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1

Strategies for exome and genome sequence data analysis in disease-gene discovery projects.  

PubMed

In whole-exome sequencing (WES), target capture methods are used to enrich the sequences of the coding regions of genes from fragmented total genomic DNA, followed by massively parallel, 'next-generation' sequencing of the captured fragments. Since its introduction in 2009, WES has been successfully used in several disease-gene discovery projects, but the analysis of whole-exome sequence data can be challenging. In this overview, we present a summary of the main computational strategies that have been applied to identify novel disease genes in whole-exome data, including intersect filters, the search for de novo mutations, and the application of linkage mapping or inference of identity-by-descent (IBD) in family studies. PMID:21615730

Robinson, Peter N; Krawitz, P; Mundlos, S

2011-06-13

2

Anopheles gambiae pilot gene discovery project: Identification of mosquito innate immunity genes from expressed sequence tags generated from immune-competent cell lines  

Microsoft Academic Search

Together with AIDS and tuberculosis, malaria is at the top of the list of devastating infectious diseases. However, molecular genetic studies of its major vector, Anopheles gambiae, are still quite limited. We have conducted a pilot gene discovery project to accelerate progress in the molecular analysis of vector biology, with emphasis on the mosquito's antimalarial immune defense. A total of

George Dimopoulos; Thomas L. Casavant; Shereen Chang; Todd Scheetz; Chad Roberts; Micca Donohue; Jörg Schultz; Vladimir Benes; Peer Bork; Wilhelm Ansorge; Marcelo Bento Soares; Fotis C. Kafatos

2000-01-01

3

Crystallography and the Gene Helix DiscoveryAn Interdisciplinary Educational Project  

Microsoft Academic Search

This interdisciplinary project was designed to give students of radiography and sonography a basic understanding of x-ray diffraction in crystallography, the dual nature of electromagnetic radiation, and the Human Genome Project. As a secondary result of the project, questions concerning the attribution and polemics of research publication arose, so this discussion is also included. This latter issue, involving Rosalind Franklin’s

Terry J. Dubose; Rebecca Ludwig

2003-01-01

4

Independent Gene Discovery and Testing  

ERIC Educational Resources Information Center

A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

2010-01-01

5

The Discovery Science Project in Japan  

Microsoft Academic Search

The Discovery Science project in Japan in which more than sixty scientists participated was a three-year project sponsored\\u000a by Grantin- Aid for Scientific Research on Priority Area from the Ministry of Education, Culture, Sports, Science and Technology\\u000a (MEXT) of Japan. This project mainly aimed to (1) develop new methods for knowledge discovery, (2) install network environments\\u000a for knowledge discovery, and

Setsuo Arikawa

2001-01-01

6

Project Discovery Revisited: Was It Worth It?  

ERIC Educational Resources Information Center

Twenty-one teachers and administrators from primary and secondary schools which participated in the 1964-67 large-scale national demonstration "Project Discovery" were interviewed to assess the long-term effects of saturation and immediate access of media. Results indicate positive and lasting effects on teaching, learning, and the school…

Taylor, William D.; DiPaolo, Anthony J.

1978-01-01

7

The Helioviewer Project: Discovery For Everyone Everywhere  

NASA Astrophysics Data System (ADS)

The Helioviewer Project: discovery for everyone everywhere There is an ever increasing amount of solar and heliospheric data gathered from multiple sources such as space-based facilities and ground based observatories. There are also multiple feature and event catalogs arising from human and computer based detection methods. The Helioviewer Project is developing a suite of technologies to allow users around the world to visualize, browse and access these heterogeneous datasets in an intuitive and highly customizable fashion. Helioviewer technologies are based on the JPEG2000 file format, an extremely flexible format that allows for the efficient transfer of data (and meta-data, such as FITS keywords) between client and server. Rather then having to download an entire image and then examine the small portion- for example, an active region - that you are interested in, the JPEG2000 file format lets you preferentially download only those portions you are interested in. This dramatically reduces the amount of data transferred, making possible responsive and flexible scientific discovery applications that can browse populous archives of large images, such as those from the Solar Dynamics Observatory. In addition, the Helioviewer Project is designed to be flexible and extensible to data sources as they become available. Helioviewer.org (www.helioviewer.org) works seamlessly with the Virtual Solar Observatory (VSO) whilst an application programming interface (API) is being developed for interaction with the Solar Dynamics Observatory Heliophysics Event Knowledgebase. After a short introduction to the underlying technology, a live demonstration of the web application www.helioviewer.org will be given. We will also comment on other client applications (Jhelioviewer, a Java-based browse tool), and the application of Helioviewer technology to existing and future solar and heliospheric data and feature/event repositories. This project is funded by NASA VxO and LWS awards and an ESA science award.

Ireland, Jack; Hughitt, K.; Müller, D.; Dimitoglou, G.; Schmiedel, P.; Fleck, B.

2009-05-01

8

Human brain evolution: from gene discovery to phenotype discovery.  

PubMed

The rise of comparative genomics and related technologies has added important new dimensions to the study of human evolution. Our knowledge of the genes that underwent expression changes or were targets of positive selection in human evolution is rapidly increasing, as is our knowledge of gene duplications, translocations, and deletions. It is now clear that the genetic differences between humans and chimpanzees are far more extensive than previously thought; their genomes are not 98% or 99% identical. Despite the rapid growth in our understanding of the evolution of the human genome, our understanding of the relationship between genetic changes and phenotypic changes is tenuous. This is true even for the most intensively studied gene, FOXP2, which underwent positive selection in the human terminal lineage and is thought to have played an important role in the evolution of human speech and language. In part, the difficulty of connecting genes to phenotypes reflects our generally poor knowledge of human phenotypic specializations, as well as the difficulty of interpreting the consequences of genetic changes in species that are not amenable to invasive research. On the positive side, investigations of FOXP2, along with genomewide surveys of gene-expression changes and selection-driven sequence changes, offer the opportunity for "phenotype discovery," providing clues to human phenotypic specializations that were previously unsuspected. What is more, at least some of the specializations that have been proposed are amenable to testing with noninvasive experimental techniques appropriate for the study of humans and apes. PMID:22723367

Preuss, Todd M

2012-06-20

9

Cancer gene discovery: exploiting insertional mutagenesis.  

PubMed

Insertional mutagenesis has been used as a functional forward genetics screen for the identification of novel genes involved in the pathogenesis of human cancers. Different insertional mutagens have been successfully used to reveal new cancer genes. For example, retroviruses are integrating viruses with the capacity to induce the deregulation of genes in the neighborhood of the insertion site. Retroviruses have been used for more than 30 years to identify cancer genes in the hematopoietic system and mammary gland. Similarly, another tool that has revolutionized cancer gene discovery is the cut-and-paste transposons. These DNA elements have been engineered to contain strong promoters and stop cassettes that may function to perturb gene expression upon integration proximal to genes. In addition, complex mouse models characterized by tissue-restricted activity of transposons have been developed to identify oncogenes and tumor suppressor genes that control the development of a wide range of solid tumor types, extending beyond those tissues accessible using retrovirus-based approaches. Most recently, lentiviral vectors have appeared on the scene for use in cancer gene screens. Lentiviral vectors are replication-defective integrating vectors that have the advantage of being able to infect nondividing cells, in a wide range of cell types and tissues. In this review, we describe the various insertional mutagens focusing on their advantages/limitations, and we discuss the new and promising tools that will improve the insertional mutagenesis screens of the future. Mol Cancer Res; 11(10); 1141-58. ©2013 AACR. PMID:23928056

Ranzani, Marco; Annunziato, Stefano; Adams, David J; Montini, Eugenio

2013-08-08

10

Virtual Cities ?? a Regional Discovery Project  

Microsoft Academic Search

This article illustrates how, during the ICEM Orlando Conference, children from Canada, Italy and the USA were brought together in the world's first Virtual Reality Satellite teleconference. (see p. 36) The ‘Virtual Cities’ project is described in detail.

Julie Stanfel

1993-01-01

11

Genome-enabled Discovery of Carbon Sequestration Genes  

SciTech Connect

The fate of carbon below ground is likely to be a major factor determining the success of carbon sequestration strategies involving plants. Despite their importance, molecular processes controlling belowground C allocation and partitioning are poorly understood. This project is leveraging the Populus trichocarpa genome sequence to discover genes important to C sequestration in plants and soils. The focus is on the identification of genes that provide key control points for the flow and chemical transformations of carbon in roots, concentrating on genes that control the synthesis of chemical forms of carbon that result in slower turnover rates of soil organic matter (i.e., increased recalcitrance). We propose to enhance carbon allocation and partitioning to roots by 1) modifying the auxin signaling pathway, and the invertase family, which controls sucrose metabolism, and by 2) increasing root proliferation through transgenesis with genes known to control fine root proliferation (e.g., ANT), 3) increasing the production of recalcitrant C metabolites by identifying genes controlling secondary C metabolism by a major mQTL-based gene discovery effort, and 4) increasing aboveground productivity by enhancing drought tolerance to achieve maximum C sequestration. This broad, integrated approach is aimed at ultimately enhancing root biomass as well as root detritus longevity, providing the best prospects for significant enhancement of belowground C sequestration.

Tuskan, Gerald A [ORNL; Tschaplinski, Timothy J [ORNL; Kalluri, Udaya C [ORNL; Yin, Tongming [ORNL; Yang, Xiaohan [ORNL; Zhang, Xinye [ORNL; Engle, Nancy L [ORNL; Ranjan, Priya [ORNL; Basu, Manojit M [ORNL; Gunter, Lee E [ORNL; Jawdy, Sara [ORNL; Martin, Madhavi Z [ORNL; Campbell, Alina S [ORNL; DiFazio, Stephen P [ORNL; Davis, John M [University of Florida; Hinchee, Maud [ORNL; Pinnacchio, Christa [U.S. Department of Energy, Joint Genome Institute; Meilan, R [Purdue University; Busov, V. [Michigan Technological University; Strauss, S [Oregon State University

2009-01-01

12

Gene Discovery Methods from Large-Scale Gene Expression Data  

NASA Astrophysics Data System (ADS)

Microarrays provide genome-wide gene expression changes. In current analyses, the majority of genes on the array are frequently eliminated for further analysis just in order for computational effort to be affordable. This strategy risks failure to discover whole sets of genes related to a quantitative trait of interest, which is generally controlled by several loci that might be eliminated in current approaches. Here, we describe a high-throughput gene discovery method based on correspondence analysis with a new index for expression ratios [arctan (1/ratio)] and three artificial marker genes. This method allows us to quickly analyze the whole microarray dataset without elimination and discover up/down-regulated genes related to a trait of interest. We employed an example dataset to show the theoretical advantage of this method. We then used the method to identify 88 cancer-related genes from a published microarray data from patients with breast cancer. This method can be easily performed and the result is also visible in three-dimensional viewing software that we have developed. Our method is useful for revaluating the wealth of microarray data available from web-sites.

Shimizu, Akifumi; Yano, Kentaro

2010-01-01

13

Class prediction and discovery using gene expression data  

Microsoft Academic Search

Classification of patient samples is a crucial aspect of cancer diagnosis and treatment. We present a method for classifying samples by computational analysis of gene expression data. We consider the classification problem in two parts: class discovery and class prediction. Class discovery refers to the process of dividing samples into reproducible classes that have similar behavior or properties, while class

Donna K. Slonim; Pablo Tamayo; Jill P. Mesirov; Todd R. Golub; Eric S. Lander

2000-01-01

14

Computational tools for prioritizing candidate genes: boosting disease gene discovery.  

PubMed

At different stages of any research project, molecular biologists need to choose - often somewhat arbitrarily, even after careful statistical data analysis - which genes or proteins to investigate further experimentally and which to leave out because of limited resources. Computational methods that integrate complex, heterogeneous data sets - such as expression data, sequence information, functional annotation and the biomedical literature - allow prioritizing genes for future study in a more informed way. Such methods can substantially increase the yield of downstream studies and are becoming invaluable to researchers. PMID:22751426

Moreau, Yves; Tranchevent, Léon-Charles

2012-07-03

15

Hereditary Hemochromatosis Since Discovery of the HFE Gene  

Microsoft Academic Search

Background: Hereditary hemochromatosis is an inher- ited disorder of iron metabolism that is characterized by excessive iron deposition in major organs of the body. Chronic increased iron absorption leads to multiorgan dysfunction. Since the discovery of the gene responsible for the majority of cases, research has progressed rapidly to identify the gene product, the effects of mutations, and the implications

Elaine Lyon; Elizabeth L. Frank

16

Genome-wide Approaches for Cancer Gene Discovery  

PubMed Central

One of the central aims of cancer research is to identify and characterize cancer-causing alterations in cancer genomes. In recent years, unprecedented advances in genome-wide sequencing, functional genomics technologies of RNA interference screens and methods to evaluate three-dimensional chromatin organization in vivo have resulted in important discoveries regarding human cancer. The cancer causing genes identified from these new genome-wide technologies have also provided opportunities for effective and personalized cancer therapy. In this review, we describe some of the most recent technologies for cancer gene discovery. We also provide specific examples where these technologies have proven remarkably successful in uncovering important cancer-causing alterations.

Lizardi, Paul M.; Forloni, Matteo; Wajapeyee, Narendra

2011-01-01

17

Discovery of the DISC1 Gene  

NSDL National Science Digital Library

Cytogenetics is the study of chromosomes and how changes in chromosome structure and number affect the individual. In this video, Professor Porteous describes the process of hunting for the DISC1 gene, a gene disrupted by a balanced translocation on chromosome 1q42.

2009-04-14

18

Discovery of genes expressed in Hydra embryogenesis.  

PubMed

Hydra's remarkable capacity to regenerate, to proliferate asexually by budding, and to form a pattern de novo from aggregates allows studying complex cellular and molecular processes typical for embryonic development. The underlying assumption is that patterning in adult hydra tissue relies on factors and genes which are active also during early embryogenesis. Previously, we reported that in Hydra the timing of expression of conserved regulatory genes, known to be involved in adult patterning, differs greatly in adults and embryos (Fröbius, A.C., Genikhovich, G., Kürn, U., Anton-Erxleben, F. and Bosch, T.C.G., 2003. Expression of developmental genes during early embryogenesis of Hydra. Dev. Genes Evol. 213, 445-455). Here, we describe an unbiased screening strategy to identify genes that are relevant to Hydra vulgaris embryogenesis. The approach yielded two sets of differentially expressed genes: one set was expressed exclusively or nearly exclusively in the embryos, while the second set was upregulated in embryos in comparison to adult polyps. Many of the genes identified in hydra embryos had no matches in the database. Among the conserved genes upregulated in embryos is the Hydra orthologue of Embryonic Ectoderm Development (HyEED). The expression pattern of HyEED in developing embryos suggests that interstitial stem cells in Hydra originate in the endoderm. Importantly, the observations uncover previously unknown differences in genes expressed by embryos and polyps and indicate that not only the timing of expression of developmental genes but also the genetic context is different in Hydra embryos compared to adults. PMID:16337937

Genikhovich, Grigory; Kürn, Ulrich; Hemmrich, Georg; Bosch, Thomas C G

2005-12-09

19

EST sequencing for gene discovery in Chinese hamster ovary cells  

Microsoft Academic Search

Chinese hamster ovary (CHO) cells are one of the most important cell lines in biological research, and are the most widely used host for industrial production of recombinant therapeutic proteins. Despite their extensive applications, little sequence information is available for molecular based research. To facilitate gene discovery and genetic engineering, two cDNA libraries were con- structed from three CHO cell

Katie Fraass Wlaschin; Peter Morin Nissom; Marcela de Leon Gatti; Peh Fern Ong; Sanny Arleen; Kher Shing Tan; Anette Rink; Breana Cham; Kathy Wong; Miranda Yap; Wei-Shou Hu

2005-01-01

20

Automated Discovery of Functional Generality of Human Gene Expression Programs  

Microsoft Academic Search

An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in

Georg K. Gerber; Robin D. Dowell; Tommi S. Jaakkola; David K. Gifford

2007-01-01

21

Rice Mutant Resources for Gene Discovery  

Microsoft Academic Search

With the completion of genomic sequencing of rice, rice has been firmly established as a model organism for both basic and applied research. The next challenge is to uncover the functions of genes predicted by sequence analysis. Considering the amount of effort and the diversity of disciplines required for functional analyses, extensive international collaboration is needed for this next goal.

Hirohiko Hirochika; Emmanuel Guiderdoni; Gynheung An; Yue-ie Hsing; Moo Young Eun; Chang-deok Han; Narayana Upadhyaya; Srinivasan Ramachandran; Qifa Zhang; Andy Pereira; Venkatesan Sundaresan; Hei Leung

2004-01-01

22

Novel venom gene discovery in the platypus  

Microsoft Academic Search

ABSTRACT: BACKGROUND: To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components. RESULTS: We identified 83 novel putative platypus venom genes from

Camilla M Whittington; Anthony T Papenfuss; Devin P Locke; Elaine R Mardis; Richard K Wilson; Sahar Abubucker; Makedonka Mitreva; Emily SW Wong; Arthur L Hsu; Philip W Kuchel; Katherine Belov; Wesley C Warren

2010-01-01

23

A Discovery Laboratory Investigating Bacterial Gene Regulation  

NSDL National Science Digital Library

This laboratory exercise introduces students to experimental design and gene regulation using different sugar ("food" sources) and an enzyme assay for beta-glalctosidase to identify different E. coli stains with respect to lac operon mutations, then designing their own experiments to study the various aspects of the lac operon.

Robert Moss (Wofford College;)

1999-01-01

24

Technology development for gene discovery and full-length sequencing  

SciTech Connect

In previous years, with support from the U.S. Department of Energy, we developed methods for construction of normalized and subtracted cDNA libraries, and constructed hundreds of high-quality libraries for production of Expressed Sequence Tags (ESTs). Our clones were made widely available to the scientific community through the IMAGE Consortium, and millions of ESTs were produced from our libraries either by collaborators or by our own sequencing laboratory at the University of Iowa. During this grant period, we focused on (1) the development of a method for preferential cloning of tissue-specific and/or rare transcripts, (2) its utilization to expedite EST-based gene discovery for the NIH Mouse Brain Molecular Anatomy Project, (3) further development and optimization of a method for construction of full-length-enriched cDNA libraries, and (4) modification of a plasmid vector to maximize efficiency of full-length cDNA sequencing by the transposon-mediated approach. It is noteworthy that the technology developed for preferential cloning of rare mRNAs enabled identification of over 2,000 mouse transcripts differentially expressed in the hippocampus. In addition, the method that we optimized for construction of full-length-enriched cDNA libraries was successfully utilized for the production of approximately fifty libraries from the developing mouse nervous system, from which over 2,500 full-ORF-containing cDNAs have been identified and accurately sequenced in their entirety either by our group or by the NIH-Mammalian Gene Collection Program Sequencing Team.

Marcelo Bento Soares

2004-07-19

25

The ROTSE Supernova Verification Project (RSVP): Status and Early Discoveries  

NASA Astrophysics Data System (ADS)

The goal of the ROTSE Supernova Verification Project is the discovery of nearby supernova shortly after shock breakout followed by multi-epoch spectral observations as the lightcurves evolve. The very early spectra effectively constrain the progenitor properties and explosion models, but only a few such observations exist for SN Ia. The sequence of spectral observations reveals deeper and deeper layers of the explosion over time that can be used to construct a detailed picture of the burning process. This program follows the concept of the Texas Supernova Search initiated and executed successfully by Robert Quimby using ROTSE-IIIb at McDonald Observatory. To enlarge the discovery rate, we have developed image subtraction code to be installed on all four ROTSE-III telescopes. By monitoring selected fields nightly to a typical limiting magnitude of 18.5, ROTSE-III is able to discover a nearby supernova earlier than many similar searches. The expected discovery rate is 3 per month at one dedicated site. Since August 2007, our pipeline has been fully operational on ROTSE-IIIb and has discovered 5 supernovae, 3 of which we reported as ATELs and CBETs while the remaining two were found concurrently and reported by others. Among these, SN 2007if is a particularly interesting example of an apparent SN Ia involving the destruction of a super-Chandrasekhar mass system. Its spectrum closely matches that of SN 2003fg which was the first such case that has been observed. Our photometry data show a lightcurve that is a factor of 2 overluminous for a SN Ia, consistent with this interpretation. This work has been supported by NASA grants NNG-04WC41G and NNX-07AF02G.

Yuan, Fang; Akerlof, C.; Quimby, R.; Aretakis, J.; McKay, T.; Miller, J. M.; Rykoff, E. S.; Swan, H. F.; Wheeler, J. C.

2007-12-01

26

Gene-Based Marker Systems in Plants: High Throughput Approaches for Marker Discovery and Genotyping  

Microsoft Academic Search

\\u000a Development and application of molecular markers derived from genes, commonly called genic markers or sometimes functional\\u000a markers, is gaining momentum in plant genetics and breeding. Availability of large amount of sequence data coming from genome\\/transcriptome\\u000a sequencing projects as well as advent of next generation sequencing technologies together with advances in bioinformatics\\u000a tools, marker discovery is becoming cheaper and faster. The

Rajeev K Varshney

27

Context-driven discovery of gene cassettes in mobile integrons using a computational grammar  

Microsoft Academic Search

Background: Gene discovery algorithms typically examine sequence data for low level patterns. A novel method to computationally discover higher order DNA structures is presented, using a context sensitive grammar. The algorithm was applied to the discovery of gene cassettes associated with integrons. The discovery and annotation of antibiotic resistance genes in such cassettes is essential for effective monitoring of antibiotic

Guy Tsafnat; Enrico W. Coiera; Sally R. Partridge; Jaron Schaeffer; Jon R. Iredell

2009-01-01

28

Novel venom gene discovery in the platypus  

PubMed Central

Background To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components. Results We identified 83 novel putative platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of platypus envenomation. Conclusions This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom.

2010-01-01

29

Integrated analysis of gene expression by association rules discovery  

PubMed Central

Background Microarray technology is generating huge amounts of data about the expression level of thousands of genes, or even whole genomes, across different experimental conditions. To extract biological knowledge, and to fully understand such datasets, it is essential to include external biological information about genes and gene products to the analysis of expression data. However, most of the current approaches to analyze microarray datasets are mainly focused on the analysis of experimental data, and external biological information is incorporated as a posterior process. Results In this study we present a method for the integrative analysis of microarray data based on the Association Rules Discovery data mining technique. The approach integrates gene annotations and expression data to discover intrinsic associations among both data sources based on co-occurrence patterns. We applied the proposed methodology to the analysis of gene expression datasets in which genes were annotated with metabolic pathways, transcriptional regulators and Gene Ontology categories. Automatically extracted associations revealed significant relationships among these gene attributes and expression patterns, where many of them are clearly supported by recently reported work. Conclusion The integration of external biological information and gene expression data can provide insights about the biological processes associated to gene expression programs. In this paper we show that the proposed methodology is able to integrate multiple gene annotations and expression data in the same analytic framework and extract meaningful associations among heterogeneous sources of data. An implementation of the method is included in the Engene software package.

Carmona-Saez, Pedro; Chagoyen, Monica; Rodriguez, Andres; Trelles, Oswaldo; Carazo, Jose M; Pascual-Montano, Alberto

2006-01-01

30

Gene Discovery and Product Development for Grain Quality Traits  

NSDL National Science Digital Library

The composition of oils, proteins, and carbohydrates in seeds of corn, soybean, and other crops has been modified to produce grains with enhanced value. Both plant breeding and molecular technologies have been used to produce plants carrying the desired traits. Genomics-based strategies for gene discovery, coupled with high-throughput transformation processes and miniaturized, automated analytical and functionality assays, have accelerated the identification of product candidates. Molecular markerâÂÂbased breeding strategies have been used to accelerate the process of moving trait genes into high-yielding germplasm for commercialization. These products are being tested for applications in food, feed, and industrial markets.

Barbara Mazur (DuPont Agricultural Products Experimental Station;); Enno Krebers (DuPont Agricultural Products Experimental Station;); Scott Tingey (DuPont Agricultural Products Experimental Station;)

1999-07-16

31

A brief history of Alzheimer's disease gene discovery.  

PubMed

The rich and colorful history of gene discovery in Alzheimer's disease (AD) over the past three decades is as complex and heterogeneous as the disease, itself. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations inAPP, PSEN1, and PSEN2 are fully penetrant for early-onset (<60 years) familial AD, which represents <5% of AD. On the other hand, common gene polymorphisms, such as the 4 and 2 variants of the APOE gene, influence susceptibility for common (>95%) late-onset AD. These four genes account for 30-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of additional highly confirmed AD candidate genes. Here, I review the past, present, and future of attempts to elucidate the complex and heterogeneous genetic underpinnings of AD along with some of the unique events that made these discoveries possible. PMID:22986781

Tanzi, Rudolph E

2013-01-01

32

Discovery of a widely distributed toxin biosynthetic gene cluster  

PubMed Central

Bacteriocins represent a large family of ribosomally produced peptide antibiotics. Here we describe the discovery of a widely conserved biosynthetic gene cluster for the synthesis of thiazole and oxazole heterocycles on ribosomally produced peptides. These clusters encode a toxin precursor and all necessary proteins for toxin maturation and export. Using the toxin precursor peptide and heterocycle-forming synthetase proteins from the human pathogen Streptococcus pyogenes, we demonstrate the in vitro reconstitution of streptolysin S activity. We provide evidence that the synthetase enzymes, as predicted from our bioinformatics analysis, introduce heterocycles onto precursor peptides, thereby providing molecular insight into the chemical structure of streptolysin S. Furthermore, our studies reveal that the synthetase exhibits relaxed substrate specificity and modifies toxin precursors from both related and distant species. Given our findings, it is likely that the discovery of similar peptidic toxins will rapidly expand to existing and emerging genomes.

Lee, Shaun W.; Mitchell, Douglas A.; Markley, Andrew L.; Hensler, Mary E.; Gonzalez, David; Wohlrab, Aaron; Dorrestein, Pieter C.; Nizet, Victor; Dixon, Jack E.

2008-01-01

33

The emerging role for rat models in gene discovery  

PubMed Central

Rat models have been used for many decades to study physiological and pathophysiological mechanisms. Prior to the release of the rat genome and new technologies for targeting gene manipulation, the rat had been the underdog in the genomics era, despite the abundance of physiological data compared to the mouse. The overarching goal of biomedical research is to improve health and advance medical science. Translating human disease gene discovery and validation in the rat, through the use of emerging technologies and integrated tools and databases, is providing power to understand the genetics, environmental influences, and biology of disease. In this review, we will briefly outline the rat models, bioinformatic tools, and technologies that are changing the landscape of translational research. The strategies used to translate disease traits to genes to function, and ultimately, to improve human health will be discussed. Finally, our perspectives on how rat models will continue to positively impact biomedical research will be provided.

Dwinell, Melinda R.; Lazar, Jozef; Geurts, Aron M.

2011-01-01

34

Gene discovery and gene function assignment in filamentous fungi  

PubMed Central

Filamentous fungi are a large group of diverse and economically important microorganisms. Large-scale gene disruption strategies developed in budding yeast are not applicable to these organisms because of their larger genomes and lower rate of targeted integration (TI) during transformation. We developed transposon-arrayed gene knockouts (TAGKO) to discover genes and simultaneously create gene disruption cassettes for subsequent transformation and mutant analysis. Transposons carrying a bacterial and fungal drug resistance marker are used to mutagenize individual cosmids or entire libraries in vitro. Cosmids are annotated by DNA sequence analysis at the transposon insertion sites, and cosmid inserts are liberated to direct insertional mutagenesis events in the genome. Based on saturation analysis of a cosmid insert and insertions in a fungal cosmid library, we show that TAGKO can be used to rapidly identify and mutate genes. We further show that insertions can create alterations in gene expression, and we have used this approach to investigate an amino acid oxidation pathway in two important fungal phytopathogens.

Hamer, Lisbeth; Adachi, Kiichi; Montenegro-Chamorro, Maria V.; Tanzer, Matthew M.; Mahanty, Sanjoy K.; Lo, Clive; Tarpey, Rex W.; Skalchunes, Amy R.; Heiniger, Ryan W.; Frank, Sheryl A.; Darveaux, Blaise A.; Lampe, David J.; Slater, Ted M.; Ramamurthy, Lakshman; DeZwaan, Todd M.; Nelson, Grant H.; Shuster, Jeffrey R.; Woessner, Jeffrey; Hamer, John E.

2001-01-01

35

DiscoverySchool.com : Your Genes, Your Future  

NSDL National Science Digital Library

DiscoverSchool.com offers a lesson plan for 6-8th graders based on a Discovery Channel program Your Genes, Your Future. The lesson plan focuses on healthy behaviors rather than genetics as such, although some of the extension activities deal with genetics more directly. Students will review the benefits of eating well, exercising, and other healthy behaviors, as well as discuss the dangers of drugs, smoking, etc. Provided Web links will help students with in-class research, and educators will find useful teaching tools for creating worksheets, quizzes, and subject-specific puzzles.

2007-12-12

36

deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data  

Microsoft Academic Search

Gene fusions created by somatic genomic rearrangements are known to play an important role in the onset and development of some cancers, such as lymphomas and sarcomas. RNA-Seq (whole transcriptome shotgun sequencing) is proving to be a useful tool for the discovery of novel gene fusions in cancer transcriptomes. However, algorithmic methods for the discovery of gene fusions using RNA-Seq

Andrew McPherson; Fereydoun Hormozdiari; Abdalnasser Zayed; Ryan Giuliany; Gavin Ha; Mark G. F. Sun; Malachi Griffith; Alireza Heravi Moussavi; Janine Senz; Nataliya Melnyk; Marina Pacheco; Marco A. Marra; Martin Hirst; Torsten O. Nielsen; S. Cenk Sahinalp; David Huntsman; Sohrab P. Shah

2011-01-01

37

Sugarcane Functional Genomics: Gene Discovery for Agronomic Trait Development  

PubMed Central

Sugarcane is a highly productive crop used for centuries as the main source of sugar and recently to produce ethanol, a renewable bio-fuel energy source. There is increased interest in this crop due to the impending need to decrease fossil fuel usage. Sugarcane has a highly polyploid genome. Expressed sequence tag (EST) sequencing has significantly contributed to gene discovery and expression studies used to associate function with sugarcane genes. A significant amount of data exists on regulatory events controlling responses to herbivory, drought, and phosphate deficiency, which cause important constraints on yield and on endophytic bacteria, which are highly beneficial. The means to reduce drought, phosphate deficiency, and herbivory by the sugarcane borer have a negative impact on the environment. Improved tolerance for these constraints is being sought. Sugarcane's ability to accumulate sucrose up to 16% of its culm dry weight is a challenge for genetic manipulation. Genome-based technology such as cDNA microarray data indicates genes associated with sugar content that may be used to develop new varieties improved for sucrose content or for traits that restrict the expansion of the cultivated land. The genes can also be used as molecular markers of agronomic traits in traditional breeding programs.

Menossi, M.; Silva-Filho, M. C.; Vincentz, M.; Van-Sluys, M.-A.; Souza, G. M.

2008-01-01

38

Second-generation sequencing for gene discovery in the Brassicaceae.  

PubMed

The Brassicaceae contains the most diverse collection of agriculturally important crop species of all plant families. Yet, this is one of the few families that do not form functional symbiotic associations with mycorrhizal fungi in the soil for improved nutrient acquisition. The genes involved in this symbiosis were more recently recruited by legumes for symbiotic association with nitrogen-fixing rhizobia bacteria. This study applied second-generation sequencing (SGS) and analysis tools to discover that two such genes, NSP1 (Nodulation Signalling Pathway 1) and NSP2, remain conserved in diverse members of the Brassicaceae despite the absence of these symbioses. We demonstrate the utility of SGS data for the discovery of putative gene homologs and their analysis in complex polyploid crop genomes with little prior sequence information. Furthermore, we show how this data can be applied to enhance downstream reverse genetics analyses. We hypothesize that Brassica NSP genes may function in the root in other plant-microbe interaction pathways that were recruited for mycorrhizal and rhizobial symbioses during evolution. PMID:22765874

Hayward, Alice; Vighnesh, Guru; Delay, Christina; Samian, Mohd Rafizan; Manoli, Sahana; Stiller, Jiri; McKenzie, Megan; Edwards, David; Batley, Jacqueline

2012-08-01

39

Genome Enabled Discovery of Carbon Sequestration Genes in Poplar  

SciTech Connect

The goals of the S.H. Strauss laboratory portion of 'Genome-enabled discovery of carbon sequestration genes in poplar' are (1) to explore the functions of candidate genes using Populus transformation by inserting genes provided by Oakridge National Laboratory (ORNL) and the University of Florida (UF) into poplar; (2) to expand the poplar transformation toolkit by developing transformation methods for important genotypes; and (3) to allow induced expression, and efficient gene suppression, in roots and other tissues. As part of the transformation improvement effort, OSU developed transformation protocols for Populus trichocarpa 'Nisqually-1' clone and an early flowering P. alba clone, 6K10. Complete descriptions of the transformation systems were published (Ma et. al. 2004, Meilan et. al 2004). Twenty-one 'Nisqually-1' and 622 6K10 transgenic plants were generated. To identify root predominant promoters, a set of three promoters were tested for their tissue-specific expression patterns in poplar and in Arabidopsis as a model system. A novel gene, ET304, was identified by analyzing a collection of poplar enhancer trap lines generated at OSU (Filichkin et. al 2006a, 2006b). Other promoters include the pGgMT1 root-predominant promoter from Casuarina glauca and the pAtPIN2 promoter from Arabidopsis root specific PIN2 gene. OSU tested two induction systems, alcohol- and estrogen-inducible, in multiple poplar transgenics. Ethanol proved to be the more efficient when tested in tissue culture and greenhouse conditions. Two estrogen-inducible systems were evaluated in transgenic Populus, neither of which functioned reliably in tissue culture conditions. GATEWAY-compatible plant binary vectors were designed to compare the silencing efficiency of homologous (direct) RNAi vs. heterologous (transitive) RNAi inverted repeats. A set of genes was targeted for post transcriptional silencing in the model Arabidopsis system; these include the floral meristem identity gene (APETALA1 or AP1), auxin response factor gene (ETTIN), the gene encoding transcriptional factor of WD40 family (TRANSPARENTTESTAGLABRA1 or TTG1), and the auxin efflux carrier (PIN-FORMED2 or PIN2) gene. More than 220 transgenic lines of the 1st, 2nd and 3rd generations were analyzed for RNAi suppression phenotypes (Filichkin et. al., manuscript submitted). A total of 108 constructs were supplied by ORNL, UF and OSU and used to generate over 1,881 PCR verified transgenic Populus and over 300 PCR verified transgenic Arabidopsis events. The Populus transgenics alone required Agrobacterium co-cultivations of 124.406 explants.

Filichkin, Sergei; Etherington, Elizabeth; Ma, Caiping; Strauss, Steve

2007-02-22

40

Amyotrophic Lateral Sclerosis: An Emerging Era of Collaborative Gene Discovery  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS.

Gwinn, Katrina; Corriveau, Roderick A.; Mitsumoto, Hiroshi; Bednarz, Kate; Brown, Robert H.; Cudkowicz, Merit; Gordon, Paul H.; Hardy, John; Kasarskis, Edward J.; Kaufmann, Petra; Miller, Robert; Sorenson, Eric; Tandan, Rup; Traynor, Bryan J.; Nash, Josefina; Sherman, Alex; Mailman, Matthew D.; Ostell, James; Bruijn, Lucie; Cwik, Valerie; Rich, Stephen S.; Singleton, Andrew; Refolo, Larry; Andrews, Jaime; Zhang, Ran; Conwit, Robin; Keller, Margaret A.

2007-01-01

41

Gene expression endophenotypes: a novel approach for gene discovery in Alzheimer's disease  

PubMed Central

Uncovering the underlying genetic component of any disease is key to the understanding of its pathophysiology and may open new avenues for development of therapeutic strategies and biomarkers. In the past several years, there has been an explosion of genome-wide association studies (GWAS) resulting in the discovery of novel candidate genes conferring risk for complex diseases, including neurodegenerative diseases. Despite this success, there still remains a substantial genetic component for many complex traits and conditions that is unexplained by the GWAS findings. Additionally, in many cases, the mechanism of action of the newly discovered disease risk variants is not inherently obvious. Furthermore, a genetic region with multiple genes may be identified via GWAS, making it difficult to discern the true disease risk gene. Several alternative approaches are proposed to overcome these potential shortcomings of GWAS, including the use of quantitative, biologically relevant phenotypes. Gene expression levels represent an important class of endophenotypes. Genetic linkage and association studies that utilize gene expression levels as endophenotypes determined that the expression levels of many genes are under genetic influence. This led to the postulate that there may exist many genetic variants that confer disease risk via modifying gene expression levels. Results from the handful of genetic studies which assess gene expression level endophenotypes in conjunction with disease risk suggest that this combined phenotype approach may both increase the power for gene discovery and lead to an enhanced understanding of their mode of action. This review summarizes the evidence in support of gene expression levels as promising endophenotypes in the discovery and characterization of novel candidate genes for complex diseases, which may also represent a novel approach in the genetic studies of Alzheimer's and other neurodegenerative diseases.

2011-01-01

42

Terrorism Knowledge Discovery Project: A Knowledge Discovery Approach to Addressing the Threats of Terrorism  

Microsoft Academic Search

Ever since the 9-11 incident, the multidisciplinary field of terrorism has experienced tremendous growth. As the domain has benefited greatly from recent advances in information technologies, more complex and challeng- ing new issues have emerged from numerous counter-terrorism-related research communities as well as governments of all levels. In this paper, we describe an advanced knowledge discovery approach to addressing terrorism

Edna Reid; Jialun Qin; Wingyan Chung; Jennifer Jie Xu; Yilu Zhou; Robert P. Schumaker; Marc Sageman; Hsinchun Chen

2004-01-01

43

A New Omics Data Resource of Pleurocybellaporrigens for Gene Discovery  

PubMed Central

Background Pleurocybellaporrigens is a mushroom-forming fungus, which has been consumed as a traditional food in Japan. In 2004, 55 people were poisoned by eating the mushroom and 17 people among them died of acute encephalopathy. Since then, the Japanese government has been alerting Japanese people to take precautions against eating the P. porrigens mushroom. Unfortunately, despite efforts, the molecular mechanism of the encephalopathy remains elusive. The genome and transcriptome sequence data of P. porrigens and the related species, however, are not stored in the public database. To gain the omics data in P. porrigens, we sequenced genome and transcriptome of its fruiting bodies and mycelia by next generation sequencing. Methodology/Principal Findings Short read sequences of genomic DNAs and mRNAs in P. porrigens were generated by Illumina Genome Analyzer. Genome short reads were de novo assembled into scaffolds using Velvet. Comparisons of genome signatures among Agaricales showed that P. porrigens has a unique genome signature. Transcriptome sequences were assembled into contigs (unigenes). Biological functions of unigenes were predicted by Gene Ontology and KEGG pathway analyses. The majority of unigenes would be novel genes without significant counterparts in the public omics databases. Conclusions Functional analyses of unigenes present the existence of numerous novel genes in the basidiomycetes division. The results mean that the omics information such as genome, transcriptome and metabolome in basidiomycetes is short in the current databases. The large-scale omics information on P. porrigens, provided from this research, will give a new data resource for gene discovery in basidiomycetes.

Dohra, Hideo; Someya, Takumi; Takano, Tomoyuki; Harada, Kiyonori; Omae, Saori; Hirai, Hirofumi; Yano, Kentaro; Kawagishi, Hirokazu

2013-01-01

44

High-Throughput Gene Discovery in the Rat  

PubMed Central

The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3? ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ?50,000 rat UniGene clusters. We have identified, arrayed, and derived 5? ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI.

Scheetz, Todd E.; Laffin, Jennifer J.; Berger, Brian; Holte, Sara; Baumes, Susan A.; Brown, Robert; Chang, Shereen; Coco, Justin; Conklin, Jim; Crouch, Keith; Donohue, Micca; Doonan, Greg; Estes, Chris; Eyestone, Mari; Fishler, Katrina; Gardiner, Jack; Guo, Lankai; Johnson, Brad; Keppel, Catherine; Kreger, Rikki; Lebeck, Mark; Marcelino, Rudy; Miljkovich, Vladan; Perdue, Mindee; Qui, Ling; Rehmann, Joshua; Reiter, Rebecca S.; Rhoads, Bridgette; Schaefer, Kelly; Smith, Christina; Sunjevaric, Ivana; Trout, Kurtis; Wu, Ning; Birkett, Clayton L.; Bischof, Jared; Gackle, Barry; Gavin, Allen; Grundstad, A. Jason; Mokrzycki, Brian; Moressi, Chris; O'Leary, Brian; Pedretti, Kevin; Roberts, Chad; Robinson, Natalie L.; Smith, Michael; Tack, Dylan; Trivedi, Nishank; Kucaba, Tamara; Freeman, Tom; Lin, Jim J.-C.; Bonaldo, Maria F.; Casavant, Thomas L.; Sheffield, Val C.; Soares, M. Bento

2004-01-01

45

Gene Discovery through Expressed Sequence Tag Sequencing in Trypanosoma cruzi  

PubMed Central

Analysis of expressed sequence tags (ESTs) constitutes a useful approach for gene identification that, in the case of human pathogens, might result in the identification of new targets for chemotherapy and vaccine development. As part of the Trypanosoma cruzi genome project, we have partially sequenced the 5? ends of 1,949 clones to generate ESTs. The clones were randomly selected from a normalized CL Brener epimastigote cDNA library. A total of 14.6% of the clones were homologous to previously identified T. cruzi genes, while 18.4% had significant matches to genes from other organisms in the database. A total of 67% of the ESTs had no matches in the database, and thus, some of them might be T. cruzi-specific genes. Functional groups of those sequences with matches in the database were constructed according to their putative biological functions. The two largest categories were protein synthesis (23.3%) and cell surface molecules (10.8%). The information reported in this paper should be useful for researchers in the field to analyze genes and proteins of their own interest.

Verdun, Ramiro E.; Di Paolo, Nelson; Urmenyi, Turan P.; Rondinelli, Edson; Frasch, Alberto C. C.; Sanchez, Daniel O.

1998-01-01

46

Gene expression endophenotypes: a novel approach for gene discovery in Alzheimer's disease  

Microsoft Academic Search

Uncovering the underlying genetic component of any disease is key to the understanding of its pathophysiology and may open\\u000a new avenues for development of therapeutic strategies and biomarkers. In the past several years, there has been an explosion\\u000a of genome-wide association studies (GWAS) resulting in the discovery of novel candidate genes conferring risk for complex\\u000a diseases, including neurodegenerative diseases. Despite

Nilüfer Ertekin-Taner

2011-01-01

47

The discovery of the microphthalmia locus and its gene, Mitf  

PubMed Central

Summary The history of the discovery of the microphthalmia locus and its gene, now called Mitf, is a testament to the triumph of serendipity. Although the first microphthalmia mutation was discovered among the descendants of a mouse that was irradiated for the purpose of mutagenesis, the mutation most likely was not radiation-induced but occurred spontaneously in one of the parents of a later breeding. Although Mitf might eventually have been identified by other molecular genetic techniques, it was first cloned from a chance transgene insertion at the microphthalmia locus. And although Mitf was found to encode a member of a well-known transcription factor family, its analysis might still be in its infancy had Mitf not turned out to be of crucial importance for the physiology and pathology of many distinct organs, including eye, ear, immune system, bone, and skin, and in particular for melanoma. In fact, near seven decades of Mitf research have led to many insights about development, function, degeneration, and malignancies of a number of specific cell types, and it is hoped that these insights will one day lead to therapies benefitting those afflicted with diseases originating in these cell types.

Arnheiter, Heinz

2010-01-01

48

Chromosome substitution strains: gene discovery, functional analysis, and systems studies.  

PubMed

Laboratory mice are valuable in biomedical research in part because of the extraordinary diversity of genetic resources that are available for studies of complex genetic traits and as models for human biology and disease. Chromosome substitution strains (CSSs) are important in this resource portfolio because of their demonstrated use for gene discovery, genetic and epigenetic studies, functional characterizations, and systems analysis. CSSs are made by replacing a single chromosome in a host strain with the corresponding chromosome from a donor strain. A complete CSS panel involves a total of 22 engineered inbred strains, one for each of the 19 autosomes, one each for the X and Y chromosomes, and one for mitochondria. A genome survey simply involves comparing each phenotype for each of the CSSs with the phenotypes of the host strain. The CSS panels that are available for laboratory mice have been used to dissect a remarkable variety of phenotypes and to characterize an impressive array of disease models. These surveys have revealed considerable phenotypic diversity even among closely related progenitor strains, evidence for strong epistasis and for heritable epigenetic changes. Perhaps most importantly, and presumably because of their unique genetic constitution, CSSs, and congenic strains derived from them, the genetic variants underlying quantitative trait loci (QTLs) are readily identified and functionally characterized. Together these studies show that CSSs are important resource for laboratory mice. PMID:22961226

Nadeau, Joseph H; Forejt, Jiri; Takada, Toyoyuki; Shiroishi, Toshihiko

2012-09-08

49

The discovery of the microphthalmia locus and its gene, Mitf.  

PubMed

The history of the discovery of the microphthalmia locus and its gene, now called Mitf, is a testament to the triumph of serendipity. Although the first microphthalmia mutation was discovered among the descendants of a mouse that was irradiated for the purpose of mutagenesis, the mutation most likely was not radiation induced but occurred spontaneously in one of the parents of a later breeding. Although Mitf might eventually have been identified by other molecular genetic techniques, it was first cloned from a chance transgene insertion at the microphthalmia locus. And although Mitf was found to encode a member of a well-known transcription factor family, its analysis might still be in its infancy had Mitf not turned out to be of crucial importance for the physiology and pathology of many distinct organs, including eye, ear, immune system, bone, and skin, and in particular for melanoma. In fact, near seven decades of Mitf research have led to many insights about development, function, degeneration, and malignancies of a number of specific cell types, and it is hoped that these insights will one day lead to therapies benefitting those afflicted with diseases originating in these cell types. PMID:20807369

Arnheiter, Heinz

2010-09-02

50

Discovery Learning and Cognitive Development--The UKU Project.  

ERIC Educational Resources Information Center

Prompted by pupil dissatisfaction and indifference, an experimental scheme of modified working routines involving approximately 500 pupils and 40 teachers was conducted in senior level classes in the Municipality of Ockero between 1976 and 1981. The purpose of the project was to transform the everyday life of school and to devise methods for…

Marklund, Inger, Ed.

1985-01-01

51

A projection and density estimation method for knowledge discovery.  

PubMed

A key ingredient to modern data analysis is probability density estimation. However, it is well known that the curse of dimensionality prevents a proper estimation of densities in high dimensions. The problem is typically circumvented by using a fixed set of assumptions about the data, e.g., by assuming partial independence of features, data on a manifold or a customized kernel. These fixed assumptions limit the applicability of a method. In this paper we propose a framework that uses a flexible set of assumptions instead. It allows to tailor a model to various problems by means of 1d-decompositions. The approach achieves a fast runtime and is not limited by the curse of dimensionality as all estimations are performed in 1d-space. The wide range of applications is demonstrated at two very different real world examples. The first is a data mining software that allows the fully automatic discovery of patterns. The software is publicly available for evaluation. As a second example an image segmentation method is realized. It achieves state of the art performance on a benchmark dataset although it uses only a fraction of the training data and very simple features. PMID:23049675

Stanski, Adam; Hellwich, Olaf

2012-10-01

52

Gene Discovery by EST Sequencing in Toxoplasma gondii Reveals Sequences Restricted to the Apicomplexa  

Microsoft Academic Search

To accelerate gene discovery and facilitate genetic mapping in the protozoan parasite Toxoplasma gondii, we have generated >7000 new ESTs from the 58 ends of randomly selected tachyzoite cDNAs. Comparison of the ESTs with the existing gene databases identified possible functions for more than 500 new T. gondii genes by virtue of sequence motifs shared with conserved protein families, including

James W. Ajioka; John C. Boothroyd; Brian P. Brunk; Adrian Hehl; Ledeana Hillier; Ian D. Manger; Marco Marra; G. Christian Overton; David S. Roos; Kiew-Lian Wan; Robert Waterston; L. David Sibley

1998-01-01

53

Project Self Discovery: Its Effects on Bright Underachievers at Nine Florida High Schools.  

ERIC Educational Resources Information Center

Project Self Discovery, an experimental program, sought to promote the social and personal development of bright underachieving students in nine Florida high schools. Prepared and evaluated were 12 discrete but interrelated chapters (units) offering readings and written exercises. These independent study units were concerned with such topics as…

Purkey, William Watson

54

An XML infrastructure for archives, libraries and museums: resource discovery in the COVAX project  

Microsoft Academic Search

Although the idea of collaborative distributed resource discovery systems in libraries, museums and archives is not new, XML (extensible markup language) offers a new technical basis for development. Contemporary Culture Virtual Archive in XML (COVAX) is a project that has used XML to build ‘’middleware” that enables integrated searches via the Web for materials held in libraries, archives and museums,

Robin Yeates

2002-01-01

55

Progress and Key Projects of the Discovery Channel Telescope at Lowell Observatory  

NASA Astrophysics Data System (ADS)

The Discovery Channel Telescope (DCT) is a 4.2-m instrument under construction 35 miles southeast of Flagstaff, Arizona. All first light components of the telescope are actively being worked, with commissioning scheduled for early 2011. Planned first generation instruments include an imager, IR spectrograph, and optical spectrograph at the RC focus. The design also provides for observations at prime and Nasmyth foci. Research and results from the telescope will be widely disseminated through Lowell Observatory's partnership with Discovery Communications. I will describe the design and construction status of the telescope, as well as the key projects identified for the initial science operations.

Hall, Jeffrey C.; Smith, B.; Chylek, T.; DeGroff, B.; Lotz, P.; Venetiou, A. J.; Westcott, K.; Bida, T.; Dunham, E. W.; Zoonematkermani, S.; Collins, P.; Millis, R. L.

2009-01-01

56

A Hybrid Approach for Biomarker Discovery from Microarray Gene Expression Data for Cancer Classification  

PubMed Central

Microarrays allow researchers to monitor the gene expression patterns for tens of thousands of genes across a wide range of cellular responses, phenotype and conditions. Selecting a small subset of discriminate genes from thousands of genes is important for accurate classification of diseases and phenotypes. Many methods have been proposed to find subsets of genes with maximum relevance and minimum redundancy, which can distinguish accurately between samples with different labels. To find the minimum subset of relevant genes is often referred as biomarker discovery. Two main approaches, filter and wrapper techniques, have been applied to biomarker discovery. In this paper, we conducted a comparative study of different biomarker discovery methods, including six filter methods and three wrapper methods. We then proposed a hybrid approach, FR-Wrapper, for biomarker discovery. The aim of this approach is to find an optimum balance between the precision of the biomarker discovery and the computation cost, by taking advantages of both filter method’s efficiency and wrapper method’s high accuracy. Our hybrid approach applies Fisher’s ratio, a simple method easy to understand and implement, to filter out most of the irrelevant genes, then a wrapper method is employed to reduce the redundancy. The performance of FR-Wrapper approach is evaluated over four widely used microarray datasets. Analysis of experimental results reveals that the hybrid approach can achieve the goal of maximum relevance with minimum redundancy.

