ligase plays a role in regulating retrograde Golgi-to-ER trafficking.

  3. Genome-wide copy number analysis using copy number inferring tool (CNIT) and DNA pooling.

    Science.gov (United States)

    Lin, Chien-hsing; Huang, Mei-chu; Li, Ling-hui; Wu, Jer-yuarn; Chen, Yuan-tsong; Fann, Cathy S J

    2008-08-01

    Copy number variation (CNV) has become an important genomic structure element in the human population, and some CNVs are related to specific traits and diseases. Moreover, analysis of human genomes has been potentiated by the use of high-resolution microarrays that assess single nucleotide polymorphisms (SNPs). Although many programs have been designed to analyze data from Affymetrix SNP microarrays, they all have high false-positive rates (FPRs) in copy number (CN) analyses. Copy number analysis tool (CNAT) 4.0 is a recently developed program that offers improved CN estimation, but small amplifications and deletions are lost when using the smoothing procedure. Here, we propose a copy number inferring tool (CNIT) algorithm for the 100K SNP microarray to investigate CNVs at 29.6-kb resolution. CNIT estimated SNP allelic and total CN with reliable P values based on intensity data. In addition, the hidden Markov model (HMM) method was applied to predict regions having altered CN by considering contiguous SNPs. Based on a CN analysis of 23 unrelated Taiwanese and 30 HapMap Centre d'Etude du Polymorphisme Humain (CEPH) trios, CNIT showed higher accuracy and power than other programs. The FPRs and false-negative rates (FNRs) of CNIT were 0.1% and 0.16%, respectively. CNIT also showed better sensitivity for detecting small amplifications and deletions. Furthermore, DNA pooling of 10 and 30 normal unrelated individuals were applied to the 100K SNP microarray, respectively, and 12 common CN-variable regions were identified, suggesting that DNA pooling can be applied to discover common CNVs.

  4. rSW-seq: Algorithm for detection of copy number alterations in deep sequencing data

    Directory of Open Access Journals (Sweden)

    Kim Tae-Min

    2010-08-01

    Full Text Available Abstract Background Recent advances in sequencing technologies have enabled generation of large-scale genome sequencing data. These data can be used to characterize a variety of genomic features, including the DNA copy number profile of a cancer genome. A robust and reliable method for screening chromosomal alterations would allow a detailed characterization of the cancer genome with unprecedented accuracy. Results We develop a method for identification of copy number alterations in a tumor genome compared to its matched control, based on application of Smith-Waterman algorithm to single-end sequencing data. In a performance test with simulated data, our algorithm shows >90% sensitivity and >90% precision in detecting a single copy number change that contains approximately 500 reads for the normal sample. With 100-bp reads, this corresponds to a ~50 kb region for 1X genome coverage of the human genome. We further refine the algorithm to develop rSW-seq, (recursive Smith-Waterman-seq to identify alterations in a complex configuration, which are commonly observed in the human cancer genome. To validate our approach, we compare our algorithm with an existing algorithm using simulated and publicly available datasets. We also compare the sequencing-based profiles to microarray-based results. Conclusion We propose rSW-seq as an efficient method for detecting copy number changes in the tumor genome.

  5. Copy number polymorphisms in new HapMap III and Singapore populations.

    Science.gov (United States)

    Ku, Chee-Seng; Teo, Shu-Mei; Naidoo, Nasheen; Sim, Xueling; Teo, Yik-Ying; Pawitan, Yudi; Seielstad, Mark; Chia, Kee-Seng; Salim, Agus

    2011-08-01

    Copy number variations can be identified using newer genotyping arrays with higher single nucleotide polymorphisms (SNPs) density and copy number probes accompanied by newer algorithms. McCarroll et al. (2008) applied these to the HapMap II samples and identified 1316 copy number polymorphisms (CNPs). In our study, we applied the same approach to 859 samples from three Singapore populations and seven HapMap III populations. Approximately 50% of the 1291 autosomal CNPs were found to be polymorphic only in populations of non-African ancestry. Pairwise comparisons among the 10 populations showed substantial differences in the CNPs frequencies. Additionally, 698 CNPs showed significant differences with false discovery rate (FDR)macular degeneration), GSTTI (metabolism of various carcinogenic compounds and cancers) and UGT2B17 (prostate cancer and graft-versus-host disease). The correlations between CNPs and genome-wide association studies-SNPs were investigated and several loci, which were previously unreported, that may potentially be implicated in complex diseases and traits were found; for example, childhood acute lymphoblastic leukaemia, age-related macular degeneration, breast cancer, response to antipsychotic treatment, rheumatoid arthritis and type-1 diabetes. Additionally, we also found 5014 novel copy number loci that have not been reported previously by McCarroll et al. (2008) in the 10 populations.

  6. An evaluation of new and established methods to determine T-DNA copy number and homozygosity in transgenic plants.

    Science.gov (United States)

    Głowacka, Katarzyna; Kromdijk, Johannes; Leonelli, Lauriebeth; Niyogi, Krishna K; Clemente, Tom E; Long, Stephen P

    2016-04-01

    Stable transformation of plants is a powerful tool for hypothesis testing. A rapid and reliable evaluation method of the transgenic allele for copy number and homozygosity is vital in analysing these transformations. Here the suitability of Southern blot analysis, thermal asymmetric interlaced (TAIL-)PCR, quantitative (q)PCR and digital droplet (dd)PCR to estimate T-DNA copy number, locus complexity and homozygosity were compared in transgenic tobacco. Southern blot analysis and ddPCR on three generations of transgenic offspring with contrasting zygosity and copy number were entirely consistent, whereas TAIL-PCR often underestimated copy number. qPCR deviated considerably from the Southern blot results and had lower precision and higher variability than ddPCR. Comparison of segregation analyses and ddPCR of T1 progeny from 26 T0 plants showed that at least 19% of the lines carried multiple T-DNA insertions per locus, which can lead to unstable transgene expression. Segregation analyses failed to detect these multiple copies, presumably because of their close linkage. This shows the importance of routine T-DNA copy number estimation. Based on our results, ddPCR is the most suitable method, because it is as reliable as Southern blot analysis yet much faster. A protocol for this application of ddPCR to large plant genomes is provided.

  7. Mitochondrial DNA copy numbers in pyramidal neurons are decreased and mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer's disease hippocampi.

    Science.gov (United States)

    Rice, Ann C; Keeney, Paula M; Algarzae, Norah K; Ladd, Amy C; Thomas, Ravindar R; Bennett, James P

    2014-01-01

    Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers compared to CTL neurons. Pyramidal neuron mtDNA copy numbers in CTL, but not AD, positively correlated with cDNA levels of multiple mitobiogenesis genes. In CTL, but not in AD, hippocampal cDNA levels of PGC1α were positively correlated with multiple downstream mitobiogenesis factors. Mitochondrial DNA copy numbers in pyramidal neurons did not correlate with hippocampal Aβ1-42 levels. After 48 h exposure of H9 human neural stem cells to the neurotoxic fragment Aβ25-35, mtDNA copy numbers were not significantly altered. In summary, AD postmortem hippocampal pyramidal neurons have reduced mtDNA copy numbers. Mitochondrial biogenesis pathway signaling relationships are disrupted in AD, but are mostly preserved in CTL. Our findings implicate complex alterations of mitochondria-host cell relationships in AD.

  8. Accuracy estimation of foamy virus genome copying

    Directory of Open Access Journals (Sweden)

    Rethwilm Axel

    2009-04-01

    Full Text Available Abstract Background Foamy viruses (FVs are the most genetically stable viruses of the retrovirus family. This is in contrast to the in vitro error rate found for recombinant FV reverse transcriptase (RT. To investigate the accuracy of FV genome copying in vivo we analyzed the occurrence of mutations in HEK 293T cell culture after a single round of reverse transcription using a replication-deficient vector system. Furthermore, the frequency of FV recombination by template switching (TS and the cross-packaging ability of different FV strains were analyzed. Results We initially sequenced 90,000 nucleotides and detected 39 mutations, corresponding to an in vivo error rate of approximately 4 × 10-4 per site per replication cycle. Surprisingly, all mutations were transitions from G to A, suggesting that APOBEC3 activity is the driving force for the majority of mutations detected in our experimental system. In line with this, we detected a late but significant APOBEC3G and 3F mRNA by quantitative PCR in the cells. We then analyzed 170,000 additional nucleotides from experiments in which we co-transfected the APOBEC3-interfering foamy viral bet gene and observed a significant 50% drop in G to A mutations, indicating that APOBEC activity indeed contributes substantially to the foamy viral replication error rate in vivo. However, even in the presence of Bet, 35 out of 37 substitutions were G to A, suggesting that residual APOBEC activity accounted for most of the observed mutations. If we subtract these APOBEC-like mutations from the total number of mutations, we calculate a maximal intrinsic in vivo error rate of 1.1 × 10-5 per site per replication. In addition to the point mutations, we detected one 49 bp deletion within the analyzed 260000 nucleotides. Analysis of the recombination frequency of FV vector genomes revealed a 27% probability for a template switching (TS event within a 1 kilobase (kb region. This corresponds to a 98% probability that FVs

  9. 45 CFR 1703.404 - Copying and transcription charges.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Copying and transcription charges. 1703.404... Copying and transcription charges. (a) The Commission will charge fees for furnishing records at the rate of ten cents per page for photocopies and at the actual cost of transcription. When the...

  10. Cover-Copy-Compare and Spelling: One versus Three Repetitions

    Science.gov (United States)

    Erion, Joel; Davenport, Cindy; Rodax, Nicole; Scholl, Bethany; Hardy, Jennifer

    2009-01-01

    Cover, copy, compare (CCC) has been used with success to improve spelling skills. This study adds to existing research by completing an analysis of the rewriting component of the intervention. The impact of varying the number of times a subject copied a word following an error was examined with four elementary age students. An adaptive alternating…

  11. Perceiving the Impossible: How Individuals with Autism Copy Paradoxical Figures

    Science.gov (United States)

    Sheppard, Elizabeth; Ropar, Danielle; Mitchell, Peter

    2009-01-01

    Mottron and colleagues found that individuals with autism were less affected by geometric impossibility than comparison participants on a copying task. The current experiment sought to determine whether a local perceptual style could account for this. Participants with and without autism copied possible and impossible geometric figures. Geometric…

  12. 48 CFR 6302.25 - Copies of papers (Rule 25).

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Copies of papers (Rule 25). 6302.25 Section 6302.25 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION BOARD OF CONTRACT APPEALS RULES OF PROCEDURE 6302.25 Copies of papers (Rule 25). When books, records, papers,...

  13. Re-thinking copyright through the copy in Russia

    NARCIS (Netherlands)

    Sezneva, O.

    2013-01-01

    How one copy of a film or a single is made illegal, while its identical twin is treated as legitimate? By drawing from the material collected in Russia on the illegal copying and distribution of video and musical contents, this paper moves beyond the definition of media piracy in legal terms, and

  14. 7 CFR 3701.2 - Public inspection, copying, and indexing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Public inspection, copying, and indexing. 3701.2 Section 3701.2 Agriculture Regulations of the Department of Agriculture (Continued) ECONOMIC RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE PUBLIC INFORMATION § 3701.2 Public inspection, copying, and indexing....

  15. 7 CFR 3801.2 - Public inspection, copying, and indexing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Public inspection, copying, and indexing. 3801.2 Section 3801.2 Agriculture Regulations of the Department of Agriculture (Continued) WORLD AGRICULTURAL... inspection, copying, and indexing. 5 U.S.C. 552(a)(2) requires that certain materials be made available...

  16. 7 CFR 3404.2 - Public inspection, copying, and indexing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Public inspection, copying, and indexing. 3404.2 Section 3404.2 Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE... inspection, copying, and indexing. 5 U.S.C. 552(a)(2) requires that certain materials be made available...

  17. 7 CFR 510.2 - Public inspection, copying, and indexing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Public inspection, copying, and indexing. 510.2 Section 510.2 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE PUBLIC INFORMATION § 510.2 Public inspection, copying, and indexing....

  18. 27 CFR 25.301 - Photographic copies of records.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Photographic copies of records. 25.301 Section 25.301 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS BEER Records and Reports § 25.301 Photographic copies...

  19. Re-thinking copyright through the copy in Russia

    NARCIS (Netherlands)

    Sezneva, O.

    2013-01-01

    How one copy of a film or a single is made illegal, while its identical twin is treated as legitimate? By drawing from the material collected in Russia on the illegal copying and distribution of video and musical contents, this paper moves beyond the definition of media piracy in legal terms, and in

  20. 40 CFR 716.30 - Submission of copies of studies.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Submission of copies of studies. 716.30 Section 716.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.30 Submission of copies of...

  1. Cache-based memory copy hardware accelerator for multicore systems

    NARCIS (Netherlands)

    Duarte, F.; Wong, S.

    2010-01-01

    In this paper, we present a new architecture of the cache-based memory copy hardware accelerator in a multicore system supporting message passing. The accelerator is able to accelerate memory data movements, in particular memory copies. We perform an analytical analysis based on open-queuing theory

  2. Schizophrenia copy number variants and associative learning

    Science.gov (United States)

    Clifton, N E; Pocklington, A J; Scholz, B; Rees, E; Walters, J T R; Kirov, G; O'Donovan, M C; Owen, M J; Wilkinson, L S; Thomas, K L; Hall, J

    2017-01-01

    Large-scale genomic studies have made major progress in identifying genetic risk variants for schizophrenia. A key finding from these studies is that there is an increased burden of genomic copy number variants (CNVs) in schizophrenia cases compared with controls. The mechanism through which these CNVs confer risk for the symptoms of schizophrenia, however, remains unclear. One possibility is that schizophrenia risk CNVs impact basic associative learning processes, abnormalities of which have long been associated with the disorder. To investigate whether genes in schizophrenia CNVs impact on specific phases of associative learning we combined human genetics with experimental gene expression studies in animals. In a sample of 11 917 schizophrenia cases and 16 416 controls, we investigated whether CNVs from patients with schizophrenia are enriched for genes expressed during the consolidation, retrieval or extinction of associative memories. We show that CNVs from cases are enriched for genes expressed during fear extinction in the hippocampus, but not genes expressed following consolidation or retrieval. These results suggest that CNVs act to impair inhibitory learning in schizophrenia, potentially contributing to the development of core symptoms of the disorder. PMID:27956746

  3. Association of nsv823469 copy number loss with decreased risk of chronic obstructive pulmonary disease and pulmonary function in Chinese.

    Science.gov (United States)

    Chen, Xiaoliang; Lu, Xiaoxiao; Chen, Jiansong; Wu, Di; Qiu, Fuman; Xiong, Huali; Pan, Zihua; Yang, Lei; Yang, Binyao; Xie, Chenli; Zhou, Yifeng; Huang, Dongsheng; Zhou, Yumin; Lu, Jiachun

    2017-01-12

    It is highly possible that copy number variations (CNVs) in susceptible regions have effects on chronic obstructive pulmonary disease (COPD) development, while long noncoding RNA (lncRNAs) have been shown to cause COPD. We hypothesized that the common CNV, named nsv823469 located on 6p22.1, and covering lncRNAs (major histocompatibility complex, class I, A (HLA-A) and HLA complex group 4B (HCG4B)) has an effect on COPD risk. This association was assessed through a two-stage case-control study, and was further confirmed with COPD and pulmonary function-based family analyses, respectively. The copy number loss (0-copy/1-copy) of nsv823469 significantly decreased risk of COPD compared with normal (2-copy) (OR = 0.77, 95% CI = 0.69-0.85). The loss allele, inducing copy number loss of nsv823469, has a tendency to transmit to offspring or siblings (P = 0.010) and is associated with forced expiratory volume in 1 second (FEV1) (P = 0.030). Furthermore, the copy number loss of nsv823469 in normal pulmonary tissue decreases the expression levels of HCG4B (r = 0.315, P = 0.031) and HLA-A (r = 0.296, P = 0.044). Our data demonstrates that nsv823469 plays a role in COPD and pulmonary function inheritance by potentially altering expression of HCG4B.

  4. Characterization of an inducible promoter in different DNA copy number conditions.

    Science.gov (United States)

    Zucca, Susanna; Pasotti, Lorenzo; Mazzini, Giuliano; De Angelis, Maria Gabriella Cusella; Magni, Paolo

    2012-03-28

    The bottom-up programming of living organisms to implement novel user-defined biological capabilities is one of the main goals of synthetic biology. Currently, a predominant problem connected with the construction of even simple synthetic biological systems is the unpredictability of the genetic circuitry when assembled and incorporated in living cells. Copy number, transcriptional/translational demand and toxicity of the DNA-encoded functions are some of the major factors which may lead to cell overburdening and thus to nonlinear effects on system output. It is important to disclose the linearity working boundaries of engineered biological systems when dealing with such phenomena. The output of an N-3-oxohexanoyl-L-homoserine lactone (HSL)-inducible RFP-expressing device was studied in Escherichia coli in different copy number contexts, ranging from 1 copy per cell (integrated in the genome) to hundreds (via multicopy plasmids). The system is composed by a luxR constitutive expression cassette and a RFP gene regulated by the luxI promoter, which is activated by the HSL-LuxR complex. System output, in terms of promoter activity as a function of HSL concentration, was assessed relative to the one of a reference promoter in identical conditions by using the Relative Promoter Units (RPU) approach. Nonlinear effects were observed in the maximum activity, which is identical in single and low copy conditions, while it decreases for higher copy number conditions. In order to properly compare the luxI promoter strength among all the conditions, a mathematical modeling approach was used to relate the promoter activity to the estimated HSL-LuxR complex concentration, which is the actual activator of transcription. During model fitting, a correlation between the copy number and the dissociation constant of HSL-LuxR complex and luxI promoter was observed. Even in a simple inducible system, nonlinear effects are observed and non-trivial data processing is necessary to fully

  5. The double copy: Bremsstrahlung and accelerating black holes

    CERN Document Server

    Luna, Andres; Nicholson, Isobel; O'Connell, Donal; White, Chris D

    2016-01-01

    Advances in our understanding of perturbation theory suggest the existence of a correspondence between classical general relativity and Yang-Mills theory. A concrete example of this correspondence, which is known as the double copy, was recently introduced for the case of stationary Kerr-Schild spacetimes. Building on this foundation, we examine the simple time-dependent case of an accelerating, radiating point source. The gravitational solution, which generalises the Schwarzschild solution, includes a non-trivial stress-energy tensor. This stress-energy tensor corresponds to a gauge theoretic current in the double copy. We interpret both of these sources as representing the radiative part of the field. Furthermore, in the simple example of Bremsstrahlung, we determine a scattering amplitude describing the radiation, maintaining the double copy throughout. Our results provide the strongest evidence yet that the classical double copy is directly related to the BCJ double copy for scattering amplitudes.

  6. CNARA: reliability assessment for genomic copy number profiles.

    Science.gov (United States)

    Ai, Ni; Cai, Haoyang; Solovan, Caius; Baudis, Michael

    2016-10-12

    DNA copy number profiles from microarray and sequencing experiments sometimes contain wave artefacts which may be introduced during sample preparation and cannot be removed completely by existing preprocessing methods. Besides, large derivative log ratio spread (DLRS) of the probes correlating with poor DNA quality is sometimes observed in genome screening experiments and may lead to unreliable copy number profiles. Depending on the extent of these artefacts and the resulting misidentification of copy number alterations/variations (CNA/CNV), it may be desirable to exclude such samples from analyses or to adapt the downstream data analysis strategy accordingly. Here, we propose a method to distinguish reliable genomic copy number profiles from those containing heavy wave artefacts and/or large DLRS. We define four features that adequately summarize the copy number profiles for reliability assessment, and train a classifier on a dataset of 1522 copy number profiles from various microarray platforms. The method can be applied to predict the reliability of copy number profiles irrespective of the underlying microarray platform and may be adapted for those sequencing platforms from which copy number estimates could be computed as a piecewise constant signal. Further details can be found at https://github.com/baudisgroup/CNARA . We have developed a method for the assessment of genomic copy number profiling data, and suggest to apply the method in addition to and after other state-of-the-art noise correction and quality control procedures. CNARA could be instrumental in improving the assessment of data used for genomic data mining experiments and support the reliable functional attribution of copy number aberrations especially in cancer research.

  7. The Differential Effects of Two Self-Managed Math Instruction Procedures: Cover, Copy, and Compare versus Copy, Cover, and Compare

    Science.gov (United States)

    Grafman, Joel M.; Cates, Gary L.

    2010-01-01

    This study compared the fluency and error rates produced when using the Cover, Copy, and Compare (CCC) and a modified CCC procedure (MCCC) called Copy, Cover, and Compare to complete subtraction math problems. Two second-grade classrooms consisting of 47 total students participated in the study. The following items were administered to…

  8. Eclipse period of R1 plasmids during downshift from elevated copy number: Nonrandom selection of copies for replication.

    Science.gov (United States)

    Olsson, Jan A; Berg, Otto; Nordström, Kurt; Dasgupta, Santanu

    2012-03-01

    The classical Meselson-Stahl density-shift method was used to study replication of pOU71, a runaway-replication derivative of plasmid R1 in Escherichia coli. The miniplasmid maintained the normal low copy number of R1 during steady growth at 30°C, but as growth temperatures were raised above 34°C, the copy number of the plasmid increased to higher levels, and at 42°C, it replicated without control in a runaway replication mode with lethal consequences for the host. The eclipse periods (minimum time between successive replication of the same DNA) of the plasmid shortened with rising copy numbers at increasing growth temperatures (Olsson et al., 2003). In this work, eclipse periods were measured during downshifts in copy number of pOU71 after it had replicated at 39 and 42°C, resulting in 7- and 50-fold higher than normal plasmid copy number per cell, respectively. Eclipse periods for plasmid replication, measured during copy number downshift, suggested that plasmid R1, normally selected randomly for replication, showed a bias such that a newly replicated DNA had a higher probability of replication compared to the bulk of the R1 population. However, even the unexpected nonrandom replication followed the copy number kinetics such that every generation, the plasmids underwent the normal inherited number of replication, n, independent of the actual number of plasmid copies in a newborn cell.

  9. Genetic copy number variation and general cognitive ability.

    Directory of Open Access Journals (Sweden)

    Andrew K MacLeod

    Full Text Available Differences in genomic structure between individuals are ubiquitous features of human genetic variation. Specific copy number variants (CNVs have been associated with susceptibility to numerous complex psychiatric disorders, including attention-deficit-hyperactivity disorder, autism-spectrum disorders and schizophrenia. These disorders often display co-morbidity with low intelligence. Rare chromosomal deletions and duplications are associated with these disorders, so it has been suggested that these deletions or duplications may be associated with differences in intelligence. Here we investigate associations between large (≥500kb, rare (<1% population frequency CNVs and both fluid and crystallized intelligence in community-dwelling older people. We observe no significant associations between intelligence and total CNV load. Examining individual CNV regions previously implicated in neuropsychological disorders, we find suggestive evidence that CNV regions around SHANK3 are associated with fluid intelligence as derived from a battery of cognitive tests. This is the first study to examine the effects of rare CNVs as called by multiple algorithms on cognition in a large non-clinical sample, and finds no effects of such variants on general cognitive ability.

  10. Copy number variation in the horse genome.

    Directory of Open Access Journals (Sweden)

    Sharmila Ghosh

    2014-10-01

    Full Text Available We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches.

  11. Copy number variation in the horse genome.

    Science.gov (United States)

    Ghosh, Sharmila; Qu, Zhipeng; Das, Pranab J; Fang, Erica; Juras, Rytis; Cothran, E Gus; McDonell, Sue; Kenney, Daniel G; Lear, Teri L; Adelson, David L; Chowdhary, Bhanu P; Raudsepp, Terje

    2014-10-01

    We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches.

  12. Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Hoh Boon-Peng

    Full Text Available Left ventricular hypertrophy (LVH is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the "foetal cardiac gene programme" which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability.

  13. Genomic variability in Mexican chicken population using Copy Number Variation

    Directory of Open Access Journals (Sweden)

    Erica Gorla

    2017-05-01

    Full Text Available Copy number variants (CNVs are polymorphisms which influence phenotypic variation and are an important source of genetic variability [1]. In Mexico the backyard poultry population is a unique widespread Creole chicken (Gallus gallus domesticus population, an undefined cross among different breeds brought to Mexico from Europe and under natural selection for almost 500 years [2-3]. The aim of this study was to investigate genomic variation in the Mexican chicken population using CNVs. A total of 256 DNA samples genotyped with Axiom® Genome-Wide Chicken Genotyping Array were used in the analyses. The individual CNV calling, based on log-R ratio and B-allele frequency values, was performed using the Hidden Markov Model (HMM of PennCNV software on the autosomes [4-5]. CNVs were summarized to CNV regions (CNVRs at a population level (i.e. overlapping CNVs, using BEDTools. The HMM detected a total of 1924 CNVs in the genome of 256 samples resulting, at population level, in 1216 CNV regions, of which 959 gains, 226 losses and 31 complex CNVRs (i.e. containing both losses and gains, covering a total of 47 Mb of sequence length corresponding to 5,12 % of the chicken galGal4 assembly autosome. A comparison among this study and 7 previous reports about CNVs in chicken was performed, finding that the 1,216 CNVRs detected in this study overlap with 617 regions (51% mapped by others studies.   This study allowed a deep insight into the structural variation in the genome of unselected Mexican chicken population, which up to now has not been never genetically characterized with SNP markers. Based on a cluster analysis (pvclust – R package on CNV markers the population, even if presenting extreme morphological variation, does not resulted divided in differentiated genetic subpopulations. Finally this study provides a CNV map based on the 600K SNP chip array jointly with a genome-wide gene copy number estimates in Mexican chicken population.

  14. Mitochondrial DNA copy number in peripheral blood and melanoma risk.

    Directory of Open Access Journals (Sweden)

    Jie Shen

    Full Text Available Mitochondrial DNA (mtDNA copy number in peripheral blood has been suggested as risk modifier in various types of cancer. However, its influence on melanoma risk is unclear. We evaluated the association between mtDNA copy number in peripheral blood and melanoma risk in 500 melanoma cases and 500 healthy controls from an ongoing melanoma study. The mtDNA copy number was measured using real-time polymerase chain reaction. Overall, mean mtDNA copy number was significantly higher in cases than in controls (1.15 vs 0.99, P<0.001. Increased mtDNA copy number was associated with a 1.45-fold increased risk of melanoma (95% confidence interval: 1.12-1.97. Significant joint effects between mtDNA copy number and variables related to pigmentation and history of sunlight exposure were observed. This study supports an association between increased mtDNA copy number and melanoma risk that is independent on the known melanoma risk factors (pigmentation and history of sunlight exposure.

  15. Memory Copy Optimization for Streaming Gateway Transco ding:Mo dels and Algorithms

    Institute of Scientific and Technical Information of China (English)

    LI Mingzhe; WANG Jinlin; CHEN Xiao; YE Xiaozhou

    2016-01-01

    Repeated memory copy during proto-col translation inhibits capacity of a streaming media gateway. Unlike existing optimization techniques that rely on platform-specific features, this paper investigates algorithm-level platform-independent strategies. A math-ematical concept of the buf-string is proposed to model the protocol transcoding process. Based on this model three payload extraction algorithms that can reduce mem-ory copy are presented. The streaming gateway used in the Next-generation broadcasting (NGB) and the Next-generation on-demand (NGOD) system is taken as an ex-ample to demonstrate and evaluate our strategies. Experi-mental results from an x86 host and an embedded system prove that our strategies can reduce CPU overhead by 15%to 45%, and optimize the linear space complexity to a con-stant one.

  16. Complexity of Formation in Holography

    CERN Document Server

    Chapman, Shira; Myers, Robert C

    2016-01-01

    It was recently conjectured that the quantum complexity of a holographic boundary state can be computed by evaluating the gravitational action on a bulk region known as the Wheeler-DeWitt patch. We apply this complexity=action duality to evaluate the `complexity of formation' (arXiv:1509.07876, arXiv:1512.04993), i.e., the additional complexity arising in preparing the entangled thermofield double state with two copies of the boundary CFT compared to preparing the individual vacuum states of the two copies. We find that for boundary dimensions $d>2$, the difference in the complexities grows linearly with the thermal entropy at high temperatures. For the special case $d=2$, the complexity of formation is a fixed constant, independent of the temperature. We compare these results to those found using the complexity=volume duality.

  17. Complexity of formation in holography

    Science.gov (United States)

    Chapman, Shira; Marrochio, Hugo; Myers, Robert C.

    2017-01-01

    It was recently conjectured that the quantum complexity of a holographic boundary state can be computed by evaluating the gravitational action on a bulk region known as the Wheeler-DeWitt patch. We apply this complexity=action duality to evaluate the `complexity of formation' [1, 2], i.e. the additional complexity arising in preparing the entangled thermofield double state with two copies of the boundary CFT compared to preparing the individual vacuum states of the two copies. We find that for boundary dimensions d > 2, the difference in the complexities grows linearly with the thermal entropy at high temperatures. For the special case d = 2, the complexity of formation is a fixed constant, independent of the temperature. We compare these results to those found using the complexity=volume duality.

  18. Properly coloured copies and rainbow copies of large graphs with small maximum degree

    CERN Document Server

    Böttcher, Julia; Procacci, Aldo

    2010-01-01

    Let G be a graph on n vertices with maximum degree D. We use the Lov\\'asz local lemma to show the following two results about colourings c of the edges of the complete graph K_n. If for each vertex v of K_n the colouring c assigns each colour to at most (n-2)/22.4D^2 edges emanating from v, then there is a copy of G in K_n which is properly edge-coloured by c. This improves on a result of Alon, Jiang, Miller, and Pritikin [Random Struct. Algorithms 23(4), 409-433, 2003]. On the other hand, if c assigns each colour to at most n/51D^2 edges of K_n, then there is a copy of G in K_n such that each edge of G receives a different colour from c. This proves a conjecture of Frieze and Krivelevich [Electron. J. Comb. 15(1), R59, 2008]. Our proofs rely on a framework developed by Lu and Sz\\'ekely [Electron. J. Comb. 14(1), R63, 2007] for applying the local lemma to random injections. In order to improve the constants in our results we use a version of the local lemma due to Bissacot, Fern\\'andez, Procacci, and Scoppola...

  19. The classical double copy for Taub-NUT spacetime

    CERN Document Server

    Luna, A; O'Connell, D; White, C D

    2015-01-01

    The double copy is a much-studied relationship between gauge theory and gravity amplitudes. Recently, this was generalised to an infinite family of classical solutions to Einstein's equations, namely stationary Kerr-Schild geometries. In this paper, we extend this to the Taub-NUT solution in gravity, which has a double Kerr-Schild form. The single copy of this solution is a dyon, whose electric and magnetic charges are related to the mass and NUT charge in the gravity theory. Finally, we find hints that the classical double copy extends to curved background geometries.

  20. The classical double copy for Taub-NUT spacetime

    Science.gov (United States)

    Luna, Andrés; Monteiro, Ricardo; O'Connell, Donal; White, Chris D.

    2015-11-01

    The double copy is a much-studied relationship between gauge theory and gravity amplitudes. Recently, this was generalised to an infinite family of classical solutions to Einstein's equations, namely stationary Kerr-Schild geometries. In this paper, we extend this to the Taub-NUT solution in gravity, which has a double Kerr-Schild form. The single copy of this solution is a dyon, whose electric and magnetic charges are related to the mass and NUT charge in the gravity theory. Finally, we find hints that the classical double copy extends to curved background geometries.

  1. Copy number gain of VCX, X-linked multi-copy gene, leads to cell proliferation and apoptosis during spermatogenesis

    Science.gov (United States)

    Ji, Juan; Qin, Yufeng; Wang, Rong; Huang, Zhenyao; Zhang, Yan; Zhou, Ran; Song, Ling; Ling, Xiufeng; Hu, Zhibin; Miao, Dengshun; Shen, Hongbing; Xia, Yankai; Wang, Xinru; Lu, Chuncheng

    2016-01-01

    Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. In recent years there has been increasing evidence to implicate the participation of X chromosome in the process of spermatogenesis. To uncover the roles of X-linked multi-copy genes in spermatogenesis, we performed systematic analysis of X-linked gene copy number variations (CNVs) and Y chromosome haplogrouping in 447 idiopathic NOA patients and 485 healthy controls. Interestingly, the frequency of individuals with abnormal level copy of Variable charge, X-linked (VCX) was significantly different between cases and controls after multiple test correction (p = 5.10 × 10−5). To discriminate the effect of gain/loss copies in these genes, we analyzed the frequency of X-linked multi-copy genes in subjects among subdivided groups. Our results demonstrated that individuals with increased copy numbers of Nuclear RNA export factor 2 (NXF2) (p = 9.21 × 10−8) and VCX (p = 1.97 × 10−4) conferred the risk of NOA. In vitro analysis demonstrated that increasing copy number of VCX could upregulate the gene expression and regulate cell proliferation and apoptosis. Our study establishes a robust association between the VCX CNVs and NOA risk. PMID:27705943

  2. Copy number gain of VCX, X-linked multi-copy gene, leads to cell proliferation and apoptosis during spermatogenesis.

    Science.gov (United States)

    Ji, Juan; Qin, Yufeng; Wang, Rong; Huang, Zhenyao; Zhang, Yan; Zhou, Ran; Song, Ling; Ling, Xiufeng; Hu, Zhibin; Miao, Dengshun; Shen, Hongbing; Xia, Yankai; Wang, Xinru; Lu, Chuncheng

    2016-11-29

    Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. In recent years there has been increasing evidence to implicate the participation of X chromosome in the process of spermatogenesis. To uncover the roles of X-linked multi-copy genes in spermatogenesis, we performed systematic analysis of X-linked gene copy number variations (CNVs) and Y chromosome haplogrouping in 447 idiopathic NOA patients and 485 healthy controls. Interestingly, the frequency of individuals with abnormal level copy of Variable charge, X-linked (VCX) was significantly different between cases and controls after multiple test correction (p = 5.10 × 10-5). To discriminate the effect of gain/loss copies in these genes, we analyzed the frequency of X-linked multi-copy genes in subjects among subdivided groups. Our results demonstrated that individuals with increased copy numbers of Nuclear RNA export factor 2 (NXF2) (p = 9.21 × 10-8) and VCX (p = 1.97 × 10-4) conferred the risk of NOA. In vitro analysis demonstrated that increasing copy number of VCX could upregulate the gene expression and regulate cell proliferation and apoptosis. Our study establishes a robust association between the VCX CNVs and NOA risk.

  3. Prevalence and pathogen load estimates for the fungus Batrachochytrium dendrobatidis are impacted by ITS DNA copy number variation.

    Science.gov (United States)

    Rebollar, Eria A; Woodhams, Douglas C; LaBumbard, Brandon; Kielgast, Jos; Harris, Reid N

    2017-03-21

    The ribosomal gene complex is a multi-copy region that is widely used for phylogenetic analyses of organisms from all 3 domains of life. In fungi, the copy number of the internal transcribed spacer (ITS) is used to detect abundance of pathogens causing diseases such as chytridiomycosis in amphibians and white nose syndrome in bats. Chytridiomycosis is caused by the fungi Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans (Bsal), and is responsible for declines and extinctions of amphibians worldwide. Over a decade ago, a qPCR assay was developed to determine Bd prevalence and pathogen load. Here, we demonstrate the effect that ITS copy number variation in Bd strains can have on the estimation of prevalence and pathogen load. We used data sets from different amphibian species to simulate how ITS copy number affects prevalence and pathogen load. In addition, we tested 2 methods (gBlocks® synthetic standards and digital PCR) to determine ITS copy number in Bd strains. Our results show that assumptions about the ITS copy number can lead to under- or overestimation of Bd prevalence and pathogen load. The use of synthetic standards replicated previously published estimates of ITS copy number, whereas dPCR resulted in estimates that were consistently lower than previously published estimates. Standardizing methods will assist with comparison across studies and produce reliable estimates of prevalence and pathogen load in the wild, while using the same Bd strain for exposure experiments and zoospore standards in qPCR remains the best method for estimating parameters used in epidemiological studies.

  4. Evolution vs the number of gene copies per primitive cell.

    Science.gov (United States)

    Koch, A L

    1984-01-01

    Computer simulations are presented of the rate at which an advantageous mutant would displace the prototype in a replicating system without an accurate segregation mechanism. If the number of gene copies in the system is indefinitely large, Darwinian evolution is essentially stopped because there is no coupling of phenotype with genotype, i.e., there is no growth advantage to the advantageous gene relative to the prototype and therefore no "survival of the fittest." The inhibition of evolution due to a number of gene copies less than 100 would have been not insurmountable. Although the presence of multiple copies would have allowed replacement by an advantageous mutant, it provided a way for the primitive cell to conserve less immediately useful genes that could evolve into different or more effective genes. This possibility was lost as accurate segregation mechanisms evolved and cells with few copies of each gene, such as modern procaryotes, arose.

  5. 7 CFR 46.42 - Copies of records; how obtained.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE MARKETING OF PERISHABLE AGRICULTURAL COMMODITIES REGULATIONS (OTHER THAN RULES OF PRACTICE) UNDER THE PERISHABLE AGRICULTURAL COMMODITIES ACT, 1930 Copies...

  6. Intron analyses reveal multiple calmodulin copies in Littorina.

    Science.gov (United States)

    Simpson, R J; Wilding, C S; Grahame, J

    2005-04-01

    Intron 3 and the flanking exons of the calmodulin gene have been amplified, cloned, and sequenced from 18 members of the gastropod genus Littorina. From the 48 sequences, at least five different gene copies have been identified and their functionality characterized using a strategy based upon the potential protein product predicted from flanking exon data. The functionality analyses suggest that four of the genes code for functional copies of calmodulin. All five copies have been identified across a wide range of littorinid species although not ubiquitously. Using this novel approach based on intron sequences, we have identified an unprecedented number of potential calmodulin copies in Littorina, exceeding that reported for any other invertebrate. This suggests a higher number of, and more ancient, gene duplications than previously detected in a single genus.

  7. Using DMA for copying performance counter data to memory

    Science.gov (United States)

    Gara, Alan; Salapura, Valentina; Wisniewski, Robert W

    2013-12-31

    A device for copying performance counter data includes hardware path that connects a direct memory access (DMA) unit to a plurality of hardware performance counters and a memory device. Software prepares an injection packet for the DMA unit to perform copying, while the software can perform other tasks. In one aspect, the software that prepares the injection packet runs on a processing core other than the core that gathers the hardware performance data.

  8. DNA replication stress restricts ribosomal DNA copy number.

    Science.gov (United States)

    Salim, Devika; Bradford, William D; Freeland, Amy; Cady, Gillian; Wang, Jianmin; Pruitt, Steven C; Gerton, Jennifer L

    2017-09-15

    Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen the yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

  9. Quantum copying and simplification of the quantum Fourier transform

    Science.gov (United States)

    Niu, Chi-Sheng

    Theoretical studies of quantum computation and quantum information theory are presented in this thesis. Three topics are considered: simplification of the quantum Fourier transform in Shor's algorithm, optimal eavesdropping in the BB84 quantum cryptographic protocol, and quantum copying of one qubit. The quantum Fourier transform preceding the final measurement in Shor's algorithm is simplified by replacing a network of quantum gates with one that has fewer and simpler gates controlled by classical signals. This simplification results from an analysis of the network using the consistent history approach to quantum mechanics. The optimal amount of information which an eavesdropper can gain, for a given level of noise in the communication channel, is worked out for the BB84 quantum cryptographic protocol. The optimal eavesdropping strategy is expressed in terms of various quantum networks. A consistent history analysis of these networks using two conjugate quantum bases shows how the information gain in one basis influences the noise level in the conjugate basis. The no-cloning property of quantum systems, which is the physics behind quantum cryptography, is studied by considering copying machines that generate two imperfect copies of one qubit. The best qualities these copies can have are worked out with the help of the Bloch sphere representation for one qubit, and a quantum network is worked out for an optimal copying machine. If the copying machine does not have additional ancillary qubits, the copying process can be viewed using a 2-dimensional subspace in a product space of two qubits. A special representation of such a two-dimensional subspace makes possible a complete characterization of this type of copying. This characterization in turn leads to simplified eavesdropping strategies in the BB84 and the B92 quantum cryptographic protocols.

  10. Establishment of TaqMan Real-time Quantitative PCR Assay for Foreign Gene Copy Numbers in Transgenic Soybean

    Institute of Scientific and Technical Information of China (English)

    Qiu You-wen; Gao Xue-jun; Qi Bang-ruo; Li Lu; Zhen Zhen

    2012-01-01

    TaqMan quantitative PCR technique was used to detect the copies of exogenous CaMV35S flanks sequence in transgenic soybean. With soybean lectin as the endogenous reference gene, and gene complex DNA in non-GMO soybeans as the endogenous reference standard, the gradient dilution method was used to separately calculate Ct value of endogenous reference gene and plasmid DNA and correlation standard curve equation of logarithm of copies, and then to calculate the copies of samples through substituting thus-obtained Ct into the standard curve equation. The standard curve equation of endogenous reference gene was y =–3.422x+35.201, R2=0.998; the standard curve equation of exogenous gene was y =–3.495x+35.303, R2=0.999. The sample copies was got by putting Ct value into the standard curve equation, and it was the ratio of exogenous gene and reference gene. We found that CaMV35S gene in transgenic soy was single copy.

  11. mtDNA copy number in oocytes of different sizes from individual pre- and post-pubertal pigs

    DEFF Research Database (Denmark)

    Pedersen, Hanne Skovsgaard; Løvendahl, Peter; Larsen, Knud Erik

    2014-01-01

    Reproduction 131, 233–245). However, the correlation between size and mtDNA copy number in single oocytes has not been determined. This study describes the relation between oocytes of defined diameters from individual pre- and postpubertal pigs and mtDNA copy number. Cumulus-oocyte complexes were aspirated......Oocyte competence has been related to mtDNA copy number, but a large variation in mtDNA copy number between oocytes has been observed, caused by, e.g. oocyte donor and oocyte size (Sato et al. 2014 PLOS ONE 9, e94488; Cotterill et al. 2013 Mol. Hum. Reprod. 19, 444–450; El Shourbagy et al. 2006...... from ovaries of 10 pre- and 10 post-pubertal pigs. Cumulus cells were removed and the oocytes were measured (inside-ZP-diameter). Oocytes were transferred to DNAase-free tubes, snap-frozen, and stored at –80°C. The genes ND1 and COX1 were used to determine the mtDNA copy number. Plasmid preparations...

  12. Demonstration of 400 Gb/s optical PDM-OFDM superchannel unrepeatered transmission by all optical phase-conjugated copy

    Science.gov (United States)

    Chen, Yuanxiang; Li, Juhao; Zhu, Paikun; Wu, Zhongying; Chen, Jingbiao; He, Yongqi; Chen, Zhangyuan

    2016-12-01

    Unrepeatered transmission delivers data over a few hundred kilometers without in-line active elements and it can effectively reduce the line complexity and the overall system cost. In this paper, we propose all optical phase-conjugated copy (OPC) to improve optical signal noise ratio (OSNR) margin and nonlinear tolerance for unrepeatered transmission of polarization division multiplexing (PDM) optical superchannel with EDFA only amplification. Orthogonal pumps FWM scheme is utilized to generate the optical phase-conjugated copy. The original superchannel and the phase-conjugated copy are simultaneously transmitted and received. The phases of the copy symbols are conjugated and summed with the original superchannel symbols to suppress both linear noise and nonlinear phase noise at the receiver. The proposed OPC scheme is simple and effective in phase-conjugated copy generation and digital signal processing (DSP). What is more, it is transparent to signal bit rate and modulation format, which applies to optical superchannel transmission. We experimentally verify the proposed scheme on a 400 Gb/s optical polarization division multiplexing orthogonal frequency division multiplexing (PDM-OFDM) superchannel. A Q-factor improvement of 2.1 dB is achieved after 180 km SSMF unrepeatered transmission. The optimum launch power in OPC scheme increases from -3 dBm to -2 dBm. To verify the maximum reach, we extend fiber length and realize 240 km SSMF unrepeatered transmission.