Peng, Yanxiong; Li, Wenyuan; Liu, Ying

2007-01-01

57

Identifying differentially expressed genes using false discovery rate controlling procedures  

Microsoft Academic Search

Motivation: DNA microarrays have recently been used for the purpose of monitoring expression levels of thousands of genes simultaneously and identifying those genes that are differentially expressed. The probability that a false identification (type I error) is committed can increase sharply when the number of tested genes gets large. Correlation between the test statistics attributed to gene co-regulation and dependency

Anat Reiner; Daniel Yekutieli; Yoav Benjamini

2003-01-01

58

A Rule-Based Framework for Gene Regulation Pathways Discovery  

SciTech Connect

We present novel approach to discover the rules that govern gene regulation mechanisms. The method is based on supervised machine learning and is designed to reveal relationships between transcription factors and gene promoters. As the representation of the gene regulatory circuit we have chosen a special form of IF-THEN rules associating certain features (a generalized idea of a Transcription Factor Binding Site) in gene promoters with specific gene expression profiles.

Wilczynski, B; Hvidsten, T; Kryshtafovych, A; Stubbs, L; Komorowski, J; Fidelis, K

2003-07-21

59

Integrated analysis of gene expression by association rules discovery  

Microsoft Academic Search

Background: Microarray technology is generating huge amounts of data about the expression level of thousands of genes, or even whole genomes, across different experimental conditions. To extract biological knowledge, and to fully understand such datasets, it is essential to include external biological information about genes and gene products to the analysis of expression data. However, most of the current approaches

Pedro Carmona-saez; Monica Chagoyen; Andrés Rodríguez; Oswaldo Trelles; José María Carazo; Alberto D. Pascual-montano

2006-01-01

60

Discovery of mammalian genes that participate in virus infection  

PubMed Central

Background Viruses are obligate intracellular parasites that rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. Results Candidate genes required for lytic reovirus infection were identified by tagged sequence mutagenesis, a process that permits rapid identification of genes disrupted by gene entrapment. One hundred fifty-one reovirus resistant clones were selected from cell libraries containing 2 × 105 independently disrupted genes, of which 111 contained mutations in previously characterized genes and functionally anonymous transcription units. Collectively, the genes associated with reovirus resistance differed from genes targeted by random gene entrapment in that known mutational hot spots were under represented, and a number of mutations appeared to cluster around specific cellular processes, including: IGF-II expression/signalling, vesicular transport/cytoskeletal trafficking and apoptosis. Notably, several of the genes have been directly implicated in the replication of reovirus and other viruses at different steps in the viral lifecycle. Conclusions Tagged sequence mutagenesis provides a rapid, genome-wide strategy to identify candidate cellular genes required for virus infection. The candidate genes provide a starting point for mechanistic studies of cellular processes that participate in the virus lifecycle and may provide targets for novel anti-viral therapies.

Organ, Edward L; Sheng, Jinsong; Ruley, H Earl; Rubin, Donald H

2004-01-01

61

Computational method for discovery of estrogen responsive genes  

PubMed Central

Estrogen has a profound impact on human physiology and affects numerous genes. The classical estrogen reaction is mediated by its receptors (ERs), which bind to the estrogen response elements (EREs) in target gene's promoter region. Due to tedious and expensive experiments, a limited number of human genes are functionally well characterized. It is still unclear how many and which human genes respond to estrogen treatment. We propose a simple, economic, yet effective computational method to predict a subclass of estrogen responsive genes. Our method relies on the similarity of ERE frames across different promoters in the human genome. Matching ERE frames of a test set of 60 known estrogen responsive genes to the collection of over 18?000 human promoters, we obtained 604 candidate genes. Evaluating our result by comparison with the published microarray data and literature, we found that more than half (53.6%, 324/604) of predicted candidate genes are responsive to estrogen. We believe this method can significantly reduce the number of testing potential estrogen target genes and provide functional clues for annotating part of genes that lack functional information.

Tang, Suisheng; Tan, Sin Lam; Ramadoss, Suresh Kumar; Kumar, Arun Prashanth; Tang, Man-Hung Eric; Bajic, Vladimir B.

2004-01-01

62

Speeding disease gene discovery by sequence based candidate prioritization  

Microsoft Academic Search

BACKGROUND: Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation to knowledge of the disease or phenotype in question. However, here we show that disease genes share patterns of sequence-based features that can provide a good basis for automatic prioritization

Euan A. Adie; Richard R. Adams; Kathryn L. Evans; David J. Porteous; Ben S. Pickard

2005-01-01

63

Discovery of Gene Expression Patterns across Multiple Cancer Types  

Microsoft Academic Search

In this paper, we investigate the underlying common gene expression signatures in related cancer types. Shared expression signatures are investigated in breast and ovarian cancers specifically through the definition of four progressively more difficult classification problems. SHEBA, a stochastic Bayesian inference approach, is introduced to identify highly predictive gene sets in the defined classification problems. The heuristics reduce the computation

Cheryl Chan; Parvin Mousavi

2005-01-01

64

Discovery of mammalian genes that participate in virus infection  

Microsoft Academic Search

BACKGROUND: Viruses are obligate intracellular parasites that rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and\\/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. RESULTS: Candidate genes required for lytic reovirus infection were identified by tagged

Edward L Organ; Jinsong Sheng; H Earl Ruley; Donald H Rubin

2004-01-01

65

Discovery of cationic polymers for non-viral gene delivery using combinatorial approaches.  

PubMed

Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141

Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal

2011-12-01

66

Apolipoprotein L gene family: tissue-specific expression, splicing, promoter regions; discovery of a new gene  

Microsoft Academic Search

Previously we identified and cloned the cDNA for a new protein, apolipoprotein L (apoL), present in plasma and mainly associated with large high density lipo- protein particles. Using 5 9 rapid amplification of cDNA ends, RT-PCR and comparison with three Human Genome Project and three expressed sequence tag sequences, we have characterized the gene for apoL and for three addi-

Philippe N. Duchateau; Clive R. Pullinger; Min H. Cho; Celeste Eng; John P. Kane

67

Literature mining for the discovery of hidden connections between drugs, genes and diseases.  

PubMed

The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs. PMID:20885778

Frijters, Raoul; van Vugt, Marianne; Smeets, Ruben; van Schaik, René; de Vlieg, Jacob; Alkema, Wynand

2010-09-23

68

Literature Mining for the Discovery of Hidden Connections between Drugs, Genes and Diseases  

PubMed Central

The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs.

Frijters, Raoul; van Vugt, Marianne; Smeets, Ruben; van Schaik, Rene; de Vlieg, Jacob; Alkema, Wynand

2010-01-01

69

Gene Expression Arrays in Pancreatic Cancer Drug Discovery Research  

Microsoft Academic Search

\\u000a The development of gene expression arrays to simultaneously quantify the expression of thousands of genes has been a leap\\u000a forward in our attempt to understand the biology of pancreatic cancer in a variety of contexts. When combined with supervised\\u000a and unsupervised interrogations using complex mathematical algorithms, researchers have been able to unveil specific molecular\\u000a features of subsets of tumors. This

Charles Gawad

70

Tissue Compartment Analysis for Biomarker Discovery by Gene Expression Profiling  

Microsoft Academic Search

BackgroundAlthough high throughput technologies for gene profiling are reliable tools, sample\\/tissue heterogeneity limits their outcomes when applied to identify molecular markers. Indeed, inter-sample differences in cell composition contribute to scatter the data, preventing detection of small but relevant changes in gene expression level. To date, attempts to circumvent this difficulty were based on isolation of the different cell structures constituting

Antoine Disset; Lydie Cheval; Olga Soutourina; Jean-Paul Duong van Huyen; Guorong Li; Christian Genin; Jacques Tostain; Alexandre Loupy; Alain Doucet; Rabary Rajerison; Ulrich Zanger

2009-01-01

71

Gene Discovery through Genomic Sequencing of Brucella abortus  

PubMed Central

Brucella abortus is the etiological agent of brucellosis, a disease that affects bovines and human. We generated DNA random sequences from the genome of B. abortus strain 2308 in order to characterize molecular targets that might be useful for developing immunological or chemotherapeutic strategies against this pathogen. The partial sequencing of 1,899 clones allowed the identification of 1,199 genomic sequence surveys (GSSs) with high homology (BLAST expect value < 10?5) to sequences deposited in the GenBank databases. Among them, 925 represent putative novel genes for the Brucella genus. Out of 925 nonredundant GSSs, 470 were classified in 15 categories based on cellular function. Seven hundred GSSs showed no significant database matches and remain available for further studies in order to identify their function. A high number of GSSs with homology to Agrobacterium tumefaciens and Rhizobium meliloti proteins were observed, thus confirming their close phylogenetic relationship. Among them, several GSSs showed high similarity with genes related to nodule nitrogen fixation, synthesis of nod factors, nodulation protein symbiotic plasmid, and nodule bacteroid differentiation. We have also identified several B. abortus homologs of virulence and pathogenesis genes from other pathogens, including a homolog to both the Shda gene from Salmonella enterica serovar Typhimurium and the AidA-1 gene from Escherichia coli. Other GSSs displayed significant homologies to genes encoding components of the type III and type IV secretion machineries, suggesting that Brucella might also have an active type III secretion machinery.

Sanchez, Daniel O.; Zandomeni, Ruben O.; Cravero, Silvio; Verdun, Ramiro E.; Pierrou, Ester; Faccio, Paula; Diaz, Gabriela; Lanzavecchia, Silvia; Aguero, Fernan; Frasch, Alberto C. C.; Andersson, Siv G. E.; Rossetti, Osvaldo L.; Grau, Oscar; Ugalde, Rodolfo A.

2001-01-01

72

GENOME-ENABLED DISCOVERY OF CARBON SEQUESTRATION GENES IN POPLAR  

SciTech Connect

Plants utilize carbon by partitioning the reduced carbon obtained through photosynthesis into different compartments and into different chemistries within a cell and subsequently allocating such carbon to sink tissues throughout the plant. Since the phytohormones auxin and cytokinin are known to influence sink strength in tissues such as roots (Skoog & Miller 1957, Nordstrom et al. 2004), we hypothesized that altering the expression of genes that regulate auxin-mediated (e.g., AUX/IAA or ARF transcription factors) or cytokinin-mediated (e.g., RR transcription factors) control of root growth and development would impact carbon allocation and partitioning belowground (Fig. 1 - Renewal Proposal). Specifically, the ARF, AUX/IAA and RR transcription factor gene families mediate the effects of the growth regulators auxin and cytokinin on cell expansion, cell division and differentiation into root primordia. Invertases (IVR), whose transcript abundance is enhanced by both auxin and cytokinin, are critical components of carbon movement and therefore of carbon allocation. Thus, we initiated comparative genomic studies to identify the AUX/IAA, ARF, RR and IVR gene families in the Populus genome that could impact carbon allocation and partitioning. Bioinformatics searches using Arabidopsis gene sequences as queries identified regions with high degrees of sequence similarities in the Populus genome. These Populus sequences formed the basis of our transgenic experiments. Transgenic modification of gene expression involving members of these gene families was hypothesized to have profound effects on carbon allocation and partitioning.

DAVIS J M

2007-10-11

73

Gene discovery in the horned beetle Onthophagus taurus  

PubMed Central

Background Horned beetles, in particular in the genus Onthophagus, are important models for studies on sexual selection, biological radiations, the origin of novel traits, developmental plasticity, biocontrol, conservation, and forensic biology. Despite their growing prominence as models for studying both basic and applied questions in biology, little genomic or transcriptomic data are available for this genus. We used massively parallel pyrosequencing (Roche 454-FLX platform) to produce a comprehensive EST dataset for the horned beetle Onthophagus taurus. To maximize sequence diversity, we pooled RNA extracted from a normalized library encompassing diverse developmental stages and both sexes. Results We used 454 pyrosequencing to sequence ESTs from all post-embryonic stages of O. taurus. Approximately 1.36 million reads assembled into 50,080 non-redundant sequences encompassing a total of 26.5 Mbp. The non-redundant sequences match over half of the genes in Tribolium castaneum, the most closely related species with a sequenced genome. Analyses of Gene Ontology annotations and biochemical pathways indicate that the O. taurus sequences reflect a wide and representative sampling of biological functions and biochemical processes. An analysis of sequence polymorphisms revealed that SNP frequency was negatively related to overall expression level and the number of tissue types in which a given gene is expressed. The most variable genes were enriched for a limited number of GO annotations whereas the least variable genes were enriched for a wide range of GO terms directly related to fitness. Conclusions This study provides the first large-scale EST database for horned beetles, a much-needed resource for advancing the study of these organisms. Furthermore, we identified instances of gene duplications and alternative splicing, useful for future study of gene regulation, and a large number of SNP markers that could be used in population-genetic studies of O. taurus and possibly other horned beetles.

2010-01-01

74

Designing and Developing a NASA Research Projects Knowledge Base and Implementing Knowledge Management and Discovery Techniques  

NASA Astrophysics Data System (ADS)

The Research Project Knowledge Base (RPKB) is currently being designed and will be implemented in a manner that is fully compatible and interoperable with enterprise architecture tools developed to support NASA's Applied Sciences Program. Through user needs assessment, collaboration with Stennis Space Center, Goddard Space Flight Center, and NASA's DEVELOP Staff personnel insight to information needs for the RPKB were gathered from across NASA scientific communities of practice. To enable efficient, consistent, standard, structured, and managed data entry and research results compilation a prototype RPKB has been designed and fully integrated with the existing NASA Earth Science Systems Components database. The RPKB will compile research project and keyword information of relevance to the six major science focus areas, 12 national applications, and the Global Change Master Directory (GCMD). The RPKB will include information about projects awarded from NASA research solicitations, project investigator information, research publications, NASA data products employed, and model or decision support tools used or developed as well as new data product information. The RPKB will be developed in a multi-tier architecture that will include a SQL Server relational database backend, middleware, and front end client interfaces for data entry. The purpose of this project is to intelligently harvest the results of research sponsored by the NASA Applied Sciences Program and related research program results. We present various approaches for a wide spectrum of knowledge discovery of research results, publications, projects, etc. from the NASA Systems Components database and global information systems and show how this is implemented in SQL Server database. The application of knowledge discovery is useful for intelligent query answering and multiple-layered database construction. Using advanced EA tools such as the Earth Science Architecture Tool (ESAT), RPKB will enable NASA and partner agencies to efficiently identify the significant results for new experiment directions and principle investigators to formulate experiment directions for new proposals.

Dabiru, L.; O'Hara, C. G.; Shaw, D.; Katragadda, S.; Anderson, D.; Kim, S.; Shrestha, B.; Aanstoos, J.; Frisbie, T.; Policelli, F.; Keblawi, N.

2006-12-01

75

Large-scale gene discovery in human airway epithelia reveals novel transcripts  

Microsoft Academic Search

apply methods of focused gene discovery to human airway epithelia. The lung is composed of airway and alveolar epithelia, submucosal glands, interstitial cells, vascular tissue, smooth muscle, cartilage, neuronal tissue, and circulating and resident hematopoietic cells. Mercer et al. (15) measured the total surface area of human airways from the trachea to the bron- chioles and found it to be

Todd E. Scheetz; Joseph Zabner; Michael J. Welsh; Justin Coco; Mari Eyestone; Maria de Fatima Bonaldo; Tamara Kucaba; Thomas L. Casavant; M. Bento Soares; Paul B. McCray

2004-01-01

76

The Gene Ontology project in 2008  

PubMed Central

The Gene Ontology (GO) project (http://www.geneontology.org/) provides a set of structured, controlled vocabularies for community use in annotating genes, gene products and sequences (also see http://www.sequenceontology.org/). The ontologies have been extended and refined for several biological areas, and improvements to the structure of the ontologies have been implemented. To improve the quantity and quality of gene product annotations available from its public repository, the GO Consortium has launched a focused effort to provide comprehensive and detailed annotation of orthologous genes across a number of ‘reference’ genomes, including human and several key model organisms. Software developments include two releases of the ontology-editing tool OBO-Edit, and improvements to the AmiGO browser interface.

2008-01-01

77

Discovery of induced point mutations in maize genes by TILLING  

Microsoft Academic Search

BACKGROUND: Going from a gene sequence to its function in the context of a whole organism requires a strategy for targeting mutations, referred to as reverse genetics. Reverse genetics is highly desirable in the modern genomics era; however, the most powerful methods are generally restricted to a few model organisms. Previously, we introduced a reverse-genetic strategy with the potential for

Bradley J Till; Steven H Reynolds; Clifford Weil; Nathan Springer; Chris Burtner; Kim Young; Elisabeth Bowers; Christine A Codomo; Linda C Enns; Anthony R Odden; Elizabeth A Greene; Luca Comai; Steven Henikoff

2004-01-01

78

Gene discovery through genomic sequencing of Brucella abortus  

Microsoft Academic Search

10(-5)) to sequences deposited in the GenBank databases. Among them, 925 represent putative novel genes for the Brucella genus. Out of 925 nonredundant GSSs, 470 were classified in 15 categories based on cellular function. Seven hundred GSSs showed no significant database matches and remain available for further studies in order to identify their function. A high number of GSSs with

DANIEL O. SANCHEZ; RUBEN O. ZANDOMENI; SILVIO CRAVERO; RAMIRO E. VERDUN; ESTER PIERROU; PAULA FACCIO; GABRIELA DIAZ; SILVIA LANZAVECCHIA; F. Aguero; ALBERTO C. C. FRASCH; SIV G. E. ANDERSSON; OSVALDO L. ROSSETTI; OSCAR GRAU; RODOLFO A. UGALDE

2001-01-01

79

Susceptibility gene discovery for common metabolic and endocrine traits  

Microsoft Academic Search

Almost all major causes of ill-health and premature death in human societies worldwide - including cancer, cardiovascular disease, diabetes and many infectious diseases - are, at least in part, genetically determined. Typically, risk of succumbing to one of these illnesses is thought to depend on both the individual repertoire of variation within a number of key susceptibility genes and the

M I McCarthy

2002-01-01

80

Discovery of epigenetically silenced genes in acute myeloid leukemias.  

PubMed

The demethylating 5-aza-2'deoxycytidine (DAC) and the histone deacetylase inhibitor (HDACi) suberoyl anilide bishydroxamide (SAHA) possess potent antitumorigenic properties in myeloid disorders. However, the transcriptome alterations mediated by these drugs are poorly understood. We analyzed the transcriptional effects of DAC and SAHA in the AML cell line KG-1. Microarray analyses revealed 76 genes expressed in normal CD34+ cells, absent in KG-1 cells but whose expression was induced after drug treatment. A total of 39 of these genes harbored CpG islands in their promoters. We examined the expression level of these genes in 120 AML patient samples representing diverse karyotpyes. Gas2l1, tfIIs, ehd3, enolase 2, mx1, dral, astml and pxdn were diminished across all AML karyotypes examined. Ehd3 was methylated in 63% of AML patients examined. This methylation was lost upon complete remission, and not observed in normal CD34+ cells. CD34+ cells expressed ehd3 at approximately 10-fold higher levels than AML samples. Another highlighted gene, alpha-catenin, is located at q31 of chromosome 5. Analyses of 29 5q- AML/myelodysplastic syndrome (MDS) samples revealed marked decreases in expression of alpha-catenin, compared to non-5q- MDS samples (6.6+/-9-fold). However, no methylation was detected, suggesting indirect effects of these drugs on the expression of alpha-catenin. PMID:17330099

Desmond, J C; Raynaud, S; Tung, E; Hofmann, W-K; Haferlach, T; Koeffler, H P

2007-03-01

81

The Magnetism in Massive Stars (MiMeS) project: First HARPSpol discoveries  

NASA Astrophysics Data System (ADS)

In the framework of the Magnetism in Massive Stars (MiMeS) project, a HARPSpol Large Program at the 3.6m-ESO telescope has recently started to collect high-resolution spectropolarimetric data of a large number of Southern massive OB stars in the field of the Galaxy and in many young clusters and associations. In this contribution, we present details of the HARPSpol survey, the first HARPSpol discoveries of magnetic fields in massive stars, and the magnetic properties of two previously known magnetic stars.

Alecian, E.; Peralta, R.; Oksala, M. E.; Neiner, C.

2012-12-01

82

iSyTE: Integrated Systems Tool for Eye Gene Discovery  

PubMed Central

Purpose. To facilitate the identification of genes associated with cataract and other ocular defects, the authors developed and validated a computational tool termed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE uses a mouse embryonic lens gene expression data set as a bioinformatics filter to select candidate genes from human or mouse genomic regions implicated in disease and to prioritize them for further mutational and functional analyses. Methods. Microarray gene expression profiles were obtained for microdissected embryonic mouse lens at three key developmental time points in the transition from the embryonic day (E)10.5 stage of lens placode invagination to E12.5 lens primary fiber cell differentiation. Differentially regulated genes were identified by in silico comparison of lens gene expression profiles with those of whole embryo body (WB) lacking ocular tissue. Results. Gene set analysis demonstrated that this strategy effectively removes highly expressed but nonspecific housekeeping genes from lens tissue expression profiles, allowing identification of less highly expressed lens disease–associated genes. Among 24 previously mapped human genomic intervals containing genes associated with isolated congenital cataract, the mutant gene is ranked within the top two iSyTE-selected candidates in approximately 88% of cases. Finally, in situ hybridization confirmed lens expression of several novel iSyTE-identified genes. Conclusions. iSyTE is a publicly available Web resource that can be used to prioritize candidate genes within mapped genomic intervals associated with congenital cataract for further investigation. Extension of this approach to other ocular tissue components will facilitate eye disease gene discovery.

Lachke, Salil A.; Ho, Joshua W. K.; Kryukov, Gregory V.; O'Connell, Daniel J.; Aboukhalil, Anton; Bulyk, Martha L.; Park, Peter J.

2012-01-01

83

The emerging role for rat models in gene discovery  

Microsoft Academic Search

Rat models have been used for many decades to study physiological and pathophysiological mechanisms. Prior to the release\\u000a of the rat genome and new technologies for targeting gene manipulation, the rat had been the underdog in the genomics era,\\u000a despite the abundance of physiological data compared to the mouse. The overarching goal of biomedical research is to improve\\u000a health and

Melinda R. Dwinell; Jozef Lazar; Aron M. Geurts

2011-01-01

84

Variations in Discovery-based Preeclampsia Candidate Genes  

PubMed Central

Preeclampsia is a common and potentially lethal pregnancy disorder with lifelong increased risk of cardiovascular disease in survivors. Our prior global gene expression microarray analysis led to a novel set of 36 candidates in first trimester placentas of women who subsequently developed preeclampsia. In this report, we present preliminary studies demonstrating biomarkers of genotype and methylation variations in a subset of these candidate genes in maternal leukocyte and fetoplacental DNA of 28 case and 27 control dyads. We tested 84 single nucleotide polymorphisms (SNPs) using MassArray iPLEX and 50 CpG sites using EpiTYPER assays. Promising prediction modeling was identified with 25 SNPs selected using Fisher's exact tests (p?0.05) and 20 CpG sites selected on fold change. Genotype Distribution Analysis identified SNP variations that differed between 9 paired cases versus paired controls. The findings validate the examined candidate genes and support feasibility of methods for further biomarker development. The integrative approach that was implemented begins to translate the 36 candidates toward clinical utility as a screening modality for preeclampsia.

Founds, Sandra A.; Shi, Haiwen; Conley, Yvette P.; Jeyabalan, Arun; Roberts, James M.; Lyons-Weiler, James

2012-01-01

85

Discovery of three novel G-protein-coupled receptor genes.  

PubMed

We report here the molecular cloning, tissue distribution, and chromosomal localization of novel genes encoding G-protein-coupled receptors (GPCRs). A search of a mouse database of expressed sequence tags revealed an EST partially encoding a GPCR, which was used to screen a mouse genomic library to obtain the translational open reading frame (ORF). The resultant clone, GPR27, contained an intronless ORF, encoding a receptor of 379 amino acids. In an alternate strategy, human genomic DNA was subjected to polymerase chain reaction (PCR) amplification, using degenerate oligonucleotides based on GPR1. Two PCR products partially encoding GPCRs were isolated and used to screen a genomic library to obtain the translational ORF. One of the resultant clones, GPR30, contained an intronless ORF encoding a receptor of 375 amino acids. The other clone, GPR35, also contained an intronless ORF encoding a receptor of 309 amino acids. Transcripts corresponding to GPR27 and GPR30 were detected in several areas of human and rat CNS, While GPR35 expression was detected only in the rat intestine. Through fluorescence in situ hybridization analysis the gene encoding GPR30 was localized to chromosome 7p22 and GPR35 to chromosome 2q37.3. PMID:9479505

O'Dowd, B F; Nguyen, T; Marchese, A; Cheng, R; Lynch, K R; Heng, H H; Kolakowski, L F; George, S R

1998-01-15

86

The Alveolate Perkinsus marinus: Biological Insights from EST Gene Discovery  

PubMed Central

Background Perkinsus marinus, a protozoan parasite of the eastern oyster Crassostrea virginica, has devastated natural and farmed oyster populations along the Atlantic and Gulf coasts of the United States. It is classified as a member of the Perkinsozoa, a recently established phylum considered close to the ancestor of ciliates, dinoflagellates, and apicomplexans, and a key taxon for understanding unique adaptations (e.g. parasitism) within the Alveolata. Despite intense parasite pressure, no disease-resistant oysters have been identified and no effective therapies have been developed to date. Results To gain insight into the biological basis of the parasite's virulence and pathogenesis mechanisms, and to identify genes encoding potential targets for intervention, we generated >31,000 5' expressed sequence tags (ESTs) derived from four trophozoite libraries generated from two P. marinus strains. Trimming and clustering of the sequence tags yielded 7,863 unique sequences, some of which carry a spliced leader. Similarity searches revealed that 55% of these had hits in protein sequence databases, of which 1,729 had their best hit with proteins from the chromalveolates (E-value ? 1e-5). Some sequences are similar to those proven to be targets for effective intervention in other protozoan parasites, and include not only proteases, antioxidant enzymes, and heat shock proteins, but also those associated with relict plastids, such as acetyl-CoA carboxylase and methyl erythrithol phosphate pathway components, and those involved in glycan assembly, protein folding/secretion, and parasite-host interactions. Conclusions Our transcriptome analysis of P. marinus, the first for any member of the Perkinsozoa, contributes new insight into its biology and taxonomic position. It provides a very informative, albeit preliminary, glimpse into the expression of genes encoding functionally relevant proteins as potential targets for chemotherapy, and evidence for the presence of a relict plastid. Further, although P. marinus sequences display significant similarity to those from both apicomplexans and dinoflagellates, the presence of trans-spliced transcripts confirms the previously established affinities with the latter. The EST analysis reported herein, together with the recently completed sequence of the P. marinus genome and the development of transfection methodology, should result in improved intervention strategies against dermo disease.

2010-01-01

87

FHIT: from gene discovery to cancer treatment and prevention.  

PubMed

Chromosomal abnormalities, including homozygous deletions and loss of heterozygosity, are among the most common features of human tumours. The short arm of human chromosome 3, particularly the region 3p14.2, is a major site of such rearrangements. The 3p14.2 region spans the most active common fragile site of the human genome, encompassing a familial-kidney-cancer-associated breakpoint and a papilloma virus integration site. 6 years ago, the FHIT gene was identified in this region. Subsequent studies have shown that FHIT is commonly the target of chromosomal aberrations involving the long arm of human chromosome 3 and is thereby inactivated in most of the common human malignant diseases, including cancers of the lung, oesophagus, stomach, breast, and kidney. During the past 5 years, evidence has accumulated in support of a tumour-suppressor function for FHIT. In this review, we describe the recent findings in the molecular biology of FHIT with particular focus on the opportunities for treatment and prevention of cancer that have emerged. PMID:12473516

Pekarsky, Yuri; Zanesi, Nicola; Palamarchuk, Alexey; Huebner, Kay; Croce, Carlo M

2002-12-01

88

Discovery and characterization of medaka miRNA genes by next generation sequencing platform  

Microsoft Academic Search

BACKGROUND: MicroRNAs (miRNAs) are endogenous non-protein-coding RNA genes which exist in a wide variety of organisms, including animals, plants, virus and even unicellular organisms. Medaka (Oryzias latipes) is a useful model organism among vertebrate animals. However, no medaka miRNAs have been investigated systematically. It is beneficial to conduct a genome-wide miRNA discovery study using the next generation sequencing (NGS) technology,

Sung-Chou Li; Wen-Ching Chan; Meng-Ru Ho; Kuo-Wang Tsai; Ling-Yueh Hu; Chun-Hung Lai; Chun-Nan Hsu; Pung-Pung Hwang; Wen-chang Lin

2010-01-01

89

GEM-TREND: a web tool for gene expression data mining toward relevant network discovery  

PubMed Central

Background DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database. Results GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories. Conclusion GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at .

Feng, Chunlai; Araki, Michihiro; Kunimoto, Ryo; Tamon, Akiko; Makiguchi, Hiroki; Niijima, Satoshi; Tsujimoto, Gozoh; Okuno, Yasushi

2009-01-01

90

MAGIC database and interfaces: an integrated package for gene discovery and expression.  

PubMed

The rapidly increasing rate at which biological data is being produced requires a corresponding growth in relational databases and associated tools that can help laboratories contend with that data. With this need in mind, we describe here a Modular Approach to a Genomic, Integrated and Comprehensive (MAGIC) Database. This Oracle 9i database derives from an initial focus in our laboratory on gene discovery via production and analysis of expressed sequence tags (ESTs), and subsequently on gene expression as assessed by both EST clustering and microarrays. The MAGIC Gene Discovery portion of the database focuses on information derived from DNA sequences and on its biological relevance. In addition to MAGIC SEQ-LIMS, which is designed to support activities in the laboratory, it contains several additional subschemas. The latter include MAGIC Admin for database administration, MAGIC Sequence for sequence processing as well as sequence and clone attributes, MAGIC Cluster for the results of EST clustering, MAGIC Polymorphism in support of microsatellite and single-nucleotide-polymorphism discovery, and MAGIC Annotation for electronic annotation by BLAST and BLAT. The MAGIC Microarray portion is a MIAME-compliant database with two components at present. These are MAGIC Array-LIMS, which makes possible remote entry of all information into the database, and MAGIC Array Analysis, which provides data mining and visualization. Because all aspects of interaction with the MAGIC Database are via a web browser, it is ideally suited not only for individual research laboratories but also for core facilities that serve clients at any distance. PMID:18629159

Cordonnier-Pratt, Marie-Michèle; Liang, Chun; Wang, Haiming; Kolychev, Dmitri S; Sun, Feng; Freeman, Robert; Sullivan, Robert; Pratt, Lee H

2004-01-01

91

Comparative Toxicogenomics Database: a knowledgebase and discovery tool for chemical-gene-disease networks  

PubMed Central

The Comparative Toxicogenomics Database (CTD) is a curated database that promotes understanding about the effects of environmental chemicals on human health. Biocurators at CTD manually curate chemical–gene interactions, chemical–disease relationships and gene–disease relationships from the literature. This strategy allows data to be integrated to construct chemical–gene–disease networks. CTD is unique in numerous respects: curation focuses on environmental chemicals; interactions are manually curated; interactions are constructed using controlled vocabularies and hierarchies; additional gene attributes (such as Gene Ontology, taxonomy and KEGG pathways) are integrated; data can be viewed from the perspective of a chemical, gene or disease; results and batch queries can be downloaded and saved; and most importantly, CTD acts as both a knowledgebase (by reporting data) and a discovery tool (by generating novel inferences). Over 116 000 interactions between 3900 chemicals and 13 300 genes have been curated from 270 species, and 5900 gene–disease and 2500 chemical–disease direct relationships have been captured. By integrating these data, 350 000 gene–disease relationships and 77 000 chemical–disease relationships can be inferred. This wealth of chemical–gene–disease information yields testable hypotheses for understanding the effects of environmental chemicals on human health. CTD is freely available at http://ctd.mdibl.org.

Davis, Allan Peter; Murphy, Cynthia G.; Saraceni-Richards, Cynthia A.; Rosenstein, Michael C.; Wiegers, Thomas C.; Mattingly, Carolyn J.

2009-01-01

92

The discovery of the fat-regulating phosphatidic acid phosphatase gene  

PubMed Central

Phosphatidic acid phosphatase is a fat-regulating enzyme that plays a major role in controlling the balance of phosphatidic acid (substrate) and diacylglycerol (product), which are lipid precursors used for the synthesis of membrane phospholipids and triacylglycerol. Phosphatidic acid is also a signaling molecule that triggers phospholipid synthesis gene expression, membrane expansion, secretion, and endocytosis. While this important enzyme has been known for several decades, its gene was only identified recently from yeast. This discovery showed the importance of phosphatidic acid phosphatase in lipid metabolism in yeast as well as in higher eukaryotes including humans.

CARMAN, George M.

2011-01-01

93

The National Laboratory Gene Library Project  

SciTech Connect

The two National Laboratories at Livermore and Los Alamos have played a prominent role in the development and application of flow cytometry and sorting to chromosome classification and purification. Both laboratories began to receive numerous requests for specific human chromosomal types purified by flow sorting for gene library construction, but these requests were difficult to satisfy due to time and personnel constraints. The Department of Energy, through its Office of Health and Environmental Research, has a long-standing interest in the human genome in general and in the mutagenic and carcinogenic effects of energy-related environmental pollutants in particular. Hence, it was decided in 1983 to use the flow construct chromosome-specific gene libraries to be made available to the genetic research community. The National Laboratory Gene Library Project was envisioned as a practical way to deal with requests for sorted chromosomes, and also as a way to promote increased understanding of the human genome and the effects of mutagens and carcinogens on it. The strategy for the project was developed with the help of an advisory committee as well as suggestions and advice from many other geneticists. 4 refs., 2 tabs.

Deaven, L.L.; Van Dilla, M.A.

1988-01-01

94

The five-gene-network data analysis with local causal discovery algorithm using causal Bayesian networks.  

PubMed

Using microarray experiments, we can model causal relationships of genes measured through mRNA expression levels. To this end, it is desirable to compare experiments of the system under complete interventions of some genes, such as by knock out of some genes, with experiments of the system under no interventions. However, it is expensive and difficult to conduct wet lab experiments of complete interventions of genes in a biological system. Thus, it will be helpful if we can discover promising causal relationships among genes with no interventions or incomplete interventions, such as by applying a treatment that has unknown effects to modeled genes, in order to identify promising genes to perturb in the system that can later be verified in wet laboratories. In this paper we use causal Bayesian networks to implement a causal discovery algorithm-the equivalence local implicit latent variable scoring method (EquLIM)-that identifies promising causal relationships even with a small dataset generated from no or incomplete interventions. We then apply EquLIM to analyze the five-gene-network data and compare EquLIM's predictions with true causal pairwise relationships between the genes. PMID:19348635

Yoo, Changwon; Brilz, Erik M

2009-03-01

95

PAGED: a pathway and gene-set enrichment database to enable molecular phenotype discoveries  

PubMed Central

Background Over the past decade, pathway and gene-set enrichment analysis has evolved into the study of high-throughput functional genomics. Owing to poorly annotated and incomplete pathway data, researchers have begun to combine pathway and gene-set enrichment analysis as well as network module-based approaches to identify crucial relationships between different molecular mechanisms. Methods To meet the new challenge of molecular phenotype discovery, in this work, we have developed an integrated online database, the Pathway And Gene Enrichment Database (PAGED), to enable comprehensive searches for disease-specific pathways, gene signatures, microRNA targets, and network modules by integrating gene-set-based prior knowledge as molecular patterns from multiple levels: the genome, transcriptome, post-transcriptome, and proteome. Results The online database we developed, PAGED http://bio.informatics.iupui.edu/PAGED is by far the most comprehensive public compilation of gene sets. In its current release, PAGED contains a total of 25,242 gene sets, 61,413 genes, 20 organisms, and 1,275,560 records from five major categories. Beyond its size, the advantage of PAGED lies in the explorations of relationships between gene sets as gene-set association networks (GSANs). Using colorectal cancer expression data analysis as a case study, we demonstrate how to query this database resource to discover crucial pathways, gene signatures, and gene network modules specific to colorectal cancer functional genomics. Conclusions This integrated online database lays a foundation for developing tools beyond third-generation pathway analysis approaches on for discovering molecular phenotypes, especially for disease-associated pathway/gene-set enrichment analysis.

2012-01-01

96

Evolving connectionist systems for knowledge discovery from gene expression data of cancer tissue.  

PubMed

Microarray techniques have made it possible to observe the expression of thousands of genes simultaneously. They have recently been applied to study gene expression patterns in tissue samples. This may lead to highly desirable improvements in the diagnosis and treatment of human diseases. Statistical and machine learning methods have recently been used to classify cancer tissue based on gene expression data. Although some of these methods have achieved a high degree of accuracy, they generally lack transparency in their classification process. This, however, is crucial for the application in the medical field. In order to overcome this obstacle, we used knowledge-based neurocomputing (KBN), since KBN seeks to gain knowledge that is comprehensible to humans. In particular, we applied evolving fuzzy neural networks (EFuNNs) to classify cancer tissue, which is illustrated on the case studies of leukaemia and colon cancer. EFuNNs belong to the evolving connectionist system paradigm (ECOS) that has been recently introduced. They are well suited for adaptive learning and knowledge discovery. Fuzzy logic rules can be extracted from the trained networks and offer knowledge about the classification process in an easily accessible form. These rules point to genes that are strongly associated with specific types of cancer and may be used for the development of new tests and treatment discoveries. PMID:12893118

Futschik, Matthias E; Reeve, Anthony; Kasabov, Nikola

2003-06-01

97

EVALUATION OF SEVEN AB INITIO GENE PREDICTION PROGRAMS FOR THE DISCOVERY OF MAIZE GENES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Seven ab initio programs (FGENESH, GeneMark.hmm, GENESCAN, GlimmerR, Grail, NetGene2 and SplicePredictor) were evaluated for their accuracy in predicting maize genes using nine maize genes (gl8a, pdc2, pdc3, rf2b, rf2c, rf2d, rf2e1,rth1, rth3). These genes could not have been included in the trainin...

98

Manic-depression genes and the new millennium: poised for discovery.  

PubMed

Manic-depressive illness is a common psychiatric disorder with complex etiology that likely involves multiple genes and non-genetic influences. The uncertain path to gene discovery has spurred considerable debate over genetic findings and gene-finding strategies. In this article, I review the main findings, with a focus on: (1) putative linked loci on chromosomes 1q31-32, 4p16, 6pter-p24, 10p14, 10q21-26, 12q23-24, 13q31-32, 18p11, 18q21-23, 21q22, 22q11-13, and Xq24-28; and (2) association studies with candidate genes, dynamic mutations, mitochondrial mutations, and chromosomal aberrations. Although no gene has been identified, promising findings are emerging. I then discuss the challenges and opportunities ahead, with special emphasis on gene-finding methods-in particular, questions pertaining to phenotype definition, linkage and association mapping, gene markers, sampling, study population, multigene systems, lessons from other disorders, animal models, and bioinformatics. The progress to date, together with rapid advances in genomics, analytical and computational methods, and bioinformatics, holds promise for new insights into the genetics of manic-depression, in the new millennium. PMID:11986978

Baron, M

2002-01-01

99

Gene Discovery of Modular Diterpene Metabolism in Nonmodel Systems1[W][OA  

PubMed Central

Plants produce over 10,000 different diterpenes of specialized (secondary) metabolism, and fewer diterpenes of general (primary) metabolism. Specialized diterpenes may have functions in ecological interactions of plants with other organisms and also benefit humanity as pharmaceuticals, fragrances, resins, and other industrial bioproducts. Examples of high-value diterpenes are taxol and forskolin pharmaceuticals or ambroxide fragrances. Yields and purity of diterpenes obtained from natural sources or by chemical synthesis are often insufficient for large-volume or high-end applications. Improvement of agricultural or biotechnological diterpene production requires knowledge of biosynthetic genes and enzymes. However, specialized diterpene pathways are extremely diverse across the plant kingdom, and most specialized diterpenes are taxonomically restricted to a few plant species, genera, or families. Consequently, there is no single reference system to guide gene discovery and rapid annotation of specialized diterpene pathways. Functional diversification of genes and plasticity of enzyme functions of these pathways further complicate correct annotation. To address this challenge, we used a set of 10 different plant species to develop a general strategy for diterpene gene discovery in nonmodel systems. The approach combines metabolite-guided transcriptome resources, custom diterpene synthase (diTPS) and cytochrome P450 reference gene databases, phylogenies, and, as shown for select diTPSs, single and coupled enzyme assays using microbial and plant expression systems. In the 10 species, we identified 46 new diTPS candidates and over 400 putatively terpenoid-related P450s in a resource of nearly 1 million predicted transcripts of diterpene-accumulating tissues. Phylogenetic patterns of lineage-specific blooms of genes guided functional characterization.

Zerbe, Philipp; Hamberger, Bjorn; Yuen, Macaire M.S.; Chiang, Angela; Sandhu, Harpreet K.; Madilao, Lina L.; Nguyen, Anh; Hamberger, Britta; Bach, S?ren Spanner; Bohlmann, Jorg

2013-01-01

100

Discovery of the rhizopodin biosynthetic gene cluster in Stigmatella aurantiaca Sg a15 by genome mining.  

PubMed

The field of bacterial natural product research is currently undergoing a paradigm change concerning the discovery of natural products. Previously most efforts were based on isolation of the most abundant compound in an extract, or on tracking bioactivity. However, traditional activity-guided approaches are limited by the available test panels and frequently lead to the rediscovery of already known compounds. The constantly increasing availability of bacterial genome sequences provides the potential for the discovery of a huge number of new natural compounds by in silico identification of biosynthetic gene clusters. Examination of the information on the biosynthetic machinery can further prevent rediscovery of known compounds, and can help identify so far unknown biosynthetic pathways of known compounds. By in silico screening of the genome of the myxobacterium Stigmatella aurantiaca Sg a15, a trans-AT polyketide synthase/non-ribosomal peptide synthetase (PKS/NRPS) gene cluster was identified that could not be correlated to any secondary metabolite known to be produced by this strain. Targeted gene inactivation and analysis of extracts from the resulting mutants by high performance liquid chromatography coupled to high resolution mass spectrometry (HPLC-HRMS), in combination with the use of statistical tools resulted in the identification of a compound that was absent in the mutants extracts. By matching with our in-house database of myxobacterial secondary metabolites, this compound was identified as rhizopodin. A detailed analysis of the rhizopodin biosynthetic machinery is presented in this manuscript. PMID:22278953

Pistorius, Dominik; Müller, Rolf

2012-01-25

101

Discovery of a novel imprinted gene by transcriptional analysis of parthenogenetic embryonic stem cells  

PubMed Central

BACKGROUND Parthenogenetic embryonic stem cells (PESCs) may have future utilities in cell replacement therapies since they are closely related to the female from which the activated oocyte was obtained. Furthermore, the avoidance of parthenogenetic development in mammals provides the most compelling rationale for the evolution of genomic imprinting, and the biological process of parthenogenesis raises complex issues regarding differential gene expression. METHODS AND RESULTS We describe here homozygous rhesus monkey PESCs derived from a spontaneously duplicated, haploid oocyte genome. Since the effect of homozygosity on PESCs pluripotency and differentiation potential is unknown, we assessed the similarities and differences in pluripotency markers and developmental potential by in vitro and in vivo differentiation of homozygous and heterozygous PESCs. To understand the differences in gene expression regulation between parthenogenetic and biparental embryonic stem cells (ESCs), we conducted microarray analysis of genome-wide mRNA profiles of primate PESCs and ESCs derived from fertilized embryos using the Affymetrix Rhesus Macaque Genome array. Several known paternally imprinted genes were in the highly down-regulated group in PESCs compared with ESCs. Furthermore, allele-specific expression analysis of other genes whose expression is also down-regulated in PESCs, led to the identification of one novel imprinted gene, inositol polyphosphate-5-phosphatase F (INPP5F), which was exclusively expressed from a paternal allele. CONCLUSION Our findings suggest that PESCs could be used as a model for studying genomic imprinting, and in the discovery of novel imprinted genes.

Sritanaudomchai, Hathaitip; Ma, Hong; Clepper, Lisa; Gokhale, Sumita; Bogan, Randy; Hennebold, Jon; Wolf, Don; Mitalipov, Shoukhrat

2010-01-01

102

PhenomeNET: a whole-phenome approach to disease gene discovery  

PubMed Central

Phenotypes are investigated in model organisms to understand and reveal the molecular mechanisms underlying disease. Phenotype ontologies were developed to capture and compare phenotypes within the context of a single species. Recently, these ontologies were augmented with formal class definitions that may be utilized to integrate phenotypic data and enable the direct comparison of phenotypes between different species. We have developed a method to transform phenotype ontologies into a formal representation, combine phenotype ontologies with anatomy ontologies, and apply a measure of semantic similarity to construct the PhenomeNET cross-species phenotype network. We demonstrate that PhenomeNET can identify orthologous genes, genes involved in the same pathway and gene–disease associations through the comparison of mutant phenotypes. We provide evidence that the Adam19 and Fgf15 genes in mice are involved in the tetralogy of Fallot, and, using zebrafish phenotypes, propose the hypothesis that the mammalian homologs of Cx36.7 and Nkx2.5 lie in a pathway controlling cardiac morphogenesis and electrical conductivity which, when defective, cause the tetralogy of Fallot phenotype. Our method implements a whole-phenome approach toward disease gene discovery and can be applied to prioritize genes for rare and orphan diseases for which the molecular basis is unknown.

Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

2011-01-01

103

Evaluation of Gene Association Methods for Coexpression Network Construction and Biological Knowledge Discovery  

PubMed Central

Background Constructing coexpression networks and performing network analysis using large-scale gene expression data sets is an effective way to uncover new biological knowledge; however, the methods used for gene association in constructing these coexpression networks have not been thoroughly evaluated. Since different methods lead to structurally different coexpression networks and provide different information, selecting the optimal gene association method is critical. Methods and Results In this study, we compared eight gene association methods – Spearman rank correlation, Weighted Rank Correlation, Kendall, Hoeffding's D measure, Theil-Sen, Rank Theil-Sen, Distance Covariance, and Pearson – and focused on their true knowledge discovery rates in associating pathway genes and construction coordination networks of regulatory genes. We also examined the behaviors of different methods to microarray data with different properties, and whether the biological processes affect the efficiency of different methods. Conclusions We found that the Spearman, Hoeffding and Kendall methods are effective in identifying coexpressed pathway genes, whereas the Theil-sen, Rank Theil-Sen, Spearman, and Weighted Rank methods perform well in identifying coordinated transcription factors that control the same biological processes and traits. Surprisingly, the widely used Pearson method is generally less efficient, and so is the Distance Covariance method that can find gene pairs of multiple relationships. Some analyses we did clearly show Pearson and Distance Covariance methods have distinct behaviors as compared to all other six methods. The efficiencies of different methods vary with the data properties to some degree and are largely contingent upon the biological processes, which necessitates the pre-analysis to identify the best performing method for gene association and coexpression network construction.

Kumari, Sapna; Nie, Jeff; Chen, Huann-Sheng; Ma, Hao; Stewart, Ron; Li, Xiang; Lu, Meng-Zhu; Taylor, William M.; Wei, Hairong

2012-01-01

104

Evaluation of five ab initio gene prediction programs for the discovery of maize genes.  

PubMed

Five ab initio programs (FGENESH, GeneMark.hmm, GENSCAN, GlimmerR and Grail) were evaluated for their accuracy in predicting maize genes. Two of these programs, GeneMark.hmm and GENSCAN had been trained for maize; FGENESH had been trained for monocots (including maize), and the others had been trained for rice or Arabidopsis. Initial evaluations were conducted using eight maize genes (gl8a, pdc2, pdc3, rf2c, rf2d, rf2e1, rth1, and rth3) of which the sequences were not released to the public prior to conducting this evaluation. The significant advantage of this data set for this evaluation is that these genes could not have been included in the training sets of the prediction programs. FGENESH yielded the most accurate and GeneMark.hmm the second most accurate predictions. The five programs were used in conjunction with RT-PCR to identify and establish the structures of two new genes in the a1-sh2 interval of the maize genome. FGENESH, GeneMark.hmm and GENSCAN were tested on a larger data set consisting of maize assembled genomic islands (MAGIs) that had been aligned to ESTs. FGENESH, GeneMark.hmm and GENSCAN correctly predicted gene models in 773, 625, and 371 MAGIs, respectively, out of the 1353 MAGIs that comprise data set 2. PMID:15830133

Yao, Hong; Guo, Ling; Fu, Yan; Borsuk, Lisa A; Wen, Tsui-Jung; Skibbe, David S; Cui, Xiangqin; Scheffler, Brian E; Cao, Jun; Emrich, Scott J; Ashlock, Daniel A; Schnable, Patrick S

2005-02-01

105

Exploiting the Natural Diversity of Microviridin Gene Clusters for Discovery of Novel Tricyclic Depsipeptides?†  

PubMed Central

Microviridins are ribosomally synthesized tricyclic depsipeptides produced by different genera of cyanobacteria. The prevalence of the microviridin gene clusters and the natural diversity of microviridin precursor sequences are currently unknown. Screening of laboratory strains and field samples of the bloom-forming freshwater cyanobacterium Microcystis via PCR revealed global occurrence of the microviridin pathway and an unexpected natural variety. We could detect 15 new variants of the precursor gene mdnA encoding microviridin backbones that differ in up to 4 amino acid positions from known isoforms of the peptide. The survey not only provides insights into the versatility of the biosynthetic enzymes in a closely related group of cyanobacteria, but also facilitates the discovery and characterization of cryptic microviridin variants. This is demonstrated for microviridin L in Microcystis aeruginosa strain NIES843 and heterologously produced variants.

Ziemert, Nadine; Ishida, Keishi; Weiz, Annika; Hertweck, Christian; Dittmann, Elke

2010-01-01

106

Targeted SNP discovery in Atlantic salmon (Salmo salar) genes using a 3'UTR-primed SNP detection approach  

PubMed Central

Background Single nucleotide polymorphisms (SNPs) represent the most widespread type of DNA variation in vertebrates and may be used as genetic markers for a range of applications. This has led to an increased interest in identification of SNP markers in non-model species and farmed animals. The in silico SNP mining method used for discovery of most known SNPs in Atlantic salmon (Salmo salar) has applied a global (genome-wide) approach. In this study we present a targeted 3'UTR-primed SNP discovery strategy that utilizes sequence data from Salmo salar full length sequenced cDNAs (FLIcs). We compare the efficiency of this new strategy to the in silico SNP mining method when using both methods for targeted SNP discovery. Results The SNP discovery efficiency of the two methods was tested in a set of FLIc target genes. The 3'UTR-primed SNP discovery method detected novel SNPs in 35% of the target genes while the in silico SNP mining method detected novel SNPs in 15% of the target genes. Furthermore, the 3'UTR-primed SNP discovery strategy was the less labor intensive one and revealed a higher success rate than the in silico SNP mining method in the initial amplification step. When testing the methods we discovered 112 novel bi-allelic polymorphisms (type I markers) in 88 salmon genes [dbSNP: ss179319972-179320081, ss250608647-250608648], and three of the SNPs discovered were missense substitutions. Conclusions Full length insert cDNAs (FLIcs) are important genomic resources that have been developed in many farmed animals. The 3'UTR-primed SNP discovery strategy successfully utilized FLIc data to detect novel SNPs in the partially tetraploid Atlantic salmon. This strategy may therefore be useful for targeted SNP discovery in several species, and particularly useful in species that, like salmonids, have duplicated genomes.

2010-01-01

107

PiggyBac Transposon Mutagenesis: A Tool for Cancer Gene Discovery in Mice  

PubMed Central

Transposons are mobile DNA segments that can disrupt gene function by inserting in or near genes. Here we show that insertional mutagenesis by the PiggyBac transposon can be used for cancer gene discovery in mice. PiggyBac transposition in genetically engineered transposon/transposase mice induced cancers whose type (hematopoietic versus solid) and latency were dependent on the regulatory elements introduced into transposons. Analysis of 63 hematopoietic tumors revealed the unique qualities of PiggyBac for genome-wide mutagenesis and discovered many cancer genes not identified in previous retroviral or Sleeping Beauty transposon screens, including Spic, which encodes a PU.1-related transcription factor, and Hdac7, a histone deacetylase gene. PiggyBac and Sleeping Beauty have different integration preferences. To maximize the utility of the tool, we engineered 20 mouse lines to be compatible with both transposases in constitutive, tissue- or temporal-specific mutagenesis. Mice with different transposon types, copy numbers and chromosomal locations support wide applicability.

Rad, Roland; Rad, Lena; Wang, Wei; Cadinanos, Juan; Vassiliou, George; Rice, Stephen; Campos, Lia S.; Yusa, Kosuke; Banerjee, Ruby; Li, Meng Amy; de la Rosa, Jorge; Strong, Alexander; Lu, Dong; Ellis, Peter; Conte, Nathalie; Yang, Fang Tang; Liu, Pentao; Bradley, Allan

2013-01-01

108

Multiconstrained gene clustering based on generalized projections  

Microsoft Academic Search

Background: Gene clustering for annotating gene functions is one of the fundamental issues in bioinformatics. The best clustering solution is often regularized by multiple constraints such as gene expressions, Gene Ontology (GO) annotations and gene network structures. How to integrate multiple pieces of constraints for an optimal clustering solution still remains an unsolved problem. Results: We propose a novel multiconstrained

Jia Zeng; Shanfeng Zhu; Alan Wee-Chung Liew; Hong Yan

2010-01-01

109

Analysis of Brassica rapa ESTs: gene discovery and expression patterns of AP2/ERF family genes.  

PubMed

Chinese cabbage (Brassica rapa subsp. pekinensis) is among the most important vegetables and is widely cultivated in world. Genes in the AP2/ERF family encode transcriptional regulators that serve a variety of functions in the plants. Expressed sequence tags (ESTs) are created by partially sequencing randomly isolated gene transcripts and have proved valuable in molecular biology. Starting from the database with 142 947 ESTs of B. rapa, 62 putative AP2/ERF family genes were identified by in silico cloning using the conserved AP2/ERF domain amino acid sequence of Arabidopsis thaliana as a probe. Based on the number of AP2/ERF domains and functions of the genes, the AP2/ERF transcription factors from B. rapa were classified into four subfamilies (DREB, ERF, AP2 and RAV). Using large-scale available EST information as a source of expression data for digital expression profiling, differentially detected genes were identified among diverse plant tissues. Roots contained the largest number of transcripts of the AP2/ERF family genes, followed by leaves and seeds. Only a few of the 62 AP2/ERF family genes were detected in all tissues: most were detected only in some tissues but not in others. The maximum detected was that of BraERF-B2-5, and it was recorded from seed tissue. PMID:19701799

Zhuang, Jing; Xiong, Ai-Sheng; Peng, Ri-He; Gao, Feng; Zhu, Bo; Zhang, Jian; Fu, Xiao-Yan; Jin, Xiao-Feng; Chen, Jian-Min; Zhang, Zhen; Qiao, Yu-Shan; Yao, Quan-Hong

2009-08-23

110

Using Osteoclast Differentiation as a Model for Gene Discovery in an Undergraduate Cell Biology Laboratory  

ERIC Educational Resources Information Center

|A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory…

Birnbaum, Mark J.; Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.

2010-01-01

111

Gene discovery in the freshwater fish parasite Trypanosoma carassii: identification of trans-sialidase-like and mucin-like genes.  

PubMed

A total of 1,921 expressed sequence tags (ESTs) were obtained from bloodstream trypomastigotes of Trypanosoma carassii, a parasite of economic importance due to its high prevalence in fish farms. Analysis of the data set allowed us to identify a trans-sialidase (TS)-like gene and three ESTs coding for putative mucin-like genes. TS activity was detected in cell extracts of bloodstream trypomastigotes. We have also used the sequence information obtained to identify genes that have not been previously described in trypanosomatids. (Additional information on these ESTs can be found at http://genoma.unsam.edu.ar/projects/tca.) PMID:12438397

Agüero, Fernán; Campo, Vanina; Cremona, Laura; Jäger, Adriana; Di Noia, Javier M; Overath, Peter; Sánchez, Daniel O; Frasch, Alberto Carlos

2002-12-01

112

Gene Discovery in the Freshwater Fish Parasite Trypanosoma carassii: Identification of trans-Sialidase-Like and Mucin-Like Genes  

PubMed Central

A total of 1,921 expressed sequence tags (ESTs) were obtained from bloodstream trypomastigotes of Trypanosoma carassii, a parasite of economic importance due to its high prevalence in fish farms. Analysis of the data set allowed us to identify a trans-sialidase (TS)-like gene and three ESTs coding for putative mucin-like genes. TS activity was detected in cell extracts of bloodstream trypomastigotes. We have also used the sequence information obtained to identify genes that have not been previously described in trypanosomatids. (Additional information on these ESTs can be found at http://genoma.unsam.edu.ar/projects/tca.)

Aguero, Fernan; Campo, Vanina; Cremona, Laura; Jager, Adriana; Di Noia, Javier M.; Overath, Peter; Sanchez, Daniel O.; Frasch, Alberto Carlos

2002-01-01

113

Molecular Epidemiologic Approaches to Urinary Tract Infection Gene Discovery in Uropathogenic Escherichia coli  

PubMed Central

Urinary tract infection (UTI) is one of the most frequently acquired bacterial infections. The vast majority of UTIs are caused by a large, genetically heterogeneous group of Escherichia coli. This genetic diversity has hampered identification of UTI-related genes. A three-step experimental strategy was used to identify genes potentially involved in E. coli UTI transmission or virulence: epidemiologic pairing of a UTI-specific strain with a fecal control, differential cloning to isolated UTI strain-specific DNA, and epidemiologic screening to identify sequences among isolated DNAs that are associated with UTI. The 37 DNA sequences initially isolated were physically located all over the tester strain genome. Only two hybridized to the total DNA of the sequenced E. coli K-12 strain; eight sequences were present significantly more frequently in UTI isolates than in fecal isolates. Three of the eight sequences matched to genes for multidrug efflux proteins, usher proteins, and pathogenicity island insertion sites, respectively. Using population characteristics to direct gene discovery and evaluation is a productive strategy applicable to any system.

Zhang, Lixin; Foxman, Betsy; Manning, Shannon D.; Tallman, Patricia; Marrs, Carl F.

2000-01-01

114

Controlling false discoveries in multidimensional directional decisions, with applications to gene expression data on ordered categories.  

PubMed

Microarray gene expression studies over ordered categories are routinely conducted to gain insights into biological functions of genes and the underlying biological processes. Some common experiments are time-course/dose-response experiments where a tissue or cell line is exposed to different doses and/or durations of time to a chemical. A goal of such studies is to identify gene expression patterns/profiles over the ordered categories. This problem can be formulated as a multiple testing problem where for each gene the null hypothesis of no difference between the successive mean gene expressions is tested and further directional decisions are made if it is rejected. Much of the existing multiple testing procedures are devised for controlling the usual false discovery rate (FDR) rather than the mixed directional FDR (mdFDR), the expected proportion of Type I and directional errors among all rejections. Benjamini and Yekutieli (2005, Journal of the American Statistical Association 100, 71-93) proved that an augmentation of the usual Benjamini-Hochberg (BH) procedure can control the mdFDR while testing simple null hypotheses against two-sided alternatives in terms of one-dimensional parameters. In this article, we consider the problem of controlling the mdFDR involving multidimensional parameters. To deal with this problem, we develop a procedure extending that of Benjamini and Yekutieli based on the Bonferroni test for each gene. A proof is given for its mdFDR control when the underlying test statistics are independent across the genes. The results of a simulation study evaluating its performance under independence as well as under dependence of the underlying test statistics across the genes relative to other relevant procedures are reported. Finally, the proposed methodology is applied to a time-course microarray data obtained by Lobenhofer et al. (2002, Molecular Endocrinology 16, 1215-1229). We identified several important cell-cycle genes, such as DNA replication/repair gene MCM4 and replication factor subunit C2, which were not identified by the previous analyses of the same data by Lobenhofer et al. (2002) and Peddada et al. (2003, Bioinformatics 19, 834-841). Although some of our findings overlap with previous findings, we identify several other genes that complement the results of Lobenhofer et al. (2002). PMID:19645703

Guo, Wenge; Sarkar, Sanat K; Peddada, Shyamal D

2009-07-23

115

Long Serial Analysis of Gene Expression for Gene Discovery and Transcriptome Profiling in the Widespread Marine Coccolithophore Emiliania huxleyi†  

PubMed Central

The abundant and widespread coccolithophore Emiliania huxleyi plays an important role in mediating CO2 exchange between the ocean and the atmosphere through its impact on marine photosynthesis and calcification. Here, we use long serial analysis of gene expression (SAGE) to identify E. huxleyi genes responsive to nitrogen (N) or phosphorus (P) starvation. Long SAGE is an elegant approach for examining quantitative and comprehensive gene expression patterns without a priori knowledge of gene sequences via the detection of 21-bp nucleotide sequence tags. E. huxleyi appears to have a robust transcriptional-level response to macronutrient deficiency, with 42 tags uniquely present or up-regulated twofold or greater in the N-starved library and 128 tags uniquely present or up-regulated twofold or greater in the P-starved library. The expression patterns of several tags were validated with reverse transcriptase PCR. Roughly 48% of these differentially expressed tags could be mapped to publicly available genomic or expressed sequence tag (EST) sequence data. For example, in the P-starved library a number of the tags mapped to genes with a role in P scavenging, including a putative phosphate-repressible permease and a putative polyphosphate synthetase. In short, the long SAGE analyses have (i) identified many new differentially regulated gene sequences, (ii) assigned regulation data to EST sequences with no database homology and unknown function, and (iii) highlighted previously uncharacterized aspects of E. huxleyi N and P physiology. To this end, our long SAGE libraries provide a new public resource for gene discovery and transcriptional analysis in this biogeochemically important marine organism.

Dyhrman, Sonya T.; Haley, Sheean T.; Birkeland, Shanda R.; Wurch, Louie L.; Cipriano, Michael J.; McArthur, Andrew G.

2006-01-01

116

Riboswitches: discovery of drugs that target bacterial gene-regulatory RNAs  

PubMed Central

Conspectus Riboswitches, which were discovered in the first years of the XXI century, are gene-regulatory mRNA domains that respond to the intracellular concentration of a variety of metabolites and second messengers. They control essential genes in many pathogenic bacteria, and represent a new class of biomolecular target for the development of antibiotics and chemical-biological tools. Five mechanisms of gene regulation are known for riboswitches. Most bacterial riboswitches modulate transcription termination or translation initiation in response to ligand binding. All known examples of eukaryotic riboswitches and some bacterial riboswitches control gene expression by alternative splicing. The glmS riboswitch, widespread in Gram-positive bacteria, is a catalytic RNA activated by ligand binding. Its self-cleavage destabilizes the mRNA of which it is part. Finally, one example of trans-acting riboswitch is known. Three-dimensional (3D) structures have been determined of representatives of thirteen structurally distinct riboswitch classes, providing atomic-level insight into their mechanisms of ligand recognition. While cellular and viral RNAs in general have attracted interest as potential drug targets, riboswitches show special promise due to the diversity and sophistication of small molecule recognition strategies on display in their ligand binding pockets. Moreover, uniquely among known structured RNA domains, riboswitches evolved to recognize small molecule ligands. Structural and biochemical advances in the study of riboswitches provide an impetus for the development of methods for the discovery of novel riboswitch activators and inhibitors. Recent rational drug design efforts focused on select riboswitch classes have yielded a small number of candidate antibiotic compounds, including one active in a mouse model of Staphylococcus aureus infection. The development of high-throughput methods suitable for riboswitch-specific drug discovery is ongoing. A fragment-based screening approach employing equilibrium dialysis that may be generically useful has had early success. Riboswitch-mediated gene regulation is widely employed by bacteria; however, only the thiamine pyrophosphate-responsive riboswitch has thus far been found in eukaryotes. Thus, riboswitches are particularly attractive as targets for antibacterials. Indeed, antimicrobials with previously unknown mechanisms have been found to function by binding riboswitches and leading to aberrant gene expression.

Deigan, Katherine E.; Ferre-D'Amare, Adrian R.

2011-01-01

117

Discovery and validation of gene classifiers for endocrine-disrupting chemicals in zebrafish (danio rerio)  

PubMed Central

Background Development and application of transcriptomics-based gene classifiers for ecotoxicological applications lag far behind those of biomedical sciences. Many such classifiers discovered thus far lack vigorous statistical and experimental validations. A combination of genetic algorithm/support vector machines and genetic algorithm/K nearest neighbors was used in this study to search for classifiers of endocrine-disrupting chemicals (EDCs) in zebrafish. Searches were conducted on both tissue-specific and tissue-combined datasets, either across the entire transcriptome or within individual transcription factor (TF) networks previously linked to EDC effects. Candidate classifiers were evaluated by gene set enrichment analysis (GSEA) on both the original training data and a dedicated validation dataset. Results Multi-tissue dataset yielded no classifiers. Among the 19 chemical-tissue conditions evaluated, the transcriptome-wide searches yielded classifiers for six of them, each having approximately 20 to 30 gene features unique to a condition. Searches within individual TF networks produced classifiers for 15 chemical-tissue conditions, each containing 100 or fewer top-ranked gene features pooled from those of multiple TF networks and also unique to each condition. For the training dataset, 10 out of 11 classifiers successfully identified the gene expression profiles (GEPs) of their targeted chemical-tissue conditions by GSEA. For the validation dataset, classifiers for prochloraz-ovary and flutamide-ovary also correctly identified the GEPs of corresponding conditions while no classifier could predict the GEP from prochloraz-brain. Conclusions The discrepancies in the performance of these classifiers were attributed in part to varying data complexity among the conditions, as measured to some degree by Fisher’s discriminant ratio statistic. This variation in data complexity could likely be compensated by adjusting sample size for individual chemical-tissue conditions, thus suggesting a need for a preliminary survey of transcriptomic responses before launching a full scale classifier discovery effort. Classifier discovery based on individual TF networks could yield more mechanistically-oriented biomarkers. GSEA proved to be a flexible and effective tool for application of gene classifiers but a similar and more refined algorithm, connectivity mapping, should also be explored. The distribution characteristics of classifiers across tissues, chemicals, and TF networks suggested a differential biological impact among the EDCs on zebrafish transcriptome involving some basic cellular functions.

2012-01-01

118

Analysis of Brassica rapa ESTs: gene discovery and expression patterns of AP2\\/ERF family genes  

Microsoft Academic Search

Chinese cabbage (Brassica rapa subsp. pekinensis) is among the most important vegetables and is widely cultivated in world. Genes in the AP2\\/ERF family encode transcriptional\\u000a regulators that serve a variety of functions in the plants. Expressed sequence tags (ESTs) are created by partially sequencing\\u000a randomly isolated gene transcripts and have proved valuable in molecular biology. Starting from the database with

Jing Zhuang; Ai-Sheng Xiong; Ri-He Peng; Feng Gao; Bo Zhu; Jian Zhang; Xiao-Yan Fu; Xiao-Feng Jin; Jian-Min Chen; Zhen Zhang; Yu-Shan Qiao; Quan-Hong Yao

2010-01-01

119

Gene Set-Based Module Discovery Decodes cis-Regulatory Codes Governing Diverse Gene Expression across Human Multiple Tissues  

PubMed Central

Decoding transcriptional programs governing transcriptomic diversity across human multiple tissues is a major challenge in bioinformatics. To address this problem, a number of computational methods have focused on cis-regulatory codes driving overexpression or underexpression in a single tissue as compared to others. On the other hand, we recently proposed a different approach to mine cis-regulatory codes: starting from gene sets sharing common cis-regulatory motifs, the method screens for expression modules based on expression coherence. However, both approaches seem to be insufficient to capture transcriptional programs that control gene expression in a subset of all samples. Especially, this limitation would be serious when analyzing multiple tissue data. To overcome this limitation, we developed a new module discovery method termed BEEM (Biclusering-based Extraction of Expression Modules) in order to discover expression modules that are functional in a subset of tissues. We showed that, when applied to expression profiles of human multiple tissues, BEEM finds expression modules missed by two existing approaches that are based on the coherent expression and the single tissue-specific differential expression. From the BEEM results, we obtained new insights into transcriptional programs controlling transcriptomic diversity across various types of tissues. This study introduces BEEM as a powerful tool for decoding regulatory programs from a compendium of gene expression profiles.

Niida, Atsushi; Imoto, Seiya; Yamaguchi, Rui; Nagasaki, Masao; Miyano, Satoru

2010-01-01

120

Gene set-based module discovery decodes cis-regulatory codes governing diverse gene expression across human multiple tissues.  

PubMed

Decoding transcriptional programs governing transcriptomic diversity across human multiple tissues is a major challenge in bioinformatics. To address this problem, a number of computational methods have focused on cis-regulatory codes driving overexpression or underexpression in a single tissue as compared to others. On the other hand, we recently proposed a different approach to mine cis-regulatory codes: starting from gene sets sharing common cis-regulatory motifs, the method screens for expression modules based on expression coherence. However, both approaches seem to be insufficient to capture transcriptional programs that control gene expression in a subset of all samples. Especially, this limitation would be serious when analyzing multiple tissue data. To overcome this limitation, we developed a new module discovery method termed BEEM (Biclusering-based Extraction of Expression Modules) in order to discover expression modules that are functional in a subset of tissues. We showed that, when applied to expression profiles of human multiple tissues, BEEM finds expression modules missed by two existing approaches that are based on the coherent expression and the single tissue-specific differential expression. From the BEEM results, we obtained new insights into transcriptional programs controlling transcriptomic diversity across various types of tissues. This study introduces BEEM as a powerful tool for decoding regulatory programs from a compendium of gene expression profiles. PMID:20544005

Niida, Atsushi; Imoto, Seiya; Yamaguchi, Rui; Nagasaki, Masao; Miyano, Satoru

2010-06-09

121

An interactive web-based Pseudomonas aeruginosa genome database: discovery of new genes, pathways and structures  

Microsoft Academic Search

Using the complete genome sequence of Pseudomonas aeruginosa PAO1, sequenced by the Pseudomonas Genome Project (ftp:\\/\\/ftp.pseudomonas.com\\/data\\/pacontigs.121599), a genome database (http:\\/\\/pseudomonas.bit.uq.edu.au\\/) has been developed containing information on more than 95% of all ORFs in Pseudomonas aeruginosa. The database is searchable by a variety of means, including gene name, position, keyword, sequence similarity and Pfam domain. Automated and manual annotation, nucleotide and

Larry Croft; Scott A. Beatson; Cynthia B. Whitchurch; Bixing Huang; Robert L. Blakeley; John S. Mattick

2000-01-01

122

Discovery of Genes Related to Diabetic Nephropathy in Various Animal Models by Current Techniques  

PubMed Central

One of the major problems facing clinical nephrology currently throughout the world is an exponential increase in patients with end-stage renal disease (ESRD), which is largely related to a high incidence of diabetic nephropathy. The latter is characterized by a multitude of metabolic and signaling events following excessive channeling of glucose, which leads to an increased synthesis of extracellular matrix (ECM) glycoproteins resulting in glomerulosclerosis, interstitial fibrosis and ultimately ESRD. With the incidence of nephropathy at pandemic levels and a high rate of ESRD, physicians around the world must treat a disproportionately large number of diabetic patients with up-to-date innovative measures. In this regard, identification of genes that are crucially involved in the progression of diabetic nephropathy would enhance the discovery of new biomarkers and could also promote the development of novel therapeutic strategies. Over the last decade, we focused on the recent methodologies of high-throughput and genome-wide screening for identification of relevant genes in various animal models, which included the following: (1) single nucleotide polymorphism-based genome-wide screening; (2) the transcriptome approach, such as differential display reverse transcription polymerase chain reaction (DDRT-PCR), representational difference analysis of cDNA (cDNA-RDA)/suppressive subtractive hybridization, SAGE (serial analysis of gene expression) and DNA Microarray; and (3) the proteomic approach and 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) coupled with mass spectroscopic analysis. Several genes, such as Tim44 (translocase of inner mitochondrial membrane-44), RSOR/MIOX (renal specific oxidoreductase/myo-inositol oxygenase), UbA52, Rap1b (Ras-related GTPase), gremlin, osteopontin, hydroxysteroid dehydrogenase-3? isotype 4 and those of the Wnt signaling pathway, were identified as differentially expressed genes in kidneys of diabetic rodents. Functional analysis of these genes and the subsequent translational research in the clinical settings would be very valuable in the prevention and treatment of diabetic nephropathy. Future trends for identification of the biomarkers and therapeutic target genes should also include genome scale DNA/histone-methylation profiling, metabolomic approaches (e.g. metabolic phenotyping by 1H spectroscopy) and lectin microarray for glycan profiling along with the development of robust data-mining strategies.

Wada, Jun; Sun, Lin; Kanwar, Yashpal S.

2013-01-01

123

The Arabidopsis SeedGenes Project  

Microsoft Academic Search

The SeedGenes database (http:\\/\\/www.seedgenes.org) presents molecular and phenotypic information on essential, non-redundant genes of Arabidopsis that give a seed phenotype when disrupted by mutation. Experimental details are synthesized for efficient use by the community and organized into two major sections in the database, one dealing with genes and the other with mutant alleles. The database can be queried for detailed

Iris Tzafrir; Allan Dickerman; Olga Brazhnik; Quoc Nguyen; John Mcelver; Catherine Frye; David Patton; David Meinke

2003-01-01

124

Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis  

PubMed Central

Summary Heme biosynthesis consists of a series of eight enzymatic reactions that originate in mitochondria and continue in the cytosol before returning to mitochondria. Although these core enzymes are well studied, additional mitochondrial transporters and regulatory factors are predicted to be required. To discover such unknown components, we utilized a large-scale computational screen to identify mitochondrial proteins whose transcripts consistently co-express with the core machinery of heme biosynthesis. We identified SLC25A39, SLC22A4 and TMEM14C, which are putative mitochondrial transporters, as well as C1orf69 and ISCA1, which are iron-sulfur cluster proteins. Targeted knockdowns of all five genes in zebrafish resulted in profound anemia without impacting erythroid lineage specification. Moreover, silencing of Slc25a39 in murine erythroleukemia cells impaired iron incorporation into protoporphyrin IX, and vertebrate Slc25a39 complemented an iron homeostasis defect in the orthologous yeast mtm1? deletion mutant. Our results advance the molecular understanding of heme biosynthesis and offer promising candidate genes for inherited anemias.

Nilsson, Roland; Schultz, Iman J.; Pierce, Eric L.; Soltis, Kathleen A.; Naranuntarat, Amornrat; Ward, Diane M.; Baughman, Joshua; Paradkar, Prasad N.; Kingsley, Paul D.; Culotta, Valeria C.; Kaplan, Jerry; Palis, James; Paw, Barry H.; Mootha, Vamsi K.

2009-01-01

125

De novo assembly of chickpea transcriptome using short reads for gene discovery and marker identification.  

PubMed

Chickpea ranks third among the food legume crops production in the world. However, the genomic resources available for chickpea are still very limited. In the present study, the transcriptome of chickpea was sequenced with short reads on Illumina Genome Analyzer platform. We have assessed the effect of sequence quality, various assembly parameters and assembly programs on the final assembly output. We assembled ~107million high-quality trimmed reads using Velvet followed by Oases with optimal parameters into a non-redundant set of 53 409 transcripts (?100 bp), representing about 28 Mb of unique transcriptome sequence. The average length of transcripts was 523 bp and N50 length of 900 bp with coverage of 25.7 rpkm (reads per kilobase per million). At the protein level, a total of 45 636 (85.5%) chickpea transcripts showed significant similarity with unigenes/predicted proteins from other legumes or sequenced plant genomes. Functional categorization revealed the conservation of genes involved in various biological processes in chickpea. In addition, we identified simple sequence repeat motifs in transcripts. The chickpea transcripts set generated here provides a resource for gene discovery and development of functional molecular markers. In addition, the strategy for de novo assembly of transcriptome data presented here will be helpful in other similar transcriptome studies. PMID:21217129

Garg, Rohini; Patel, Ravi K; Tyagi, Akhilesh K; Jain, Mukesh

2011-01-07

126

De Novo Assembly of Chickpea Transcriptome Using Short Reads for Gene Discovery and Marker Identification  

PubMed Central

Chickpea ranks third among the food legume crops production in the world. However, the genomic resources available for chickpea are still very limited. In the present study, the transcriptome of chickpea was sequenced with short reads on Illumina Genome Analyzer platform. We have assessed the effect of sequence quality, various assembly parameters and assembly programs on the final assembly output. We assembled ?107million high-quality trimmed reads using Velvet followed by Oases with optimal parameters into a non-redundant set of 53 409 transcripts (?100 bp), representing about 28 Mb of unique transcriptome sequence. The average length of transcripts was 523 bp and N50 length of 900 bp with coverage of 25.7 rpkm (reads per kilobase per million). At the protein level, a total of 45 636 (85.5%) chickpea transcripts showed significant similarity with unigenes/predicted proteins from other legumes or sequenced plant genomes. Functional categorization revealed the conservation of genes involved in various biological processes in chickpea. In addition, we identified simple sequence repeat motifs in transcripts. The chickpea transcripts set generated here provides a resource for gene discovery and development of functional molecular markers. In addition, the strategy for de novo assembly of transcriptome data presented here will be helpful in other similar transcriptome studies.

Garg, Rohini; Patel, Ravi K.; Tyagi, Akhilesh K.; Jain, Mukesh

2011-01-01

127

Metadata Creation, Transformation and Discovery for Social Science Data Management: The DAMES Project Infrastructure  

Microsoft Academic Search

This paper discusses the use of metadata, underpinned by DDI (Data Documentation Initiative), to support social science data management. This term refers broadly to the discovery, preparation and manipulation of social science data for the purposes of research and analysis. Typical tasks include recoding variables within a dataset, and linking data from different sources. A description is given of the

Jesse M. Blum; Guy C. Warner; Simon B. Jones; Paul S. Lambert; Alison S. F. Dawson; Kenneth J. Turner

2009-01-01

128

Gene network analysis of Aeromonas hydrophila for novel drug target discovery.  

PubMed

Increasing the multi-drug resistance Aeromonas hydrophila creates a health problem regularly thus, an urgent needs to develop and screen potent antibiotics for controlling of the infections. There are many studies have focused on interactions between specific drugs, little is known about the system properties of a full drug interaction in gene network. Thus, an attractive approach for developing novel antibiotics against DNA gyrase, an enzyme essential for DNA replication, transcription, repair and recombination mechanisms which is important for bacterial growth and cell division. Homology modeling method was used to generate the 3-D structure of B subunit of DNA gyrase (gyrB) using known crystal structure. The active amino acids in 3-D structure of gyrB were targeted for structure based virtual screening of potent drugs by molecular docking. Number of drugs and analogs were selected and used for docking against gryB. The drugs Cinodine I, Cyclothialidine and Novobiocin were found to be more binding affinity with gyrB-drug interaction. The homology of gyrB protein sequence of A. hydrophila resembles with other species of Aeromonas closely showed relationship in phylogenetic tree. We have also demonstrated the gene network interactions of gyrB with other cellular proteins which are playing the key role in gene regulation. These findings provide new insight to understand the 3-D structure of gyrB which can be used in structure-based drug discovery; and development of novel, potent and specific drug against B subunit of DNA gyrase. PMID:23730361

Singh, Vijai; Chaudhary, Dharmendra Kumar; Mani, Indra

2012-05-22

129

Estimation of false discovery rates in multiple testing: application to gene microarray data.  

PubMed

Testing for significance with gene expression data from DNA microarray experiments involves simultaneous comparisons of hundreds or thousands of genes. If R denotes the number of rejections (declared significant genes) and V denotes the number of false rejections, then V/R, if R > 0, is the proportion of false rejected hypotheses. This paper proposes a model for the distribution of the number of rejections and the conditional distribution of V given R, V / R. Under the independence assumption, the distribution of R is a convolution of two binomials and the distribution of V / R has a noncentral hypergeometric distribution. Under an equicorrelated model, the distributions are more complex and are also derived. Five false discovery rate probability error measures are considered: FDR = E(V/R), pFDR = E(V/R / R > 0) (positive FDR), cFDR = E(V/R / R = r) (conditional FDR), mFDR = E(V)/E(R) (marginal FDR), and eFDR = E(V)/r (empirical FDR). The pFDR, cFDR, and mFDR are shown to be equivalent under the Bayesian framework, in which the number of true null hypotheses is modeled as a random variable. We present a parametric and a bootstrap procedure to estimate the FDRs. Monte Carlo simulations were conducted to evaluate the performance of these two methods. The bootstrap procedure appears to perform reasonably well, even when the alternative hypotheses are correlated (rho = .25). An example from a toxicogenomic microarray experiment is presented for illustration. PMID:14969487

Tsai, Chen-An; Hsueh, Huey-miin; Chen, James J

2003-12-01

130

Snpdat: Easy and rapid annotation of results from de novo snp discovery projects for model and non-model organisms  

PubMed Central

Background Single nucleotide polymorphisms (SNPs) are the most abundant genetic variant found in vertebrates and invertebrates. SNP discovery has become a highly automated, robust and relatively inexpensive process allowing the identification of many thousands of mutations for model and non-model organisms. Annotating large numbers of SNPs can be a difficult and complex process. Many tools available are optimised for use with organisms densely sampled for SNPs, such as humans. There are currently few tools available that are species non-specific or support non-model organism data. Results Here we present SNPdat, a high throughput analysis tool that can provide a comprehensive annotation of both novel and known SNPs for any organism with a draft sequence and annotation. Using a dataset of 4,566 SNPs identified in cattle using high-throughput DNA sequencing we demonstrate the annotations performed and the statistics that can be generated by SNPdat. Conclusions SNPdat provides users with a simple tool for annotation of genomes that are either not supported by other tools or have a small number of annotated SNPs available. SNPdat can also be used to analyse datasets from organisms which are densely sampled for SNPs. As a command line tool it can easily be incorporated into existing SNP discovery pipelines and fills a niche for analyses involving non-model organisms that are not supported by many available SNP annotation tools. SNPdat will be of great interest to scientists involved in SNP discovery and analysis projects, particularly those with limited bioinformatics experience.

2013-01-01

131

Display technologies: application for the discovery of drug and gene delivery agents  

PubMed Central

Recognition of molecular diversity of cell surface proteomes in disease is essential for the development of targeted therapies. Progress in targeted therapeutics requires establishing effective approaches for high-throughput identification of agents specific for clinically relevant cell surface markers. Over the past decade, a number of platform strategies have been developed to screen polypeptide libraries for ligands targeting receptors selectively expressed in the context of various cell surface proteomes. Streamlined procedures for identification of ligand-receptor pairs that could serve as targets in disease diagnosis, profiling, imaging and therapy have relied on the display technologies, in which polypeptides with desired binding profiles can be serially selected, in a process called biopanning, based on their physical linkage with the encoding nucleic acid. These technologies include virus/phage display, cell display, ribosomal display, mRNA display and covalent DNA display (CDT), with phage display being by far the most utilized. The scope of this review is the recent advancements in the display technologies with a particular emphasis on molecular mapping of cell surface proteomes with peptide phage display. Prospective applications of targeted compounds derived from display libraries in the discovery of targeted drugs and gene therapy vectors are discussed.

Sergeeva, Anna; Kolonin, Mikhail G.; Molldrem, Jeffrey J.; Pasqualini, Renata; Arap, Wadih

2007-01-01

132

Paradigm of Tunable Clustering Using Binarization of Consensus Partition Matrices (Bi-CoPaM) for Gene Discovery  

PubMed Central

Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.

Abu-Jamous, Basel; Fa, Rui; Roberts, David J.; Nandi, Asoke K.

2013-01-01

133

Gene invasion in distant eukaryotic lineages: discovery of mutually exclusive genetic elements reveals marine biodiversity  

PubMed Central

Inteins are rare, translated genetic parasites mainly found in bacteria and archaea, while spliceosomal introns are distinctly eukaryotic features abundant in most nuclear genomes. Using targeted metagenomics, we discovered an intein in an Atlantic population of the photosynthetic eukaryote, Bathycoccus, harbored by the essential spliceosomal protein PRP8 (processing factor 8 protein). Although previously thought exclusive to fungi, we also identified PRP8 inteins in parasitic (Capsaspora) and predatory (Salpingoeca) protists. Most new PRP8 inteins were at novel insertion sites that, surprisingly, were not in the most conserved regions of the gene. Evolutionarily, Dikarya fungal inteins at PRP8 insertion site a appeared more related to the Bathycoccus intein at a unique insertion site, than to other fungal and opisthokont inteins. Strikingly, independent analyses of Pacific and Atlantic samples revealed an intron at the same codon as the Bathycoccus PRP8 intein. The two elements are mutually exclusive and neither was found in cultured Bathycoccus or other picoprasinophyte genomes. Thus, wild Bathycoccus contain one of few non-fungal eukaryotic inteins known and a rare polymorphic intron. Our data indicate at least two Bathycoccus ecotypes exist, associated respectively with oceanic or mesotrophic environments. We hypothesize that intein propagation is facilitated by marine viruses; and, while intron gain is still poorly understood, presence of a spliceosomal intron where a locus lacks an intein raises the possibility of new, intein-primed mechanisms for intron gain. The discovery of nucleus-encoded inteins and associated sequence polymorphisms in uncultivated marine eukaryotes highlights their diversity and reveals potential sexual boundaries between populations indistinguishable by common marker genes.

Monier, Adam; Sudek, Sebastian; Fast, Naomi M; Worden, Alexandra Z

2013-01-01

134

European approach to the human gene project  

SciTech Connect

In the history of gene mapping, which extends through most of the present century, Europe has played an important role. This has continued during the evolution of the 10 International Human Gene Mapping Workshops that have been held in seven different countries since 1973. Nationally coordinated programs have been a recent development, and several European countries, including the United Kingdom and Italy, have followed the lead of the United States in investing substantial sums of money in research on the human genome. In addition, the European Community has launched a multinational program of research on Human Genome Analysis to complement the various national initiatives. The particular approach in Europe has been to support those in the field by establishing resource centers for distributing biomaterials and accessing databases, by assisting in the training of scientists, and by funding programs of research directed at present needs in both physical and genetic mapping.

Ferguson-Smith, M.A. (Cambridge Univ. (England))

1991-01-01

135

European approach to the Human Gene Project.  

PubMed

In the history of gene mapping, which extends through most of the present century, Europe has played an important role. This has continued during the evolution of the 10 International Human Gene Mapping Workshops that have been held in seven different countries since 1973. Nationally coordinated programs have been a recent development, and several European countries, including the United Kingdom and Italy, have followed the lead of the United States in investing substantial sums of money in research on the human genome. In addition, the European Community has launched a multinational program of research on Human Genome Analysis to complement the various national initiatives. The particular approach in Europe has been to support those in the field by establishing resource centers for distributing biomaterials and accessing databases, by assisting in the training of scientists, and by funding programs of research directed at present needs in both physical and genetic mapping. PMID:1991586

Ferguson-Smith, M A

1991-01-01

136

Project Quest: A Journey of Discovery with Beginning Teachers in Urban Schools  

Microsoft Academic Search

Seven higher education institutions in Massachusetts collaborated to develop and implement Project QUEST (Quality Urban Education and Support for Teachers), a support program for beginning urban teachers. Motivated by both the need to retain beginning teachers beyond the first few years of teaching and the desire to increase urban school children's achievement, Project QUEST teachers, mentors, and researchers concentrated on

Kimberley Alkins; Linda Banks-Santilli; Paula Elliott; Nicole Guttenberg; Mieko Kamii

2006-01-01

137

Using false discovery rates to benchmark SNP-callers in next-generation sequencing projects.  

PubMed

Sequence alignments form the basis for many comparative and population genomic studies. Alignment tools provide a range of accuracies dependent on the divergence between the sequences and the alignment methods. Despite widespread use, there is no standard method for assessing the accuracy of a dataset and alignment strategy after resequencing. We present a framework and tool for determining the overall accuracies of an input read dataset, alignment and SNP-calling method providing an isolate in that dataset has a corresponding, or closely related reference sequence available. In addition to this tool for comparing False Discovery Rates (FDR), we include a method for determining homozygous and heterozygous positions from an alignment using binomial probabilities for an expected error rate. We benchmark this method against other SNP callers using our FDR method with three fungal genomes, finding that it was able achieve a high level of accuracy. These tools are available at http://cfdr.sourceforge.net/. PMID:23518929

Farrer, Rhys A; Henk, Daniel A; MacLean, Dan; Studholme, David J; Fisher, Matthew C

2013-01-01

138

Using False Discovery Rates to Benchmark SNP-callers in next-generation sequencing projects  

PubMed Central

Sequence alignments form the basis for many comparative and population genomic studies. Alignment tools provide a range of accuracies dependent on the divergence between the sequences and the alignment methods. Despite widespread use, there is no standard method for assessing the accuracy of a dataset and alignment strategy after resequencing. We present a framework and tool for determining the overall accuracies of an input read dataset, alignment and SNP-calling method providing an isolate in that dataset has a corresponding, or closely related reference sequence available. In addition to this tool for comparing False Discovery Rates (FDR), we include a method for determining homozygous and heterozygous positions from an alignment using binomial probabilities for an expected error rate. We benchmark this method against other SNP callers using our FDR method with three fungal genomes, finding that it was able achieve a high level of accuracy. These tools are available at http://cfdr.sourceforge.net/.

Farrer, Rhys A.; Henk, Daniel A.; MacLean, Dan; Studholme, David J.; Fisher, Matthew C.

2013-01-01

139

International Gene Trap Project: towards gene-driven saturation mutagenesis in mice.  

PubMed

While the human genome project has been completed, analysis of functions of each gene is still underway. Knockout and knock down of gene products offer useful tools to understand functions of a single gene in vivo. Production of knockout mice using homologous recombination in embryonic stem (ES) cells is a powerful and established strategy. However, it is laborious, time-consuming and expensive if expanding large scale. In mice, the gene trap is an alternative strategy to disrupt gene functions by random disruption of gene. The functions of a gene in vivo can be analyzed by production of mice from trapped ES clones. Large-scale gene trap projects have been started in some research centers of the world, and the International Gene Trap Consortium (IGTC) was established to strengthen interactions among centers involved. Moreover, the website of the IGTC has been constructed to integrate information of trap clones from each gene trap project. The database of the IGTC is expanding rapidly because of accumulation of information about gene trap clones from ongoing gene trap projects; approximately 135,000 trapped ES lines are registered in June, 2008. These clones are freely available to academic community. At moment, the IGTC cell lines have covered approximately 10,000 genes in the mouse genome database. Therefore, it is recommended to check the IGTC database before starting knockout experiment, even when annotations of genes are not available. In this review, we introduce principle and short history of gene trap, and then use of the IGTC database is described to obtain trapped ES clones for the experiments. PMID:19199955

Araki, Masatake; Araki, Kimi; Yamamura, Ken-ichi

2009-02-01

140

A fast document classification algorithm for gene symbol disambiguation in the BITOLA literature-based discovery support system.  

PubMed

Gene symbol disambiguation is an important problem for biomedical text mining systems. When detecting gene symbols in MEDLINE citations one of the biggest challenges is the fact that many gene symbols also denote other, more general biomedical concepts (e.g. CT, MR). Our approach to this problem is first to classify the citations into genetic and non-genetic domains and then to detect gene symbols only in the genetic domain. We used ontological information provided by Medical Subject Headings (MeSH) for this classification task. The proposed algorithm is fast and is able to process the full MEDLINE distribution in a few hours. It achieves predictive accuracy of 0.91. The algorithm is currently implemented in the BITOLA literature-based discovery support system (http://www.mf.uni-lj.si/bitola/). PMID:18998999

Kastrin, Andrej; Hristovski, Dimitar

2008-11-06

141

The Venus Transit 2004 (VT-2004) Programme: The Exceptional Impact of a Unique Public Science Discovery Project  

NASA Astrophysics Data System (ADS)

We report on a major pan-European educational activity: the Venus Transit 2004 Public Science Discovery Programme. The key objectives were to use the 2004 Transit as a vehicle for disseminating knowledge about the Solar System, for raising awareness of exoplanet research, to enable the public to re-enact the historical measurement of the Sun-Earth distance, to raise public appreciation of the scientific method and to collectively obtain a basic scientific result based on geographically distributed observations. This very successful pilot project encompassed the development of an extensive set of teaching materials for schools, an effective web-based information and reporting system, observational activities as well as a video contest and a thorough post-event evaluation during a final meeting.

Boffin, H.; West, R.

2005-12-01

142

Discovery of Gene Families and Alternatively Spliced Variants by RecA-Mediated Cloning  

Microsoft Academic Search

Probing the functional complexity of the human genome will require new gene cloning techniques, not only to discover intraspecies gene homologs and interspecies gene orthologs, but also to identify alternatively spliced gene variants. We report homologous cDNA cloning methods that allow cloning of gene family members, genes from different species, and alternatively spliced gene variants. We cloned human 14-3-3 gene

Hong Zeng; Elizabeth Allen; Chris W. Lehman; R. Geoffrey Sargent; Sushma Pati; David A. Zarling

2002-01-01

143

Project Quest: A Journey of Discovery with Beginning Teachers in Urban Schools  

ERIC Educational Resources Information Center

|Seven higher education institutions in Massachusetts collaborated to develop and implement Project QUEST (Quality Urban Education and Support for Teachers), a support program for beginning urban teachers. Motivated by both the need to retain beginning teachers beyond the first few years of teaching and the desire to increase urban school…

Alkins, Kimberley; Banks-Santilli, Linda; Elliott, Paula; Guttenberg, Nicole; Kamii, Mieko

2006-01-01

144

Breccia-Hosted Gold-Silver Discovery Enhances Exploration Potential Of Scotgold's Grampian Gold Project  

Microsoft Academic Search

SUMMARY Scotgold Resources Limited (ASX:SGZ) has identified significant breccia-hosted gold-silver mineralization at the Beinn Udlaidh prospect in association with a lamprophyre field. The prospect is located five kilometers north northwest of the high grade Cononish Gold and Silver Deposit, highlighting the potential of Beinn Udlaidh prospect to host a large additional gold\\/silver resource in the Grampian Gold Project, Scotland. The

2009-01-01

145

A Road to Discovery Science  

Microsoft Academic Search

\\u000a We have started a project: Grant-in-Aid for Scientific Research on Priority Area “Discovery Science” sponsored by Ministry\\u000a of ESSC, Japan. The “Discovery Science” is a three-year project from 1998 to 2000 that targets to develop new methods for\\u000a knowledge discovery, install network environments for knowledge discovery, and establish the Discovery Science as a new area\\u000a of Computer Science. A systematic

Setsuo Arikawa

146

Gene discovery using massively parallel pyrosequencing to develop ESTs for the flesh fly Sarcophaga crassipalpis  

PubMed Central

Background Flesh flies in the genus Sarcophaga are important models for investigating endocrinology, diapause, cold hardiness, reproduction, and immunity. Despite the prominence of Sarcophaga flesh flies as models for insect physiology and biochemistry, and in forensic studies, little genomic or transcriptomic data are available for members of this genus. We used massively parallel pyrosequencing on the Roche 454-FLX platform to produce a substantial EST dataset for the flesh fly Sarcophaga crassipalpis. To maximize sequence diversity, we pooled RNA extracted from whole bodies of all life stages and normalized the cDNA pool after reverse transcription. Results We obtained 207,110 ESTs with an average read length of 241 bp. These reads assembled into 20,995 contigs and 31,056 singletons. Using BLAST searches of the NR and NT databases we were able to identify 11,757 unique gene elements (E<0.0001) representing approximately 9,000 independent transcripts. Comparison of the distribution of S. crassipalpis unigenes among GO Biological Process functional groups with that of the Drosophila melanogaster transcriptome suggests that our ESTs are broadly representative of the flesh fly transcriptome. Insertion and deletion errors in 454 sequencing present a serious hurdle to comparative transcriptome analysis. Aided by a new approach to correcting for these errors, we performed a comparative analysis of genetic divergence across GO categories among S. crassipalpis, D. melanogaster, and Anopheles gambiae. The results suggest that non-synonymous substitutions occur at similar rates across categories, although genes related to response to stimuli may evolve slightly faster. In addition, we identified over 500 potential microsatellite loci and more than 12,000 SNPs among our ESTs. Conclusion Our data provides the first large-scale EST-project for flesh flies, a much-needed resource for exploring this model species. In addition, we identified a large number of potential microsatellite and SNP markers that could be used in population and systematic studies of S. crassipalpis and other flesh flies.

Hahn, Daniel A; Ragland, Gregory J; Shoemaker, D DeWayne; Denlinger, David L

2009-01-01

147

Discovery of the faithfulness gene: A model of transmission and transformation of scientific information  

Microsoft Academic Search

The purpose of this paper is to study the diffusion and transformation of scientific information in everyday discussions. Based on rumour models and social representations theory, the impact of interpersonal communication and pre-existing beliefs on transmission of the content of a scientific discovery was analysed. In three experiments, a communication chain was simulated to investigate how laypeople make sense of

Eva G. T. Green; Alain Clémence

2008-01-01

148

Model selection for prognostic time-to-event gene signature discovery with applications in early breast cancer data.  

PubMed

Abstract Model selection between competing models is a key consideration in the discovery of prognostic multigene signatures. The use of appropriate statistical performance measures as well as verification of biological significance of the signatures is imperative to maximise the chance of external validation of the generated signatures. Current approaches in time-to-event studies often use only a single measure of performance in model selection, such as logrank test p-values, or dichotomise the follow-up times at some phase of the study to facilitate signature discovery. In this study we improve the prognostic signature discovery process through the application of the multivariate partial Cox model combined with the concordance index, hazard ratio of predictions, independence from available clinical covariates and biological enrichment as measures of signature performance. The proposed framework was applied to discover prognostic multigene signatures from early breast cancer data. The partial Cox model combined with the multiple performance measures were used in both guiding the selection of the optimal panel of prognostic genes and prediction of risk within cross validation without dichotomising the follow-up times at any stage. The signatures were successfully externally cross validated in independent breast cancer datasets, yielding a hazard ratio of 2.55 [1.44, 4.51] for the top ranking signature. PMID:24077567

Ahdesmäki, Miika; Lancashire, Lee; Proutski, Vitali; Wilson, Claire; Davison, Timothy S; Harkin, D Paul; Kennedy, Richard D

2013-10-01

149

A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules  

Microsoft Academic Search

To elucidate gene function on a global scale, we identified pairs of genes that are coexpressed over 3182 DNA microarrays from humans, flies, worms, and yeast. We found 22,163 such coexpression relationships, each of which has been conserved across evolution. This conservation implies that the coexpression of these gene pairs confers a selective advantage and therefore that these genes are

Joshua M. Stuart; Eran Segal; Daphne Koller; Stuart K. Kim

2003-01-01

150

Ataxin1L Is a Regulator of HSC Function Highlighting the Utility of Cross-Tissue Comparisons for Gene Discovery  

PubMed Central

Hematopoietic stem cells (HSCs) are rare quiescent cells that continuously replenish the cellular components of the peripheral blood. Observing that the ataxia-associated gene Ataxin-1-like (Atxn1L) was highly expressed in HSCs, we examined its role in HSC function through in vitro and in vivo assays. Mice lacking Atxn1L had greater numbers of HSCs that regenerated the blood more quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L null HSCs had gene expression changes that regulate a program consistent with their higher level of proliferation, suggesting that Atxn1L is a novel regulator of HSC quiescence. To determine if additional brain-associated genes were candidates for hematologic regulation, we examined genes encoding proteins from autism- and ataxia-associated protein–protein interaction networks for their representation in hematopoietic cell populations. The interactomes were found to be highly enriched for proteins encoded by genes specifically expressed in HSCs relative to their differentiated progeny. Our data suggest a heretofore unappreciated similarity between regulatory modules in the brain and HSCs, offering a new strategy for novel gene discovery in both systems.

Yu, Peng; Zohren, Fabian; Lee, Yoontae; Shaw, Chad A.; Zoghbi, Huda Y.; Goodell, Margaret A.

2013-01-01

151

High-throughput and parallel SNP discovery in selected candidate genes in Eucalyptus camaldulensis using Illumina NGS platform.  