  13. Translation, copying and variation in two Castilian copies of the Epistola de cura rei familiaris by Pseudo Bernardus

    Directory of Open Access Journals (Sweden)

    Ruth Miguel Franco

    2011-12-01

    Full Text Available In this paper we attempt to analyse the differences between two copies, a printed exemplar (Burgos, Fadrique de Basilea c. 1495-1499 and a manuscript one (Madrid, BNE, 10445 of a Castilian translation of the Epistola de cura rei familiaris, a pseudo Bernardine tractate that belongs to the genre of the Oeconomica. Firstly, we will compare these two translations to a Latin copy of the Epistola printed by the same editor at around the same time. Secondly, we will compare the Castilian texts with one another in order to describe their main features. Last, on the basis of that description, we will try to distinguish between translation and copying mistakes, so that we are able to determine whether one of the Castilian texts may be a direct translation from Latin or whether both exemplars are copies of a former translation.

  14. Potential Value of Genomic Copy Number Variations in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Chuanjun Zhuo

    2017-06-01

    Full Text Available Schizophrenia is a devastating neuropsychiatric disorder affecting approximately 1% of the global population, and the disease has imposed a considerable burden on families and society. Although, the exact cause of schizophrenia remains unknown, several lines of scientific evidence have revealed that genetic variants are strongly correlated with the development and early onset of the disease. In fact, the heritability among patients suffering from schizophrenia is as high as 80%. Genomic copy number variations (CNVs are one of the main forms of genomic variations, ubiquitously occurring in the human genome. An increasing number of studies have shown that CNVs account for population diversity and genetically related diseases, including schizophrenia. The last decade has witnessed rapid advances in the development of novel genomic technologies, which have led to the identification of schizophrenia-associated CNVs, insight into the roles of the affected genes in their intervals in schizophrenia, and successful manipulation of the target CNVs. In this review, we focus on the recent discoveries of important CNVs that are associated with schizophrenia and outline the potential values that the study of CNVs will bring to the areas of schizophrenia research, diagnosis, and therapy. Furthermore, with the help of the novel genetic tool known as the Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9 system, the pathogenic CNVs as genomic defects could be corrected. In conclusion, the recent novel findings of schizophrenia-associated CNVs offer an exciting opportunity for schizophrenia research to decipher the pathological mechanisms underlying the onset and development of schizophrenia as well as to provide potential clinical applications in genetic counseling, diagnosis, and therapy for this complex mental disease.

  15. A Single-Array-Based Method for Detecting Copy Number Variants Using Affymetrix High Density SNP Arrays and its Application to Breast Cancer.

    Science.gov (United States)

    Li, Ming; Wen, Yalu; Fu, Wenjiang

    2014-01-01

    Cumulative evidence has shown that structural variations, due to insertions, deletions, and inversions of DNA, may contribute considerably to the development of complex human diseases, such as breast cancer. High-throughput genotyping technologies, such as Affymetrix high density single-nucleotide polymorphism (SNP) arrays, have produced large amounts of genetic data for genome-wide SNP genotype calling and copy number estimation. Meanwhile, there is a great need for accurate and efficient statistical methods to detect copy number variants. In this article, we introduce a hidden-Markov-model (HMM)-based method, referred to as the PICR-CNV, for copy number inference. The proposed method first estimates copy number abundance for each single SNP on a single array based on the raw fluorescence values, and then standardizes the estimated copy number abundance to achieve equal footing among multiple arrays. This method requires no between-array normalization, and thus, maintains data integrity and independence of samples among individual subjects. In addition to our efforts to apply new statistical technology to raw fluorescence values, the HMM has been applied to the standardized copy number abundance in order to reduce experimental noise. Through simulations, we show our refined method is able to infer copy number variants accurately. Application of the proposed method to a breast cancer dataset helps to identify genomic regions significantly associated with the disease.

  16. Proteomic changes resulting from gene copy number variations in cancer cells.

    Directory of Open Access Journals (Sweden)

    Tamar Geiger

    2010-09-01

    Full Text Available Along the transformation process, cells accumulate DNA aberrations, including mutations, translocations, amplifications, and deletions. Despite numerous studies, the overall effects of amplifications and deletions on the end point of gene expression--the level of proteins--is generally unknown. Here we use large-scale and high-resolution proteomics combined with gene copy number analysis to investigate in a global manner to what extent these genomic changes have a proteomic output and therefore the ability to affect cellular transformation. We accurately measure expression levels of 6,735 proteins and directly compare them to the gene copy number. We find that the average effect of these alterations on the protein expression is only a few percent. Nevertheless, by using a novel algorithm, we find the combined impact that many of these regional chromosomal aberrations have at the protein level. We show that proteins encoded by amplified oncogenes are often overexpressed, while adjacent amplified genes, which presumably do not promote growth and survival, are attenuated. Furthermore, regulation of biological processes and molecular complexes is independent of general copy number changes. By connecting the primary genome alteration to their proteomic consequences, this approach helps to interpret the data from large-scale cancer genomics efforts.

  17. Copy number analysis identifies novel interactions between genomic loci in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Kylie L Gorringe

    Full Text Available Ovarian cancer is a heterogeneous disease displaying complex genomic alterations, and consequently, it has been difficult to determine the most relevant copy number alterations with the scale of studies to date. We obtained genome-wide copy number alteration (CNA data from four different SNP array platforms, with a final data set of 398 ovarian tumours, mostly of the serous histological subtype. Frequent CNA aberrations targeted many thousands of genes. However, high-level amplicons and homozygous deletions enabled filtering of this list to the most relevant. The large data set enabled refinement of minimal regions and identification of rare amplicons such as at 1p34 and 20q11. We performed a novel co-occurrence analysis to assess cooperation and exclusivity of CNAs and analysed their relationship to patient outcome. Positive associations were identified between gains on 19 and 20q, gain of 20q and loss of X, and between several regions of loss, particularly 17q. We found weak correlations of CNA at genomic loci such as 19q12 with clinical outcome. We also assessed genomic instability measures and found a correlation of the number of higher amplitude gains with poorer overall survival. By assembling the largest collection of ovarian copy number data to date, we have been able to identify the most frequent aberrations and their interactions.

  18. Copy number analysis identifies novel interactions between genomic loci in ovarian cancer.

    Science.gov (United States)

    Gorringe, Kylie L; George, Joshy; Anglesio, Michael S; Ramakrishna, Manasa; Etemadmoghadam, Dariush; Cowin, Prue; Sridhar, Anita; Williams, Louise H; Boyle, Samantha E; Yanaihara, Nozomu; Okamoto, Aikou; Urashima, Mitsuyoshi; Smyth, Gordon K; Campbell, Ian G; Bowtell, David D L

    2010-09-10

    Ovarian cancer is a heterogeneous disease displaying complex genomic alterations, and consequently, it has been difficult to determine the most relevant copy number alterations with the scale of studies to date. We obtained genome-wide copy number alteration (CNA) data from four different SNP array platforms, with a final data set of 398 ovarian tumours, mostly of the serous histological subtype. Frequent CNA aberrations targeted many thousands of genes. However, high-level amplicons and homozygous deletions enabled filtering of this list to the most relevant. The large data set enabled refinement of minimal regions and identification of rare amplicons such as at 1p34 and 20q11. We performed a novel co-occurrence analysis to assess cooperation and exclusivity of CNAs and analysed their relationship to patient outcome. Positive associations were identified between gains on 19 and 20q, gain of 20q and loss of X, and between several regions of loss, particularly 17q. We found weak correlations of CNA at genomic loci such as 19q12 with clinical outcome. We also assessed genomic instability measures and found a correlation of the number of higher amplitude gains with poorer overall survival. By assembling the largest collection of ovarian copy number data to date, we have been able to identify the most frequent aberrations and their interactions.

  19. Copy number variation in the genomes of twelve natural isolates of Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Flibotte Stephane

    2010-01-01

    Full Text Available Abstract Background Copy number variation is an important component of genetic variation in higher eukaryotes. The extent of natural copy number variation in C. elegans is unknown outside of 2 highly divergent wild isolates and the canonical N2 Bristol strain. Results We have used array comparative genomic hybridization (aCGH to detect copy number variation in the genomes of 12 natural isolates of Caenorhabditis elegans. Deletions relative to the canonical N2 strain are more common in these isolates than duplications, and indels are enriched in multigene families on the autosome arms. Among the strains in our study, the Hawaiian and Madeiran strains (CB4856 and JU258 carry the largest number of deletions, followed by the Vancouver strain (KR314. Overall we detected 510 different deletions affecting 1136 genes, or over 5% of the genes in the canonical N2 genome. The indels we identified had a median length of 2.7 kb. Since many deletions are found in multiple isolates, deletion loci were used as markers to derive an unrooted tree to estimate genetic relatedness among the strains. Conclusion Copy number variation is extensive in C. elegans, affecting over 5% of the genes in the genome. The deletions we have detected in natural isolates of C. elegans contribute significantly to the number of deletion alleles available to researchers. The relationships between strains are complex and different regions of the genome possess different genealogies due to recombination throughout the natural history of the species, which may not be apparent in studies utilizing smaller numbers of genetic markers.

  20. Copy number variations exploration of multiple genes in Graves' disease.

    Science.gov (United States)

    Song, Rong-Hua; Shao, Xiao-Qing; Li, Ling; Wang, Wen; Zhang, Jin-An

    2017-01-01

    Few previous published papers reported copy number variations of genes could affect the predisposition of Graves' disease (GD). Herein, the aim of this study was to explore the association between copy number variations (CNV) profile and GD. The preliminary copy number microarray used to screen copy number variant genes was performed in 6 GD patients. Five CNV candidate genes (CFH, CFHR1, KIAA0125, UGT2B15, and UGT2B17) were then validated in an independent set of samples (50 GD patients and 50 matched healthy ones) by the Accucopy assay method. The CNV of the other 2 genes TRY6 and CCL3L1 was investigated in 144 GD patients and 144 healthy volunteers by the definitive genotyping technique using the Taqman quantitative polymerase-chain-reaction (Taqman qPCR). TRY6 gene-associated single nucleotide polymorphism (SNP), rs13230029, was genotyped by the PCR-ligase detection reaction (LDR) in 675 GD patients and 898 healthy controls. There were no correlation of the gene copy number (GCN) of CFH, CFHR1, KIAA0125, UGT2B15, and UGT2B17 with GD. In comparison with that of controls, the GCN distribution of TRY6 and CCL3L1 in GD patients did not show significantly differ (P > 0.05). Furthermore, TRY6-related polymorphism (rs13230029) showed no difference between GD patients and controls. No correlation was found between CNV or SNP genotype and clinical phenotypes. Generally, there were no link of the copy numbers of several genes, including CFH, CFHR1, KIAA0125, UGT2B15, UGT2B17, TRY6, and CCL3L1 to GD. Our results clearly indicated that the copy number variations of multiple genes, namely CFH, CFHR1, KIAA0125, UGT2B15, UGT2B17, TRY6, and CCL3L1, were not associated with the development of GD.

  1. Food preference and copying behaviour in zebra finches, Taeniopygia guttata.

    Science.gov (United States)

    Guillette, Lauren M; Morgan, Kate V; Hall, Zachary J; Bailey, Ida E; Healy, Susan D

    2014-11-01

    As a social species zebra finches might be expected to copy the food choices of more experienced conspecifics. This prediction has been tested previously by presenting observers with two demonstrator birds that differ in some way (e.g., sex, familiarity), each feeding on a different colour food source. However, if the observer subsequently exhibits a preference, it is unclear whether it has copied the choice of one demonstrator or avoided the choice of the other. Furthermore, this choice may actually be influenced by pre-existing preferences, a potential bias that is rarely tested. Here we examine whether apparent copying or avoidance can be explained by pre-existing preferences. In Experiment 1, observers had the opportunity to watch a conspecific forage from one of the two differently coloured food hoppers. In Experiment 2, the observers did not have this opportunity. In both experiments observers were subsequently tested for their food hopper preference and all but one preferred one colour over the other. In Experiment 1 some observers showed evidence for copying, while others seemed to avoid the colour preferred by the demonstrator. In Experiment 2 females generally preferred the white hopper. Pre-existing colour preferences could, therefore, explain the apparent copying/avoidance we observed. This article is part of a Special Issue entitled: Cognition in the wild. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Endogenous RNA interference is driven by copy number

    Science.gov (United States)

    Cruz, Cristina; Houseley, Jonathan

    2014-01-01

    A plethora of non-protein coding RNAs are produced throughout eukaryotic genomes, many of which are transcribed antisense to protein-coding genes and could potentially instigate RNA interference (RNAi) responses. Here we have used a synthetic RNAi system to show that gene copy number is a key factor controlling RNAi for transcripts from endogenous loci, since transcripts from multi-copy loci form double stranded RNA more efficiently than transcripts from equivalently expressed single-copy loci. Selectivity towards transcripts from high-copy DNA is therefore an emergent property of a minimal RNAi system. The ability of RNAi to selectively degrade transcripts from high-copy loci would allow suppression of newly emerging transposable elements, but such a surveillance system requires transcription. We show that low-level genome-wide pervasive transcription is sufficient to instigate RNAi, and propose that pervasive transcription is part of a defense mechanism capable of directing a sequence-independent RNAi response against transposable elements amplifying within the genome. DOI: http://dx.doi.org/10.7554/eLife.01581.001 PMID:24520161

  3. Major copy proportion analysis of tumor samples using SNP arrays

    Directory of Open Access Journals (Sweden)

    Li Cheng

    2008-04-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the most common genetic variations in the human genome and are useful as genomic markers. Oligonucleotide SNP microarrays have been developed for high-throughput genotyping of up to 900,000 human SNPs and have been used widely in linkage and cancer genomics studies. We have previously used Hidden Markov Models (HMM to analyze SNP array data for inferring copy numbers and loss-of-heterozygosity (LOH from paired normal and tumor samples and unpaired tumor samples. Results We proposed and implemented major copy proportion (MCP analysis of oligonucleotide SNP array data. A HMM was constructed to infer unobserved MCP states from observed allele-specific signals through emission and transition distributions. We used 10 K, 100 K and 250 K SNP array datasets to compare MCP analysis with LOH and copy number analysis, and showed that MCP performs better than LOH analysis for allelic-imbalanced chromosome regions and normal contaminated samples. The major and minor copy alleles can also be inferred from allelic-imbalanced regions by MCP analysis. Conclusion MCP extends tumor LOH analysis to allelic imbalance analysis and supplies complementary information to total copy numbers. MCP analysis of mixing normal and tumor samples suggests the utility of MCP analysis of normal-contaminated tumor samples. The described analysis and visualization methods are readily available in the user-friendly dChip software.

  4. Endogenous RNA interference is driven by copy number.

    Science.gov (United States)

    Cruz, Cristina; Houseley, Jonathan

    2014-02-11

    A plethora of non-protein coding RNAs are produced throughout eukaryotic genomes, many of which are transcribed antisense to protein-coding genes and could potentially instigate RNA interference (RNAi) responses. Here we have used a synthetic RNAi system to show that gene copy number is a key factor controlling RNAi for transcripts from endogenous loci, since transcripts from multi-copy loci form double stranded RNA more efficiently than transcripts from equivalently expressed single-copy loci. Selectivity towards transcripts from high-copy DNA is therefore an emergent property of a minimal RNAi system. The ability of RNAi to selectively degrade transcripts from high-copy loci would allow suppression of newly emerging transposable elements, but such a surveillance system requires transcription. We show that low-level genome-wide pervasive transcription is sufficient to instigate RNAi, and propose that pervasive transcription is part of a defense mechanism capable of directing a sequence-independent RNAi response against transposable elements amplifying within the genome. DOI: http://dx.doi.org/10.7554/eLife.01581.001.

  5. Secure Copier Which Allows Reuse Copied Documents with Sorting Capability in Accordance with Document Types

    OpenAIRE

    Kohei Arai

    2013-01-01

    Secure copy machine which allows reuse copied documents with sorting capability in accordance with the document types. Through experiments with a variety of document types, it is found that copied documents can be shared and stored in database in accordance with automatically classified document types securely. The copied documents are protected by data hiding based on wavelet Multi Resolution Analysis: MRA.

  6. Secure Copier Which Allows Reuse Copied Documents with Sorting Capability in Accordance with Document Types

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2013-09-01

    Full Text Available Secure copy machine which allows reuse copied documents with sorting capability in accordance with the document types. Through experiments with a variety of document types, it is found that copied documents can be shared and stored in database in accordance with automatically classified document types securely. The copied documents are protected by data hiding based on wavelet Multi Resolution Analysis: MRA.

  7. Mitochondrial DNA Copy Number in Sleep Duration Discordant Monozygotic Twins

    DEFF Research Database (Denmark)

    Wrede, Joanna E; Mengel-From, Jonas; Buchwald, Dedra

    2015-01-01

    STUDY OBJECTIVES: Mitochondrial DNA (mtDNA) copy number is an important component of mitochondrial function and varies with age, disease, and environmental factors. We aimed to determine whether mtDNA copy number varies with habitual differences in sleep duration within pairs of monozygotic twins....... SETTING: Academic clinical research center. PARTICIPANTS: 15 sleep duration discordant monozygotic twin pairs (30 twins, 80% female; mean age 42.1 years [SD 15.0]). DESIGN: Sleep duration was phenotyped with wrist actigraphy. Each twin pair included a "normal" (7-9 h/24) and "short" (sleeping...... twin. Fasting peripheral blood leukocyte DNA was assessed for mtDNA copy number via the n-fold difference between qPCR measured mtDNA and nuclear DNA creating an mtDNA measure without absolute units. We used generalized estimating equation linear regression models accounting for the correlated data...

  8. Gribov horizon and Gribov copies effect in lattice Coulomb gauge

    CERN Document Server

    Burgio, Giuseppe; Reinhardt, Hugo; Vogt, Hannes

    2016-01-01

    Following a recent proposal by Cooper and Zwanziger we investigate via lattice simulations the effect on the Coulomb gauge propagators and on the Gribov-Zwanziger confinement mechanism of selecting the Gribov copy with the smallest non-trivial eigenvalue of the Faddeev-Popov operator, i.e. the one closest to the Gribov horizon. Although such choice of gauge drives the ghost propagator towards the prediction of continuum calculations, we find that it actually overshoots the goal. With increasing computer time, we observe that Gribov copies with arbitrarily small eigenvalues can be found. For such a method to work one would therefore need further restrictions on the gauge condition to isolate the physically relevant copies, since e.g. the Coulomb potential $V_C$ defined through the Faddeev-Popov operator becomes otherwise physically meaningless. Interestingly, the Coulomb potential alternatively defined through temporal link correlators is only marginally affected by the smallness of the eigenvalues.

  9. Number matters: control of mammalian mitochondrial DNA copy number.

    Science.gov (United States)

    Clay Montier, Laura L; Deng, Janice J; Bai, Yidong

    2009-03-01

    Regulation of mitochondrial biogenesis is essential for proper cellular functioning. Mitochondrial DNA (mtDNA) depletion and the resulting mitochondrial malfunction have been implicated in cancer, neurodegeneration, diabetes, aging, and many other human diseases. Although it is known that the dynamics of the mammalian mitochondrial genome are not linked with that of the nuclear genome, very little is known about the mechanism of mtDNA propagation. Nevertheless, our understanding of the mode of mtDNA replication has advanced in recent years, though not without some controversies. This review summarizes our current knowledge of mtDNA copy number control in mammalian cells, while focusing on both mtDNA replication and turnover. Although mtDNA copy number is seemingly in excess, we reason that mtDNA copy number control is an important aspect of mitochondrial genetics and biogenesis and is essential for normal cellular function.

  10. Genome wide copy number analysis of single cells

    Science.gov (United States)

    Baslan, Timour; Kendall, Jude; Rodgers, Linda; Cox, Hilary; Riggs, Mike; Stepansky, Asya; Troge, Jennifer; Ravi, Kandasamy; Esposito, Diane; Lakshmi, B.; Wigler, Michael; Navin, Nicholas; Hicks, James

    2016-01-01

    Summary Copy number variation (CNV) is increasingly recognized as an important contributor to phenotypic variation in health and disease. Most methods for determining CNV rely on admixtures of cells, where information regarding genetic heterogeneity is lost. Here, we present a protocol that allows for the genome wide copy number analysis of single nuclei isolated from mixed populations of cells. Single nucleus sequencing (SNS), combines flow sorting of single nuclei based on DNA content, whole genome amplification (WGA), followed by next generation sequencing to quantize genomic intervals in a genome wide manner. Multiplexing of single cells is discussed. Additionally, we outline informatic approaches that correct for biases inherent in the WGA procedure and allow for accurate determination of copy number profiles. All together, the protocol takes ~3 days from flow cytometry to sequence-ready DNA libraries. PMID:22555242

  11. Histotype-specific copy-number alterations in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Huang Ruby YunJu

    2012-10-01

    Full Text Available Abstract Background Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses. Methods To dissect the heterogeneity of ovarian cancer and identify histotype-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer. Results In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6% but deleted in serous tumors (15.1%. Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007. There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors. Conclusions The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.

  12. Chromosome Conformation Capture Carbon Copy (5C) in Budding Yeast.

    Science.gov (United States)

    Belton, Jon-Matthew; Dekker, Job

    2015-06-01

    Chromosome conformation capture carbon copy (5C) is a high-throughput method for detecting ligation products of interest in a chromosome conformation capture (3C) library. 5C uses ligation-mediated amplification (LMA) to generate carbon copies of 3C ligation product junctions using single-stranded oligonucleotide probes. This procedure produces a 5C library of short DNA molecules which represent the interactions between the corresponding restriction fragments. The 5C library can be amplified using universal primers containing the Illumina paired-end adaptor sequences for subsequent high-throughput sequencing.

  13. A quantum-copying machine for equatorial qubits

    OpenAIRE

    Fan, Heng; Wang, Xiang-Bin; Matsumoto, Keiji

    2000-01-01

    Bu\\v{z}ek and Hillery proposed a universal quantum-copying machine (UQCM) (i.e., transformation) to analyze the possibility of cloning arbitrary states. The UQCM copies quantum-mechanical states with the quality of its output does not depend on the input. We propose a slightly different transformation to analyze a restricted set of input states. We impose the conditions (I) the density matrices of the two output states are the same, and that (II) the distance between input density operator an...

  14. Copy-number variants in neurodevelopmental disorders: promises and challenges.

    LENUS (Irish Health Repository)

    Merikangas, Alison K

    2012-02-01

    Copy-number variation (CNV) is the most prevalent type of structural variation in the human genome. There is emerging evidence that copy-number variants (CNVs) provide a new vista on understanding susceptibility to neuropsychiatric disorders. Some challenges in the interpretation of current CNV studies include the use of overlapping samples, differing phenotypic definitions, an absence of population norms for CNVs and a lack of consensus in methods for CNV detection and analysis. Here, we review current CNV association study methods and results in autism spectrum disorders (ASD) and schizophrenia, and provide suggestions for design approaches to future studies that might maximize the translation of this work to etiological understanding.

  15. An Enhanced Approach to Detect Copy Move Forgery

    Directory of Open Access Journals (Sweden)

    Ruchita Singh

    2014-07-01

    Full Text Available Due to the enhancement in the availability and quality of image manipulation tools, it is easy for a forger to forge any image without living any traces of modification. Digital Image tampering is now-a-days very common. Most obvious practice for doing forgery is Copy Move Forgery. In this research, a novel approach to detect Copy Move forgery is proposed. In this approach block based method and feature based method is employed to extract features from the image and extracted features are than matched to detect forgery and also perform the localization of the Forged Regions in the Digital Image

  16. Quantum state discrimination using the minimum average number of copies

    CERN Document Server

    Slussarenko, Sergei; Li, Jun-Gang; Campbell, Nicholas; Wiseman, Howard M; Pryde, Geoff J

    2016-01-01

    In the task of discriminating between nonorthogonal quantum states from multiple copies, the key parameters are the error probability and the resources (number of copies) used. Previous studies have considered the task of minimizing the average error probability for fixed resources. Here we consider minimizing the average resources for a fixed admissible error probability. We derive a detection scheme optimized for the latter task, and experimentally test it, along with schemes previously considered for the former task. We show that, for our new task, our new scheme outperforms all previously considered schemes.

  17. Dosage sensitivity shapes the evolution of copy-number varied regions.

    Directory of Open Access Journals (Sweden)

    Benjamin Schuster-Böckler

    Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

  18. Association of Copy Number Variations in Autism Spectrum Disorders: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Elif Funda Sener

    2014-01-01

    Full Text Available Autism spectrum disorders (ASDs are characterized by language impairments, social deficits, and repetitive behaviors. The onset of symptoms occurs by the age of 3 and shows a lifelong persistence. Genetics plays a major role in the etiology of ASD. Except genetics, several potential risk factors (environmental factors and epigenetics may contribute to ASD. Copy number variations (CNVs are the most widespread structural variations in the human genome. These variations can alter the genome structure either by deletion or by duplication. CNVs can be de novo or inherited. Chromosomal rearrangements have been detected in 5–10% of the patients with ASD and recently copy number changes ranging from a few kilobases (kb to several megabases (Mb in size have been reported. Recent data have also revealed that submicroscopic CNVs can have a role in ASD, and de novo CNVs seem to be a more common risk factor in sporadic compared with inherited forms of ASD. CNVs are being implicated as a contributor to the pathophysiology of complex neurodevelopmental disorders and they can affect a wide range of human phenotypes including mental retardation (MR, autism, neuropsychiatric disorders, and susceptibility to other complex traits such as HIV, Crohn’s disease, and psoriasis. This review emphasizes the major CNVs reported to date in ASD.

  19. Genomic Copy Number Variation in Disorders of Cognitive Development

    Science.gov (United States)

    Morrow, Eric M.

    2010-01-01

    Objective: To highlight recent discoveries in the area of genomic copy number variation in neuropsychiatric disorders including intellectual disability, autism, and schizophrenia. To emphasize new principles emerging from this area, involving the genetic architecture of disease, pathophysiology, and diagnosis. Method: Review of studies published…

  20. 75 FR 4031 - Streamlining Hard-Copy Postage Statement Processing

    Science.gov (United States)

    2010-01-26

    ... From the Federal Register Online via the Government Publishing Office POSTAL SERVICE 39 CFR Part 111 Streamlining Hard-Copy Postage Statement Processing AGENCY: Postal Service\\TM\\. ACTION: Proposed rule. SUMMARY: The Postal Service\\TM\\ is proposing to revise Mailing Standards of the United States...

  1. Single-copy insertion of transgenes in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Frøkjaer-Jensen, Christian; Davis, M Wayne; Hopkins, Christopher E;

    2008-01-01

    At present, transgenes in Caenorhabditis elegans are generated by injecting DNA into the germline. The DNA assembles into a semistable extrachromosomal array composed of many copies of injected DNA. These transgenes are typically overexpressed in somatic cells and silenced in the germline. We have...

  2. The blessing effect of an extra copy of chromosome 21

    African Journals Online (AJOL)

    Solaf M. Elsayed

    2014-02-25

    Feb 25, 2014 ... The protective effect of the extra copy of chromosome against the ... genesis by decreasing the vascular endothelial growth factor. C (VEGF-C) levels in .... [8] Sun Y, Wang J, Liu Y, Song X, Zhang Y, Li K, et al. Results of.

  3. IKONPAINT -- Ikon and GWM window to Inkjet Hard-copy

    Science.gov (United States)

    Page, Clive G.; Mellor, G. R.

    IKONPAINT provides ``push-button'' colour hard-copy from the Ikon screen or from a GWM window to an inkjet printer. The DEC Companion Colour Printer (LJ250/LJ252) and the Hewlett-Packard Paintjet are both supported. These printers normally take 8 by 11 inch fan-fold paper but single transparency sheets can be hand-fed.

  4. Copy number variations in affective disorders and meta-analysis

    DEFF Research Database (Denmark)

    Olsen, Line; Hansen, Thomas; Djurovic, Srdjan

    2011-01-01

    In two recent studies 10 copy number variants (CNV) were found to be overrepresented either among patients suffering from affective disorders in an Amish family or in the Wellcome Trust Case-Control Consortium study. Here, we investigate if these variants are associated with affective disorders...

  5. Content-based video copy detection benchmarking at TRECVID

    NARCIS (Netherlands)

    Awad, G.; Over, P.; Kraaij, W.

    2014-01-01

    This article presents an overview of the video copy detection benchmarkwhichwas run over a period of 4 years (2008-2011) as part of the TREC Video Retrieval (TRECVID) workshop series. The main contributions of the article include i) an examination of the evolving design of the evaluation framework

  6. Using Copy Change with Trade Books to Teach Earth Science

    Science.gov (United States)

    Bintz, William P.; Wright, Pam; Sheffer, Julie

    2010-01-01

    Developing and implementing relevant, challenging, integrative, and exploratory curriculum is critical at all levels of schooling. This article describes one attempt to develop and implement an instance of interdisciplinary curriculum by using copy change with trade books to teach earth science. Specifically, it introduces trade books as a way to…

  7. Advertising Copy: Short Route to the Argumentative Essay.

    Science.gov (United States)

    Brown, Stephen G.

    1994-01-01

    Describes how generating effective advertising copy affords students practice in aspects of persuasive writing, such as developing a thesis, refuting counter-arguments, and writing in a comparison-contrast mode. Notes that this approach helps students negotiate the problematic shift from expressive to persuasive discourse without losing their…

  8. From Copy-and-Paste to Trace-and-Learn

    DEFF Research Database (Denmark)

    Klitgård, Ida

    2009-01-01

    of them even use the term ‹copy-and-paste› to illustrate this, suggesting that their perception is closely linked to their use of the internet. This generally one-dimensional perception calls for immediate repair work in the teaching of English academic writing in International Study Programmes...

  9. Evidence for nonconscious behavior-copying in young children

    NARCIS (Netherlands)

    Schaik, J.E. van; Baaren, R.B. van; Bekkering, H.; Hunnius, S.

    2013-01-01

    Behavioral mimicry is the nonconscious copying of an interaction partner’s behavior and is affected by social dynamics. Whereas it has been studied extensively in adults, little is known about the development of mimicry. The aims of this study were twofold, first to identify whether young children

  10. Chimpanzees copy dominant and knowledgeable individuals: implications for cultural diversity.

    Science.gov (United States)

    Kendal, Rachel; Hopper, Lydia M; Whiten, Andrew; Brosnan, Sarah F; Lambeth, Susan P; Schapiro, Steven J; Hoppitt, Will

    2015-01-01

    Evolutionary theory predicts that natural selection will fashion cognitive biases to guide when, and from whom, individuals acquire social information, but the precise nature of these biases, especially in ecologically valid group contexts, remains unknown. We exposed four captive groups of chimpanzees (Pan troglodytes) to a novel extractive foraging device and, by fitting statistical models, isolated four simultaneously operating transmission biases. These include biases to copy (i) higher-ranking and (ii) expert individuals, and to copy others when (iii) uncertain or (iv) of low rank. High-ranking individuals were relatively un-strategic in their use of acquired knowledge, which, combined with the bias for others to observe them, may explain reports that high innovation rates (in juveniles and subordinates) do not generate a correspondingly high frequency of traditions in chimpanzees. Given the typically low rank of immigrants in chimpanzees, a 'copying dominants' bias may contribute to the observed maintenance of distinct cultural repertoires in neighboring communities despite sharing similar ecology and knowledgeable migrants. Thus, a copying dominants strategy may, as often proposed for conformist transmission, and perhaps in concert with it, restrict the accumulation of traditions within chimpanzee communities whilst maintaining cultural diversity.

  11. Using Copy Change with Trade Books to Teach Earth Science

    Science.gov (United States)

    Bintz, William P.; Wright, Pam; Sheffer, Julie

    2010-01-01

    Developing and implementing relevant, challenging, integrative, and exploratory curriculum is critical at all levels of schooling. This article describes one attempt to develop and implement an instance of interdisciplinary curriculum by using copy change with trade books to teach earth science. Specifically, it introduces trade books as a way to…

  12. 7 CFR 3601.2 - Public inspection, copying, and indexing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Public inspection, copying, and indexing. 3601.2 Section 3601.2 Agriculture Regulations of the Department of Agriculture (Continued) NATIONAL AGRICULTURAL... indexing. 5 U.S.C. 552(a)(2) requires that certain materials be made available for public inspection...

  13. Bovine copy number variation and its implication in animal health

    Science.gov (United States)

    Recently it has become apparent that previously unappreciated genomic structural variation, including copy number variations (CNV), contributes significantly to individual health and disease in humans and rodents. As a complement to the bovine HapMap project, we initiated a systematic study of the C...

  14. From Copy-and-Paste to Trace-and-Learn

    DEFF Research Database (Denmark)

    Klitgård, Ida

    2009-01-01

    This paper presents an investigation of both Danish and international second-semester BA-students' perceptions of the problem of plagiarism. Surprisingly, the investigation proves that the students unanimously perceive plagiarism as directly copying other people's texts or entire works. Some...

  15. European Union. European Commission: Private Copying Recommendations Following Stakeholder Mediation

    NARCIS (Netherlands)

    J.P. Quintais

    2013-01-01

    Private copying levies are a constant topic of debate in EU copyright law and policy. They have been on the harmonization agenda since the 1988 Green Paper on Copyright and the Challenge of Technology and, following stakeholder consultations (in 2006 and 2008) and the 2011 IPR Strategy, remain an on

  16. 36 CFR 1290.6 - Originals and copies.

    Science.gov (United States)

    2010-07-01

    ... Section 1290.6 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION JFK... ASSASSINATION RECORDS COLLECTION ACT OF 1992 (JFK ACT) § 1290.6 Originals and copies. (a) For purposes of.... Kennedy Assassination Records Collection (JFK Assassination Records Collection) established under the...

  17. Copy number variation of functional RBMY1 is associated with sperm motility: an azoospermia factor-linked candidate for asthenozoospermia.

    Science.gov (United States)

    Yan, Yuanlong; Yang, Xiling; Liu, Yunqiang; Shen, Ying; Tu, Wenling; Dong, Qiang; Yang, Dong; Ma, Yongyi; Yang, Yuan

    2017-05-12

    population. A difference in the distribution of RBMY1 copy number was observed between the group with normal sperm motility and the group with asthenozoospermia. A positive correlation between the RBMY1 copy dosage and sperm motility was identified, and the males with fewer than six copies of RBMY1 showed an elevated risk for asthenozoospermia relative to those with six RBMY1 copies, the most common dosage in the population. The RBMY1 copy dosage was positively correlated with its mRNA and protein level in the testis. Sperm with high motility were found to carry more RBMY1 protein than those with relatively low motility. The RBMY1 protein was confirmed to predominantly localize in the neck and mid-piece region of sperm as well as the principal piece of the sperm tail. Our population study completes a chain of evidence suggesting that RBMY1 influences the susceptibility of males to asthenozoospermia by modulating sperm motility. High sequence similarity between the RBMY1 functional copies and a large number of pseudogenes potentially reduces the accuracy of the copy number detection. The mechanism underlying the CNV in RBMY1 is still unclear, and the effect of the structural variations in the RBMY1 copy cluster on the copy dosage of other protein-coding genes located in the region cannot be excluded, which may potentially bias our observations. Asthenozoospermia is a multi-factor complex disease with a limited number of proven susceptibility genes. This study identified a novel genomic candidate independently contributing to the condition, enriching our understanding of the role of AZF-linked genes in male reproduction. Our finding provides insight into the physiological and pathological characteristics of RBMY1 in terms of sperm motility, supplies persuasive evidence of the significance of RBMY1 copy number analysis in the clinical counselling of male infertility resulting from asthenozoospermia. This work was funded by the National Natural Science Foundation of China (Nos

  18. Copy Number Variation at the APOL1 Locus.

    Directory of Open Access Journals (Sweden)

    Rupam Ruchi

    Full Text Available Two coding variants in the APOL1 gene (G1 and G2 explain most of the high rate of kidney disease in African Americans. APOL1-associated kidney disease risk inheritance follows an autosomal recessive pattern: The relative risk of kidney disease associated with inheritance of two high-risk variants is 7-30 fold, depending on the specific kidney phenotype. We wished to determine if the variability in phenotype might in part reflect structural differences in APOL1 gene. We analyzed sequence coverage from 1000 Genomes Project Phase 3 samples as well as exome sequencing data from African American kidney disease cases for copy number variation. 8 samples sequenced in the 1000 Genomes Project showed increased coverage over a ~100kb region that includes APOL2, APOL1 and part of MYH9, suggesting the presence of APOL1 copy number greater than 2. We reasoned that such duplications should be enriched in apparent G1 heterozygotes with kidney disease. Using a PCR-based assay, we observed the presence of this duplication in additional samples from apparent G0G1 or G0G2 individuals. The frequency of this APOL1 duplication was compared among cases (n = 123 and controls (n = 255 with apparent G0G1 heterozygosity. The presence of APOL1 duplication was observed in 4.06% of cases and 0.78% controls, preliminary evidence that this APOL1 duplication may alter susceptibility to kidney disease (p = 0.03. Taqman-based copy number assays confirmed the presence of 3 APOL1 copies in individuals positive for this specific duplication by PCR assay, but also identified a small number of individuals with additional APOL1 copies of presumably different structure. These observations motivate further studies to better assess the contribution of APOL1 copy number on kidney disease risk and on APOL1 function. Investigators and clinicians genotyping APOL1 should also consider whether the particular genotyping platform used is subject to technical errors when more than two copies of

  19. Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability. | Office of Cancer Genomics

    Science.gov (United States)

    Genomic instability is a hallmark of human cancer, and results in widespread somatic copy number alterations. We used a genome-scale shRNA viability screen in human cancer cell lines to systematically identify genes that are essential in the context of particular copy-number alterations (copy-number associated gene dependencies). The most enriched class of copy-number associated gene dependencies was CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) genes, and spliceosome components were the most prevalent.

  20. Distinct Copy Number, Coding Sequence, and Locus Methylation Patterns Underlie Rhg1-Mediated Soybean Resistance to Soybean Cyst Nematode1[W][OPEN

    Science.gov (United States)

    Cook, David E.; Bayless, Adam M.; Wang, Kai; Guo, Xiaoli; Song, Qijian; Jiang, Jiming; Bent, Andrew F.

    2014-01-01

    Copy number variation of kilobase-scale genomic DNA segments, beyond presence/absence polymorphisms, can be an important driver of adaptive traits. Resistance to Heterodera glycines (Rhg1) is a widely utilized quantitative trait locus that makes the strongest known contribution to resistance against soybean cyst nematode (SCN), Heterodera glycines, the most damaging pathogen of soybean (Glycine max). Rhg1 was recently discovered to be a complex locus at which resistance-conferring haplotypes carry up to 10 tandem repeat copies of a 31-kb DNA segment, and three disparate genes present on each repeat contribute to SCN resistance. Here, we use whole-genome sequencing, fiber-FISH (fluorescence in situ hybridization), and other methods to discover the genetic variation at Rhg1 across 41 diverse soybean accessions. Based on copy number variation, transcript abundance, nucleic acid polymorphisms, and differentially methylated DNA regions, we find that SCN resistance is associated with multicopy Rhg1 haplotypes that form two distinct groups. The tested high-copy-number Rhg1 accessions, including plant introduction (PI) 88788, contain a flexible number of copies (seven to 10) of the 31-kb Rhg1 repeat. The identified low-copy-number Rhg1 group, including PI 548402 (Peking) and PI 437654, contains three copies of the Rhg1 repeat and a newly identified allele of Glyma18g02590 (a predicted α-SNAP [α-soluble N-ethylmaleimide–sensitive factor attachment protein]). There is strong evidence for a shared origin of the two resistance-conferring multicopy Rhg1 groups and subsequent independent evolution. Differentially methylated DNA regions also were identified within Rhg1 that correlate with SCN resistance. These data provide insights into copy number variation of multigene segments, using as the example a disease resistance trait of high economic importance. PMID:24733883

  1. Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC

    Directory of Open Access Journals (Sweden)

    Cheng Yuanyuan

    2012-03-01

    Full Text Available Abstract Background The Tasmanian devil (Sarcophilus harrisii is currently under threat of extinction due to an unusual fatal contagious cancer called Devil Facial Tumour Disease (DFTD. DFTD is caused by a clonal tumour cell line that is transmitted between unrelated individuals as an allograft without triggering immune rejection due to low levels of Major Histocompatibility Complex (MHC diversity in Tasmanian devils. Results Here we report the characterization of the genomic regions encompassing MHC Class I and Class II genes in the Tasmanian devil. Four genomic regions approximately 960 kb in length were assembled and annotated using BAC contigs and physically mapped to devil Chromosome 4q. 34 genes and pseudogenes were identified, including five Class I and four Class II loci. Interestingly, when two haplotypes from two individuals were compared, three genomic copy number variants with sizes ranging from 1.6 to 17 kb were observed within the classical Class I gene region. One deletion is particularly important as it turns a Class Ia gene into a pseudogene in one of the haplotypes. This deletion explains the previously observed variation in the Class I allelic number between individuals. The frequency of this deletion is highest in the northwestern devil population and lowest in southeastern areas. Conclusions The third sequenced marsupial MHC provides insights into the evolution of this dynamic genomic region among the diverse marsupial species. The two sequenced devil MHC haplotypes revealed three copy number variations that are likely to significantly affect immune response and suggest that future work should focus on the role of copy number variations in disease susceptibility in this species.

  2. Generalized scalable multiple copy algorithms for molecular dynamics simulations in NAMD

    Science.gov (United States)

    Jiang, Wei; Phillips, James C.; Huang, Lei; Fajer, Mikolai; Meng, Yilin; Gumbart, James C.; Luo, Yun; Schulten, Klaus; Roux, Benoît

    2014-03-01

    Computational methodologies that couple the dynamical evolution of a set of replicated copies of a system of interest offer powerful and flexible approaches to characterize complex molecular processes. Such multiple copy algorithms (MCAs) can be used to enhance sampling, compute reversible work and free energies, as well as refine transition pathways. Widely used examples of MCAs include temperature and Hamiltonian-tempering replica-exchange molecular dynamics (T-REMD and H-REMD), alchemical free energy perturbation with lambda replica-exchange (FEP/λ-REMD), umbrella sampling with Hamiltonian replica exchange (US/H-REMD), and string method with swarms-of-trajectories conformational transition pathways. Here, we report a robust and general implementation of MCAs for molecular dynamics (MD) simulations in the highly scalable program NAMD built upon the parallel programming system Charm++. Multiple concurrent NAMD instances are launched with internal partitions of Charm++ and located continuously within a single communication world. Messages between NAMD instances are passed by low-level point-to-point communication functions, which are accessible through NAMD’s Tcl scripting interface. The communication-enabled Tcl scripting provides a sustainable application interface for end users to realize generalized MCAs without modifying the source code. Illustrative applications of MCAs with fine-grained inter-copy communication structure, including global lambda exchange in FEP/λ-REMD, window swapping US/H-REMD in multidimensional order parameter space, and string method with swarms-of-trajectories were carried out on IBM Blue Gene/Q to demonstrate the versatility and massive scalability of the present implementation.

  3. A Jigsaw Lesson for Operations of Complex Numbers.

    Science.gov (United States)

    Lucas, Carol A.

    2000-01-01

    Explains the cooperative learning technique of jigsaw. Details the use of a jigsaw lesson for explaining complex numbers to intermediate algebra students. Includes copies of the handouts given to the expert groups. (Author/ASK)

  4. Comparison of medical students' learning approaches between electronic and hard copy team-based learning.

    Science.gov (United States)

    Sharaf, Fawzy; Alnohair, Sultan

    2017-01-01

    To compare the students' perception of team-based learning (TBL): The paper (hard copy) compared with the e-copy (electronic copy) in the family medicine course of the fifth year medical students, Qassim University College of Medicine. A cross-sectional study was conducted during the family medicine course in 2015-2016 to compare the hard copy and the e-copy TBL sessions. We used Google drive to distribute, collect and analyze the questionnaire. The results of the e-copy TBL are shown and displayed directly with each session to the students, which was not the same as practiced with hard copy. We used also SPSS (version 17 for Windows) for more statistical analysis. The total number of respondents of students in each was 96; a phase of TBL phase 1 (hard copy) and phase 2 (e-copy). Male were 64 (66.7%) and females 32 (33.3%). The first three knowledge questions showed no difference between the mean score between paper and e-copy TBL, but of the perception questions showed a significant difference between the paper and e-copy TBL. The results of the survey showed that the students prefer e-copy TBL as a course format, as it was an attraction for most of the students and making them even more successful in the key exam and e-copy TBL develop the skills needed to work productively in task-groups.