PubMed

Next generation sequencing (NGS) technologies have revolutionized the pace and scale of genomics- and transcriptomics-based SNP discovery across different plant and animal species. Herein, 72-base paired-end Illumina sequencing was employed for high-throughput, parallel and large-scale SNP discovery in 41 growth-related candidate genes in Eucalyptus camaldulensis. Approximately 100?kb of genome from 96 individuals was amplified and sequenced using a hierarchical DNA/PCR pooling strategy and assembled over corresponding E. grandis reference. A total of 1191 SNPs (minimum 5% other allele frequency) were identified with an average frequency of 1 SNP/83.9?bp, whereas in exons and introns, it was 1 SNP/108.4?bp and 1 SNP/65.6?bp, respectively. A total of 75 insertions and 89 deletions were detected of which approximately 15% were exonic. Transitions (Tr) were in excess than transversions (Tv) (Tr/Tv: 1.89), but exceeded in exons (Tr/Tv: 2.73). In exons, synonymous SNPs (Ka) prevailed over the non-synonymous SNPs (Ks; average Ka/Ks ratio: 0.72, range: 0-3.00 across genes). Many of the exonic SNPs/indels had potential to change amino acid sequence of respective genes. Transcription factors appeared more conserved, whereas enzyme coding genes appeared under relaxed control. Further, 541 SNPs were classified into 196 'equal frequency' (EF) blocks with almost similar minor allele frequencies to facilitate selection of one tag-SNP/EF-block. There were 241 (approximately 20%) 'zero-SNP' blocks with absence of SNPs in surrounding ±60?bp windows. The data thus indicated enormous extant and unexplored diversity in E. camaldulensis in the studied genes with potential applications for marker-trait associations. PMID:22607345

Hendre, Prasad S; Kamalakannan, R; Varghese, Mohan

2012-05-18

152

Discovery of Genes Activated by the Mitochondrial Unfolded Protein Response (mtUPR) and Cognate Promoter Elements  

PubMed Central

In an accompanying paper, we show that the mitochondrial Unfolded Protein Response or mtUPR is initiated by the activation of transcription of chop through an AP-1 element in the chop promoter. Further, we show that the c/ebp? gene is similarly activated and CHOP and C/EBP? subsequently hetero-dimerise to activate transcription of mtUPR responsive genes. Here, we report the discovery of six additional mtUPR responsive genes. We found that these genes encoding mitochondrial proteases YME1L1 and MPP?, import component Tim17A and enzymes NDUFB2, endonuclease G and thioredoxin 2, all contain a CHOP element in their promoters. In contrast, genes encoding mitochondrial proteins Afg3L2, Paraplegin, Lon and SAM 50, which do not have a CHOP element, were not up-regulated. Conversely, genes with CHOP elements encoding cytosolic proteins were not induced by the accumulation of unfolded proteins in mitochondria. These results indicate that mtUPR responsive genes appear to share a requirement for a CHOP element, but that this is not sufficient for the regulation of the mtUPR. A more detailed analysis of promoters of mtUPR responsive genes revealed at least two additional highly conserved, putative regulatory sites either side of the CHOP element, one a motif of 12 bp which lies 14 bp upstream of the CHOP site and another 9 bp element, 2 bp downstream of the CHOP site. Both of these additional elements are conserved in the promoters of 9 of the ten mtUPR responsive genes we have identified so far, the exception being the Cpn60/10 bidirectional promoter. Mutation of each of these elements substantially reduced the mtUPR responsiveness of the promoters suggesting that these elements coordinately regulate mtUPR.

Aldridge, Jonathan E.; Horibe, Tomohisa; Hoogenraad, Nicholas J.

2007-01-01

153

The Discovery Method in Training.  

ERIC Educational Resources Information Center

|In the form of a discussion between faceless people, this booklet concerns discovery learning and its advantages. Subjects covered in the discussions are: Introducing the Discovery Method; An Experiment with British Railways; The OECD Research Projects in U.S.A., Austria, and Sweden; How the Discovery Method Differs from Other Methods; Discovery

Belbin, R. M.

154

Two Pulsar Discoveries from the Einstein@Home Distributed Computing Project  

NASA Astrophysics Data System (ADS)

We present two pulsars discovered by Einstein@Home, a distributed computing project that runs on volunteers' computers and searches for gravitational waves in LIGO data and binary pulsars in Arecibo PALFA data. J2007+27 is an isolated pulsar with a period of 24.49 ms. Its unusually large duty cycle and the presence of emission almost throughout the rotation period suggests that its magnetic and spin axes are nearly aligned. Limits on the period derivative, magnetic field, and age indicate that this is the fastest-spinning disrupted recycled pulsar known to date. J1952+26 has a period of 20.73 ms and is in a 7-hour binary. Assuming a pulsar mass of 1.4 Msun, the system's mass function indicates that the minimum companion mass is 0.95 Msun. The companion is likely a neutron star or a massive white dwarf, which makes the system an excellent candidate for Shapiro delay measurement and therefore an accurate estimate of the pulsar and companion masses.

Deneva, Julia S.; Knispel, B.; Allen, B.; Cordes, J.; Bogdanov, S.; Brazier, A.; Bhat, R.; Camilo, F.; Chatterjee, S.; Crawford, F.; Desvignes, G.; Freire, P.; Hessels, J.; Jenet, F.; Kaspi, V.; Kramer, M.; Lazarus, P.; Lorimer, D.; van Leeuwen, J.; Lyne, A.; McLaughlin, M.; Nice, D.; Ransom, S.; Siemens, X.; Stairs, I.; Stappers, B.; Stovall, K.

2011-01-01

155

Discovery of a novel esterase subfamily sharing an identified arm sequence (ArmEst) by gene-specific metagenomic PCR.  

PubMed

A gene-specific, metagenomic PCR method has led to the discovery of a novel esterase subfamily consisting of five homologous members. Sequence analysis of this esterase subfamily, named the ArmEst subfamily, revealed a unique conserved pattern with a significant variable interior sequence flanked by two symmetric and identical long arm sequences. The two homologous long arm sequences had 100 % sequence identity and symmetry at both ends between the five members of this esterase class, but only 17-58 % identity was shared for the internal sequence. The biochemical properties of two of the ArmEst esterases definitively demonstrated that they are true active esterases rather than pseudogenes. This is the first report presenting an esterase subfamily containing a unique arm sequence, indicating a rare homologous recombination occurring in the coding area of a functional gene to generate their functional diversity. PMID:23881330

Zhang, Ao; Zhao, Rong; Jin, Peng; Ma, Lifang; Xiong, Xiaolong; Xie, Tian; Pei, Xiaolin; Yu, Li; Yin, Xiaopu; Wang, Qiuyan

2013-07-24

156

An inflection point in gene discovery efforts for neurodegenerative diseases: from syndromic diagnoses toward endophenotypes and the epigenome.  

PubMed

We are at an inflection point in our study of the human genome as it relates to neurodegenerative disease. The sequencing of the human genome, and its associated cataloging of human genetic variation and technological as well as methodological development, introduced a period of rapid gene discovery over the past decade. These efforts have yielded many new insights and will continue to uncover the genetic architecture of syndromically defined neurodegenerative diseases in the coming decades. More recently, these successful study designs have been applied to the investigation of intermediate traits that relate to and inform our understanding of clinical syndromes and to exploration of the epigenome, the higher-order structure of DNA that dictates the expression of a given genetic risk factor. While still nascent, given the challenges of accumulating large numbers of subjects with detailed phenotypes and technological hurdles in characterizing the state of chromatin, these efforts represent key investments that will enable the study of the functional consequences of a genetic risk factor and, eventually, its contribution to the clinical manifestations of a given disease. As a community of investigators, we are therefore at an exciting inflection point at which gene discovery efforts are transitioning toward the functional characterization of implicated genetic variation; this transition is crucial for understanding the molecular, cellular, and systemic events that lead to a syndromic diagnosis for a neurodegenerative disease. PMID:23571780

De Jager, Philip L; Bennett, David A

2013-06-01

157

Discovery, phylogeny and expression patterns of AP2-like genes in maize  

Microsoft Academic Search

A transcription factor (TF) is a protein that binds to specific DNA sequences and thereby controls transcription. A large\\u000a number of TFs are found in plants. The AP2\\/ERF family of TFs contain the AP2 DNA-binding domain, which play important roles\\u000a in transcriptional regulation in plant life. To understand the AP2\\/ERF family TFs of maize, the discovery, phylogeny and expression\\u000a pattern

Jing Zhuang; De-Xiang Deng; Quan-Hong Yao; Jian Zhang; Fei Xiong; Jian-Min Chen; Ai-Sheng Xiong

2010-01-01

158

Implementation of functional genomics for gene discovery in alkaloid producing plants  

Microsoft Academic Search

Two centuries after the discovery of the first alkaloids, many enzymes involved in plant alkaloid biosynthesis have been identified.\\u000a Nevertheless, the biosynthetic pathways for most of the plant alkaloids still remain incompletely characterised and understanding\\u000a the regulatory mechanisms controlling the onset and flux of alkaloid biosynthesis is virtually inexistent. This information\\u000a is however crucial to allow modelling of metabolic networks

Alain Goossens; Heiko Rischer

2007-01-01

159

DISCOVERY OF A LOW-MASS COMPANION TO A METAL-RICH F STAR WITH THE MARVELS PILOT PROJECT  

SciTech Connect

We report the discovery of a low-mass companion orbiting the metal-rich, main sequence F star TYC 2949-00557-1 during the Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS) pilot project. The host star has an effective temperature T{sub eff} = 6135 {+-} 40 K, logg = 4.4 {+-} 0.1, and [Fe/H] = 0.32 {+-} 0.01, indicating a mass of M = 1.25 {+-} 0.09 M{sub sun} and R = 1.15 {+-} 0.15 R{sub sun}. The companion has an orbital period of 5.69449 {+-} 0.00023 days and straddles the hydrogen burning limit with a minimum mass of 64 M{sub J} , and thus may be an example of the rare class of brown dwarfs orbiting at distances comparable to those of 'Hot Jupiters'. We present relative photometry that demonstrates that the host star is photometrically stable at the few millimagnitude level on time scales of hours to years, and rules out transits for a companion of radius {approx}>0.8 R{sub J} at the 95% confidence level. Tidal analysis of the system suggests that the star and companion are likely in a double synchronous state where both rotational and orbital synchronization have been achieved. This is the first low-mass companion detected with a multi-object, dispersed, fixed-delay interferometer.

Fleming, Scott W.; Ge Jian; Mahadevan, Suvrath; Lee, Brian; Cuong Nguyen, Duy; Morehead, Robert C.; Wan Xiaoke; Zhao Bo; Liu Jian; Guo Pengcheng; Kane, Stephen R. [Department of Astronomy, University of Florida, 211 Bryant Space Science Center, Gainesville, FL 326711-2055 (United States); Eastman, Jason D.; Siverd, Robert J.; Scott Gaudi, B. [Department of Astronomy, Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Niedzielski, Andrzej [Torun Center for Astronomy, Nicolaus Copernicus University, ul. Gagarina 11, 87-100, Torun (Poland); Sivarani, Thirupathi [Indian Institute of Astrophysics, Bangalore 560034 (India); Stassun, Keivan G.; Gary, Bruce [Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235 (United States); Wolszczan, Alex [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Barnes, Rory, E-mail: scfleming@astro.ufl.ed [Department of Astronomy, University of Washington, P.O. Box 351580, Seattle, WA 98195 (United States)

2010-08-01

160

GEM-TREND: a web tool for gene expression data mining toward relevant network discovery  

Microsoft Academic Search

BACKGROUND: DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through

Chunlai Feng; Michihiro Araki; Ryo Kunimoto; Akiko Tamon; Hiroki Makiguchi; Satoshi Niijima; Gozoh Tsujimoto; Yasushi Okuno

2009-01-01

161

Discovery of single-nucleotide mutations in acetolactate synthase genes by Ecotilling  

Microsoft Academic Search

TILLING (Targeting Induced Local Lesions IN Genomes) is a powerful reverse genetic technique that employs a mismatch-specific endonuclease to discover induced point mutations in genes of interest. The use of the TILLING technique to survey natural variation in genes is called Ecotilling. We report an adaptation of Ecotilling for rapid detection of single-nucleotide mutations in the acetolactate synthase (ALS) genes

Guang-Xi Wang; Mui-Keng Tan; Sujay Rakshit; Hiromasa Saitoh; Ryohei Terauchi; Toshiyuki Imaizumi; Takanori Ohsako; Tohru Tominaga

2007-01-01

162

Computational discovery of DNA motifs associated with cell type-specific gene expression in Ciona  

Microsoft Academic Search

Temporally and spatially co-expressed genes are expected to be regulated by common transcription factors and therefore to share cis-regulatory elements. In the ascidian Ciona intestinalis, the whole-genome sequences and genome-scale gene expression profiles allow the use of computational techniques to investigate cis-elements that control transcription. We collected 5? flanking sequences of 50 tissue-specific genes from genome databases of C. intestinalis

Takehiro Kusakabe; Reiko Yoshida; Yoko Ikeda; Motoyuki Tsuda

2004-01-01

163

A multi-gene transcriptional profiling approach to the discovery of cell signature markers  

Microsoft Academic Search

A profile of transcript abundances from multiple genes constitutes a molecular signature if the expression pattern is unique\\u000a to one cell type. Here we measure mRNA copy numbers per cell by normalizing per million copies of 18S rRNA and identify 6\\u000a genes (TIE1, KDR, CDH5, TIE2, EFNA1 and MYO5C) out of 79 genes tested as excellent molecular signature markers for

Youichiro Wada; Dan Li; Anne Merley; Andrew Zukauskas; William C. Aird; Harold F. Dvorak; Shou-Ching Shih

2011-01-01

164

EST-based gene discovery in pig: virtual expression patterns and comparative mapping to human  

Microsoft Academic Search

A molecular understanding of porcine reproduction is of biological interest and economic importance. Our Midwest Consortium has produced cDNA libraries containing the majority of genes expressed in major female reproductive tissues, and we have deposited into public databases 21,499 expressed sequence tag (EST) gene sequences from the 3' end of clones from these libraries. These sequences represent 10,574 different genes,

Christopher K. Tuggle; Jon A. Green; Carolyn Fitzsimmons; Rami Woods; Randall S. Prather; Sergei Malchenko; Bento M. Soares; Tamara Kucaba; Keith Crouch; Christina Smith; Dylan Tack; Natalie Robinson; Brian O'Leary; Todd Scheetz; Thomas Casavant; Daniel Pomp; Brad J. Edeal; Yuandan Zhang; Max F. Rothschild; Kevin Garwood; William Beavis

2003-01-01

165

Genome-wide discovery of missing genes in biological pathways of prokaryotes  

Microsoft Academic Search

BACKGROUND: Reconstruction of biological pathways is typically done through mapping well-characterized pathways of model organisms to a target genome, through orthologous gene mapping. A limitation of such pathway-mapping approaches is that the mapped pathway models are constrained by the composition of the template pathways, e.g., some genes in a target pathway may not have corresponding genes in the template pathways,

Yong Chen; Fenglou Mao; Guojun Li; Ying Xu

2011-01-01

166

Discovery of estrogen receptor ? target genes and response elements in breast tumor cells  

Microsoft Academic Search

Background: Estrogens and their receptors are important in human development, physiology and disease. In this study, we utilized an integrated genome-wide molecular and computational approach to characterize the interaction between the activated estrogen receptor (ER) and the regulatory elements of candidate target genes. Results: Of around 19,000 genes surveyed in this study, we observed 137 ER-regulated genes in T-47D cells,

Chin-Yo Lin; Anders Ström; Vinsensius Berlian Vega; Say Li Kong; Ai Li Yeo; Jane S Thomsen; Wan Ching Chan; Balraj Doray; Dhinoth K Bangarusamy; Adaikalavan Ramasamy; Liza A Vergara; Suisheng Tang; Allen Chong; Vladimir B Bajic; Lance D Miller; Edison T Liu

2004-01-01

167

Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression  

PubMed Central

We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8?±?2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.

Kohannim, Omid; Hibar, Derrek P.; Stein, Jason L.; Jahanshad, Neda; Hua, Xue; Rajagopalan, Priya; Toga, Arthur W.; Jack, Clifford R.; Weiner, Michael W.; de Zubicaray, Greig I.; McMahon, Katie L.; Hansell, Narelle K.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.

2012-01-01

168

Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression.  

PubMed

We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8?±?2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain. PMID:22888310

Kohannim, Omid; Hibar, Derrek P; Stein, Jason L; Jahanshad, Neda; Hua, Xue; Rajagopalan, Priya; Toga, Arthur W; Jack, Clifford R; Weiner, Michael W; de Zubicaray, Greig I; McMahon, Katie L; Hansell, Narelle K; Martin, Nicholas G; Wright, Margaret J; Thompson, Paul M

2012-08-06

169

An extended association rule mining strategy for gene relationship discovery from microarray data  

Microsoft Academic Search

DNA microarrays allow for measuring expression levels of a large number of genes between different experimental conditions and\\/or samples. Association rule mining (ARM) methods are helpful in finding associational relationships between genes. However, classical association rule mining (CARM) algorithms extract only a subset of the associations that exist among different binary states; therefore can only infer part of the relationships

Bin Peng; Dianwen Zhu; Xiaowei Yang; Ling Liu; Wenquan Huang; Xiaohua Zhou; Dong Yi

2012-01-01

170

Human gene discovery through experimental definition of transcribed regions of the human genome  

Microsoft Academic Search

The sequencing of the human genome has failed to realize its primary goal: the identification of all human genes. We have learned that genes can only be identified with certainty within this vast and information-sparse structure by comparison with transcript sequences. Significantly more sequence data of this kind is required before we can claim to have deciphered our genetic blueprint.

Anamaria A Camargo; Sandro J de Souza; Ricardo R Brentani; Andrew J. G Simpson

2002-01-01

171

Serious limitations of the QTL\\/Microarray approach for QTL gene discovery  

Microsoft Academic Search

BACKGROUND: It has been proposed that the use of gene expression microarrays in nonrecombinant parental or congenic strains can accelerate the process of isolating individual genes underlying quantitative trait loci (QTL). However, the effectiveness of this approach has not been assessed. RESULTS: Thirty-seven studies that have implemented the QTL\\/microarray approach in rodents were reviewed. About 30% of studies showed enrichment

Ricardo A Verdugo; Charles R Farber; Craig H Warden; Juan F Medrano

2010-01-01

172

Gene expression profiling, genetic networks, and cellular states: an integrating concept for tumorigenesis and drug discovery  

Microsoft Academic Search

Genome-wide expression monitoring, a novel tool of functional genomics, is currently used mainly to identify groups of coregulated genes and to discover genes expressed differentially in distinct situations that could serve as drug targets. This descriptive approach, however, fails to extract \\

Sui Huang

1999-01-01

173

SNP discovery and marker development for disease resistance candidate genes in common carp (Cyprinus carpio)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Single nucleotide polymorphisms (SNPs) in immune response genes have been reported as markers of susceptibility to infectious diseases in human and livestock. A disease caused by cyprinid herpes virus 3 (CyHV-3) is highly contagious and virulent in common carp. With the aim to investigate the gene...

174

Comparison of the current RefSeq, Ensembl and EST databases for counting genes and gene discovery.  

PubMed

Large amounts of refined sequence material in the form of predicted, curated and annotated genes and expressed sequences tags (ESTs) have recently been added to the NCBI databases. We matched the transcript-sequences of RefSeq, Ensembl and dbEST in an attempt to provide an updated overview of how many unique human genes can be found. The results indicate that there are about 25000 unique genes in the union of RefSeq and Ensembl with 12-18% and 8-13% of the genes in each set unique to the other set, respectively. About 20% of all genes had splice variants. There are a considerable number of ESTs (2200000) that do not match the identified genes and we used an in-house pipeline to identify 22 novel genes from Genscan predictions that have considerable EST coverage. The study provides an insight into the current status of human gene catalogues and shows that considerable refinement of methods and datasets is needed to come to a conclusive gene count. PMID:15670830

Larsson, Thomas P; Murray, Christian G; Hill, Tobias; Fredriksson, Robert; Schiöth, Helgi B

2005-01-31

175

A multi-gene transcriptional profiling approach to the discovery of cell signature markers  

PubMed Central

A profile of transcript abundances from multiple genes constitutes a molecular signature if the expression pattern is unique to one cell type. Here we measure mRNA copy numbers per cell by normalizing per million copies of 18S rRNA and identify 6 genes (TIE1, KDR, CDH5, TIE2, EFNA1 and MYO5C) out of 79 genes tested as excellent molecular signature markers for endothelial cells (ECs) in vitro. The selected genes are uniformly expressed in ECs of 4 different origins but weakly or not expressed in 4 non-EC cell lines. A multi-gene transcriptional profile of these 6 genes clearly distinguishes ECs from non-ECs in vitro. We conclude that (i) a profile of mRNA copy numbers per cell from a well-chosen multi-gene panel can act as a sensitive and accurate cell type signature marker, and (ii) the method described here can be applied to in vivo cell fingerprinting and molecular diagnosis.

Wada, Youichiro; Li, Dan; Merley, Anne; Zukauskas, Andrew; Aird, William C.; Dvorak, Harold F.

2010-01-01

176

Gene discovery for the bark beetle-vectored fungal tree pathogen Grosmannia clavigera  

PubMed Central

Background Grosmannia clavigera is a bark beetle-vectored fungal pathogen of pines that causes wood discoloration and may kill trees by disrupting nutrient and water transport. Trees respond to attacks from beetles and associated fungi by releasing terpenoid and phenolic defense compounds. It is unclear which genes are important for G. clavigera's ability to overcome antifungal pine terpenoids and phenolics. Results We constructed seven cDNA libraries from eight G. clavigera isolates grown under various culture conditions, and Sanger sequenced the 5' and 3' ends of 25,000 cDNA clones, resulting in 44,288 high quality ESTs. The assembled dataset of unique transcripts (unigenes) consists of 6,265 contigs and 2,459 singletons that mapped to 6,467 locations on the G. clavigera reference genome, representing ~70% of the predicted G. clavigera genes. Although only 54% of the unigenes matched characterized proteins at the NCBI database, this dataset extensively covers major metabolic pathways, cellular processes, and genes necessary for response to environmental stimuli and genetic information processing. Furthermore, we identified genes expressed in spores prior to germination, and genes involved in response to treatment with lodgepole pine phloem extract (LPPE). Conclusions We provide a comprehensively annotated EST dataset for G. clavigera that represents a rich resource for gene characterization in this and other ophiostomatoid fungi. Genes expressed in response to LPPE treatment are indicative of fungal oxidative stress response. We identified two clusters of potentially functionally related genes responsive to LPPE treatment. Furthermore, we report a simple method for identifying contig misassemblies in de novo assembled EST collections caused by gene overlap on the genome.

2010-01-01

177

Gene-Expression-Guided Selection of Candidate Loci and Molecular Phenotype Analyses Enhance Genetic Discovery in Systemic Lupus Erythematosus  

PubMed Central

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disorder characterized by differences in autoantibody profiles, serum cytokines, and clinical manifestations. We have previously conducted a case-case genome-wide association study (GWAS) of SLE patients to detect associations with autoantibody profile and serum interferon alpha (IFN-?). In this study, we used public gene expression data sets to rationally select additional single nucleotide polymorphisms (SNPs) for validation. The top 200?GWAS SNPs were searched in a database which compares genome-wide expression data to genome-wide SNP genotype data in HapMap cell lines. SNPs were chosen for validation if they were associated with differential expression of 15 or more genes at a significance of P < 9 × 10?5. This resulted in 11?SNPs which were genotyped in 453?SLE patients and 418 matched controls. Three SNPs were associated with SLE-associated autoantibodies, and one of these SNPs was also associated with serum IFN-? (P < 4.5 × 10?3 for all). One additional SNP was associated exclusively with serum IFN-?. Case-control analysis was insensitive to these molecular subphenotype associations. This study illustrates the use of gene expression data to rationally select candidate loci in autoimmune disease, and the utility of stratification by molecular phenotypes in the discovery of additional genetic associations in SLE.

Koldobskaya, Yelena; Ko, Kichul; Kumar, Akaash A.; Agik, Sandra; Arrington, Jasmine; Kariuki, Silvia N.; Franek, Beverly S.; Kumabe, Marissa; Utset, Tammy O.; Jolly, Meenakshi; Skol, Andrew D.; Niewold, Timothy B.

2012-01-01

178

Discovery and validation of gene classifiers for endocrine-disrupting chemicals in zebrafish (Danio rerio)  

EPA Science Inventory

Development and application of transcriptomics-based gene classifiers for ecotoxicological applications lag far behind those of human biomedical science. Many such classifiers discovered thus far lack vigorous statistical and experimental validations, with their stability and rel...

179

Biochemical genomics for gene discovery in benzylisoquinoline alkaloid biosynthesis in opium poppy and related species.  

PubMed

Benzylisoquinoline alkaloids (BIAs) are a large, diverse group of ?2500 specialized plant metabolites. Many BIAs display potent pharmacological activities, including the narcotic analgesics codeine and morphine, the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine, the antimicrobial agents sanguinarine and berberine, and the muscle relaxant (+)-tubocurarine. Opium poppy remains the sole commercial source for codeine, morphine, and a variety of semisynthetic drugs, including oxycodone and buprenorphine, derived primarily from the biosynthetic pathway intermediate thebaine. Recent advances in transcriptomics, proteomics, and metabolomics have created unprecedented opportunities for isolating and characterizing novel BIA biosynthetic genes. Here, we describe the application of next-generation sequencing and cDNA microarrays for selecting gene candidates based on comparative transcriptome analysis. We outline the basic mass spectrometric techniques to perform deep proteome and targeted metabolite analyses on BIA-producing plant tissues and provide methodologies for functionally characterizing biosynthetic gene candidates through in vitro enzyme assays and transient gene silencing in planta. PMID:22999177

Dang, Thu Thuy T; Onoyovwi, Akpevwe; Farrow, Scott C; Facchini, Peter J

2012-01-01

180

Gene Discovery in the Threatened Elkhorn Coral: 454 Sequencing of the Acropora palmata Transcriptome  

Microsoft Academic Search

BackgroundCnidarians, including corals and anemones, offer unique insights into metazoan evolution because they harbor genetic similarities with vertebrates beyond that found in model invertebrates and retain genes known only from non-metazoans. Cataloging genes expressed in Acropora palmata, a foundation-species of reefs in the Caribbean and western Atlantic, will advance our understanding of the genetic basis of ecologically important traits in

Nicholas R. Polato; J. Cristobal Vera; Iliana B. Baums

2011-01-01

181

Discovery of genes associated with fruit ripening in Carica papaya using expressed sequence tags  

Microsoft Academic Search

To identify genes involved in papaya fruit ripening, a total of 1171 expressed sequence tags (ESTs) were generated from randomly selected clones of two independent fruit cDNA libraries derived from yellow and red-fleshed fruit varieties. The most abundant sequences encoded: chitinase, 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase, catalase and methionine synthase, respectively. DNA sequence comparisons identified ESTs with significant similarity to genes

Luke C. Devitt; Tim Sawbridge; Timothy A. Holton; Keith Mitchelson; Ralf G. Dietzgen

2006-01-01

182

An ensemble method for gene discovery based on DNA microarray data  

Microsoft Academic Search

The advent of DNA microarray technology has offered the promise of casting new insights onto deciphering secrets of life by\\u000a monitoring activities of thousands of genes simultaneously. Current analyses of microarray data focus on precise classification\\u000a of biological types, for example, tumor versus normal tissues. A further scientific challenging task is to extract disease-relevant\\u000a genes from the bewildering amounts of

Xia Li; Shaoqi Rao; Tianwen Zhang; Zheng Guo; Qingpu Zhang; Kathy L. Moser; Eric J. Topol

2004-01-01

183

Discovery of diversity in xylan biosynthetic genes by transcriptional profiling of a heteroxylan containing mucilaginous tissue  

PubMed Central

The exact biochemical steps of xylan backbone synthesis remain elusive. In Arabidopsis, three non-redundant genes from two glycosyltransferase (GT) families, IRX9 and IRX14 from GT43 and IRX10 from GT47, are candidates for forming the xylan backbone. In other plants, evidence exists that different tissues express these three genes at widely different levels, which suggests that diversity in the makeup of the xylan synthase complex exists. Recently we have profiled the transcripts present in the developing mucilaginous tissue of psyllium (Plantago ovata Forsk). This tissue was found to have high expression levels of an IRX10 homolog, but very low levels of the two GT43 family members. This contrasts with recent wheat endosperm tissue profiling that found a relatively high abundance of the GT43 family members. We have performed an in-depth analysis of all GTs genes expressed in four developmental stages of the psyllium mucilagenous layer and in a single stage of the psyllium stem using RNA-Seq. This analysis revealed several IRX10 homologs, an expansion in GT61 (homologs of At3g18170/At3g18180), and several GTs from other GT families that are highly abundant and specifically expressed in the mucilaginous tissue. Our current hypothesis is that the four IRX10 genes present in the mucilagenous tissues have evolved to function without the GT43 genes. These four genes represent some of the most divergent IRX10 genes identified to date. Conversely, those present in the psyllium stem are very similar to those in other eudicots. This suggests these genes are under selective pressure, likely due to the synthesis of the various xylan structures present in mucilage that has a different biochemical role than that present in secondary walls. The numerous GT61 family members also show a wide sequence diversity and may be responsible for the larger number of side chain structures present in the psyllium mucilage.

Jensen, Jacob K.; Johnson, Nathan; Wilkerson, Curtis G.

2013-01-01

184

Gene discovery in the hamster: a comparative genomics approach for gene annotation by sequencing of hamster testis cDNAs  

PubMed Central

Background Complete genome annotation will likely be achieved through a combination of computer-based analysis of available genome sequences combined with direct experimental characterization of expressed regions of individual genomes. We have utilized a comparative genomics approach involving the sequencing of randomly selected hamster testis cDNAs to begin to identify genes not previously annotated on the human, mouse, rat and Fugu (pufferfish) genomes. Results 735 distinct sequences were analyzed for their relatedness to known sequences in public databases. Eight of these sequences were derived from previously unidentified genes and expression of these genes in testis was confirmed by Northern blotting. The genomic locations of each sequence were mapped in human, mouse, rat and pufferfish, where applicable, and the structure of their cognate genes was derived using computer-based predictions, genomic comparisons and analysis of uncharacterized cDNA sequences from human and macaque. Conclusion The use of a comparative genomics approach resulted in the identification of eight cDNAs that correspond to previously uncharacterized genes in the human genome. The proteins encoded by these genes included a new member of the kinesin superfamily, a SET/MYND-domain protein, and six proteins for which no specific function could be predicted. Each gene was expressed primarily in testis, suggesting that they may play roles in the development and/or function of testicular cells.

Oduru, Sreedhar; Campbell, Janee L; Karri, SriTulasi; Hendry, William J; Khan, Shafiq A; Williams, Simon C

2003-01-01

185

Discovery and Characterization of Novel Vascular and Hematopoietic Genes Downstream of Etsrp in Zebrafish  

PubMed Central

The transcription factor Etsrp is required for vasculogenesis and primitive myelopoiesis in zebrafish. When ectopically expressed, etsrp is sufficient to induce the expression of many vascular and myeloid genes in zebrafish. The mammalian homolog of etsrp, ER71/Etv2, is also essential for vascular and hematopoietic development. To identify genes downstream of etsrp, gain-of-function experiments were performed for etsrp in zebrafish embryos followed by transcription profile analysis by microarray. Subsequent in vivo expression studies resulted in the identification of fourteen genes with blood and/or vascular expression, six of these being completely novel. Regulation of these genes by etsrp was confirmed by ectopic induction in etsrp overexpressing embryos and decreased expression in etsrp deficient embryos. Additional functional analysis of two newly discovered genes, hapln1b and sh3gl3, demonstrates their importance in embryonic vascular development. The results described here identify a group of genes downstream of etsrp likely to be critical for vascular and/or myeloid development.

Zhao, Yan; Burgess, Shawn; Lin, Shuo

2009-01-01

186

Discovery and characterization of nutritionally regulated genes associated with muscle growth in Atlantic salmon  

PubMed Central

A genomics approach was used to identify nutritionally regulated genes involved in growth of fast skeletal muscle in Atlantic salmon (Salmo salar L.). Forward and reverse subtractive cDNA libraries were prepared comparing fish with zero growth rates to fish growing rapidly. We produced 7,420 ESTs and assembled them into nonredundant clusters prior to annotation. Contigs representing 40 potentially unrecognized nutritionally responsive candidate genes were identified. Twenty-three of the subtractive library candidates were also differentially regulated by nutritional state in an independent fasting-refeeding experiment and their expression placed in the context of 26 genes with established roles in muscle growth regulation. The expression of these genes was also determined during the maturation of a primary myocyte culture, identifying 13 candidates from the subtractive cDNA libraries with putative roles in the myogenic program. During early stages of refeeding DNAJA4, HSPA1B, HSP90A, and CHAC1 expression increased, indicating activation of unfolded protein response pathways. Four genes were considered inhibitory to myogenesis based on their in vivo and in vitro expression profiles (CEBPD, ASB2, HSP30, novel transcript GE623928). Other genes showed increased expression with feeding and highest in vitro expression during the proliferative phase of the culture (FOXD1, DRG1) or as cells differentiated (SMYD1, RTN1, MID1IP1, HSP90A, novel transcript GE617747). The genes identified were associated with chromatin modification (SMYD1, RTN1), microtubule stabilization (MID1IP1), cell cycle regulation (FOXD1, CEBPD, DRG1), and negative regulation of signaling (ASB2) and may play a role in the stimulation of myogenesis during the transition from a catabolic to anabolic state in skeletal muscle.

Johnston, Ian A.

2010-01-01

187

Discovery of Molecular Mechanisms of Traditional Chinese Medicinal Formula Si-Wu-Tang Using Gene Expression Microarray and Connectivity Map  

PubMed Central

To pursue a systematic approach to discovery of mechanisms of action of traditional Chinese medicine (TCM), we used microarrays, bioinformatics and the “Connectivity Map” (CMAP) to examine TCM-induced changes in gene expression. We demonstrated that this approach can be used to elucidate new molecular targets using a model TCM herbal formula Si-Wu-Tang (SWT) which is widely used for women's health. The human breast cancer MCF-7 cells treated with 0.1 µM estradiol or 2.56 mg/ml of SWT showed dramatic gene expression changes, while no significant change was detected for ferulic acid, a known bioactive compound of SWT. Pathway analysis using differentially expressed genes related to the treatment effect identified that expression of genes in the nuclear factor erythroid 2-related factor 2 (Nrf2) cytoprotective pathway was most significantly affected by SWT, but not by estradiol or ferulic acid. The Nrf2-regulated genes HMOX1, GCLC, GCLM, SLC7A11 and NQO1 were upreguated by SWT in a dose-dependent manner, which was validated by real-time RT-PCR. Consistently, treatment with SWT and its four herbal ingredients resulted in an increased antioxidant response element (ARE)-luciferase reporter activity in MCF-7 and HEK293 cells. Furthermore, the gene expression profile of differentially expressed genes related to SWT treatment was used to compare with those of 1,309 compounds in the CMAP database. The CMAP profiles of estradiol-treated MCF-7 cells showed an excellent match with SWT treatment, consistent with SWT's widely claimed use for women's diseases and indicating a phytoestrogenic effect. The CMAP profiles of chemopreventive agents withaferin A and resveratrol also showed high similarity to the profiles of SWT. This study identified SWT as an Nrf2 activator and phytoestrogen, suggesting its use as a nontoxic chemopreventive agent, and demonstrated the feasibility of combining microarray gene expression profiling with CMAP mining to discover mechanisms of actions and to identify new health benefits of TCMs.

Wen, Zhining; Wang, Zhijun; Wang, Steven; Ravula, Ranadheer; Yang, Lun; Xu, Jun; Wang, Charles; Zuo, Zhong; Chow, Moses S. S.; Shi, Leming; Huang, Ying

2011-01-01

188

Gene discovery in the freshwater fish parasite Trypanosoma carassii: identification of trans-sialidase-like and mucin-like genes  

Microsoft Academic Search

A total of 1,921 expressed sequence tags (ESTs) were obtained from bloodstream trypomastigotes of Trypanosoma carassii, a parasite of economic importance due to its high prevalence in fish farms. Analysis of the data set allowed us to identify a trans-sialidase (TS)-like gene and three ESTs coding for putative mucin-like genes. TS activity was detected in cell extracts of bloodstream trypomastigotes.

F. Aguero; Vanina Campo; Laura Cremona; Adriana Jager; Javier M. Di Noia; Peter Overath; Daniel O. Sanchez; Alberto Carlos Frasch

2002-01-01

189

The use of gene-specific IgY antibodies for drug target discovery.  

PubMed

Genomics and gene expression data require interpretation at the protein level to validate the biological or pathological findings. To match with the efficiency and capacity of DNA microarray application, methods and approaches of protein analysis in multiplex and high-throughput manner are required for effectively discovering disease-related proteins. Two-dimensional gel and MS-based technologies provide researchers with such approaches, but neither of them can directly and selectively detect target proteins in situ. Antibodies are one of the most crucial tools for meeting this need. Efficient generation of antibodies based on genomics and gene-expression information is an important strategy for producing gene-specific antibodies to link genome to proteome. Avian immunoglobulins isolated from egg yolk (so-called IgY) have several attractive advantages over conventional IgG antibodies. PMID:12681940

Zhang, Wei-Wei

2003-04-15

190

New strategies for drug discovery: activation of silent or weakly expressed microbial gene clusters.  

PubMed

Genome sequencing of Streptomyces, myxobacteria, and fungi showed that although each strain contains genes that encode the enzymes to synthesize a plethora of potential secondary metabolites, only a fraction are expressed during fermentation. Interest has therefore grown in the activation of these cryptic pathways. We review current progress on this topic, describing concepts for activating silent genes, utilization of "natural" mutant-type RNA polymerases and rare earth elements, and the applicability of ribosome engineering to myxobacteria and fungi, the microbial groups known as excellent searching sources, as well as actinomycetes, for secondary metabolites. PMID:23143535

Ochi, Kozo; Hosaka, Takeshi

2012-11-11

191

SNP discovery, validation, haplotype structure and linkage disequilibrium in full-length herbage nutritive quality genes of perennial ryegrass ( Lolium perenne L.)  

Microsoft Academic Search

Development of accurate high-throughput molecular marker systems such as SNPs permits evaluation and selection of favourable\\u000a gene variants to accelerate elite varietal production. SNP discovery in perennial ryegrass has been based on PCR amplification\\u000a and sequencing of multiple amplicons designed to scan all components of the transcriptional unit. Full-length genes (with\\u000a complete intron–exon structure and promoter information) corresponding to well-defined

Rebecca C. Ponting; Michelle C. Drayton; Noel O. I. Cogan; Mark P. Dobrowolski; Germán C. Spangenberg; Kevin F. Smith; John W. Forster

2007-01-01

192

Discovery and assessment of conserved Pax6 target genes and enhancers.  

PubMed

The characterization of transcriptional networks (TNs) is essential for understanding complex biological phenomena such as development, disease, and evolution. In this study, we have designed and implemented a procedure that combines in silico target screens with zebrafish and mouse validation, in order to identify cis-elements and genes directly regulated by Pax6. We chose Pax6 as the paradigm because of its crucial roles in organogenesis and human disease. We identified over 600 putative Pax6 binding sites and more than 200 predicted direct target genes, conserved in evolution from zebrafish to human and to mouse. This was accomplished using hidden Markov models (HMMs) generated from experimentally validated Pax6 binding sites. A small sample of genes, expressed in the neural lineage, was chosen from the predictions for RNA in situ validation using zebrafish and mouse models. Validation of DNA binding to some predicted cis-elements was also carried out using chromatin immunoprecipitation (ChIP) and zebrafish reporter transgenic studies. The results show that this combined procedure is a highly efficient tool to investigate the architecture of TNs and constitutes a useful complementary resource to ChIP and expression data sets because of its inherent spatiotemporal independence. We have identified several novel direct targets, including some putative disease genes, among them Foxp2; these will allow further dissection of Pax6 function in development and disease. PMID:21617155

Coutinho, Pedro; Pavlou, Sofia; Bhatia, Shipra; Chalmers, Kevin J; Kleinjan, Dirk A; van Heyningen, Veronica

2011-05-26

193

Discovery of (hemi-) cellulase genes in a metagenomic library from a biogas digester using 454 pyrosequencing.  

PubMed

In this study, 341, 246, and 386 positive clones with endo-?-1,4-glucanase, ?-glucosidase, and endo-?-1,4-xylanase activities, respectively, were identified by screening from a metagenomic fosmid library constructed from a biogas digester. Subsequently, pools of 4, 10, and 16 positive clones were subjected to 454 pyrosequencing in different subruns. In total, 21 unique glycosyl hydrolase (GH) genes were predicted by bioinformatic analysis, which showed similarities to their nearest neighbors from 39 % to 72 %. In addition to bioinformatics prediction, nine GH genes were expressed and purified to identify their activity with four kinds of substrates. The activities of the most expressed proteins were consistent with their annotation based on bioinformatics prediction; however, three GH genes belonging to the GH5 family showed different activities from their annotation. An efficient acidic cellulase En1 had an optimal condition at 55 °C, pH 5.5, with a specific activity toward carboxymethylcellulose at 118 U/mg and K m at 12.8 g/L. This study demonstrated that there are diverse GHs in the biogas digester system with potential industrial application in lignocellulose hydrolysis, and their activities should be investigated with different substrates before their application. Additionally, pool sequencing of positive fosmid clones might be a cost-effective approach to obtain functional genes from metagenomic libraries. PMID:23653123

Yan, Xing; Geng, Alei; Zhang, Jun; Wei, Yongjun; Zhang, Lei; Qian, Changli; Wang, Qianfu; Wang, Shengyue; Zhou, Zhihua

2013-05-08

194

Discovery of Metastatic Breast Cancer Suppressor Genes Using Functional Genome Analysis.  

National Technical Information Service (NTIS)

To identify metastatic suppressor genes (MSGs), I proposed to perform genome-scale genetic perturbation using lentiviral delivered shRNA library in a mouse model of breast cancer metastasis and an in vitro metastasis assay. To enhance the screening throug...

X. Wang

2012-01-01

195

Human embryonic stem cells as a model for cardiac gene discovery : from chip to chap  

Microsoft Academic Search

Here we described the use of human embryonic stem cells (hESCs) as a model to obtain insights into commitment to the mesoderm and endoderm lineages and the early steps in human cardiac cell differentiation by means of whole-genome temporal expression profiling. Furthermore, we used it as an approach to identify new genes that may be associated with (abnormal) human heart

A. Beqqali

2008-01-01

196

Structure-based gene targeting discovery of sphaerimicin, a bacterial translocase?i inhibitor.  

PubMed

Rise and shine: Using a gene-targeting approach aimed at identifying potential L-threonine:uridine-5'-transaldolases that catalyze the formation of (5'S,6'S)-C-glycyluridine, a new bacterial translocase?I inhibitor was discovered from an actinomycete following fermentation optimization. PMID:24014169

Funabashi, Masanori; Baba, Satoshi; Takatsu, Toshio; Kizuka, Masaaki; Ohata, Yasuo; Tanaka, Masahiro; Nonaka, Koichi; Spork, Anatol P; Ducho, Christian; Chen, Wei-Chen Leyla; Van Lanen, Steven G

2013-09-06

197

Use of eQTL Analysis for the Discovery of Target Genes Identified by GWAS.  

National Technical Information Service (NTIS)

The goals of this grant proposal are to: (1) construct a prostate tissue-specific expression quantitative trait loci (eQTL) dataset; and (2) utilize this dataset to identify candidate genes for existing prostate cancer (PC) risk-single nucleotide polymorp...

S. Thibodeau

2012-01-01

198

Gene Discovery in the Threatened Elkhorn Coral: 454 Sequencing of the Acropora palmata Transcriptome  

PubMed Central

Background Cnidarians, including corals and anemones, offer unique insights into metazoan evolution because they harbor genetic similarities with vertebrates beyond that found in model invertebrates and retain genes known only from non-metazoans. Cataloging genes expressed in Acropora palmata, a foundation-species of reefs in the Caribbean and western Atlantic, will advance our understanding of the genetic basis of ecologically important traits in corals and comes at a time when sequencing efforts in other cnidarians allow for multi-species comparisons. Results A cDNA library from a sample enriched for symbiont free larval tissue was sequenced on the 454 GS-FLX platform. Over 960,000 reads were obtained and assembled into 42,630 contigs. Annotation data was acquired for 57% of the assembled sequences. Analysis of the assembled sequences indicated that 83–100% of all A. palmata transcripts were tagged, and provided a rough estimate of the total number genes expressed in our samples (?18,000–20,000). The coral annotation data contained many of the same molecular components as in the Bilateria, particularly in pathways associated with oxidative stress and DNA damage repair, and provided evidence that homologs of p53, a key player in DNA repair pathways, has experienced selection along the branch separating Cnidaria and Bilateria. Transcriptome wide screens of paralog groups and transition/transversion ratios highlighted genes including: green fluorescent proteins, carbonic anhydrase, and oxidative stress proteins; and functional groups involved in protein and nucleic acid metabolism, and the formation of structural molecules. These results provide a starting point for study of adaptive evolution in corals. Conclusions Currently available transcriptome data now make comparative studies of the mechanisms underlying coral's evolutionary success possible. Here we identified candidate genes that enable corals to maintain genomic integrity despite considerable exposure to genotoxic stress over long life spans, and showed conservation of important physiological pathways between corals and bilaterians.

Polato, Nicholas R.; Vera, J. Cristobal; Baums, Iliana B.

2011-01-01

199

Discovery of nuclear-encoded genes for the neurotoxin saxitoxin in dinoflagellates.  

PubMed

Saxitoxin is a potent neurotoxin that occurs in aquatic environments worldwide. Ingestion of vector species can lead to paralytic shellfish poisoning, a severe human illness that may lead to paralysis and death. In freshwaters, the toxin is produced by prokaryotic cyanobacteria; in marine waters, it is associated with eukaryotic dinoflagellates. However, several studies suggest that saxitoxin is not produced by dinoflagellates themselves, but by co-cultured bacteria. Here, we show that genes required for saxitoxin synthesis are encoded in the nuclear genomes of dinoflagellates. We sequenced >1.2×10(6) mRNA transcripts from the two saxitoxin-producing dinoflagellate strains Alexandrium fundyense CCMP1719 and A. minutum CCMP113 using high-throughput sequencing technology. In addition, we used in silico transcriptome analyses, RACE, qPCR and conventional PCR coupled with Sanger sequencing. These approaches successfully identified genes required for saxitoxin-synthesis in the two transcriptomes. We focused on sxtA, the unique starting gene of saxitoxin synthesis, and show that the dinoflagellate transcripts of sxtA have the same domain structure as the cyanobacterial sxtA genes. But, in contrast to the bacterial homologs, the dinoflagellate transcripts are monocistronic, have a higher GC content, occur in multiple copies, contain typical dinoflagellate spliced-leader sequences and eukaryotic polyA-tails. Further, we investigated 28 saxitoxin-producing and non-producing dinoflagellate strains from six different genera for the presence of genomic sxtA homologs. Our results show very good agreement between the presence of sxtA and saxitoxin-synthesis, except in three strains of A. tamarense, for which we amplified sxtA, but did not detect the toxin. Our work opens for possibilities to develop molecular tools to detect saxitoxin-producing dinoflagellates in the environment. PMID:21625593

Stüken, Anke; Orr, Russell J S; Kellmann, Ralf; Murray, Shauna A; Neilan, Brett A; Jakobsen, Kjetill S

2011-05-18

200

Allele mining and haplotype discovery in barley candidate genes for drought tolerance  

Microsoft Academic Search

In the present study, allele mining was conducted on a panel of drought related candidate genes in a set of 96 barley genotypes\\u000a using EcoTILLING, which is a variant of the targeting induced local lesions in genomes (TILLING) technology. Analyzing approximately\\u000a 1.5 million basepairs in barley a total number of 94 verified unique haplotypes were identified in 18 amplicons designed

András Cseri; Mátyás Cserháti; Maria von Korff; Bettina Nagy; Gábor V. Horváth; András Palágyi; János Pauk; Dénes Dudits; Ottó Törjék

201

Discovery of Nuclear-Encoded Genes for the Neurotoxin Saxitoxin in Dinoflagellates  

PubMed Central

Saxitoxin is a potent neurotoxin that occurs in aquatic environments worldwide. Ingestion of vector species can lead to paralytic shellfish poisoning, a severe human illness that may lead to paralysis and death. In freshwaters, the toxin is produced by prokaryotic cyanobacteria; in marine waters, it is associated with eukaryotic dinoflagellates. However, several studies suggest that saxitoxin is not produced by dinoflagellates themselves, but by co-cultured bacteria. Here, we show that genes required for saxitoxin synthesis are encoded in the nuclear genomes of dinoflagellates. We sequenced >1.2×106 mRNA transcripts from the two saxitoxin-producing dinoflagellate strains Alexandrium fundyense CCMP1719 and A. minutum CCMP113 using high-throughput sequencing technology. In addition, we used in silico transcriptome analyses, RACE, qPCR and conventional PCR coupled with Sanger sequencing. These approaches successfully identified genes required for saxitoxin-synthesis in the two transcriptomes. We focused on sxtA, the unique starting gene of saxitoxin synthesis, and show that the dinoflagellate transcripts of sxtA have the same domain structure as the cyanobacterial sxtA genes. But, in contrast to the bacterial homologs, the dinoflagellate transcripts are monocistronic, have a higher GC content, occur in multiple copies, contain typical dinoflagellate spliced-leader sequences and eukaryotic polyA-tails. Further, we investigated 28 saxitoxin-producing and non-producing dinoflagellate strains from six different genera for the presence of genomic sxtA homologs. Our results show very good agreement between the presence of sxtA and saxitoxin-synthesis, except in three strains of A. tamarense, for which we amplified sxtA, but did not detect the toxin. Our work opens for possibilities to develop molecular tools to detect saxitoxin-producing dinoflagellates in the environment.

Stuken, Anke; Orr, Russell J. S.; Kellmann, Ralf; Murray, Shauna A.; Neilan, Brett A.; Jakobsen, Kjetill S.

2011-01-01

202

Progress toward discovery of susceptibility genes for bipolar manic-depressive illness and schizophrenia.  

PubMed

The inconsistency in linkage results that has bedeviled psychiatric genetics has been observed to occur regularly in common diseases with complex inheritance. Nonetheless, in two such instances--noninsulin-dependent diabetes mellitus (NIDDM) and inflammatory bowel disease (IBD)--susceptibility genes have been discovered based on the follow-ups of linkage findings. In bipolar illness disorder (BPD) and schizophrenia (SZ), there are some linkage reports with replication of other studies similar to the situation in NIDDM and IBD before the successful positional cloning efforts. Two of the regions with linkage reports, BPD and SZ, on the long arms of chromosomes 13 and 22, show linkage to the same markers in both diseases. This lends some plausibility to the hypothesis of some shared genetic predispositions for both disorders. Cytogenetic evidence offers another positional approach to susceptibility genes. The velocardiofacial syndrome is associated with deletions very close to the linkage region on chromosome 22, and with psychiatric manifestations of both BPD and SZ. Endophenotypes of SZ, previously demonstrated to the be heritable, have been found to have chromosomal linkage in at least one study. These include eye-tracking abnormalities linked to 6p, and an abnormality of the P50 cortical evoked potential linked to chromosome 15. Variants in specific genes have been associated with susceptibility to the psychiatric illnesses. These genetic findings may contribute to etiologic subcategorization of BPD and SZ, and the development of new treatment approaches. A table of genetic terms is included for review PMID:15311192

Gershon, E S; Badner, J A

2001-12-01

203

Genome-wide discovery of cis-elements in promoter sequences using gene expression.  

PubMed

The availability of complete or nearly complete genome sequences, a large number of 5' expressed sequence tags, and significant public expression data allow for a more accurate identification of cis-elements regulating gene expression. We have implemented a global approach that takes advantage of available expression data, genomic sequences, and transcript information to predict cis-elements associated with specific expression patterns. The key components of our approach are: (1) precise identification of transcription start sites, (2) specific locations of cis-elements relative to the transcription start site, and (3) assessment of statistical significance for all sequence motifs. By applying our method to promoters of Arabidopsis thaliana and Mus musculus, we have identified motifs that affect gene expression under specific environmental conditions or in certain tissues. We also found that the presence of the TATA box is associated with increased variability of gene expression. Strong correlation between our results and experimentally determined motifs shows that the method is capable of predicting new functionally important cis-elements in promoter sequences. PMID:19231992

Troukhan, Maxim; Tatarinova, Tatiana; Bouck, John; Flavell, Richard B; Alexandrov, Nickolai N

2009-04-01

204

Robust discovery of genetic associations incorporating gene-environment interaction and independence.  

PubMed

This article considers the detection and evaluation of genetic effects incorporating gene-environment interaction and independence. Whereas ordinary logistic regression cannot exploit the assumption of gene-environment independence, the proposed approach makes explicit use of the independence assumption to improve estimation efficiency. This method, which uses both cases and controls, fits a constrained retrospective regression in which the genetic variant plays the role of the response variable, and the disease indicator and the environmental exposure are the independent variables. The regression model constrains the association of the environmental exposure with the genetic variant among the controls to be null, thus explicitly encoding the gene-environment independence assumption, which yields substantial gain in accuracy in the evaluation of genetic effects. The proposed retrospective regression approach has several advantages. It is easy to implement with standard software, and it readily accounts for multiple environmental exposures of a polytomous or of a continuous nature, while easily incorporating extraneous covariates. Unlike the profile likelihood approach of Chatterjee and Carroll (Biometrika. 2005;92:399-418), the proposed method does not require a model for the association of a polytomous or continuous exposure with the disease outcome, and, therefore, it is agnostic to the functional form of such a model and completely robust to its possible misspecification. PMID:21228701

Tchetgen Tchetgen, Eric

2011-03-01

205

Discovery of second gene for solid dark green versus light green rind pattern in watermelon.  

PubMed

The watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai var. lanatus) has high variability for fruit size, shape, rind pattern, and flesh color. This study was designed to measure the qualitative inheritance of rind phenotypes (solid dark green vs. light green). For each of the 2 families, "Mountain Hoosier" × "Minilee" and "Early Arizona" × "Minilee," 6 generations (P(a)S(1), P(b)S(1), F(1), F(2), BC(1)P(a), BC(1)P(b)) were developed. Each family was tested in summer 2008 in 3 environments in North Carolina. Phenotypic data were analyzed with the ?(2) method to test the segregation of Mendelian genes. Deviations from the expected segregation ratios based on hypothesized single dominant gene for solid dark green versus light green rind pattern were recorded, raising questions on the inheritance of this trait. Inheritance of solid dark green rind versus light (gray) rind showed duplicate dominant epistasis. Duplicate dominant epistasis gives rise to a 15:1 ratio (solid dark green:light rind pattern) in F(2) generation. When both the loci are homozygous recessive, we observe light rind pattern. The g-1 and g-2 genes were identified to control light green rind when in homozygous recessive form. PMID:21566001

Kumar, Rakesh; Wehner, Todd C

2011-05-12

206

[Hereditary hemochromatosis--new developments after discovery of the HFE gene].  

PubMed

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism, resulting in an increased iron deposition and multiorgan failure. Recently a candidate gene of HH, termed HFE, has been identified on chromosome 6, coding for a protein homologous to major histocompatibility complex (MHC) class I molecules. Two mutations of the hemochromatosis gene leading to an exchange of cysteine to tyrosine at aminoacid 282 and histidine to asparagine at aminoacid 63, are retained responsible for the development of hereditary hemochromatosis. The Cys282Tyr-mutation disrupts a disulfid bond and thus abrogates binding of the mutant HFE-protein to beta 2-microglobulin and its presentation on the cell surface. The His63Asp-mutation seems to play a role in pH-regulated dissociation of the transferrin receptor/transferrin complex in the lysosome. Mutations of the HFE-protein alter the affinity of the transferrin receptor for its ligand transferrin and may thus cause an intracellular accumulation of iron. Knowledge of the responsible gene allows a molecular diagnosis of HH. The new genetic marker can be used for screening and confirmation of HH reducing the need for confirmatory liver biopsies. Compared to standard screening parameters like ferritin and transferrin saturation genetic testing will allow the diagnosis of HH in an early, asymptomatic state before iron accumulation has occurred. As a normal life expectancy of patients with HH can be achieved if iron reduction is initiated early, genetic testing may thus be of great benefit for patients with HH. PMID:10666843

Erhardt, A; Niederau, C; Osman, Y; Häussinger, D

1999-12-01

207

Gene discovery in Carcinus maenas and Homarus americanus via expressed sequence tags.  

PubMed

Expressed sequence tags (ESTs) were produced for normalized cDNA libraries prepared from several tissues of 2 marine crustaceans, the green shore crab Carcinus maenas and the American lobster Homarus americanus. Tissues represented in the Carcinus library were anterior and posterior gills, hypodermis, heart, hepatopancreas, antennal gland, brain, testis, and skeletal muscle, obtained from animals acclimated to 35 and 10‰ salinity. Tissues represented in the Homarus library were gill, epipodite, branchiostegite, heart, ovary, testis, antennal gland, skeletal muscle, hepatopancreas, and brain, obtained from intermolt and post-molt animals. Directional libraries from oligo-dT-primed cDNA were constructed in the pCMVsport6.1 vector and normalized by self-subtraction at 2 different Cot values. Randomly picked clones were single-pass sequenced from the 5' end. Raw sequence data were trimmed and prepared for submission to dbEST using phred, cross-match, and blastx protocols embedded within trace2dbest software. A total of 4604 Homarus and 12 401 Carcinus ESTs produced 540 and 2651 clusters, respectively, as determined by TIGR Gene Index Clustering software. Gene Ontology analysis with reference to a Drosophila melanogaster database using GOblet revealed 187 positive hits (35%) with the Homarus clusters and 1037 positive hits (39%) with the Carcinus clusters. Combining the number of assembled sequences with the number of singlets obtained after cluster analysis suggested that transcripts representing as much as 25% of the total number of genes in Carcinus have been isolated. PMID:21672795

Towle, David W; Smith, Christine M

2006-05-17

208

Ac/Ds-transposon activation tagging in poplar: a powerful tool for gene discovery  

PubMed Central

Background Rapid improvements in the development of new sequencing technologies have led to the availability of genome sequences of more than 300 organisms today. Thanks to bioinformatic analyses, prediction of gene models and protein-coding transcripts has become feasible. Various reverse and forward genetics strategies have been followed to determine the functions of these gene models and regulatory sequences. Using T-DNA or transposons as tags, significant progress has been made by using "Knock-in" approaches ("gain-of-function" or "activation tagging") in different plant species but not in perennial plants species, e.g. long-lived trees. Here, large scale gene tagging resources are still lacking. Results We describe the first application of an inducible transposon-based activation tagging system for a perennial plant species, as example a poplar hybrid (P. tremula L. × P. tremuloides Michx.). Four activation-tagged populations comprising a total of 12,083 individuals derived from 23 independent "Activation Tagging Ds" (ATDs) transgenic lines were produced and phenotyped. To date, 29 putative variants have been isolated and new ATDs genomic positions were successfully determined for 24 of those. Sequences obtained were blasted against the publicly available genome sequence of P. trichocarpa v2.0 (Phytozome v7.0; http://www.phytozome.net/poplar) revealing possible transcripts for 17 variants. In a second approach, 300 randomly selected individuals without any obvious phenotypic alterations were screened for ATDs excision. For one third of those transposition of ATDs was confirmed and in about 5% of these cases genes were tagged. Conclusions The novel strategy of first genotyping and then phenotyping a tagging population as proposed here is, in particular, applicable for long-lived, difficult to transform plant species. We could demonstrate the power of the ATDs transposon approach and the simplicity to induce ATDs transposition in vitro. Since a transposon is able to pass chromosomal boundaries, only very few primary transposon-carrying transgenic lines are required for the establishment of large transposon tagging populations. In contrast to T-DNA-based activation tagging, which is plagued by a lack of transformation efficiency and its time consuming nature, this for the first time, makes it feasible one day to tag (similarly to Arabidopsis) every gene within a perennial plant genome.

2012-01-01

209

Discovery of Inhibitors of Aberrant Gene Transcription from Libraries of DNA Binding Molecules: Inhibition of LEF-1 Mediated Gene Transcription and Oncogenic Transformation  

PubMed Central

The screening of a >9000 compound library of synthetic DNA binding molecules for selective binding to the consensus sequence of the transcription factor LEF-1 followed by assessment of the candidate compounds in a series of assays that characterized functional activity (disruption of DNA–LEF-1 binding) at the intended target and site (inhibition of intracellular LEF-1 mediated gene transcription) resulting in a desired phenotypic cellular change (inhibit LEF-1 driven cell transformation) provided two lead compounds: lefmycin-1 and lefmycin-2. The sequence of screens defining the approach assures that activity in the final functional assay may be directly related to the inhibition of gene transcription and DNA binding properties of the identified molecules. Central to the implementation of this generalized approach to the discovery of DNA binding small molecule inhibitors of gene transcription was: (1) the use of a technically non-demanding fluorescent intercalator displacement (FID) assay for initial assessment of the DNA binding affinity and selectivity of a library of compounds for any sequence of interest, and (2) the technology used to prepare a sufficiently large library of DNA binding compounds.

Stover, James S.; Shi, Jin; Jin, Wei; Vogt, Peter K.; Boger, Dale L.

2009-01-01

210

Genome-wide target profiling of piggyBac and Tol2 in HEK 293: pros and cons for gene discovery and gene therapy  

PubMed Central

Background DNA transposons have emerged as indispensible tools for manipulating vertebrate genomes with applications ranging from insertional mutagenesis and transgenesis to gene therapy. To fully explore the potential of two highly active DNA transposons, piggyBac and Tol2, as mammalian genetic tools, we have conducted a side-by-side comparison of the two transposon systems in the same setting to evaluate their advantages and disadvantages for use in gene therapy and gene discovery. Results We have observed that (1) the Tol2 transposase (but not piggyBac) is highly sensitive to molecular engineering; (2) the piggyBac donor with only the 40 bp 3'-and 67 bp 5'-terminal repeat domain is sufficient for effective transposition; and (3) a small amount of piggyBac transposases results in robust transposition suggesting the piggyBac transpospase is highly active. Performing genome-wide target profiling on data sets obtained by retrieving chromosomal targeting sequences from individual clones, we have identified several piggyBac and Tol2 hotspots and observed that (4) piggyBac and Tol2 display a clear difference in targeting preferences in the human genome. Finally, we have observed that (5) only sites with a particular sequence context can be targeted by either piggyBac or Tol2. Conclusions The non-overlapping targeting preference of piggyBac and Tol2 makes them complementary research tools for manipulating mammalian genomes. PiggyBac is the most promising transposon-based vector system for achieving site-specific targeting of therapeutic genes due to the flexibility of its transposase for being molecularly engineered. Insights from this study will provide a basis for engineering piggyBac transposases to achieve site-specific therapeutic gene targeting.

2011-01-01

211

Large-scale gene discovery in the pea aphid Acyrthosiphon pisum (Hemiptera)  

PubMed Central

Aphids are the leading pests in agricultural crops. A large-scale sequencing of 40,904 ESTs from the pea aphid Acyrthosiphon pisum was carried out to define a catalog of 12,082 unique transcripts. A strong AT bias was found, indicating a compositional shift between Drosophila melanogaster and A. pisum. An in silico profiling analysis characterized 135 transcripts specific to pea-aphid tissues (relating to bacteriocytes and parthenogenetic embryos). This project is the first to address the genetics of the Hemiptera and of a hemimetabolous insect.

Sabater-Munoz, Beatriz; Legeai, Fabrice; Rispe, Claude; Bonhomme, Joel; Dearden, Peter; Dossat, Carole; Duclert, Aymeric; Gauthier, Jean-Pierre; Ducray, Daniele Giblot; Hunter, Wayne; Dang, Phat; Kambhampati, Srini; Martinez-Torres, David; Cortes, Teresa; Moya, Andres; Nakabachi, Atsushi; Philippe, Cathy; Prunier-Leterme, Nathalie; Rahbe, Yvan; Simon, Jean-Christophe; Stern, David L; Wincker, Patrick; Tagu, Denis

2006-01-01

212

Functional Analysis and Discovery of Microbial Genes Transforming Metallic and Organic Pollutants: Database and Experimental Tools  

SciTech Connect

Microbial functional genomics is faced with a burgeoning list of genes which are denoted as unknown or hypothetical for lack of any knowledge about their function. The majority of microbial genes encode enzymes. Enzymes are the catalysts of metabolism; catabolism, anabolism, stress responses, and many other cell functions. A major problem facing microbial functional genomics is proposed here to derive from the breadth of microbial metabolism, much of which remains undiscovered. The breadth of microbial metabolism has been surveyed by the PIs and represented according to reaction types on the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD): http://umbbd.ahc.umn.edu/search/FuncGrps.html The database depicts metabolism of 49 chemical functional groups, representing most of current knowledge. Twice that number of chemical groups are proposed here to be metabolized by microbes. Thus, at least 50% of the unique biochemical reactions catalyzed by microbes remain undiscovered. This further suggests that many unknown and hypothetical genes encode functions yet undiscovered. This gap will be partly filled by the current proposal. The UM-BBD will be greatly expanded as a resource for microbial functional genomics. Computational methods will be developed to predict microbial metabolism which is not yet discovered. Moreover, a concentrated effort to discover new microbial metabolism will be conducted. The research will focus on metabolism of direct interest to DOE, dealing with the transformation of metals, metalloids, organometallics and toxic organics. This is precisely the type of metabolism which has been characterized most poorly to date. Moreover, these studies will directly impact functional genomic analysis of DOE-relevant genomes.

Lawrence P. Wackett; Lynda B.M. Ellis

2004-12-09

213

Assessing computational tools for the discovery of small RNA genes in bacteria  

PubMed Central

Over the past decade, a number of biocomputational tools have been developed to predict small RNA (sRNA) genes in bacterial genomes. In this study, several of the leading biocomputational tools, which use different methodologies, were investigated. The performance of the tools, both individually and in combination, was evaluated on ten sets of benchmark data, including data from a novel RNA-seq experiment conducted in this study. The results of this study offer insight into the utility as well as the limitations of the leading biocomputational tools for sRNA identification and provide practical guidance for users of the tools.

Lu, Xiaojun; Goodrich-Blair, Heidi; Tjaden, Brian

2011-01-01

214

FAF-Drugs2: Free ADME\\/tox filtering tool to assist drug discovery and chemical biology projects  

Microsoft Academic Search

BACKGROUND: Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting\\/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying

David Lagorce; Olivier Sperandio; Hervé Galons; Maria A. Miteva; Bruno O. Villoutreix

2008-01-01

215

The discovery of common recurrent transmembrane protease serine 2 (TMPRSS2)-erythroblastosis virus E26 transforming sequence (ETS) gene fusions in prostate cancer: significance and clinical implications.  

PubMed

Recurrent gene fusions and chromosomal rearrangements were previously thought to be the primary oncogenic mechanism of hematological malignancies and sarcomas. The recent discovery of recurrent gene fusions in a majority of prostate cancers represents a paradigm shift in understanding the molecular mechanisms of one of the most prevalent epithelial malignancies, with important clinical and biologic implications. The prostate cancer gene fusions that have been identified so far are characterized by 5'-genomic regulatory elements, most notably the androgen-controlled prostate specific gene, transmembrane protease serine 2, fused to members of the erythroblastosis virus E26 transforming sequence family of transcription factors, most notably ERG, leading to the overexpression of oncogenic transcription factors. The erythroblastosis virus E26 transforming sequence gene fusions most likely define a distinct class of prostate cancer with potential implications for early diagnosis, prognosis, and rational therapeutic targeting. In this review, we summarize the bioinformatics approach that led to the discovery of gene fusions, the current state of the frequency, and diversity of gene fusions that define the molecular heterogeneity of prostate cancer, their associations with prostate cancer progression and clinical outcome, the subsequent morphological characteristics, and the potential application of gene fusions as biomarkers in the diagnosis and management of prostate cancer. PMID:19395877

Shah, Rajal B; Chinnaiyan, Arul M

2009-05-01

216

The Hexosamine Template - A Platform for Modulating Gene Expression and for Sugar-based Drug Discovery  

PubMed Central

This study investigates the breadth of cellular responses engendered by short chain fatty acid (SCFA)-hexosamine hybrid molecules, a class of compounds long used in ‘metabolic glycoengineering’ that are now emerging as drug candidates. First, a ‘mix-and-match’ strategy showed that different SCFA (n-butyrate and acetate) appended to the same core sugar altered biological activity, complementing previous results [Campbell et al., (2008) J. Med. Chem. 51, 8135–8147] where a single type of SCFA elicited distinct responses. Microarray profiling then compared transcriptional responses engendered by regioisomerically-modified ManNAc, GlcNAc, and GalNAc analogs in MDA-MB-231 cells. These data – which were validated by qRT-PCR or Western analysis for ID1, TP53, HPSE, NQO1, EGR1 and VEGFA – showed a two-pronged response where a core set of genes was coordinately regulated by all analogs while each analog simultaneously uniquely regulated a larger number of genes. Finally, AutoDock modeling supported a mechanism where the analogs directly interact with elements of the NF-?B pathway. Together, these results establish the SCFA-hexosamine template as a versatile platform for modulating biological activity and developing new therapeutics.

Elmouelhi, Noha; Aich, Udayanath; Paruchuri, Venkata D.P.; Meledeo, M. Adam; Campbell, Christopher T.; Wang, Jean J.; Srinivas, Raja; Khanna, Hargun S.; Yarema, Kevin J.

2009-01-01

217

Positive selection systems for discovery of novel polyester biosynthesis genes based on fatty acid detoxification.  

PubMed Central

The photosynthetic bacterium Rhodobacter capsulatus can grow with short- to long-chain fatty acids as the sole carbon source (R. G. Kranz, K. K. Gabbert, T. A. Locke, and M. T. Madigan, Appl. Environ. Microbiol. 63:3003-3009, 1997). Concomitant with growth on fatty acids is the production to high levels of the polyester storage compounds called polyhydroxyalkanoates (PHAs). Here, we describe colony screening and selection systems to analyze the production of PHAs in R. capsulatus. A screen with Nile red dissolved in acetone distinguishes between PHA producers and nonproducers. Unlike the wild type, an R. capsulatus PhaC- strain with the gene encoding PHA synthase deleted is unable to grow on solid media containing high concentrations of certain fatty acids. It is proposed that this deficiency is due to the inability of the PhaC- strain to detoxify the surrounding medium by consumption of fatty acids and their incorporation into PHAs. This fatty acid toxicity phenotype is used in selection for the cloning and characterization of heterologous phaC genes.

Kranz, R G; Gabbert, K K; Madigan, M T

1997-01-01

218

Discovery and preclinical validation of drug indications using compendia of public gene expression data.  

PubMed

The application of established drug compounds to new therapeutic indications, known as drug repositioning, offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval. Recent approaches to drug repositioning use high-throughput experimental approaches to assess a compound's potential therapeutic qualities. Here, we present a systematic computational approach to predict novel therapeutic indications on the basis of comprehensive testing of molecular signatures in drug-disease pairs. We integrated gene expression measurements from 100 diseases and gene expression measurements on 164 drug compounds, yielding predicted therapeutic potentials for these drugs. We recovered many known drug and disease relationships using computationally derived therapeutic potentials and also predict many new indications for these 164 drugs. We experimentally validated a prediction for the antiulcer drug cimetidine as a candidate therapeutic in the treatment of lung adenocarcinoma, and demonstrate its efficacy both in vitro and in vivo using mouse xenograft models. This computational method provides a systematic approach for repositioning established drugs to treat a wide range of human diseases. PMID:21849665

Sirota, Marina; Dudley, Joel T; Kim, Jeewon; Chiang, Annie P; Morgan, Alex A; Sweet-Cordero, Alejandro; Sage, Julien; Butte, Atul J

2011-08-17

219

Discovery and characterization of gene cassettes-containing integrons in clinical strains of Riemerella anatipestifer.  

PubMed

Forty-eight prevalent strains of Riemerella anatipestifer (RA) isolated in China were tested for susceptibility to eighteen antibiotics and investigated for the frequencies and characteristics of integrons and gene cassettes. All isolates were resistant to between three and ten antimicrobial drugs. Forty-seven isolates contained class 1 integron (97.92%), and 15 of the 47 isolates contained class 2 integron (31.25%). Class 3 integron was not detected in the strains analysed. Three different cassette arrays (aadA1, aadA5 and aacA4-aadA1) of class 1 integron and one gene cassette (sat2-aadA1) of class 2 integron were discovered. Three out of the four cassette arrays were novel, with the exception of aadA5. The location of integrons was confirmed by transforming extracted plasmids into an integron-negative strain of Escherichia coli (E. coli) BL21 (DE3). Class 1 integrons were always discovered in plasmids, while class 2 integrons could be located on plasmids or in the chromosome. This is the first description of class 2 integrons, three novel cassette arrays and the location of integrons in RA species. PMID:22112855

Zheng, Fuying; Lin, Guozhen; Zhou, Jizhang; Cao, Xiaoan; Gong, Xiaowei; Wang, Guanghua; Qiu, Changqing

2011-11-06

220

Gene discovery and transcript analyses in the corn smut pathogen Ustilago maydis: expressed sequence tag and genome sequence comparison  

PubMed Central

Background Ustilago maydis is the basidiomycete fungus responsible for common smut of corn and is a model organism for the study of fungal phytopathogenesis. To aid in the annotation of the genome sequence of this organism, several expressed sequence tag (EST) libraries were generated from a variety of U. maydis cell types. In addition to utility in the context of gene identification and structure annotation, the ESTs were analyzed to identify differentially abundant transcripts and to detect evidence of alternative splicing and anti-sense transcription. Results Four cDNA libraries were constructed using RNA isolated from U. maydis diploid teliospores (U. maydis strains 518 × 521) and haploid cells of strain 521 grown under nutrient rich, carbon starved, and nitrogen starved conditions. Using the genome sequence as a scaffold, the 15,901 ESTs were assembled into 6,101 contiguous expressed sequences (contigs); among these, 5,482 corresponded to predicted genes in the MUMDB (MIPS Ustilago maydis database), while 619 aligned to regions of the genome not yet designated as genes in MUMDB. A comparison of EST abundance identified numerous genes that may be regulated in a cell type or starvation-specific manner. The transcriptional response to nitrogen starvation was assessed using RT-qPCR. The results of this suggest that there may be cross-talk between the nitrogen and carbon signalling pathways in U. maydis. Bioinformatic analysis identified numerous examples of alternative splicing and anti-sense transcription. While intron retention was the predominant form of alternative splicing in U. maydis, other varieties were also evident (e.g. exon skipping). Selected instances of both alternative splicing and anti-sense transcription were independently confirmed using RT-PCR. Conclusion Through this work: 1) substantial sequence information has been provided for U. maydis genome annotation; 2) new genes were identified through the discovery of 619 contigs that had previously escaped annotation; 3) evidence is provided that suggests the regulation of nitrogen metabolism in U. maydis differs from that of other model fungi, and 4) Alternative splicing and anti-sense transcription were identified in U. maydis and, amid similar observations in other basidiomycetes, this suggests these phenomena may be widespread in this group of fungi. These advances emphasize the importance of EST analysis in genome annotation.

Ho, Eric CH; Cahill, Matt J; Saville, Barry J

2007-01-01

221

Pattern discovery and cancer gene identification in integrated cancer genomic data.  

PubMed

Large-scale integrated cancer genome characterization efforts including the cancer genome atlas and the cancer cell line encyclopedia have created unprecedented opportunities to study cancer biology in the context of knowing the entire catalog of genetic alterations. A clinically important challenge is to discover cancer subtypes and their molecular drivers in a comprehensive genetic context. Curtis et al. [Nature (2012) 486(7403):346-352] has recently shown that integrative clustering of copy number and gene expression in 2,000 breast tumors reveals novel subgroups beyond the classic expression subtypes that show distinct clinical outcomes. To extend the scope of integrative analysis for the inclusion of somatic mutation data by massively parallel sequencing, we propose a framework for joint modeling of discrete and continuous variables that arise from integrated genomic, epigenomic, and transcriptomic profiling. The core idea is motivated by the hypothesis that diverse molecular phenotypes can be predicted by a set of orthogonal latent variables that represent distinct molecular drivers, and thus can reveal tumor subgroups of biological and clinical importance. Using the cancer cell line encyclopedia dataset, we demonstrate our method can accurately group cell lines by their cell-of-origin for several cancer types, and precisely pinpoint their known and potential cancer driver genes. Our integrative analysis also demonstrates the power for revealing subgroups that are not lineage-dependent, but consist of different cancer types driven by a common genetic alteration. Application of the cancer genome atlas colorectal cancer data reveals distinct integrated tumor subtypes, suggesting different genetic pathways in colon cancer progression. PMID:23431203

Mo, Qianxing; Wang, Sijian; Seshan, Venkatraman E; Olshen, Adam B; Schultz, Nikolaus; Sander, Chris; Powers, R Scott; Ladanyi, Marc; Shen, Ronglai

2013-02-21

222

The fragile x mental retardation syndrome 20 years after the FMR1 gene discovery: an expanding universe of knowledge.  

PubMed

The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the potential of screening for FMR1 mutations. PMID:21912443

Rousseau, François; Labelle, Yves; Bussières, Johanne; Lindsay, Carmen

2011-08-01

223

Use and discovery of chemical elicitors that stimulate biosynthetic gene clusters in Streptomyces bacteria.  

PubMed

Secondary metabolite production from Streptomyces bacteria is primarily controlled at the level of transcription. Under normal laboratory conditions, the majority of the biosynthetic pathways of Streptomyces coelicolor are transcriptionally silent. These are often referred to as "cryptic" pathways and it is thought that they may encode the biosynthesis of yet unseen natural products with novel structures that may be valuable leads for therapeutics and as bioactive compounds. Sequencing of microbial genomes has supported the notion that cryptic pathways are widely distributed and likely to be a source of new chemical diversity. Hence, techniques that can reverse the silencing will be valuable for natural product screening as well as giving access to interesting new biology. We have focused on the identification of chemical elicitors capable of inducing expression of secondary metabolic gene clusters and to do so have drawn a parallel with fungal biology where inhibitors of histone acetylation change chromatin structure to derepress biosynthetic pathways. Similarly, we find that the same chemicals can also modify the expression of pathways in S. coelicolor and other Streptomyces spp. They variously act to increase expression from known pathways as well as inducing cryptic pathways. We hypothesize that nucleoid structure may be playing an analogous role to fungal chromatin structure in controlling transcriptional programs. Further, we speculate that microbial natural product collections could themselves be a rich source of new histone deacetylase inhibitors that have many applications in human health, such as anticancer therapeutics, beyond their traditional use as antimicrobials. PMID:23084948

Moore, Jane M; Bradshaw, Elizabeth; Seipke, Ryan F; Hutchings, Matthew I; McArthur, Michael

2012-01-01

224

An integrated approach to gene discovery and marker development in Atlantic cod (Gadus morhua).  

PubMed

Atlantic cod is a species that has been overexploited by the capture fishery. Programs to domesticate this species are underway in several countries, including Canada, to provide an alternative route for production. Selective breeding programs have been successfully applied in the domestication of other species, with genomics-based approaches used to augment conventional methods of animal production in recent years. Genomics tools, such as gene sequences and sets of variable markers, also have the potential to enhance and accelerate selective breeding programs in aquaculture, and to provide better monitoring tools to ensure that wild cod populations are well managed. We describe the generation of significant genomics resources for Atlantic cod through an integrated genomics/selective breeding approach. These include 158,877 expressed sequence tags (ESTs), a set of annotated putative transcripts and several thousand single nucleotide polymorphism markers that were developed from, and have been shown to be highly variable in, fish enrolled in two selective breeding programs. Our EST collection was generated from various tissues and life cycle stages. In some cases, tissues from which libraries were generated were isolated from fish exposed to stressors, including elevated temperature, or antigen stimulation (bacterial and viral) to enrich for transcripts that are involved in these response pathways. The genomics resources described here support the developing aquaculture industry, enabling the application of molecular markers within selective breeding programs. Marker sets should also find widespread application in fisheries management. PMID:20396923

Bowman, Sharen; Hubert, Sophie; Higgins, Brent; Stone, Cynthia; Kimball, Jennifer; Borza, Tudor; Bussey, Jillian Tarrant; Simpson, Gary; Kozera, Catherine; Curtis, Bruce A; Hall, Jennifer R; Hori, Tiago S; Feng, Charles Y; Rise, Marlies; Booman, Marije; Gamperl, A Kurt; Trippel, Edward; Symonds, Jane; Johnson, Stewart C; Rise, Matthew L

2010-04-16

225

Discovery techniques for calcitonin gene-related peptide receptor antagonists for potential antimigraine therapies.  

PubMed

Introduction: Calcitonin gene-related peptide (CGRP) exerts a key function in migraine pathophysiology through the trigeminovascular system. Influencing this system via CGRP receptor antagonists seems to be an important new option in treating migraine attacks. To characterize new compounds, models are used to study the vascular effects as well as their effects on the central nervous system. Areas covered: The authors review the clinical trials and many different in vitro and in vivo experimental models that have been used to investigate the effects and side effects in animals, healthy subjects and patients. These experimental models are essential, not only in characterizing new CGRP receptor antagonists, but also in gaining more insight into the pathophysiological mechanisms behind migraines. Expert opinion: Although triptans were a major breakthrough in migraine treatment, they are not effective for every patient and contraindicated in patients with cardiovascular disease. There is still a demand for other acute antimigraine acting drugs with CGRP receptor antagonists being the most promising candidates. CGRP plays a role in protection against ischemia, but CGRP receptor antagonists do not seem to affect this protection to a harmfull extent, when used incidentally as acute antimigraine treatment. In order for drug specificity to be increased, the site of action needs to be identified; this consequently may lead to a decrease in dosing with fewer side effects. PMID:23962310

Labruijere, Sieneke; Ibrahimi, Khatera; Chan, Kayi Y; Maassenvandenbrink, Antoinette

2013-08-21

226

Discovery of potent, cyclic calcitonin gene-related peptide receptor antagonists.  

PubMed

Calcitonin gene-related peptide (CGRP), a potent dilator of cerebral and dural vasculature, is known to be elevated in plasma and cerebral spinal fluid during migraine attacks. Selective blockade of the CGRP receptor offers the promise of controlling migraine headache more effectively and without the side-effects associated with the use of triptans. Our efforts to develop a novel, peptide-based CGRP antagonist focused on the C-terminal portion of the peptide which is known to bind the receptor but lack agonist properties. Extensive SAR studies of the C-terminal CGRP (27-37) region identified a novel cyclic structure: Bz-Val-Tyr-cyclo[Cys-Thr-Asp-Val-Gly-Pro-Phe-Cys]-Phe-NH(2) (23) with a kb value of 0.126 nM against the cloned human CGRP receptor. Additional SAR studies directed at enhancement of potency and improvement of physicochemical properties yielded a series of analogs with kb values in the 0.05-0.10 nM range. PMID:21412957

Yan, Liang Zeng; Johnson, Kirk W; Rothstein, Emily; Flora, David; Edwards, Patrick; Li, Baolin; Li, Junqing; Lynch, Renee; Vaughn, Renee; Clemens-Smith, Amy; McCarty, Deborah; Chow, Charles; McKnight, Kevin L; Lu, Jirong; Nisenbaum, Eric S; Mayer, John P

2011-03-15

227

The role of digital airborne imaging spectrometer data in the discovery of the Arcopunco epithermal gold project; Huancavelica, Central Peru  

Microsoft Academic Search

The high Andes of Central Peru present significant logistical problems to mineral exploration and remote sensing is a valuable primary tool. Landsat TM data have been widely used but extensive clay-iron color anomalies need to be mapped in more detail to optimize follow-up exploration and land holdings. Major discoveries have little or no clay-iron anomalism and so it was decided

R. A. Agar

2001-01-01

228

Guided Discoveries.  

ERIC Educational Resources Information Center

|Presented are four mathematical discoveries made by students on an arithmetical function using the Fibonacci sequence. Discussed is the nature of the role of the teacher in directing the students' discovery activities. (KR)|

Ehrlich, Amos

1991-01-01

229

Integration of Cot Analysis, DNA Cloning, and High-Throughput Sequencing Facilitates Genome Characterization and Gene Discovery  

PubMed Central

Cot-based sequence discovery represents a powerful means by which both low-copy and repetitive sequences can be selectively and efficiently fractionated, cloned, and characterized. Based upon the results of a Cot analysis, hydroxyapatite chromatography was used to fractionate sorghum (Sorghum bicolor) genomic DNA into highly repetitive (HR), moderately repetitive (MR), and single/low-copy (SL) sequence components that were consequently cloned to produce HRCot, MRCot, and SLCot genomic libraries. Filter hybridization (blotting) and sequence analysis both show that the HRCot library is enriched in sequences traditionally found in high-copy number (e.g., retroelements, rDNA, centromeric repeats), the SLCot library is enriched in low-copy sequences (e.g., genes and “nonrepetitive ESTs”), and the MRCot library contains sequences of moderate redundancy. The Cot analysis suggests that the sorghum genome is approximately 700 Mb (in agreement with previous estimates) and that HR, MR, and SL components comprise 15%, 41%, and 24% of sorghum DNA, respectively. Unlike previously described techniques to sequence the low-copy components of genomes, sequencing of Cot components is independent of expression and methylation patterns that vary widely among DNA elements, developmental stages, and taxa. High-throughput sequencing of Cot clones may be a means of “capturing” the sequence complexity of eukaryotic genomes at unprecedented efficiency. [Online supplementary material is available at www.genome.org. The sequence data described in this paper have been submitted to the GenBank under accession nos. AZ921847-AZ923007. Reagents, samples, and unpublished information freely provided by H. Ma and J. Messing.

Peterson, Daniel G.; Schulze, Stefan R.; Sciara, Erica B.; Lee, Scott A.; Bowers, John E.; Nagel, Alexander; Jiang, Ning; Tibbitts, Deanne C.; Wessler, Susan R.; Paterson, Andrew H.

2002-01-01

230

Relationships between inhibitory activity against a cancer cell line panel, profiles of plants collected, and compound classes isolated in an anticancer drug discovery project.  

PubMed

In an attempt to determine the relationships between the plant profiles (country of collection, taxonomy, plant part) and the compound classes isolated with cytotoxic activity against a panel of human tumor cell lines, the data compiled from a 15-year anticancer drug-discovery project were subjected to an analysis of variance (ANOVA). The results indicate significant trends in cytotoxic activity relative to collection location, taxonomy, plant part, and compound classes isolated. Plant collections were made in tropical forests in six countries, with collections from Ecuador resulting in higher activity than those from Indonesia and Peru. Interestingly, collections from Florida were not statistically different than those from the countries with higher biodiversity. One hundred and forty-five families were represented in the collections, with the Clusiaceae, Elaeocarpaceae, Meliaceae, and Rubiaceae having low ED50 (half maximal effective dose) values. Especially active genera included Aglaia, Casearia, Exostema, Mallotus, and Trichosanthes. Roots and below-ground plant materials were significantly more active than above-ground materials. Cucurbitacins, flavaglines, anthraquinones, fatty acids, tropane alkaloids, lignans, and sesquiterpenoids were significantly more active than xanthones and oligorhamnosides. The results from this study should serve as a guide for future plant collection endeavors for anticancer drug discovery. PMID:17193321

Balunas, Marcy J; Jones, William P; Chin, Young-Won; Mi, Qiuwen; Farnsworth, Norman R; Soejarto, Djaja D; Cordell, Geoffrey A; Swanson, Steven M; Pezzuto, John M; Chai, Hee-Byung; Kinghorn, A Douglas

2006-08-01

231

Design of the DISCovery project: tailored work-oriented interventions to improve employee health, well-being, and performance-related outcomes in hospital care  

PubMed Central

Background It is well-known that health care workers in today’s general hospitals have to deal with high levels of job demands, which could have negative effects on their health, well-being, and job performance. A way to reduce job-related stress reactions and to optimize positive work-related outcomes is to raise the level of specific job resources and opportunities to recover from work. However, the question remains how to translate the optimization of the balance between job demands, job resources, and recovery opportunities into effective workplace interventions. The aim of the DISCovery project is to develop and implement tailored work-oriented interventions to improve health, well-being, and performance of health care personnel. Methods/Design A quasi-experimental field study with a non-equivalent control group pretest-posttest design will be conducted in a top general hospital. Four existing organizational departments will provide both an intervention and a comparison group. Two types of research methods are used: (1) a longitudinal web-based survey study, and (2) a longitudinal daily diary study. After base-line measures of both methods, existing and yet to be developed interventions will be implemented within the experimental groups. Follow-up measurements will be taken one and two years after the base-line measures to analyze short-term and long-term effects of the interventions. Additionally, a process evaluation and a cost-effectiveness analysis will be carried out. Discussion The DISCovery project fulfills a strong need for theory-driven and scientifically well-performed research on job stress and performance interventions. It will provide insight into (1) how a balance between job demands, job resources, and recovery from work can be optimized, (2) the short-term and long-term effects of tailored work-oriented effects, and (3) indicators for successful or unsuccessful implementation of interventions.

2013-01-01

232

Discoveries 1969  

Microsoft Academic Search

The Sacramento Valley had the following discoveries: (1) Grimes gas field extension; (2) Pinole (a new oil field); (3) Black Butte (shallower pool); (4) Cache Slough (deeper pool); (5) Maine Prairie (extension and deeper pool); (6) Van Sickle Island (new gas field) and (7) Green's Lake (new gas field). The San Joaquin Valley had the following discoveries; (1) Riverdale (oil

Munger

1970-01-01

233

The Genetics of Obsessive-Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway-Based Approach for Gene Discovery  

ERIC Educational Resources Information Center

|Objective: To provide a contemporary perspective on genetic discovery methods applied to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Method: A review of research trends in genetics research in OCD and TS is conducted, with emphasis on novel approaches. Results: Genome-wide association studies (GWAS) are now in progress in OCD…

Grados, Marco A.

2010-01-01

234

Discovery of Isotopes  

Microsoft Academic Search

We started a project to document the discovery of all known isotopes. The information for the isotopes are summarized for each element, including the discoverers, the laboratory and year in which it was first observed, the production method and the method of mass assignment used. Only refereed publications were considered, but unpublished reports and other various discrepancies pertaining to the

A. Schuh; A. Shore; A. Bury; A. Fritsch; J. Q. Ginepro; M. Heim; J. Snyder; M. Thoennessen

2008-01-01

235

Scientific Discovery for All  

ERIC Educational Resources Information Center

|The scientific discovery process comes alive for 70 minority students each year at Uniondale High School in New York where students have won top awards for "in-house" projects. Uniondale High School is in a middle-income school district where over 95% of students are from minority groups. Founded in 2000, the Uniondale High School Research…

Zaikowski, Lori; Lichtman, Paul; Quarless, Duncan

2007-01-01

236

The Analysis of Multiple Genome Comparisons in Genus Escherichia and Its Application to the Discovery of Uncharacterised Metabolic Genes in Uropathogenic Escherichia coli CFT073.  

PubMed

A survey of a complete gene synteny comparison has been carried out between twenty fully sequenced strains from the genus Escherichia with the aim of finding yet uncharacterised genes implicated in the metabolism of uropathogenic strains of E. coli (UPEC). Several sets of adjacent colinear genes have been identified which are present in all four UPEC included in this study (CFT073, F11, UTI89, and 536), annotated with putative metabolic functions, but are not found in any other strains considered. An operon closely homologous to that encoding the L-sorbose degradation pathway in Klebsiella pneumoniae has been identified in E. coli CFT073; this operon is present in all of the UPEC considered, but only in 7 of the other 16 strains. The operon's function has been confirmed by cloning the genes into E. coli DH5alpha and testing for growth on L-sorbose. The functional genomic approach combining in silico and in vitro work presented here can be used as a basis for the discovery of other uncharacterised genes contributing to bacterial survival in specific environments. PMID:20204180

Bryant, William A; Krabben, Preben; Baganz, Frank; Zhou, Yuhong; Ward, John M

2010-03-02

237

Gene disruptions using P transposable elements: An integral component of the Drosophila genome project  

SciTech Connect

Biologists require genetic as well as molecular tools to decipher genomic information and ultimately to understand gene function. The Berkeley Drosophila Genome Project is addressing these needs with a massive gene disruption project that uses individual, genetically engineered P transposable elements to target open reading frames throughout the Drosophila genome DNA flanking the insertions is sequenced thereby placing and extensive series of genetic markers on the physical genomic map and associating insertions with specific open reading frames and genes. Insertions from the collection now lie within or near most Drosophila genes, greatly reducing the time required to identify new mutations and analyze gene functions. Information revealed from these studies about P element site specificity is being used to target the remaining open reading frames. 38 refs., 5 figs., 1 tab.

Spradling, A.C.; Stern, D.M. [Howard Hughes Medical Institute Research Labs., Baltimore, MD (United States); Kiss, I. [Institute of Genetics, Szeged (Hungary)] [and others

1995-11-21

238

Discovery Bottles  

NSDL National Science Digital Library

Discover discovery bottles! These wide-mouth plastic containers of any size filled with objects of different kinds can be terrific tools for science explorations and a great way to cultivate science minds in a K--2 science classroom. In addition, the author has found them to be a useful, inexpensive, and engaging way to help students develop skills in making predictions, observations, and comparisons. Here she shares a few of her favorite physical science lesson ideas using discovery bottles.

Watson, Sandy

2008-07-01

239

The Gene Ontology (GO) project: structured vocabularies for molecular biology and their application to genome and expression analysis  

Microsoft Academic Search

Scientists wishing to utilize genomic data have quickly come to realize the benefit of standardizing descriptions of experimental procedures and results for computer-driven information retrieval systems. The focus of the Gene Ontology project is three-fold. First, the project goal is to compile the Gene Ontologies; structured vocabularies describing domains of molecular biology. Second, the project supports the use of these

J A Blake; M A Harris

2002-01-01

240

The Gene Ontology (GO) project: structured vocabularies for molecular biology and their application to genome and expression analysis  

Microsoft Academic Search

Scientists wishing to utilize genomic data have quickly come to realize the benefit of standardizing descriptions of experimental procedures and results for computer-driven information retrieval systems. The focus of the Gene Ontology project is three-fold. First, the project goal is to compile the Gene Ontologies: structured vocabularies describing domains of molecular biology. Second, the project supports the use of these

J A Blake; M A Harris

2008-01-01

241

Associating Gene Therapy with the Human Genome Project  

Microsoft Academic Search

As is often the case with cutting-edge biomedical technology, the introduction of gene therapy in Japan provoked discussions\\u000a of ethics and safety while offering little hope for dramatic recovery. Nevertheless, only 5 years after the first authorized\\u000a clinical trial in the USA, the first Japanese trial was conducted in 1995. This trial event garnered extensive media coverage\\u000a but yielded little opposition.

Makoto Hayashi

2010-01-01

242

National Research Council endorses human gene mapping project  

SciTech Connect

A news article discusses the Human Genome Initiative. The National Research Council, an arm of the National Academy of Sciences that is empowered by Congress to advise the federal government, is recommending a $3-billion effort to map and sequence the human genome. The committee advises appropriating $200 million each year for the project over the next 15 years. It emphasizes that funding should be generated de novo, not diverted from existing biologic and medical research efforts. As envisioned, the project would be executed in two stages: genome mapping and DNA sequencing. The first would involve preparing both physical maps, in which previously identified DNA segments are aligned in proper order on the appropriate chromosome, and genetic maps, which demonstrate the frequency with which two traits are likely to be inherited together. The recommendation paralleled provisions of two Senate bills-the science initiative bill introduced last summer by Senator Pete Domenici of New Mexico and the biotechnology bill, which senators Edward Kennedy of Massachusetts, Lawton Chiles of Florida, and Domenici introduced in December.

Not Available

1988-03-11

243

Combining SNP discovery from next-generation sequencing data with bulked segregant analysis (BSA) to fine-map genes in polyploid wheat  

PubMed Central

Background Next generation sequencing (NGS) technologies are providing new ways to accelerate fine-mapping and gene isolation in many species. To date, the majority of these efforts have focused on diploid organisms with readily available whole genome sequence information. In this study, as a proof of concept, we tested the use of NGS for SNP discovery in tetraploid wheat lines differing for the previously cloned grain protein content (GPC) gene GPC-B1. Bulked segregant analysis (BSA) was used to define a subset of putative SNPs within the candidate gene region, which were then used to fine-map GPC-B1. Results We used Illumina paired end technology to sequence mRNA (RNAseq) from near isogenic lines differing across a ~30-cM interval including the GPC-B1 locus. After discriminating for SNPs between the two homoeologous wheat genomes and additional quality filtering, we identified inter-varietal SNPs in wheat unigenes between the parental lines. The relative frequency of these SNPs was examined by RNAseq in two bulked samples made up of homozygous recombinant lines differing for their GPC phenotype. SNPs that were enriched at least 3-fold in the corresponding pool (6.5% of all SNPs) were further evaluated. Marker assays were designed for a subset of the enriched SNPs and mapped using DNA from individuals of each bulk. Thirty nine new SNP markers, corresponding to 67% of the validated SNPs, mapped across a 12.2-cM interval including GPC-B1. This translated to 1 SNP marker per 0.31 cM defining the GPC-B1 gene to within 13-18 genes in syntenic cereal genomes and to a 0.4 cM interval in wheat. Conclusions This study exemplifies the use of RNAseq for SNP discovery in polyploid species and supports the use of BSA as an effective way to target SNPs to specific genetic intervals to fine-map genes in unsequenced genomes.

2012-01-01

244

Microarray-based discovery of highly expressed olfactory mucosal genes: potential roles in the various functions of the olfactory system.  

PubMed

We sought to gain a global view of tissue-specific gene expression in the olfactory mucosa (OM), the major site of neurogenesis and neuroregeneration in adult vertebrates, by examination of its overexpressed genes relative to that in 81 other developing and adult mouse tissues. We used a combination of statistical and fold-difference criteria to identify the top 269 cloned cDNAs from an array of 8,734 mouse cDNA elements on the Incyte Mouse GEM1 array. These clones, representing known and poorly characterized gene transcripts, were grouped according to their relative expression patterns across the other tissues and then further examined with respect to gene ontology categories. Approximately one-third of the 269 genes were also highly expressed in developing and/or adult central nervous system tissues. Several of these have been suggested or demonstrated to play roles in neurogenesis, neuronal differentiation, and/or neuronal migration, further suggesting that many of the unknown genes that share this expression pattern may play similar roles. Highly OM-specific genes included a palate, lung, and nasal epithelium carcinoma-associated gene (Plunc); sphingosine phosphate lyase (Sgpl1), and paraoxonase 1 (Pon1). Cell-type-specific expression within OM was established using in situ hybridization for several representative expression pattern clusters. Using the ENSEMBL-assembled mouse genome and comparative genomics analyses to the human genome, we assigned many of the unknown expressed sequence tags (ESTs) and poorly characterized genes to either novel or known gene products and provided predictive classification. Further exploration of this database will provide additional insights into genes and pathways critical for olfactory neurogenesis, neuronal differentiation, olfaction, and mucosal defense. PMID:14570983

Genter, Mary Beth; Van Veldhoven, Paul P; Jegga, Anil G; Sakthivel, Bhuvana; Kong, Sue; Stanley, Kristin; Witte, David P; Ebert, Catherine L; Aronow, Bruce J

2003-12-16

245

Immune gene discovery by expressed sequence tag (EST) analysis of hemocytes in the ridgetail white prawn Exopalaemon carinicauda  

PubMed Central

The ridgetail white prawn Exopalaemon carinicauda is one of the most important commercial species in eastern China. However, little information of immune genes in E. carinicauda has been reported. To identify distinctive genes associated with immunity, an expressed sequence tag (EST) library was constructed from hemocytes of E. carinicauda. A total of 3411 clones were sequenced, yielding 2853 ESTs and the average sequence length is 436 bp. The cluster and assembly analysis yielded 1053 unique sequences including 329 contigs and 724 singletons. Blast analysis identified 593 (56.3%) of the unique sequences as orthologs of genes from other organisms (E-value < 1e-5). Based on the COG and Gene Ontology (GO), 593 unique sequences were classified. Through comparison with previous studies, 153 genes assembled from 367 ESTs have been identified as possibly involved in defense or immune functions. These genes are categorized into seven categories according to their putative functions in shrimp immune system: antimicrobial peptides, prophenoloxidase activating system, antioxidant defense systems, chaperone proteins, clottable proteins, pattern recognition receptors and other immune-related genes. According to EST abundance, the major immune-related genes were thioredoxin (141, 4.94% of all ESTs) and calmodulin (14, 0.49% of all ESTs). The EST sequences of E. carinicauda hemocytes provide important information of the immune system and lay the groundwork for development of molecular markers related to disease resistance in prawn species.

Duan, Yafei; Liu, Ping; Li, Jitao; Li, Jian; Chen, Ping

2013-01-01

246

Expressed sequence tags in cultivated peanut (Arachis hypogaea): discovery of genes in seed development and response to Ralstonia solanacearum challenge.  

PubMed

Although an important oil crop, peanut has only 162,030 expressed sequence tags (ESTs) publicly available, 86,943 of which are from cultivated plants. More ESTs from cultivated peanuts are needed for isolation of stress-resistant, tissue-specific and developmentally important genes. Here, we generated 63,234 ESTs from our 5 constructed peanut cDNA libraries of Ralstonia solanacearum challenged roots, R. solanacearum challenged leaves, and unchallenged cultured peanut roots, leaves and developing seeds. Among these ESTs, there were 14,547 unique sequences with 7,961 tentative consensus sequences and 6,586 singletons. Putative functions for 47.8 % of the sequences were identified, including transcription factors, tissue-specific genes, genes involved in fatty acid biosynthesis and oil formation regulation, and resistance gene analogue genes. Additionally, differentially expressed genes, including those involved in ethylene and jasmonic acid signal transduction pathways, from both peanut leaves and roots, were identified in R. solanacearum challenged samples. This large expression dataset from different peanut tissues will be a valuable source for marker development and gene expression analysis. It will also be helpful for finding candidate genes for fatty acid synthesis and oil formation regulation as well as for studying mechanisms of interactions between the peanut host and R. solanacearum pathogen. PMID:22648474

Huang, Jiaquan; Yan, Liying; Lei, Yong; Jiang, Huifang; Ren, Xiaoping; Liao, Boshou

2012-05-31

247

Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes  

PubMed Central

Background Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

2011-01-01

248

The fungal mitochondrial genome project: evolution of fungal mitochondrial genomes and their gene expression  

Microsoft Academic Search

The goal of the fungal mitochondrial genome project (FMGP) is to sequence complete mitochondrial genomes for a representative\\u000a sample of the major fungal lineages; to analyze the genome structure, gene content, and conserved sequence elements of these\\u000a sequences; and to study the evolution of gene expression in fungal mitochondria. By using our new sequence data for evolutionary\\u000a studies, we were

Bruno Paquin; Marie-Josée Laforest; Lise Forget; Ingeborg Roewer; Zhang Wang; Joyce Longcore; B. Franz Lang

1997-01-01

249

Progress in mapping agronomic genes in apple (The European Apple Genome Mapping Project)  

Microsoft Academic Search

Summary  The progress of the European Apple Genome Mapping Project is described. Populations segregating for a range of agronomic genes\\u000a have been established in six European countries. The need for robust methods of analysis has been identified, especially with\\u000a regard to the development of molecular markers. Isozyme systems, RAPDs, RFLPs and amplified genes are being used to construct\\u000a a reference genetic

Graham J. King

1994-01-01

250

The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project.  