  5. What does motor efference copy represent? Evidence from speech production.

    Science.gov (United States)

    Niziolek, Caroline A; Nagarajan, Srikantan S; Houde, John F

    2013-10-09

    How precisely does the brain predict the sensory consequences of our actions? Efference copy is thought to reflect the predicted sensation of self-produced motor acts, such as the auditory feedback heard while speaking. Here, we use magnetoencephalographic imaging (MEG-I) in human speakers to demonstrate that efference copy prediction does not track movement variability across repetitions of the same motor task. Specifically, spoken vowels were less accurately predicted when they were less similar to a speaker's median production, even though the prediction is thought to be based on the very motor commands that generate each vowel. Auditory cortical responses to less prototypical speech productions were less suppressed, resembling responses to speech errors, and were correlated with later corrective movement, suggesting that the suppression may be functionally significant for error correction. The failure of the motor system to accurately predict less prototypical speech productions suggests that the efferent-driven suppression does not reflect a sensory prediction, but a sensory goal.

  6. COPY – MOVE IMAGE FORGERY DETECTION IN A PARALLEL ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    M.Sridevi

    2012-07-01

    Full Text Available Image forgery is the manipulation of digital images to conceal meaningful information or objects in the image. Among different image forgery techniques, copy – move forgery is one of the frequently used passive image forgery approach. The existing methods such as Principle Component Analysis (PCA, Discrete Wavelet Transform (DWT & Singular Value Decomposition (SVD are time consuming. Hence it is not suited for digital forensic science, surveillance system applications which uses image, video or multimedia security. This paper proposes a parallel algorithm for the copy – move image forgery detection to decrease execution time of the algorithm. The method uses overlapping blocks and lexicographical sorting in a parallel manner. The simulation results show that the proposed parallel version detects the forged region faster, so that it is best suited for real time applications.

  7. Electromagnetic fields, size, and copy of a single photon

    CERN Document Server

    Liu, Shan-Liang

    2016-01-01

    We propose the expressions of electromagnetic fields of a single photon which properly describe the known characteristics of a photon, derive the relations between the photon size and wavelength on basis of the expressions, reveal the differences between a photon and its copy, and give the specific expressions of annihilation and creation operators of a photon. The results show that a photon has length of half the wavelength, and its radius is proportional to square root of the wavelength; a photon and its copy have the phase difference of {\\pi} and constitute a phase-entangled state; the N-photon phase-entangled state, which is formed by the sequential stimulated emission and corresponds to the wave train in optics, is not a coherent state, but it is the eigenstate of the number operator of photons.

  8. Research on copying system of dynamic multiplex holographic stereograms

    Science.gov (United States)

    Fu, Huaiping; Yang, Hong; Zheng, Tong

    2003-05-01

    The most important advantage of holographic stereograms over conventional hologram is that they can produce 3D images at any desired scale with movement, holographers in many countries involved in the studies towards it. We began our works in the early 80's and accomplished two research projects automatic system for making synthetic holograms and multiplex synthetic rainbow holograms, Based on these works, a large scale holographic stereogram of an animated goldfish was made by us for practical advertisement. In order to meet the needs of the market, a copying system for making multiplex holographic stereograms, and a special kind of silver halide holographic film developed by us recently. The characteristic of the copying system and the property of the special silver-halide emulsion are introduced in this paper.

  9. Building Hot Snapshot Copy Based on Windows File System

    Institute of Scientific and Technical Information of China (English)

    WANG Lina; GUO Chi; WANG Dejun; ZHU Qin

    2006-01-01

    This paper describes a method for building hot snapshot copy based on windows-file system (HSCF). The architecture and running mechanism of HSCF are discussed after giving a comparison with other on-line backup technology. HSCF, based on a file system filter driver, protects computer data and ensures their integrity and consistency with following three steps:access to open files, synchronization and copy-on-write. Its strategies for improving system performance are analyzed including priority setting, incremental snapshot and load balance. HSCF is a new kind of snapshot technology to solve the data integrity and consistency problem in online backup, which is different from other storage-level snapshot and Open File Solution.

  10. Perceiving the impossible: how individuals with autism copy paradoxical figures.

    Science.gov (United States)

    Sheppard, Elizabeth; Ropar, Danielle; Mitchell, Peter

    2009-07-01

    Mottron and colleagues found that individuals with autism were less affected by geometric impossibility than comparison participants on a copying task. The current experiment sought to determine whether a local perceptual style could account for this. Participants with and without autism copied possible and impossible geometric figures. Geometric impossibility had a larger effect on drawing time for comparison participants than for those with autism. However, participants with autism did not use more localized drawing strategies. Strength of impossibility effect was associated with a global strategy amongst comparison participants but this relationship was not found amongst participants with autism. The findings suggest that differences in high-level conceptual processing may account for group differences in effects of impossibility.

  11. The copying power of one-state tree transducers

    DEFF Research Database (Denmark)

    Engelfriet, Joost; Skyum, Sven

    1982-01-01

    One-state deterministic top-down tree transducers (or, tree homomorphisms) cannot handle “prime copying,” i.e., their class of output (string) languages is not closed under the operation L → {$(w$)f(n) short parallel w ε L, f(n) greater-or-equal, slanted 1}, where f is any integer function whose...... range contains numbers with arbitrarily large prime factors (such as a polynomial). The exact amount of nonclosure under these copying operations is established for several classes of input (tree) languages. These results are relevant to the extended definable (or, restricted parallel level) languages......, to the syntax-directed translation of context-free languages, and to the tree transducer hierarchy....

  12. Analysis of the Multi-Phase Copying Garbage Collection Algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Podhorszki, Norbert [ORNL

    2009-01-01

    The multi-phase copying garbage collection was designed to avoid the need for large amount of reserved memory usually required for the copying types of garbage collection algorithms. The collection is performed in multiple phases using the available free memory. This paper proves that the number of phases depends on the size of the reserved memory and the ratio of the garbage and accessible objects. The performance of the implemented algorithm is tested in a fine-grained parallel Prolog system. We find that reserving only 10% of memory for garbage collection is sufficient for good performance in practice. Additionally, an improvement of the generic algorithm specifically for the tested parallel Prolog system is described.

  13. Novel population specific autosomal copy number variation and its functional analysis amongst Negritos from Peninsular Malaysia.

    Science.gov (United States)

    Mokhtar, Siti Shuhada; Marshall, Christian R; Phipps, Maude E; Thiruvahindrapuram, Bhooma; Lionel, Anath C; Scherer, Stephen W; Peng, Hoh Boon

    2014-01-01

    Copy number variation (CNV) has been recognized as a major contributor to human genome diversity. It plays an important role in determining phenotypes and has been associated with a number of common and complex diseases. However CNV data from diverse populations is still limited. Here we report the first investigation of CNV in the indigenous populations from Peninsular Malaysia. We genotyped 34 Negrito genomes from Peninsular Malaysia using the Affymetrix SNP 6.0 microarray and identified 48 putative novel CNVs, consisting of 24 gains and 24 losses, of which 5 were identified in at least 2 unrelated samples. These CNVs appear unique to the Negrito population and were absent in the DGV, HapMap3 and Singapore Genome Variation Project (SGVP) datasets. Analysis of gene ontology revealed that genes within these CNVs were enriched in the immune system (GO:0002376), response to stimulus mechanisms (GO:0050896), the metabolic pathways (GO:0001852), as well as regulation of transcription (GO:0006355). Copy number gains in CNV regions (CNVRs) enriched with genes were significantly higher than the losses (P value Malaysia.

  14. NF1 single and multi-exons copy number variations in neurofibromatosis type 1.

    Science.gov (United States)

    Imbard, Apolline; Pasmant, Eric; Sabbagh, Audrey; Luscan, Armelle; Soares, Magali; Goussard, Philippe; Blanché, Hélène; Laurendeau, Ingrid; Ferkal, Salah; Vidaud, Michel; Pinson, Stéphane; Bellanne-Chantelot, Christine; Vidaud, Dominique; Wolkenstein, Pierre; Parfait, Béatrice

    2015-04-01

    Neurofibromatosis type 1 (NF1) is caused by dominant loss-of-function mutations of the tumor suppressor NF1 containing 57 constitutive coding exons. A huge number of different pathogenic NF1 alterations has been reported. The aim of the present study was to evaluate the usefulness of a multiplex ligation-dependent probe amplification (MLPA) approach in NF1 patients to detect single and multi-exon NF1 gene copy number variations. A genotype-phenotype correlation was then performed in NF1 patients carrying these types of genetic alterations. Among 565 NF1 index cases from the French NF1 cohort, single and multi-exon deletions/duplications screening identified NF1 partial deletions/duplications in 22 patients (~4%) using MLPA analysis. Eight single exon deletions, 11 multiple exons deletions, 1 complex rearrangement and 2 duplications were identified. All results were confirmed using a custom array-CGH. MLPA and custom array-CGH allowed the identification of rearrangements that were missed by cDNA/DNA sequencing or microsatellite analysis. We then performed a targeted next-generation sequencing of NF1 that allowed confirmation of all 22 rearrangements. No clear genotype-phenotype correlations were found for the most clinically significant disease features of NF1 in patients with single and multi-exons NF1 gene copy number changes.

  15. On-chip real-time single-copy polymerase chain reaction in picoliter droplets

    Energy Technology Data Exchange (ETDEWEB)

    Beer, N R; Hindson, B; Wheeler, E; Hall, S B; Rose, K A; Kennedy, I; Colston, B

    2007-04-20

    The first lab-on-chip system for picoliter droplet generation and PCR amplification with real-time fluorescence detection has performed PCR in isolated droplets at volumes 10{sup 6} smaller than commercial real-time PCR systems. The system utilized a shearing T-junction in a silicon device to generate a stream of monodisperse picoliter droplets that were isolated from the microfluidic channel walls and each other by the oil phase carrier. An off-chip valving system stopped the droplets on-chip, allowing them to be thermal cycled through the PCR protocol without droplet motion. With this system a 10-pL droplet, encapsulating less than one copy of viral genomic DNA through Poisson statistics, showed real-time PCR amplification curves with a cycle threshold of {approx}18, twenty cycles earlier than commercial instruments. This combination of the established real-time PCR assay with digital microfluidics is ideal for isolating single-copy nucleic acids in a complex environment.

  16. Genome Architecture and Its Roles in Human Copy Number Variation

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-12-01

    Full Text Available Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs, are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

  17. Mate-choice copying as Bayesian decision making.

    Science.gov (United States)

    Uehara, Takashi; Yokomizo, Hiroyuki; Iwasa, Yo

    2005-03-01

    Mate-choice copying by females has been reported in fishes (e.g., guppies) and lekking birds. Presumably, females assess males' quality using both information from direct observation of males and information acquired by observing other females' choices. Here, we study mathematically the conditions under which mate-choice copying is advantageous on the basis of Bayesian decision theory. A female may observe the mate choice of another female, called the model female, who has performed an optimal choice based on her own judgment. The conditions required for the focal female to choose the same mate as that chosen by the model female should depend on the male's appearance to her, the reliability of her own judgment of male quality, and the reliability of the model females. When three or more females are involved, the optimal mate choice critically depends on whether multiple model females make decisions independently or they themselves copy the choices of others. If two equally reliable females choose different males, the choice of the second female, made knowing the choice of the first, should have a stronger effect on the choice of the third (focal) female. This "last-choice precedence" should be tested experimentally.

  18. Copy number variation of KIR genes influences HIV-1 control

    DEFF Research Database (Denmark)

    Pelak, Kimberly; Need, Anna C; Fellay, Jacques

    2011-01-01

    A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses...... the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3...... individuals with multiple copies of KIR3DL1, in the presence of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly, and associated with a significant expansion in the frequency of KIR3DS1+, but not KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the relative...

  19. Large multi-allelic copy number variations in humans

    Science.gov (United States)

    Handsaker, Robert E.; Van Doren, Vanessa; Berman, Jennifer R.; Genovese, Giulio; Kashin, Seva; Boettger, Linda M.; McCarroll, Steven A.

    2015-01-01

    Thousands of genome segments appear to be present in widely varying copy number in different human genomes. We developed ways to use increasingly abundant whole genome sequence data to identify the copy numbers, alleles and haplotypes present at most large, multi-allelic CNVs (mCNVs). We analyzed 849 genomes sequenced by the 1000 Genomes Project to identify most large (>5 kb) mCNVs, including 3,878 duplications, of which 1,356 appear to have three or more segregating alleles. We find that mCNVs give rise to most human gene-dosage variation – exceeding sevenfold the contribution of deletions and biallelic duplications – and that this variation in gene dosage generates abundant variation in gene expression. We describe “runaway duplication haplotypes” in which genes, including HPR and ORM1, have mutated to high copy number on specific haplotypes. We describe partially successful initial strategies for analyzing mCNVs via imputation and provide an initial data resource to support such analyses. PMID:25621458

  20. A Method for Calling Copy Number Polymorphism Using Haplotypes

    Directory of Open Access Journals (Sweden)

    Gun Ho eJang

    2013-09-01

    Full Text Available Single nucleotide polymorphism (SNP and copy number variation (CNV are both widespread characteristic of the human genome, but are often called separately on common genotyping platforms. To capture integrated SNP and CNV information, methods have been developed for calling allelic specific copy numbers or so called copy number polymorphism (CNP, using limited inter-marker correlation. In this paper, we proposed a haplotype-based maximum likelihood method to call CNP, which takes advantage of the valuable multi-locus linkage disequilibrium (LD information in the population. We also developed a computationally efficient EM algorithm to estimate haplotype frequencies and optimize individual CNP calls simultaneously, even at presence of missing data. Through simulations, we demonstrated our model is more sensitive and accurate in detecting various CNV regions, compared with commonly-used CNV calling methods including PennCNV, another hidden Markov model using CNP, a scan statistic, segCNV, and cnvHap. Our method often performs better in the regions with higher LD, in longer CNV regions, and in common CNV than the opposite. We implemented our method on the genotypes of 90 HapMap CEU samples and 23 patients with acute lung injury (ALI. For each ALI patient the genotyping was performed twice. The CNPs from our method show good consistency and accuracy comparable to others.

  1. VESICULAR TRANSPORT. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly.

    Science.gov (United States)

    Dodonova, S O; Diestelkoetter-Bachert, P; von Appen, A; Hagen, W J H; Beck, R; Beck, M; Wieland, F; Briggs, J A G

    2015-07-10

    Transport of material within cells is mediated by trafficking vesicles that bud from one cellular compartment and fuse with another. Formation of a trafficking vesicle is driven by membrane coats that localize cargo and polymerize into cages to bend the membrane. Although extensive structural information is available for components of these coats, the heterogeneity of trafficking vesicles has prevented an understanding of how complete membrane coats assemble on the membrane. We combined cryo-electron tomography, subtomogram averaging, and cross-linking mass spectrometry to derive a complete model of the assembled coat protein complex I (COPI) coat involved in traffic between the Golgi and the endoplasmic reticulum. The highly interconnected COPI coat structure contradicted the current "adaptor-and-cage" understanding of coated vesicle formation.

  2. Copy number variations genotyping technology%拷贝数变异的分型检测技术

    Institute of Scientific and Technical Information of China (English)

    李朋祥; 晁天柱; 肖君华

    2012-01-01

    CNV ( copy number variant) is an important form of genetic variation in the genome.Studies have shown that CNVs are associated with many human complex diseases.CNVs play a significant role in the studies of individual phenotypic differences and genome evolution.In this article,we reviewed the principle,advances,advantages and disadvantages,significance of technologies of detecting CNVs.%拷贝数变异(copy number variants,CNVs)是生物基因组中一种重要的遗传变异形式.研究发现CNVs与许多人类复杂疾病相关,在研究个体表型差异和基因组进化上具有重要意义.现就各CNVs检测技术的原理、发展现状、优缺点及意义作一综述.

  3. Cyanobacteria Maintain Constant Protein Concentration despite Genome Copy-Number Variation.

    Science.gov (United States)

    Zheng, Xiao-Yu; O'Shea, Erin K

    2017-04-18

    The cyanobacterium Synechococcus elongatus PCC 7942 has multiple copies of its single chromosome, and the copy number varies in individual cells, providing an ideal system to study the effect of genome copy-number variation on cell size and gene expression. Using single-cell fluorescence imaging, we found that protein concentration remained constant across individual cells regardless of genome copy number. Cell volume and the total protein amount from a single gene were both positively, linearly correlated with genome copy number, suggesting that changes in cell volume play an important role in buffering genome copy-number variance. This study provides a quantitative examination of gene expression regulation in cells with variable genome copies and sheds light on the compensation mechanisms for variance in genome copy number. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. The yeast Ski complex is a hetero-tetramer

    OpenAIRE

    Synowsky, S.A.; Heck, A.J.R.

    2008-01-01

    The yeast Ski complex assists the exosome in the degradation of mRNA. The Ski complex consists of three components; Ski2, Ski3, and Ski8, believed to be present in a 1:1:1 stoichiometry. Measuring the mass of intact isolated endogenously expressed Ski complexes by native mass spectrometry we unambiguously demonstrate that the Ski complex has a hetero-tetrameric stoichiometry consisting of one copy of Ski2 and Ski3 and two copies of Ski8. To validate the stoichiometry of the Ski complex, we pe...

  5. An integrated Bayesian analysis of LOH and copy number data

    Directory of Open Access Journals (Sweden)

    Hutter Marcus

    2010-06-01

    Full Text Available Abstract Background Cancer and other disorders are due to genomic lesions. SNP-microarrays are able to measure simultaneously both genotype and copy number (CN at several Single Nucleotide Polymorphisms (SNPs along the genome. CN is defined as the number of DNA copies, and the normal is two, since we have two copies of each chromosome. The genotype of a SNP is the status given by the nucleotides (alleles which are present on the two copies of DNA. It is defined homozygous or heterozygous if the two alleles are the same or if they differ, respectively. Loss of heterozygosity (LOH is the loss of the heterozygous status due to genomic events. Combining CN and LOH data, it is possible to better identify different types of genomic aberrations. For example, a long sequence of homozygous SNPs might be caused by either the physical loss of one copy or a uniparental disomy event (UPD, i.e. each SNP has two identical nucleotides both derived from only one parent. In this situation, the knowledge of the CN can help in distinguishing between these two events. Results To better identify genomic aberrations, we propose a method (called gBPCR which infers the type of aberration occurred, taking into account all the possible influence in the microarray detection of the homozygosity status of the SNPs, resulting from an altered CN level. Namely, we model the distributions of the detected genotype, given a specific genomic alteration and we estimate the parameters involved on public reference datasets. The estimation is performed similarly to the modified Bayesian Piecewise Constant Regression, but with improved estimators for the detection of the breakpoints. Using artificial and real data, we evaluate the quality of the estimation of gBPCR and we also show that it outperforms other well-known methods for LOH estimation. Conclusions We propose a method (gBPCR for the estimation of both LOH and CN aberrations, improving their estimation by integrating both types

  6. 17 CFR 232.104 - Unofficial PDF copies included in an electronic submission.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Unofficial PDF copies included... Filing Requirements § 232.104 Unofficial PDF copies included in an electronic submission. (a) An... (§ 249.101 of this chapter) or a Form D (§ 239.500 of this chapter), may include one unofficial PDF copy...

  7. 36 CFR 703.19 - Requests for authenticated copies of Library documents.

    Science.gov (United States)

    2010-07-01

    ... copies of Library documents. 703.19 Section 703.19 Parks, Forests, and Public Property LIBRARY OF... Documents in Certain Legal Proceedings Where the Library Is Not a Party § 703.19 Requests for authenticated copies of Library documents. Requests for authenticated copies of Library documents for purposes...

  8. 78 FR 40156 - Agency Information Collection Activities; Proposed Collection; Comment Request; Copy Testing of...

    Science.gov (United States)

    2013-07-03

    ... Collection; Comment Request; Copy Testing of the Food and Drug Administration's General Market Youth Tobacco... allow 60 days for public comment in response to the notice. This notice solicits comments on Copy... appropriate, and other forms of information technology. Copy Testing of FDA's General Market Youth Tobacco...

  9. Integrated analysis of DNA copy number and gene expression microarray data using gene sets

    NARCIS (Netherlands)

    R.X. de Menezes (Renee); M. Boetzer (Marten); M. Sieswerda (Melle); G.J.B. van Ommen; J.M. Boer (Judith)

    2009-01-01

    textabstractBackground: Genes that play an important role in tumorigenesis are expected to show association between DNA copy number and RNA expression. Optimal power to find such associations can only be achieved if analysing copy number and gene expression jointly. Furthermore, some copy number

  10. Does Visual Attention Span Relate to Eye Movements during Reading and Copying?

    Science.gov (United States)

    Bosse, Marie-Line; Kandel, Sonia; Prado, Chloé; Valdois, Sylviane

    2014-01-01

    This research investigated whether text reading and copying involve visual attention-processing skills. Children in grades 3 and 5 read and copied the same text. We measured eye movements while reading and the number of gaze lifts (GL) during copying. The children were also administered letter report tasks that constitute an estimation of the…

  11. Distributed memory compiler methods for irregular problems: Data copy reuse and runtime partitioning

    Science.gov (United States)

    Das, Raja; Ponnusamy, Ravi; Saltz, Joel; Mavriplis, Dimitri

    1991-01-01

    Outlined here are two methods which we believe will play an important role in any distributed memory compiler able to handle sparse and unstructured problems. We describe how to link runtime partitioners to distributed memory compilers. In our scheme, programmers can implicitly specify how data and loop iterations are to be distributed between processors. This insulates users from having to deal explicitly with potentially complex algorithms that carry out work and data partitioning. We also describe a viable mechanism for tracking and reusing copies of off-processor data. In many programs, several loops access the same off-processor memory locations. As long as it can be verified that the values assigned to off-processor memory locations remain unmodified, we show that we can effectively reuse stored off-processor data. We present experimental data from a 3-D unstructured Euler solver run on iPSC/860 to demonstrate the usefulness of our methods.

  12. Platform comparison of detecting copy number variants with microarrays and whole-exome sequencing

    Directory of Open Access Journals (Sweden)

    Joep de Ligt

    2014-12-01

    Full Text Available Copy number variation (CNV is a common source of genetic variation that has been implicated in many genomic disorders, Mendelian diseases, and common/complex traits. Genomic microarrays are often employed for CNV detection. More recently, whole-exome sequencing (WES has enabled detection of clinically relevant point mutations and small insertion—deletion exome wide. We evaluated (de Ligt et al. 2013 [1] the utility of short-read WES (SOLiD 5500xl to detect clinically relevant CNVs in DNA from 10 patients with intellectual disability and compared these results to data from three independent high-resolution microarray platforms. Calls made by the different platforms and detection software are available at dbVar under nstd84.

  13. Inverted Low-Copy Repeats and Genome Instability—A Genome-Wide Analysis

    Science.gov (United States)

    Dittwald, Piotr; Gambin, Tomasz; Gonzaga-Jauregui, Claudia; Carvalho, Claudia M.B.; Lupski, James R.; Stankiewicz, Paweł; Gambin, Anna

    2013-01-01

    Inverse paralogous low-copy repeats (IP-LCRs) can cause genome instability by nonallelic homologous recombination (NAHR)-mediated balanced inversions. When disrupting a dosage-sensitive gene(s), balanced inversions can lead to abnormal phenotypes. We delineated the genome-wide distribution of IP-LCRs >1 kB in size with >95% sequence identity and mapped the genes, potentially intersected by an inversion, that overlap at least one of the IP-LCRs. Remarkably, our results show that 12.0% of the human genome is potentially susceptible to such inversions and 942 genes, 99 of which are on the X chromosome, are predicted to be disrupted secondary to such an inversion! In addition, IP-LCRs larger than 800 bp with at least 98% sequence identity (duplication/triplication facilitating IP-LCRs, DTIP-LCRs) were recently implicated in the formation of complex genomic rearrangements with a duplication-inverted triplication–duplication (DUP-TRP/INV-DUP) structure by a replication-based mechanism involving a template switch between such inverted repeats. We identified 1,551 DTIP-LCRs that could facilitate DUP-TRP/INV-DUP formation. Remarkably, 1,445 disease-associated genes are at risk of undergoing copy-number gain as they map to genomic intervals susceptible to the formation of DUP-TRP/INV-DUP complex rearrangements. We implicate inverted LCRs as a human genome architectural feature that could potentially be responsible for genomic instability associated with many human disease traits. PMID:22965494

  14. Environmental change drives accelerated adaptation through stimulated copy number variation

    Science.gov (United States)

    Hull, Ryan M.; Cruz, Cristina; Jack, Carmen V.

    2017-01-01

    Copy number variation (CNV) is rife in eukaryotic genomes and has been implicated in many human disorders, particularly cancer, in which CNV promotes both tumorigenesis and chemotherapy resistance. CNVs are considered random mutations but often arise through replication defects; transcription can interfere with replication fork progression and stability, leading to increased mutation rates at highly transcribed loci. Here we investigate whether inducible promoters can stimulate CNV to yield reproducible, environment-specific genetic changes. We propose a general mechanism for environmentally-stimulated CNV and validate this mechanism for the emergence of copper resistance in budding yeast. By analysing a large cohort of individual cells, we directly demonstrate that CNV of the copper-resistance gene CUP1 is stimulated by environmental copper. CNV stimulation accelerates the formation of novel alleles conferring enhanced copper resistance, such that copper exposure actively drives adaptation to copper-rich environments. Furthermore, quantification of CNV in individual cells reveals remarkable allele selectivity in the rate at which specific environments stimulate CNV. We define the key mechanistic elements underlying this selectivity, demonstrating that CNV is regulated by both promoter activity and acetylation of histone H3 lysine 56 (H3K56ac) and that H3K56ac is required for CUP1 CNV and efficient copper adaptation. Stimulated CNV is not limited to high-copy CUP1 repeat arrays, as we find that H3K56ac also regulates CNV in 3 copy arrays of CUP1 or SFA1 genes. The impact of transcription on DNA damage is well understood, but our research reveals that this apparently problematic association forms a pathway by which mutations can be directed to particular loci in particular environments and furthermore that this mutagenic process can be regulated through histone acetylation. Stimulated CNV therefore represents an unanticipated and remarkably controllable pathway

  15. Copy number variation plays an important role in clinical epilepsy

    Science.gov (United States)

    Olson, Heather; Shen, Yiping; Avallone, Jennifer; Sheidley, Beth R.; Pinsky, Rebecca; Bergin, Ann M.; Berry, Gerard T.; Duffy, Frank H.; Eksioglu, Yaman; Harris, David J.; Hisama, Fuki M.; Ho, Eugenia; Irons, Mira; Jacobsen, Christina M.; James, Philip; Kothare, Sanjeev; Khwaja, Omar; Lipton, Jonathan; Loddenkemper, Tobias; Markowitz, Jennifer; Maski, Kiran; Megerian, J. Thomas; Neilan, Edward; Raffalli, Peter C.; Robbins, Michael; Roberts, Amy; Roe, Eugene; Rollins, Caitlin; Sahin, Mustafa; Sarco, Dean; Schonwald, Alison; Smith, Sharon E.; Soul, Janet; Stoler, Joan M.; Takeoka, Masanori; Tan, Wen-Han; Torres, Alcy R.; Tsai, Peter; Urion, David K.; Weissman, Laura; Wolff, Robert; Wu, Bai-Lin; Miller, David T.; Poduri, Annapurna

    2015-01-01

    Objective To evaluate the role of copy number abnormalities detectable by chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. Methods We identified patients with ICD-9 codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children’s Hospital. We reviewed medical records and included patients meeting criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. Results Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1–4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18 kb to 142 Mb, and 34% were over 500 kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or “hotspots.” We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. Interpretation Copy number abnormalities play an important role in patients with epilepsy. Given that the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy. PMID:24811917

  16. Bias of selection on human copy-number variants.

    Directory of Open Access Journals (Sweden)

    2006-02-01

    Full Text Available Although large-scale copy-number variation is an important contributor to conspecific genomic diversity, whether these variants frequently contribute to human phenotype differences remains unknown. If they have few functional consequences, then copy-number variants (CNVs might be expected both to be distributed uniformly throughout the human genome and to encode genes that are characteristic of the genome as a whole. We find that human CNVs are significantly overrepresented close to telomeres and centromeres and in simple tandem repeat sequences. Additionally, human CNVs were observed to be unusually enriched in those protein-coding genes that have experienced significantly elevated synonymous and nonsynonymous nucleotide substitution rates, estimated between single human and mouse orthologues. CNV genes encode disproportionately large numbers of secreted, olfactory, and immunity proteins, although they contain fewer than expected genes associated with Mendelian disease. Despite mouse CNVs also exhibiting a significant elevation in synonymous substitution rates, in most other respects they do not differ significantly from the genomic background. Nevertheless, they encode proteins that are depleted in olfactory function, and they exhibit significantly decreased amino acid sequence divergence. Natural selection appears to have acted discriminately among human CNV genes. The significant overabundance, within human CNVs, of genes associated with olfaction, immunity, protein secretion, and elevated coding sequence divergence, indicates that a subset may have been retained in the human population due to the adaptive benefit of increased gene dosage. By contrast, the functional characteristics of mouse CNVs either suggest that advantageous gene copies have been depleted during recent selective breeding of laboratory mouse strains or suggest that they were preferentially fixed as a consequence of the larger effective population size of wild mice. It

  17. Fundamental Costs in the Production and Destruction of Persistent Polymer Copies

    Science.gov (United States)

    Ouldridge, Thomas E.; Rein ten Wolde, Pieter

    2017-04-01

    Producing a polymer copy of a polymer template is central to biology, and effective copies must persist after template separation. We show that this separation has three fundamental thermodynamic effects. First, polymer-template interactions do not contribute to overall reaction thermodynamics and hence cannot drive the process. Second, the equilibrium state of the copied polymer is template independent and so additional work is required to provide specificity. Finally, the mixing of copies from distinct templates makes correlations between template and copy sequences unexploitable, combining with copying inaccuracy to reduce the free energy stored in a polymer ensemble. These basic principles set limits on the underlying costs and resource requirements, and suggest design principles, for autonomous copying and replication in biological and synthetic systems.

  18. CNVrd, a read-depth algorithm for assigning copy-number at the FCGR locus: population-specific tagging of copy number variation at FCGR3B.

    Directory of Open Access Journals (Sweden)

    Hoang tan Nguyen

    Full Text Available The extent of contribution from common gene copy number (CN variants in human disease is currently unresolved. Part of the reason for this is the technical difficulty in directly measuring CN variation (CNV using molecular methods, and the lack of single nucleotide polymorphisms (SNPs that can tag complex CNV that has arisen multiple times on different SNP haplotypes. One CNV locus implicated in human disease is FCGR. Here we aimed to use next-generation sequencing (NGS data from the 1000 Genomes Project to assign CN at FCGR3A and FCGR3B and to comprehensively assess the ability of SNPs to tag specific CN variants. A read-depth algorithm was developed (CNVrd and validated on a subset of HapMap samples using CN assignments that had previously been determined using molecular and microarray methods. At 7 out of 9 other complex loci there was >90% concordance with microarray data. However, given that some prior knowledge of CN is required, the generalizability of CNVrd is limited and should be applied to other complex CNV loci with caution. Subsequently, CN was assigned et FCGR3B using CNVrd in a total of 952 samples from the 1000 Genomes Project, using three classes and SNPs that correlated with duplication were identified. The best tag SNP was observed in the Mexican-American sample set for duplication at FCGR3B. This SNP (rs117435514, r² = 0.79 also tagged similar duplication in Chinese and Japanese (r² = 0.35-0.60, but not in Caucasian or African. No tag SNP for duplication at FCGR3A or deletion at FCGR3B was identified in any population. We conclude that it is possible to tag CNV at the FCGR locus, but CN and SNPs have to be characterized and correlated on a population-specific basis.

  19. Conserved genetic regions across angiosperms as tools to develop single-copy nuclear markers in gymnosperms: an example using cycads.

    Science.gov (United States)

    Salas-Leiva, Dayana E; Meerow, Alan W; Francisco-Ortega, Javier; Calonje, Michael; Griffith, M Patrick; Stevenson, Dennis W; Nakamura, Kyoko

    2014-07-01

    Several individuals of the Caribbean Zamia clade and other cycad genera were used to identify single-copy nuclear genes for phylogeographic and phylogenetic studies in Cycadales. Two strategies were employed to select target loci: (i) a tblastX search of Arabidopsis conserved ortholog sequence (COS) set and (ii) a tblastX search of Arabidopsis-Populus-Vitis-Oryza Shared Single-Copy genes (APVO SSC) against the EST Zamia databases in GenBank. From the first strategy, 30 loci were selected, and from the second, 16 loci. In both cases, the matching GenBank accessions of Zamia were used as a query for retrieving highly similar sequences from Cycas, Picea, Pinus species or Ginkgo biloba. After retrieving and aligning all the sequences in each locus, intron predictions were completed to assist in primer design. PCR was carried out in three rounds to detect paralogous loci. A total of 29 loci were successfully amplified as a single band of which 20 were likely single-copy loci. These loci showed different diversity and divergence levels. A preliminary screening allowed us to select 8 promising loci (40S, ATG2, BG, GroES, GTP, LiSH, PEX4 and TR) for the Zamia pumila complex and 4 loci (COS26, GroES, GTP and HTS) for all other cycad genera.

  20. CONAN: copy number variation analysis software for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Wichmann Heinz-Erich

    2010-06-01

    Full Text Available Abstract Background Genome-wide association studies (GWAS based on single nucleotide polymorphisms (SNPs revolutionized our perception of the genetic regulation of complex traits and diseases. Copy number variations (CNVs promise to shed additional light on the genetic basis of monogenic as well as complex diseases and phenotypes. Indeed, the number of detected associations between CNVs and certain phenotypes are constantly increasing. However, while several software packages support the determination of CNVs from SNP chip data, the downstream statistical inference of CNV-phenotype associations is still subject to complicated and inefficient in-house solutions, thus strongly limiting the performance of GWAS based on CNVs. Results CONAN is a freely available client-server software solution which provides an intuitive graphical user interface for categorizing, analyzing and associating CNVs with phenotypes. Moreover, CONAN assists the evaluation process by visualizing detected associations via Manhattan plots in order to enable a rapid identification of genome-wide significant CNV regions. Various file formats including the information on CNVs in population samples are supported as input data. Conclusions CONAN facilitates the performance of GWAS based on CNVs and the visual analysis of calculated results. CONAN provides a rapid, valid and straightforward software solution to identify genetic variation underlying the 'missing' heritability for complex traits that remains unexplained by recent GWAS. The freely available software can be downloaded at http://genepi-conan.i-med.ac.at.

  1. Copy number variation of KIR genes influences HIV-1 control

    DEFF Research Database (Denmark)

    Pelak, Kimberly; Need, Anna C; Fellay, Jacques;

    2011-01-01

    A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses...... the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3......DS1 count associates with a lower viral set point if its putative ligand is present (p = 0.00028), as does an increase in KIR3DL1 count in the presence of KIR3DS1 and appropriate ligands for both receptors (p = 0.0015). We further provide functional data that demonstrate that NK cells from...

  2. Copy Number Alterations and Methylation in Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Mona S. Jahromi

    2011-01-01

    Full Text Available Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease.

  3. Flip-invariant SIFT for copy and object detection.

    Science.gov (United States)

    Zhao, Wan-Lei; Ngo, Chong-Wah

    2013-03-01

    Scale-invariant feature transform (SIFT) feature has been widely accepted as an effective local keypoint descriptor for its invariance to rotation, scale, and lighting changes in images. However, it is also well known that SIFT, which is derived from directionally sensitive gradient fields, is not flip invariant. In real-world applications, flip or flip-like transformations are commonly observed in images due to artificial flipping, opposite capturing viewpoint, or symmetric patterns of objects. This paper proposes a new descriptor, named flip-invariant SIFT (or F-SIFT), that preserves the original properties of SIFT while being tolerant to flips. F-SIFT starts by estimating the dominant curl of a local patch and then geometrically normalizes the patch by flipping before the computation of SIFT. We demonstrate the power of F-SIFT on three tasks: large-scale video copy detection, object recognition, and detection. In copy detection, a framework, which smartly indices the flip properties of F-SIFT for rapid filtering and weak geometric checking, is proposed. F-SIFT not only significantly improves the detection accuracy of SIFT, but also leads to a more than 50% savings in computational cost. In object recognition, we demonstrate the superiority of F-SIFT in dealing with flip transformation by comparing it to seven other descriptors. In object detection, we further show the ability of F-SIFT in describing symmetric objects. Consistent improvement across different kinds of keypoint detectors is observed for F-SIFT over the original SIFT.

  4. Plasmid copy number noise in monoclonal populations of bacteria

    Science.gov (United States)

    Wong Ng, Jérôme; Chatenay, Didier; Robert, Jérôme; Poirier, Michael Guy

    2010-01-01

    Plasmids are extra chromosomal DNA that can confer to their hosts’ supplementary characteristics such as antibiotic resistance. Plasmids code for their copy number through their own replication frequency. Even though the biochemical networks underlying the plasmid copy number (PCN) regulation processes have been studied and modeled, no measurement of the heterogeneity in PCN within a whole population has been done. We have developed a fluorescent-based measurement system, which enables determination of the mean and noise in PCN within a monoclonal population of bacteria. Two different fluorescent protein reporters were inserted: one on the chromosome and the other on the plasmid. The fluorescence of these bacteria was measured with a microfluidic flow cytometry device. We show that our measurements are consistent with known plasmid characteristics. We find that the partitioning system lowers the PCN mean and standard deviation. Finally, bacterial populations were allowed to grow without selective pressure. In this case, we were able to determine the plasmid loss rate and growth inhibition effect.

  5. One Method for Inhibiting the Copying of Online Homework

    Science.gov (United States)

    Busch, Hauke

    2017-10-01

    Over the last several years online homework solutions have become ever more accessible to students. This is due in part to programs like Yahoo Answers, Chegg, publisher solution manuals, and other web resources that are readily available online. The student can easily search any physics homework problem posted on the web in a matter of seconds and have the solution. The results of this are an apparent increase in students copying the answers without solving the problem, which may lead to an increase in homework scores but a reduction in exam scores and an overall lower grade in the class. A secondary effect that may be observed is that tutoring centers, recitations, and supplemental instructor sessions have reduced student attendance. Some might say that the readily available solutions for homework systems such as MasteringPhysics (MP), WebAssign, etc. have greatly diminished them as a teaching tool, and for grading and assessing students' performance in a course. It is the purpose of this paper to offer a possible solution for preventing students from potentially copying online homework solutions.

  6. BCJ duality and double copy in the closed string sector

    Energy Technology Data Exchange (ETDEWEB)

    Ochirov, Alexander; Tourkine, Piotr [Institut de Physique Théorique, CEA-Saclay,F-91191 Gif-sur-Yvette cedex (France)

    2014-05-28

    This paper is focused on the loop-level understanding of the Bern-Carrasco-Johansson double copy procedure that relates the integrands of gauge theory and gravity scattering amplitudes. At four points, the first non-trivial example of that construction is one-loop amplitudes in N = 2 super-Yang-Mills theory and the symmetric realization of N = 4 matter-coupled supergravity. Our approach is to use both field and string theory in parallel to analyze these amplitudes. The closed string provides a natural framework to analyze the BCJ construction, in which the left- and right-moving sectors separately create the color and kinematics at the integrand level. At tree level, in a five-point example, we show that the Mafra-Schlotterer-Stieberger procedure gives a new direct proof of the color-kinematics double copy. We outline the extension of that argument to n points. At loop level, the field-theoretic BCJ construction of N = 2 SYM amplitudes introduces new terms, unexpected from the string theory perspective. We discuss to what extent we can relate them to the terms coming from the interactions between left- and right-movers in the string-theoretic gravity construction.

  7. Developmental environment, cultural transmission, and mate choice copying

    Science.gov (United States)

    Dugatkin, Lee Alan

    2007-08-01

    Using female mate choice copying as a rudimentary form of cultural transmission, this study provides evidence that social environment during development has a significant effect on the tendency to use culturally acquired information. Groups of newborn guppies (Poecilia reticulata) were raised for 35 days in 1 of 5 “developmental environments”. Groups of 15 newborns were raised in pools with no adults (treatment 1), both adult male and female guppies (treatments 2 and 3), only adult females (treatment 4) or only adult males (treatment 5). Mature females raised in treatments 1 and 2, but not treatments 3, 4, and 5, copied the mate choice of others. Treatments 1 and 2 correspond to social structures that guppies experience during their development in the wild. Newborn guppies swim together in shoals (analogous to treatment 1). As they mature, juveniles join schools of adult males and females (analogous to treatments 2). At no time during the normal developmental process are juveniles found with males, but only unreceptive females (as was the case for long periods in treatment 3) or in the presence of adults of only one sex (analogous to treatments 4 and 5). As such, normal developmental environments prime guppies for cultural transmission, while unnatural environments fail to do so.

  8. Developmental environment, cultural transmission, and mate choice copying.

    Science.gov (United States)

    Dugatkin, Lee Alan

    2007-08-01

    Using female mate choice copying as a rudimentary form of cultural transmission, this study provides evidence that social environment during development has a significant effect on the tendency to use culturally acquired information. Groups of newborn guppies (Poecilia reticulata) were raised for 35 days in 1 of 5 "developmental environments". Groups of 15 newborns were raised in pools with no adults (treatment 1), both adult male and female guppies (treatments 2 and 3), only adult females (treatment 4) or only adult males (treatment 5). Mature females raised in treatments 1 and 2, but not treatments 3, 4, and 5, copied the mate choice of others. Treatments 1 and 2 correspond to social structures that guppies experience during their development in the wild. Newborn guppies swim together in shoals (analogous to treatment 1). As they mature, juveniles join schools of adult males and females (analogous to treatments 2). At no time during the normal developmental process are juveniles found with males, but only unreceptive females (as was the case for long periods in treatment 3) or in the presence of adults of only one sex (analogous to treatments 4 and 5). As such, normal developmental environments prime guppies for cultural transmission, while unnatural environments fail to do so.

  9. Chromosomal Copy Number Variation in Saccharomyces pastorianus Is Evidence for Extensive Genome Dynamics in Industrial Lager Brewing Strains.

    Science.gov (United States)

    van den Broek, M; Bolat, I; Nijkamp, J F; Ramos, E; Luttik, M A H; Koopman, F; Geertman, J M; de Ridder, D; Pronk, J T; Daran, J-M

    2015-09-01

    Lager brewing strains of Saccharomyces pastorianus are natural interspecific hybrids originating from the spontaneous hybridization of Saccharomyces cerevisiae and Saccharomyces eubayanus. Over the past 500 years, S. pastorianus has been domesticated to become one of the most important industrial microorganisms. Production of lager-type beers requires a set of essential phenotypes, including the ability to ferment maltose and maltotriose at low temperature, the production of flavors and aromas, and the ability to flocculate. Understanding of the molecular basis of complex brewing-related phenotypic traits is a prerequisite for rational strain improvement. While genome sequences have been reported, the variability and dynamics of S. pastorianus genomes have not been investigated in detail. Here, using deep sequencing and chromosome copy number analysis, we showed that S. pastorianus strain CBS1483 exhibited extensive aneuploidy. This was confirmed by quantitative PCR and by flow cytometry. As a direct consequence of this aneuploidy, a massive number of sequence variants was identified, leading to at least 1,800 additional protein variants in S. pastorianus CBS1483. Analysis of eight additional S. pastorianus strains revealed that the previously defined group I strains showed comparable karyotypes, while group II strains showed large interstrain karyotypic variability. Comparison of three strains with nearly identical genome sequences revealed substantial chromosome copy number variation, which may contribute to strain-specific phenotypic traits. The observed variability of lager yeast genomes demonstrates that systematic linking of genotype to phenotype requires a three-dimensional genome analysis encompassing physical chromosomal structures, the copy number of individual chromosomes or chromosomal regions, and the allelic variation of copies of individual genes.

  10. Variability of rRNA Operon Copy Number and Growth Rate Dynamics of Bacillus Isolated from an Extremely Oligotrophic Aquatic Ecosystem.