PubMed

The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions. PMID:20150743

de Marco, R; Accordini, S; Antonicelli, L; Bellia, V; Bettin, M D; Bombieri, C; Bonifazi, F; Bugiani, M; Carosso, A; Casali, L; Cazzoletti, L; Cerveri, I; Corsico, A G; Ferrari, M; Fois, A G; Lo Cascio, V; Marcon, A; Marinoni, A; Olivieri, M; Perbellini, L; Pignatti, P; Pirina, P; Poli, A; Rolla, G; Trabetti, E; Verlato, G; Villani, S; Zanolin, M E

2010-02-11

251

Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N=1198) using genome-wide search  

PubMed Central

The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural MRI and genome-wide genotypes were acquired from two large cohorts, the Alzheimer’s Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at SNP rs163030 in the ADNI discovery sample (P=2.36×10?6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79% and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.

Stein, Jason L.; Hibar, Derrek P.; Madsen, Sarah K.; Khamis, Mathew; McMahon, Katie L.; de Zubicaray, Greig I.; Hansell, Narelle K.; Montgomery, Grant W.; Martin, Nicholas G.; Wright, Margaret J.; Saykin, Andrew J.; Jack, Clifford R.; Weiner, Michael W.; Toga, Arthur W.; Thompson, Paul M.

2011-01-01

252

Generation of ESTs in Vitis vinifera wine grape (Cabernet Sauvignon) and table grape (Muscat Hamburg) and discovery of new candidate genes with potential roles in berry development.  

PubMed

We report the generation and analysis of a total of 77,583 expressed sequence tags (ESTs) from two grapevine (Vitis vinifera L.) cultivars, Cabernet Sauvignon (wine grape) and Muscat Hamburg (table grape) with a focus on EST sequence quality and assembly optimization. The majority of the ESTs were derived from normalized cDNA libraries representing berry pericarp and seed developmental series, pooled non-berry tissues including root, flower, and leaf in Cabernet Sauvignon, and pooled tissues of berry, seed, and flower in Muscat Hamburg. EST and unigene sequence quality were determined by computational filtering coupled with small-scale contig reassembly, manual review, and BLAST analyses. EST assembly was optimized to better discriminate among closely related paralogs using two independent grape sequence sets, a previously published set of Vitis spp. gene families and our EST dataset derived from pooled leaf, flower, and root tissues of Cabernet Sauvignon. Sequence assembly within individual libraries indicated that those prepared from pooled tissues contributed the most to gene discovery. Annotations based upon searches against multiple databases including tomato and strawberry sequences helped to identify putative functions of ESTs and unigenes, particularly with respect to fleshy fruit development. Sequence comparison among the three wine grape libraries identified a number of genes preferentially expressed in the pericarp tissue, including transcription factors, receptor-like protein kinases, and hexose transporters. Gene ontology (GO) classification in the biological process aspect showed that GO categories corresponding to 'transport' and 'cell organization and biogenesis', which are associated with metabolite movement and cell wall structural changes during berry ripening, were higher in pericarp than in other tissues in the wine grape studied. The sequence data were used to characterize potential roles of new genes in berry development and composition. PMID:17761391

Peng, Fred Y; Reid, Karen E; Liao, Nancy; Schlosser, James; Lijavetzky, Diego; Holt, Robert; Martínez Zapater, José M; Jones, Steven; Marra, Marco; Bohlmann, Jörg; Lund, Steven T

2007-07-31

253

Space Discovery.  

ERIC Educational Resources Information Center

|Describes one teacher's experience taking Space Discovery courses that were sponsored by the United States Space Foundation (USSF). These courses examine the history of space science, theory of orbits and rocketry, the effects of living in outer space on humans, and space weather. (DDR)|

Blackman, Joan

1998-01-01

254

Accidental Discoveries  

NSDL National Science Digital Library

The students will understand that science theories change in the face of new evidence, but those changes can be slow in coming. To download the lesson plan as a pdf, see the document below. Students willResearch scientific discoveries that happened by accident in the past and learn how gamma-rays were discovered by 20th century scientists

2010-01-01

255

Validation of the Intact Zwittermicin A Biosynthetic Gene Cluster and Discovery of a Complementary Resistance Mechanism in Bacillus thuringiensis?†  

PubMed Central

Zwittermicin A (ZmA) is a hybrid polyketide-nonribosomal peptide produced by certain Bacillus cereus group strains. It displays broad-spectrum antimicrobial activity. Its biosynthetic pathway in B. cereus has been proposed through analysis of the nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules involved in ZmA biosynthesis. In this study, we constructed a bacterial artificial chromosome (BAC) library from Bacillus thuringiensis subsp. kurstaki strain YBT-1520 genomic DNA. The presence of known genes involved in the biosynthesis of ZmA in this BAC library was investigated by PCR techniques. Nine positive clones were identified, two of which (covering an approximately 60-kb region) could confer ZmA biosynthesis ability upon B. thuringiensis BMB171 after simultaneous transfer into this host by two compatible shuttle BAC vectors. Another previously unidentified gene cluster, named zmaWXY, was found to improve the yield of ZmA and was experimentally defined to function as a ZmA resistance transporter which expels ZmA from the cells. Putative transposase genes were detected on the flanking regions of the two gene clusters (the ZmA synthetic cluster and zmaWXY), which suggests a mobile nature of these two gene clusters. The intact ZmA gene cluster was validated, and a resistance mechanism complementary to that for zmaR (the previously identified ZmA self-resistance gene) was revealed. This study also provided a straightforward strategy to isolate and identify a huge gene cluster from Bacillus.

Luo, Yi; Ruan, Li-Fang; Zhao, Chang-Ming; Wang, Cheng-Xian; Peng, Dong-Hai; Sun, Ming

2011-01-01

256

Validation of the intact zwittermicin A biosynthetic gene cluster and discovery of a complementary resistance mechanism in Bacillus thuringiensis.  

PubMed

Zwittermicin A (ZmA) is a hybrid polyketide-nonribosomal peptide produced by certain Bacillus cereus group strains. It displays broad-spectrum antimicrobial activity. Its biosynthetic pathway in B. cereus has been proposed through analysis of the nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules involved in ZmA biosynthesis. In this study, we constructed a bacterial artificial chromosome (BAC) library from Bacillus thuringiensis subsp. kurstaki strain YBT-1520 genomic DNA. The presence of known genes involved in the biosynthesis of ZmA in this BAC library was investigated by PCR techniques. Nine positive clones were identified, two of which (covering an approximately 60-kb region) could confer ZmA biosynthesis ability upon B. thuringiensis BMB171 after simultaneous transfer into this host by two compatible shuttle BAC vectors. Another previously unidentified gene cluster, named zmaWXY, was found to improve the yield of ZmA and was experimentally defined to function as a ZmA resistance transporter which expels ZmA from the cells. Putative transposase genes were detected on the flanking regions of the two gene clusters (the ZmA synthetic cluster and zmaWXY), which suggests a mobile nature of these two gene clusters. The intact ZmA gene cluster was validated, and a resistance mechanism complementary to that for zmaR (the previously identified ZmA self-resistance gene) was revealed. This study also provided a straightforward strategy to isolate and identify a huge gene cluster from Bacillus. PMID:21730118

Luo, Yi; Ruan, Li-Fang; Zhao, Chang-Ming; Wang, Cheng-Xian; Peng, Dong-Hai; Sun, Ming

2011-07-05

257

Discovery of genes related to insecticide resistance in Bactrocera dorsalis by functional genomic analysis of a de novo assembled transcriptome.  

PubMed

Insecticide resistance has recently become a critical concern for control of many insect pest species. Genome sequencing and global quantization of gene expression through analysis of the transcriptome can provide useful information relevant to this challenging problem. The oriental fruit fly, Bactrocera dorsalis, is one of the world's most destructive agricultural pests, and recently it has been used as a target for studies of genetic mechanisms related to insecticide resistance. However, prior to this study, the molecular data available for this species was largely limited to genes identified through homology. To provide a broader pool of gene sequences of potential interest with regard to insecticide resistance, this study uses whole transcriptome analysis developed through de novo assembly of short reads generated by next-generation sequencing (NGS). The transcriptome of B. dorsalis was initially constructed using Illumina's Solexa sequencing technology. Qualified reads were assembled into contigs and potential splicing variants (isotigs). A total of 29,067 isotigs have putative homologues in the non-redundant (nr) protein database from NCBI, and 11,073 of these correspond to distinct D. melanogaster proteins in the RefSeq database. Approximately 5,546 isotigs contain coding sequences that are at least 80% complete and appear to represent B. dorsalis genes. We observed a strong correlation between the completeness of the assembled sequences and the expression intensity of the transcripts. The assembled sequences were also used to identify large numbers of genes potentially belonging to families related to insecticide resistance. A total of 90 P450-, 42 GST-and 37 COE-related genes, representing three major enzyme families involved in insecticide metabolism and resistance, were identified. In addition, 36 isotigs were discovered to contain target site sequences related to four classes of resistance genes. Identified sequence motifs were also analyzed to characterize putative polypeptide translational products and associate them with specific genes and protein functions. PMID:22879883

Hsu, Ju-Chun; Chien, Ting-Ying; Hu, Chia-Cheng; Chen, Mei-Ju May; Wu, Wen-Jer; Feng, Hai-Tung; Haymer, David S; Chen, Chien-Yu

2012-08-07

258

High Throughput Screening of Co-Expressed Gene Pairs with Controlled False Discovery Rate (FDR) and Minimum Acceptable Strength (MAS)  

Microsoft Academic Search

Many exploratory microarray data analysis tools such as gene clustering and relevance networks rely on detecting pairwise gene co-expression. Traditional screening of pairwise co-expression either controls bio- logical significance or statistical significance, but not both. The former approach does not provide stochastic error control, and the later approach screens many co-expressions with excessively low correlation. We have designed and implemented

Dongxiao Zhu; Alfred O. Hero; Zhaohui S. Qin; Anand Swaroop

2005-01-01

259

Transcriptome-based discovery of pathways and genes related to resistance against Fusarium head blight in wheat landrace Wangshuibai  

PubMed Central

Background Fusarium head blight (FHB), caused mainly by Fusarium graminearum (Fg) Schwabe (teleomorph: Gibberellazeae Schwble), brings serious damage to wheat production. Chinese wheat landrace Wangshuibai is one of the most important resistance sources in the world. The knowledge of mechanism underlying its resistance to FHB is still limited. Results To get an overview of transcriptome characteristics of Wangshuibai during infection by Fg, a high-throughput RNA sequencing based on next generation sequencing (NGS) technology (Illumina) were performed. Totally, 165,499 unigenes were generated and assigned to known protein databases including NCBI non-redundant protein database (nr) (82,721, 50.0%), Gene Ontology (GO) (38,184, 23.1%), Swiss-Prot (50,702, 30.6%), Clusters of orthologous groups (COG) (51,566, 31.2%) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) (30,657, 18.5%), as determined by Blastx search. With another NGS based platform, a digital gene expression (DGE) system, gene expression in Wangshuibai and its FHB susceptible mutant NAUH117 was profiled and compared at two infection stages by inoculation of Fg at 24 and 48 hour, with the aim of identifying genes involved in FHB resistance. Conclusion Pathogen-related proteins such as PR5, PR14 and ABC transporter and JA signaling pathway were crucial for FHB resistance, especially that mediated by Fhb1. ET pathway and ROS/NO pathway were not activated in Wangshuibai and may be not pivotal in defense to FHB. Consistent with the fact that in NAUH117 there presented a chromosome fragment deletion, which led to its increased FHB susceptibility, in Wangshuibai, twenty out of eighty-nine genes showed changed expression patterns upon the infection of Fg. The up-regulation of eight of them was confirmed by qRT-PCR, revealing they may be candidate genes for Fhb1 and need further functional analysis to confirm their roles in FHB resistance.

2013-01-01

260

A Comparison of Digital Gene Expression Profiling and Methyl DNA Immunoprecipitation as Methods for Gene Discovery in Honeybee (Apis mellifera) Behavioural Genomic Analyses.  

PubMed

The honey bee has a well-organized system of division of labour among workers. Workers typically progress through a series of discrete behavioural castes as they age, and this has become an important case study for exploring how dynamic changes in gene expression can influence behaviour. Here we applied both digital gene expression analysis and methyl DNA immunoprecipitation analysis to nurse, forager and reverted nurse bees (nurses that have returned to the nursing state after a period spent foraging) from the same colony in order to compare the outcomes of these different forms of genomic analysis. A total of 874 and 710 significantly differentially expressed genes were identified in forager/nurse and reverted nurse/forager comparisons respectively. Of these, 229 genes exhibited reversed directions of gene expression differences between the forager/nurse and reverted nurse/forager comparisons. Using methyl-DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq) we identified 366 and 442 significantly differentially methylated genes in forager/nurse and reverted nurse/forager comparisons respectively. Of these, 165 genes were identified as differentially methylated in both comparisons. However, very few genes were identified as both differentially expressed and differentially methylated in our comparisons of nurses and foragers. These findings confirm that changes in both gene expression and DNA methylation are involved in the nurse and forager behavioural castes, but the different analytical methods reveal quite distinct sets of candidate genes. PMID:24040006

Guan, Cui; Barron, Andrew B; He, Xu Jiang; Wang, Zi Long; Yan, Wei Yu; Zeng, Zhi Jiang

2013-09-09

261

Breast Cancer Biomarker Discovery in the Functional Genomic Age: A Systematic Review of 42 Gene Expression Signatures  

PubMed Central

In this review we provide a systematic analysis of transcriptomic signatures derived from 42 breast cancer gene expression studies, in an effort to identify the most relevant breast cancer biomarkers using a meta-analysis method. Meta-data revealed a set of 117 genes that were the most commonly affected ranging from 12% to 36% of overlap among breast cancer gene expression studies. Data mining analysis of transcripts and protein-protein interactions of these commonly modulated genes indicate three functional modules significantly affected among signatures, one module related with the response to steroid hormone stimulus, and two modules related to the cell cycle. Analysis of a publicly available gene expression data showed that the obtained meta-signature is capable of predicting overall survival (P < 0.0001) and relapse-free survival (P < 0.0001) in patients with early-stage breast carcinomas. In addition, the identified meta-signature improves breast cancer patient stratification independently of traditional prognostic factors in a multivariate Cox proportional-hazards analysis.

Abba, M.C; Lacunza, E; Butti, M; Aldaz, C.M

2010-01-01

262

Discovery of a novel human G protein-coupled receptor gene (GPR25) located on chromosome 1.  

PubMed

We amplified human genomic DNA by the polymerase chain reaction (PCR) using oligonucleotides based on the primary sequence of the genes encoding the somatostatin receptors (SSTR) and the somatostatin-like receptor gene SLC-1. One resultant DNA fragment was used to screen a genomic DNA library resulting in the isolation of a gene, GPR25, encoding an additional member of the G protein-coupled receptor family (GPCR). GPR25 is intronless throughout its open reading frame (ORF) and encodes a protein of 360 amino acids. The receptor encoded by GPR25 shares highest identity to the receptor encoded by GPR15, angiotensin II type 1A receptor, and somatostatin receptor 5. Northern analysis found no transcripts expressed in liver or any of the 12 brain regions analyzed. Fluorescence in situ hybridization analysis localized GPR25 to chromosome 1q32.1. PMID:9020062

Jung, B P; Nguyen, T; Kolakowski, L F; Lynch, K R; Heng, H H; George, S R; O'Dowd, B F

1997-01-01

263

An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits.  

PubMed

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6x10(-8)), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6x10(-13); SOX6, p = 6.4x10(-10)) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation. PMID:20548944

Hsu, Yi-Hsiang; Zillikens, M Carola; Wilson, Scott G; Farber, Charles R; Demissie, Serkalem; Soranzo, Nicole; Bianchi, Estelle N; Grundberg, Elin; Liang, Liming; Richards, J Brent; Estrada, Karol; Zhou, Yanhua; van Nas, Atila; Moffatt, Miriam F; Zhai, Guangju; Hofman, Albert; van Meurs, Joyce B; Pols, Huibert A P; Price, Roger I; Nilsson, Olle; Pastinen, Tomi; Cupples, L Adrienne; Lusis, Aldons J; Schadt, Eric E; Ferrari, Serge; Uitterlinden, André G; Rivadeneira, Fernando; Spector, Timothy D; Karasik, David; Kiel, Douglas P

2010-06-10

264

In silico discovery of gene-coding variants in murine quantitative trait loci using strain-specific genome sequence databases  

Microsoft Academic Search

BACKGROUND: The identification of genes underlying complex traits has been aided by quantitative trait locus (QTL) mapping approaches, which in turn have benefited from advances in mammalian genome research. Most recently, whole-genome draft sequences and assemblies have been generated for mouse strains that have been used for a large fraction of QTL mapping studies. Here we show how such strain-specific

Kriste E Marshall; Elizabeth L Godden; Fan Yang; Sonya Burgers; Kari J Buck; James M Sikela

2002-01-01

265

De Novo Transcriptomic Analysis of an Oleaginous Microalga: Pathway Description and Gene Discovery for Production of Next-Generation Biofuels  

PubMed Central

Background Eustigmatos cf. polyphem is a yellow-green unicellular soil microalga belonging to the eustimatophyte with high biomass and considerable production of triacylglycerols (TAGs) for biofuels, which is thus referred to as an oleaginous microalga. The paucity of microalgae genome sequences, however, limits development of gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for a non-model microalgae species, E. cf. polyphem, and identify pathways and genes of importance related to biofuel production. Results We performed the de novo assembly of E. cf. polyphem transcriptome using Illumina paired-end sequencing technology. In a single run, we produced 29,199,432 sequencing reads corresponding to 2.33 Gb total nucleotides. These reads were assembled into 75,632 unigenes with a mean size of 503 bp and an N50 of 663 bp, ranging from 100 bp to >3,000 bp. Assembled unigenes were subjected to BLAST similarity searches and annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology identifiers. These analyses identified the majority of carbohydrate, fatty acids, TAG and carotenoids biosynthesis and catabolism pathways in E. cf. polyphem. Conclusions Our data provides the construction of metabolic pathways involved in the biosynthesis and catabolism of carbohydrate, fatty acids, TAG and carotenoids in E. cf. polyphem and provides a foundation for the molecular genetics and functional genomics required to direct metabolic engineering efforts that seek to enhance the quantity and character of microalgae-based biofuel feedstock.

Wan, LingLin; Han, Juan; Sang, Min; Li, AiFen; Wu, Hong; Yin, ShunJi; Zhang, ChengWu

2012-01-01

266

Functional Gene-Guided Discovery of Type II Polyketides from Culturable Actinomycetes Associated with Soft Coral Scleronephthya sp  

PubMed Central

Compared with the actinomycetes in stone corals, the phylogenetic diversity of soft coral-associated culturable actinomycetes is essentially unexplored. Meanwhile, the knowledge of the natural products from coral-associated actinomycetes is very limited. In this study, thirty-two strains were isolated from the tissue of the soft coral Scleronephthya sp. in the East China Sea, which were grouped into eight genera by 16S rDNA phylogenetic analysis: Micromonospora, Gordonia, Mycobacterium, Nocardioides, Streptomyces, Cellulomonas, Dietzia and Rhodococcus. 6 Micromonospora strains and 4 Streptomyces strains were found to be with the potential for producing aromatic polyketides based on the analysis of KS? (ketoacyl-synthase) gene in the PKS II (type II polyketides synthase) gene cluster. Among the 6 Micromonospora strains, angucycline cyclase gene was amplified in 2 strains (A5-1 and A6-2), suggesting their potential in synthesizing angucyclines e.g. jadomycin. Under the guidance of functional gene prediction, one jadomycin B analogue (7b, 13-dihydro-7-O-methyl jadomycin B) was detected in the fermentation broth of Micromonospora sp. strain A5-1. This study highlights the phylogenetically diverse culturable actinomycetes associated with the tissue of soft coral Scleronephthya sp. and the potential of coral-derived actinomycetes especially Micromonospora in producing aromatic polyketides.

Sun, Wei; Peng, Chongsheng; Zhao, Yunyu; Li, Zhiyong

2012-01-01

267

Discovery of single nucleotide polymorphisms in candidate genes associated with fertility and production traits in Holstein cattle  

Technology Transfer Automated Retrieval System (TEKTRAN)

Identification of single nucleotide polymorphisms (SNPs) for specific genes involved in reproduction might improve reliability of genomic estimates for these low- heritability traits. Semen from 550 Holstein bulls of high (>= 1.7; n=288) or low (<= -2; n = 262) daughter pregnancy rate (DPR) was geno...

268

A comprehensive resource of drought- and salinity- responsive ESTs for gene discovery and marker development in chickpea (Cicer arietinum L.)  

Microsoft Academic Search

BACKGROUND: Chickpea (Cicer arietinum L.), an important grain legume crop of the world is seriously challenged by terminal drought and salinity stresses. However, very limited number of molecular markers and candidate genes are available for undertaking molecular breeding in chickpea to tackle these stresses. This study reports generation and analysis of comprehensive resource of drought- and salinity-responsive expressed sequence tags

Rajeev K Varshney; Pavana J Hiremath; Pazhamala Lekha; Junichi Kashiwagi; Jayashree Balaji; Amit A Deokar; Vincent Vadez; Yongli Xiao; Ramamurthy Srinivasan; Pooran M Gaur; Kadambot HM Siddique; Christopher D Town; David A Hoisington

2009-01-01

269

Discovery of Virulence Genes of Legionella pneumophila by Using Signature Tagged Mutagenesis in a Guinea Pig Pneumonia Model  

Microsoft Academic Search

Legionella pneumophila is the cause of Legionnaires' disease, which is a form of potentially fatal pneumonia. To identify genes required for virulence of the bacterium, a library of 1,386 L. pneumophila signature tagged transposon mutants was studied for guinea pig virulence. The mutants were screened in pools of 96 each in a guinea pig model of L. pneumophila pneumonia. Sixteen

Paul H. Edelstein; Martha A. C. Edelstein; Futoshi Higa; Stanley Falkow

1999-01-01

270

Discovery of a Gene Involved in a Third Bacterial Protoporphyrinogen Oxidase Activity through Comparative Genomic Analysis and Functional Complementation ? †  

PubMed Central

Tetrapyrroles are ubiquitous molecules in nearly all living organisms. Heme, an iron-containing tetrapyrrole, is widely distributed in nature, including most characterized aerobic and facultative bacteria. A large majority of bacteria that contain heme possess the ability to synthesize it. Despite this capability and the fact that the biosynthetic pathway has been well studied, enzymes catalyzing at least three steps have remained “missing” in many bacteria. In the current work, we have employed comparative genomics via the SEED genomic platform, coupled with experimental verification utilizing Acinetobacter baylyi ADP1, to identify one of the missing enzymes, a new protoporphyrinogen oxidase, the penultimate enzyme in heme biosynthesis. COG1981 was identified by genomic analysis as a candidate protein family for the missing enzyme in bacteria that lacked HemG or HemY, two known protoporphyrinogen oxidases. The predicted amino acid sequence of COG1981 is unlike those of the known enzymes HemG and HemY, but in some genomes, the gene encoding it is found neighboring other heme biosynthetic genes. When the COG1981 gene was deleted from the genome of A. baylyi, a bacterium that lacks both hemG and hemY, the organism became auxotrophic for heme. Cultures accumulated porphyrin intermediates, and crude cell extracts lacked protoporphyrinogen oxidase activity. The heme auxotrophy was rescued by the presence of a plasmid-borne protoporphyrinogen oxidase gene from a number of different organisms, such as hemG from Escherichia coli, hemY from Myxococcus xanthus, or the human gene for protoporphyrinogen oxidase.

Boynton, Tye O.; Gerdes, Svetlana; Craven, Sarah H.; Neidle, Ellen L.; Phillips, John D.; Dailey, Harry A.

2011-01-01

271

The human genome project and the future of medical practice  

Microsoft Academic Search

Contrary to the scepticism that characterised the planning stages of the human genome project, the technology and sequence data resulting from the project are set to revolutionise medical practice for good. The expected benefits include: enhanced discovery of disease genes, which will lead to improved knowledge on the genetic basis of diseases; availability of DNA-based diagnostic methods, which will find

Bennett C. Nwanguma

2003-01-01

272

A supervised orthogonal discriminant projection for tumor classification using gene expression data.  

PubMed

An important application of gene expression data is tumor classification. Dimensionality reduction is a key step of tumor classification, as gene expression data is of high dimensionality and small sample size (SSS) and it contains a large number of redundant genes irrelevant to tumor phenotypes. Manifold learning is an excellent tool for dimensionality reduction and it is promising for gene expression data analysis. In this paper, an improved supervised orthogonal discriminant projection (SODP) is proposed for tumor classification. In SODP, an effective weight measurement between two nodes of the weight graph is designed according to both sample class information and local information. With the novel measurement, SODP can maximize the weighted difference between the non-local scatter and the local scatter, on the basis of locality preserving. The experimental results with five public tumor datasets demonstrate that the proposed SODP is quite efficient and feasible for tumor classification. PMID:23452931

Zhang, Chuanlei; Zhang, Shanwen

2013-02-26

273

Large-scale gene discovery in the oomycete Phytophthora infestans reveals likely components of phytopathogenicity shared with true fungi  

Microsoft Academic Search

o overview the gene content of the important pathogen Phytophthora infestans, large-scale cDNA and genomic sequencing was performed. A set of 75,757 high-quality expressed sequence tags (ESTs) from P. infestans was obtained from 20 cDNA libraries representing a broad range of growth conditions, stress responses, and developmental stages. These included libraries from P. infestans¿potato and ¿tomato interactions, from which 963

Thomas A. Randall; Rex A. Dwyer; Edgar Huitema; Katinka Beyer; Cristina Cvitanich; Hemant Kelkar; Audrey M. V. Ah Fong; Krista Gates; Samuel Roberts; Einat Yatzkan; Thomas Gaffney; Marcus Law; Antonino Testa; Trudy Torto-Alalibo; Zhang Meng; Zheng Li; Elisabeth Mueller; John Windass; Andres Binder; Paul R. J. Birch; Ulrich Gisi; Francine Govers; Neil A. Gow; Felix Mauch; Pieter van West; Mark E. Waugh; Yu Jun; Thomas Boller; Sophien Kamoun; Stephen T. Lam; Howard S. Judelson

2005-01-01

274

Annotation of Genes Involved in Glycerolipid Biosynthesis in Chlamydomonas reinhardtii: Discovery of the Betaine Lipid Synthase BTA1Cr  

PubMed Central

Lipid metabolism in flowering plants has been intensely studied, and knowledge regarding the identities of genes encoding components of the major fatty acid and membrane lipid biosynthetic pathways is very extensive. We now present an in silico analysis of fatty acid and glycerolipid metabolism in an algal model, enabled by the recent availability of expressed sequence tag and genomic sequences of Chlamydomonas reinhardtii. Genes encoding proteins involved in membrane biogenesis were predicted on the basis of similarity to proteins with confirmed functions and were organized so as to reconstruct the major pathways of glycerolipid synthesis in Chlamydomonas. This analysis accounts for the majority of genes predicted to encode enzymes involved in anabolic reactions of membrane lipid biosynthesis and compares and contrasts these pathways in Chlamydomonas and flowering plants. As an important result of the bioinformatics analysis, we identified and isolated the C. reinhardtii BTA1 (BTA1Cr) gene and analyzed the bifunctional protein that it encodes; we predicted this protein to be sufficient for the synthesis of the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine (DGTS), a major membrane component in Chlamydomonas. Heterologous expression of BTA1Cr led to DGTS accumulation in Escherichia coli, which normally lacks this lipid, and allowed in vitro analysis of the enzymatic properties of BTA1Cr. In contrast, in the bacterium Rhodobacter sphaeroides, two separate proteins, BtaARs and BtaBRs, are required for the biosynthesis of DGTS. Site-directed mutagenesis of the active sites of the two domains of BTA1Cr allowed us to study their activities separately, demonstrating directly their functional homology to the bacterial orthologs BtaARs and BtaBRs.

Riekhof, Wayne R.; Sears, Barbara B.; Benning, Christoph

2005-01-01

275

Bayesian hierarchical model for transcriptional module discovery by jointly modeling gene expression and ChIP-chip data  

PubMed Central

Background Transcriptional modules (TM) consist of groups of co-regulated genes and transcription factors (TF) regulating their expression. Two high-throughput (HT) experimental technologies, gene expression microarrays and Chromatin Immuno-Precipitation on Chip (ChIP-chip), are capable of producing data informative about expression regulatory mechanism on a genome scale. The optimal approach to joint modeling of data generated by these two complementary biological assays, with the goal of identifying and characterizing TMs, is an important open problem in computational biomedicine. Results We developed and validated a novel probabilistic model and related computational procedure for identifying TMs by jointly modeling gene expression and ChIP-chip binding data. We demonstrate an improved functional coherence of the TMs produced by the new method when compared to either analyzing expression or ChIP-chip data separately or to alternative approaches for joint analysis. We also demonstrate the ability of the new algorithm to identify novel regulatory relationships not revealed by ChIP-chip data alone. The new computational procedure can be used in more or less the same way as one would use simple hierarchical clustering without performing any special transformation of data prior to the analysis. The R and C-source code for implementing our algorithm is incorporated within the R package gimmR which is freely available at http://eh3.uc.edu/gimm. Conclusion Our results indicate that, whenever available, ChIP-chip and expression data should be analyzed within the unified probabilistic modeling framework, which will likely result in improved clusters of co-regulated genes and improved ability to detect meaningful regulatory relationships. Given the good statistical properties and the ease of use, the new computational procedure offers a worthy new tool for reconstructing transcriptional regulatory networks.

Liu, Xiangdong; Jessen, Walter J; Sivaganesan, Siva; Aronow, Bruce J; Medvedovic, Mario

2007-01-01

276

Discovery of [NiFe] Hydrogenase Genes in Metagenomic DNA: Cloning and Heterologous Expression in Thiocapsa roseopersicina?  

PubMed Central

Using a metagenomics approach, we have cloned a piece of environmental DNA from the Sargasso Sea that encodes an [NiFe] hydrogenase showing 60% identity to the large subunit and 64% to the small subunit of a Thiocapsa roseopersicina O2-tolerant [NiFe] hydrogenase. The DNA sequence of the hydrogenase identified by the metagenomic approach was subsequently found to be 99% identical to the hyaA and hyaB genes of an Alteromonas macleodii hydrogenase, indicating that it belongs to the Alteromonas clade. We were able to express our new Alteromonas hydrogenase in T. roseopersicina. Expression was accomplished by coexpressing only two accessory genes, hyaD and hupH, without the need to express any of the hyp accessory genes (hypABCDEF). These results suggest that the native accessory proteins in T. roseopersicina could substitute for the Alteromonas counterparts that are absent in the host to facilitate the assembly of a functional Alteromonas hydrogenase. To further compare the complex assembly machineries of these two [NiFe] hydrogenases, we performed complementation experiments by introducing the new Alteromonas hyaD gene into the T. roseopersicina hynD mutant. Interestingly, Alteromonas endopeptidase HyaD could complement T. roseopersicina HynD to cleave endoproteolytically the C-terminal end of the T. roseopersicina HynL hydrogenase large subunit and activate the enzyme. This study refines our knowledge on the selectivity and pleiotropy of the elements of the [NiFe] hydrogenase assembly machineries. It also provides a model for functionally analyzing novel enzymes from environmental microbes in a culture-independent manner.

Maroti, Gergely; Tong, Yingkai; Yooseph, Shibu; Baden-Tillson, Holly; Smith, Hamilton O.; Kovacs, Kornel L.; Frazier, Marvin; Venter, J. Craig; Xu, Qing

2009-01-01

277

Discovery of candidate genes and pathways that may help explain fertility cycle stage dependent post-resection breast cancer outcome  

Microsoft Academic Search

Breast cancer relapse and death occur more often and sooner among young pre-menopausal women. Breast cancer resected during\\u000a luteal phase cures about a quarter more women than if the operation is performed during follicular phase. We have identified\\u000a candidate breast cancer gene signatures that may point to the potential mechanisms of cycle stage-dependent surgical cure.\\u000a We performed whole murine genome

Eun-Young Oh; Patricia A. Wood; Xiaoming Yang; William J. M. Hrushesky

2009-01-01

278

Discovery of a Linear Peptide for Improving Tumor Targeting of Gene Products and Treatment of Distal Tumors by IL12 Gene Therapy  

Microsoft Academic Search

Like many effective therapeutics, interleukin-12 (IL-12) therapy often causes side effects. Tumor targeted delivery may improve the efficacy and decrease the toxicity of systemic IL-12 treatments. In this study, a novel targeting approach was investigated. A secreted alkaline phosphatase (SEAP) reporter gene-based screening process was used to identify a mini-peptide which can be produced in vivo to target gene products

Jeffry Cutrera; Denada Dibra; Xueqing Xia; Azeem Hasan; Scott Reed; Shulin Li

2011-01-01

279

Discovery of the rpl10 gene in diverse plant mitochondrial genomes and its probable replacement by the nuclear gene for chloroplast RPL10 in two lineages of angiosperms.  

PubMed

Mitochondrial genomes of plants are much larger than those of mammals and often contain conserved open reading frames (ORFs) of unknown function. Here, we show that one of these conserved ORFs is actually the gene for ribosomal protein L10 (rpl10) in plant. No rpl10 gene has heretofore been reported in any mitochondrial genome other than the exceptionally gene-rich genome of the protist Reclinomonas americana. Conserved ORFs corresponding to rpl10 are present in a wide diversity of land plant and green algal mitochondrial genomes. The mitochondrial rpl10 genes are transcribed in all nine land plants examined, with five seed plant genes subject to RNA editing. In addition, mitochondrial-rpl10-like cDNAs were identified in EST libraries from numerous land plants. In three lineages of angiosperms, rpl10 is either lost from the mitochondrial genome or a pseudogene. In two of them (Brassicaceae and monocots), no nuclear copy of mitochondrial rpl10 is identifiably present, and instead a second copy of nuclear-encoded chloroplast rpl10 is present. Transient assays using green fluorescent protein indicate that this duplicate gene is dual targeted to mitochondria and chloroplasts. We infer that mitochondrial rpl10 has been functionally replaced by duplicated chloroplast counterparts in Brassicaceae and monocots. PMID:19934175

Kubo, Nakao; Arimura, Shin-ichi

2009-11-24

280

High-throughput discovery of mutations in tef semi-dwarfing genes by next-generation sequencing analysis.  

PubMed

Tef (Eragrostis tef) is a major cereal crop in Ethiopia. Lodging is the primary constraint to increasing productivity in this allotetraploid species, accounting for losses of ?15-45% in yield each year. As a first step toward identifying semi-dwarf varieties that might have improved lodging resistance, an ?6× fosmid library was constructed and used to identify both homeologues of the dw3 semi-dwarfing gene of Sorghum bicolor. An EMS mutagenized population, consisting of ?21,210 tef plants, was planted and leaf materials were collected into 23 superpools. Two dwarfing candidate genes, homeologues of dw3 of sorghum and rht1 of wheat, were sequenced directly from each superpool with 454 technology, and 120 candidate mutations were identified. Out of 10 candidates tested, six independent mutations were validated by Sanger sequencing, including two predicted detrimental mutations in both dw3 homeologues with a potential to improve lodging resistance in tef through further breeding. This study demonstrates that high-throughput sequencing can identify potentially valuable mutations in under-studied plant species like tef and has provided mutant lines that can now be combined and tested in breeding programs for improved lodging resistance. PMID:22904035

Zhu, Qihui; Smith, Shavannor M; Ayele, Mulu; Yang, Lixing; Jogi, Ansuya; Chaluvadi, Srinivasa R; Bennetzen, Jeffrey L

2012-08-17

281

Automated conserved non-coding sequence (CNS) discovery reveals differences in gene content and promoter evolution among grasses.  

PubMed

Conserved non-coding sequences (CNS) are islands of non-coding sequence that, like protein coding exons, show less divergence in sequence between related species than functionless DNA. Several CNSs have been demonstrated experimentally to function as cis-regulatory regions. However, the specific functions of most CNSs remain unknown. Previous searches for CNS in plants have either anchored on exons and only identified nearby sequences or required years of painstaking manual annotation. Here we present an open source tool that can accurately identify CNSs between any two related species with sequenced genomes, including both those immediately adjacent to exons and distal sequences separated by >12 kb of non-coding sequence. We have used this tool to characterize new motifs, associate CNSs with additional functions, and identify previously undetected genes encoding RNA and protein in the genomes of five grass species. We provide a list of 15,363 orthologous CNSs conserved across all grasses tested. We were also able to identify regulatory sequences present in the common ancestor of grasses that have been lost in one or more extant grass lineages. Lists of orthologous gene pairs and associated CNSs are provided for reference inbred lines of arabidopsis, Japonica rice, foxtail millet, sorghum, brachypodium, and maize. PMID:23874343

Turco, Gina; Schnable, James C; Pedersen, Brent; Freeling, Michael

2013-07-02

282

Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1 ortholog critical for efficient nuclear trafficking  

PubMed Central

Eukaryotic parasites are a leading cause of morbidity and mortality worldwide, yet little is known about the genetic basis of their virulence. Here, we present a forward genetic screen to study pathogenesis in the protozoan parasite Toxoplasma gondii. By using modified signature-tagged mutagenesis, the growth of 6,300 T. gondii insertional mutants was compared in cell culture and murine infection to identify genes required specifically in vivo. One of the 39 avirulent mutants is disrupted in a divergent ortholog of the regulator of chromosome condensation 1 (RCC1), which is critical for nuclear trafficking in model systems. Although this RCC1 mutant grows similar to wild type in standard tissue culture conditions, it is growth-impaired under nutrient limitation. Genetic complementation of mutant parasites with the T. gondii RCC1 gene fully restores both virulence in mice and growth under low-nutrient conditions. Further analysis shows that there is a significant defect in nuclear trafficking in the RCC1 mutant. These findings suggest that the rate of nuclear transport is a critical factor affecting growth in low-nutrient conditions in vivo and in vitro. Additionally, we observed that although RCC1 proteins are highly conserved in organisms from humans to yeast, no protozoan parasite encodes a characteristic RCC1. This protein divergence may represent a unique mechanism of nucleocytoplasmic transport. This study illustrates the power of this forward genetics approach to identify atypical virulence mechanisms.

Frankel, Matthew B.; Mordue, Dana G.; Knoll, Laura J.

2007-01-01

283

First Discovery of Two Polyketide Synthase Genes for Mitorubrinic Acid and Mitorubrinol Yellow Pigment Biosynthesis and Implications in Virulence of Penicillium marneffei  

PubMed Central

Background The genome of P. marneffei, the most important thermal dimorphic fungus causing respiratory, skin and systemic mycosis in China and Southeast Asia, possesses 23 polyketide synthase (PKS) genes and 2 polyketide synthase nonribosomal peptide synthase hybrid (PKS-NRPS) genes, which is of high diversity compared to other thermal dimorphic pathogenic fungi. We hypothesized that the yellow pigment in the mold form of P. marneffei could also be synthesized by one or more PKS genes. Methodology/Principal Findings All 23 PKS and 2 PKS-NRPS genes of P. marneffei were systematically knocked down. A loss of the yellow pigment was observed in the mold form of the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants. Sequence analysis showed that PKS11 and PKS12 are fungal non-reducing PKSs. Ultra high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry (MS) and MS/MS analysis of the culture filtrates of wild type P. marneffei and the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants showed that the yellow pigment is composed of mitorubrinic acid and mitorubrinol. The survival of mice challenged with the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants was significantly better than those challenged with wild type P. marneffei (P<0.05). There was also statistically significant decrease in survival of pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants compared to wild type P. marneffei in both J774 and THP1 macrophages (P<0.05). Conclusions/Significance The yellow pigment of the mold form of P. marneffei is composed of mitorubrinol and mitorubrinic acid. This represents the first discovery of PKS genes responsible for mitorubrinol and mitorubrinic acid biosynthesis. pks12 and pks11 are probably responsible for sequential use in the biosynthesis of mitorubrinol and mitorubrinic acid. Mitorubrinol and mitorubrinic acid are virulence factors of P. marneffei by improving its intracellular survival in macrophages.

Leung, Chris K. F.; Wong, Samson S. Y.; Lau, Susanna K. P.; Yuen, Kwok-Yung

2012-01-01

284

Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus.  

PubMed

Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination. PMID:22278237

Woo, Patrick C Y; Lau, Susanna K P; Lam, Carol S F; Lau, Candy C Y; Tsang, Alan K L; Lau, John H N; Bai, Ru; Teng, Jade L L; Tsang, Chris C C; Wang, Ming; Zheng, Bo-Jian; Chan, Kwok-Hung; Yuen, Kwok-Yung

2012-01-25

285

Discovery Channel: Extreme Engineering  

NSDL National Science Digital Library

Extreme Engineering is a program on the Discovery Channel that unveils "some of the most ambitious architectural plans of our times." The projects highlighted in each episode come from locations around the world. Some are in the planning stages, while others are only theoretical. This Web site serves as a companion to the television broadcasts and has interactive multimedia tours that offer a glimpse of what the projects would look like when completed. An underwater train tunnel linking New York and London, a massive skyscraper city in Tokyo, and a bridge over the Bering Strait are just some of the remarkable projects featured. The online elements are added after the corresponding episode is aired.

2005-12-21

286

Discovery Channel: Extreme Engineering  

NSDL National Science Digital Library

Extreme Engineering is a program on the Discovery Channel that unveils "some of the most ambitious architectural plans of our times." The projects highlighted in each episode come from locations around the world. Some are in the planning stages, while others are only theoretical. This Web site serves as a companion to the television broadcasts and has interactive multimedia tours that offer a glimpse of what the projects would look like when completed. An underwater train tunnel linking New York and London, a massive skyscraper city in Tokyo, and a bridge over the Bering Strait are just some of the remarkable projects featured. The online elements are added after the corresponding episode is aired.

2003-01-01

287

Genetic Predictors of Adverse Radiotherapy Effects: The Gene-PARE project  

SciTech Connect

Purpose: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal. Methods and Materials: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work. Results: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy. Conclusions: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.

Ho, Alice Y. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Atencio, David P. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Peters, Sheila [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Stock, Richard G.; Cesaretti, Jamie A.; Green, Sheryl [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Formenti, Silvia C. [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States); Haffty, Bruce [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States); Drumea, Karen [Department of Oncology, Rambam Medical Center, Haifa (Israel); Leitzin, Larisa M.D. [Department of Oncology, Rambam Medical Center, Haifa (Israel); Kuten, Abraham [Department of Oncology, Rambam Medical Center, Haifa (Israel); Azria, David [Department of Radiation Oncology, CRLC Val d'Aurelle, Montpellier (France); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne (Switzerland); Overgaard, Jens; Andreassen, Christian N. [Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus (Denmark); Trop, Cynthia S. [Department of Urology, Bronx VA Medical Center, Bronx, NY (United States); Park, Janelle [Department of Radiation Oncology, Bronx VA Medical Center, Bronx, NY (United States); Rosenstein, Barry S. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States)]|[Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York NY (United States)]|[Department of Dermatology, Mount Sinai School of Medicine, New York, NY (United States)]|[Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States)]. E-mail: barry.rosenstein@mssm.edu

2006-07-01

288

The SILVA ribosomal RNA gene database project: improved data processing and web-based tools.  

PubMed

SILVA (from Latin silva, forest, http://www.arb-silva.de) is a comprehensive web resource for up to date, quality-controlled databases of aligned ribosomal RNA (rRNA) gene sequences from the Bacteria, Archaea and Eukaryota domains and supplementary online services. The referred database release 111 (July 2012) contains 3 194 778 small subunit and 288 717 large subunit rRNA gene sequences. Since the initial description of the project, substantial new features have been introduced, including advanced quality control procedures, an improved rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. Furthermore, the extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches. PMID:23193283

Quast, Christian; Pruesse, Elmar; Yilmaz, Pelin; Gerken, Jan; Schweer, Timmy; Yarza, Pablo; Peplies, Jörg; Glöckner, Frank Oliver

2012-11-28

289

A random sequencing approach for the analysis of the Trypanosoma cruzi genome: general structure, large gene and repetitive DNA families, and gene discovery.  

PubMed

A random sequence survey of the genome of Trypanosoma cruzi, the agent of Chagas disease, was performed and 11,459 genomic sequences were obtained, resulting in approximately 4.3 Mb of readable sequences or approximately 10% of the parasite haploid genome. The estimated total GC content was 50.9%, with a high representation of A and T di- and trinucleotide repeats. Out of the estimated 5000 parasite genes, 947 putative new genes were identified. Another 1723 sequences corresponded to genes detected previously in T. cruzi through expression sequence tag analysis. 7735 sequences had no matches in the database, but the presence of open reading frames that passed Fickett's test suggests that some might contain coding DNA. The survey was highly redundant, with approximately 35% of the sequences included in a few large sequence families. Some of them code for protein families present in dozens of copies, including proteins essential for parasite survival and retrotransposons. Other sequence families include repetitive DNA present in thousands of copies per haploid genome. Some families in the latter group are new, parasite-specific, repetitive DNAs. These results suggest that T. cruzi could constitute an interesting model to analyze gene and genome evolution due to its plasticity in terms of sequence amplification and divergence. Additional information can be found at http://www.iib.unsam.edu.ar/tcruzi.gss. html. PMID:11116094

Agüero, F; Verdún, R E; Frasch, A C; Sánchez, D O

2000-12-01

290

An artifact derived from a pseudogene led to the discovery of microRNA binding site polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene.  

PubMed

A novel single-nucleotide polymorphism (SNP) in the 3'-untranslated region of the human dihydrofolate reductase (DHFR) gene with enhanced expression was identified in 2001. In 2007, it was reported that this SNP, DHFR C829T, was located close to a microRNA binding site and contributed to the stability of mRNA. Many researchers have analyzed this SNP in several races including Asians and Caucasians. However, the mutation allele is not yet confirmed in most populations. In this study, we reinvestigated the frequency of this SNP using three methods. First, this SNP in genomic DNA was analyzed by a PCR-restriction fragment length polymorphism method. Second, this SNP in mRNA was analyzed by a single nucleotide extension method following a reverse transcription reaction. Third, the mRNA expression level was analyzed by a real-time PCR method. The findings in our study, regarding the discovery of this SNP, suggest that the SNP is an artifact caused by contamination by the genomic DNA of the pseudogene DHFRP1. This study is a reinvestigation of a newly discovered genetic polymorphism. PMID:22201119

Hayashi, Hideki; Tazoe, Yui; Horino, Masato; Fujimaki-Katoh, Chihiro; Tsuboi, Seiji; Matsuyama, Taiji; Kosuge, Kazuhiro; Yamada, Hiroshi; Tsuji, Daiki; Inoue, Kazuyuki; Itoh, Kunihiko

2011-12-27

291

In Vitro Assessment of the Inflammatory Breast Cancer Cell Line SUM 149: Discovery of 2 Single Nucleotide Polymorphisms in the RNase L Gene  

PubMed Central

Background: Inflammatory breast cancer (IBC) is a rare, highly aggressive form of breast cancer. The mechanism of IBC carcinogenesis remains unknown. We sought to evaluate potential genetic risk factors for IBC and whether or not the IBC cell lines SUM149 and SUM190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We evaluated dose-response to treatment with interferon-alpha (IFN-?); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated in IBC) in SUM149 cells. A bioinformatic analysis was performed to evaluate expression of RNase L in IBC and non-IBC. Results: 2 of 2 IBC cell lines were homozygous for RNase L common missense variants 462 and 541; whereas 2 of 10 non-IBC cell lines were homozygous positive for the 462 variant (p= 0.09) and 0 of 10 non-IBC cell lines were homozygous positive for the 541 variant (p = 0.015). Our real-time polymerase chain reaction (RT-PCR) and Southern blot analysis for sequences of HMTV revealed no evidence of the putative viral genome. Conclusion: We discovered 2 SNPs in the RNase L gene that were homozygously present in IBC cell lines. The 462 variant was absent in non-IBC lines. Our discovery of these SNPs present in IBC cell lines suggests a possible biomarker for risk of IBC. We found no evidence of HMTV in SUM149 cells. A query of a panel of human IBC and non-IBC samples showed no difference in RNase L expression. Further studies of the RNase L 462 and 541 variants in IBC tissues are warranted to validate our in vitro findings.

Nokes, Brandon T.; Cunliffe, Heather E.; LaFleur, Bonnie; Mount, David W.; Livingston, Robert B.; Futscher, Bernard W.; Lang, Julie E.

2013-01-01

292

Genome-wide target profiling of piggyBac and Tol2 in HEK 293: pros and cons for gene discovery and gene therapy  

Microsoft Academic Search

Background  DNA transposons have emerged as indispensible tools for manipulating vertebrate genomes with applications ranging from insertional\\u000a mutagenesis and transgenesis to gene therapy. To fully explore the potential of two highly active DNA transposons, piggyBac and Tol2, as mammalian genetic tools, we have conducted a side-by-side comparison of the two transposon systems in the same setting\\u000a to evaluate their advantages and

Yaa-Jyuhn J Meir; Matthew T Weirauch; Herng-Shing Yang; Pei-Cheng Chung; Robert K Yu; Sareina C-Y Wu

2011-01-01

293

From amplification to gene in thyroid cancer: a high-resolution mapped bacterial-artificial-chromosome resource for cancer chromosome aberrations guides gene discovery after comparative genome hybridization.  

PubMed Central

Chromosome rearrangements associated with neoplasms provide a rich resource for definition of the pathways of tumorigenesis. The power of comparative genome hybridization (CGH) to identify novel genes depends on the existence of suitable markers, which are lacking throughout most of the genome. We now report a general approach that translates CGH data into higher-resolution genomic-clone data that are then used to define the genes located in aneuploid regions. We used CGH to study 33 thyroid-tumor DNAs and two tumor-cell-line DNAs. The results revealed amplifications of chromosome band 2p21, with less-intense amplification on 2p13, 19q13.1, and 1p36 and with least-intense amplification on 1p34, 1q42, 5q31, 5q33-34, 9q32-34, and 14q32. To define the 2p21 region amplified, a dense array of 373 FISH-mapped chromosome 2 bacterial artificial chromosomes (BACs) was constructed, and 87 of these were hybridized to a tumor-cell line. Four BACs carried genomic DNA that was amplified in these cells. The maximum amplified region was narrowed to 3-6 Mb by multicolor FISH with the flanking BACs, and the minimum amplicon size was defined by a contig of 420 kb. Sequence analysis of the amplified BAC 1D9 revealed a fragment of the gene, encoding protein kinase C epsilon (PKCepsilon), that was then shown to be amplified and rearranged in tumor cells. In summary, CGH combined with a dense mapped resource of BACs and large-scale sequencing has led directly to the definition of PKCepsilon as a previously unmapped candidate gene involved in thyroid tumorigenesis.