    Science.gov (United States)

    Valdivia-Anistro, Jorge A; Eguiarte-Fruns, Luis E; Delgado-Sapién, Gabriela; Márquez-Zacarías, Pedro; Gasca-Pineda, Jaime; Learned, Jennifer; Elser, James J; Olmedo-Alvarez, Gabriela; Souza, Valeria

    2015-01-01

    The ribosomal RNA (rrn) operon is a key suite of genes related to the production of protein synthesis machinery and thus to bacterial growth physiology. Experimental evidence has suggested an intrinsic relationship between the number of copies of this operon and environmental resource availability, especially the availability of phosphorus (P), because bacteria that live in oligotrophic ecosystems usually have few rrn operons and a slow growth rate. The Cuatro Ciénegas Basin (CCB) is a complex aquatic ecosystem that contains an unusually high microbial diversity that is able to persist under highly oligotrophic conditions. These environmental conditions impose a variety of strong selective pressures that shape the genome dynamics of their inhabitants. The genus Bacillus is one of the most abundant cultivable bacterial groups in the CCB and usually possesses a relatively large number of rrn operon copies (6-15 copies). The main goal of this study was to analyze the variation in the number of rrn operon copies of Bacillus in the CCB and to assess their growth-related properties as well as their stoichiometric balance (N and P content). We defined 18 phylogenetic groups within the Bacilli clade and documented a range of from six to 14 copies of the rrn operon. The growth dynamic of these Bacilli was heterogeneous and did not show a direct relation to the number of operon copies. Physiologically, our results were not consistent with the Growth Rate Hypothesis, since the copies of the rrn operon were decoupled from growth rate. However, we speculate that the diversity of the growth properties of these Bacilli as well as the low P content of their cells in an ample range of rrn copy number is an adaptive response to oligotrophy of the CCB and could represent an ecological mechanism that allows these taxa to coexist. These findings increase the knowledge of the variability in the number of copies of the rrn operon in the genus Bacillus and give insights about the

  11. Integrative Structure–Function Mapping of the Nucleoporin Nup133 Suggests a Conserved Mechanism for Membrane Anchoring of the Nuclear Pore Complex

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Joong; Fernandez-Martinez, Javier; Sampathkumar, Parthasarathy; Martel, Anne; Matsui, Tsutomu; Tsuruta, Hiro; Weiss, Thomas M.; Shi, Yi; Markina-Inarrairaegui, Ane; Bonanno, Jeffery B.; Sauder, J. Michael; Burley, Stephen K.; Chait, Brian T.; Almo, Steven C.; Rout, Michael P.; Sali, Andrej

    2014-08-19

    The nuclear pore complex (NPC) is the sole passageway for the transport of macromolecules across the nuclear envelope. Nup133, a major component in the essential Y-shaped Nup84 complex, is a large scaffold protein of the NPC's outer ring structure. Here, we describe an integrative modeling approach that produces atomic models for multiple states of Saccharomyces cerevisiae (Sc) Nup133, based on the crystal structures of the sequence segments and their homologs, including the related Vanderwaltozyma polyspora (Vp) Nup133 residues 55 to 502 (VpNup13355–502) determined in this study, small angle X-ray scattering profiles for 18 constructs of ScNup133 and one construct of VpNup133, and 23 negative-stain electron microscopy class averages of ScNup1332–1157. Using our integrative approach, we then computed a multi-state structural model of the full-length ScNup133 and validated it with mutational studies and 45 chemical cross-links determined via mass spectrometry. Finally, the model of ScNup133 allowed us to annotate a potential ArfGAP1 lipid packing sensor (ALPS) motif in Sc and VpNup133 and discuss its potential significance in the context of the whole NPC; we suggest that ALPS motifs are scattered throughout the NPC's scaffold in all eukaryotes and play a major role in the assembly and membrane anchoring of the NPC in the nuclear envelope. Our results are consistent with a common evolutionary origin of Nup133 with membrane coating complexes (the protocoatomer hypothesis); the presence of the ALPS motifs in coatomer-like nucleoporins suggests an ancestral mechanism for membrane recognition present in early membrane coating complexes.

  12. Copy number alteration and uniparental disomy analysis categorizes Japanese papillary thyroid carcinomas into distinct groups.

    Directory of Open Access Journals (Sweden)

    Michiko Matsuse

    Full Text Available The aim of the present study was to investigate chromosomal aberrations in sporadic Japanese papillary thyroid carcinomas (PTCs, concomitant with the analysis of oncogene mutational status. Twenty-five PTCs (11 with BRAF(V600E, 4 with RET/PTC1, and 10 without mutation in HRAS, KRAS, NRAS, BRAF, RET/PTC1, or RET/PTC3 were analyzed using Genome-Wide Human SNP Array 6.0 which allows us to detect copy number alteration (CNA and uniparental disomy (UPD, also referred to as copy neutral loss of heterozygosity, in a single experiment. The Japanese PTCs showed relatively stable karyotypes. Seven cases (28% showed CNA(s, and 6 (24% showed UPD(s. Interestingly, CNA and UPD were rarely overlapped in the same tumor; the only one advanced case showed both CNA and UPD with a highly complex karyotype. Thirteen (52% showed neither CNA nor UPD. Regarding CNA, deletions tended to be more frequent than amplifications. The most frequent and recurrent region was the deletion in chromosome 22; however, it was found in only 4 cases (16%. The degree of genomic instability did not depend on the oncogene status. However, in oncogene-positive cases (BRAF(V600E and RET/PTC1, tumors with CNA/UPD were less frequent (5/15, 33%, whereas tumors with CNA/UPD were more frequent in oncogene-negative cases (7/10, 70%, suggesting that chromosomal aberrations may play a role in the development of PTC, especially in oncogene-negative tumors. These data suggest that Japanese PTCs may be classified into three distinct groups: CNA(+, UPD(+, and no chromosomal aberrations. BRAF(V600E mutational status did not correlate with any parameters of chromosomal defects.

  13. Diversity and population-genetic properties of copy number variations and multicopy genes in cattle.

    Science.gov (United States)

    Bickhart, Derek M; Xu, Lingyang; Hutchison, Jana L; Cole, John B; Null, Daniel J; Schroeder, Steven G; Song, Jiuzhou; Garcia, Jose Fernando; Sonstegard, Tad S; Van Tassell, Curtis P; Schnabel, Robert D; Taylor, Jeremy F; Lewin, Harris A; Liu, George E

    2016-06-01

    The diversity and population genetics of copy number variation (CNV) in domesticated animals are not well understood. In this study, we analysed 75 genomes of major taurine and indicine cattle breeds (including Angus, Brahman, Gir, Holstein, Jersey, Limousin, Nelore, and Romagnola), sequenced to 11-fold coverage to identify 1,853 non-redundant CNV regions. Supported by high validation rates in array comparative genomic hybridization (CGH) and qPCR experiments, these CNV regions accounted for 3.1% (87.5 Mb) of the cattle reference genome, representing a significant increase over previous estimates of the area of the genome that is copy number variable (∼2%). Further population genetics and evolutionary genomics analyses based on these CNVs revealed the population structures of the cattle taurine and indicine breeds and uncovered potential diversely selected CNVs near important functional genes, including AOX1, ASZ1, GAT, GLYAT, and KRTAP9-1 Additionally, 121 CNV gene regions were found to be either breed specific or differentially variable across breeds, such as RICTOR in dairy breeds and PNPLA3 in beef breeds. In contrast, clusters of the PRP and PAG genes were found to be duplicated in all sequenced animals, suggesting that subfunctionalization, neofunctionalization, or overdominance play roles in diversifying those fertility-related genes. These CNV results provide a new glimpse into the diverse selection histories of cattle breeds and a basis for correlating structural variation with complex traits in the future. Published by Oxford University Press on behalf of Kazusa DNA Research Institute 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. Improved determination of plasmid copy number using quantitative real-time PCR for monitoring fermentation processes

    Directory of Open Access Journals (Sweden)

    Štrukelj Borut

    2008-03-01

    Full Text Available Abstract Background Recombinant protein production in Escherichia coli cells is a complex process, where among other parameters, plasmid copy number, structural and segregational stability of plasmid have an important impact on the success of productivity. It was recognised that a method for accurate and rapid quantification of plasmid copy number is necessary for optimization and better understanding of this process. Lately, qPCR is becoming the method of choice for this purpose. In the presented work, an improved qPCR method adopted for PCN determination in various fermentation processes was developed. Results To avoid experimental errors arising from irreproducible DNA isolation, whole cells, treated by heating at 95°C for 10 minutes prior to storage at -20°C, were used as a template source. Relative quantification, taking into account different amplification efficiencies of amplicons for chromosome and plasmid, was used in the PCN calculation. The best reproducibility was achieved when the efficiency estimated for specific amplicon, obtained within one run, was averaged. It was demonstrated that the quantification range of 2 log units (100 to 10000 bacteria per well enable quantification in each time point during fermentation. The method was applied to study PCN variation in fermentation at 25°C and the correlation between PCN and protein accumulation was established. Conclusion Using whole cells as a template source and relative quantification considering different PCR amplification efficiencies are significant improvements of the qPCR method for PCN determination. Due to the approaches used, the method is suitable for PCN determination in fermentation processes using various media and conditions.

  15. The Making of the Copy-cat City

    DEFF Research Database (Denmark)

    Ooi, Can-Seng

    2014-01-01

    , as if it were New York or London. Such comments can be considered flattering to the Chinese. Or the comments may merely reflect a lack of understanding of Shanghai. Or perhaps the comments are insulting because they insinuate that the Chinese metropolis is just another copy-cat city. Whatever the reason......, and the trendy bars like Bar Rouge and Mint. They have seen it all before, and the Shanghai they are visiting seems to lack a unique Chinese character. Today, places, particularly cities, broadly compete in terms of livability, economic opportunities, attractiveness, and vibrancy to attract international...... investors, businesses, visitors, talented workers, and audiences (Dinnie, 2011; Florida, 2002). This competition has also led to a proliferation of branded places. Places must stand out in the competition. So, in the place branding literature, the concern is differentiation and uniqueness (see various...

  16. Radiation and the classical double copy for color charges

    Science.gov (United States)

    Goldberger, Walter D.; Ridgway, Alexander K.

    2017-06-01

    We construct perturbative classical solutions of the Yang-Mills equations coupled to dynamical point particles carrying color charge. By applying a set of color to kinematics replacement rules first introduced by Bern, Carrasco and Johansson, these are shown to generate solutions of d -dimensional dilaton gravity, which we also explicitly construct. Agreement between the gravity result and the gauge theory double copy implies a correspondence between non-Abelian particles and gravitating sources with dilaton charge. When the color sources are highly relativistic, dilaton exchange decouples, and the solutions we obtain match those of pure gravity. We comment on possible implications of our findings to the calculation of gravitational waveforms in astrophysical black hole collisions, directly from computationally simpler gluon radiation in Yang-Mills theory.

  17. Radiation and the classical double copy for color charges

    CERN Document Server

    Goldberger, Walter D

    2016-01-01

    We construct perturbative classical solutions of the Yang-Mills equations coupled to dynamical point particles carrying color charge. By applying a set of color to kinematics replacement rules first introduced by Bern, Carrasco and Johansson (BCJ), these are shown to generate solutions of d-dimensional dilaton gravity, which we also explicitly construct. Agreement between the gravity result and the gauge theory double copy implies a correspondence between non-Abelian particles and gravitating sources with dilaton charge. When the color sources are highly relativistic, dilaton exchange decouples, and the solutions we obtain match those of pure gravity. We comment on possible implications of our findings to the calculation of gravitational waveforms in astrophysical black hole collisions, directly from computationally simpler gluon radiation in Yang-Mills theory.

  18. Template-Directed Biopolymerization: Tape-Copying Turing Machines

    Science.gov (United States)

    Sharma, Ajeet K.; Chowdhury, Debashish

    2012-10-01

    DNA, RNA and proteins are among the most important macromolecules in a living cell. These molecules are polymerized by molecular machines. These natural nano-machines polymerize such macromolecules, adding one monomer at a time, using another linear polymer as the corresponding template. The machine utilizes input chemical energy to move along the template which also serves as a track for the movements of the machine. In the Alan Turing year 2012, it is worth pointing out that these machines are "tape-copying Turing machines". We review the operational mechanisms of the polymerizer machines and their collective behavior from the perspective of statistical physics, emphasizing their common features in spite of the crucial differences in their biological functions. We also draw the attention of the physics community to another class of modular machines that carry out a different type of template-directed polymerization. We hope this review will inspire new kinetic models for these modular machines.

  19. Template-directed biopolymerization: tape-copying Turing machines

    CERN Document Server

    Sharma, Ajeet K; 10.1142/S1793048012300083

    2013-01-01

    DNA, RNA and proteins are among the most important macromolecules in a living cell. These molecules are polymerized by molecular machines. These natural nano-machines polymerize such macromolecules, adding one monomer at a time, using another linear polymer as the corresponding template. The machine utilizes input chemical energy to move along the template which also serves as a track for the movements of the machine. In the Alan Turing year 2012, it is worth pointing out that these machines are "tape-copying Turing machines". We review the operational mechanisms of the polymerizer machines and their collective behavior from the perspective of statistical physics, emphasizing their common features in spite of the crucial differences in their biological functions. We also draw attention of the physics community to another class of modular machines that carry out a different type of template-directed polymerization. We hope this review will inspire new kinetic models for these modular machines.

  20. Quantitative assessment of impairment in constructional ability by cube copying in patients with aphasia.

    Science.gov (United States)

    Maeshima, Shinichiro; Ueyoshi, Akitaka; Matsumoto, Tomoko; Boh-Oka, Shin-Ichi; Yoshida, Munehito; Itakura, Toru

    2002-02-01

    Constructional apraxia was evaluated in patients with aphasia using a cube-copying task. It was assessed whether quantitative assessment of cube copying could be used to estimate the performance intelligence quotient (IQ) according to neuropsychological tests. Abnormality in the cube-copying test was observed in 42 of 46 patients (91.3%). Performance according to Raven's coloured progressive matrices and the revised Wechshler adult intelligence scale (WAIS-R) in patients with poor cube copying was significantly lower than in the other four patients. Numbers of the connections completed and plane-orientation errors made in the cube-copying test were significantly correlated with performance IQ on the WAIS-R, correlating particularly with block design, digit symbol, and object assembly in performance IQ subtests. The quantitatively scored cube-copying test, then, can roughly predict non-verbal IQ in patients with aphasia.

  1. Entanglement Preserving in Quantum Copying of Three-Qubit Entangled State

    Institute of Scientific and Technical Information of China (English)

    TONGZhao-Yang; KUANGLe-Man

    2002-01-01

    We study the degree to which quantum entanglement survives when a three-qubit entangled state is copied by using local and non-local processes,respectively,and investigate iterating quantum copying for the three-qubit system.There may exist inter-three-qubit entanglement and inter-two-qubit entanglement for the three-qubit system.We show that both local and non-local copying processes degrade quantum entanglement in the three-particle system due to a residual correlation between the copied output and the copying machine.we also show that the inter-two-qubit entanglement is preserved better than the inter-three-qubit entanglement in the local cloning process.We find that non-local cloning is much more efficient than the local copying for broadcasting entanglement,and output state via non-local cloning exhiits the fidelity better than local cloning.

  2. Copy Chic: Status Representation and Intellectual Property Rights in Contemporary Fashion

    DEFF Research Database (Denmark)

    Mackinney-Valentin, Maria; Teilmann-Lock, Stina

    2014-01-01

    Copying in fashion has a variety of meanings and implications. Copying is socially, creatively and commercially ingrained in the very nature of fashion. Consumers copy early-adopters in an ongoing process of style emulation. Designers are inspired by the world around them, including other designers....... And the luxury fashion industry has historically benefited from mass-market as a way of stimulating consumers’ appetite for innovation. The article explores the presence of “copy chic” in luxury fashion as an ambiguous celebration of the conspicuously inauthentic through a study of luxury version...... of the inexpensive, plaid bag often referred to as a “Chinatown tote.” The article explores fashion copying from an interdisciplinary position integrating legal and consumer perspectives within the framework of the luxury fashion industry. It will be proposed that the regulation of copying in luxury fashion takes...

  3. Copy number variants in the kallikrein gene cluster.

    Directory of Open Access Journals (Sweden)

    Pernilla Lindahl

    Full Text Available The kallikrein gene family (KLK1-KLK15 is the largest contiguous group of protease genes within the human genome and is associated with both risk and outcome of cancer and other diseases. We searched for copy number variants in all KLK genes using quantitative PCR analysis and analysis of inheritance patterns of single nucleotide polymorphisms. Two deletions were identified: one 2235-bp deletion in KLK9 present in 1.2% of alleles, and one 3394-bp deletion in KLK15 present in 4.0% of alleles. Each deletion eliminated one complete exon and created out-of-frame coding that eliminated the catalytic triad of the resulting truncated gene product, which therefore likely is a non-functional protein. Deletion breakpoints identified by DNA sequencing located the KLK9 deletion breakpoint to a long interspersed element (LINE repeated sequence, while the deletion in KLK15 is located in a single copy sequence. To search for an association between each deletion and risk of prostate cancer (PC, we analyzed a cohort of 667 biopsied men (266 PC cases and 401 men with no evidence of PC at biopsy using short deletion-specific PCR assays. There was no association between evidence of PC in this cohort and the presence of either gene deletion. Haplotyping revealed a single origin of each deletion, with most recent common ancestor estimates of 3000-8000 and 6000-14 000 years for the deletions in KLK9 and KLK15, respectively. The presence of the deletions on the same haplotypes in 1000 Genomes data of both European and African populations indicate an early origin of both deletions. The old age in combination with homozygous presence of loss-of-function variants suggests that some kallikrein-related peptidases have non-essential functions.

  4. Atrazine exposure elicits copy number alterations in the zebrafish genome.

    Science.gov (United States)

    Wirbisky, Sara E; Freeman, Jennifer L

    2017-04-01

    Atrazine is an agricultural herbicide used throughout the Midwestern United States that frequently contaminates potable water supplies resulting in human exposure. Using the zebrafish model system, an embryonic atrazine exposure was previously reported to decrease spawning rates with an increase in progesterone and ovarian follicular atresia in adult females. In addition, alterations in genes associated with distinct molecular pathways of the endocrine system were observed in brain and gonad tissue of the adult females and males. Current hypotheses for mechanistic changes in the developmental origins of health and disease include genetic (e.g., copy number alterations) or epigenetic (e.g., DNA methylation) mechanisms. As such, in the current study we investigated whether an atrazine exposure would generate copy number alterations (CNAs) in the zebrafish genome. A zebrafish fibroblast cell line was used to limit detection to CNAs caused by the chemical exposure. First, cells were exposed to a range of atrazine concentrations and a crystal violet assay was completed, showing confluency decreased by ~60% at 46.3μM. Cells were then exposed to 0, 0.463, 4.63, or 46.3μM atrazine and array comparative genomic hybridization completed. Results showed 34, 21, and 44 CNAs in the 0.463, 4.63, and 46.3μM treatments, respectively. Furthermore, CNAs were associated with previously reported gene expression alterations in adult male and female zebrafish. This study demonstrates that atrazine exposure can generate CNAs that are linked to gene expression alterations observed in adult zebrafish exposed to atrazine during embryogenesis providing a mechanism of the developmental origins of atrazine endocrine disruption. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk.

    Directory of Open Access Journals (Sweden)

    Daria Salyakina

    Full Text Available Copy number variations (CNVs are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than by single nucleotide polymorphisms (SNPs. In the multifaceted etiology of autism spectrum disorders (ASDs, CNVs appear to contribute significantly to our understanding of the pathogenesis of this complex disease. A unique resource of 42 extended ASD families was genotyped for over 1 million SNPs to detect CNVs that may contribute to ASD susceptibility. Each family has at least one avuncular or cousin pair with ASD. Families were then evaluated for co-segregation of CNVs in ASD patients. We identified a total of five deletions and seven duplications in eleven families that co-segregated with ASD. Two of the CNVs overlap with regions on 7p21.3 and 15q24.1 that have been previously reported in ASD individuals and two additional CNVs on 3p26.3 and 12q24.32 occur near regions associated with schizophrenia. These findings provide further evidence for the involvement of ICA1 and NXPH1 on 7p21.3 in ASD susceptibility and highlight novel ASD candidates, including CHL1, FGFBP3 and POUF41. These studies highlight the power of using extended families for gene discovery in traits with a complex etiology.

  6. Genetic variation in human disease and a new role for copy number variants.

    Science.gov (United States)

    Shelling, Andrew N; Ferguson, Lynnette R

    2007-09-01

    While complex diseases, such as inflammatory bowel disease, do not follow distinctive Mendelian inheritance patterns, there is now considerable evidence from twin and pedigree studies to show that there are significant genetic influences in the development of many such diseases. In times past, this type of information was considered to be interesting, and was used mainly to alert other members of the families that they may also be at increased risk of developing the disease. However, with the ability to evaluate the genetic basis of common disease, this information will have important consequences for the diagnosis, prevention and treatment of the disorder. The genetic basis for common disease is likely to be more complicated than we had previously anticipated, since we now recognise epigenetic causes of disease, and other subtle gene regulatory mechanisms. Copy number variants have been highlighted in this review, as being a phenomenon that we have known about for a long time, but that has not previously been clearly associated with human disease. As complex disease is related to changes in gene expression, any variation in the human genome that alters gene expression is now a candidate for being involved in the disease process.

  7. Application of droplet digital PCR to determine copy number of endogenous genes and transgenes in sugarcane.

    Science.gov (United States)

    Sun, Yue; Joyce, Priya Aiyar

    2017-08-28

    Droplet digital PCR combined with the low copy ACT allele as endogenous reference gene, makes accurate and rapid estimation of gene copy number in Q208 (A) and Q240 (A) attainable. Sugarcane is an important cultivated crop with both high polyploidy and aneuploidy in its 10 Gb genome. Without a known copy number reference gene, it is difficult to accurately estimate the copy number of any gene of interest by PCR-based methods in sugarcane. Recently, a new technology, known as droplet digital PCR (ddPCR) has been developed which can measure the absolute amount of the target DNA in a given sample. In this study, we deduced the true copy number of three endogenous genes, actin depolymerizing factor (ADF), adenine phosphoribosyltransferase (APRT) and actin (ACT) in three Australian sugarcane varieties, using ddPCR by comparing the absolute amounts of the above genes with a transgene of known copy number. A single copy of the ACT allele was detected in Q208 (A) , two copies in Q240 (A) , but was absent in Q117. Copy number variation was also observed for both APRT and ADF, and ranged from 9 to 11 in the three tested varieties. Using this newly developed ddPCR method, transgene copy number was successfully determined in 19 transgenic Q208 (A) and Q240 (A) events using ACT as the reference endogenous gene. Our study demonstrates that ddPCR can be used for high-throughput genetic analysis and is a quick, accurate and reliable alternative method for gene copy number determination in sugarcane. This discovered ACT allele would be a suitable endogenous reference gene for future gene copy number variation and dosage studies of functional genes in Q208 (A) and Q240 (A) .

  8. Macronuclear Actin copy number variations in single cells of different Pseudokeronopsis (Alveolata, Ciliophora) populations.

    Science.gov (United States)

    Huang, Lijuan; Lu, Xuefen; Zhu, Changyu; Lin, Xiaofeng; Yi, Zhenzhen

    2017-06-01

    Macronuclear chromosomes of ciliates, especially those of Spirotrichea, Armophorea and Phyllopharyngea, are extensively fragmented and their copy numbers vary significantly. A recent study suggested that parental RNA molecules regulate macronuclear copy number in offspring cells after conjugation. However, variations in patterns of macronuclear copy number during vegetative growth are not clear. Previous studies have reported macronuclear copy numbers of population averages, potentially masking individual variation. In the present investigation, we studied copy number variations among closely related species of Pseudokeronopsis and among individual cells during vegetative growth. We found that macronuclear copy numbers of Actin I, II in our Pseudokeronopsis populations are in the same range as in other spirotrichean species, but no close relationship is detected among morphologically related Pseudokeronopsis species. Copy numbers of three cells within each Pseudokeronopsis population range from 1.01 to 4.55 fold, suggesting that stochastic influences copy number during vegetative growth. Furthermore, the absence of a relationship between macronuclear copy numbers of Actin I and Actin II within Pseudokeronopsis is consistent with the fact that these genes are located on different gene-sized macronuclear chromosomes. Additionally, Actin II might have disappeared in P. carnea during evolution within the Actin gene family. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Mitochondrial DNA copy number in whole blood and glioma risk: A case control study.

    Science.gov (United States)

    Shen, Jie; Song, Renduo; Lu, Zhimin; Zhao, Hua

    2016-12-01

    Alterations in mitochondrial DNA (mtDNA) copy number are observed in human gliomas. However, whether variations in mtDNA copy number in whole blood play any role in glioma carcinogenesis is still largely unknown. In current study with 395 glioma patients and 425 healthy controls, we intended to investigate the association between mtDNA copy number in whole blood and glioma risk. Overall, we found that levels of mtDNA copy number were significantly higher in glioma cases than healthy controls (mean: 1.48 vs. 1.32, P copy number were inversely correlated with age (P copy number than their counterparts (P = 0.02, P copy number levels were associated with a 1.63-fold increased risk of glioma (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.23-2.14). In further quartile analysis, study subjects who had highest levels of mtNDA copy number had 1.75-fold increased risk of gliomas (adjOR = 1.75, 95%CI = 1.18-2.61). In brief, our findings support the role of mtDNA copy number in the glioma carcinogenesis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Determination of beta-defensin genomic copy number in different populations

    DEFF Research Database (Denmark)

    Fode, Peder; Jespersgaard, Cathrine; Hardwick, Robert J

    2011-01-01

    There have been conflicting reports in the literature on association of gene copy number with disease, including CCL3L1 and HIV susceptibility, and ß-defensins and Crohn's disease. Quantification of precise gene copy numbers is important in order to define any association of gene copy number...... with disease. At present, real-time quantitative PCR (QPCR) is the most commonly used method to determine gene copy number, however the Paralogue Ratio Test (PRT) is being used in more and more laboratories....

  11. Low copy number of the salivary amylase gene predisposes to obesity.

    Science.gov (United States)

    Falchi, Mario; El-Sayed Moustafa, Julia Sarah; Takousis, Petros; Pesce, Francesco; Bonnefond, Amélie; Andersson-Assarsson, Johanna C; Sudmant, Peter H; Dorajoo, Rajkumar; Al-Shafai, Mashael Nedham; Bottolo, Leonardo; Ozdemir, Erdal; So, Hon-Cheong; Davies, Robert W; Patrice, Alexandre; Dent, Robert; Mangino, Massimo; Hysi, Pirro G; Dechaume, Aurélie; Huyvaert, Marlène; Skinner, Jane; Pigeyre, Marie; Caiazzo, Robert; Raverdy, Violeta; Vaillant, Emmanuel; Field, Sarah; Balkau, Beverley; Marre, Michel; Visvikis-Siest, Sophie; Weill, Jacques; Poulain-Godefroy, Odile; Jacobson, Peter; Sjostrom, Lars; Hammond, Christopher J; Deloukas, Panos; Sham, Pak Chung; McPherson, Ruth; Lee, Jeannette; Tai, E Shyong; Sladek, Robert; Carlsson, Lena M S; Walley, Andrew; Eichler, Evan E; Pattou, Francois; Spector, Timothy D; Froguel, Philippe

    2014-05-01

    Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10(-14)) and serum enzyme levels (P copy number was associated with increased BMI (change in BMI per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.

  12. Development of a copy-peeling machine for machining the surface of hot rolled square billets

    Science.gov (United States)

    Koch, R. E.; Fangmeier, R.; Seppelt, B.

    1986-01-01

    A copy-peeling system to replace the high-pressure grinding method, especially for stainless steel qualities, was developed. The copy-peeling process for square billets was accomplished on an existing planing machine with special test attachments as well as on a specially developed copy-peeling machine. The attainable material removals and the tool life reached during the tests with stainless steel are not sufficient to offer an economic and technically advanced alternative to high-pressure grinding. The advantages of copy peeling with respect to safety and health of the operational personnel are obvious. However, it cannot be expected that this process will be applied extensively.

  13. 36 CFR 1254.70 - How may I make my own copies of documents?

    Science.gov (United States)

    2010-07-01

    ... RECORDS ADMINISTRATION PUBLIC AVAILABILITY AND USE USING RECORDS AND DONATED HISTORICAL MATERIALS Copying... and architectural drawings, or aerial photographic film, the appropriate staff can advise you on...

  14. Forty years of ``unnatural'' natural deduction and quantification: a history of first-order systems of natural deduction from Gentzen to Copi

    OpenAIRE

    Anellis, Irving H.

    1991-01-01

    Systems of natural deduction as a method of theorem proving were first developed in detail by Gentzen and Jáskowski. The complex nature of the rules for quantification in these early systems of natural deduction, and in particular of the parallel rules of Universal Generalization (UG) and Existential Instantiation (El) led to an active research program in the period from the late 1950's to the late 1960's in an effort by Quine, Suppes, Leblanc, and Copi to develop simplified...

  15. Genome-Wide Copy Number Variation Analysis in Extended Families and Unrelated Individuals Characterized for Musical Aptitude and Creativity in Music

    OpenAIRE

    Ukkola-Vuoti, Liisa; Kanduri, Chakravarthi; Oikkonen, Jaana; Buck, Gemma; Blancher, Christine; Raijas, Pirre; Karma, Kai; Lähdesmäki, Harri; Järvelä, Irma

    2013-01-01

    Music perception and practice represent complex cognitive functions of the human brain. Recently, evidence for the molecular genetic background of music related phenotypes has been obtained. In order to further elucidate the molecular background of musical phenotypes we analyzed genome wide copy number variations (CNVs) in five extended pedigrees and in 172 unrelated subjects characterized for musical aptitude and creative functions in music. Musical aptitude was defined by combination of the...

  16. Phosphatidylinositol- and phosphatidylcholine-transfer activity of PITPβ is essential for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum

    OpenAIRE

    Carvou, Nicolas; Holic, Roman; Li, Michelle; Futter, Clare; Skippen, Alison; Cockcroft, Shamshad

    2010-01-01

    Vesicles formed by the COPI complex function in retrograde transport from the Golgi to the endoplasmic reticulum (ER). Phosphatidylinositol transfer protein β (PITPβ), an essential protein that possesses phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) lipid transfer activity is known to localise to the Golgi and ER but its role in these membrane systems is not clear. To examine the function of PITPβ at the Golgi-ER interface, RNA interference (RNAi) was used to knockdown PITPβ ...

  17. Low-copy episomal vector pFY20 and high-saturation coverage genomic libraries for the fission yeast Schizosaccharomyces pombe.

    Science.gov (United States)

    Wahls, Wayne P; Davidson, Mari K

    2008-09-01

    In fission yeast, as in many organisms, episomally replicating plasmid DNA molecules can be used for a wide variety of applications. However, replicating plasmids described previously are each propagated at a high copy number per cell. Plasmid fission yeast twenty (pFY20) contains the ura4(+) gene for positive and negative selection, an origin of replication (ars1) and a stability element (stb). Although this plasmid does not have a centromere, it is propagated with a copy number of about two plasmids per haploid genome equivalent and it is transmitted with relatively high fidelity in mitosis and meiosis. This low-copy vector is useful for screens and mutational studies where overexpression (e.g. from high copy plasmids) is undesirable. We therefore constructed multiple partial-digest, size-fractionated, fission yeast genomic DNA libraries in pFY20 and in the cloning vector pBluescript KS(+). These libraries have sufficient complexity (average of 2100 genome equivalents each) for saturation screening by complementation, plasmid shuffle or hybridization.

  18. Copy number variations and cognitive phenotypes in unselected populations.

    Science.gov (United States)

    Männik, Katrin; Mägi, Reedik; Macé, Aurélien; Cole, Ben; Guyatt, Anna L; Shihab, Hashem A; Maillard, Anne M; Alavere, Helene; Kolk, Anneli; Reigo, Anu; Mihailov, Evelin; Leitsalu, Liis; Ferreira, Anne-Maud; Nõukas, Margit; Teumer, Alexander; Salvi, Erika; Cusi, Daniele; McGue, Matt; Iacono, William G; Gaunt, Tom R; Beckmann, Jacques S; Jacquemont, Sébastien; Kutalik, Zoltán; Pankratz, Nathan; Timpson, Nicholas; Metspalu, Andres; Reymond, Alexandre

    2015-05-26

    The association of copy number variations (CNVs), differing numbers of copies of genetic sequence at locations in the genome, with phenotypes such as intellectual disability has been almost exclusively evaluated using clinically ascertained cohorts. The contribution of these genetic variants to cognitive phenotypes in the general population remains unclear. To investigate the clinical features conferred by CNVs associated with known syndromes in adult carriers without clinical preselection and to assess the genome-wide consequences of rare CNVs (frequency ≤0.05%; size ≥250 kilobase pairs [kb]) on carriers' educational attainment and intellectual disability prevalence in the general population. The population biobank of Estonia contains 52,000 participants enrolled from 2002 through 2010. General practitioners examined participants and filled out a questionnaire of health- and lifestyle-related questions, as well as reported diagnoses. Copy number variant analysis was conducted on a random sample of 7877 individuals and genotype-phenotype associations with education and disease traits were evaluated. Our results were replicated on a high-functioning group of 993 Estonians and 3 geographically distinct populations in the United Kingdom, the United States, and Italy. Phenotypes of genomic disorders in the general population, prevalence of autosomal CNVs, and association of these variants with educational attainment (from less than primary school through scientific degree) and prevalence of intellectual disability. Of the 7877 in the Estonian cohort, we identified 56 carriers of CNVs associated with known syndromes. Their phenotypes, including cognitive and psychiatric problems, epilepsy, neuropathies, obesity, and congenital malformations are similar to those described for carriers of identical rearrangements ascertained in clinical cohorts. A genome-wide evaluation of rare autosomal CNVs (frequency, ≤0.05%; ≥250 kb) identified 831 carriers (10.5%) of the

  19. Copy Number Variation in Brown Swiss Dairy Cattle

    DEFF Research Database (Denmark)

    Dolezal, Marlies A; Bagnato, Alessandro; Schiavini, F

    CNVs are increasingly recognized as substantial source of genetic variation, fueling studies that assess their impact on complex traits. In particular rare CNVs have been suggested to potentially explain part of the missing heritability problem in genome wide association studies for complex trait...

  20. 39 CFR 955.23 - Copies of papers, withdrawal of exhibits.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Copies of papers, withdrawal of exhibits. 955.23 Section 955.23 Postal Service UNITED STATES POSTAL SERVICE PROCEDURES RULES OF PRACTICE BEFORE THE POSTAL SERVICE BOARD OF CONTRACT APPEALS § 955.23 Copies of papers, withdrawal of exhibits. (a) When books...

  1. Why People Copy Software and Create Computer Viruses: Individual Characteristics or Situational Factors?

    Science.gov (United States)

    Harrington, Susan J.

    1989-01-01

    Examines individual and situational variables as factors in the behavior of computer users, namely copying of software and distribution of computer viruses. The results indicate that situational variables explain much of the variance in copying software, while the individual variable of sex is strongly related to computer virus distribution. (17…

  2. Statistical methods for the detection of answer copying on achievement tests

    NARCIS (Netherlands)

    Sotaridona, Leonardo Sitchirita

    2003-01-01

    This thesis contains a collection of studies where statistical methods for the detection of answer copying on achievement tests in multiple-choice format are proposed and investigated. Although all methods are suited to detect answer copying, each method is designed to address specific characteristi

  3. 5 CFR 2429.25 - Number of copies and paper size.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Number of copies and paper size. 2429.25... Requirements § 2429.25 Number of copies and paper size. Unless otherwise provided by the Authority or the... the exception of any prescribed forms, any document or paper filed with the Authority, General Counsel...

  4. Accurate measure of transgene copy number in crop plants using droplet digital PCR

    Science.gov (United States)

    Genetic transformation is a powerful means for the improvement of crop plants, but requires labor- and resource-intensive methods. An efficient method for identifying single-copy transgene insertion events from a population of independent transgenic lines is desirable. Currently, transgene copy numb...

  5. Spelling Errors in Text Copying by Children with Dyslexia and ADHD Symptoms

    Science.gov (United States)

    Re, Anna Maria; Cornoldi, Cesare

    2015-01-01

    Spelling errors are usually studied in dictations, but teachers report that children with school difficulties often make spelling mistakes when they copy a text too. The present study examines the performance on a text copying task and a text dictation task of two groups of children known for their difficulties in spelling, that is, 22 with…

  6. Cover-Copy-Compare: A Method for Enhancing Evidence-Based Instruction

    Science.gov (United States)

    Konrad, Moira; Joseph, Laurice M.

    2014-01-01

    Cover-copy-compare is a practical, low-cost, effective strategy for teachers to add to their repertoires of evidence-based practices. This article describes the cover-copy-compare strategy and how it can be applied to teach both self-management and basic academic skills. A variety of ways this strategy can be used across content areas are…

  7. ALK Gene Copy Number Gain and Immunohistochemical Expression Status Using Three Antibodies in Neuroblastoma.

    Science.gov (United States)

    Kim, Eun Kyung; Kim, Sewha

    2017-01-01

    Anaplastic lymphoma kinase ( ALK) gene aberrations-such as mutations, amplifications, and copy number gains-represent a major genetic predisposition to neuroblastoma (NB). This study aimed to evaluate the correlation between ALK gene copy number status, ALK protein expression, and clinicopathological parameters. We retrospectively retrieved 30 cases of poorly differentiated NB and constructed tissue microarrays (TMAs). ALK copy number changes were assessed by fluorescence in situ hybridization (FISH) assays, and ALK immunohistochemistry (IHC) testing was performed using three different antibodies (ALK1, D5F3, and 5A4 clones). ALK amplification and copy number gain were observed in 10% (3/30) and 53.3% (16/30) of the cohort, respectively. There were positive correlations between ALK copy number and IHC-positive rate in ALK1 and 5A4 antibodies ( P copy number gain differed among the three antibodies, with 75% sensitivity in D5F3 and 0% sensitivity in ALK1. ALK-amplified NBs were correlated with synchronous MYCN amplification and chromosome 1p deletion. ALK IHC positivity was frequently observed in INSS stage IV and high-risk group patients. In conclusion, this study identified that an increase in the ALK copy number is a frequent genetic alteration in poorly differentiated NB. ALK-amplified NBs showed consistent ALK IHC positivity with all kinds of antibodies. In contrast, the detection performance of ALK copy number gain was antibody dependent, with the D5F3 antibody showing the best sensitivity.

  8. 75 FR 28848 - Culturally Significant Objects Imported for Exhibition Determinations: “The Original Copy...

    Science.gov (United States)

    2010-05-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Objects Imported for Exhibition Determinations: ``The Original Copy: Photography of... hereby determine that the objects to be included in the exhibition ``The Original Copy: Photography of...

  9. TNO at TRECVID 2008, Combining Audio and Video Fingerprinting for Robust Copy Detection

    NARCIS (Netherlands)

    Doets, P.J.; Eendebak, P.T.; Ranguelova, E.; Kraaij, W.

    2009-01-01

    TNO has evaluated a baseline audio and a video fingerprinting system based on robust hashing for the TRECVID 2008 copy detection task. We participated in the audio, the video and the combined audio-video copy detection task. The audio fingerprinting implementation clearly outperformed the video fing

  10. Reduced purifying selection prevails over positive selection in human copy number variant evolution.

    NARCIS (Netherlands)

    Nguyen, D.Q.; Webber, C.; Hehir-Kwa, J.; Pfundt, R.; Veltman, J.A.; Ponting, C.P.

    2008-01-01

    Copy number variation is a dominant contributor to genomic variation and may frequently underlie an individual's variable susceptibilities to disease. Here we question our previous proposition that copy number variants (CNVs) are often retained in the human population because of their adaptive

  11. 20 CFR 416.804 - Certified copy in lieu of original.

    Science.gov (United States)

    2010-04-01

    ... AGED, BLIND, AND DISABLED Determination of Age § 416.804 Certified copy in lieu of original. In lieu of the original of any record, except a Bible or other family record, there may be submitted as evidence... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Certified copy in lieu of original....

  12. Why People Copy Software and Create Computer Viruses: Individual Characteristics or Situational Factors?

    Science.gov (United States)

    Harrington, Susan J.

    1989-01-01

    Examines individual and situational variables as factors in the behavior of computer users, namely copying of software and distribution of computer viruses. The results indicate that situational variables explain much of the variance in copying software, while the individual variable of sex is strongly related to computer virus distribution. (17…

  13. Evolutionary dynamics of copy number variation in pig genomes in the context of adaptation and domestication

    NARCIS (Netherlands)

    Paudel, Y.; Madsen, O.; Megens, H.J.W.C.; Frantz, L.A.F.; Bosse, M.; Bastiaansen, J.W.M.; Crooijmans, R.P.M.A.; Groenen, M.

    2013-01-01

    Background Copy number variable regions (CNVRs) can result in drastic phenotypic differences and may therefore be subject to selection during domestication. Studying copy number variation in relation to domestication is highly relevant in pigs because of their very rich natural and domestication

  14. Copy number variation in Fayoumi and Leghorn chickens analyzed using array comparative genomic hybridization

    NARCIS (Netherlands)

    Abernathy, J.; Li, X.; Jia, X.; Chou, W.; Lamont, S.J.; Crooijmans, R.P.M.A.; Zhou, H.

    2014-01-01

    Copy number variation refers to regions along chromosomes that harbor a type of structural variation, such as duplications or deletions. Copy number variants (CNVs) play a role in many important traits as well as in genetic diversity. Previous analyses of chickens using array comparative genomic hyb

  15. Chromosome copy number variation and control in the ciliate Chilodonella uncinata.

    Directory of Open Access Journals (Sweden)

    Kevin J Spring

    Full Text Available Copy number variations are widespread in eukaryotes. The unusual genome architecture of ciliates, in particular, with its process of amitosis in macronuclear division, provides a valuable model in which to study copy number variation. The current model of amitosis envisions stochastic distribution of macronuclear chromosomes during asexual reproduction. This suggests that amitosis is likely to result in high levels of copy number variation in ciliates, as dividing daughter cells can have variable copy numbers of chromosomes if chromosomal distribution during amitosis is a stochastic process. We examined chromosomal distribution during amitosis in Chilodonella uncinata, a ciliate with gene-size macronuclear chromosomes. We quantified 4 chromosomes in evolving populations of C. uncinata and modeled the amitotic distribution process. We found that macronuclear chromosomes differ in copy number from one another but that copy number does not change as expected under a stochastic process. The chromosome carrying SSU increased in copy number, which is consistent with selection to increase abundance; however, two other studied chromosomes displayed much lower than expected among-line variance. Our models suggest that balancing selection is sufficient to explain the observed maintenance of chromosome copy during asexual reproduction.

  16. Copy-writing Post-Soviet Russia. Viktor Pelevin's work in Postcolonial Terms

    NARCIS (Netherlands)

    Noordenbos, Boris; Brouwer, S

    2008-01-01

    The copywriters and creatives in Viktor Pelevin's novel Generation "II" (1999) both 'copy' and 'write' Russian identity. Through advertising texts, video scripts, and written scenario's for Russia's stage-set democracy, the commercial elite makes Russia into a superficial and virtual copy of 'the We

  17. 17 CFR 270.24b-2 - Filing copies of sales literature.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Filing copies of sales literature. 270.24b-2 Section 270.24b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... literature. Copies of material filed with the Commission for the sole purpose of complying with section...

  18. Evolutionary dynamics of copy number variation in pig genomes in the context of adaptation and domestication

    NARCIS (Netherlands)

    Paudel, Y.; Madsen, O.; Megens, H.J.W.C.; Frantz, L.A.F.; Bosse, M.; Bastiaansen, J.W.M.; Crooijmans, R.P.M.A.; Groenen, M.

    2013-01-01

    Background Copy number variable regions (CNVRs) can result in drastic phenotypic differences and may therefore be subject to selection during domestication. Studying copy number variation in relation to domestication is highly relevant in pigs because of their very rich natural and domestication his

  19. Multi-centered ${\\mathcal N}=2$ BPS black holes: a double copy description

    CERN Document Server

    Cardoso, Gabriel; Nampuri, Suresh

    2016-01-01

    We present the on-shell double copy dictionary for linearised ${\\mathcal N}=2$ supergravity coupled to an arbitrary number of vector multiplets in four dimensions. Subsequently, we use it to construct a double copy description of multi-centered BPS black hole solutions in these theories in the weak-field approximation.

  20. 10 CFR 205.307 - Form and style; number of copies

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Form and style; number of copies 205.307 Section 205.307 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Electric Power System Permits and... Electric Energy to A Foreign Country § 205.307 Form and style; number of copies An original and...

  1. ATLAS copies its first PetaByte out of CERN

    CERN Multimedia

    M. Branco; P. Salgado; L. Goossens; A. Nairz

    2006-01-01

    On 6th August ATLAS reached a major milestone for its Distributed Data Management project - copying its first PetaByte (1015 Bytes) of data out from CERN to computing centers around the world. This achievement is part of the so-called 'Tier-0 exercise' running since 19th June, where simulated fake data is used to exercise the expected data flow within the CERN computing centre and out over the Grid to the Tier-1 computing centers as would happen during the real data taking. The expected rate of data output from CERN when the detector is running at full trigger rate is 780 MB/s shared among 10 external Tier-1 sites(*), amounting to around 8 PetaBytes per year. The idea of the exercise was to try to reach this data rate and sustain it for as long as possible. The exercise was run as part of the LCG's Service Challenges and allowed ATLAS to test successfully the integration of ATLAS software with the LCG middleware services that are used for low level cataloging and the actual data movement. When ATLAS is produ...

  2. Determining frequent patterns of copy number alterations in cancer.

    Directory of Open Access Journals (Sweden)

    Franck Rapaport

    Full Text Available Cancer progression is often driven by an accumulation of genetic changes but also accompanied by increasing genomic instability. These processes lead to a complicated landscape of copy number alterations (CNAs within individual tumors and great diversity across tumor samples. High resolution array-based comparative genomic hybridization (aCGH is being used to profile CNAs of ever larger tumor collections, and better computational methods for processing these data sets and identifying potential driver CNAs are needed. Typical studies of aCGH data sets take a pipeline approach, starting with segmentation of profiles, calls of gains and losses, and finally determination of frequent CNAs across samples. A drawback of pipelines is that choices at each step may produce different results, and biases are propagated forward. We present a mathematically robust new method that exploits probe-level correlations in aCGH data to discover subsets of samples that display common CNAs. Our algorithm is related to recent work on maximum-margin clustering. It does not require pre-segmentation of the data and also provides grouping of recurrent CNAs into clusters. We tested our approach on a large cohort of glioblastoma aCGH samples from The Cancer Genome Atlas and recovered almost all CNAs reported in the initial study. We also found additional significant CNAs missed by the original analysis but supported by earlier studies, and we identified significant correlations between CNAs.

  3. A comprehensive Software Copy Protection and Digital Rights Management platform

    Directory of Open Access Journals (Sweden)

    Ayman Mohammad Bahaa-Eldin

    2014-09-01

    Full Text Available This article proposes a Powerful and Flexible System for Software Copy Protection (SCP and Digital Rights Management (DRM based on Public Key Infrastructure (PKI standards. Software protection is achieved through a multi-phase methodology with both static and dynamic processing of the executable file. The system defeats most of the attacks and cracking techniques and makes sure that the protected software is never in a flat form, with a suitable portion of it always being encrypted during execution. A novel performance-tuning algorithm is proposed to lower the overhead of the protection process to its minimum depending on the software dynamic execution behavior. All system calls to access resources and objects such as files, and input/output devices are intercepted and encapsulated with secure rights management code to enforce the required license model. The system can be integrated with hardware authentication techniques (like dongles, and to Internet based activation and DRM servers over the cloud. The system is flexible to apply any model of licensing including state-based license such as expiration dates and number of trials. The usage of a standard markup language (XrML to describe the license makes it easier to apply new licensing operations like re-sale and content rental.

  4. AN EFFICIENT CONTENT AND SEGMENTATION BASED VIDEO COPY DETECTION

    Directory of Open Access Journals (Sweden)

    N. Kalaiselvi

    2015-10-01

    Full Text Available The field of multimedia technology has become easier to store, creation and access large amount of video data. This technology has editing and duplication of video data that will cause to violation of digital rights. So in this project we implemented an efficient content and segmentation based video copy detection concept to detect the illegal manipulation of video. In this Work or proposed system, Instead of SIFT matching algorithms, used combination of SIFT and SURF matching algorithms to detect the matching features in images. Because, SIFT is slow and not good at illumination changes, while it is invariant to rotation, scale changes and affine transformations and then SURF is fast and has good performance, but it is also have some issues that it is not stable to rotation and affine transformations. So combined the above two algorithms SIFT and SURF to extract the image features. Auto dual Threshold method is used to segment the video into segments and extract key frames from each segment and it also eliminate the redundant frame. SIFT and SURF features based on SVD is used to compare the two frames features sets points, where the SIFT and SURF features are extracted from the key frames of the segments. Graph-based video sequence matching method is used to match the sequence of query video and train video. It skillfully converts the video sequence matching result to a matching result graph.

  5. ASYMPTOTICALLY ISOMETRIC COPIES OF lp (1≤p<∞) AND c0 IN BANACH SPACES

    Institute of Scientific and Technical Information of China (English)

    Chen Dongyang

    2006-01-01

    Let X be a Banach space. If there exists a quotient space of X which is asymptotically isometric to l1, then X contains complemented asymptotically isometric copies of l1. Every infinite dimensional closed subspace of l1 contains a complemented subspace of l1 which is asymptotically isometric to l1. Let X be a separable Banach space such that X* contains asymptotically isometric copies of lp (1 < p <∞). Then there exists a quotient space of X which is asymptotically isometric to lq (1/p+1/q=1). Complementedasymptotically isometric copies of c0 in K(X, Y) and W(X, Y) are discussed. Let X be a Gelfand-Phillips space. If X contains asymptotically isometric copies of c0, it has to contain complemented asymptotically isometric copies of c0.

  6. Increased pfmdr1 copy number in Plasmodium falciparum isolates from Suriname.

    Science.gov (United States)

    Labadie-Bracho, Mergiory; Adhin, Malti R

    2013-07-01

    Amplification of the pfmdr1 gene is associated with clinical failures and reduced in vivo and in vitro sensitivity to both mefloquine and artemether-lumefantrine in South-East Asia. Several African countries have reported the absence or very low prevalence of increased copy number, whilst South American reports are limited to Peru without and Venezuela with increased pfmdr1 multiplication. The relative pfmdr1 copy numbers were assessed in 68 isolates from Suriname collected from different endemic villages (2005) and from mining areas (2009). 11% of the isolates harbour multiple copies of the pfmdr1 gene. Isolates originating from mining areas do not yet display a higher tendency for increased copy number and no significant differences could be registered within a time span of 4 years, but the mere presence of increased copy number warrants caution and should be considered as an early warning sign for emerging drug resistance in Suriname and South America.

  7. Carney Complex

    Science.gov (United States)

    ... Types of Cancer > Carney Complex Request Permissions Carney Complex Approved by the Cancer.Net Editorial Board , 11/2015 What is Carney complex? Carney complex is a hereditary condition associated with: ...

  8. Use of Quantitative Polymerase Chain Reaction for Determining Copy Numbers of Transgenes in Lesquerella fendleri

    Directory of Open Access Journals (Sweden)

    Grace Q. Chen

    2010-01-01

    Full Text Available Problem statement: In transgenic plants, the number of transgene copies could greatly influence the level of expression and genetic stability of the target gene, thus it is important to develop an efficient method for accurate estimation of transgene copies. The quantitative Polymerase Chain Reaction (qPCR technique is becoming more efficient nowadays to determine copy numbers of transgenes in transgenic plants, being used here, for the first time in quantifying copy numbers of transgenes in Lesquerella fendleri. Approach: The system utilized a known one copy gene, LfKCS4/5, from L. fendleri as an endogenous calibrator and the threshold Crossing point (Ct measured by Applied Biosystem 7500 system to calculate the copy numbers of transgenes in primary transgenic lines (T0 generation. Results: The qPCR condition was optimized and each primer set had a PCR efficiency of 0.99 or 1.01. Our data demonstrated unambiguous 2-fold discrimination of the copy number of β-glucuronidase gene (gusA and hygromycine phosphotransferase II (hptII genes in 12 T0 lines. Most of the lines contained one or two copies of each gene. Eight out of 12 samples (66.7% showed more copies of gusA gene than that of hptII gene, suggesting rearrangements of the Transferred (T-DNA. Possible modifications of the T-DNA cassette in L. fendleri are discussed based on main models of T-DNA integration in the plant genome. Conclusion: The qPCR described in this study is an efficient method and it is particularly useful in identification and selection of transgenic plants with desirable copy numbers at early stage.

  9. Droplet digital PCR-aided screening and characterization of Pichia pastoris multiple gene copy strains.

    Science.gov (United States)

    Cámara, Elena; Albiol, Joan; Ferrer, Pau

    2016-07-01

    Pichia (syn. Komagataella) pastoris is a widely used yeast platform for heterologous protein production. Expression cassettes are usually stably integrated into the genome of this host via homologous recombination. Although increasing gene dosage is a powerful strategy to improve recombinant protein production, an excess in the number of gene copies often leads to decreased product yields and increased metabolic burden, particularly for secreted proteins. We have constructed a series of strains harboring different copy numbers of a Rhizopus oryzae lipase gene (ROL), aiming to find the optimum gene dosage for secreted Rol production. In order to accurately determine ROL gene dosage, we implemented a novel protocol based on droplet digital PCR (ddPCR), and cross validated it with conventional real-time PCR. Gene copy number determination based on ddPCR allowed for an accurate ranking of transformants according to their ROL gene dosage. Results indicated that ddPCR was particularly superior at lower gene dosages (one to five copies) over quantitative real-time PCR (qPCR). This facilitated the determination of the optimal ROL gene dosage as low as two copies. The ranking of ROL gene dosage versus Rol yield was consistent at both small scale and bioreactor chemostat cultures, thereby easing clone characterization in terms of gene dosage dependent physiological effects, which could be discriminated even among strains differing by only one ROL copy. A selected two-copy strain showed twofold increase in Rol specific production in a chemostat culture over the single copy strain. Conversely, strains harboring more than two copies of the ROL gene showed decreased product and biomass yields, as well as altered substrate consumption specific rates, compared to the reference (one-copy) strain. Biotechnol. Bioeng. 2016;113: 1542-1551. © 2015 Wiley Periodicals, Inc.

  10. Abundant copy-number loss of CYCLOPS and STOP genes in gastric adenocarcinoma.

    Science.gov (United States)

    Cutcutache, Ioana; Wu, Alice Yingting; Suzuki, Yuka; McPherson, John Richard; Lei, Zhengdeng; Deng, Niantao; Zhang, Shenli; Wong, Wai Keong; Soo, Khee Chee; Chan, Weng Hoong; Ooi, London Lucien; Welsch, Roy; Tan, Patrick; Rozen, Steven G

    2016-04-01

    Gastric cancer, a leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar health burdens. Our goal is to assess genomic copy-number loss and the possible functional consequences and therapeutic implications thereof across a large series of gastric adenocarcinomas. We used high-density single-nucleotide polymorphism microarrays to determine patterns of copy-number loss and allelic imbalance in 74 gastric adenocarcinomas. We investigated whether suppressor of tumorigenesis and/or proliferation (STOP) genes are associated with genomic copy-number loss. We also analyzed the extent to which copy-number loss affects Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes-genes that may be attractive targets for therapeutic inhibition when partially deleted. The proportion of the genome subject to copy-number loss varies considerably from tumor to tumor, with a median of 5.5 %, and a mean of 12 % (range 0-58.5 %). On average, 91 STOP genes were subject to copy-number loss per tumor (median 35, range 0-452), and STOP genes tended to have lower copy-number compared with the rest of the genes. Furthermore, on average, 1.6 CYCLOPS genes per tumor were both subject to copy-number loss and downregulated, and 51.4 % of the tumors had at least one such gene. The enrichment of STOP genes in regions of copy-number loss indicates that their deletion may contribute to gastric carcinogenesis. Furthermore, the presence of several deleted and downregulated CYCLOPS genes in some tumors suggests potential therapeutic targets in these tumors.

  11. Advances in the Research of Copy Number Variation%拷贝数目变异研究进展

    Institute of Scientific and Technical Information of China (English)

    钱源; 褚嘉祐

    2008-01-01

    DNA copy number variation has been associated with variable susceptibility to complex diseases and genomic disorders,but its ubiquity in human genomes was not fully realized until recently with the progress of Hapmap.Many CNVs are observed in the corresponding regions in both chimpanzees and humans with high frequency.It seems likely that at least in humans,copy number variants account for a substantial amount of genetic variation.This review disusses the recent advances in the research of CNVs in normal individual and the relationship with gene disorder,potential mechanisms of CNVs formation and evolution.%人类基因组中的DNA拷贝数目变异(copy number variation,CNVs)一直以来都被认为分布频率较低,并与疾病的发生以及不同个体对于疾病的易感性相关.随着Hapmap研究计划的顺利进行,研究者逐渐发现CNVs广泛分布于人类基因组中.黑猩猩和实验室近交系的小鼠基因组也存在CNVs的广泛分布.目前已有多项研究证明了CNVs是人类基因组变异的主要原因,本综述将从CNVs的定义及其在健康人群的分布研究以及与疾病的相关性研究、CNVs的形成机制和CNVs的进化等方面对CNVs研究进展作较为全面的概述.

  12. A genome-wide association study of copy number variations with umbilical hernia in swine.

    Science.gov (United States)

    Long, Yi; Su, Ying; Ai, Huashui; Zhang, Zhiyan; Yang, Bin; Ruan, Guorong; Xiao, Shijun; Liao, Xinjun; Ren, Jun; Huang, Lusheng; Ding, Nengshui

    2016-06-01

    Umbilical hernia (UH) is one of the most common congenital defects in pigs, leading to considerable economic loss and serious animal welfare problems. To test whether copy number variations (CNVs) contribute to pig UH, we performed a case-control genome-wide CNV association study on 905 pigs from the Duroc, Landrace and Yorkshire breeds using the Porcine SNP60 BeadChip and penncnv algorithm. We first constructed a genomic map comprising 6193 CNVs that pertain to 737 CNV regions. Then, we identified eight CNVs significantly associated with the risk for UH in the three pig breeds. Six of seven significantly associated CNVs were validated using quantitative real-time PCR. Notably, a rare CNV (CNV14:13030843-13059455) encompassing the NUGGC gene was strongly associated with UH (permutation-corrected P = 0.0015) in Duroc pigs. This CNV occurred exclusively in seven Duroc UH-affected individuals. SNPs surrounding the CNV did not show association signals, indicating that rare CNVs may play an important role in complex pig diseases such as UH. The NUGGC gene has been implicated in human omphalocele and inguinal hernia. Our finding supports that CNVs, including the NUGGC CNV, contribute to the pathogenesis of pig UH.

  13. Investigation of modifier genes within copy number variations in Rett syndrome.

    Science.gov (United States)

    Artuso, Rosangela; Papa, Filomena T; Grillo, Elisa; Mucciolo, Mafalda; Yasui, Dag H; Dunaway, Keith W; Disciglio, Vittoria; Mencarelli, Maria A; Pollazzon, Marzia; Zappella, Michele; Hayek, Giuseppe; Mari, Francesca; Renieri, Alessandra; Lasalle, Janine M; Ariani, Francesca

    2011-07-01

    MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis. We did not identify one major common gene/region, suggesting that modifiers may be complex and variable between cases. However, we detected CNVs correlating with disease severity that contain candidate modifiers. CROCC (1p36.13) is a potential MeCP2 target, in which a duplication in a Z-RTT and a deletion in a classic patient were observed. CROCC encodes a structural component of ciliary motility that is required for correct brain development. CFHR1 and CFHR3, on 1q31.3, may be involved in the regulation of complement during synapse elimination, and were found to be deleted in a Z-RTT but duplicated in two classic patients. The duplication of 10q11.22, present in two Z-RTT patients, includes GPRIN2, a regulator of neurite outgrowth and PPYR1, involved in energy homeostasis. Functional analyses are necessary to confirm candidates and to define targets for future therapies.

  14. New class of gene-termini-associated human RNAs suggests a novel RNA copying mechanism.

    Science.gov (United States)

    Kapranov, Philipp; Ozsolak, Fatih; Kim, Sang Woo; Foissac, Sylvain; Lipson, Doron; Hart, Chris; Roels, Steve; Borel, Christelle; Antonarakis, Stylianos E; Monaghan, A Paula; John, Bino; Milos, Patrice M

    2010-07-29

    Small (<200 nucleotide) RNA (sRNA) profiling of human cells using various technologies demonstrates unexpected complexity of sRNAs with hundreds of thousands of sRNA species present. Genetic and in vitro studies show that these RNAs are not merely degradation products of longer transcripts but could indeed have a function. Furthermore, profiling of RNAs, including the sRNAs, can reveal not only novel transcripts, but also make clear predictions about the existence and properties of novel biochemical pathways operating in a cell. For example, sRNA profiling in human cells indicated the existence of an unknown capping mechanism operating on cleaved RNA, a biochemical component of which was later identified. Here we show that human cells contain a novel type of sRNA that has non-genomically encoded 5' poly(U) tails. The presence of these RNAs at the termini of genes, specifically at the very 3' ends of known mRNAs, strongly argues for the presence of a yet uncharacterized endogenous biochemical pathway in cells that can copy RNA. We show that this pathway can operate on multiple genes, with specific enrichment towards transcript-encoding components of the translational machinery. Finally, we show that genes are also flanked by sense, 3' polyadenylated sRNAs that are likely to be capped.

  15. COPI activity coupled with fatty acid biosynthesis is required for viral replication.

    Directory of Open Access Journals (Sweden)

    Sara Cherry

    2006-10-01

    Full Text Available During infection by diverse viral families, RNA replication occurs on the surface of virally induced cytoplasmic membranes of cellular origin. How this process is regulated, and which cellular factors are required, has been unclear. Moreover, the host-pathogen interactions that facilitate the formation of this new compartment might represent critical determinants of viral pathogenesis, and their elucidation may lead to novel insights into the coordination of vesicular trafficking events during infection. Here we show that in Drosophila cells, Drosophila C virus remodels the Golgi apparatus and forms a novel vesicular compartment, on the surface of which viral RNA replication takes place. Using genome-wide RNA interference screening, we found that this step in the viral lifecycle requires at least two host encoded pathways: the coat protein complex I (COPI coatamer and fatty acid biosynthesis. Our results integrate, clarify, and extend numerous observations concerning the cell biology of viral replication, allowing us to conclude that the coupling of new cellular membrane formation with the budding of these vesicles from the Golgi apparatus allows for the regulated generation of this new virogenic organelle, which is essential for viral replication. Additionally, because these pathways are also limiting in flies and in human cells infected with the related RNA virus poliovirus, they may represent novel targets for antiviral therapies.

  16. Contribution of Copy Number Variation to Down Syndrome-associated Atrioventricular Septal Defects

    Science.gov (United States)

    Ramachandran, Dhanya; Mulle, Jennifer G.; Locke, Adam E.; Bean, Lora J.H.; Rosser, Tracie C.; Bose, Promita; Dooley, Kenneth J.; Cua, Clifford L.; Capone, George T.; Reeves, Roger H.; Maslen, Cheryl L.; Cutler, David J.; Sherman, Stephanie L.; Zwick, Michael E.

    2014-01-01

    Purpose The goal of this study was to identify the contribution of large copy number variants (CNV) to Down syndrome (DS) associated atrioventricular septal defects (AVSD), whose risk in the trisomic population is 2000-fold more compared to general disomic population. Methods Genome-wide CNV analysis was performed on 452 individuals with DS (210 cases with complete AVSD; 242 controls with structurally normal hearts) using Affymetrix SNP 6.0 arrays, making this the largest heart study conducted to date on a trisomic background. Results Large common CNVs with substantial effect sizes (OR>2.0) do not account for the increased risk observed in DS-associated AVSD. In contrast, cases had a greater burden of large rare deletions (p<0.01) and intersected more genes (p<0.007) when compared to controls. We also observed a suggestive enrichment of deletions intersecting ciliome genes in cases compared to controls. Conclusion Our data provide strong evidence that large rare deletions increase the risk of DS-associated AVSD, while large common CNVs do not appear to increase the risk of DS-associated AVSD. The genetic architecture of AVSD is complex and multifactorial in nature. PMID:25341113

  17. ParseCNV integrative copy number variation association software with quality tracking.

    Science.gov (United States)

    Glessner, Joseph T; Li, Jin; Hakonarson, Hakon

    2013-03-01

    A number of copy number variation (CNV) calling algorithms exist; however, comprehensive software tools for CNV association studies are lacking. We describe ParseCNV, unique software that takes CNV calls and creates probe-based statistics for CNV occurrence in both case-control design and in family based studies addressing both de novo and inheritance events, which are then summarized based on CNV regions (CNVRs). CNVRs are defined in a dynamic manner to allow for a complex CNV overlap while maintaining precise association region. Using this approach, we avoid failure to converge and non-monotonic curve fitting weaknesses of programs, such as CNVtools and CNVassoc, and although Plink is easy to use, it only provides combined CNV state probe-based statistics, not state-specific CNVRs. Existing CNV association methods do not provide any quality tracking information to filter confident associations, a key issue which is fully addressed by ParseCNV. In addition, uncertainty in CNV calls underlying CNV associations is evaluated to verify significant results, including CNV overlap profiles, genomic context, number of probes supporting the CNV and single-probe intensities. When optimal quality control parameters are followed using ParseCNV, 90% of CNVs validate by polymerase chain reaction, an often problematic stage because of inadequate significant association review. ParseCNV is freely available at http://parsecnv.sourceforge.net.

  18. A genome-wide copy number variant study of suicidal behavior.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Gross

    Full Text Available Suicide and suicide attempts are complex behaviors that result from the interaction of different factors, including genetic variants that increase the predisposition to suicidal behaviors. Copy number variations (CNVs are deletions or duplications of a segment of DNA usually larger than one kilobase. These structural genetic changes, although quite rare, have been associated with genetic liability to mental disorders, such as autism, schizophrenia, and bipolar disorder. No genome-wide level studies have been published investigating the potential role of CNVs in suicidal behaviors. Based on single-nucleotide polymorphism array data, we followed the Penn-CNV standards to detect CNVs in 1,608 subjects, comprising 475 suicide and suicide attempt cases and 1,133 controls. Although the initial algorithms determined the presence of CNVs on chromosomes 6 and 12 in seven and eight cases, respectively, compared with none of the controls, visual inspection of the raw data did not support this finding. Furthermore we were unable to validate these findings by CNV-specific real-time polymerase chain reaction. Additionally, rare CNV burden analysis did not find an association between the frequency or length of rare CNVs and suicidal behavior in our sample population. Although our findings suggest CNVs do not play an important role in the etiology of suicidal behaviors, they are not inconsistent with the strong evidence from the literature suggesting that other genetic variants account for a portion of the total phenotypic variability in suicidal behavior.

  19. Copy Protection in Jet Set Willy: developing methodology for retrogame archaeology

    Directory of Open Access Journals (Sweden)

    John Aycock

    2017-04-01

    Full Text Available Video games, and more generally computer games, are unquestionably technological artefacts that have cultural significance. Old computer games in particular had to function under technical constraints that would be alien to many modern programmers, while at the same time providing something novel and at first foreign to consumers. How did their creators accomplish their technical feats, and what impact did that have for the player-consumer? The study of 'retro' computer games' implementation is one topic within the nascent area of archaeogaming. Digital rights management (DRM continues to be a major issue in the protection and distribution of content in electronic form. In this article, we study an early example of the implementation of copy protection in the 1984 game Jet Set Willy, something that comprises both physical and digital artefacts. It acts as a vehicle to illustrate a number of methods that we used to understand game implementation, culminating in a full reconstruction of the technique. The methods we cover include: 'traditional' research, along with its limitations in this context; code and data analysis; hypothesis testing; reconstruction. Through this positivist experimental approach, our results are both independently verifiable and repeatable. We also approach the complex context of early DRM, its hacks and workarounds by the player community, and what precipitated the design choices made for this particular game.

  20. Comparative analysis of methods for identifying recurrent copy number alterations in cancer.

    Directory of Open Access Journals (Sweden)

    Xiguo Yuan

    Full Text Available Recurrent copy number alterations (CNAs play an important role in cancer genesis. While a number of computational methods have been proposed for identifying such CNAs, their relative merits remain largely unknown in practice since very few efforts have been focused on comparative analysis of the methods. To facilitate studies of recurrent CNA identification in cancer genome, it is imperative to conduct a comprehensive comparison of performance and limitations among existing methods. In this paper, six representative methods proposed in the latest six years are compared. These include one-stage and two-stage approaches, working with raw intensity ratio data and discretized data respectively. They are based on various techniques such as kernel regression, correlation matrix diagonal segmentation, semi-parametric permutation and cyclic permutation schemes. We explore multiple criteria including type I error rate, detection power, Receiver Operating Characteristics (ROC curve and the area under curve (AUC, and computational complexity, to evaluate performance of the methods under multiple simulation scenarios. We also characterize their abilities on applications to two real datasets obtained from cancers with lung adenocarcinoma and glioblastoma. This comparison study reveals general characteristics of the existing methods for identifying recurrent CNAs, and further provides new insights into their strengths and weaknesses. It is believed helpful to accelerate the development of novel and improved methods.

  1. High resolution measurement of DUF1220 domain copy number from whole genome sequence data.

    Science.gov (United States)

    Astling, David P; Heft, Ilea E; Jones, Kenneth L; Sikela, James M

    2017-08-14

    DUF1220 protein domains found primarily in Neuroblastoma BreakPoint Family (NBPF) genes show the greatest human lineage-specific increase in copy number of any coding region in the genome. There are 302 haploid copies of DUF1220 in hg38 (~160 of which are human-specific) and the majority of these can be divided into 6 different subtypes (referred to as clades). Copy number changes of specific DUF1220 clades have been associated in a dose-dependent manner with brain size variation (both evolutionarily and within the human population), cognitive aptitude, autism severity, and schizophrenia severity. However, no published methods can directly measure copies of DUF1220 with high accuracy and no method can distinguish between domains within a clade. Here we describe a novel method for measuring copies of DUF1220 domains and the NBPF genes in which they are found from whole genome sequence data. We have characterized the effect that various sequencing and alignment parameters and strategies have on the accuracy and precision of the method and defined the parameters that lead to optimal DUF1220 copy number measurement and resolution. We show that copy number estimates obtained using our read depth approach are highly correlated with those generated by ddPCR for three representative DUF1220 clades. By simulation, we demonstrate that our method provides sufficient resolution to analyze DUF1220 copy number variation at three levels: (1) DUF1220 clade copy number within individual genes and groups of genes (gene-specific clade groups) (2) genome wide DUF1220 clade copies and (3) gene copy number for DUF1220-encoding genes. To our knowledge, this is the first method to accurately measure copies of all six DUF1220 clades and the first method to provide gene specific resolution of these clades. This allows one to discriminate among the ~300 haploid human DUF1220 copies to an extent not possible with any other method. The result is a greatly enhanced capability to analyze the

  2. Copy number variations in three children with sudden infant death.

    Science.gov (United States)

    Toruner, G A; Kurvathi, R; Sugalski, R; Shulman, L; Twersky, S; Pearson, P G; Tozzi, R; Schwalb, M N; Wallerstein, R

    2009-07-01

    Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty-seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array-based comparative genomic hybridization (array-CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 x 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an approximately 3-Mb (chr 8: 143,211,215-qter) duplication on 8q24.3-qter and a 4.4-Mb deletion on the 22q13.3-qter (chr 22: 45,047,068-qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240-kb (chr 6: 26,139,810-26,380,787) duplication and a 1.9-Mb deletion (chr 6: 26,085,971-27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array-CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array-CGH analysis may be beneficial during the investigations after sudden infant death.

  3. Analysis of copy number variations among diverse cattle breeds

    Science.gov (United States)

    Liu, George E.; Hou, Yali; Zhu, Bin; Cardone, Maria Francesca; Jiang, Lu; Cellamare, Angelo; Mitra, Apratim; Alexander, Leeson J.; Coutinho, Luiz L.; Dell'Aquila, Maria Elena; Gasbarre, Lou C.; Lacalandra, Gianni; Li, Robert W.; Matukumalli, Lakshmi K.; Nonneman, Dan; de A. Regitano, Luciana C.; Smith, Tim P.L.; Song, Jiuzhou; Sonstegard, Tad S.; Van Tassell, Curt P.; Ventura, Mario; Eichler, Evan E.; McDaneld, Tara G.; Keele, John W.

    2010-01-01

    Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 megabases or ∼1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions, such as immunity, lactation, reproduction, and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research. PMID:20212021

  4. A map of copy number variations in Chinese populations.

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    Haiyi Lou

    Full Text Available It has been shown that the human genome contains extensive copy number variations (CNVs. Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of them within and between populations. However, CNV study of Chinese minorities, which harbor the majority of genetic diversity of Chinese populations, has been underrepresented considering the same efforts in other populations. Here we constructed, to our knowledge, a first CNV map in seven Chinese populations representing the major linguistic groups in China with 1,440 CNV regions identified using Affymetrix SNP 6.0 Array. Considerable differences in distributions of CNV regions between populations and substantial population structures were observed. We showed that ∼35% of CNV regions identified in minority ethnic groups are not shared by Han Chinese population, indicating that the contribution of the minorities to genetic architecture of Chinese population could not be ignored. We further identified highly differentiated CNV regions between populations. For example, a common deletion in Dong and Zhuang (44.4% and 50%, which overlaps two keratin-associated protein genes contributing to the structure of hair fibers, was not observed in Han Chinese. Interestingly, the most differentiated CNV deletion between HapMap CEU and YRI containing CCL3L1 gene reported in previous studies was also the highest differentiated regions between Tibetan and other populations. Besides, by jointly analyzing CNVs and SNPs, we found a CNV region containing gene CTDSPL were in almost perfect linkage disequilibrium between flanking SNPs in Tibetan while not in other populations except HapMap CHD. Furthermore, we found the SNP taggability of CNVs in Chinese populations was much lower than that in European populations. Our results suggest the necessity of a full characterization of CNVs in Chinese populations, and the CNV map we constructed serves as a

  5. Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences.

    Science.gov (United States)

    Nygren, Anders O H; Ameziane, Najim; Duarte, Helena M B; Vijzelaar, Raymon N C P; Waisfisz, Quinten; Hess, Corine J; Schouten, Jan P; Errami, Abdellatif

    2005-08-16

    Copy number changes and CpG methylation of various genes are hallmarks of tumor development but are not yet widely used in diagnostic settings. The recently developed multiplex ligation-dependent probe amplification (MLPA) method has increased the possibilities for multiplex detection of gene copy number aberrations in a routine laboratory. Here we describe a novel robust method: the methylation-specific MLPA (MS-MLPA) that can detect changes in both CpG methylation as well as copy number of up to 40 chromosomal sequences in a simple reaction. In MS-MLPA, the ligation of MLPA probe oligonucleotides is combined with digestion of the genomic DNA-probe hybrid complexes with methylation-sensitive endonucleases. Digestion of the genomic DNA-probe complex, rather than double-stranded genomic DNA, allowed the use of DNA derived from the formalin treated paraffin-embedded tissue samples, enabling retrospective studies. To validate this novel method, we used MS-MLPA to detect aberrant methylation in DNA samples of patients with Prader-Willy syndrome, Angelman syndrome or acute myeloid leukemia.

  6. High-Resolution Analysis of Gene Copy Number Alterations in Human Prostate Cancer Using CGH on cDNA Microarrays: Impact of Copy Number on Gene Expression

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    Maija Wolf

    2004-05-01

    Full Text Available Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classical chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28 and loss (18 were found, their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13% and gains at iq and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, 74-76 Mbp from the p-telomere, which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, 17q (losses, at 3q, 5p, 6p (gains. Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P < .0001 overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, corresponding to common deletions and gains of often large chromosomal regions.

  7. PINCH-2 presents functional copy number variation and suppresses migration of colon cancer cells by paracrine activity.

    Science.gov (United States)

    Park, Chan Hee; Rha, Sun Young; Ahn, Joong Bae; Shin, Sang Joon; Kwon, Woo Sun; Kim, Tae Soo; An, Sungwhan; Kim, Nam Kyu; Yang, Woo-ick; Chung, Hyun Cheol

    2015-05-15

    In recent years, characterization of cancer and its environment has become necessary. However, studies of the cancer microenvironment remain insufficient. Copy number variations (CNVs) occur in 40% of cancer-related genes, but few studies have reported the correlation between CNVs in morphologically normal tissues adjacent to cancer and cancer progression. In this study, we evaluated cancer cell migration and invasion according to the genetic differences between cancer tissues and their surrounding normal tissues. To study the field cancerization effect, we screened 89 systemic metastasis-related CNVs from morphologically normal tissues adjacent to colon cancers. Among these CNVs, LIM and senescent cell antigen-like domain 2 (PINCH-2) showed copy number amplification and upregulation of mRNA in the nonrelapsed group compared to the systemic relapse group. PINCH-2 expression in colon cancer cells was lower than that in normal epithelial colon cells at both the protein and mRNA levels. Suppression of PINCH-2 resulted in decreased formation of the PINCH-2-IPP (PINCH-2, integrin-linked kinase and α-parvin) complex and reciprocally increased formation of the PINCH-1-IPP complex. Although PINCH-2 expression of survival pathway-related proteins (Akt and phospho-Akt) did not change upon suppression of PINCH-2 expression, cell migration-related proteins [matrix-metalloproteinase (MMP)-9 and -11] were upregulated through autocrine and paracrine activation. Thus, PINCH-2 participates in decreased systemic recurrence by competitively regulating IPP complex formation with PINCH-1, thereby suppressing autocrine and paracrine effects on motility in colon cancer. This genetic change in morphologically normal tissue suggests a field cancerization effect of the tumor microenvironment in cancer progression.

  8. Copy, edit, and paste: natural product approaches to biomaterials and neuroengineering.

    Science.gov (United States)

    Gademann, Karl

    2015-03-17

    Progress in the chemical sciences has formed the world we live in, both on a macroscopic and on a nanoscopic scale. The last century witnessed the development of high performance materials that interact with humans on many layers, from clothing to construction, from media to medical devices. On a molecular level, natural products and their derivatives influence many biological processes, and these compounds have enormously contributed to the health and quality of living of humans. Although coatings of stone materials with oils or resins (containing natural products) have led to improved tools already millennia ago, in contrast today, natural product approaches to designer materials, that is, combining the best of both worlds, remain scarce. In this Account, we will summarize our recent research efforts directed to the generation of natural product functionalized materials, exploiting the strategy of "copy, edit, and paste with natural products". Natural products embody the wisdom of evolution, and only total synthesis is able to unlock the secrets enshrined in their molecular structure. We employ total synthesis ("copy") as a scientific approach to address problems related to molecular structure, the biosynthesis of natural products, and their bioactivity. Additionally, the fundamental desire to investigate the mechanism of action of natural products constitutes a key driver for scientific inquiry. In an emerging area of relevance to society, we have prepared natural products such as militarinone D that can stimulate neurite outgrowth and facilitate nerve regeneration. This knowledge obtained by synthetic organic chemistry on complex natural products can then be used to design structurally simplified compounds that retain the biological power of the parent natural product ("edit"). This process, sometimes referred to as function-oriented synthesis, allows obtaining derivatives with better properties, improving their chemical tractability and reducing the step count

  9. DNA copy number changes in high-grade malignant peripheral nerve sheath tumors by array CGH

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    Bjerkehagen Bodil

    2008-06-01

    Full Text Available Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs are rare and highly aggressive soft tissue tumors showing complex chromosomal aberrations. In order to identify recurrent chromosomal regions of gain and loss, and thereby novel gene targets of potential importance for MPNST development and/or progression, we have analyzed DNA copy number changes in seven high-grade MPNSTs using microarray-based comparative genomic hybridization (array CGH. Results Considerable more gains than losses were observed, and the most frequent minimal recurrent regions of gain included 1q24.1-q24.2, 1q24.3-q25.1, 8p23.1-p12, 9q34.11-q34.13 and 17q23.2-q25.3, all gained in five of seven samples. The 17q23.2-q25.3 region was gained in all five patients with poor outcome and not in the two patients with disease-free survival. cDNA microarray analysis and quantitative real-time reverse transcription PCR were used to investigate expression of genes located within these regions. The gene lysyl oxidase-like 2 (LOXL2 was identified as a candidate target for the 8p23.1-p12 gain. Within 17q, the genes topoisomerase II-α (TOP2A, ets variant gene 4 (E1A enhancer binding protein, E1AF (ETV4 and baculoviral IAP repeat-containing 5 (survivin (BIRC5 showed increased expression in all samples compared to two benign tumors. Increased expression of these genes has previously been associated with poor survival in other malignancies, and for TOP2A, in MPNSTs as well. In addition, we have analyzed the expression of five micro RNAs located within the 17q23.2-q25.3 region, but none of them showed high expression levels compared to the benign tumors. Conclusion Our study shows the potential of using DNA copy number changes obtained by array CGH to predict the prognosis of MPNST patients. Although no clear correlations between the expression level and patient outcome were observed, the genes TOP2A, ETV4 and BIRC5 are interesting candidate targets for the 17q gain associated

  10. Analysis of copy loss and gain variations in Holstein cattle autosomes using BeadChip SNPs

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    Weller Joel I

    2010-11-01

    Full Text Available Abstract Background Copy number variation (CNV has been recently identified in human and other mammalian genomes, and there is a growing awareness of CNV's potential as a major source for heritable variation in complex traits. Genomic selection is a newly developed tool based on the estimation of breeding values for quantitative traits through the use of genome-wide genotyping of SNPs. Over 30,000 Holstein bulls have been genotyped with the Illumina BovineSNP50 BeadChip, which includes 54,001 SNPs (~SNP/50,000 bp, some of which fall within CNV regions. Results We used the BeadChip data obtained for 912 Israeli bulls to investigate the effects of CNV on SNP calls. For each of the SNPs, we estimated the frequencies of occurrence of loss of heterozygosity (LOH and of gain, based either on deviation from the expected Hardy-Weinberg equilibrium (HWE or on signal intensity (SI using the PennCNV "detect" option. Correlations between LOH/CNV frequencies predicted by the two methods were low (up to r = 0.08. Nevertheless, 418 locations displayed significantly high frequencies by both methods. Efficiency of designating large genomic clusters of olfactory receptors as CNVs was 29%. Frequency values for copy loss were distinguishable in non-autosomal regions, indicating misplacement of a region in the current BTA7 map. Analysis of BTA18 placed major quantitative trait loci affecting net merit in the US Holstein population in regions rich in segmental duplications and CNVs. Enrichment of transporters in CNV loci suggested their potential effect on milk-production traits. Conclusions Expansion of HWE and PennCNV analyses allowed estimating LOH/CNV frequencies, and combining the two methods yielded more sensitive detection of inherited CNVs and better estimation of their possible effects on cattle genetics. Although this approach was more effective than methodologies previously applied in cattle, it has severe limitations. Thus the number of CNVs reported here

  11. Copy number variations in Saudi family with intellectual disability and epilepsy

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    Muhammad I. Naseer

    2016-10-01

    Full Text Available Abstract Background Epilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups. Novel Copy number variations (CNVs are considered as important reason for the numerous neurodevelopmental disorders along with intellectual disability and epilepsy. DNA array based studies contribute to explain a more severe clinical presentation of the disease but interoperation of many detected CNVs are still challenging. Results In order to study novel CNVs with epilepsy related genes in Saudi family with six affected and two normal individuals with several forms of epileptic seizures, intellectual disability (ID, and minor dysmorphism, we performed the high density whole genome Agilent sure print G3 Hmn CGH 2x 400 K array-CGH chips analysis. Our results showed de novo deletions, duplications and deletion plus duplication on differential chromosomal regions in the affected individuals that were not shown in the normal fathe and normal kids by using Agilent CytoGenomics 3.0.6.6 softwear. Copy number gain were observed in the chromosome 1, 16 and 22 with LCE3C, HPR, GSTT2, GSTTP2, DDT and DDTL genes respectively whereas the deletions observed in the chromosomal regions 8p23-p21 (4303127–4337759 and the potential gene in this region is CSMD1 (OMIM: 612279. Moreover, the array CGH results deletions and duplication were also validated by using primer design of deleted regions utilizing the flanked SNPs using simple PCR and also by using quantitative real time PCR. Conclusions We found some of the de novo deletions and duplication in our study in Saudi family with intellectual disability and epilepsy. Our results suggest that array-CGH should be used as a first line of genetic test for epilepsy except there is a strong indication for a monogenic syndrome. The advanced high through put array-CGH technique used in this study aim to collect the data base and to identify new mechanisms describing

  12. Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics

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    Liu Melissa M

    2012-08-01

    Full Text Available Abstract Age-related macular degeneration (AMD is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs, and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3 and glutathione S transferase genes (GSTM1 and GSTT1 have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.

  13. An evolutionary history of defensins: a role for copy number variation in maximizing host innate and adaptive immune responses.

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    Lee R Machado

    2015-03-01

    Full Text Available Defensins represent an evolutionary ancient family of antimicrobial peptides that play diverse roles in human health and disease. Defensins are cationic cysteine-containing multifunctional peptides predominantly expressed by epithelial cells or neutrophils. Defensins play a key role in host innate immune responses to infection and, in addition to their classically described role as antimicrobial peptides, have also been implicated in immune modulation, fertility, development and wound healing. Aberrant expression of defensins is important in a number of inflammatory diseases as well as modulating host immune responses to bacteria, unicellular pathogens and viruses. In parallel with their role in immunity, in other species, defensins have evolved alternative functions, including the control of coat color in dogs. Defensin genes reside in complex genomic regions that are prone to structural variations and some defensin family members exhibit copy number variation (CNV. Structural variations have mediated, and continue to influence, the diversification and expression of defensin family members. This review highlights the work currently being done to better understand the genomic architecture of the β-defensin locus. It evaluates current evidence linking defensin copy number variation to autoimmune disease (i.e. Crohn’s disease and psoriasis as well as the contribution CNV has in influencing immune responses to HIV infection.

  14. Complex Beauty

    OpenAIRE

    Franceschet, Massimo

    2014-01-01

    Complex systems and their underlying convoluted networks are ubiquitous, all we need is an eye for them. They pose problems of organized complexity which cannot be approached with a reductionist method. Complexity science and its emergent sister network science both come to grips with the inherent complexity of complex systems with an holistic strategy. The relevance of complexity, however, transcends the sciences. Complex systems and networks are the focal point of a philosophical, cultural ...

  15. Copying skills in relation to word reading and writing in Chinese children with and without dyslexia.

    Science.gov (United States)

    McBride-Chang, Catherine; Chung, Kevin K H; Tong, Xiuhong

    2011-11-01

    Because Chinese character learning typically relies heavily on rote character copying, we tested independent copying skill in third- and fourth-grade Chinese children with and without dyslexia. In total, 21 Chinese third and fourth graders with dyslexia and 33 without dyslexia (matched on age, nonverbal IQ, and mother's education level) were given tasks of copying unfamiliar print in Vietnamese, Korean, and Hebrew as well as tests of word reading and writing, morphological awareness, rapid automatized naming (RAN), and orthographic processing. All three copying tasks distinguished dyslexic children from nondyslexic children with moderate effect sizes (.67-.80). Zero-order correlations of the three copying tasks with dictation and reading ranged from .37 to .58. With age, Raven's, group status, RAN, morphological awareness, and orthographic measures statistically controlled, the copying tasks uniquely explained 6% and 3% variance in word reading and dictation, respectively. Results suggest that copying skill itself may be useful in understanding the development and impairment of literacy skills in Chinese.

  16. An efficient method for measuring copy number variation applied to improvement of nematode resistance in soybean.

    Science.gov (United States)

    Lee, Tong Geon; Diers, Brian W; Hudson, Matthew E

    2016-10-01

    Copy number variation (CNV) is implicated in important traits in multiple crop plants, but can be challenging to genotype using conventional methods. The Rhg1 locus of soybean, which confers resistance to soybean cyst nematode (SCN), is a CNV of multiple 31.2-kb genomic units each containing four genes. Reliable, high-throughput methods to quantify Rhg1 and other CNVs for selective breeding were developed. The CNV genotyping assay described here uses a homeologous gene copy within the paleopolyploid soybean genome to provide the internal control for a single-tube TaqMan copy number assay. Using this assay, CNV in breeding populations can be tracked with high precision. We also show that extensive CNV exists within Fayette, a released, inbred SCN-resistant soybean cultivar with a high copy number at Rhg1 derived from a single donor parent. Copy number at Rhg1 is therefore unstable within a released variety over a relatively small number of generations. Using this assay to select for individuals with altered copy number, plants were obtained with both increased copy number and increased SCN resistance relative to control plants. Thus, CNV genotyping technologies can be used as a new type of marker-assisted selection to select for desirable traits in breeding populations, and to control for undesirable variation within cultivars. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  17. Decreases in average bacterial community rRNA operon copy number during succession.