Chen, X; Knauf, J A; Gonsky, R; Wang, M; Lai, E H; Chissoe, S; Fagin, J A; Korenberg, J R

1998-01-01

294

A Random Sequencing Approach for the Analysis of the Trypanosoma cruzi Genome: General Structure, Large Gene and Repetitive DNA Families, and Gene Discovery  

PubMed Central

A random sequence survey of the genome of Trypanosoma cruzi, the agent of Chagas disease, was performed and 11,459 genomic sequences were obtained, resulting in ?4.3 Mb of readable sequences or ?10% of the parasite haploid genome. The estimated total GC content was 50.9%, with a high representation of A and T di- and trinucleotide repeats. Out of the estimated 5000 parasite genes, 947 putative new genes were identified. Another 1723 sequences corresponded to genes detected previously in T. cruzi through expression sequence tag analysis. 7735 sequences had no matches in the database, but the presence of open reading frames that passed Fickett's test suggests that some might contain coding DNA. The survey was highly redundant, with ?35% of the sequences included in a few large sequence families. Some of them code for protein families present in dozens of copies, including proteins essential for parasite survival and retrotransposons. Other sequence families include repetitive DNA present in thousands of copies per haploid genome. Some families in the latter group are new, parasite-specific, repetitive DNAs. These results suggest that T. cruzi could constitute an interesting model to analyze gene and genome evolution due to its plasticity in terms of sequence amplification and divergence. Additional information can be found at http://www.iib.unsam.edu.ar/tcruzi.gss.html. [The sequence data described in this paper have been submitted to the dbGSS database under the following GenBank accession nos.: AQ443439–AQ443513, AQ443743–AQ445667, AQ902981–AQ911366, AZ049857–AZ051184, and AZ302116–AZ302563.

Aguero, Fernan; Verdun, Ramiro E.; Frasch, Alberto Carlos C.; Sanchez, Daniel O.

2000-01-01

295

Developmental gene discovery in a hemimetabolous insect: de novo assembly and annotation of a transcriptome for the cricket Gryllus bimaculatus.  

PubMed

Most genomic resources available for insects represent the Holometabola, which are insects that undergo complete metamorphosis like beetles and flies. In contrast, the Hemimetabola (direct developing insects), representing the basal branches of the insect tree, have very few genomic resources. We have therefore created a large and publicly available transcriptome for the hemimetabolous insect Gryllus bimaculatus (cricket), a well-developed laboratory model organism whose potential for functional genetic experiments is currently limited by the absence of genomic resources. cDNA was prepared using mRNA obtained from adult ovaries containing all stages of oogenesis, and from embryo samples on each day of embryogenesis. Using 454 Titanium pyrosequencing, we sequenced over four million raw reads, and assembled them into 21,512 isotigs (predicted transcripts) and 120,805 singletons with an average coverage per base pair of 51.3. We annotated the transcriptome manually for over 400 conserved genes involved in embryonic patterning, gametogenesis, and signaling pathways. BLAST comparison of the transcriptome against the NCBI non-redundant protein database (nr) identified significant similarity to nr sequences for 55.5% of transcriptome sequences, and suggested that the transcriptome may contain 19,874 unique transcripts. For predicted transcripts without significant similarity to known sequences, we assessed their similarity to other orthopteran sequences, and determined that these transcripts contain recognizable protein domains, largely of unknown function. We created a searchable, web-based database to allow public access to all raw, assembled and annotated data. This database is to our knowledge the largest de novo assembled and annotated transcriptome resource available for any hemimetabolous insect. We therefore anticipate that these data will contribute significantly to more effective and higher-throughput deployment of molecular analysis tools in Gryllus. PMID:23671567

Zeng, Victor; Ewen-Campen, Ben; Horch, Hadley W; Roth, Siegfried; Mito, Taro; Extavour, Cassandra G

2013-05-06

296

Discovery of Cadmium, Indium, and Tin Isotopes  

Microsoft Academic Search

As of today, no comprehensive study has been made covering the initial observations and identifications of isotopes. A project has been undertaken at MSU to document the discovery of all the known isotopes. The criteria defining discovery of a given isotope is the publication of clear mass and element assignment in a refereed journal. Prior to the current work the

Stephanie Amos; Michael Thoennessen

2009-01-01

297

Harry Stottlemier's Discovery [Revised Edition].  

ERIC Educational Resources Information Center

|"Harry Stottlemeier's Discovery" is the student book for the project in philosophical thinking described in SO 008 123-126. It offers a model of dialogue -- both of children with one another and of children with adults. The story is set among a classroom of children who begin to understand the basics of logical reasoning when Harry, who isn't…

Lipman, Matthew

298

The extragalactic distance scale Key Project. III. The discovery of Cepheids and a new distance to M101 using the {ital Hubble} {ital Space} {ital Telescope}  

Microsoft Academic Search

We report on the discovery of 29 Cepheid variables in the galaxy M101 using the original Wide Field Camera (WFC) and the new Wide Field and Planetary Camera 2 (WFPC2) on the {ital Hubble} {ital Space} {ital Telescope}. We observed a field in M101 at 17 independent epochs in {ital V} (F555W), five epochs in {ital I} (F785LP\\/F814W), and one

D. D. Kelson; G. D. Illingworth; W. F. Freedman; J. A. Graham; R. Hill; B. F. Madore; A. Saha; P. B. Stetson; R. C. Jr. Kennicutt; J. R. Mould; S. M. Hughes; L. Ferrarese; R. Phelps; A. Turner; K. H. Cook; H. Ford

1996-01-01

299

Targeted discovery of novel human exons by comparative genomics  

PubMed Central

A complete and accurate set of human protein-coding gene annotations is perhaps the single most important resource for genomic research after the human-genome sequence itself, yet the major gene catalogs remain incomplete and imperfect. Here we describe a genome-wide effort, carried out as part of the Mammalian Gene Collection (MGC) project, to identify human genes not yet in the gene catalogs. Our approach was to produce gene predictions by algorithms that rely on comparative sequence data but do not require direct cDNA evidence, then to test predicted novel genes by RT–PCR. We have identified 734 novel gene fragments (NGFs) containing 2188 exons with, at most, weak prior cDNA support. These NGFs correspond to an estimated 563 distinct genes, of which >160 are completely absent from the major gene catalogs, while hundreds of others represent significant extensions of known genes. The NGFs appear to be predominantly protein-coding genes rather than noncoding RNAs, unlike novel transcribed sequences identified by technologies such as tiling arrays and CAGE. They tend to be expressed at low levels and in a tissue-specific manner, and they are enriched for roles in motor activity, cell adhesion, connective tissue, and central nervous system development. Our results demonstrate that many important genes and gene fragments have been missed by traditional approaches to gene discovery but can be identified by their evolutionary signatures using comparative sequence data. However, they suggest that hundreds—not thousands—of protein-coding genes are completely missing from the current gene catalogs.

Siepel, Adam; Diekhans, Mark; Brejova, Brona; Langton, Laura; Stevens, Michael; Comstock, Charles L.G.; Davis, Colleen; Ewing, Brent; Oommen, Shelly; Lau, Christopher; Yu, Hung-Chun; Li, Jianfeng; Roe, Bruce A.; Green, Phil; Gerhard, Daniela S.; Temple, Gary; Haussler, David; Brent, Michael R.

2007-01-01

300

The Discovery Channel Telescope  

NASA Astrophysics Data System (ADS)

The Discovery Channel Telescope (DCT) is a 4.2-m telescope to be built at a new site near Happy Jack, Arizona. The DCT features a large prime focus mosaic CCD camera with a 2-degree-diameter field of view especially designed for surveys of KBOs, Centaurs, NEAs and other moving or time-variable targets. The telescope can be switched quickly to a Ritchey-Chretien configuration for optical/IR spectroscopy or near-IR imaging. This flexibility allows timely follow-up physical studies of high priority objects discovered in survey mode. The ULE (ultra-low-expansion) meniscus primary and secondary mirror blanks for the telescope are currently in fabrication by Corning Glass. Goodrich Aerospace, Vertex RSI, M3 Engineering and Technology Corp., and e2v Technologies have recently completed in-depth conceptual design studies of the optics, mount, enclosure, and mosaic focal plane, respectively. The results of these studies were subjected to a formal design review in July, 2004. Site testing at the 7760-ft altitude Happy Jack site began in 2001. Differential image motion observations from 117 nights since January 1, 2003 gave median seeing of 0.84 arcsec FWHM, and the average of the first quartile was 0.62 arcsec. The National Environmental Policy Act (NEPA) process for securing long-term access to this site on the Coconino National Forest is nearing completion and ground breaking is expected in the spring of 2005. The Discovery Channel Telescope is a project of the Lowell Observatory with major financial support from Discovery Communications, Inc. (DCI). DCI plans ongoing television programming featuring the construction of the telescope and the research ultimately undertaken with the DCT. An additional partner can be accommodated in the project. Interested parties should contact the lead author.

Millis, R. L.; Dunham, E. W.; Sebring, T. A.; Smith, B. W.; de Kock, M.; Wiecha, O.

2004-11-01

301

Mapping our genes: Federal genome projects: How vast. How fast. : Volume 1, Contractor reports  

SciTech Connect

This report contains contractor contributions solicited by the US Office of Technology Assessment in support of its recommendations for federal organization of the human genome project. The individual reports contained herein are entitled: Bibliometric analysis of work on human gene mapping; Medical implications of extensive physical and sequence characterization of the human genome; Mapping the human genome: Some implications; Mapping and sequencing the human genome: Considerations from the history of particle accelerators; Mapping the human genome: Historical background; Long-term implications of mapping and sequencing the human genome: Ethical and philosophical implications. Each report is also separately abstracted and indexed for the Energy Data Base. (DT)

Reisher, S.R.; Friedmann, T.; Glover, J.; Heilbron, J.L.; Judson, H.F.

1988-02-01

302

Analysis of expressed sequence tags from the Huperzia serrata leaf for gene discovery in the areas of secondary metabolite biosynthesis and development regulation.  

PubMed

Huperzia serrata produces various types of lycopodium alkaloids, especially the huperzine A (HupA) that is a promising drug candidate for Alzheimer's disease. Despite the medicinal importance of H. serrata, little genomic or transcriptomic data are available from the public databases. A cDNA library was thus generated from RNA isolated from the leaves of H. serrata. A total of 4012 clones were randomly selected from the library, and 3451 high-quality expressed sequence tags (ESTs) were assembled to yield 1510 unique sequences with an average length of 712 bp. The majority (79.4%) of the unique sequences were assigned to the putative functions based on the BLAST searches against the public databases. The functions of these unique sequences covered a broad set of molecular functions, biological processes and biochemical pathways according to GO and KEGG assignments. The transcripts involved in the secondary metabolite biosynthesis of alkaloids, terpenoids and flavone/flavonoids, such as cytochrome P450, lysine decarboxylase (LDC), flavanone 3-hydroxylase, squalene synthetase and 2-oxoglutarate 3-dioxygenase, were well represented by 34 unique sequences in this EST dataset. The corresponding peptide sequence of the LDC contained the Pfam 03641 domain and was annotated as a putative LDC. The unique sequences encoding transcription factors, phytohormone biosynthetic enzymes and signaling components were also found in this EST collection. In addition, a total of 501 potential SSR-motif microsatellite loci were identified from the 393 H. serrata leaf unique sequences. This set of non-redundant ESTs and the molecular markers obtained in this study will establish valuable resources for a wide range of applications including gene discovery and identification, genetic mapping and analysis of genetic diversity, cultivar identification and marker-assisted selections in this important medicinal plant. PMID:20059733

Luo, Hongmei; Sun, Chao; Li, Ying; Wu, Qiong; Song, Jingyuan; Wang, Deli; Jia, Xiaocheng; Li, Rongtao; Chen, Shilin

2009-12-03

303

Characterization of Capsicum annuum Genetic Diversity and Population Structure Based on Parallel Polymorphism Discovery with a 30K Unigene Pepper GeneChip  

PubMed Central

The widely cultivated pepper, Capsicum spp., important as a vegetable and spice crop world-wide, is one of the most diverse crops. To enhance breeding programs, a detailed characterization of Capsicum diversity including morphological, geographical and molecular data is required. Currently, molecular data characterizing Capsicum genetic diversity is limited. The development and application of high-throughput genome-wide markers in Capsicum will facilitate more detailed molecular characterization of germplasm collections, genetic relationships, and the generation of ultra-high density maps. We have developed the Pepper GeneChip® array from Affymetrix for polymorphism detection and expression analysis in Capsicum. Probes on the array were designed from 30,815 unigenes assembled from expressed sequence tags (ESTs). Our array design provides a maximum redundancy of 13 probes per base pair position allowing integration of multiple hybridization values per position to detect single position polymorphism (SPP). Hybridization of genomic DNA from 40 diverse C. annuum lines, used in breeding and research programs, and a representative from three additional cultivated species (C. frutescens, C. chinense and C. pubescens) detected 33,401 SPP markers within 13,323 unigenes. Among the C. annuum lines, 6,426 SPPs covering 3,818 unigenes were identified. An estimated three-fold reduction in diversity was detected in non-pungent compared with pungent lines, however, we were able to detect 251 highly informative markers across these C. annuum lines. In addition, an 8.7 cM region without polymorphism was detected around Pun1 in non-pungent C. annuum. An analysis of genetic relatedness and diversity using the software Structure revealed clustering of the germplasm which was confirmed with statistical support by principle components analysis (PCA) and phylogenetic analysis. This research demonstrates the effectiveness of parallel high-throughput discovery and application of genome-wide transcript-based markers to assess genetic and genomic features among Capsicum annuum.

Hill, Theresa A.; Ashrafi, Hamid; Reyes-Chin-Wo, Sebastian; Yao, JiQiang; Stoffel, Kevin; Truco, Maria-Jose; Kozik, Alexander; Michelmore, Richard W.; Van Deynze, Allen

2013-01-01

304

Characterization of Capsicum annuum genetic diversity and population structure based on parallel polymorphism discovery with a 30K unigene Pepper GeneChip.  

PubMed

The widely cultivated pepper, Capsicum spp., important as a vegetable and spice crop world-wide, is one of the most diverse crops. To enhance breeding programs, a detailed characterization of Capsicum diversity including morphological, geographical and molecular data is required. Currently, molecular data characterizing Capsicum genetic diversity is limited. The development and application of high-throughput genome-wide markers in Capsicum will facilitate more detailed molecular characterization of germplasm collections, genetic relationships, and the generation of ultra-high density maps. We have developed the Pepper GeneChip® array from Affymetrix for polymorphism detection and expression analysis in Capsicum. Probes on the array were designed from 30,815 unigenes assembled from expressed sequence tags (ESTs). Our array design provides a maximum redundancy of 13 probes per base pair position allowing integration of multiple hybridization values per position to detect single position polymorphism (SPP). Hybridization of genomic DNA from 40 diverse C. annuum lines, used in breeding and research programs, and a representative from three additional cultivated species (C. frutescens, C. chinense and C. pubescens) detected 33,401 SPP markers within 13,323 unigenes. Among the C. annuum lines, 6,426 SPPs covering 3,818 unigenes were identified. An estimated three-fold reduction in diversity was detected in non-pungent compared with pungent lines, however, we were able to detect 251 highly informative markers across these C. annuum lines. In addition, an 8.7 cM region without polymorphism was detected around Pun1 in non-pungent C. annuum. An analysis of genetic relatedness and diversity using the software Structure revealed clustering of the germplasm which was confirmed with statistical support by principle components analysis (PCA) and phylogenetic analysis. This research demonstrates the effectiveness of parallel high-throughput discovery and application of genome-wide transcript-based markers to assess genetic and genomic features among Capsicum annuum. PMID:23409153

Hill, Theresa A; Ashrafi, Hamid; Reyes-Chin-Wo, Sebastian; Yao, JiQiang; Stoffel, Kevin; Truco, Maria-Jose; Kozik, Alexander; Michelmore, Richard W; Van Deynze, Allen

2013-02-08

305

Discovery of mutated subnetworks associated with clinical data in cancer.  

PubMed

A major goal of cancer sequencing projects is to identify genetic alterations that determine clinical phenotypes, such as survival time or drug response. Somatic mutations in cancer are typically very diverse, and are found in different sets of genes in different patients. This mutational heterogeneity complicates the discovery of associations between individual mutations and a clinical phenotype. This mutational heterogeneity is explained in part by the fact that driver mutations, the somatic mutations that drive cancer development, target genes in cellular pathways, and only a subset of pathway genes is mutated in a given patient. Thus, pathway-based analysis of associations between mutations and phenotype are warranted. Here, we introduce an algorithm to find groups of genes, or pathways, whose mutational status is associated to a clinical phenotype without prior definition of the pathways. Rather, we find subnetworks of genes in an gene interaction network with the property that the mutational status of the genes in the subnetwork are significantly associated with a clinical phenotype. This new algorithm is built upon HotNet, an algorithm that finds groups of mutated genes using a heat diffusion model and a two-stage statistical test. We focus here on discovery of statistically significant correlations between mutated subnetworks and patient survival data. A similar approach can be used for correlations with other types of clinical data, through use of an appropriate statistical test. We apply our method to simulated data as well as to mutation and survival data from ovarian cancer samples from The Cancer Genome Atlas. In the TCGA data, we discover nine subnetworks containing genes whose mutational status is correlated with survival. Genes in four of these subnetworks overlap known pathways, including the focal adhesion and cell adhesion pathways, while other subnetworks are novel. PMID:22174262

Vandin, Fabio; Clay, Patrick; Upfal, Eli; Raphael, Benjamin J

2012-01-01

306

Characterisation of the wheat (triticum aestivum L.) transcriptome by de novo assembly for the discovery of phosphate starvation-responsive genes: gene expression in Pi-stressed wheat  

PubMed Central

Background Phosphorus (P) is an essential macronutrient for plant growth and development. To modulate their P homeostasis, plants must balance P uptake, mobilisation, and partitioning to various organs. Despite the worldwide importance of wheat as a cultivated food crop, molecular mechanisms associated with phosphate (Pi) starvation in wheat remain unclear. To elucidate these mechanisms, we used RNA-Seq methods to generate transcriptome profiles of the wheat variety ‘Chinese Spring’ responding to 10 days of Pi starvation. Results We carried out de novo assembly on 73.8 million high-quality reads generated from RNA-Seq libraries. We then constructed a transcript dataset containing 29,617 non-redundant wheat transcripts, comprising 15,047 contigs and 14,570 non-redundant full-length cDNAs from the TriFLDB database. When compared with barley full-length cDNAs, 10,656 of the 15,047 contigs were unalignable, suggesting that many might be distinct from barley transcripts. The average expression level of the contigs was lower than that of the known cDNAs, implying that these contigs included transcripts that were rarely represented in the full-length cDNA library. Within the non-redundant transcript set, we identified 892–2,833 responsive transcripts in roots and shoots, corresponding on average to 23.4% of the contigs not covered by cDNAs in TriFLDB under Pi starvation. The relative expression level of the wheat IPS1 (Induced by Phosphate Starvation 1) homologue, TaIPS1, was 341-fold higher in roots and 13-fold higher in shoots; this finding was further confirmed by qRT-PCR analysis. A comparative analysis of the wheat- and rice-responsive transcripts for orthologous genes under Pi-starvation revealed commonly upregulated transcripts, most of which appeared to be involved in a general response to Pi starvation, namely, an IPS1-mediated signalling cascade and its downstream functions such as Pi remobilisation, Pi uptake, and changes in Pi metabolism. Conclusions Our transcriptome profiles demonstrated the impact of Pi starvation on global gene expression in wheat. This study revealed that enhancement of the Pi-mediated signalling cascade using IPS1 is a potent adaptation mechanism to Pi starvation that is conserved in both wheat and rice and validated the effectiveness of using short-read next-generation sequencing data for wheat transcriptome analysis in the absence of reference genome information.

2013-01-01

307

Open PHACTS: semantic interoperability for drug discovery.  

PubMed

Open PHACTS is a public-private partnership between academia, publishers, small and medium sized enterprises and pharmaceutical companies. The goal of the project is to deliver and sustain an 'open pharmacological space' using and enhancing state-of-the-art semantic web standards and technologies. It is focused on practical and robust applications to solve specific questions in drug discovery research. OPS is intended to facilitate improvements in drug discovery in academia and industry and to support open innovation and in-house non-public drug discovery research. This paper lays out the challenges and how the Open PHACTS project is hoping to address these challenges technically and socially. PMID:22683805

Williams, Antony J; Harland, Lee; Groth, Paul; Pettifer, Stephen; Chichester, Christine; Willighagen, Egon L; Evelo, Chris T; Blomberg, Niklas; Ecker, Gerhard; Goble, Carole; Mons, Barend

2012-06-07

308

Discovery Learning Community  

NSDL National Science Digital Library

Discovery Communications (better known as The Discovery Channel and The Learning Channel) has announced the launch of a pilot Internet site designed to help teachers, students, and their educational partners devise innovative uses of Discovery programming. The Discovery Learning Community provides resources, relationships and collaborative tools to promote academic inquiry and knowledge building.

309

Construction and Evaluation of Normalized cDNA Libraries Enriched with Full-Length Sequences for Rapid Discovery of New Genes from Sisal (Agave sisalana Perr.) Different Developmental Stages  

PubMed Central

To provide a resource of sisal-specific expressed sequence data and facilitate this powerful approach in new gene research, the preparation of normalized cDNA libraries enriched with full-length sequences is necessary. Four libraries were produced with RNA pooled from Agave sisalana multiple tissues to increase efficiency of normalization and maximize the number of independent genes by SMART™ method and the duplex-specific nuclease (DSN). This procedure kept the proportion of full-length cDNAs in the subtracted/normalized libraries and dramatically enhanced the discovery of new genes. Sequencing of 3875 cDNA clones of libraries revealed 3320 unigenes with an average insert length about 1.2 kb, indicating that the non-redundancy of libraries was about 85.7%. These unigene functions were predicted by comparing their sequences to functional domain databases and extensively annotated with Gene Ontology (GO) terms. Comparative analysis of sisal unigenes and other plant genomes revealed that four putative MADS-box genes and knotted-like homeobox (knox) gene were obtained from a total of 1162 full-length transcripts. Furthermore, real-time PCR showed that the characteristics of their transcripts mainly depended on the tight expression regulation of a number of genes during the leaf and flower development. Analysis of individual library sequence data indicated that the pooled-tissue approach was highly effective in discovering new genes and preparing libraries for efficient deep sequencing.

Zhou, Wen-Zhao; Zhang, Yan-Mei; Lu, Jun-Ying; Li, Jun-Feng

2012-01-01

310

High throughput sequencing approaches to mutation discovery in the mouse  

PubMed Central

Phenotype driven approaches in mice are powerful strategies for the discovery of genes, gene functions and for unravelling complex biological mechanisms. Traditional methods for mutation discovery are reliable and robust, but they can also be laborious and time consuming. Recently, high throughput sequencing (HTS) technologies have revolutionised the process of forward genetics in mice by paving the way to rapid mutation discovery. However, successful application of HTS for mutation discovery is relies heavily on the sequencing approach employed and strategies for data analysis. Here, we review current HTS applications and resources for mutation discovery and provide an overview of the practical considerations for HTS implementation and data analysis.

Simon, Michelle M; Mallon, Ann-Marie; Howell, Gareth R.; Reinholdt, Laura G.

2013-01-01

311

GENE DIFFERENTIAL EXPRESSION OF CORN LINES AT THE LATE DEVELOPMENT STAGE UNDER DROUGHT STRESS AND ASPERGILLUS FLAVUS INFECTION  

Technology Transfer Automated Retrieval System (TEKTRAN)

We have been using maize microarray chips-Master Unigene from Maize Gene Discovery Project, which has over 20,000 unique ESTs (expressed sequence tags), to analyze gene expression profiles and to identify the genes associated with the stress responses. Research experiments have been conducted in the...

312

In Pursuit of Interesting Patterns with Undirected Discovery of Exception Rules  

Microsoft Academic Search

This paper reports our progress on interesting pattern discovery in the discovery science project. We first introduce undirected\\u000a discovery of exception rules, in which a pattern represents a pair of an exception rule and its corresponding strong rule.\\u000a Then, we explain scheduled discovery, exception rule discovery guided by a meta-pattern, and data mining contests as our contribution\\u000a to the project.

Einoshin Suzuki

2002-01-01

313

Whole-animal Imaging, Gene Function, and the Zebrafish Phenome Project  

PubMed Central

Imaging can potentially make a major contribution to the zebrafish phenome project, which will probe the functions of vertebrate genes through the generation and phenotyping of mutants. Imaging of whole animals at different developmental stages through adulthood will be used to infer biological function. Cell resolutions will be required to identify cellular mechanism and to detect a full range of organ effects. Light-based imaging of live zebrafish embryos is practical only up to ~2 days of development, due to increasing pigmentation and diminishing tissue lucency with age. The small size of the zebrafish makes possible whole-animal imaging at cell resolutions by histology and micron-scale tomography (microCT). The histological study of larvae is facilitated by the use of arrays, and histology’s standard use in the study of human disease enhances its translational value. Synchrotron microCT with X-rays of moderate energy (10-25 keV) is unimpeded by pigmentation or the tissue thicknesses encountered in zebrafish of larval stages and beyond, and is well-suited to detecting phenotypes that may require 3D modeling. The throughput required for this project will require robotic sample preparation and loading, increases in the dimensions and sensitivity of scintillator and CCD chips, increases in computer power, and the development of new approaches to image processing, segmentation, and quantification.

Cheng, Keith C.; Xin, Xuying; Clark, Darin; La Riviere, Patrick

2011-01-01

314

Effective Dimension Reduction Using Sequential Projection Pursuit On Gene Expression Data for Cancer Classification  

SciTech Connect

Motiviation: Classification is a powerful tool for uncovering interesting phenomena, for example classes of cancer, in microarray data. Due to the small number of observations (n) in comparison to the number of variables (p), genes, classification on microarray data is challenging. Thus, multivariate dimension reduction techniques are commonly used as a precursor to classification of microarray data; typically this is principal component analysis (PCA) or singular value decomposition (SVD). Since PCA and SVD are concerned with explaining the variance-covariance structure of the data, they may not be the best choice when the between-cluster variance is smaller than the within-cluster variance. Recently an attractive alternative to PCA, sequential projection pursuit (SPP), has been introduced which is designed to elicit clustering tendencies in the data. Thus, in some cases SPP may be more appropriate when performing clustering or classification analysis. Results: We compare the performance of SPP to PCA on two cancer gene expression datasets related to leukemia and colon cancer. Using PCA and SPP to reduce the dimensionality of the data to m<

Webb-Robertson, Bobbie-Jo M.; Havre, Susan L.

2004-06-23

315

Compensatory regulation of dopamine after ablation of the tyrosine hydroxylase gene in the nigrostriatal projection.  

PubMed

The tyrosine hydroxylase (TH; EC 1.14.16.2) is a rate-limiting enzyme in the dopamine synthesis and important for the central dopaminergic system, which controls voluntary movements and reward-dependent behaviors. Here, to further explore the regulatory mechanism of dopamine levels by TH in adult mouse brains, we employed a genetic method to inactivate the Th gene in the nigrostriatal projection using the Cre-loxP system. Stereotaxic injection of adeno-associated virus expressing Cre recombinase (AAV-Cre) into the substantia nigra pars compacta (SNc), where dopaminergic cell bodies locate, specifically inactivated the Th gene. Whereas the number of TH-expressing cells decreased to less than 40% in the SNc 2 weeks after the AAV-Cre injection, the striatal TH protein level decreased to 75%, 50%, and 39% at 2, 4, and 8 weeks, respectively, after the injection. Thus, unexpectedly, the reduction of TH protein in the striatum, where SNc dopaminergic axons innervate densely, was slower than in the SNc. Moreover, despite the essential requirement of TH for dopamine synthesis, the striatal dopamine contents were only moderately decreased, to 70% even 8 weeks after AAV-Cre injection. Concurrently, in vivo synthesis activity of l-dihydroxyphenylalanine, the dopamine precursor, per TH protein level was augmented, suggesting up-regulation of dopamine synthesis activity in the intact nigrostriatal axons. Collectively, our conditional Th gene targeting method demonstrates two regulatory mechanisms of TH in axon terminals for dopamine homeostasis in vivo: local regulation of TH protein amount independent of soma and trans-axonal regulation of apparent L-dihydroxyphenylalanine synthesis activity per TH protein. PMID:22027820

Tokuoka, Hirofumi; Muramatsu, Shin-ichi; Sumi-Ichinose, Chiho; Sakane, Hiroaki; Kojima, Masayo; Aso, Yoshinori; Nomura, Takahide; Metzger, Daniel; Ichinose, Hiroshi

2011-10-25

316

Compensatory Regulation of Dopamine after Ablation of the Tyrosine Hydroxylase Gene in the Nigrostriatal Projection*  

PubMed Central

The tyrosine hydroxylase (TH; EC 1.14.16.2) is a rate-limiting enzyme in the dopamine synthesis and important for the central dopaminergic system, which controls voluntary movements and reward-dependent behaviors. Here, to further explore the regulatory mechanism of dopamine levels by TH in adult mouse brains, we employed a genetic method to inactivate the Th gene in the nigrostriatal projection using the Cre-loxP system. Stereotaxic injection of adeno-associated virus expressing Cre recombinase (AAV-Cre) into the substantia nigra pars compacta (SNc), where dopaminergic cell bodies locate, specifically inactivated the Th gene. Whereas the number of TH-expressing cells decreased to less than 40% in the SNc 2 weeks after the AAV-Cre injection, the striatal TH protein level decreased to 75%, 50%, and 39% at 2, 4, and 8 weeks, respectively, after the injection. Thus, unexpectedly, the reduction of TH protein in the striatum, where SNc dopaminergic axons innervate densely, was slower than in the SNc. Moreover, despite the essential requirement of TH for dopamine synthesis, the striatal dopamine contents were only moderately decreased, to 70% even 8 weeks after AAV-Cre injection. Concurrently, in vivo synthesis activity of l-dihydroxyphenylalanine, the dopamine precursor, per TH protein level was augmented, suggesting up-regulation of dopamine synthesis activity in the intact nigrostriatal axons. Collectively, our conditional Th gene targeting method demonstrates two regulatory mechanisms of TH in axon terminals for dopamine homeostasis in vivo: local regulation of TH protein amount independent of soma and trans-axonal regulation of apparent l-dihydroxyphenylalanine synthesis activity per TH protein.

Tokuoka, Hirofumi; Muramatsu, Shin-ichi; Sumi-Ichinose, Chiho; Sakane, Hiroaki; Kojima, Masayo; Aso, Yoshinori; Nomura, Takahide; Metzger, Daniel; Ichinose, Hiroshi

2011-01-01

317

The Extragalactic Distance Scale Key Project. IV. The Discovery of Cepheids and a New Distance to M100 Using the Hubble Space Telescope  

Microsoft Academic Search

We report on observations of Cepheids in the Virgo spiral galaxy M100, based on data obtained with the Wide Field and Planetary Camera 2 (WFPC2) on board the Hubble Space Telescope (HST). The observations are part of the HST Key Project on the Extragalactic Distance Scale, which aims to provide a measurement of the Hubble constant H_0_ with 10% accuracy.

Laura Ferrarese; Wendy L. Freedman; Robert J. Hill; Abhijit Saha; Barry F. Madore; Robert C. Kennicutt Jr.; Peter B. Stetson; Holland C. Ford; John A. Graham; John G. Hoessel; Mingsheng Han; John Huchra; Shaun M. Hughes; Garth D. Illingworth; Daniel Kelson; Jeremy R. Mould; Randy Phelps; N. A. Silbermann; Shoko Sakai; Anne Turner; Paul Harding; Fabio Bresolin

1996-01-01

318

Metagenomic biomarker discovery and explanation  

PubMed Central

This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

2011-01-01

319

NCI DTP Discovery Services  

Cancer.gov

Discovery Services Home Discovery Development Pathways Grants/Contracts Books/Publications Site Search Data Search What's New FAQs Repositories Synthetics, Natural Products, Radiolabeled Materials, Biologics Reference Standards and Reagents, Tumor Repository Animal

320

De novo assembly of the pepper transcriptome (Capsicum annuum): a benchmark for in silico discovery of SNPs, SSRs and candidate genes  

PubMed Central

Background Molecular breeding of pepper (Capsicum spp.) can be accelerated by developing DNA markers associated with transcriptomes in breeding germplasm. Before the advent of next generation sequencing (NGS) technologies, the majority of sequencing data were generated by the Sanger sequencing method. By leveraging Sanger EST data, we have generated a wealth of genetic information for pepper including thousands of SNPs and Single Position Polymorphic (SPP) markers. To complement and enhance these resources, we applied NGS to three pepper genotypes: Maor, Early Jalapeño and Criollo de Morelos-334 (CM334) to identify SNPs and SSRs in the assembly of these three genotypes. Results Two pepper transcriptome assemblies were developed with different purposes. The first reference sequence, assembled by CAP3 software, comprises 31,196 contigs from >125,000 Sanger-EST sequences that were mainly derived from a Korean F1-hybrid line, Bukang. Overlapping probes were designed for 30,815 unigenes to construct a pepper Affymetrix GeneChip® microarray for whole genome analyses. In addition, custom Python scripts were used to identify 4,236 SNPs in contigs of the assembly. A total of 2,489 simple sequence repeats (SSRs) were identified from the assembly, and primers were designed for the SSRs. Annotation of contigs using Blast2GO software resulted in information for 60% of the unigenes in the assembly. The second transcriptome assembly was constructed from more than 200 million Illumina Genome Analyzer II reads (80–120 nt) using a combination of Velvet, CLC workbench and CAP3 software packages. BWA, SAMtools and in-house Perl scripts were used to identify SNPs among three pepper genotypes. The SNPs were filtered to be at least 50 bp from any intron-exon junctions as well as flanking SNPs. More than 22,000 high-quality putative SNPs were identified. Using the MISA software, 10,398 SSR markers were also identified within the Illumina transcriptome assembly and primers were designed for the identified markers. The assembly was annotated by Blast2GO and 14,740 (12%) of annotated contigs were associated with functional proteins. Conclusions Before availability of pepper genome sequence, assembling transcriptomes of this economically important crop was required to generate thousands of high-quality molecular markers that could be used in breeding programs. In order to have a better understanding of the assembled sequences and to identify candidate genes underlying QTLs, we annotated the contigs of Sanger-EST and Illumina transcriptome assemblies. These and other information have been curated in a database that we have dedicated for pepper project.

2012-01-01

321

The extragalactic distance scale Key Project. III. The discovery of Cepheids and a new distance to M101 using the {ital Hubble} {ital Space} {ital Telescope}  

SciTech Connect

We report on the discovery of 29 Cepheid variables in the galaxy M101 using the original Wide Field Camera (WFC) and the new Wide Field and Planetary Camera 2 (WFPC2) on the {ital Hubble} {ital Space} {ital Telescope}. We observed a field in M101 at 17 independent epochs in {ital V} (F555W), five epochs in {ital I} (F785LP/F814W), and one epoch in {ital B} (F439W), with a time interval baseline of 381 days. We have found Cepheids with periods ranging from 10 to 60 days. The data have been calibrated using WFPC2 observations with zero points derived from {omega} Cen, Pal 4, and NGC 2419 observations. This calibration has been verified by using the Medium Deep Survey (MDS) WFC photometric zero points, and ground-based secondary standards in {ital V} and {ital I}. The {ital V} calibrations agree to {plus_minus}0.06 mag, and the {ital I} calibrations agree to {plus_minus}0.04 mag. We have constructed {ital V} and {ital I} period-luminosity (PL) relations and have derived apparent distance moduli based on a distance modulus for the Large Magellanic Cloud (LMC) of 18.50 mag and a reddening of {ital E}({ital B}{minus}{ital V})=0.10 mag to the LMC Cepheids. Period-residual minimization was used to minimize the effects of Malmquist bias on the period-luminosity relation fitting process. Using a Galactic extinction law and the apparent {ital V} and {ital I} distance moduli, we have found a mean reddening for the M101 sample of {ital E}({ital B}{minus}{ital V})=0.03 mag and a true distance modulus to M101 of 29.34{plus_minus}0.17 mag, corresponding to a distance of 7.4{plus_minus}0.6 Mpc. The sources of error have been rigorously tracked through an error budget; systematic and random errors contribute roughly equally to the quoted error. The mean gas-phase metal abundances in the LMC and in the M101 outer field are similar so we expect metallicity effects to be minimal. (Abstract Truncated)

Kelson, D.D.; Illingworth, G.D. [UCO/Lick Observatory, University of California, Santa Cruz, California 95064 (United States); Freedman, W.F. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States); Graham, J.A. [Department of Terrestrial Magnetism, Carnegie Institution of Washington, 5241 Broad Branch Road NW, Washington, District of Columbia 20015 (United States); Hill, R. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States); Madore, B.F. [NASA/IPAC Extragalactic Database, Infrared Processing and Analysis Center, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California 91125 (United States); Saha, A. [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States); Stetson, P.B. [Dominion Astrophysical Observatory, National Research Council, 5071 West Saanich Road, Victoria, BC, V8X 4M6 (CANADA); Kennicutt, R.C. Jr. [Steward Observatory, University of Arizona, Tucson, Arizona 85721 (United States); Mould, J.R. [Mt. Stromlo and Siding Springs Observatories, Private Bag, Weston Creek Post Office ACT 2611 (Australia); Hughes, S.M. [Royal Greenwich Observatory, Madingley Road, Cambridge, (United Kingdom) CB3 0EZ; Ferrarese, L. [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States)]|[Department of Physics and Astronomy, Bloomberg 501, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218 (United States); Phelps, R. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States); Turner, A. [Steward Observatory, University of Arizona, Tucson, Arizona 85721 (United States); Cook, K.H. [Lawrence Livermore National Laboratory, Mississippi L-401, P.O. Box 808, Livermore, California 94550 (United States); Ford, H. [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States)

1996-05-01

322

Antarctic macrozooplankton of the southwest Atlantic sector and Bellingshausen Sea: Baseline historical distributions ( Discovery Investigations, 1928-1935) related to temperature and food, with projections for subsequent ocean warming  

NASA Astrophysics Data System (ADS)

Since the Discovery Investigations of the 1920s and 1930s, seawater temperatures have increased in the Atlantic sector by ˜1 °C; greater than the global mean rise. The aims of this paper were first to rescue the Discovery macrozooplankton data, second to provide quantitative "baseline" distribution maps, relating these to indices of temperature and food. Our third aim was to use the relationships we derived between abundance and temperature to project the potential affect of a 1 °C warming on the Discovery era distribution patterns. Based on the 1 m ringnet data retrieved from 615 stations (Nov-March), four taxa comprised >90% of the Antarctic macrozooplankton abundance: Rhincalanus gigas, Thysanoessa spp., Euphausia superba, and Chaetognaths. Most of the taxa, especially the more abundant ones, were warm water species penetrating into Antarctica and thus total macrozooplankton abundance decreased about 100-fold from 50°S to 70°S. While temperature correlated best with distribution at this large scale, food availability (proxied by a present-day satellite-based Chlorophyll a climatology) had a secondary effect, with the major euphausiids Euphausia superba and Thysanoessa spp. concentrated in high chl a areas. A modelled uniform 1 °C temperature rise produced a poleward shift for all taxa, but the Antarctic continent blocked this re-adjustment for the high latitude species, constricting their predicted range. More widespread polar/sub-polar species were predicted to increase their penetration into Antarctica by 4-12° in latitude, whereas the poleward shift in potential range of sub-Antarctic taxa were limited by the steep temperature gradient across the Antarctic Polar Front (APF). However, within the Scotia Sea the relatively warm temperatures of the northern Antarctic Zone, abundant food due to iron fertilisation and intense eddy activity provide a "gateway" for northern species to penetrate south of the APF. Our model predictions, based on measured distributional ranges and observed temperature increases, provide a yardstick with which to compare modern day data compilations and assess the potential effects of future temperature increases.

Mackey, A. P.; Atkinson, A.; Hill, S. L.; Ward, P.; Cunningham, N. J.; Johnston, N. M.; Murphy, E. J.

2012-01-01

323

Glutamatergic gene expression is specifically reduced in thalamocortical projecting relay neurons in schizophrenia  

PubMed Central

Background Impairment of glutamate neurons which relay sensory and cognitive information from the medial dorsal thalamus to the dorsolateral prefrontal cortex and other cortical regions may contribute to the pathophysiology of schizophrenia. In this study we have assessed the cell-specific expression of glutamatergic transcripts in the medial dorsal thalamus. Methods and Materials We used laser-capture microdissection to harvest two populations of medial dorsal thalamic cells, one enriched with glutamatergic relay neurons, and the other with GABAergic neurons and astroglia, from postmortem brains of subjects with schizophrenia (n=14) and a comparison group (n=20). Quantitative polymerase chain reaction (QPCR) of extracted RNA was used to assay gene expression in different cell populations. Results The transcripts encoding the ionotropic glutamate receptor subunits NR2D, GluR3, GluR6, GluR7, and the intracellular proteins GRIP1 and SynGAP1 were significantly decreased in relay neurons but not in the mixed glial and interneuron population in schizophrenia. Discussion Our data suggest that reduced ionotropic glutamatergic expression occurs selectively in neurons giving rise to the cortical projections of the medial dorsal thalamus in schizophrenia, rather than in thalamic cells which function locally. Our findings indicate that glutamatergic innervation is dysfunctional in the circuitry between the medial dorsal thalamus and cortex.

Sodhi, Monsheel S.; Simmons, Micah; McCullumsmith, Robert; Haroutunian, Vahram; Meador-Woodruff, James H.

2011-01-01

324

Discovery of Western European R1b1a2 Y chromosome variants in 1000 genomes project data: an online community approach.  

PubMed

The authors have used an online community approach, and tools that were readily available via the Internet, to discover genealogically and therefore phylogenetically relevant Y-chromosome polymorphisms within core haplogroup R1b1a2-L11/S127 (rs9786076). Presented here is the analysis of 135 unrelated L11 derived samples from the 1000 Genomes Project. We were able to discover new variants and build a much more complex phylogenetic relationship for L11 sub-clades. Many of the variants were further validated using PCR amplification and Sanger sequencing. The identification of these new variants will help further the understanding of population history including patrilineal migrations in Western and Central Europe where R1b1a2 is the most frequent haplogroup. The fine-grained phylogenetic tree we present here will also help to refine historical genetic dating studies. Our findings demonstrate the power of citizen science for analysis of whole genome sequence data. PMID:22911832

Rocca, Richard A; Magoon, Gregory; Reynolds, David F; Krahn, Thomas; Tilroe, Vincent O; Op den Velde Boots, Peter M; Grierson, Andrew J

2012-07-24

325

THE BIOCATALYTIC DESULFURIZATION PROJECT  

SciTech Connect

During the first quarter of the Biological Desulfurization project several activities were pursued. A project kickoff meeting was held at the Diversa facility in San Diego, CA. Activities that were in process before the meeting and begun afterwards by Diversa Corporation and Petro Star Inc. include: Technology transfer in the form of information generated by Enchira to Diversa, the purchase and installation of equipment by Diversa, development of synthetic methods and preparation of organo-sulfur substrates for use in determining enzyme activities, production of extract via Petro Star's CED process, detailed analysis of Petro Star Inc. diesel and CED extract, and several activities in molecular biology. Diversa Corporation, in the area of molecular biology, engaged in several activities in support of the task list of the contract. These included: construction of a genomic library; development and utilization of a sequence-based gene discovery effort; a parallel discovery approach based on functional expression of enzymes with the ability to oxidize organosulfur compounds. Biodesulfurization genes have already been identified and are being sequenced and subcloned for expression in heterologous biological hosts. Diversa has evaluated and adapted assays developed by Enchira used to assess the activities of DBT and DBTO{sub 2} monooxygenases. Finally, Diversa personnel have developed two novel selection/screen strategies for the improvement of biocatalyst strains by directed evolution.

Steven E. Bonde; David Nunn

2003-01-01

326

Physical activity and sex modulate obesity risk linked to 3111T/C gene variant of the CLOCK gene in an elderly population: the SUN Project.  

PubMed

Genetic factors may interact with physical activity levels to modify obesity risk. Our aim was to explore the influence of rs1801260 single-nucleotide polymorphism (SNP) (3111T/C) of CLOCK gene on obesity risk, and to examine its potential interaction with lifestyle factors in an elderly population within the SUN ("Seguimiento Universidad de Navarra") Project. Subjects (n?=?903, aged 69?±?6 yrs) were recruited from the SUN Project. DNA was obtained from saliva, whereas lifestyle and dietary data were collected by validated self-report questionnaires. Genotype was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) plus allele discrimination. A significant interaction was observed between the 3111T/C SNP of CLOCK gene and sex for overweight/obesity risk (p for sex?×?CLOCK interaction <.001). Our results showed that women carrying the C allele of CLOCK gene had a marginally significant lower risk of overweight/obesity compared with noncarrier-TT-subjects (odds ratio [OR]: .61, 95% confidence interval [CI]: .36-1.04; p?=?.069). Moreover, this association of the C allele with a decreased overweight/obesity risk might be enhanced in those women with a high physical activity level. Women practicing more than 16.8 metabolic equivalent tasks (hours per week) had a significantly lower overweight/obesity risk (OR: .36, 95% CI: .17-.79; p?=?.011). Furthermore, a significant interaction between the 3111T/C gene variant and physical activity (PA) for overweight/obesity risk was observed but only in women (p for PA?×?CLOCK interaction <.050). In conclusion, it appears that physical activity levels may act by modifying the association of the 3111T/C SNP (rs1801260) of the CLOCK gene with overweight/obesity risk in elderly women in the SUN Project. PMID:23131019

Galbete, Cecilia; Contreras, Rafael; Martínez, J Alfredo; Martínez-González, Miguel Ángel; Guillén-Grima, Francisco; Marti, Amelia

2012-11-06

327

A Seriation Approach for Visualization-Driven Discovery of CoExpression Patterns in Serial Analysis of Gene Expression (SAGE) Data  

Microsoft Academic Search

Background: Serial Analysis of Gene Expression (SAGE) is a DNA sequencing-based method for large-scale gene expression profiling that provides an alternative to microarray analysis. Most analyses of SAGE data aimed at identifying co-expressed genes have been accomplished using various versions of clustering approaches that often result in a number of false positives. Principal Findings: Here we explore the use of

Olena Morozova; Vyacheslav Morozov; Brad G. Hoffman; Cheryl D. Helgason; Marco A. Marra

2008-01-01

328

Towards a proteome project of cyanobacterium Synechocystis sp. strain PCC6803: linking 130 protein spots with their respective genes.  

PubMed

Following the complete sequencing of the genome of the univellular cyanobacterium, Synechocystis sp. strain PCC6803 within our institute, a protein-gene linkage map of this photosynthetic microorganism was successfully constructed for 130 high abundance proteins present on two-dimensional gels. An additional six proteins were analyzed, but were probably encoded extrachromosomally. In order to demonstrate the usefulness of this protein-gene linkage map, we analyzed the changes that occur in cellular proteins after illumination of PCC6803 cells. The results indicate that this protein-gene linkage map greatly simplifies the identification process of such modulated genes. After illumination, at least three distinctive spots with reduced intensity were detected on two-dimensional gels and the corresponding genes of two of these were successfully identified as chaperonin 2 and a Tortula ruralis rehydrin-related gene. Thus, the combination of the protein-gene linkage map and two-dimensional gel electrophoresis should permit a comprehensive analyses of the proteins encoded by the genome (i.e., "proteome") of this photosynthetic autotroph. This post-genome project represents a productive way of exploiting the information obtained from the sequencing of the cyanobacterium genome. PMID:9298645

Sazuka, T; Ohara, O

1997-08-01

329

Evolution of hedgehog and hedgehog-related genes, their origin from Hog proteins in ancestral eukaryotes and discovery of a novel Hint motif  

PubMed Central

Background The Hedgehog (Hh) signaling pathway plays important roles in human and animal development as well as in carcinogenesis. Hh molecules have been found in both protostomes and deuterostomes, but curiously the nematode Caenorhabditis elegans lacks a bona-fide Hh. Instead a series of Hh-related proteins are found, which share the Hint/Hog domain with Hh, but have distinct N-termini. Results We performed extensive genome searches such as the cnidarian Nematostella vectensis and several nematodes to gain further insights into Hh evolution. We found six genes in N. vectensis with a relationship to Hh: two Hh genes, one gene with a Hh N-terminal domain fused to a Willebrand factor type A domain (VWA), and three genes containing Hint/Hog domains with distinct novel N-termini. In the nematode Brugia malayi we find the same types of hh-related genes as in C. elegans. In the more distantly related Enoplea nematodes Xiphinema and Trichinella spiralis we find a bona-fide Hh. In addition, T. spiralis also has a quahog gene like C. elegans, and there are several additional hh-related genes, some of which have secreted N-terminal domains of only 15 to 25 residues. Examination of other Hh pathway components revealed that T. spiralis - like C. elegans - lacks some of these components. Extending our search to all eukaryotes, we recovered genes containing a Hog domain similar to Hh from many different groups of protists. In addition, we identified a novel Hint gene family present in many eukaryote groups that encodes a VWA domain fused to a distinct Hint domain we call Vint. Further members of a poorly characterized Hint family were also retrieved from bacteria. Conclusion In Cnidaria and nematodes the evolution of hh genes occurred in parallel to the evolution of other genes that contain a Hog domain but have different N-termini. The fact that Hog genes comprising a secreted N-terminus and a Hog domain are found in many protists indicates that this gene family must have arisen in very early eukaryotic evolution, and gave rise eventually to hh and hh-related genes in animals. The results indicate a hitherto unsuspected ability of Hog domain encoding genes to evolve new N-termini. In one instance in Cnidaria, the Hh N-terminal signaling domain is associated with a VWA domain and lacks a Hog domain, suggesting a modular mode of evolution also for the N-terminal domain. The Hog domain proteins, the inteins and VWA-Vint proteins are three families of Hint domain proteins that evolved in parallel in eukaryotes.

Burglin, Thomas R

2008-01-01

330

The Alabama Drug Discovery Alliance: a collaborative partnership to facilitate academic drug discovery.  