    Science.gov (United States)

    Nemergut, Diana R; Knelman, Joseph E; Ferrenberg, Scott; Bilinski, Teresa; Melbourne, Brett; Jiang, Lin; Violle, Cyrille; Darcy, John L; Prest, Tiffany; Schmidt, Steven K; Townsend, Alan R

    2016-05-01

    Trait-based studies can help clarify the mechanisms driving patterns of microbial community assembly and coexistence. Here, we use a trait-based approach to explore the importance of rRNA operon copy number in microbial succession, building on prior evidence that organisms with higher copy numbers respond more rapidly to nutrient inputs. We set flasks of heterotrophic media into the environment and examined bacterial community assembly at seven time points. Communities were arrayed along a geographic gradient to introduce stochasticity via dispersal processes and were analyzed using 16 S rRNA gene pyrosequencing, and rRNA operon copy number was modeled using ancestral trait reconstruction. We found that taxonomic composition was similar between communities at the beginning of the experiment and then diverged through time; as well, phylogenetic clustering within communities decreased over time. The average rRNA operon copy number decreased over the experiment, and variance in rRNA operon copy number was lowest both early and late in succession. We then analyzed bacterial community data from other soil and sediment primary and secondary successional sequences from three markedly different ecosystem types. Our results demonstrate that decreases in average copy number are a consistent feature of communities across various drivers of ecological succession. Importantly, our work supports the scaling of the copy number trait over multiple levels of biological organization, ranging from cells to populations and communities, with implications for both microbial ecology and evolution.

  18. Does testing with feedback improve adult spelling skills relative to copying and reading?

    Science.gov (United States)

    Pan, Steven C; Rubin, Benjamin R; Rickard, Timothy C

    2015-12-01

    We examined testing's ability to enhance adult spelling acquisition, relative to copying and reading. Across 3 experiments in which testing with feedback was compared with copying, the spelling improvement after testing matched that following the same amount of time spent copying. A potent testing advantage, however, was observed for spelling words free-recalled. In the fourth experiment, a large testing advantage for both word free recall and spelling was observed, versus reading. Subjects also generally preferred testing and rated it as more effective than copying or reading. The equivalent performance of testing and copying for spelling contrasts with prior work involving children and suggests that retrieval practice may not be the only effective mechanism for spelling skill acquisition. Rather, we suggest that the critical learning event for spelling is focused study on phoneme-to-grapheme mappings for previously unlearned letter sequences. For adults with extensive spelling expertise, focused study is more automatic during both copying and testing with feedback than for individuals with beginning spelling skills. Reading, however, would not be expected to produce efficient focused study of phoneme-to-grapheme mappings, regardless of expertise level. Overall, adult spelling skill acquisition benefits both from testing and copying, and substantially less from reading. (c) 2015 APA, all rights reserved).

  19. 78 FR 39327 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-DVD Copy Control...

    Science.gov (United States)

    2013-07-01

    ... Research and Production Act of 1993--DVD Copy Control Association Notice is hereby given that, on May 31....C. 4301 et seq. (``the Act''), DVD Copy Control Association (``DVD CCA'') has filed written...

  20. Low AMY1 Gene Copy Number Is Associated with Increased Body Mass Index in Prepubertal Boys.

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    M Loredana Marcovecchio

    Full Text Available Genome-wide association studies have identified more than 60 single nucleotide polymorphisms associated with Body Mass Index (BMI. Additional genetic variants, such as copy number variations (CNV, have also been investigated in relation to BMI. Recently, the highly polymorphic CNV in the salivary amylase (AMY1 gene, encoding an enzyme implicated in the first step of starch digestion, has been associated with obesity in adults and children. We assessed the potential association between AMY1 copy number and a wide range of BMI in a population of Italian school-children.744 children (354 boys, 390 girls, mean age (±SD: 8.4±1.4years underwent anthropometric assessments (height, weight and collection of saliva samples for DNA extraction. AMY1 copies were evaluated by quantitative PCR.A significant increase of BMI z-score by decreasing AMY1 copy number was observed in boys (β: -0.117, p = 0.033, but not in girls. Similarly, waist circumference (β: -0.155, p = 0.003, adjusted for age was negatively influenced by AMY1 copy number in boys. Boys with 8 or more AMY1 copy numbers presented a significant lower BMI z-score (p = 0.04 and waist circumference (p = 0.01 when compared to boys with less than 8 copy numbers.In this pediatric-only, population-based study, a lower AMY1 copy number emerged to be associated with increased BMI in boys. These data confirm previous findings from adult studies and support a potential role of a higher copy number of the salivary AMY1 gene in protecting from excess weight gain.

  1. Association between TLR7 copy number variations and hepatitis B virus infection outcome in Chinese.

    Science.gov (United States)

    Li, Fang; Li, Xu; Zou, Gui-Zhou; Gao, Yu-Feng; Ye, Jun

    2017-03-07

    To explore whether copy number variations (CNVs) of toll-like receptor 7 (TLR7) are associated with susceptibility to chronic hepatitis B virus (HBV) infection. This study included 623 patients (495 males and 128 females) with chronic hepatitis B virus infection (CHB) and 300 patients (135 females and 165 males) with acute hepatitis B virus infection (AHB) as controls. All CHB patients were further categorized according to disease progression after HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). Copy numbers of the TLR7 gene were measured using the AccuCopy method. χ(2) tests were used to evaluate the association between TLR7 CNVs and infection type. P values, odds ratios, and 95% confidence intervals (CIs) were used to estimate the effects of risk. Among male patients, there were significant differences between the AHB group and CHB group in the distribution of TLR7 CNVs. Low copy number of TLR7 was significantly associated with chronic HBV infection (OR = 0.329, 95%CI: 0.229-0.473, P copy number was also found between AHB and CHB female patients, with low copy number again associated with an increased risk of chronic HBV infection (OR = 0.292, 95%CI: 0.173-0.492, P copy number among the three types of chronic HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). In addition, there was no association between TLR7 copy number and titer of the HBV e antigen. Low TLR7 copy number is a risk factor for chronic HBV infection but is not associated with later stages of disease progression.

  2. Peripheral blood mitochondrial DNA copy number is associated with prostate cancer risk and tumor burden.

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    Weimin Zhou

    Full Text Available Alterations of mitochondrial DNA (mtDNA have been associated with the risk of a number of human cancers; however, the relationship between mtDNA copy number in peripheral blood leukocytes (PBLs and the risk of prostate cancer (PCa has not been investigated. In a case-control study of 196 PCa patients and 196 age-paired healthy controls in a Chinese Han population, the association between mtDNA copy number in PBLs and PCa risk was evaluated. The relative mtDNA copy number was measured using quantitative real-time PCR; samples from three cases and two controls could not be assayed, leaving 193 cases and 194 controls for analysis. PCa patients had significantly higher mtDNA copy numbers than controls (medians 0.91 and 0.82, respectively; P<0.001. Dichotomized at the median value of mtDNA copy number in the controls, high mtDNA copy number was significantly associated with an increased risk of PCa (adjusted odds ratio= 1.85, 95% confidence interval: 1.21-2.83. A significant dose-response relationship was observed between mtDNA copy number and risk of PCa in quartile analysis (Ptrend = 0.011. Clinicopathological analysis showed that high mtDNA copy numbers in PCa patients were significantly associated with high Gleason score and advanced tumor stage, but not serum prostate-specific antigen level (P = 0.002, 0.012 and 0.544, respectively. These findings of the present study indicate that increased mtDNA copy number in PBLs is significantly associated with an increased risk of PCa and may be a reflection of tumor burden.

  3. A multilevel model to address batch effects in copy number estimation using SNP arrays.

    Science.gov (United States)

    Scharpf, Robert B; Ruczinski, Ingo; Carvalho, Benilton; Doan, Betty; Chakravarti, Aravinda; Irizarry, Rafael A

    2011-01-01

    Submicroscopic changes in chromosomal DNA copy number dosage are common and have been implicated in many heritable diseases and cancers. Recent high-throughput technologies have a resolution that permits the detection of segmental changes in DNA copy number that span thousands of base pairs in the genome. Genomewide association studies (GWAS) may simultaneously screen for copy number phenotype and single nucleotide polymorphism (SNP) phenotype associations as part of the analytic strategy. However, genomewide array analyses are particularly susceptible to batch effects as the logistics of preparing DNA and processing thousands of arrays often involves multiple laboratories and technicians, or changes over calendar time to the reagents and laboratory equipment. Failure to adjust for batch effects can lead to incorrect inference and requires inefficient post hoc quality control procedures to exclude regions that are associated with batch. Our work extends previous model-based approaches for copy number estimation by explicitly modeling batch and using shrinkage to improve locus-specific estimates of copy number uncertainty. Key features of this approach include the use of biallelic genotype calls from experimental data to estimate batch-specific and locus-specific parameters of background and signal without the requirement of training data. We illustrate these ideas using a study of bipolar disease and a study of chromosome 21 trisomy. The former has batch effects that dominate much of the observed variation in the quantile-normalized intensities, while the latter illustrates the robustness of our approach to a data set in which approximately 27% of the samples have altered copy number. Locus-specific estimates of copy number can be plotted on the copy number scale to investigate mosaicism and guide the choice of appropriate downstream approaches for smoothing the copy number as a function of physical position. The software is open source and implemented in the R

  4. Association between TLR7 copy number variations and hepatitis B virus infection outcome in Chinese

    Science.gov (United States)

    Li, Fang; Li, Xu; Zou, Gui-Zhou; Gao, Yu-Feng; Ye, Jun

    2017-01-01

    AIM To explore whether copy number variations (CNVs) of toll-like receptor 7 (TLR7) are associated with susceptibility to chronic hepatitis B virus (HBV) infection. METHODS This study included 623 patients (495 males and 128 females) with chronic hepatitis B virus infection (CHB) and 300 patients (135 females and 165 males) with acute hepatitis B virus infection (AHB) as controls. All CHB patients were further categorized according to disease progression after HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). Copy numbers of the TLR7 gene were measured using the AccuCopy method. χ2 tests were used to evaluate the association between TLR7 CNVs and infection type. P values, odds ratios, and 95% confidence intervals (CIs) were used to estimate the effects of risk. RESULTS Among male patients, there were significant differences between the AHB group and CHB group in the distribution of TLR7 CNVs. Low copy number of TLR7 was significantly associated with chronic HBV infection (OR = 0.329, 95%CI: 0.229-0.473, P < 0.001). Difference in TLR7 copy number was also found between AHB and CHB female patients, with low copy number again associated with an increased risk of chronic HBV infection (OR = 0.292, 95%CI: 0.173-0.492, P < 0.001). However, there were no significant differences in TLR7 copy number among the three types of chronic HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). In addition, there was no association between TLR7 copy number and titer of the HBV e antigen. CONCLUSION Low TLR7 copy number is a risk factor for chronic HBV infection but is not associated with later stages of disease progression.

  5. Functional analysis of the three HMA4 copies of the metal hyperaccumulator Arabidopsis halleri.

    Science.gov (United States)

    Nouet, Cécile; Charlier, Jean-Benoit; Carnol, Monique; Bosman, Bernard; Farnir, Frédéric; Motte, Patrick; Hanikenne, Marc

    2015-09-01

    In Arabidopsis halleri, the HMA4 gene has an essential function in Zn/Cd hypertolerance and hyperaccumulation by mediating root-to-shoot translocation of metals. Constitutive high expression of AhHMA4 results from a tandem triplication and cis-activation of the promoter of all three copies. The three AhHMA4 copies possess divergent promoter sequences, but highly conserved coding sequences, and display identical expression profiles in the root and shoot vascular system. Here, an AhHMA4::GFP fusion was expressed under the control of each of the three A. halleri HMA4 promoters in a hma2hma4 double mutant of A. thaliana to individually examine the function of each AhHMA4 copy. The protein showed non-polar localization at the plasma membrane of the root pericycle cells of both A. thaliana and A. halleri. The expression of each AhHMA4::GFP copy complemented the severe Zn-deficiency phenotype of the hma2hma4 mutant by restoring root-to-shoot translocation of Zn. However, each copy had a different impact on metal homeostasis in the A. thaliana genetic background: AhHMA4 copies 2 and 3 were more highly expressed and provided higher Zn tolerance in roots and accumulation in shoots than copy 1, and AhHMA4 copy 3 also increased Cd tolerance in roots. These data suggest a certain extent of functional differentiation among the three A. halleri HMA4 copies, stemming from differences in expression levels rather than in expression profile. HMA4 is a key node of the Zn homeostasis network and small changes in expression level can have a major impact on Zn allocation to root or shoot tissues. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  6. A genome wide association study between copy number variation (CNV) and human height in Chinese population

    Institute of Scientific and Technical Information of China (English)

    Xi Li; Liang Zhang; Han Yan; Feng Pan; Zhixin Zhang; Yumei Peng; Qi Zhou; Lina He; Xuezhen Zhu; Jing Cheng; Lishu Zhang; Lijun Tan; Yaozhong Liu; Qing Tian; Hongwen Deng; Xiaogang Liu; Shufeng Lei; Tielin Yang; Xiangding Chen; Fang Zhang; Yue Fang; Yan Guo

    2010-01-01

    Copy number variation (CNV) is a type of genetic variation which may have important roles in phenotypic variability and disease susceptibility. To hunt for genetic variants underlying human height variation, we performed a genome wide CNV association study for human height in 618 Chinese unrelated subjects using Affymetrix 500K array set. After adjusting for age and sex, we found that four CNVs at 6p21.3, 8p23.3-23.2, 9p23 and 16p12.1 were associated with human height (with borderline significant p value: 0.013, 0.011, 0.024, 0.049; respectively). However, after multiple tests correction, none of them was associated with human height. We observed that the gain of copy number (more than 2 copies) at 8p23.3-23.2 was associated with lower height (normal copy number vs. gain of copy number; 161.2 cm vs. 153.7 cm, p = 0.011), which accounted for 0.9% of height variation. Loss of copy number (less than 2 copies) at 6p21.3 was associated with 0.8% lower height (loss of copy number vs. normal copy number: 154.5 cm vs. 161.1 cm, p = 0.013). Since no important genes influencing height located in CNVs at loci of 8p23.3-23.2 and 6p21.3, the two CNVs may cause the structural rearrangements of neighbored important candidate genes, thus regulates the variation of height. Our results expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.

  7. Low AMY1 Gene Copy Number Is Associated with Increased Body Mass Index in Prepubertal Boys

    Science.gov (United States)

    Verginelli, Fabio; De Lellis, Laura; Capelli, Cristian; Verzilli, Delfina; Chiarelli, Francesco; Mohn, Angelika; Cama, Alessandro

    2016-01-01

    Background Genome-wide association studies have identified more than 60 single nucleotide polymorphisms associated with Body Mass Index (BMI). Additional genetic variants, such as copy number variations (CNV), have also been investigated in relation to BMI. Recently, the highly polymorphic CNV in the salivary amylase (AMY1) gene, encoding an enzyme implicated in the first step of starch digestion, has been associated with obesity in adults and children. We assessed the potential association between AMY1 copy number and a wide range of BMI in a population of Italian school-children. Methods 744 children (354 boys, 390 girls, mean age (±SD): 8.4±1.4years) underwent anthropometric assessments (height, weight) and collection of saliva samples for DNA extraction. AMY1 copies were evaluated by quantitative PCR. Results A significant increase of BMI z-score by decreasing AMY1 copy number was observed in boys (β: -0.117, p = 0.033), but not in girls. Similarly, waist circumference (β: -0.155, p = 0.003, adjusted for age) was negatively influenced by AMY1 copy number in boys. Boys with 8 or more AMY1 copy numbers presented a significant lower BMI z-score (p = 0.04) and waist circumference (p = 0.01) when compared to boys with less than 8 copy numbers. Conclusions In this pediatric-only, population-based study, a lower AMY1 copy number emerged to be associated with increased BMI in boys. These data confirm previous findings from adult studies and support a potential role of a higher copy number of the salivary AMY1 gene in protecting from excess weight gain. PMID:27149670

  8. Understanding the impact of 1q21.1 copy number variant

    Directory of Open Access Journals (Sweden)

    Harvard Chansonette

    2011-08-01

    Full Text Available Abstract Background 1q21.1 Copy Number Variant (CNV is associated with a highly variable phenotype ranging from congenital anomalies, learning deficits/intellectual disability (ID, to a normal phenotype. Hence, the clinical significance of this CNV can be difficult to evaluate. Here we described the consequences of the 1q21.1 CNV on genome-wide gene expression and function of selected candidate genes within 1q21.1 using cell lines from clinically well described subjects. Methods and Results Eight subjects from 3 families were included in the study: six with a 1q21.1 deletion and two with a 1q21.1 duplication. High resolution Affymetrix 2.7M array was used to refine the 1q21.1 CNV breakpoints and exclude the presence of secondary CNVs of pathogenic relevance. Whole genome expression profiling, studied in lymphoblast cell lines (LBCs from 5 subjects, showed enrichment of genes from 1q21.1 in the top 100 genes ranked based on correlation of expression with 1q21.1 copy number. The function of two top genes from 1q21.1, CHD1L/ALC1 and PRKAB2, was studied in detail in LBCs from a deletion and a duplication carrier. CHD1L/ALC1 is an enzyme with a role in chromatin modification and DNA damage response while PRKAB2 is a member of the AMP kinase complex, which senses and maintains systemic and cellular energy balance. The protein levels for CHD1L/ALC1 and PRKAB2 were changed in concordance with their copy number in both LBCs. A defect in chromatin remodeling was documented based on impaired decatenation (chromatid untangling checkpoint (DCC in both LBCs. This defect, reproduced by CHD1L/ALC1 siRNA, identifies a new role of CHD1L/ALC1 in DCC. Both LBCs also showed elevated levels of micronuclei following treatment with a Topoisomerase II inhibitor suggesting increased DNA breaks. AMP kinase function, specifically in the deletion containing LBCs, was attenuated. Conclusion Our studies are unique as they show for the first time that the 1q21.1 CNV not only

  9. Distillation of GHZ State from Multiple Copies of Arbitrary W-Class State

    Institute of Scientific and Technical Information of China (English)

    WU Qin; WU Chun-Wang; FANG Mao-Fa; CHEN Ping-Xing; LI Shao-Xin; LI Cheng-Zu; LI Ying; HU Yao-Hua

    2008-01-01

    W. Dür et al. have shown that it is impossible to obtain a GHZ state from one copy of arbitrary W-class (2000) 062314]. In our paper, the more general case is carefully investigated. We first show that, with a supply of two copies of arbitrary W-class state, we can always construct an explicit procedure to distill a GHZ state with a nonzero probability. Then based on this result, a simple procedure for distilling GHZ state from n copies of arbitrary W-class state is presented. Finaily, we briefly discuss the applications.

  10. Do female Siamese fighting fish copy the mate choice of others?

    DEFF Research Database (Denmark)

    Durey, Maëlle; Dabelsteen, Torben; Matessi, Giuliano

    Choosing the right partner may be a difficult task. Therefore, observing the choice of another individual in order to copy its decision is an option which may have lower costs and present additional benefits. Mate choice copying has been documented in several species, including fish such as sailfin...... mollies and guppies. Female Siamese fighting fish (Betta splendens) have been reported to eavesdrop and exploit social information in aggressive interactions and may therefore also use information contained in other’s mate choice. In this experiment, we aimed at establishing if female fighting fish copy...

  11. A Survey of Partition-Based Techniques for Copy-Move Forgery Detection

    Directory of Open Access Journals (Sweden)

    Wandji Nanda Nathalie Diane

    2014-01-01

    Full Text Available A copy-move forged image results from a specific type of image tampering procedure carried out by copying a part of an image and pasting it on one or more parts of the same image generally to maliciously hide unwanted objects/regions or clone an object. Therefore, detecting such forgeries mainly consists in devising ways of exposing identical or relatively similar areas in images. This survey attempts to cover existing partition-based copy-move forgery detection techniques.

  12. Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Burgess Juliana

    2005-12-01

    Full Text Available Abstract Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2 is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF, and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.

  13. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  14. On-chip single-copy real-time reverse-transcription PCR in isolated picoliter droplets

    Energy Technology Data Exchange (ETDEWEB)

    Beer, N R; Wheeler, E; Lee-Houghton, L; Watkins, N; Nasarabadi, S; Hebert, N; Leung, P; Arnold, D; Bailey, C; Colston, B

    2007-12-19

    The first lab-on-chip system for picoliter droplet generation and RNA isolation, followed by reverse transcription, and PCR amplification with real-time fluorescence detection in the trapped droplets has been developed. The system utilized a shearing T-junction in a fused silica device to generate a stream of monodisperse picoliter-scale droplets that were isolated from the microfluidic channel walls and each other by the oil phase carrier. An off-chip valving system stopped the droplets on-chip, allowing thermal cycling for reverse transcription and subsequent PCR amplification without droplet motion. This combination of the established real-time reverse transcription-PCR assay with digital microfluidics is ideal for isolating single-copy RNA and virions from a complex environment, and will be useful in viral discovery and gene-profiling applications.

  15. DUF1220-domain copy number implicated in human brain-size pathology and evolution

    National Research Council Canada - National Science Library

    Dumas, Laura J; O'Bleness, Majesta S; Davis, Jonathan M; Dickens, C Michael; Anderson, Nathan; Keeney, J G; Jackson, Jay; Sikela, Megan; Raznahan, Armin; Giedd, Jay; Rapoport, Judith; Nagamani, Sandesh S C; Erez, Ayelet; Brunetti-Pierri, Nicola; Sugalski, Rachel; Lupski, James R; Fingerlin, Tasha; Cheung, Sau Wai; Sikela, James M

    2012-01-01

    ... have been associated with microcephaly and macrocephaly, respectively. Given these findings and the high correlation between DUF1220 copy number and brain size across primate lineages (R(2) = 0.98; p = 1.8 × 10(-6...

  16. The relationship between mitochondrial DNA copy number and stallion sperm function.

    Science.gov (United States)

    Darr, Christa R; Moraes, Luis E; Connon, Richard E; Love, Charles C; Teague, Sheila; Varner, Dickson D; Meyers, Stuart A

    2017-05-01

    Mitochondrial DNA (mtDNA) copy number has been utilized as a measure of sperm quality in several species including mice, dogs, and humans, and has been suggested as a potential biomarker of fertility in stallion sperm. The results of the present study extend this recent discovery using sperm samples from American Quarter Horse stallions of varying age. By determining copy number of three mitochondrial genes, cytochrome b (CYTB), NADH dehydrogenase 1 (ND1) and NADH dehydrogenase 4 (ND4), instead of a single gene, we demonstrate an improved understanding of mtDNA fate in stallion sperm mitochondria following spermatogenesis. Sperm samples from 37 stallions ranging from 3 to 24 years old were collected at four breeding ranches in north and central Texas during the 2015 breeding season. Samples were analyzed for sperm motion characteristics, nuclear DNA denaturability and mtDNA copy number. Mitochondrial DNA content in individual sperm was determined by real-time qPCR and normalized with a single copy nuclear gene, Beta actin. Exploratory correlation analysis revealed that total motility was negatively correlated with CYTB copy number and sperm chromatin structure. Stallion age did not have a significant effect on copy number for any of the genes. Copy number differences existed between the three genes with CYTB having the greatest number of copies (20.6 ± 1.2 copies, range: 6.0 to 41.1) followed by ND4 (15.5 ± 0.8 copies, range: 6.7 to 27.8) and finally ND1 (12.0 ± 1.0 copies, range: 0.4 to 26.6) (P copy number across mitochondrial genes is likely to be a result of mtDNA fragmentation and degradation since downregulation of sperm mtDNA occurs during spermatogenesis and may be important for normal sperm function. Beta regression analysis suggested that for every unit increase in mtDNA copy number of CYTB, there was a 4% decrease in the odds of sperm movement (P = 0.001). Influential analysis suggested that results are robust and not highly influenced by

  17. 76 FR 60810 - Agency Information Collection Activities: Notice of Intent To Renew Collection, Copies of Crop...

    Science.gov (United States)

    2011-09-30

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection, Copies of Crop and Market Information Reports AGENCY: Commodity Futures Trading Commission. ACTION: Notice. SUMMARY:...

  18. Entanglement Preserving in Quantum Copying of Three-Qubit Entangled State

    Institute of Scientific and Technical Information of China (English)

    TONG Zhao-Yang; KUANG Le-Man

    2002-01-01

    We study the degree to which quantum entanglement survives when a three-qubit entangled state iscopied by using local and non-local processes, respectively, and investigate iterating quantum copyingfor the three-qubitsystem. There may exist inter-three-qubit entanglement and inter-two-qubit entanglement for the three-qubit system.We show that both local and non-local copying processes degrade quantum entanglement in the three-particle systemdue to a residual correlation between the copied output and the copying machine. We also show that the inter-two-qubitentanglement is preserved better than the inter-three-qubit entanglement in the local cloning process. We find thatnon-local cloning is much more efficient than the local copying for broadcasting entanglement, and output state vianon-local cloning exhibits the fidelity better than local cloning.

  19. Elimination of Parallel Copies using Code Motion on Data Dependence Graphs

    DEFF Research Database (Denmark)

    Brandner, Florian; Colombet, Quentin

    2013-01-01

    Register allocation regained much interest in recent years due to the development of decoupled strategies that split the problem into separate phases: spilling, register assignment, and copy elimination. Traditional approaches to copy elimination during register allocation are based on interference...... graphs and register coalescing. Variables are represented as nodes in a graph, which are coalesced, if they can be assigned the same register. However, decoupled approaches strive to avoid interference graphs and thus often resort to local recoloring. A common assumption of existing coalescing......, while at the same time a valid register assignment is preserved. Our results show that even after traditional register allocation with coalescing our technique is able to eliminate an additional 3% (up to 9%) of the remaining copies and reduce the weighted costs of register copies by up to 25...

  20. 37 CFR 202.19 - Deposit of published copies or phonorecords for the Library of Congress.

    Science.gov (United States)

    2010-07-01

    .... (3) The terms architectural works, copies, collective work, device, fixed, literary work, machine... an anatomical model. (2) Greeting cards, picture postcards, and stationery. (3) Lectures, sermons... authors. (4) Literary, dramatic, and musical works published only as embodied in phonorecords....

  1. Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs.

    Science.gov (United States)

    Mei, H; Sun, S; Bai, Y; Chen, Y; Chai, R; Li, H

    2015-04-02

    Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors.

  2. Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs

    Science.gov (United States)

    Mei, H; Sun, S; Bai, Y; Chen, Y; Chai, R; Li, H

    2015-01-01

    Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors. PMID:25837486

  3. CNVkit: Genome-Wide Copy Number Detection and Visualization from Targeted DNA Sequencing.

    Directory of Open Access Journals (Sweden)

    Eric Talevich

    2016-04-01

    Full Text Available Germline copy number variants (CNVs and somatic copy number alterations (SCNAs are of significant importance in syndromic conditions and cancer. Massively parallel sequencing is increasingly used to infer copy number information from variations in the read depth in sequencing data. However, this approach has limitations in the case of targeted re-sequencing, which leaves gaps in coverage between the regions chosen for enrichment and introduces biases related to the efficiency of target capture and library preparation. We present a method for copy number detection, implemented in the software package CNVkit, that uses both the targeted reads and the nonspecifically captured off-target reads to infer copy number evenly across the genome. This combination achieves both exon-level resolution in targeted regions and sufficient resolution in the larger intronic and intergenic regions to identify copy number changes. In particular, we successfully inferred copy number at equivalent to 100-kilobase resolution genome-wide from a platform targeting as few as 293 genes. After normalizing read counts to a pooled reference, we evaluated and corrected for three sources of bias that explain most of the extraneous variability in the sequencing read depth: GC content, target footprint size and spacing, and repetitive sequences. We compared the performance of CNVkit to copy number changes identified by array comparative genomic hybridization. We packaged the components of CNVkit so that it is straightforward to use and provides visualizations, detailed reporting of significant features, and export options for integration into existing analysis pipelines. CNVkit is freely available from https://github.com/etal/cnvkit.

  4. Performance of Molecular Inversion Probes (MIP) in Allele CopyNumber Determination

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuker; Moorhead, Martin; Karlin-Neumann, George; Wang,Nicolas J.; Ireland, James; Lin, Steven; Chen, Chunnuan; Heiser, LauraM.; Chin, Koei; Esserman, Laura; Gray, Joe W.; Spellman, Paul T.; Faham,Malek

    2007-05-14

    We have developed a new protocol for using MolecularInversion Probes (MIP) to accurately and specifically measure allele copynumber (ACN). The new protocol provides for significant improvementsincluding the reduction of input DNA (from 2?g) by more than 25 fold (to75ng total genomic DNA), higher overall precision resulting in one orderof magnitude lower false positive rate, and greater dynamic range withaccurate absolute copy number up to 60 copies.

  5. Do female fruit flies (Drosophila serrata) copy the mate choice of others?

    Science.gov (United States)

    Auld, Heather L; Punzalan, David; Godin, Jean-Guy J; Rundle, Howard D

    2009-09-01

    Female mate-choice copying is a social learning phenomenon whereby a female's observation of a successful sexual interaction between a male and another female increases her likelihood of subsequently preferring that male. Although mate-choice copying has been documented in several vertebrate species, to our knowledge it has not yet been investigated in insects. Here, we investigated whether female mate-choice copying occurs in the fruit fly Drosophila serrata, a model system for the study of mate preferences and the sexual selection they generate. We used two complementary experiments in which focal females were given a choice between two males that differed in either their apparent (as determined visually by the focal female) or actual recent mating success. Mate-choice copying was evaluated by testing whether focal females mated more frequently with the 'preferred' male as opposed to the other male. In both experiments, however, we found no evidence for mate-choice copying. We discuss possible reasons for the apparent absence of mate-choice copying in this species.

  6. Telomere length is correlated with mitochondrial DNA copy number in intestinal, but not diffuse, gastric cancer.

    Science.gov (United States)

    Jung, Soo-Jung; Cho, Ji-Hyoung; Park, Won-Jin; Heo, Yu-Ran; Lee, Jae-Ho

    2017-07-01

    A positive correlation between telomere length and mitochondrial DNA (mtDNA) copy number has previously been observed in healthy individuals, and in patients with psychiatric disorders. In the present study, telomere length and mtDNA copy number were evaluated in gastric cancer (GC) tissue samples. DNA was extracted from 109 GC samples (including 82 intestinal, and 27 diffuse cases), and the telomere length and mtDNA copy number were analyzed using a quantitative-polymerase chain reaction assay. The relative telomere length and mtDNA copy number in tumor tissue, as compared with in normal tissue, (mean ± standard deviation) in all GC samples were 11.48±1.14 and 14.86±1.35, respectively. Telomere length and mtDNA copy number were not identified as exhibiting clinical or prognostic value for GC. However, positive correlations between telomere length and mitochondrial DNA copy number were identified in GC (r=0.408, P<0.001) and in the adjacent normal mucosa (r=0.363; P<0.001). When stratified by Lauren classification, the correlation was identified in intestinal type GC samples (r=0.461; P<0.001), but not in diffuse type GC samples (r=0.225; P=0.260). This result indicated that loss of the correlation of telomeres and mitochondrial function may induce the initiation or progression of GC pathogenesis.

  7. TOP1 gene copy numbers are increased in cancers of the bile duct and pancreas

    DEFF Research Database (Denmark)

    Grunnet, Mie; Calatayud, Dan; Schultz, Nicolai Aa.

    2015-01-01

    ) poison. Top1 protein, TOP1 gene copy number and mRNA expression, respectively, have been proposed as predictive biomarkers of response to irinotecan in other cancers. Here we investigate the occurrence of TOP1 gene aberrations in cancers of the bile ducts and pancreas. Material and methods. TOP1...... and centromere 20 (CEN-20) numbers were investigated by fluorescence in situ hybridization analyses in tumor tissue from 226 patients. The frequencies of aberration in the TOP1 gene copy number, the CEN-20 copy number and the TOP1/CEN-20 ratio were analyzed. As TOP1 is located on chromosome 20, the CEN-20 probe...... was included to distinguish between chromosomal and gene amplifications. Results. In PC, 29.8% had an increased TOP1 copy number (≥3.5n gene copies per cell) and 10.8% had a TOP1/CEN-20 ratio >1.5. In bile duct cancer, 12.8 % had an increased TOP1 copy number and 6.4% had a TOP1/CEN-20 ratio >1.5. Neither...

  8. CCL3L1 copy number, HIV load, and immune reconstitution in sub-Saharan Africans

    Science.gov (United States)

    2013-01-01

    Background The role of copy number variation of the CCL3L1 gene, encoding MIP1α, in contributing to the host variation in susceptibility and response to HIV infection is controversial. Here we analyse a sub-Saharan African cohort from Tanzania and Ethiopia, two countries with a high prevalence of HIV-1 and a high co-morbidity of HIV with tuberculosis. Methods We use a form of quantitative PCR called the paralogue ratio test to determine CCL3L1 gene copy number in 1134 individuals and validate our copy number typing using array comparative genomic hybridisation and fiber-FISH. Results We find no significant association of CCL3L1 gene copy number with HIV load in antiretroviral-naïve patients prior to initiation of combination highly active anti-retroviral therapy. However, we find a significant association of low CCL3L1 gene copy number with improved immune reconstitution following initiation of highly active anti-retroviral therapy (p = 0.012), replicating a previous study. Conclusions Our work supports a role for CCL3L1 copy number in immune reconstitution following antiretroviral therapy in HIV, and suggests that the MIP1α -CCR5 axis might be targeted to aid immune reconstitution. PMID:24219137

  9. Simple screening method for copy number variations associated with physical features.

    Science.gov (United States)

    Ueki, Misuzu; Takeshita, Haruo; Fujihara, Junko; Kimura-Kataoka, Kaori; Iida, Reiko; Yasuda, Toshihiro

    2017-03-01

    Recent studies of copy number variations (CNVs) associated with physical features, such as body mass index, body height or bone length, have suggested that such CNVs could serve as markers in forensic cases involving unidentified individuals. However, the process of cataloging CNVs has been slow because of the cumbersome nature and low reliability of the procedures involved. Here we describe a simple quantitative real-time PCR (Q-PCR) method for screening of medicolegally useful CNVs, which does not require reference DNA with known copy number. The first step is to prepare a chimeric plasmid vector including one copy each of the single-copy gene-specific sequence as the internal standard, and the target CNV-specific sequence. To assess the validity of this new method, we analyzed CNVs in the LTBP1 and ETV6 gene regions, both of which are candidate CNVs associated with body height. The PCR efficiencies for the single-copy (reference) gene and the target CNV were similar, indicating that quantitation was reliable. Furthermore, simulated analysis of the LTBP1 CNV using mock samples prepared by mixing vectors in varying proportions showed that this analytical method allowed correct determination of the LTBP1 copy number. These results demonstrated that our simple method has considerable potential for screening of trait-related CNVs that would be useful for forensic casework. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Mitochondrial DNA copy number variation as a potential predictor of renal cell carcinoma.

    Science.gov (United States)

    Elsayed, Eman T; Hashad, Mohamed M; Elgohary, Iman E

    2017-07-24

    Peripheral blood mitochondrial DNA (mtDNA) copy number alteration has been suggested as a risk factor for several types of cancer. The aim of the present study was to assess the role of peripheral blood mtDNA copy number variation as a noninvasive biomarker in the prediction and early detection of renal cell carcinoma (RCC) in a cohort of Egyptian patients. Quantitative real-time polymerase chain reaction (qPCR) was used to measure peripheral blood mtDNA copy numbers in 57 patients with newly diagnosed, early-stage localized RCC and 60 age- and sex-matched healthy individuals as a control group. Median mtDNA copy number was significantly higher in RCC cases than in controls (166 vs. 91, pcopy number was associated with an 18-fold increased risk of RCC (95% confidence interval: 5.065-63.9). On receiver operating characteristic curve analysis, it was found that mtDNA could distinguish between RCC patients and healthy controls, with 86% sensitivity, 80% specificity, 80.3% positive predictive value and 85.7% negative predictive value at a cutoff value of 108.5. Our results showed that increased peripheral blood mtDNA copy number was associated with increased risk of RCC. Therefore, RCC might be considered as part of a range of potential tumors in cases with elevated blood mtDNA copy number.

  11. Toward accurate high-throughput SNP genotyping in the presence of inherited copy number variation

    Directory of Open Access Journals (Sweden)

    Aldred Micheala A

    2007-07-01

    Full Text Available Abstract Background The recent discovery of widespread copy number variation in humans has forced a shift away from the assumption of two copies per locus per cell throughout the autosomal genome. In particular, a SNP site can no longer always be accurately assigned one of three genotypes in an individual. In the presence of copy number variability, the individual may theoretically harbor any number of copies of each of the two SNP alleles. Results To address this issue, we have developed a method to infer a "generalized genotype" from raw SNP microarray data. Here we apply our approach to data from 48 individuals and uncover thousands of aberrant SNPs, most in regions that were previously unreported as copy number variants. We show that our allele-specific copy numbers follow Mendelian inheritance patterns that would be obscured in the absence of SNP allele information. The interplay between duplication and point mutation in our data shed light on the relative frequencies of these events in human history, showing that at least some of the duplication events were recurrent. Conclusion This new multi-allelic view of SNPs has a complicated role in disease association studies, and further work will be necessary in order to accurately assess its importance. Software to perform generalized genotyping from SNP array data is freely available online 1.

  12. Copy number analysis of ductal carcinoma in situ with and without recurrence.

    Science.gov (United States)

    Gorringe, Kylie L; Hunter, Sally M; Pang, Jia-Min; Opeskin, Ken; Hill, Prue; Rowley, Simone M; Choong, David Y H; Thompson, Ella R; Dobrovic, Alexander; Fox, Stephen B; Mann, G Bruce; Campbell, Ian G

    2015-09-01

    Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer and a frequent mammographic finding requiring treatment. Up to 25% of DCIS can recur and half of recurrences are invasive, but there are no reliable biomarkers for recurrence. We hypothesised that copy number aberrations could predict likelihood of recurrence. We analysed a cohort of pure DCIS cases treated only with wide local excision for genome-wide copy number and loss of heterozygosity using Affymetrix OncoScan MIP arrays. Cases included those without recurrence within 7 years (n = 25) and with recurrence between 1 and 5 years after diagnosis (n = 15). Pure DCIS were broadly similar in copy number changes compared with invasive breast cancer, with the consistent exception of a greater frequency of ERBB2 amplification in DCIS. There were no significant differences in age or ER status between the cases with a recurrence vs those without. Overall, the DCIS cases with recurrence had more copy number events than the DCIS without recurrence. The increased copy number appeared non-random with several genomic regions showing an increase in frequency in recurrent cases, including 20 q gain, ERBB2 amplification and 15q loss. Copy number changes may provide prognostic information for DCIS recurrence, but validation in additional cohorts is required.

  13. Peer—to—Peer Computing for secure High Performance Data Copying

    Institute of Scientific and Technical Information of China (English)

    AndrewHanushevsky; ArtemTrunov; 等

    2001-01-01

    The BaBar Copy Program(bbcp) is an excellent representative of peer-to-peer(P2P) computing.It is also a pioneering application of its type in the p2p arena.Built upon the foundation of its predecessor,Secure Fast Copy(sfctp),bbcp incorporates significant improvements performance and usability,As with sfcp,bbcp usec ssh for authentication;providing an elegant and simple working model-if you can ssh to a location, you can copy files to or from that location.To fully support this notion,bbcp transparently supports 3rd party copy operations.The program also incorporates several mechanism to deal with firewall security;the bane of P2P computing,To achieve high performance in a wide area network,bbcp allows a user to independently specily,the number of parallel network streams,tcp window size,and the file I/O blocking factor.Using these parameters data is pipelined from source to target to provide a uniform traffic pattern that maximizes router efficiency.For improved recoveralbiltiy,bbcp also keeps track of copy operations so that an operation can be restarted from the point of failure at a later time;minimizing the amount of network traffic in the event of a copy failure,Here,we preset the bbcp architecture,it's various features,and the reasons for their inclusion.

  14. Spelling errors in text copying by children with dyslexia and ADHD symptoms.

    Science.gov (United States)

    Re, Anna Maria; Cornoldi, Cesare

    2015-01-01

    Spelling errors are usually studied in dictations, but teachers report that children with school difficulties often make spelling mistakes when they copy a text too. The present study examines the performance on a text copying task and a text dictation task of two groups of children known for their difficulties in spelling, that is, 22 with symptoms of ADHD and 13 with dyslexia, comparing them with matched controls to see whether children with spelling difficulties make more copying task errors than do controls, whether they make fewer mistakes when copying than when writing under dictation, and whether the pattern of errors remains the same or differs in copy and dictation tasks. Our results show that although children with spelling difficulties made fewer errors in the copying task than under dictation, they still made phonological errors and mistakes relating to accents and duplicates. The pattern of errors differed slightly between the children with dyslexia and those with ADHD, presumably as a consequence of their different underlying weaknesses-related mainly to phonology and orthographic representation in the case of dyslexia and to attentional control in the case of ADHD. © Hammill Institute on Disabilities 2013.

  15. Bucolic Complexes

    CERN Document Server

    Brešar, Bostjan; Chepoi, Victor; Gologranc, Tanja; Osajda, Damian

    2012-01-01

    In this article, we introduce and investigate bucolic complexes, a common generalization of systolic complexes and of CAT(0) cubical complexes. This class of complexes is closed under Cartesian products and amalgamations over some convex subcomplexes. We study various approaches to bucolic complexes: from graph-theoretic and topological viewpoints, as well as from the point of view of geometric group theory. Bucolic complexes can be defined as locally-finite simply connected prism complexes satisfying some local combinatorial conditions. We show that bucolic complexes are contractible, and satisfy some nonpositive-curvature-like properties. In particular, we prove a version of the Cartan-Hadamard theorem, the fixed point theorem for finite group actions, and establish some results on groups acting geometrically on such complexes. We also characterize the 1-skeletons (which we call bucolic graphs) and the 2-skeletons of bucolic complexes. In particular, we prove that bucolic graphs are precisely retracts of Ca...

  16. Fc-Gamma Receptor 3B Copy Number Variation Is Not a Risk Factor for Behçet’s Disease

    Directory of Open Access Journals (Sweden)

    Rachel Black

    2012-01-01

    Full Text Available Behçet’s disease (BD is an immune-mediated systemic vasculitis associated with HLAB51. Other gene associations are likely and may provide further insight into the pathogenesis of this disease. Fc-gamma receptors play an important role in regulating immune function. Copy number variation (CNV of the Fc-gamma receptor 3B (FCGR3B gene is associated with other inflammatory conditions and may also play a role in BD. The aim of this study was to determine whether CNV of the FCGR3B gene is associated with BD or its clinical features. FCGR3B copy number was determined for 187 Iranian patients and 178 ethnicity-matched controls using quantitative real-time PCR. The genotype frequencies were comparable in both BD patients and controls. The odds ratio for low copy number (2CN was 0.75 (=0.50. There was no association found between high or low CN of the FCGR3B gene and BD or its clinical features in this Iranian population. We are the first to report this finding which, when looked at in the context of other genetic studies, gives us further insight into the complex pathogenesis of BD.

  17. High-throughput single-cell analysis of low copy number β-galactosidase by a laboratory-built high-sensitivity flow cytometer.

    Science.gov (United States)

    Yang, Lingling; Huang, Tianxun; Zhu, Shaobin; Zhou, Yingxing; Jiang, Yunbin; Wang, Shuo; Chen, Yuqing; Wu, Lina; Yan, Xiaomei

    2013-10-15

    Single-cell analysis is vital in providing insights into the heterogeneity in molecular content and phenotypic characteristics of complex or clonal cell populations. As many essential proteins and most transcription factors are produced at a low copy number, analytical tools with superior sensitivity to enable the analysis of low abundance proteins in single cells are in high demand. β-galactosidase (β-gal) has been the standard cellular reporter for gene expression in both prokaryotic and eukaryotic cells. Here we report the development of a high-throughput method for the single-cell analysis of low copy number β-gal proteins using a laboratory-built high-sensitivity flow cytometer (HSFCM). Upon fluorescence staining with a fluorogenic substrate, quantitative measurements of the basal and near-basal expression of β-gal in single Escherichia coli BL21(DE3) cells were demonstrated. Statistical distribution can be determined quickly by analyzing thousands of individual cells in 1-2min, which reveals the heterogeneous expression pattern that is otherwise masked by the ensemble analysis. Combined with the quantitative fluorometric assay and the rapid bacterial enumeration by HSFCM, the β-gal expression distribution profile could be converted from arbitrary fluorescence units to protein copy numbers per cell. The sensitivity and speed of the HSFCM offers great capability in quantitative analysis of low abundance proteins in single cells, which would help gaining a deeper insight into the heterogeneity and fundamental biological processes in microbial populations.

  18. Statistical tools for transgene copy number estimation based on real-time PCR.

    Science.gov (United States)

    Yuan, Joshua S; Burris, Jason; Stewart, Nathan R; Mentewab, Ayalew; Stewart, C Neal

    2007-11-01

    As compared with traditional transgene copy number detection technologies such as Southern blot analysis, real-time PCR provides a fast, inexpensive and high-throughput alternative. However, the real-time PCR based transgene copy number estimation tends to be ambiguous and subjective stemming from the lack of proper statistical analysis and data quality control to render a reliable estimation of copy number with a prediction value. Despite the recent progresses in statistical analysis of real-time PCR, few publications have integrated these advancements in real-time PCR based transgene copy number determination. Three experimental designs and four data quality control integrated statistical models are presented. For the first method, external calibration curves are established for the transgene based on serially-diluted templates. The Ct number from a control transgenic event and putative transgenic event are compared to derive the transgene copy number or zygosity estimation. Simple linear regression and two group T-test procedures were combined to model the data from this design. For the second experimental design, standard curves were generated for both an internal reference gene and the transgene, and the copy number of transgene was compared with that of internal reference gene. Multiple regression models and ANOVA models can be employed to analyze the data and perform quality control for this approach. In the third experimental design, transgene copy number is compared with reference gene without a standard curve, but rather, is based directly on fluorescence data. Two different multiple regression models were proposed to analyze the data based on two different approaches of amplification efficiency integration. Our results highlight the importance of proper statistical treatment and quality control integration in real-time PCR-based transgene copy number determination. These statistical methods allow the real-time PCR-based transgene copy number estimation

  19. Quantification of Plasmid Copy Number with Single Colour Droplet Digital PCR.

    Science.gov (United States)

    Plotka, Magdalena; Wozniak, Mateusz; Kaczorowski, Tadeusz

    2017-01-01

    Bacteria can be considered as biological nanofactories that manufacture a cornucopia of bioproducts most notably recombinant proteins. As such, they must perfectly match with appropriate plasmid vectors to ensure successful overexpression of target genes. Among many parameters that correlate positively with protein productivity plasmid copy number plays pivotal role. Therefore, development of new and more accurate methods to assess this critical parameter will result in optimization of expression of plasmid-encoded genes. In this study, we present a simple and highly accurate method for quantifying plasmid copy number utilizing an EvaGreen single colour, droplet digital PCR. We demonstrate the effectiveness of this method by examining the copy number of the pBR322 vector within Escherichia coli DH5α cells. The obtained results were successfully validated by real-time PCR. However, we observed a strong dependency of the plasmid copy number on the method chosen for isolation of the total DNA. We found that application of silica-membrane-based columns for DNA purification or DNA isolation with use of bead-beating, a mechanical cell disruption lead to determination of an average of 20.5 or 7.3 plasmid copies per chromosome, respectively. We found that recovery of the chromosomal DNA from purification columns was less efficient than plasmid DNA (46.5 ± 1.9% and 87.4 ± 5.5%, respectively) which may lead to observed differences in plasmid copy number. Besides, the plasmid copy number variations dependent on DNA template isolation method, we found that droplet digital PCR is a very convenient method for measuring bacterial plasmid content. Careful determination of plasmid copy number is essential for better understanding and optimization of recombinant proteins production process. Droplet digital PCR is a very precise method that allows performing thousands of individual PCR reactions in a single tube. The ddPCR does not depend on running standard curves and is a

  20. Systematic Inference of Copy-Number Genotypes from Personal Genome Sequencing Data Reveals Extensive Olfactory Receptor Gene Content Diversity

    Science.gov (United States)

    Waszak, Sebastian M.; Hasin, Yehudit; Zichner, Thomas; Olender, Tsviya; Keydar, Ifat; Khen, Miriam; Stütz, Adrian M.; Schlattl, Andreas; Lancet, Doron; Korbel, Jan O.

    2010-01-01

    Copy-number variations (CNVs) are widespread in the human genome, but comprehensive assignments of integer locus copy-numbers (i.e., copy-number genotypes) that, for example, enable discrimination of homozygous from heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel computational approach with an underlying statistical framework that analyzes the depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate paired-end and breakpoint junction analysis based CNV-analysis approaches, to infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500 chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The assessed copy-number genotypes were highly concordant with our performed qPCR experiments (Pearson correlation coefficient 0.94), and with the published results of two microarray platforms (95–99% concordance). We further demonstrated the utility of CopySeq for analyzing gene regions enriched for segmental duplications by comprehensively inferring copy-number genotypes in the CNV-enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq revealed that OR loci display an extensive range of locus copy-numbers across individuals, with zero to two copies in some OR loci, and two to nine copies in others. Among genetic variants affecting OR loci we identified deleterious variants including CNVs and SNPs affecting ∼15% and ∼20% of the human OR gene repertoire, respectively, implying that genetic variants with a possible impact on smell perception are widespread. Finally, we found that for several OR loci the reference genome appears to represent a minor-frequency variant, implying a necessary revision of the OR repertoire for future functional studies. CopySeq can ascertain genomic structural variation in specific gene families as well as at a genome-wide scale, where it may enable the quantitative evaluation of CNVs in genome-wide association studies involving high

  1. The Influence of Copy Number of Targeted Extrachromosomal Genetic Elements on the Outcome of CRISPR-Cas Defense

    Directory of Open Access Journals (Sweden)

    Konstantin Severinov

    2016-08-01

    Full Text Available Prokaryotic type I CRISPR-Cas systems respond to the presence of mobile genetic elements such as plasmids and phages in two different ways. CRISPR interference efficiently destroys foreign DNA harbouring protospacers fully matching CRISPR RNA spacers. In contrast, even a single mismatch between a spacer and a protospacer can render CRISPR interference ineffective but causes primed adaptation - efficient and specific acquisition of additional spacers from foreign DNA into the CRISPR array of the host. It has been proposed that the interference and primed adaptation pathways are mediated by structurally different complexes formed by the effector Cascade complex on matching and mismatched protospacers. Here, we present experimental evidence and present a simple mathematical model that shows that when plasmid copy number maintenance/phage genome replication is taken into account, the two apparently different outcomes of the CRISPR-Cas response can be accounted for by just one kind of effector complex on both targets. The results underscore the importance of consideration of targeted genome biology when considering consequences of CRISPR-Cas systems action.

  2. Copy number variations of the ATP-binding cassette transporter ABCC6 gene and its pseudogenes

    Directory of Open Access Journals (Sweden)

    Kringen Marianne K

    2012-08-01

    Full Text Available Abstract Background The ATP-binding cassette transporter ABCC6 gene is located on chromosome 16 between its two pseudogenes (ABCC6P1 and ABCC6P2. Previously, we have shown that ABCC6P1 is transcribed and affects ABCC6 at the transcriptional level. In this study we aimed to determine copy number variations of ABCC6, ABCC6P1 and ABCC6P2 in different populations. Moreover, we sought to study the transcription pattern of ABCC6 and ABCC6 pseudogenes in 39 different human tissues. Findings Genomic DNA from healthy individuals from five populations, Chinese (n = 24, Middle East (n = 20, Mexicans (n = 24, Caucasians (n = 50 and Africans (n = 24, were examined for copy number variations of ABCC6 and its pseudogenes by pyrosequencing and quantitative PCR. Copy number variation of ABCC6 was very rare (2/142; 1.4%. However, one or three copies of ABCC6P1 were relatively common (3% and 8%, respectively. Only one person had a single copy of ABCC6P2 while none had three copies. In Chinese, deletions or duplications of ABCC6P1 were more frequent than in any other population (9/24; 37.5%. The transcription pattern of ABCC6P2 was highly similar to ABCC6 and ABCC6P1, with highest transcription in liver and kidney. Interestingly, the total transcription level of pseudogenes, ABCC6P1 + ABCC6P2, was higher than ABCC6 in most tissues, including liver and kidney. Conclusions Copy number variations of the ABCC6 pseudogenes are quite common, especially in populations of Chinese ancestry. The expression pattern of ABCC6P2 in 39 human tissues was highly similar to that of ABCC6 and ABCC6P1 suggesting similar regulatory mechanisms for ABCC6 and its pseudogenes.

  3. HaplotypeCN: copy number haplotype inference with Hidden Markov Model and localized haplotype clustering.

    Directory of Open Access Journals (Sweden)

    Yen-Jen Lin

    Full Text Available Copy number variation (CNV has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states.

  4. Modulation of Mitochondrial DNA Copy Number to Induce Hepatocytic Differentiation of Human Amniotic Epithelial Cells.

    Science.gov (United States)

    Vaghjiani, Vijesh; Cain, Jason E; Lee, William; Vaithilingam, Vijayaganapathy; Tuch, Bernard E; St John, Justin C

    2017-09-05

    Mitochondrial deoxyribonucleic acid (mtDNA) copy number is tightly regulated during pluripotency and differentiation. There is increased demand of cellular adenosine triphosphate (ATP) during differentiation for energy-intensive cell types such as hepatocytes and neurons to meet the cell's functional requirements. During hepatocyte differentiation, mtDNA copy number should be synchronously increased to generate sufficient ATP through oxidative phosphorylation. Unlike bone marrow mesenchymal cells, mtDNA copy number failed to increase by 28 days of differentiation of human amniotic epithelial cells (hAEC) into hepatocyte-like cells (HLC) despite their expression of some end-stage hepatic markers. This was due to higher levels of DNA methylation at exon 2 of POLGA, the mtDNA-specific replication factor. Treatment with a DNA demethylation agent, 5-azacytidine, resulted in increased mtDNA copy number, reduced DNA methylation at exon 2 of POLGA, and reduced hepatic gene expression. Depletion of mtDNA followed by subsequent differentiation did not increase mtDNA copy number, but reduced DNA methylation at exon 2 of POLGA and increased expression of hepatic and pluripotency genes. We encapsulated hAEC in barium alginate microcapsules and subsequently differentiated them into HLC. Encapsulation resulted in no net increase of mtDNA copy number but a significant reduction in DNA methylation of POLGA. RNAseq analysis showed that differentiated HLC express hepatocyte-specific genes but also increased expression of inflammatory interferon genes. Differentiation in encapsulated cells showed suppression of inflammatory genes as well as increased expression of genes associated with hepatocyte function pathways and networks. This study demonstrates that an increase in classical hepatic gene expression can be achieved in HLC through encapsulation, although they fail to effectively regulate mtDNA copy number.

  5. Single-Copy Genes as Molecular Markers for Phylogenomic Studies in Seed Plants.

    Science.gov (United States)

    Li, Zhen; De La Torre, Amanda R; Sterck, Lieven; Cánovas, Francisco M; Avila, Concepción; Merino, Irene; Cabezas, José Antonio; Cervera, María Teresa; Ingvarsson, Pär K; Van de Peer, Yves

    2017-05-01

    Phylogenetic relationships among seed plant taxa, especially within the gymnosperms, remain contested. In contrast to angiosperms, for which several genomic, transcriptomic and phylogenetic resources are available, there are few, if any, molecular markers that allow broad comparisons among gymnosperm species. With few gymnosperm genomes available, recently obtained transcriptomes in gymnosperms are a great addition to identifying single-copy gene families as molecular markers for phylogenomic analysis in seed plants. Taking advantage of an increasing number of available genomes and transcriptomes, we identified single-copy genes in a broad collection of seed plants and used these to infer phylogenetic relationships between major seed plant taxa. This study aims at extending the current phylogenetic toolkit for seed plants, assessing its ability for resolving seed plant phylogeny, and discussing potential factors affecting phylogenetic reconstruction. In total, we identified 3,072 single-copy genes in 31 gymnosperms and 2,156 single-copy genes in 34 angiosperms. All studied seed plants shared 1,469 single-copy genes, which are generally involved in functions like DNA metabolism, cell cycle, and photosynthesis. A selected set of 106 single-copy genes provided good resolution for the seed plant phylogeny except for gnetophytes. Although some of our analyses support a sister relationship between gnetophytes and other gymnosperms, phylogenetic trees from concatenated alignments without 3rd codon positions and amino acid alignments under the CAT + GTR model, support gnetophytes as a sister group to Pinaceae. Our phylogenomic analyses demonstrate that, in general, single-copy genes can uncover both recent and deep divergences of seed plant phylogeny. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. A prospective study of mitochondrial DNA copy number and the risk of prostate cancer.

    Science.gov (United States)

    Moore, Amy; Lan, Qing; Hofmann, Jonathan N; Liu, Chin-San; Cheng, Wen-Ling; Lin, Ta-Tsung; Berndt, Sonja I

    2017-06-01

    Evidence suggests that mitochondrial DNA (mtDNA) copy number increases in response to DNA damage. Increased mtDNA copy number has been observed in prostate cancer (PCa) cells, suggesting a role in PCa development, but this association has not yet been investigated prospectively. We conducted a nested case-control study (793 cases and 790 controls) of men randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) to evaluate the association between pre-diagnosis mtDNA copy number, measured in peripheral blood leukocytes, and the risk of PCa. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) and polytomous logistic regression to analyze differences in associations by non-aggressive (Stage I/II AND Gleason grade copy number was not significantly associated with PCa risk overall (OR 1.23, 95% CI 0.97-1.55, p = 0.089), increasing mtDNA copy number was associated with an increased risk of non-aggressive PCa (OR 1.29, 95% CI 1.01-1.65, p = 0.044) compared to controls. No association was observed with aggressive PCa (OR 1.02, 95% CI 0.64-1.63, p = 0.933). Higher mtDNA copy number was also associated with increased PSA levels among controls (p = 0.014). These results suggest that alterations in mtDNA copy number may reflect disruption of the normal prostate glandular architecture seen in early-stage disease, as opposed to reflecting the large number of tumor cells seen with advanced PCa.

  7. HaplotypeCN: Copy Number Haplotype Inference with Hidden Markov Model and Localized Haplotype Clustering

    Science.gov (United States)

    Lin, Yen-Jen; Chen, Yu-Tin; Hsu, Shu-Ni; Peng, Chien-Hua; Tang, Chuan-Yi; Yen, Tzu-Chen; Hsieh, Wen-Ping

    2014-01-01

    Copy number variation (CNV) has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states. PMID:24849202

  8. Prognostic significance of centromere 17 copy number gain in breast cancer depends on breast cancer subtype.

    Science.gov (United States)

    Lee, Kyuongyul; Jang, Min Hye; Chung, Yul Ri; Lee, Yangkyu; Kang, Eunyoung; Kim, Sung-Won; Kim, Yu Jung; Kim, Jee Hyun; Kim, In Ah; Park, So Yeon

    2017-03-01

    Increased copy number of chromosome enumeration probe (CEP) targeting centromere 17 is frequently encountered during HER2 in situ hybridization (ISH) in breast cancer. The aim of this study was to clarify the clinicopathologic significance of CEP17 copy number gain in a relatively large series of breast cancer patients. We analyzed 945 cases of invasive breast cancers whose HER2 fluorescence ISH reports were available from 2004 to 2011 at a single institution and evaluated the association of CEP17 copy number gain with clinicopathologic features of tumors and patient survival. We detected 186 (19.7%) cases of CEP17 copy number gain (CEP17≥3.0) among 945 invasive breast cancers. In survival analysis, CEP17 copy number gain was not associated with disease-free survival of the patients in the whole group. Nonetheless, it was found to be an independent adverse prognostic factor in the HER2-negative group but not in the HER2-positive group. In further subgroup analyses, CEP17 copy number gain was revealed as an independent poor prognostic factor in HER2-negative and hormone receptor-positive breast cancers, and it was associated with aggressive histologic variables including high T stage, high histologic grade, lymphovascular invasion, p53 overexpression, and high Ki-67 proliferative index. In conclusion, we found that elevated CEP17 count can serve as a prognostic marker in luminal/HER2-negative subtype of invasive breast cancer. We advocate the use of the dual-colored fluorescence ISH using CEP17 rather than the single-colored one because it gives additional valuable information on CEP17 copy number alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH

    Directory of Open Access Journals (Sweden)

    Bejjani Bassem A

    2010-06-01

    Full Text Available Abstract Background Microarray-based comparative genomic hybridization (aCGH is a powerful diagnostic tool for the detection of DNA copy number gains and losses associated with chromosome abnormalities, many of which are below the resolution of conventional chromosome analysis. It has been presumed that whole-genome oligonucleotide (oligo arrays identify more clinically significant copy-number abnormalities than whole-genome bacterial artificial chromosome (BAC arrays, yet this has not been systematically studied in a clinical diagnostic setting. Results To determine the difference in detection rate between similarly designed BAC and oligo arrays, we developed whole-genome BAC and oligonucleotide microarrays and validated them in a side-by-side comparison of 466 consecutive clinical specimens submitted to our laboratory for aCGH. Of the 466 cases studied, 67 (14.3% had a copy-number imbalance of potential clinical significance detectable by the whole-genome BAC array, and 73 (15.6% had a copy-number imbalance of potential clinical significance detectable by the whole-genome oligo array. However, because both platforms identified copy number variants of unclear clinical significance, we designed a systematic method for the interpretation of copy number alterations and tested an additional 3,443 cases by BAC array and 3,096 cases by oligo array. Of those cases tested on the BAC array, 17.6% were found to have a copy-number abnormality of potential clinical significance, whereas the detection rate increased to 22.5% for the cases tested by oligo array. In addition, we validated the oligo array for detection of mosaicism and found that it could routinely detect mosaicism at levels of 30% and greater. Conclusions Although BAC arrays have faster turnaround times, the increased detection rate of oligo arrays makes them attractive for clinical cytogenetic testing.

  10. Selection of suitable endogenous reference genes for relative copy number detection in sugarcane.

    Science.gov (United States)

    Xue, Bantong; Guo, Jinlong; Que, Youxiong; Fu, Zhiwei; Wu, Luguang; Xu, Liping

    2014-05-19

    Transgene copy number has a great impact on the expression level and stability of exogenous gene in transgenic plants. Proper selection of endogenous reference genes is necessary for detection of genetic components in genetically modification (GM) crops by quantitative real-time PCR (qPCR) or by qualitative PCR approach, especially in sugarcane with polyploid and aneuploid genomic structure. qPCR technique has been widely accepted as an accurate, time-saving method on determination of copy numbers in transgenic plants and on detection of genetically modified plants to meet the regulatory and legislative requirement. In this study, to find a suitable endogenous reference gene and its real-time PCR assay for sugarcane (Saccharum spp. hybrids) DNA content quantification, we evaluated a set of potential "single copy" genes including P4H, APRT, ENOL, CYC, TST and PRR, through qualitative PCR and absolute quantitative PCR. Based on copy number comparisons among different sugarcane genotypes, including five S. officinarum, one S. spontaneum and two S. spp. hybrids, these endogenous genes fell into three groups: ENOL-3--high copy number group, TST-1 and PRR-1--medium copy number group, P4H-1, APRT-2 and CYC-2--low copy number group. Among these tested genes, P4H, APRT and CYC were the most stable, while ENOL and TST were the least stable across different sugarcane genotypes. Therefore, three primer pairs of P4H-3, APRT-2 and CYC-2 were then selected as the suitable reference gene primer pairs for sugarcane. The test of multi-target reference genes revealed that the APRT gene was a specific amplicon, suggesting this gene is the most suitable to be used as an endogenous reference target for sugarcane DNA content quantification. These results should be helpful for establishing accurate and reliable qualitative and quantitative PCR analysis of GM sugarcane.

  11. Polymorphisms of cpb multicopy genes in the Leishmania (Leishmania) donovani complex.

    Science.gov (United States)

    Hide, M; Bañuls, A L

    2008-02-01

    In leishmaniasis, cysteine protease b (cpb) multicopy genes have been extensively studied because of their implication in host-parasite interactions. In the Leishmania donovani complex, responsible for visceral leishmaniasis, a set of interesting polymorphisms has been revealed, such as copy sequence or expression according to the parasite's life stage. The single nucleotide polymorphisms observed among these copies could be related to clinical characteristics such as dermotropic versus viscerotropic status. CPB COOH-terminal extension (CTE) is mainly responsible for genetic variability among the copies and appears highly immunogenic. These results suggest that further study of the role of CPBs, especially CTE in clinical outcome, is warranted.

  12. Complexity and Entropy Analysis of DNMT1 Gene

    Science.gov (United States)

    Background: The application of complexity information on DNA sequence and protein in biological processes are well established in this study. Available sequences for DNMT1 gene, which is a maintenance methyltransferase is responsible for copying DNA methylation patterns to the daughter strands durin...

  13. A copy number variation in human NCF1 and its pseudogenes

    Directory of Open Access Journals (Sweden)

    Chambers Isfahan

    2010-02-01

    Full Text Available Abstract Background Neutrophil cytosolic factor-1 (NCF1 is a component of NADPH oxidase. The NCF1 gene colocalizes with two pseudogenes (NCF1B and NCF1C. These two pseudogenes have a GT deletion in exon 2, resulting in a frameshift and an early stop codon. Here, we report a copy number variation (CNV of the NCF1 pseudogenes and their alternative spliced expressions. Results We examined three normal populations (86 individuals. We observed the 2:2:2 pattern (NCF1B:NCF1:NCF1C in only 26 individuals. On average, each African- American has 1.4 ± 0.8 (Mean ± SD copies of NCF1B and 2.3 ± 0.6 copies of NCF1C; each Caucasian has 1.8 ± 0.7 copies of NCF1B and 1.9 ± 0.4 copies of NCF1C; and each Mexican has 1.6 ± 0.6 copies of NCF1B and 1.0 ± 0.4 copies of NCF1C. Mexicans have significantly less NCF1C copies than African-Americans (p = 6e-15 and Caucasians (p = 3e-11. Mendelian transmission of this CNV was observed in two CEPH pedigrees. Moreover, we cloned two alternative spliced transcripts generated from these two pseudogenes that adopt alternative exon-2 instead of their defective exon 2. The NCF1 pseudogene expression responded robustly to PMA induction during macrophage differentiation. NCF1B decreased from 32.9% to 8.3% in the cDNA pool transcribed from 3 gene copies. NCF1Ψs also displayed distinct expression patterns in different human tissues. Conclusions Our results suggest that these two pseudogenes may adopt an alternative exon-2 in different tissues and in response to external stimuli. The GT deletion is insufficient to define them as functionless pseudogenes; this CNV may have biological relevance.

  14. Application of BAC-probes to visualize copy number variants (CNVs).

    Science.gov (United States)

    Weise, Anja; Othman, Moneeb A K; Bhatt, Samarth; Löhmer, Sharon; Liehr, Thomas

    2015-01-01

    Copy number variations (CNVs) are structural variations of the human genome. These alterations result in variant copy numbers of certain stretches of DNA. In other words, some regions may be present in more or less copies than in a reference genome; however, these copy number changes do not have any impact on the phenotype. Also, CNVs may be extremely large and cytogenetically detectable or submicroscopic but still spanning several megabasepairs (Mb). In the recent years, array technology has identified especially the latter ones as so-called copy number variant (CNV) polymorphisms. These CNVs are detected in ~12 % of the human genome sequences and may comprise several hundred kilobasepairs. CNVs contribute significantly to the inter-individual differences in humans, and can range between 0.5 and 1.5 Mb amongst different genomes, well within the level of detection using cytogenetics techniques. Thus, they can be visualized by FISH using bacterial artificial chromosomes (BACs) as probes. Here we describe a method that enables discrimination of individual homologous chromosomes at the single cell level based on CNVs in the genome, called parental origin determination fluorescence in situ hybridization (POD-FISH). Possible fields of applications of this single cell-directed approach are in analyses of the parental origin of single chromosomes in inherited and acquired chromosomal aberrations.

  15. Cardiometabolic phenotypes and mitochondrial DNA copy number in two cohorts of UK women.

    Science.gov (United States)

    Guyatt, Anna L; Burrows, Kimberley; Guthrie, Philip A I; Ring, Sue; McArdle, Wendy; Day, Ian N M; Ascione, Raimondo; Lawlor, Debbie A; Gaunt, Tom R; Rodriguez, Santiago

    2017-08-15

    The mitochondrial genome is present at variable copy number between individuals. Mitochondria are vulnerable to oxidative stress, and their dysfunction may be associated with cardiovascular disease. The association of mitochondrial DNA copy number with cardiometabolic risk factors (lipids, glycaemic traits, inflammatory markers, anthropometry and blood pressure) was assessed in two independent cohorts of European origin women, one in whom outcomes were measured at mean (SD) age 30 (4.3) years (N=2278) and the second at 69.4 (5.5) years (N=2872). Mitochondrial DNA copy number was assayed by quantitative polymerase chain reaction. Associations were adjusted for smoking, sociodemographic status, laboratory factors and white cell traits. Out of a total of 12 outcomes assessed in both cohorts, mitochondrial DNA copy number showed little or no association with the majority (point estimates were close to zero and nearly all p-values were >0.01). The strongest evidence was for an inverse association in the older cohort with insulin (standardised beta [95%CI]: -0.06, [-0.098, -0.022], p=0.002), but this association did not replicate in the younger cohort. Our findings do not provide support for variation in mitochondrial DNA copy number having an important impact on cardio-metabolic risk factors in European origin women. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Enhancing yields of low and single copy number plasmid DNAs from Escherichia coli cells.

    Science.gov (United States)

    Wood, Whitney N; Smith, Kyle D; Ream, Jennifer A; Kevin Lewis, L

    2017-02-01

    Many plasmids used for gene cloning and heterologous protein expression in Escherichia coli cells are low copy number or single copy number plasmids. The extraction of these types of plasmids from small bacterial cell cultures produces low DNA yields. In this study, we have quantitated yields of low copy and single copy number plasmid DNAs after growth of cells in four widely used broths (SB, SOC, TB, and 2xYT) and compared results to those obtained with LB, the most common E. coli cell growth medium. TB (terrific broth) consistently generated the greatest amount of plasmid DNA, in agreement with its ability to produce higher cell titers. The superiority of TB was primarily due to its high levels of yeast extract (24g/L) and was independent of glycerol, a unique component of this broth. Interestingly, simply preparing LB with similarly high levels of yeast extract (LB24 broth) resulted in plasmid yields that were equivalent to those of TB. By contrast, increasing ampicillin concentration to enhance plasmid retention did not improve plasmid DNA recovery. These experiments demonstrate that yields of low and single copy number plasmid DNAs from minipreps can be strongly enhanced using simple and inexpensive media. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Association between Leukocyte Mitochondrial DNA Copy Number and Regular Exercise in Postmenopausal Women.

    Science.gov (United States)

    Chang, Yu Kyung; Kim, Da Eun; Cho, Soo Hyun; Kim, Jung-Ha

    2016-11-01

    Previous studies suggest that habitual exercise can improve skeletal mitochondrial function; however, to date, the association between exercise and mitochondrial function in peripheral leukocytes has not been reported. The aim of this study was to evaluate the relationship between regular exercise and mitochondrial function by measuring leukocyte mitochondrial DNA (mtDNA) copy number in postmenopausal women. This cross-sectional study included 144 relatively healthy, non-diabetic, non-smoking, postmenopausal women. Clinical parameters, including anthropometric measurements and cardio-metabolic parameters, were assessed. Regular exercise was defined as at least 150 minutes per week of moderate-intensity activity, or an equivalent combination of moderate and vigorous-intensity activity, over a duration of at least 6 months. Leukocyte mtDNA copy numbers were measured using real-time polymerase chain reaction assays, and these were normalized to the β-globin copy number to give the relative mtDNA copy number. The mtDNA copy number of peripheral leukocytes was significantly greater in the exercise group (1.33±0.02) than in the no exercise group (1.05±0.02, Pcopy number (β=0.25, Pcopy number in postmenopausal women.

  18. Use of competitive PCR to assay copy number of repetitive elements in banana.

    Science.gov (United States)

    Baurens, F C; Noyer, J L; Lanaud, C; Lagoda, P J

    1996-11-27

    Banana is one of the most important subtropical fruit crops. Genetic improvement by traditional breeding strategies is difficult and better knowledge of genomic structure is needed. Repeated sequences are powerful markers for genetic fingerprinting. The method proposed here to determine the copy number of nuclear repetitive elements is based on competitive reverse transcription-polymerase chain reaction and can also be used for quantifying cytosolic sequences. The reliability of this method was investigated on crude preparations of total DNA. Variations due to the heterogeneity of crude DNA extracts showed that a single locus reference is needed for accurate quantification. A mapped microsatellite locus was used to normalize copy number measurements. Copy number assay of repetitive elements using this method clearly distinguishes between the two banana subspecies investigated: Musa acuminata spp. banskii and M. acuminata spp. malaccensis. Two repetitive sequence families, pMaCIR1115 and pA9-26, were assayed that cover up to 1% of the M. acuminata genome. Their copy number varied up to six fold between the two subspecies. Furthermore, sequence quantification showed that mitochondrial genomes are present in crude leaf-extracted banana DNA at up to 40 copies per cell.

  19. Dietary Variation and Evolution of Gene Copy Number among Dog Breeds.

    Science.gov (United States)

    Reiter, Taylor; Jagoda, Evelyn; Capellini, Terence D

    2016-01-01

    Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR), phytanol-CoA 2-hydroxylase (PHYH), and pancreatic α-amylase 2B (AMY2B). These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs.

  20. DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer

    Science.gov (United States)

    Mamlouk, Soulafa; Childs, Liam Harold; Aust, Daniela; Heim, Daniel; Melching, Friederike; Oliveira, Cristiano; Wolf, Thomas; Durek, Pawel; Schumacher, Dirk; Bläker, Hendrik; von Winterfeld, Moritz; Gastl, Bastian; Möhr, Kerstin; Menne, Andrea; Zeugner, Silke; Redmer, Torben; Lenze, Dido; Tierling, Sascha; Möbs, Markus; Weichert, Wilko; Folprecht, Gunnar; Blanc, Eric; Beule, Dieter; Schäfer, Reinhold; Morkel, Markus; Klauschen, Frederick; Leser, Ulf; Sers, Christine

    2017-01-01

    Genetic heterogeneity between and within tumours is a major factor determining cancer progression and therapy response. Here we examined DNA sequence and DNA copy-number heterogeneity in colorectal cancer (CRC) by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary tumours and matched metastases from 27 patients, we observe inter-tumour concordance for coding mutations; in contrast, gene copy numbers are highly discordant between primary tumours and metastases as validated by fluorescent in situ hybridization. To further investigate intra-tumour heterogeneity, we dissected a single tumour into 68 spatially defined samples and sequenced them separately. We identify evenly distributed coding mutations in APC and TP53 in all tumour areas, yet highly variable gene copy numbers in numerous genes. 3D morpho-molecular reconstruction reveals two clusters with divergent copy number aberrations along the proximal–distal axis indicating that DNA copy number variations are a major source of tumour heterogeneity in CRC. PMID:28120820

  1. Dietary Variation and Evolution of Gene Copy Number among Dog Breeds.

    Directory of Open Access Journals (Sweden)

    Taylor Reiter

    Full Text Available Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR, phytanol-CoA 2-hydroxylase (PHYH, and pancreatic α-amylase 2B (AMY2B. These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs.

  2. Copy-Move Forgery Detection Technique for Forensic Analysis in Digital Images

    Directory of Open Access Journals (Sweden)

    Toqeer Mahmood

    2016-01-01

    Full Text Available Due to the powerful image editing tools images are open to several manipulations; therefore, their authenticity is becoming questionable especially when images have influential power, for example, in a court of law, news reports, and insurance claims. Image forensic techniques determine the integrity of images by applying various high-tech mechanisms developed in the literature. In this paper, the images are analyzed for a particular type of forgery where a region of an image is copied and pasted onto the same image to create a duplication or to conceal some existing objects. To detect the copy-move forgery attack, images are first divided into overlapping square blocks and DCT components are adopted as the block representations. Due to the high dimensional nature of the feature space, Gaussian RBF kernel PCA is applied to achieve the reduced dimensional feature vector representation that also improved the efficiency during the feature matching. Extensive experiments are performed to evaluate the proposed method in comparison to state of the art. The experimental results reveal that the proposed technique precisely determines the copy-move forgery even when the images are contaminated with blurring, noise, and compression and can effectively detect multiple copy-move forgeries. Hence, the proposed technique provides a computationally efficient and reliable way of copy-move forgery detection that increases the credibility of images in evidence centered applications.

  3. Regulation of Transient Site-specific Copy Gain by MicroRNA.

    Science.gov (United States)

    Black, Joshua C; Zhang, Hailei; Kim, Jaegil; Getz, Gad; Whetstine, Johnathan R

    2016-03-04

    Intra-tumor copy number heterogeneity is commonly observed in cancer; however, the molecular mechanisms that contribute to heterogeneity remain poorly understood. Up-regulation of the histone demethylase KDM4A promotes transient site-specific copy gain (TSSG) in cells; therefore, uncovering how KDM4A levels are controlled is important for understanding the regulation of copy number heterogeneity. Here, we demonstrate that KDM4A is regulated by hsa-mir-23a-3p, hsa-mir-23b-3p, and hsa-mir-137. Altering expression of these microRNAs (miRNAs) regulates KDM4A-dependent TSSG. miRNA inhibition promoted copy gains and increased expression of the drug-resistant oncogene CKS1B, which was further substantiated in primary breast tumors. Consistent with increased CKS1B expression, miRNA inhibition reduced breast cancer cell sensitivity to cisplatin. Our data identify these miRNAs as regulators of TSSG and copy gains of a drug resistance gene.

  4. Regulation of Transient Site-specific Copy Gain by MicroRNA*♦

    Science.gov (United States)

    Black, Joshua C.; Zhang, Hailei; Kim, Jaegil; Getz, Gad; Whetstine, Johnathan R.

    2016-01-01

    Intra-tumor copy number heterogeneity is commonly observed in cancer; however, the molecular mechanisms that contribute to heterogeneity remain poorly understood. Up-regulation of the histone demethylase KDM4A promotes transient site-specific copy gain (TSSG) in cells; therefore, uncovering how KDM4A levels are controlled is important for understanding the regulation of copy number heterogeneity. Here, we demonstrate that KDM4A is regulated by hsa-mir-23a-3p, hsa-mir-23b-3p, and hsa-mir-137. Altering expression of these microRNAs (miRNAs) regulates KDM4A-dependent TSSG. miRNA inhibition promoted copy gains and increased expression of the drug-resistant oncogene CKS1B, which was further substantiated in primary breast tumors. Consistent with increased CKS1B expression, miRNA inhibition reduced breast cancer cell sensitivity to cisplatin. Our data identify these miRNAs as regulators of TSSG and copy gains of a drug resistance gene. PMID:26755726

  5. Accurate and objective copy number profiling using real-time quantitative PCR.

    Science.gov (United States)

    D'haene, Barbara; Vandesompele, Jo; Hellemans, Jan

    2010-04-01

    Copy number changes are known to be involved in numerous human genetic disorders. In this context, qPCR-based copy number screening may serve as the method of choice for targeted screening of the relevant disease genes and their surrounding regulatory landscapes. qPCR has many advantages over alternative methods, such as its low consumable and instrumentation costs, fast turnaround and assay development time, high sensitivity and open format (independent of a single supplier). In this chapter we provide all relevant information for a successfully implement of qPCR-based copy number analysis. We emphasize the significance of thorough in silico and empirical validation of the primers, the need for a well thought-out experiment design, and the importance of quality controls along the entire workflow. Furthermore, we suggest an appropriate and practical way to calculate copy numbers and to objectively interpret the results. The provided guidelines will most certainly improve the quality and reliability of your qPCR-based copy number screening.

  6. Strategies to improve low copy transgenic events in Agrobacterium-mediated transformation of maize.

    Science.gov (United States)

    Sivamani, Elumalai; Li, Xianggan; Nalapalli, Samson; Barron, Yoshimi; Prairie, Anna; Bradley, David; Doyle, Michele; Que, Qiudeng

    2015-12-01

    Transgenic plants containing low copy transgene insertion free of vector backbone are highly desired for many biotechnological applications. We have investigated two different strategies for increasing the percentage of low copy events in Agrobacterium-mediated transformation experiments in maize. One of the strategies is to use a binary vector with two separate T-DNAs, one T-DNA containing an intact E.coli manA gene encoding phosphomannose isomerase (PMI) as selectable marker gene cassette and another T-DNA containing an RNAi cassette of PMI sequences. By using this strategy, low copy transgenic events containing the transgenes were increased from 43 to 60 % in maize. An alternate strategy is using selectable marker gene cassettes containing regulatory or coding sequences derived from essential plant genes such as 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) or MADS box transcription factor. In this paper we demonstrate that higher percentage of low copy transgenic events can be obtained in Agrobacterium-mediated maize transformation experiments using both strategies. We propose that the above two strategies can be used independently or in combination to increase transgenic events that contain low copy transgene insertion in Agrobacterium-mediated transformation experiments.

  7. Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene

    Science.gov (United States)

    Bassuk, Alexander G.; Muthuswamy, Lakshmi B.; Boland, Riley; Smith, Tiffany L.; Hulstrand, Alissa M.; Northrup, Hope; Hakeman, Matthew; Dierdorff, Jason M.; Yung, Christina K.; Long, Abby; Brouillette, Rachel B.; Au, Kit Sing; Gurnett, Christina; Houston, Douglas W.; Cornell, Robert A.; Manak, J. Robert

    2013-01-01

    Neural tube defects (NTDs) are common birth defects of complex etiology. Family and population-based studies have confirmed a genetic component to NTDs. However, despite more than three decades of research, the genes involved in human NTDs remain largely unknown. We tested the hypothesis that rare copy number variants (CNVs), especially de novo germline CNVs, are a significant risk factor for NTDs. We used array-based comparative genomic hybridization (aCGH) to identify rare CNVs in 128 Caucasian and 61 Hispanic patients with non-syndromic lumbar-sacral myelomeningocele. We also performed aCGH analysis on the parents of affected individuals with rare CNVs where parental DNA was available (42 sets). Among the eight de novo CNVs that we identified, three generated copy number changes of entire genes. One large heterozygous deletion removed 27 genes, including PAX3, a known spina bifida-associated gene. A second CNV altered genes (PGPD8, ZC3H6) for which little is known regarding function or expression. A third heterozygous deletion removed GPC5 and part of GPC6, genes encoding glypicans. Glypicans are proteoglycans that modulate the activity of morphogens such as Sonic Hedgehog (SHH) and bone morphogenetic proteins (BMPs), both of which have been implicated in NTDs. Additionally, glypicans function in the planar cell polarity (PCP) pathway, and several PCP genes have been associated with NTDs. Here, we show that GPC5 orthologs are expressed in the neural tube, and that inhibiting their expression in frog and fish embryos results in NTDs. These results implicate GPC5 as a gene required for normal neural tube development. PMID:23223018

  8. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways

    Science.gov (United States)

    Giordano, L; Deceglie, S; d'Adamo, P; Valentino, M L; La Morgia, C; Fracasso, F; Roberti, M; Cappellari, M; Petrosillo, G; Ciaravolo, S; Parente, D; Giordano, C; Maresca, A; Iommarini, L; Del Dotto, V; Ghelli, A M; Salomao, S R; Berezovsky, A; Belfort, R; Sadun, A A; Carelli, V; Loguercio Polosa, P; Cantatore, P

    2015-01-01

    Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that

  9. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways.

    Science.gov (United States)

    Giordano, L; Deceglie, S; d'Adamo, P; Valentino, M L; La Morgia, C; Fracasso, F; Roberti, M; Cappellari, M; Petrosillo, G; Ciaravolo, S; Parente, D; Giordano, C; Maresca, A; Iommarini, L; Del Dotto, V; Ghelli, A M; Salomao, S R; Berezovsky, A; Belfort, R; Sadun, A A; Carelli, V; Loguercio Polosa, P; Cantatore, P

    2015-12-17

    Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that

  10. Communication complexity and information complexity

    Science.gov (United States)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  11. Mate-choice copying: A fitness-enhancing behavior that evolves by indirect selection.

    Science.gov (United States)

    Santos, Mauro; Sapage, Manuel; Matos, Margarida; Varela, Susana A M

    2017-06-01

    A spatially explicit, individual-based simulation model is used to study the spread of an allele for mate-choice copying (MCC) through horizontal cultural transmission when female innate preferences do or do not coevolve with a male viability-increasing trait. Evolution of MCC is unlikely when innate female preferences coevolve with the trait, as copier females cannot express a higher preference than noncopier females for high-fitness males. However, if a genetic polymorphism for innate preference persists in the population, MCC can evolve by indirect selection through hitchhiking: the copying allele hitchhikes on the male trait. MCC can be an adaptive behavior-that is, a behavior that increases a population's average fitness relative to populations without MCC-even though the copying allele itself may be neutral or mildly deleterious. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  12. Dynamics of the spelling process during a copy task: effects of regularity and frequency.

    Science.gov (United States)

    Lambert, Eric; Alamargot, Denis; Larocque, Denis; Caporossi, Gilles

    2011-09-01

    This study investigated the time course of spelling, and its influence on graphomotor execution, in a successive word copy task. According to the cascade model, these two processes may be engaged either sequentially or in parallel, depending on the cognitive demands of spelling. In this experiment, adults were asked to copy a series of words varying in frequency and spelling regularity. A combined analysis of eye and pen movements revealed periods where spelling occurred in parallel with graphomotor execution, but concerned different processing units. The extent of this parallel processing depended on the words' orthographic characteristics. Results also highlighted the specificity of word recognition for copying purposes compared with recognition for reading tasks. The results confirm the validity of the cascade model and clarify the nature of the dependence between spelling and graphomotor processes. © 2011 Canadian Psychological Association

  13. EPSPS Gene Copy Number and Whole-Plant Glyphosate Resistance Level in Kochia scoparia.

    Science.gov (United States)

    Gaines, Todd A; Barker, Abigail L; Patterson, Eric L; Westra, Philip; Westra, Eric P; Wilson, Robert G; Jha, Prashant; Kumar, Vipan; Kniss, Andrew R

    2016-01-01

    Glyphosate-resistant (GR) Kochia scoparia has evolved in dryland chemical fallow systems throughout North America and the mechanism of resistance involves 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene duplication. Agricultural fields in four states were surveyed for K. scoparia in 2013 and tested for glyphosate-resistance level and EPSPS gene copy number. Glyphosate resistance was confirmed in K. scoparia populations collected from sugarbeet fields in Colorado, Wyoming, and Nebraska, and Montana. Glyphosate resistance was also confirmed in K. scoparia accessions collected from wheat-fallow fields in Montana. All GR samples had increased EPSPS gene copy number, with median population values up to 11 from sugarbeet fields and up to 13 in Montana wheat-fallow fields. The results indicate that glyphosate susceptibility can be accurately diagnosed using EPSPS gene copy number.

  14. Negative public information in mate choice copying helps the spread of a novel trait.

    Science.gov (United States)

    Santos, Mauro; Matos, Margarida; Varela, Susana A M

    2014-11-01

    Numerous field and laboratory experiments have shown that many species have the capacity for social learning, including mate choice decisions that can be influenced by witnessing the mating decisions of others. Here we develop a numerical model of mate choice copying that follows the population genetics tradition, consisting in tracking allele frequencies in a population over time under various scenarios. In contrast to previous evolutionary models, we consider both positive social information and negative social information because many mating systems are driven by males in pursuit of a mate and female refusal of copulation may provide negative social information. The inclusion of negative social information to mate choice copying helps the spread of a novel trait, even if female innate mate choice preference is biased toward the common male type. We argue that the presence or absence of copying might simply mirror the associated cost-benefit relationship of the mating system of a given species and suggest how to test this prediction.

  15. CCL3L gene copy number and survival in an HIV-1 infected Zimbabwean population

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Thørner, Lise Wegner; Zinyama, Rutendo

    2012-01-01

    The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility and progre......The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility.......9), viral load (P=0.9), or CCL3 protein levels (P=1.0). Survival among the HIV infected individuals did not differ according to CCL3L copy number. In this cohort, CCL3L CNV did not affect HIV status, pathogenesis, or survival....

  16. Relative Copy Number Variations of CYP2C19 in South Indian Population

    Directory of Open Access Journals (Sweden)

    Anichavezhi Devendran

    2012-01-01

    Full Text Available CYP2C19 is a polymorphic enzyme involved in the metabolism of clinically important drugs. Genotype-phenotype association studies of CYP2C19 have reported wide ranges in the metabolic ratios of its substrates. These discrepancies could be attributed to the variations in the promoter region and this aspect has been reported recently. The observations in the recent reports on the influence of promoter region variants on the metabolism of CYP2C19 substrates might also have been influenced by the copy number variations of CYP2C19. In this paper, we describe copy number variations of CYP2C19 using real-time polymerase chain reaction by comparative Ct method. No copy number variations were observed in the south Indian population indicating the observed discrepancies in genotype-phenotype association studies might be due to the regulatory region polymorphisms as reported earlier.

  17. Copi et Puig, ovnis du théâtre argentin ?

    OpenAIRE

    Souquet, Lionel

    2015-01-01

    C’est en 1968 que Copi (Raúl Damonte Botana, 1939-1987) publie sa première pièce, La journée d’une rêveuse puis, un an plus tard, la très iconoclaste Eva Peron. Par son milieu familial, Copi a baigné dès l’enfance dans la vie théâtrale internationale et a été fortement influencé par sa grand-mère, la dramaturge anarcho-féministe Salvadora Medina Onrubia de Botana. Mais, vivant en exil avec sa famille, Copi est coupé de la réalité de la scène argentine et il écrit d’ailleurs ses premières pièc...

  18. Genome-wide copy number profiling to detect gene amplifications in neural progenitor cells

    Directory of Open Access Journals (Sweden)

    U. Fischer

    2014-12-01

    Full Text Available DNA sequence amplification occurs at defined stages during normal development in amphibians and flies and seems to be restricted in humans to drug-resistant and tumor cells only. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of human neural progenitor cells. Here, we describe cell culture features, DNA extraction, and comparative genomic hybridization (CGH analysis tailored towards the identification of genomic copy number changes. Further detailed analysis of amplified chromosome regions associated with this experiment, was published by Fischer and colleagues in PLOS One in 2012 (Fischer et al., 2012. We provide detailed information on deleted chromosome regions during differentiation and give an overview on copy number changes during differentiation induction for two representative chromosome regions.

  19. Extra-copy nifA enhances the nodulation efficiency of Sinorhizobium fredii

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Previous investigations have shown that nifA gene is involved in nodulation and symbiotic nitrogen fixation regulation of Rhizobium. We study the role of nifA on nodulation of leguminous plants. We found that Sinorhizobium fredii harboring multi-copy plasmid carrying the constitutively expressed Klebsiella pneumoniae nifA exhibited an increase of noduiation activity and nodulation competitiveness on soybean plants. The Nod-factor secreted by the rhizobia cells containing the multi-copied nifA was assayed,and preliminary results showed that S. fredii containing the multi-copy plasmid carrying nifA produced higher strength of Nod-factor than the rhizobia containing the same plasmid carrying the vector did.

  20. An Efficient Method for Detection of Copy-Move Forgery Using Discrete Wavelet Transform

    Directory of Open Access Journals (Sweden)

    Er. Saiqa Khan

    2010-08-01

    Full Text Available Copy-Move forgery is a specific type of image forgery, in which a part of digital image is copied and pasted to another part in the same image. This paper describes blind forensics approach for detecting Copy-Move forgery. Our technique works by first applying DWT (Discrete Wavelet Transform to the input image to yield a reduced dimension representation [1]. Then the compressed image is divided into overlapping blocks. These blocks are then sorted and duplicated blocks are identified using Phase Correlation as similarity criterion. Due to DWT usage, detection is first carried out on lowest level image representation. This approach drastically reduces the time needed for the detection process.

  1. Gyrase activity and number of copies of the gyrase B subunit gene in Haemophilus influenzae

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera-Juarez, E.; Setlow, J.K.

    1985-11-01

    Gyrase activities in extracts of various strains of Haemophilus influenzae can differ by more than an order of magnitude. Measurements of in vitro activity and copy number indicated that most of these differences arose from variations in the number of copies of the gene for the gyrase B subunit, with some strains containing multicopy plasmids coding for that subunit. The quantitative relationship between gyrase and copy number depended on the mutations in the plasmids and in the host. The possibility that the in vivo gyrase activity did not reflect the in vitro data was explored by measurement of alkaline phosphatase and ATPase activity in the extracts. Alkaline phosphatase activity increased with increasing gyrase activity measured in vitro, but ATPase activity did not. The authors conclude that extra supercoiling enhanced transcription of the alkaline phosphatase gene but not the ATPase gene and that it is unlikely that there is much discrepancy between gyrase activity assayed in vitro and the activity in the cell.

  2. Inducible amplification of gene copy number and heterologous protein production in the yeast Kluyveromyces lactis.

    Science.gov (United States)

    Morlino, G B; Tizzani, L; Fleer, R; Frontali, L; Bianchi, M M

    1999-11-01

    Heterologous protein production can be doubled by increasing the copy number of the corresponding heterologous gene. We constructed a host-vector system in the yeast Kluyveromyces lactis that was able to induce copy number amplification of pKD1 plasmid-based vectors upon expression of an integrated copy of the plasmid recombinase gene. We increased the production and secretion of two heterologous proteins, glucoamylase from the yeast Arxula adeninivorans and mammalian interleukin-1beta, following gene dosage amplification when the heterologous genes were carried by pKD1-based vectors. The choice of the promoters for expression of the integrated recombinase gene and of the episomal heterologous genes are critical for the mitotic stability of the host-vector system.

  3. Written object naming, spelling to dictation, and immediate copying: Different tasks, different pathways?

    Science.gov (United States)

    Bonin, Patrick; Méot, Alain; Lagarrigue, Aurélie; Roux, Sébastien

    2015-01-01

    We report an investigation of cross-task comparisons of handwritten latencies in written object naming, spelling to dictation, and immediate copying. In three separate sessions, adults had to write down a list of concrete nouns from their corresponding pictures (written naming), from their spoken (spelling to dictation) and from their visual presentation (immediate copying). Linear mixed models without random slopes were performed on the latencies in order to study and compare within-task fixed effects. By-participants random slopes were then included to investigate individual differences within and across tasks. Overall, the findings suggest that written naming, spelling to dictation, and copying all involve a lexical pathway, but that written naming relies on this pathway more than the other two tasks do. Only spelling to dictation strongly involves a nonlexical pathway. Finally, the analyses performed at the level of participants indicate that, depending on the type of task, the slower participants are more or less influenced by certain psycholinguistic variables.

  4. Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly

    DEFF Research Database (Denmark)

    Mengel-From, Jonas; Thinggaard, Mikael; Dalgård, Christine

    2014-01-01

    compared to nuclear DNA, i.e. the mitochondrial DNA copy number, was measured by PCR technology and used as a proxy for the content of mitochondria copies. In 1,067 Danish twins and singletons (18-93 years of age), with the majority being elderly individuals, the estimated mean mitochondrial DNA copy...... an individual was more than twice as steep as observed in the cross-sectional analysis [decline of mtDNA content: -1.27; 95 % CI (-1.71; -0.82)]. Subjects with low mitochondrial DNA copy number had poorer outcomes in terms of cognitive performance, physical strength, self-rated health, and higher all......-cause mortality than subjects with high mitochondrial DNA copy number, also when age was controlled for. The copy number mortality association can contribute to the smaller decline in a cross-sectional sample of the population compared to the individual, longitudinal decline. This study suggests that high...

  5. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants.

    Science.gov (United States)

    Kearney, Hutton M; Thorland, Erik C; Brown, Kerry K; Quintero-Rivera, Fabiola; South, Sarah T

    2011-07-01

    Genomic microarrays used to assess DNA copy number are now recommended as first-tier tests for the postnatal evaluation of individuals with intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies. Application of this technology has resulted in the discovery of widespread copy number variation in the human genome, both polymorphic variation in healthy individuals and novel pathogenic copy number imbalances. To assist clinical laboratories in the evaluation of copy number variants and to promote consistency in interpretation and reporting of genomic microarray results, the American College of Medical Genetics has developed the following professional guidelines for the interpretation and reporting of copy number variation. These guidelines apply primarily to evaluation of constitutional copy number variants detected in the postnatal setting.

  6. Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer.

    Science.gov (United States)

    Lemnrau, Alina; Brook, Mark N; Fletcher, Olivia; Coulson, Penny; Tomczyk, Katarzyna; Jones, Michael; Ashworth, Alan; Swerdlow, Anthony; Orr, Nick; Garcia-Closas, Montserrat

    2015-07-15

    Increased mitochondrial DNA (mtDNA) copy number in peripheral blood cells (PBC) has been associated with the risk of developing several tumor types. Here we evaluate sources of variation of this biomarker and its association with breast cancer risk in a prospective cohort study. mtDNA copy number was measured using quantitative real-time PCR on PBC DNA samples from participants in the UK-based Breakthrough Generations Study. Temporal and assay variation was evaluated in a serial study of 91 women, with two blood samples collected approximately 6-years apart. Then, associations with breast cancer risk factors and risk were evaluated in 1,108 cases and 1,099 controls using a nested case-control design. In the serial study, mtDNA copy number showed low assay variation but large temporal variation [assay intraclass correlation coefficient (ICC), 79.3%-87.9%; temporal ICC, 38.3%). Higher mtDNA copy number was significantly associated with younger age at blood collection, being premenopausal, having an older age at menopause, and never taking HRT, both in cases and controls. Based on measurements in a single blood sample taken on average 6 years before diagnosis, higher mtDNA copy number was associated with increased breast cancer risk [OR (95% CI) for highest versus lowest quartile, 1.37 (1.02-1.83); P trend = 0.007]. In conclusion, mtDNA copy number is associated with breast cancer risk and represents a promising biomarker for risk assessment. The relatively large temporal variation should be taken into account in future analyses.

  7. Reliable transgene-independent method for determining Sleeping Beauty transposon copy numbers

    Directory of Open Access Journals (Sweden)

    Kolacsek Orsolya

    2011-03-01

    Full Text Available Abstract Background The transposon-based gene delivery technique is emerging as a method of choice for gene therapy. The Sleeping Beauty (SB system has become one of the most favored methods, because of its efficiency and its random integration profile. Copy-number determination of the delivered transgene is a crucial task, but a universal method for measuring this is lacking. In this paper, we show that a real-time quantitative PCR-based, transgene-independent (qPCR-TI method is able to determine SB transposon copy numbers regardless of the genetic cargo. Results We designed a specific PCR assay to amplify the left inverted repeat-direct repeat region of SB, and used it together with the single-copy control gene RPPH1 and a reference genomic DNA of known copy number. The qPCR-TI method allowed rapid and accurate determination of SB transposon copy numbers in various cell types, including human embryonic stem cells. We also found that this sensitive, rapid, highly reproducible and non-radioactive method is just as accurate and reliable as the widely used blotting techniques or the transposon display method. Because the assay is specific for the inverted repeat region of the transposon, it could be used in any system where the SB transposon is the genetic vehicle. Conclusions We have developed a transgene-independent method to determine copy numbers of transgenes delivered by the SB transposon system. The technique is based on a quantitative real-time PCR detection method, offering a sensitive, non-radioactive, rapid and accurate approach, which has a potential to be used for gene therapy.

  8. The association between DNA copy number aberrations at chromosome 5q22 and gastric cancer.

    Directory of Open Access Journals (Sweden)

    Pei-Chien Tsai

    Full Text Available BACKGROUND: Gastric cancer is common cancer. Discovering novel genetic biomarkers might help to identify high-risk individuals. Copy number variation (CNV has recently been shown to influence risk for several cancers. The aim of the present study was sought to test the association between copy number at a variant region and GC. METHODS: A total of 110 gastric cancer patients and 325 healthy volunteers were enrolled in this study. We searched for a CNV and found a CNV (Variation 7468 containing part of the APC gene, the SRP19 gene and the REEP5 gene. We chose four probes targeting at APC-intron8, APC-exon9, SRP19 and REEP5 to interrogate this CNV. Specific Taqman probes labeled by different reporter fluorophores were used in a real-time PCR platform to obtain copy number. Both the original non-integer data and transformed integer data on copy number were used for analyses. RESULTS: Gastric caner patients had a lower non-integer copy number than controls for the APC-exon9 probe (Adjusted p = 0.026 and SRP19 probe (Adjusted p = 0.002. The analysis of integer copy number yielded a similar pattern although less significant (Adjusted p = 0.07 for APC-exon9 probe and Adjusted p = 0.02 for SRP19 probe. CONCLUSIONS: Losses of a CNV at 5q22, especially in the DNA region surrounding APC-exon 9, may be associated with a higher risk of gastric cancer.

  9. Accurate measurement of transgene copy number in crop plants using droplet digital PCR.

    Science.gov (United States)

    Collier, Ray; Dasgupta, Kasturi; Xing, Yan-Ping; Hernandez, Bryan Tarape; Shao, Min; Rohozinski, Dominica; Kovak, Emma; Lin, Jeanie; de Oliveira, Maria Luiza P; Stover, Ed; McCue, Kent F; Harmon, Frank G; Blechl, Ann; Thomson, James G; Thilmony, Roger

    2017-06-01

    Genetic transformation is a powerful means for the improvement of crop plants, but requires labor- and resource-intensive methods. An efficient method for identifying single-copy transgene insertion events from a population of independent transgenic lines is desirable. Currently, transgene copy number is estimated by either Southern blot hybridization analyses or quantitative polymerase chain reaction (qPCR) experiments. Southern hybridization is a convincing and reliable method, but it also is expensive, time-consuming and often requires a large amount of genomic DNA and radioactively labeled probes. Alternatively, qPCR requires less DNA and is potentially simpler to perform, but its results can lack the accuracy and precision needed to confidently distinguish between one- and two-copy events in transgenic plants with large genomes. To address this need, we developed a droplet digital PCR-based method for transgene copy number measurement in an array of crops: rice, citrus, potato, maize, tomato and wheat. The method utilizes specific primers to amplify target transgenes, and endogenous reference genes in a single duplexed reaction containing thousands of droplets. Endpoint amplicon production in the droplets is detected and quantified using sequence-specific fluorescently labeled probes. The results demonstrate that this approach can generate confident copy number measurements in independent transgenic lines in these crop species. This method and the compendium of probes and primers will be a useful resource for the plant research community, enabling the simple and accurate determination of transgene copy number in these six important crop species. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  10. Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data.

    Science.gov (United States)

    Favero, F; Joshi, T; Marquard, A M; Birkbak, N J; Krzystanek, M; Li, Q; Szallasi, Z; Eklund, A C

    2015-01-01

    Exome or whole-genome deep sequencing of tumor DNA along with paired normal DNA can potentially provide a detailed picture of the somatic mutations that characterize the tumor. However, analysis of such sequence data can be complicated by the presence of normal cells in the tumor specimen, by intratumor heterogeneity, and by the sheer size of the raw data. In particular, determination of copy number variations from exome sequencing data alone has proven difficult; thus, single nucleotide polymorphism (SNP) arrays have often been used for this task. Recently, algorithms to estimate absolute, but not allele-specific, copy number profiles from tumor sequencing data have been described. We developed Sequenza, a software package that uses paired tumor-normal DNA sequencing data to estimate tumor cellularity and ploidy, and to calculate allele-specific copy number profiles and mutation profiles. We applied Sequenza, as well as two previously published algorithms, to exome sequence data from 30 tumors from The Cancer Genome Atlas. We assessed the performance of these algorithms by comparing their results with those generated using matched SNP arrays and processed by the allele-specific copy number analysis of tumors (ASCAT) algorithm. Comparison between Sequenza/exome and SNP/ASCAT revealed strong correlation in cellularity (Pearson's r = 0.90) and ploidy estimates (r = 0.42, or r = 0.94 after manual inspecting alternative solutions). This performance was noticeably superior to previously published algorithms. In addition, in artificial data simulating normal-tumor admixtures, Sequenza detected the correct ploidy in samples with tumor content as low as 30%. The agreement between Sequenza and SNP array-based copy number profiles suggests that exome sequencing alone is sufficient not only for identifying small scale mutations but also for estimating cellularity and inferring DNA copy number aberrations. © The Author 2014. Published by Oxford University Press on behalf of

  11. Loss of the Association between Telomere Length and Mitochondrial DNA Copy Number Contribute to Colorectal Carcinogenesis.

    Science.gov (United States)

    Lee, Hyunsu; Cho, Ji-Hyoung; Park, Won-Jin; Jung, Soo-Jung; Choi, In-Jang; Lee, Jae-Ho

    2017-05-09

    Positive association between telomere length and mitochondrial DNA (mtDNA) copy number were introduced in healthy and patients with psychiatric disorder. Based on frequent genetic changes of telomere and mitochondria in colorectal carcinomas (CRC), we studied their clinical characteristics and their association in colorectal carcinogenesis. DNA was extracted from 109 CRCs, 64 colorectal tubular adenomas (TAs), and 28 serrated polyps (SPs), and then, telomere length and mtDNA copy number were analyzed in these legions by using a real-time PCR assay. Telomere length and mtDNA copy number (mean ± S.D) in CRCs was 1.87 ± 1.52 and 1.61 ± 1.37, respectively. In TAs and SPs, relative mtDNA copy number was 0.92 ± 0.71 and 1.84 ± 1.06, respectively, shoing statistical difference (p = 0.017). However, telomere length was similar in these precancerous legions. Telomere length and mtDNA copy number did not show clinical and prognostic values in CRCs, however, positive correlation between telomere length and mitochondrial DNA copy number were found in CRC (r = 0.408, p < 0.001). However, this association was not shown in precancerous lesions (r = -0.031, p = 0.765). This result suggests that loss of co-regulation between telomeres and mitochondrial function may induce the initiation or play a role as trigger factor of colorectal carcinogenesis.

  12. An experimental test of the accumulated copying error model of cultural mutation for Acheulean handaxe size.

    Science.gov (United States)

    Kempe, Marius; Lycett, Stephen; Mesoudi, Alex

    2012-01-01

    Archaeologists interested in explaining changes in artifact morphology over long time periods have found it useful to create models in which the only source of change is random and unintentional copying error, or 'cultural mutation'. These models can be used as null hypotheses against which to detect non-random processes such as cultural selection or biased transmission. One proposed cultural mutation model is the accumulated copying error model, where individuals attempt to copy the size of another individual's artifact exactly but make small random errors due to physiological limits on the accuracy of their perception. Here, we first derive the model within an explicit mathematical framework, generating the predictions that multiple independently-evolving artifact chains should diverge over time such that their between-chain variance increases while the mean artifact size remains constant. We then present the first experimental test of this model in which 200 participants, split into 20 transmission chains, were asked to faithfully copy the size of the previous participant's handaxe image on an iPad. The experimental findings supported the model's prediction that between-chain variance should increase over time and did so in a manner quantitatively in line with the model. However, when the initial size of the image that the participants resized was larger than the size of the image they were copying, subjects tended to increase the size of the image, resulting in the mean size increasing rather than staying constant. This suggests that items of material culture formed by reductive vs. additive processes may mutate differently when individuals attempt to replicate faithfully the size of previously-produced artifacts. Finally, we show that a dataset of 2601 Acheulean handaxes shows less variation than predicted given our empirically measured copying error variance, suggesting that other processes counteracted the variation in handaxe size generated by perceptual

  13. Copy number variations of 11 macronuclear chromosomes and their gene expression in Oxytricha trifallax.

    Science.gov (United States)

    Xu, Ke; Doak, Thomas G; Lipps, Hans J; Wang, Jingmei; Swart, Estienne C; Chang, Wei-Jen

    2012-08-15

    Ciliated protozoa are peculiar for their nuclear dimorphism, wherein two types of nuclei divide nuclear functions: a germline micronucleus (MIC) is transcriptionally inert during vegetative growth, but serves as the genetic blueprint for the somatic macronucleus (MAC), which is responsible for all transcripts supporting cell growth and reproduction. While all the advantages/disadvantages associated with nuclear dimorphism are not clear, an essential advantage seems to be the ability to produce a highly polyploid MAC, which then allows for the maintenance of extremely large single cells - many ciliate cells are larger than small metazoa. In some ciliate classes, chromosomes in the MAC are extensively fragmented to create extremely short chromosomes that often carry single genes, and these chromosomes may be present in different copy numbers, resulting in different ploidies. While using gene copy number to regulate gene expression is limited in most eukaryotic systems, the extensive fragmentation in some ciliate classes provides this opportunity to every MAC gene. However, it is still unclear if this mechanism is in fact used extensively in these ciliates. To address this, we have quantified copy numbers of 11 MAC chromosomes and their gene expression in Oxytricha trifallax (CI: Spirotrichea). We compared copy numbers between two subpopulations of O. trifallax, and copy numbers of 7 orthologous genes between O. trifallax and the closely related Stylonychia lemnae. We show that copy numbers of MAC chromosomes are variable, dynamic, and positively correlated to gene expression. These features might be conserved in all spirotrichs, and might exist in other classes of ciliates with heavily fragmented MAC chromosomes.

  14. Selection of Suitable Endogenous Reference Genes for Relative Copy Number Detection in Sugarcane

    Directory of Open Access Journals (Sweden)

    Bantong Xue

    2014-05-01

    Full Text Available Transgene copy number has a great impact on the expression level and stability of exogenous gene in transgenic plants. Proper selection of endogenous reference genes is necessary for detection of genetic components in genetically modification (GM crops by quantitative real-time PCR (qPCR or by qualitative PCR approach, especially in sugarcane with polyploid and aneuploid genomic structure. qPCR technique has been widely accepted as an accurate, time-saving method on determination of copy numbers in transgenic plants and on detection of genetically modified plants to meet the regulatory and legislative requirement. In this study, to find a suitable endogenous reference gene and its real-time PCR assay for sugarcane (Saccharum spp. hybrids DNA content quantification, we evaluated a set of potential “single copy” genes including P4H, APRT, ENOL, CYC, TST and PRR, through qualitative PCR and absolute quantitative PCR. Based on copy number comparisons among different sugarcane genotypes, including five S. officinarum, one S. spontaneum and two S. spp. hybrids, these endogenous genes fell into three groups: ENOL-3—high copy number group, TST-1 and PRR-1—medium copy number group, P4H-1, APRT-2 and CYC-2—low copy number group. Among these tested genes, P4H, APRT and CYC were the most stable, while ENOL and TST were the least stable across different sugarcane genotypes. Therefore, three primer pairs of P4H-3, APRT-2 and CYC-2 were then selected as the suitable reference gene primer pairs for sugarcane. The test of multi-target reference genes revealed that the APRT gene was a specific amplicon, suggesting this gene is the most suitable to be used as an endogenous reference target for sugarcane DNA content quantification. These results should be helpful for establishing accurate and reliable qualitative and quantitative PCR analysis of GM sugarcane.

  15. Quantification of protein copy number in single mitochondria: The Bcl-2 family proteins.

    Science.gov (United States)

    Chen, Chaoxiang; Zhang, Xiang; Zhang, Shuyue; Zhu, Shaobin; Xu, Jingyi; Zheng, Yan; Han, Jinyan; Zeng, Jin-Zhang; Yan, Xiaomei

    2015-12-15

    Bcl-2 family proteins, represented by antiapoptotic protein Bcl-2 and proapoptotic protein Bax, are key regulators of mitochondria-mediated apoptosis pathway. To build a quantitative model of how Bcl-2 family protein interactions control mitochondrial outer membrane permeabilization and subsequent cytochrome c release, it is essential to know the number of proteins in individual mitochondria. Here, we report an effective method to quantify the copy number and distribution of proteins in single mitochondria via immunofluorescent labeling and sensitive detection by a laboratory-built high sensitivity flow cytometer (HSFCM). Mitochondria isolated from HeLa cells were stained with Alexa Fluor 488 (AF488)-labeled monoclonal antibodies specifically targeting Bcl-2 or Bax and with nucleic acid dye. A series of fluorescent nanospheres with fluorescence intensity calibrated in the unit of molecules of equivalent soluble fluorochrome (MESF)-AF488 were used to construct a calibration curve for converting the immunofluorescence of a single mitochondrion to the number of antibodies bound to it and then to the number of proteins per mitochondrion. Under the normal condition, the measured mean copy numbers were 1300 and 220 per mitochondrion for Bcl-2 and Bax, respectively. A significant variation in protein copy number was identified, which ranged from 130 to 6000 (2.5-97.5%) for Bcl-2 and from 65 to 700 (2.5-97.5%) for Bax, respectively. We observed an approximately 4.4 fold increase of Bax copy number per mitochondrion upon 9h of apoptosis stimulation while the abundance of Bcl-2 remained almost unchanged. To the best of our knowledge, this is the first report of Bcl-2 family protein copy number and variance in single mitochondria. Collectively, we demonstrate that the HSFCM-based immunoassay provides a rapid and sensitive method for determining protein copy number distribution in single mitochondria. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Data analysis considerations for detecting copy number changes in formalin-fixed, paraffin-embedded tissues.

    Science.gov (United States)

    Jacobs, Sharoni

    2012-11-01

    The Whole Genome Sampling Analysis (WGSA) assay in combination with Affymetrix GeneChip Mapping Arrays is used for copy number analysis of high-quality DNA samples (i.e., samples that have been collected from blood, fresh or frozen tissue, or cell lines). Formalin-fixed, paraffin-embedded (FFPE) samples, however, represent the most prevalent form of archived clinical samples, but they provide additional challenges for molecular assays. FFPE processing usually results in the degradation of FFPE DNA and in the contamination and chemical modification of these DNA samples. In this article, we describe the steps needed to obtain reliable copy number predictions from degraded and contaminated FFPE samples.

  17. Juvenile Galápagos Pelicans Increase Their Foraging Success by Copying Adult Behaviour

    Science.gov (United States)

    Brumm, Henrik; Teschke, Irmgard

    2012-01-01

    Social learning is the building block of culture and traditions in humans and nonhuman animals, and its study has a long history. Most investigations have addressed either the causation or the function of social learning. Though much is known about the underlying mechanisms of social learning, demonstrations of its adaptive value in a natural setting are lacking. Here we show that juvenile brown pelicans (Pelecanus occidentalis) can increase their foraging efficiency by copying adult diving behaviour, suggesting that social learning helps juveniles to find profitable food patches. Our findings demonstrate the potential fitness consequences of behavioural copying and thus highlight the possible adaptive importance of social learning. PMID:23251646

  18. [The copy of De humani corporis fabrica of Andreas Vesalius of the municipal library of Reims].

    Science.gov (United States)

    Ségal, Alain

    2014-01-01

    The author presents a copy of the De humani corporis fabrica by Andreas Vesalius; this book is preserved in the department of rare books of the municipal Library in Reims. This copy is a first edition as the author gives positive proofs. This book results of a donation to the Minimes's congregation of Reims by Seigneur Guillaume Le Vergeur, Count of Saint Souplet and Baillif of Vermandois in the 17th century. Guillaume Le Vergeur has also given other precious books to the monastery's library and his name is inscribed on the register of obituaries and on the pediment of the Minimes' Church.

  19. Juvenile Galapagos pelicans increase their foraging success by copying adult behaviour.

    Directory of Open Access Journals (Sweden)

    Henrik Brumm

    Full Text Available Social learning is the building block of culture and traditions in humans and nonhuman animals, and its study has a long history. Most investigations have addressed either the causation or the function of social learning. Though much is known about the underlying mechanisms of social learning, demonstrations of its adaptive value in a natural setting are lacking. Here we show that juvenile brown pelicans (Pelecanus occidentalis can increase their foraging efficiency by copying adult diving behaviour, suggesting that social learning helps juveniles to find profitable food patches. Our findings demonstrate the potential fitness consequences of behavioural copying and thus highlight the possible adaptive importance of social learning.

  20. Topoisomerase I copy number alterations as biomarker for irinotecan efficacy in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Palshof, Jesper Andreas; Høgdall, Estrid Vilma Solyom; Poulsen, Tim Svenstrup

    2017-01-01

    Background No biomarker exists to guide the optimal choice of chemotherapy for patients with metastatic colorectal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients with metasta......Background No biomarker exists to guide the optimal choice of chemotherapy for patients with metastatic colorectal cancer. We examined the copy numbers (CN) of topoisomerase I (TOP1) as well as the ratios of TOP1/CEN-20 and TOP1/CEN-2 as biomarkers for irinotecan efficacy in patients...

  1. Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia

    Directory of Open Access Journals (Sweden)

    Wongsrichanalai Chansuda

    2009-01-01

    Full Text Available Abstract Background The combination of artesunate and mefloquine was introduced as the national first-line treatment for Plasmodium falciparum malaria in Cambodia in 2000. However, recent clinical trials performed at the Thai-Cambodian border have pointed to the declining efficacy of both artesunate-mefloquine and artemether-lumefantrine. Since pfmdr1 modulates susceptibility to mefloquine and artemisinin derivatives, the aim of this study was to assess the link between pfmdr1 copy number, in vitro susceptibility to individual drugs and treatment failure to combination therapy. Methods Blood samples were collected from P. falciparum-infected patients enrolled in two in vivo efficacy studies in north-western Cambodia: 135 patients were treated with artemether-lumefantrine (AL group in Sampovloun in 2002 and 2003, and 140 patients with artesunate-mefloquine (AM group in Sampovloun and Veal Veng in 2003 and 2004. At enrollment, the in vitro IC50 was tested and the strains were genotyped for pfmdr1 copy number by real-time PCR. Results The pfmdr1 copy number was analysed for 115 isolates in the AM group, and for 109 isolates in the AL group. Parasites with increased pfmdr1 copy number had significantly reduced in vitro susceptibility to mefloquine, lumefantrine and artesunate. There was no association between pfmdr1 polymorphisms and in vitro susceptibilities. In the patients treated with AM, the mean pfmdr1copy number was lower in subjects with adequate clinical and parasitological response compared to those who experienced late treatment failure (n = 112, p p = 0.364. The presence of three or more copies of pfmdr1 were associated with recrudescence in artesunate-mefloquine treated patients (hazard ratio (HR = 7.80 [95%CI: 2.09–29.10], N = 115, p = 0.002 but not with recrudescence in artemether-lumefantrine treated patients (HR = 1.03 [95%CI: 0.24–4.44], N = 109, p = 0.969. Conclusion This study shows that pfmdr1 copy number is a molecular

  2. Copy Number Variation Analysis by Array Analysis of Single Cells Following Whole Genome Amplification.

    Science.gov (United States)

    Dimitriadou, Eftychia; Zamani Esteki, Masoud; Vermeesch, Joris Robert

    2015-01-01

    Whole genome amplification is required to ensure the availability of sufficient material for copy number variation analysis of a genome deriving from an individual cell. Here, we describe the protocols we use for copy number variation analysis of non-fixed single cells by array-based approaches following single-cell isolation and whole genome amplification. We are focusing on two alternative protocols, an isothermal and a PCR-based whole genome amplification method, followed by either comparative genome hybridization (aCGH) or SNP array analysis, respectively.

  3. Importance of rare gene copy number alterations for personalized tumor characterization and survival analysis.

    Science.gov (United States)

    Seifert, Michael; Friedrich, Betty; Beyer, Andreas

    2016-10-03

    It has proven exceedingly difficult to ascertain rare copy number alterations (CNAs) that may have strong effects in individual tumors. We show that a regulatory network inferred from gene expression and gene copy number data of 768 human cancer cell lines can be used to quantify the impact of patient-specific CNAs on survival signature genes. A focused analysis of tumors from six tissues reveals that rare patient-specific gene CNAs often have stronger effects on signature genes than frequent gene CNAs. Further comparison to a related network-based approach shows that the integration of indirectly acting gene CNAs significantly improves the survival analysis.

  4. Viremia Copy-Years Predicts Mortality Among Treatment-Naive HIV-Infected Patients Initiating Antiretroviral Therapy

    Science.gov (United States)

    Napravnik, Sonia; Cole, Stephen R.; Eron, Joseph J.; Lau, Bryan; Crane, Heidi M.; Kitahata, Mari M.; Willig, James H.; Moore, Richard D.; Deeks, Steven G.; Saag, Michael S.

    2011-01-01

    Background. Cross-sectional plasma human immunodeficiency virus (HIV) viral load (VL) measures have proven invaluable for clinical and research purposes. However, cross-sectional VL measures fail to capture cumulative plasma HIV burden longitudinally. We evaluated the cumulative effect of exposure to HIV replication on mortality following initiation of combination antiretroviral therapy (ART). Methods. We included treatment-naive HIV-infected patients starting ART from 2000 to 2008 at 8 Center for AIDS Research Network of Integrated Clinical Systems sites. Viremia copy-years, a time-varying measure of cumulative plasma HIV exposure, were determined for each patient using the area under the VL curve. Multivariable Cox models were used to evaluate the independent association of viremia copy-years for all-cause mortality. Results. Among 2027 patients contributing 6579 person-years of follow-up, the median viremia copy-years was 5.3 log10 copy × y/mL (interquartile range: 4.9–6.3 log10 copy × y/mL), and 85 patients (4.2%) died. When evaluated separately, viremia copy-years (hazard ratio [HR] = 1.81 per log10 copy × y/mL; 95% confidence interval [CI], 1.51–2.18 per log10 copy × y/mL), 24-week VL (1.74 per log10 copies/mL; 95% CI, 1.48–2.04 per log10 copies/mL), and most recent VL (HR = 1.89 per log10 copies/mL; 95% CI: 1.63–2.20 per log10 copies/mL) were associated with increased mortality. When simultaneously evaluating VL measures and controlling for other covariates, viremia copy-years increased mortality risk (HR = 1.44 per log10 copy × y/mL; 95% CI, 1.07–1.94 per log10 copy × y/mL), whereas no cross-sectional VL measure was independently associated with mortality. Conclusions. Viremia copy-years predicted all-cause mortality independent of traditional, cross-sectional VL measures and time-updated CD4+ T-lymphocyte count in ART-treated patients, suggesting cumulative HIV replication causes harm independent of its effect on the degree of

  5. Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography

    NARCIS (Netherlands)

    Dudkina, Natalya V.; Kudryashev, Mikhail; Stahlberg, Henning; Boekema, Egbert J.

    2011-01-01

    The respirasome is a multisubunit supercomplex of the respiratory chain in mitochondria. Here we report the 3D reconstruction of the bovine heart respirasome, composed of dimeric complex III and single copies of complex I and IV, at about 2.2-nm resolution, determined by cryoelectron tomography and

  6. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  7. Phosphatidylinositol- and phosphatidylcholine-transfer activity of PITPβ is essential for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum

    Science.gov (United States)

    Carvou, Nicolas; Holic, Roman; Li, Michelle; Futter, Clare; Skippen, Alison; Cockcroft, Shamshad

    2010-01-01

    Vesicles formed by the COPI complex function in retrograde transport from the Golgi to the endoplasmic reticulum (ER). Phosphatidylinositol transfer protein β (PITPβ), an essential protein that possesses phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) lipid transfer activity is known to localise to the Golgi and ER but its role in these membrane systems is not clear. To examine the function of PITPβ at the Golgi-ER interface, RNA interference (RNAi) was used to knockdown PITPβ protein expression in HeLa cells. Depletion of PITPβ leads to a decrease in PtdIns(4)P levels, compaction of the Golgi complex and protection from brefeldin-A-mediated dispersal to the ER. Using specific transport assays, we show that anterograde traffic is unaffected but that KDEL-receptor-dependent retrograde traffic is inhibited. This phenotype can be rescued by expression of wild-type PITPβ but not by mutants defective in docking, PtdIns transfer and PtdCho transfer. These data demonstrate that the PtdIns and PtdCho exchange activity of PITPβ is essential for COPI-mediated retrograde transport from the Golgi to the ER. PMID:20332109

  8. Phosphatidylinositol- and phosphatidylcholine-transfer activity of PITPbeta is essential for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum.

    Science.gov (United States)

    Carvou, Nicolas; Holic, Roman; Li, Michelle; Futter, Clare; Skippen, Alison; Cockcroft, Shamshad

    2010-04-15

    Vesicles formed by the COPI complex function in retrograde transport from the Golgi to the endoplasmic reticulum (ER). Phosphatidylinositol transfer protein beta (PITPbeta), an essential protein that possesses phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) lipid transfer activity is known to localise to the Golgi and ER but its role in these membrane systems is not clear. To examine the function of PITPbeta at the Golgi-ER interface, RNA interference (RNAi) was used to knockdown PITPbeta protein expression in HeLa cells. Depletion of PITPbeta leads to a decrease in PtdIns(4)P levels, compaction of the Golgi complex and protection from brefeldin-A-mediated dispersal to the ER. Using specific transport assays, we show that anterograde traffic is unaffected but that KDEL-receptor-dependent retrograde traffic is inhibited. This phenotype can be rescued by expression of wild-type PITPbeta but not by mutants defective in docking, PtdIns transfer and PtdCho transfer. These data demonstrate that the PtdIns and PtdCho exchange activity of PITPbeta is essential for COPI-mediated retrograde transport from the Golgi to the ER.

  9. Engaging complexity

    Directory of Open Access Journals (Sweden)

    Gys M. Loubser

    2014-01-01

    Full Text Available In this article, I discuss studies in complexity and its epistemological implications for systematic and practical theology. I argue that engagement with complexity does not necessarily assurea non-reductionist approach. However, if complexity is engaged transversally, it becomes possible to transcend reductionist approaches. Moreover, systematic and practical the ologians can draw on complexity in developing new ways of understanding and, therefore, new ways of describing the focus, epistemic scope and heuristic structures of systematic and practical theology. Firstly, Edgar Morin draws a distinction between restricted and general complexity based on the epistemology drawn upon in studies in complexity. Moving away from foundationalist approaches to epistemology, Morin argues for a paradigm of systems. Secondly,I discuss Kees van Kooten Niekerk�s distinction between epistemology, methodology andontology in studies in complexity and offer an example of a theological argument that drawson complexity. Thirdly, I argue for the importance of transversality in engaging complexity by drawing on the work of Wentzel van Huyssteen and Paul Cilliers. In conclusion, I argue that theologians have to be conscious of the epistemic foundations of each study in complexity, and these studies illuminate the heart of Reformed theology.Intradisciplinary and/or interdisciplinary implications: Therefore, this article has both intradisciplinary and interdisciplinary implications. When theologians engage studies incomplexity, the epistemological roots of these studies need to be considered seeing thatresearchers in complexity draw on different epistemologies. Drawing on transversality wouldenhance such considerations. Furthermore, Edgar Morin�s and Paul Cilliers� approach tocomplexity will inform practical and theoretical considerations in church polity and unity.

  10. Effective Normalization for Copy Number Variation Detection from Whole Genome Sequencing

    NARCIS (Netherlands)

    Janevski, A.; Varadan, V.; Kamalakaran, S.; Banerjee, N.; Dimitrova, D.

    2012-01-01

    Background Whole genome sequencing enables a high resolution view ofthe human genome and provides unique insights into genome structureat an unprecedented scale. There have been a number of tools to infer copy number variation in the genome. These tools while validatedalso include a number of parame

  11. Whole-genome sequencing reveals the diversity of cattle copy number variations and multicopy genes

    Science.gov (United States)

    Structural and functional impacts of copy number variations (CNVs) on livestock genomes are not yet well understood. We identified 1853 CNV regions using population-scale sequencing data generated from 75 cattle representing 8 breeds (Angus, Brahman, Gir, Holstein, Jersey, Limousin, Nelore, Romagnol...

  12. Diversity and population-genetic properties of copy number variations and multicopy genes in cattle

    Science.gov (United States)

    The diversity and population-genetics of copy number variation (CNV) in domesticated animals are not well understood. In this study, we analyzed 75 genomes of major taurine and indicine cattle breeds (including Angus, Brahman, Gir, Holstein, Jersey, Limousin, Nelore, Romagnola), sequenced to 11-fold...

  13. Copy number variations of chromosome 16p13.1 region associated with schizophrenia

    NARCIS (Netherlands)

    Ingason, A.; Rujescu, D.; Cichon, S.; Sigurdsson, E.; Sigmundsson, T.; Pietilainen, O.P.H.; Buizer-Voskamp, J.E.; Strengman, E.; Francks, C.; Muglia, P.; Gylfason, A.; Gustafsson, O.; Olason, P.I.; Steinberg, S.; Hansen, T.; Jakobsen, K.D.; Rasmussen, H.B.; Giegling, I.; Moller, H.J.; Hartmann, A.; Crombie, C.; Fraser, G.; Walker, N.; Lonnqvist, J.; Suvisaari, J.; Tuulio-Henriksson, A.; Bramon, E.; Kiemeney, L.A.L.M.; Franke, B.; Murray, R.; Vassos, E.; Toulopoulou, T.; Muhleisen, T.W.; Tosato, S.; Ruggeri, M.; Djurovic, S.; Andreassen, O.A.; Zhang, Z.; Werge, T.; Ophoff, R.A.; Rietschel, M.; Nothen, M.M.; Petursson, H.; Stefansson, H.; Peltonen, L.; Collier, D.; Stefansson, K.; St Clair, D.M.

    2011-01-01

    Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 3

  14. Distribution of Disease-Associated Copy Number Variants across Distinct Disorders of Cognitive Development

    Science.gov (United States)

    Pescosolido, Matthew F.; Gamsiz, Ece D.; Nagpal, Shailender; Morrow, Eric M.

    2013-01-01

    Objective: The purpose of the present study was to discover the extent to which distinct "DSM" disorders share large, highly recurrent copy number variants (CNVs) as susceptibility factors. We also sought to identify gene mechanisms common to groups of diagnoses and/or specific to a given diagnosis based on associations with CNVs. Method:…

  15. Genome-Wide Analysis Shows Increased Frequency of Copy Number Variation Deletions in Dutch Schizophrenia Patients

    NARCIS (Netherlands)

    Buizer-Voskamp, Jacobine E.; Muntjewerff, Jan-Willem; Strengman, Eric; Sabatti, Chiara; Stefansson, Hreinn; Vorstman, Jacob A. S.; Ophoff, Roel A.; GROUP investigators, [No Value

    2011-01-01

    Background: Since 2008, multiple studies have reported on copy number variations (CNVs) in schizophrenia. However, many regions are unique events with minimal overlap between studies. This makes it difficult to gain a comprehensive overview of all CNVs involved in the etiology of schizophrenia. We p

  16. An Algorithm to Improve Test Answer Copying Detection Using the Omega Statistic

    Science.gov (United States)

    Maeda, Hotaka; Zhang, Bo

    2017-01-01

    The omega (?) statistic is reputed to be one of the best indices for detecting answer copying on multiple choice tests, but its performance relies on the accurate estimation of copier ability, which is challenging because responses from the copiers may have been contaminated. We propose an algorithm that aims to identify and delete the suspected…

  17. 77 FR 27125 - Periodicals-Recognition of Distribution of Periodicals via Electronic Copies

    Science.gov (United States)

    2012-05-09

    ... From the Federal Register Online via the Government Publishing Office POSTAL SERVICE 39 CFR Part 111 Periodicals--Recognition of Distribution of Periodicals via Electronic Copies AGENCY: Postal Service\\TM\\. ACTION: Final rule. SUMMARY: The Postal Service will revise the Mailing Standards of the...

  18. Differential effects of motor efference copies and proprioceptive information on response evaluation processes.

    Science.gov (United States)

    Stock, Ann-Kathrin; Wascher, Edmund; Beste, Christian

    2013-01-01

    It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response.

  19. 19 CFR 141.45 - Certified copies of power of attorney.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Certified copies of power of attorney. 141.45 Section 141.45 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... power of attorney. Upon request of a party in interest, a port director having on file an original...

  20. The Levy Runs Dry: A Legal and Economic Analysis of EU Private Copying Levies

    NARCIS (Netherlands)

    Poort, J.; Quintais, J.P.

    2013-01-01

    This article provides a legal and economic analysis of private copying levies in the EU, against the background of the Copyright Directive (2001/29), a number of recent rulings by the European Court of Justice and the recommendations presented by mediator Vitorino earlier this year. It concludes tha