PubMed

The Alabama Drug Discovery Alliance is a collaboration between the University of Alabama at Birmingham and Southern Research Institute that aims to support the discovery and development of therapeutic molecules that address an unmet medical need. The alliance builds on the expertise present at both institutions and has the dedicated commitment of their respective technology transfer and intellectual property offices to guide any commercial opportunities that may arise from the supported efforts. Although most projects involve high throughput screening, projects at any stage in the drug discovery and development pathway are eligible for support. Irrespective of the target and stage of any project, well-functioning interdisciplinary teams are crucial to a project's progress. These teams consist of investigators with a wide variety of expertise from both institutions to contribute to the program's success. PMID:21448756

Everts, Maaike; Knight, W Blaine; Harris, David R; Secrist, John A; Whitley, Richard J

2011-03-30

331

The Discovery Channel Telescope  

NASA Astrophysics Data System (ADS)

Lowell Observatory has joined forces with Discovery Communications, Inc. of Silver Spring, MD to build a 4-meter telescope in Northern Arizona. The proposed site is at 7760 ft. altitude at the edge of the Mogollon Rim approximately 40 miles south of Flagstaff, AZ. Intensive DIMM measurements at this site over the past two-and-a-half years have consistently shown median image quality near 0.8 arcsec FWHM. The telescope will have two modes of operation. In survey mode, a prime focus mosaic CCD camera will cover a two-degree-diameter field-of-view. UV/optical spectroscopy, infrared imaging and spectroscopy, and other applications will be supported at the alternate f/6.5 Ritchey-Chretien focus. The ULE primary and secondary mirror blanks are being manufactured by Corning. Goodrich Aerospace is doing the detailed optical design, Vertex RSI is responsible for the design of the telescope's mechanical structure, and M3 is designing the enclosure. Ground-breaking is scheduled for mid-2004 with first light in December 2007. Institutions interested in the possibility of joining this project should contact one of the authors.

Millis, R. L.; Dunham, E. W.; Sebring, T. A.

2003-12-01

332

High-throughput target discovery using cell-based genetics  

Microsoft Academic Search

High-throughput target discovery requires robust disease models and the ability to rapidly survey the genome for function. In the post-genomics era, there has been a strong emphasis placed upon ‘gene-to-function’ approaches that take advantage of the large amount of gene sequence information now available. Here, we advocate a return to ‘function-to-gene’ approaches as a first step in target discovery (and

P. David Jackson; John J. Harrington

2005-01-01

333

Discovery of new genes and deletion editing in Physarum mitochondria enabled by a novel algorithm for finding edited mRNAs  

Microsoft Academic Search

Gene finding is complicated in organisms that exhibit insertional RNA editing. Here, we demonstrate how our new algorithm Predictor of Insertional Editing (PIE) can be used to locate genes whose mRNAs are subjected to multiple frameshifting events, and extend the algorithm to include probabilistic predic- tions for sites of nucleotide insertion; this feature is particularly useful when designing primers for

Jonatha M. Gott; Neeta Parimi; Ralf Bundschuh

2005-01-01

334

Final report on LDRD project : elucidating performance of proton-exchange-membrane fuel cells via computational modeling with experimental discovery and validation.  

SciTech Connect

In this report, we document the accomplishments in our Laboratory Directed Research and Development project in which we employed a technical approach of combining experiments with computational modeling and analyses to elucidate the performance of hydrogen-fed proton exchange membrane fuel cells (PEMFCs). In the first part of this report, we document our focused efforts on understanding water transport in and removal from a hydrogen-fed PEMFC. Using a transparent cell, we directly visualized the evolution and growth of liquid-water droplets at the gas diffusion layer (GDL)/gas flow channel (GFC) interface. We further carried out a detailed experimental study to observe, via direct visualization, the formation, growth, and instability of water droplets at the GDL/GFC interface using a specially-designed apparatus, which simulates the cathode operation of a PEMFC. We developed a simplified model, based on our experimental observation and data, for predicting the onset of water-droplet instability at the GDL/GFC interface. Using a state-of-the-art neutron imaging instrument available at NIST (National Institute of Standard and Technology), we probed liquid-water distribution inside an operating PEMFC under a variety of operating conditions and investigated effects of evaporation due to local heating by waste heat on water removal. Moreover, we developed computational models for analyzing the effects of micro-porous layer on net water transport across the membrane and GDL anisotropy on the temperature and water distributions in the cathode of a PEMFC. We further developed a two-phase model based on the multiphase mixture formulation for predicting the liquid saturation, pressure drop, and flow maldistribution across the PEMFC cathode channels. In the second part of this report, we document our efforts on modeling the electrochemical performance of PEMFCs. We developed a constitutive model for predicting proton conductivity in polymer electrolyte membranes and compared model prediction with experimental data obtained in our laboratory and from literature. Moreover, we developed a one-dimensional analytical model for predicting electrochemical performance of an idealized PEMFC with small surface over-potentials. Furthermore, we developed a multi-dimensional computer model, which is based on the finite-element method and a fully-coupled implicit solution scheme via Newton's technique, for simulating the performance of PEMFCs. We demonstrated utility of our finite-element model by comparing the computed current density distribution and overall polarization with those measured using a segmented cell. In the last part of this report, we document an exploratory experimental study on MEA (membrane electrode assembly) degradation.

Wang, Chao Yang (Pennsylvania State University, University Park, PA); Pasaogullari, Ugur (Pennsylvania State University, University Park, PA); Noble, David R.; Siegel, Nathan P.; Hickner, Michael A.; Chen, Ken Shuang

2006-11-01

335

Radiation Detection Material Discovery Initiative at PNNL  

NASA Astrophysics Data System (ADS)

Today's security threats are being met with 30-year old radiation technology. Discovery of new radiation detection materials is currently a slow and Edisonian process. With heightened concerns over nuclear proliferation, terrorism and unconventional warfare, an alternative strategy for identification and development of potential radiation detection materials must be adopted. Through the Radiation Detection Materials Discovery Initiative, PNNL focuses on the science-based discovery of next generation materials for radiation detection by addressing three ``grand challenges'': fundamental understanding of radiation detection, identification of new materials, and accelerating the discovery process. The new initiative has eight projects addressing these challenges, which will be described, including early work, paths forward and the opportunities for collaboration.

Milbrath, Brian

2006-05-01

336

Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to cardiovascular disease events: the MORGAM Project  

Microsoft Academic Search

Interleukin-18 (IL-18) is a key inflammatory molecule suspected of being involved in the etiology of cardiovascular diseases (CVD). Five single nucleotide polymorphisms (SNPs) capturing the common genetic variation of the IL-18 gene (tag SNPs) were genotyped in five European prospective CVD cohorts including 1933 cases and 1938 non-cases as part of the MORGAM Project. Not a single SNP was found

Marie-Lise Grisoni; Carole Proust; Mervi Alanne; Maylis DeSuremain; Veikko Salomaa; Kari Kuulasmaa; François Cambien; Viviane Nicaud; Birgitta Stegmayr; Jarmo Virtamo; Denis Shields; Frank Kee; Laurence Tiret; Alun Evans; David-Alexandre Tregouet; D-A Trégouët

2008-01-01

337

SitEx: a computer system for analysis of projections of protein functional sites on eukaryotic genes.  

PubMed

Search of interrelationships between the structural-functional protein organization and exon structure of encoding gene provides insights into issues concerned with the function, origin and evolution of genes and proteins. The functions of proteins and their domains are defined mostly by functional sites. The relation of the exon-intron structure of the gene to the protein functional sites has been little studied. Development of resources containing data on projections of protein functional sites on eukaryotic genes is needed. We have developed SitEx, a database that contains information on functional site amino acid positions in the exon structure of encoding gene. SitEx is integrated with the BLAST and 3DExonScan programs. BLAST is used for searching sequence similarity between the query protein and polypeptides encoded by single exons stored in SitEx. The 3DExonScan program is used for searching for structural similarity of the given protein with these polypeptides using superimpositions. The developed computer system allows users to analyze the coding features of functional sites by taking into account the exon structure of the gene, to detect the exons involved in shuffling in protein evolution, also to design protein-engineering experiments. SitEx is accessible at http://www-bionet.sscc.ru/sitex/. Currently, it contains information about 9994 functional sites presented in 2021 proteins described in proteomes of 17 organisms. PMID:22139920

Medvedeva, Irina; Demenkov, Pavel; Kolchanov, Nikolay; Ivanisenko, Vladimir

2011-12-01

338

SitEx: a computer system for analysis of projections of protein functional sites on eukaryotic genes  

PubMed Central

Search of interrelationships between the structural–functional protein organization and exon structure of encoding gene provides insights into issues concerned with the function, origin and evolution of genes and proteins. The functions of proteins and their domains are defined mostly by functional sites. The relation of the exon–intron structure of the gene to the protein functional sites has been little studied. Development of resources containing data on projections of protein functional sites on eukaryotic genes is needed. We have developed SitEx, a database that contains information on functional site amino acid positions in the exon structure of encoding gene. SitEx is integrated with the BLAST and 3DExonScan programs. BLAST is used for searching sequence similarity between the query protein and polypeptides encoded by single exons stored in SitEx. The 3DExonScan program is used for searching for structural similarity of the given protein with these polypeptides using superimpositions. The developed computer system allows users to analyze the coding features of functional sites by taking into account the exon structure of the gene, to detect the exons involved in shuffling in protein evolution, also to design protein-engineering experiments. SitEx is accessible at http://www-bionet.sscc.ru/sitex/. Currently, it contains information about 9994 functional sites presented in 2021 proteins described in proteomes of 17 organisms.

Medvedeva, Irina; Demenkov, Pavel; Kolchanov, Nikolay; Ivanisenko, Vladimir

2012-01-01

339

Discovery and Deduction  

Microsoft Academic Search

Deduction is usually considered to be the opposite of induction. However, deduction and induction can be related in many ways. In this paper, two endeavors that try to relate discovery science and verification technology are described. The first is discovery by deduction, where attempts to find algorithms are made using verifiers. Case studies of finding algorithms for concurrent garbage collection

Masami Hagiya; Koichi Tagahashi

2000-01-01

340

Israel's petroleum discovery curve  

Microsoft Academic Search

Oil exploration in Israel began in 1953. Until 1991 a total of 263 exploration wells and 122 development wells were drilled, 3 oil fields and 5 gas fields were discovered, and 4 noncommercial oil discoveries and 1 noncommercial gas discovery were made. Proven in-place reserves amount to 70 million barrels of oil equivalent (MMBOE). Exploration focused on six main plays:

Dan Gill

1992-01-01

341

Supermarket Discovery Center, Pilot Study, May - September, 1968. Initial Report.  

ERIC Educational Resources Information Center

|The objectives of this research pilot project were (1) to train 3- and 4-year-olds in cognitive and tactile discovery tasks; (2) to provide guidance for parents, enabling them to reinforce and review the concepts taught; and (3) to establish training and employment, as tutors, for central city high school and junior college students. A "discovery

Filep, Robert T.

342

Self-Discovery and Professional Development.  

ERIC Educational Resources Information Center

This paper explores the role of self discovery in the early stages of caregiver professional development, with a focus on the array of choices available to university students. The assumption is that many people do not know their repertoire of skills until asked to complete a project requiring those skills; thus, "the heart of becoming a…

Margolin, Edythe

343

Discovery of Candidate Disease Genes in ENU-Induced Mouse Mutants by Large-Scale Sequencing, Including a Splice-Site Mutation in Nucleoredoxin  

PubMed Central

An accurate and precisely annotated genome assembly is a fundamental requirement for functional genomic analysis. Here, the complete DNA sequence and gene annotation of mouse Chromosome 11 was used to test the efficacy of large-scale sequencing for mutation identification. We re-sequenced the 14,000 annotated exons and boundaries from over 900 genes in 41 recessive mutant mouse lines that were isolated in an N-ethyl-N-nitrosourea (ENU) mutation screen targeted to mouse Chromosome 11. Fifty-nine sequence variants were identified in 55 genes from 31 mutant lines. 39% of the lesions lie in coding sequences and create primarily missense mutations. The other 61% lie in noncoding regions, many of them in highly conserved sequences. A lesion in the perinatal lethal line l11Jus13 alters a consensus splice site of nucleoredoxin (Nxn), inserting 10 amino acids into the resulting protein. We conclude that point mutations can be accurately and sensitively recovered by large-scale sequencing, and that conserved noncoding regions should be included for disease mutation identification. Only seven of the candidate genes we report have been previously targeted by mutation in mice or rats, showing that despite ongoing efforts to functionally annotate genes in the mammalian genome, an enormous gap remains between phenotype and function. Our data show that the classical positional mapping approach of disease mutation identification can be extended to large target regions using high-throughput sequencing.

Wilming, Laurens G.; Liu, Bin; Probst, Frank J.; Harrow, Jennifer; Grafham, Darren; Hentges, Kathryn E.; Woodward, Lanette P.; Maxwell, Andrea; Mitchell, Karen; Risley, Michael D.; Johnson, Randy; Hirschi, Karen; Lupski, James R.; Funato, Yosuke; Miki, Hiroaki; Marin-Garcia, Pablo; Matthews, Lucy; Coffey, Alison J.; Parker, Anne; Hubbard, Tim J.; Rogers, Jane; Bradley, Allan; Adams, David J.; Justice, Monica J.

2009-01-01

344

Knowledge Discovery in Heterogeneous Environments.  

National Technical Information Service (NTIS)

This chapter addresses the topic of knowledge discovery in heterogeneous environments. It begins with an overview of the knowledge- discovery process. Because of the importance of using clean, consistent data in the knowledge-discovery process, the chapte...

M. N. Kamel M. G. Ceruti

2002-01-01

345

Whole-exome Sequencing and an iPSC-Derived Cardiomyocyte Model Provides a Powerful Platform for Gene Discovery in Left Ventricular Hypertrophy  

PubMed Central

Rationale: Left ventricular hypertrophy (LVH) is a heritable predictor of cardiovascular disease, particularly in blacks. Objective: Determine the feasibility of combining evidence from two distinct but complementary experimental approaches to identify novel genetic predictors of increased LV mass. Methods: Whole-exome sequencing (WES) was conducted in seven African-American sibling trios ascertained on high average familial LV mass indexed to height (LVMHT) using Illumina HiSeq technology. Identified missense or nonsense (MS/NS) mutations were examined for association with LVMHT using linear mixed models adjusted for age, sex, body weight, and familial relationship. To functionally assess WES findings, human induced pluripotent stem cell-derived cardiomyocytes (induced pluripotent stem cell-CM) were stimulated to induce hypertrophy; mRNA sequencing (RNA-seq) was used to determine gene expression differences associated with hypertrophy onset. Statistically significant findings under both experimental approaches identified LVH candidate genes. Candidate genes were further prioritized by seven supportive criteria that included additional association tests (two criteria), regional linkage evidence in the larger HyperGEN cohort (one criterion), and publically available gene and variant based annotations (four criteria). Results: WES reads covered 91% of the target capture region (of size 37.2?MB) with an average coverage of 65×. WES identified 31,426 MS/NS mutations among the 21 individuals. A total of 295 MS/NS variants in 265 genes were associated with LVMHT with q-value <0.25. Of the 265 WES genes, 44 were differentially expressed (P?genes identified, 5, including HLA-B, HTT, MTSS1, SLC5A12, and THBS1, met 3 of 7 supporting criteria. THBS1 encodes an adhesive glycoprotein that promotes matrix preservation in pressure-overload LVH. THBS1 gene expression was 34% higher in hypertrophied cells (P?=?0.0003) and a predicted conserved and damaging NS variant in exon 13 (A2099G) was significantly associated with LVHMT (P?=?4?×?10?6). Conclusion: Combining evidence from cutting-edge genetic and cellular experiments can enable identification of novel LVH risk loci.

Zhi, D.; Irvin, M. R.; Gu, C. C.; Stoddard, A. J.; Lorier, R.; Matter, A.; Rao, D. C.; Srinivasasainagendra, V.; Tiwari, H. K.; Turner, A.; Broeckel, U.; Arnett, D. K.

2012-01-01

346

Whole-exome sequencing and an iPSC-derived cardiomyocyte model provides a powerful platform for gene discovery in left ventricular hypertrophy.  

PubMed

Rationale: Left ventricular hypertrophy (LVH) is a heritable predictor of cardiovascular disease, particularly in blacks. Objective: Determine the feasibility of combining evidence from two distinct but complementary experimental approaches to identify novel genetic predictors of increased LV mass. Methods: Whole-exome sequencing (WES) was conducted in seven African-American sibling trios ascertained on high average familial LV mass indexed to height (LVMHT) using Illumina HiSeq technology. Identified missense or nonsense (MS/NS) mutations were examined for association with LVMHT using linear mixed models adjusted for age, sex, body weight, and familial relationship. To functionally assess WES findings, human induced pluripotent stem cell-derived cardiomyocytes (induced pluripotent stem cell-CM) were stimulated to induce hypertrophy; mRNA sequencing (RNA-seq) was used to determine gene expression differences associated with hypertrophy onset. Statistically significant findings under both experimental approaches identified LVH candidate genes. Candidate genes were further prioritized by seven supportive criteria that included additional association tests (two criteria), regional linkage evidence in the larger HyperGEN cohort (one criterion), and publically available gene and variant based annotations (four criteria). Results: WES reads covered 91% of the target capture region (of size 37.2?MB) with an average coverage of 65×. WES identified 31,426 MS/NS mutations among the 21 individuals. A total of 295 MS/NS variants in 265 genes were associated with LVMHT with q-value <0.25. Of the 265 WES genes, 44 were differentially expressed (P?genes identified, 5, including HLA-B, HTT, MTSS1, SLC5A12, and THBS1, met 3 of 7 supporting criteria. THBS1 encodes an adhesive glycoprotein that promotes matrix preservation in pressure-overload LVH. THBS1 gene expression was 34% higher in hypertrophied cells (P?=?0.0003) and a predicted conserved and damaging NS variant in exon 13 (A2099G) was significantly associated with LVHMT (P?=?4?×?10(-6)). Conclusion: Combining evidence from cutting-edge genetic and cellular experiments can enable identification of novel LVH risk loci. PMID:22654895

Zhi, D; Irvin, M R; Gu, C C; Stoddard, A J; Lorier, R; Matter, A; Rao, D C; Srinivasasainagendra, V; Tiwari, H K; Turner, A; Broeckel, U; Arnett, D K

2012-05-28

347

Discovery of miR-mRNA interactions via simultaneous Bayesian inference of gene networks and clusters using sequence-based predictions and expression data.  

PubMed

MicroRNAs (miRs) are known to interfere with mRNA expression, and much work has been put into predicting and inferring miR-mRNA interactions. Both sequence-based interaction predictions as well as interaction inference based on expression data have been proven somewhat successful; furthermore, models that combine the two methods have had even more success. In this paper, I further refine and enrich the methods of miRmRNA interaction discovery by integrating a Bayesian clustering algorithm into a model of prediction-enhanced miR-mRNA target inference, creating an algorithm called PEACOAT, which is written in the R language. I show that PEACOAT improves the inference of miR-mRNA target interactions using both simulated data and a data set of microarrays from samples of multiple myeloma patients. In simulated networks of 25 miRs and mRNAs, our methods using clustering can improve inference in roughly two-thirds of cases, and in the multiple myeloma data set, KEGG pathway enrichment was found to be more significant with clustering than without. Our findings are consistent with previous work in clustering of non-miR genetic networks and indicate that there could be a significant advantage to clustering of miR and mRNA expression data as a part of interaction inference. PMID:23846182

Godsey, Brian

2013-07-10

348

Breast Cancer Drug Discovery with Combinatorial Chemical Libraries.  

National Technical Information Service (NTIS)

The goal of this project is to discover new drugs that have specificity and significant anticancer activity against breast cancer. The approach uses several novel aspects that permit high volume screening for drug discovery. To maximize the number of uniq...

K. S. Lam

1998-01-01

349

Breast Cancer Drug Discovery with Combinatorial Chemical Libraries.  

National Technical Information Service (NTIS)

The goal of this project is to discover new drugs that have specificity and significant anticancer activity against breast cancer. The approach uses several novel aspects that permit high volume screening for drug discovery. To maximize the number of uniq...

S. Salmon

1997-01-01

350

The Deinococcus radiodurans uvrA gene: identification of mutation sites in two mitomycin-sensitive strains and the first discovery of insertion sequence element from deinobacteria  

Microsoft Academic Search

Deinococcus radiodurans (Dr) possesses a prominent ability to repair the DNA injury induced by various DNA-damaging agents including mitomycin C (MC), ultraviolet light (UV) and ionizing radiation. DNA damage resistance was restored in MC sensitive (MCS) mutants 2621 and 3021 by transforming with DNAs of four cosmid clones derived from the gene library of strain KD8301, which showed wild type

Issay Narumi; Korbkit Cherdchu; Shigeru Kitayama; Hiroshi Watanabe

1997-01-01

351

Analysis of expressed sequence tags from Actinidia: applications of a cross species EST database for gene discovery in the areas of flavor, health, color and ripening  

Microsoft Academic Search

BACKGROUND: Kiwifruit (Actinidia spp.) are a relatively new, but economically important crop grown in many different parts of the world. Commercial success is driven by the development of new cultivars with novel consumer traits including flavor, appearance, healthful components and convenience. To increase our understanding of the genetic diversity and gene-based control of these key traits in Actinidia, we have

Ross N Crowhurst; Andrew P Gleave; Elspeth A MacRae; Charles Ampomah-Dwamena; Ross G Atkinson; Lesley L Beuning; Sean M Bulley; David Chagne; Ken B Marsh; Adam J Matich; Mirco Montefiori; Richard D Newcomb; Robert J Schaffer; Björn Usadel; Andrew C Allan; Helen L Boldingh; Judith H Bowen; Marcus W Davy; Rheinhart Eckloff; A Ross Ferguson; Lena G Fraser; Emma Gera; Roger P Hellens; Bart J Janssen; Karin Klages; Kim R Lo; Robin M MacDiarmid; Bhawana Nain; Mark A McNeilage; Maysoon Rassam; Annette C Richardson; Erik HA Rikkerink; Gavin S Ross; Roswitha Schröder; Kimberley C Snowden; Edwige JF Souleyre; Matt D Templeton; Eric F Walton; Daisy Wang; Mindy Y Wang; Yanming Y Wang; Marion Wood; Rongmei Wu; Yar-Khing Yauk; William A Laing

2008-01-01

352

Biomimicry as a basis for drug discovery.  

PubMed

Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term "natural product" is often used synonymously with "secondary metabolite." Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed "inventive evolution." It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products ("unnatural natural products"), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery. PMID:9949862

Kolb, V M

1998-01-01

353

The Learning Discovery  

ERIC Educational Resources Information Center

|The learning discovery of youngsters is a do-it-yourself teaching method for clerical, administrative, and accountant trainees at the Bankside House headquarters of the Central Electricity Generating Board's South Eastern Region, London. (Author)|

Prout, Joan

1975-01-01

354

The Discovery of Noggin.  

ERIC Educational Resources Information Center

|Discusses recently published work that appears to have many of the answers to the question of how the nervous system develops. Focuses on the discovery of what is believed to be neural inducer, a protein called noggin. (LZ)|

Oppenheimer, Steven B.

1995-01-01

355

The requirements discovery process  

SciTech Connect

Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirement process. This paper provides a high-level overview of the requirements discovery process.

Bahill, A.T. [Univ. of Arizona, Tucson, AZ (United States). Systems and Industrial Engineering; Dean, F.F. [Sandia National Lab., Albuquerque, NM (United States)

1997-02-01

356

Design of the Discovery Channel Telescope enclosure  

NASA Astrophysics Data System (ADS)

The Discovery Channel Telescope (DCT) is a project of Lowell Observatory in conjuction with the Discovery Channel to design and construct a 4.2-meter clear aperture telescope and support facility on a site approximately 40 miles southeast of Flagstaff, Arizona, USA. The site is an undisturbed mountain top at an altitude of 7800-feet. Design and construction of the telescope enclosure includes all of the site utilities, access road to the site along with the fixed base enclosure, telescope pier and rotating dome structure. The details covered in this paper are the decisions and rationale of the DCT enclosure conceptual design completed by M3 Engineering & Technology Corporation (M3).

Terán U., José; Sebring, Thomas A.; Neff, Daniel H.; de Kock, Mariana

2004-10-01

357

Discovery Channel Telescope software key technologies  

NASA Astrophysics Data System (ADS)

The Discovery Channel Telescope (DCT) is a 4.3-meter astronomical research telescope being built in northern Arizona as a partnership between Discovery Communications and Lowell Observatory. The project software team has designed and partially implemented a component-based system. We describe here the key features of that design (state-based components that respond to signals) and detail specific implementation technologies we expect to be of most interest: examples of the Command Pattern, State Pattern, and XML-based configuration file handling using LabVIEW classes and shared variables with logging and alarming features.

Lotz, Paul J.

2010-07-01

358

Discovery Channel Telescope software development overview  

NASA Astrophysics Data System (ADS)

The Discovery Channel Telescope (DCT) is a 4.3-meter astronomical research telescope being built in northern Arizona as a partnership between Discovery Communications and Lowell Observatory. We present an overview of the current status of the project software effort, including the iterative development process (including planning, requirements management and traceability, design, code, test, issue tracking, and version control), our experience with management and design techniques and tools the team uses that support the effort, key features of the component-based architectural design, and implementation examples that leverage new LabVIEW-based technologies.

Lotz, Paul J.; Greenspan, Daniel; Godwin, Ryan; Taylor, Philip

2010-07-01

359

Drug Discovery — 1990  

Microsoft Academic Search

\\u000a This is the first of what we hope will become a regular meeting held on the alternate years of the EORTC-NCI joint European\\u000a (Amsterdam) meeting. Our focus is on the presentation and discussion of cytotoxic agents, with a significant portion of the\\u000a Symposium to include the exciting frontiers of drug discovery being explored by the National Cooperative Drug Discovery Groups

Frederick Valeriote; Thomas Corbett; Laurence Baker

360

Population differences in the International Multi-Centre ADHD Gene Project  

Microsoft Academic Search

The International Multi-Centre ADHD Gene sample consists of 674 families from eight countries (Belgium, England, Germany, Holland, Ireland, Israel, Spain, and Switzerland) ascertained from clinics for combined-type attention definity hyperactivity disorder in an offspring. 863 SNPs were successfully genotyped across 47 autosomal genes implicated in psychiatric disorders yielding a single nucleotide polymorphism (SNP) density of approximately one SNP per 2.5

Benjamin M. Neale; Pak C. Sham; Shaun Purcell; Tobias Banaschewski; Jan Buitelaar; Barbara Franke; Edmund Sonuga-Barke; Richard Ebstein; Jacques Eisenberg; Aisling Mulligan; Michael Gill; Iris Manor; Ana Miranda; Fernando Mulas; Robert D. Oades; Herbert Roeyers; Aribert Rothenberger; Joseph Sergeant; Hans-Christoph Steinhausen; Eric Taylor; Margaret Thompson; W. Chen; K. Zhou; P. Asherson; S. V. Faraone

2008-01-01

361

From Genes to Proteins to Behavior: A Laboratory Project That Enhances Student Understanding in Cell and Molecular Biology  

PubMed Central

In the laboratory, students can actively explore concepts and experience the nature of scientific research. We have devised a 5-wk laboratory project in our introductory college biology course whose aim was to improve understanding in five major concepts that are central to basic cellular, molecular biology, and genetics while teaching molecular biology techniques. The project was focused on the production of adenine in Saccharomyces cerevisiae and investigated the nature of mutant red colonies of this yeast. Students created red mutants from a wild-type strain, amplified the two genes capable of giving rise to the red phenotype, and then analyzed the nucleotide sequences. A quiz assessing student understanding in the five areas was given at the start and the end of the course. Analysis of the quiz showed significant improvement in each of the areas. These areas were taught in the laboratory and the classroom; therefore, students were surveyed to determine whether the laboratory played a role in their improved understanding of the five areas. Student survey data demonstrated that the laboratory did have an important role in their learning of the concepts. This project simulated steps in a research project and could be adapted for an advanced course in genetics.

Silveira, Linda A.

2009-01-01

362

Replication by the Epistasis Project of the interaction between the genes for IL6 and IL10 in the risk of Alzheimer's disease  

Microsoft Academic Search

BACKGROUND: Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 AD

Onofre Combarros; Cornelia M van Duijn; Naomi Hammond; Olivia Belbin; Alejandro Arias-Vásquez; Mario Cortina-Borja; Michael G Lehmann; Yurii S Aulchenko; Maaike Schuur; Heike Kölsch; Reinhard Heun; Gordon K Wilcock; Kristelle Brown; Patrick G Kehoe; Rachel Harrison; Eliecer Coto; Victoria Alvarez; Panos Deloukas; Ignacio Mateo; Rhian Gwilliam; Kevin Morgan; Donald R Warden; A David Smith; Donald J Lehmann

2009-01-01

363

Human lung project: evaluating variance of gene expression in the human lung.  

PubMed

Nondiseased tissue is an important reference for microarray studies of pulmonary disease. We obtained 23 single lungs from multiorgan donors at time of procurement. Donors varied in age, sex, smoking history, and ethnicity. Lungs were dissected into upper and lower lobe peripheral sections for RNA extraction. Microarray analysis was performed using Affymetrix Hu-133 Plus 2.0 arrays. We observed that the relative variability of gene expression increased rapidly from technical (lowest), to regional, to population (highest). In addition, age and sex have measurable effects on gene expression. Gene expression variability is heterogeneously distributed among biologic categories. We conclude that gene expression variability is greater between individuals than within individuals and that population variability is the most important factor in the study design of microarray experiments of the human lung. Classes of genes with high population variability are biologically important and provide a novel perspective into lung physiology and pathobiology. Our study represents the first comprehensive analysis of nondiseased lung tissue. The generation of this robust dataset has important implications for the design and implementation of future comparative expression analysis with pulmonary disease states. PMID:16498083

Gruber, Michael P; Coldren, Christopher D; Woolum, Malcolm D; Cosgrove, Gregory P; Zeng, Chan; Barón, Anna E; Moore, Mark D; Cool, Carlyne D; Worthen, G Scott; Brown, Kevin K; Geraci, Mark W

2006-02-23

364

Human Lung Project: Evaluating Variance of Gene Expression in the Human Lung  

PubMed Central

Nondiseased tissue is an important reference for microarray studies of pulmonary disease. We obtained 23 single lungs from multiorgan donors at time of procurement. Donors varied in age, sex, smoking history, and ethnicity. Lungs were dissected into upper and lower lobe peripheral sections for RNA extraction. Microarray analysis was performed using Affymetrix Hu-133 Plus 2.0 arrays. We observed that the relative variability of gene expression increased rapidly from technical (lowest), to regional, to population (highest). In addition, age and sex have measurable effects on gene expression. Gene expression variability is heterogeneously distributed among biologic categories. We conclude that gene expression variability is greater between individuals than within individuals and that population variability is the most important factor in the study design of microarray experiments of the human lung. Classes of genes with high population variability are biologically important and provide a novel perspective into lung physiology and pathobiology. Our study represents the first comprehensive analysis of nondiseased lung tissue. The generation of this robust dataset has important implications for the design and implementation of future comparative expression analysis with pulmonary disease states.

Gruber, Michael P.; Coldren, Christopher D.; Woolum, Malcolm D.; Cosgrove, Gregory P.; Zeng, Chan; Baron, Anna E.; Moore, Mark D.; Cool, Carlyne D.; Worthen, G. Scott; Brown, Kevin K.; Geraci, Mark W.

2006-01-01

365

Studying Human Disease Genes in Caenorhabditis elegans: A Molecular Genetics Laboratory Project  

PubMed Central

Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether Caenorhabditis elegans can be a useful model system for studying genes associated with human disease. In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1). Students compared observable phenotypes of wild-type C. elegans and C. elegans with a homozygous deletion in the assigned gene. They confirmed the genetic deletion with nested polymerase chain reaction and performed a bioinformatics analysis to predict how the deletion would affect the encoded mRNA and protein. Students also performed RNA interference (RNAi) against their assigned gene and evaluated whether RNAi caused a phenotype similar to that of the genetic deletion. As a capstone activity, students prepared scientific posters in which they presented their data, evaluated whether C. elegans was a useful model system for studying their assigned genes, and proposed future directions. Assessment showed gains in understanding genotype versus phenotype, RNAi, common bioinformatics tools, and the utility of model organisms.

Cox-Paulson, Elisabeth A.; Grana, Theresa M.; Harris, Michelle A.; Batzli, Janet M.

2012-01-01

366

Environmental regulation of plant gene expression: An RT-qPCR laboratory project for an upper-level undergraduate biochemistry or molecular biology course.  

PubMed

We present a novel laboratory project employing "real-time" RT-qPCR to measure the effect of environment on the expression of the FLOWERING LOCUS C gene, a key regulator of floral timing in Arabidopsis thaliana plants. The project requires four 3-hr laboratory sessions and is aimed at upper-level undergraduate students in biochemistry or molecular biology courses. The project provides students with hands-on experience with RT-qPCR, the current "gold standard" for gene expression analysis, including detailed data analysis using the common 2-??CT method. Moreover, it provides a convenient starting point for many inquiry-driven projects addressing diverse questions concerning ecological biochemistry, naturally occurring genetic variation, developmental biology, and the regulation of gene expression in nature. © 2013 by The International Union of Biochemistry and Molecular Biology, 41(5):325-333, 2013. PMID:24038665

Eickelberg, Garrett J; Fisher, Alison J

2013-09-10

367

Discovery of the autonomously replicating plasmid pMF1 from Myxococcus fulvus and development of a gene cloning system in Myxococcus xanthus.  

PubMed

Myxobacteria are very important due to their unique characteristics, such as multicellular social behavior and the production of diverse and novel bioactive secondary metabolites. However, the lack of autonomously replicating plasmids has hindered genetic manipulation of myxobacteria for decades. To determine whether indigenous plasmids are present, we screened about 150 myxobacterial strains, and a circular plasmid designated pMF1 was isolated from Myxococcus fulvus 124B02. Sequence analysis showed that this plasmid was 18,634 bp long and had a G+C content of 68.7%. Twenty-three open reading frames were found in the plasmid, and 14 of them were not homologous to any known sequence. Plasmids containing the gene designated pMF1.14, which encodes a large unknown protein, were shown to transform Myxococcus xanthus DZ1 and DK1622 at high frequencies ( approximately 10(5) CFU/microg DNA), suggesting that the locus is responsible for the autonomous replication of pMF1. Shuttle vectors were constructed for both M. xanthus and Escherichia coli. The pilA gene, which is essential for pilus formation and social motility in M. xanthus, was cloned into the shuttle vectors and introduced into the pilA-deficient mutant DK10410. The transformants subsequently exhibited the ability to form pili and social motility. Autonomously replicating plasmid pMF1 provides a new tool for genetic manipulation in Myxococcus. PMID:18245244

Zhao, Jing-Yi; Zhong, Li; Shen, Mei-Juan; Xia, Zhi-Jie; Cheng, Qiu-Xiang; Sun, Xia; Zhao, Guo-Ping; Li, Yue-Zhong; Qin, Zhong-Jun

2008-02-01

368

Studying Human Disease Genes in "Caenorhabditis Elegans": A Molecular Genetics Laboratory Project  

ERIC Educational Resources Information Center

|Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether "Caenorhabditis elegans" can be a useful model system for studying genes

Cox-Paulson, Elisabeth A.; Grana, Theresa M.; Harris, Michelle A.; Batzli, Janet M.

2012-01-01

369

A SCREEN FOR XYLELLA FASTIDIOSA GENES INVOLVED IN TRANSMISSION BY INSECT VECTORS Project Leaders  

Microsoft Academic Search

A strategy is being pursued that will identify genes involved in insect transmission of Xylella fastidiosa (Xf) by both gain of function and loss of function mutagenesis of a Xf mutant that is unable to be transmitted by sharpshooters. KLN61 is an rpfF mutant strain of Xf (Newman et al. 2004) that cannot be transmitted to plants by the sharpshooter

Alexander H. Purcell; Steven E. Lindow; Clelia Baccari

370

The Finite State Projection Approach for the Analysis of Stochastic Noise in Gene Networks  

Microsoft Academic Search

In order to capture important subcellular dy- namics, researchers in computational biology have begun to turn to mesoscopic models in which molecular interactions at the gene level behave as discrete stochastic events. While the trajectories of such models cannot be described with deterministic expressions, the probability distributions of these trajectories can be described by the set of linear ordinary differential

Brian Munsky; Mustafa Khammash

2007-01-01

371

The Finite State Projection Approach for the Analysis of Stochastic Noise in Gene Networks  

Microsoft Academic Search

In order to capture important subcellular dynamics, researchers in computational biology have begun to turn to mesoscopic models in which molecular interactions at the gene level behave as discrete stochastic events. While the trajectories of such models cannot be described with deterministic expressions, the probability distributions of these trajectories can be described by the set of linear ordinary differential equations

Brian Munsky; Mustafa Khammash

2008-01-01

372

Gene discovery and comparative analysis of X-degenerate genes from the domestic cat Y chromosome ? ? Sequence data from this article have been deposited with the EMBL\\/GenBank Data Libraries under Accession No. EU879967EU879988  

Microsoft Academic Search

Mammalian sex chromosomes are the remnants of an ancient autosomal pair present in the ancestral mammalian karyotype. As a consequence of random decay and chromosome rearrangements over evolutionary time, Y chromosome gene repertoires differ between eutherian lineages. To investigate the gene repertoire and transcriptional analysis of the domestic cat Y chromosome, and their potential roles in spermatogenesis, we obtained full-length

Alison J. Pearks Wilkerson; Terje Raudsepp; Tina Graves; Derek Albracht; Wesley Warren; Bhanu P. Chowdhary; Loren C. Skow; William J. Murphy

2008-01-01

373

Discoveries, financial strength lift Colombia  

SciTech Connect

Colombia plans to play a growing role in international oil markets while expanding and privatizing its domestic gas and electricity industries. Officials intend to curb the government`s spending on energy development while increasing its energy revenues. Their plans imply growing participation in energy projects by private companies. Also certain to help attract investment capital is the country`s new standing as a world-class oil and gas province. Discovery of Cusiana oil field in 1989 and of Cupiagua oil field in 1992 added 2 billion bbl of oil and 3 tcf of gas reserves, effectively doubling Colombia`s totals. Exploration near the giant Cusiana-Cupiagua complex, in the eastern foothills of the Andes about 100 miles northeast of Bogota, has turned up an estimated 10 tcf of gas and 1 billion bbl of oil in Volcanera field and two discoveries overlying it, Florena and Pauto Sur. Colombia`s critics say that, despite its laudable economic stability and improving oil and gas prospectivity, political impediments could interfere with progress toward its lofty energy goals. The paper discusses the heightened political risks, unequal pace of reform, gas pipeline construction, gas regulations, tying gas to power, reform in the oil sector, achieving sustainable change, and the appeal to investors.

Koen, A.D.

1996-07-15

374

DiscoveryResources.org  

NSDL National Science Digital Library

An interesting site that is packed full of up-to-date info, discoveryresources.org is "where you will find the most up-to-date information, resources and news available about electronic discovery...(the site) offers much needed resources for legal professionals who seek to understand the many new technological and legal challenges associated with electronic discovery." As fast as the technology revolution is booming, so too is are all of the legal strings attached. This site seeks to provide professionals in the field with a means to stay up on discovery news. With links to Legal News, Featured Articles, a weblog, and a Reading Room, there is lots of useful information on this unique site.

375

Exploring the Planets: Discovery  

NSDL National Science Digital Library

This site describes what early civilizations knew about our solar system and how astronomy developed over the centuries. The early theories describing the movements of the planets, development of the first telescopes, and discoveries of the planets Uranus, Neptune and Pluto are some of the topics addressed in Discovery. Here you will find the Pluto discovery plate, the photographic plate taken the day Pluto's position was discovered by Clyde Tombaugh. Other topics covered at this site include: the Renaissance with the ideas of Copernicus and Kepler; the age of the telescope, which traces its development; Galileo, who is credited with discovering the moons of Jupiter, phases of Venus, and the craters on the Moon; and planetary satellites.

376

Discovery of Companion Asteroids  

NSDL National Science Digital Library

This site displays the first-ever images of a large, double asteroid once assumed to be a single asteroid called Antiope. The images were recently released by the Southwest Research Institute (SWRI). Each asteroid in the pair is approximately 50 miles across, separated by about 100 miles. This discovery was made using the W.M. Keck Observatory, Mauna Kea, Hawaii. Images of another discovery, that of a small moon orbiting the large asteroid Pulcova, is featured at this site. In addition to still images, movies show the motion of the asteroids.

1999-01-01

377

Titanic: Discovery Channel  

NSDL National Science Digital Library

RMS Titanic raised a 23- by 14-foot section of the Titanic's outer hull this week, and the Discovery Channel, who helped sponsor the expedition, will be webcasting live from the interior of the Titanic via robot cameras August 16 at 8:00 and 10:00 p.m. (Eastern Time). In addition to their live webcase, the Discovery Channel site (discussed in the December 5, 1997 issue of the Scout Report) features virtual reality tours of sections of the Titanic before and after its crash, quicktime videos of the expeditions, a computer animated simulation of the crash, and more.

378

Lhc SUSY Discovery Potential  

NASA Astrophysics Data System (ADS)

The SUSY discovery potential of CMS and ATLAS detectors at the LHC is evaluated in different regions of the mSUGRA parameter space. In inclusive searches the parameters can be constrained by considering the event topology. The observation of kinematic end points at large statistics makes possible to infer the SUSY mass spectrum. The LHC SUSY discovery region extents up to the mass scale of 2 TeV at Lint > 10fb-1 and is limited by uncertainties in the Standard Model backgrounds.

Zhukov, V.

2007-11-01

379

Projecting 2D gene expression data into 3D and 4D space.  

PubMed

Video games typically generate virtual 3D objects by texture mapping an image onto a 3D polygonal frame. The feeling of movement is then achieved by mathematically simulating camera movement relative to the polygonal frame. We have built customized scripts that adapt video game authoring software to texture mapping images of gene expression data onto b-spline based embryo models. This approach, known as UV mapping, associates two-dimensional (U and V) coordinates within images to the three dimensions (X, Y, and Z) of a b-spline model. B-spline model frameworks were built either from confocal data or de novo extracted from 2D images, once again using video game authoring approaches. This system was then used to build 3D models of 182 genes expressed in developing Xenopus embryos and to implement these in a web-accessible database. Models can be viewed via simple Internet browsers and utilize openGL hardware acceleration via a Shockwave plugin. Not only does this database display static data in a dynamic and scalable manner, the UV mapping system also serves as a method to align different images to a common framework, an approach that may make high-throughput automated comparisons of gene expression patterns possible. Finally, video game systems also have elegant methods for handling movement, allowing biomechanical algorithms to drive the animation of models. With further development, these biomechanical techniques offer practical methods for generating virtual embryos that recapitulate morphogenesis. PMID:17366623

Gerth, Victor E; Katsuyama, Kaori; Snyder, Kevin A; Bowes, Jeff B; Kitayama, Atsushi; Ueno, Naoto; Vize, Peter D

2007-04-01

380

Characterization of the Metabochip in diverse populations from the International HapMap Project in the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) project.  

PubMed

Genome-wide association studies (GWAS) have identified hundreds of genomic regions associated with common human disease and quantitative traits. A major research avenue for mature genotype-phenotype associations is the identification of the true risk or functional variant for downstream molecular studies or personalized medicine applications. As part of the Population Architecture using Genomics and Epidemiology (PAGE) study, we as Epidemiologic Architecture for Genes Linked to Environment (EAGLE) are fine-mapping GWAS-identified genomic regions for common diseases and quantitative traits. We are currently genotyping the Metabochip, a custom content BeadChip designed for fine-mapping metabolic diseases and traits, in?15,000 DNA samples from patients of African, Hispanic, and Asian ancestry linked to de-identified electronic medical records from the Vanderbilt University biorepository (BioVU). As an initial study of quality control, we report here the genotyping data for 360 samples of European, African, Asian, and Mexican descent from the International HapMap Project. In addition to quality control metrics, we report the overall allele frequency distribution, overall population differentiation (as measured by FST), and linkage disequilibrium patterns for a select GWAS-identified region associated with low-density lipoprotein cholesterol levels to illustrate the utility of the Metabochip for fine-mapping studies in the diverse populations expected in EAGLE, the PAGE study, and other efforts underway designed to characterize the complex genetic architecture underlying common human disease and quantitative traits. PMID:23424124

Crawford, Dana C; Goodloe, Robert; Brown-Gentry, Kristin; Wilson, Sarah; Roberson, Jamie; Gillani, Niloufar B; Ritchie, Marylyn D; Dilks, Holli H; Bush, William S

2013-01-01

381

CHARACTERIZATION OF THE METABOCHIP IN DIVERSE POPULATIONS FROM THE INTERNATIONAL HAPMAP PROJECT IN THE EPIDEMIOLOGIC ARCHITECTURE FOR GENES LINKED TO ENVIRONMENT (EAGLE) PROJECT  

PubMed Central

Genome-wide association studies (GWAS) have identified hundreds of genomic regions associated with common human disease and quantitative traits. A major research avenue for mature genotype-phenotype associations is the identification of the true risk or functional variant for downstream molecular studies or personalized medicine applications. As part of the Population Architecture using Genomics and Epidemiology (PAGE) study, we as Epidemiologic Architecture for Genes Linked to Environment (EAGLE) are fine-mapping GWAS-identified genomic regions for common diseases and quantitative traits. We are currently genotyping the Metabochip, a custom content BeadChip designed for fine-mapping metabolic diseases and traits, in~15,000 DNA samples from patients of African, Hispanic, and Asian ancestry linked to deidentified electronic medical records from the Vanderbilt University biorepository (BioVU). As an initial study of quality control, we report here the genotyping data for 360 samples of European, African, Asian, and Mexican descent from the International HapMap Project. In addition to quality control metrics, we report the overall allele frequency distribution, overall population differentiation (as measured by FST), and linkage disequilibrium patterns for a select GWAS-identified region associated with low-density lipoprotein cholesterol levels to illustrate the utility of the Metabochip for fine-mapping studies in the diverse populations expected in EAGLE, the PAGE study, and other efforts underway designed to characterize the complex genetic architecture underlying common human disease and quantitative traits.

CRAWFORD, DANA C.; GOODLOE, ROBERT; BROWN-GENTRY, KRISTIN; WILSON, SARAH; ROBERSON, JAMIE; GILLANI, NILOUFAR B.; RITCHIE, MARYLYN D.; DILKS, HOLLI H.; BUSH, WILLIAM S.

2013-01-01

382

Advancing drug discovery for schizophrenia  

PubMed Central

Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, “Advancing Drug Discovery for Schizophrenia” was held March 9–11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia.

Marder, Stephen R.; Roth, Bryan; Sullivan, Patrick F.; Scolnick, Edward M.; Nestler, Eric J.; Geyer, Mark A.; Welnberger, Daniel R.; Karayiorgou, Maria; Guidotti, Alessandro; Gingrich, Jay; Akbarian, Schahram; Buchanan, Robert W.; Lieberman, Jeffrey A.; Conn, P. Jeffrey; Haggarty, Stephen J.; Law, Amanda J.; Campbell, Brian; Krystal, John H.; Moghaddam, Bita; Saw, Akira; Caron, Marc G.; George, Susan R.; Allen, John A.; Solis, Michelle

2013-01-01

383

The path to open-angle glaucoma gene discovery: endophenotypic status of intraocular pressure, cup-to-disc ratio, and central corneal thickness.  

PubMed

PURPOSE. Primary open-angle glaucoma (POAG) is a complex disease with a genetic architecture that can be simplified through the investigation of individual traits underlying disease risk. It has been well studied in twin models, and this study was undertaken to investigate the heritability of some of these key endophenotypes in extended pedigrees. METHODS. These data are derived from a large, multicenter study of extended, Caucasian POAG families from Australia and the United States. The study included 1181 people from 22 extended pedigrees. Variance components modeling was used to determine the heritabilities of maximum intraocular pressure (IOP), maximum vertical cup-to-disc ratio (VCDR), and mean central corneal thickness (CCT). Bivariate quantitative genetic analysis between these eye-related phenotypes and POAG itself was performed to determine whether any of these traits represent true endophenotypes. RESULTS. Heritability estimates for IOP, VCDR, and CCT (0.42, 0.66, and 0.72, respectively) were significant and show strong concordance with data in previous studies. Bivariate analysis revealed that both IOP (RhoG = 0.80; P = 9.6 x 10(-6)) and VCDR (RhoG = 0.76; P = 4.8 x 10(-10)) showed strong evidence of genetic correlation with POAG susceptibility. These two traits also correlated genetically with each other (RhoG = 0.45; P = 0.0012). Alternatively, CCT did not correlate genetically with risk of POAG. CONCLUSIONS. All the proposed POAG-related traits have genetic components. However, the significant genetic correlations observed between IOP, VCDR, and POAG itself suggest that they most likely represent true endophenotypes that could aid in the identification of genes underlying POAG susceptibility. CCT did not correlate genetically with disease and is unlikely to be a useful surrogate endophenotype for POAG. PMID:20237253

Charlesworth, Jac; Kramer, Patricia L; Dyer, Tom; Diego, Victor; Samples, John R; Craig, Jamie E; Mackey, David A; Hewitt, Alex W; Blangero, John; Wirtz, Mary K

2010-03-17

384

A Genome-wide Analysis of Admixture in Uyghurs and a High-Density Admixture Map for Disease-Gene Discovery  

PubMed Central

Following up on our previous study, we conducted a genome-wide analysis of admixture for two Uyghur population samples (HGDP-UG and PanAsia-UG), collected from the northern and southern regions of Xinjiang in China, respectively. Both HGDP-UG and PanAsia-UG showed a substantial admixture of East-Asian (EAS) and European (EUR) ancestries, with an empirical estimation of ancestry contribution of 53:47 (EAS:EUR) and 48:52 for HGDP-UG and PanAsia-UG, respectively. The effective admixture time under a model with a single pulse of admixture was estimated as 110 generations and 129 generations, or admixture events occurred about 2200 and 2580 years ago for HGDP-UG and PanAsia-UG, respectively, assuming an average of 20 yr per generation. Despite Uyghurs' earlier history compared to other admixture populations, admixture mapping, holds promise for this population, because of its large size and its mixture of ancestry from different continents. We screened multiple databases and identified a genome-wide single-nucleotide polymorphism panel that can distinguish EAS and EUR ancestry of chromosomal segments in Uyghurs. The panel contains 8150 ancestry-informative markers (AIMs) showing large frequency differences between EAS and EUR populations (FST > 0.25, mean FST = 0.43) but small frequency differences (7999 AIMs validated) within both populations (FST < 0.05, mean FST < 0.01). We evaluated the effectiveness of this admixture map for localizing disease genes in two Uyghur populations. To our knowledge, our map constitutes the first practical resource for admixture mapping in Uyghurs, and it will enable studies of diseases showing differences in genetic risk between EUR and EAS populations.

Xu, Shuhua; Jin, Li

2008-01-01

385

Discovery Channel Global Education Partnership, Program Performance Report 2 to USAID Namibia.  

National Technical Information Service (NTIS)

This report covers project activities from January to December 17, 2004. This year, Discovery Channel Global Education Partnership (DCGEP) strengthened its local and international partnerships, which have helped fuel the projects growth in Namibia. Thanks...

2004-01-01

386

Discovery Touches Down!  

NASA Video Gallery

Discovery has completed its final mission, STS-133, for NASA's Space Shuttle Program landing on-time at Kennedy Space Center in Florida at 11:57 a.m. EST, March 9, 2011 after 202 orbits around Earth and a journey of 5,304,140 miles.

KSC Web Team

2011-03-09

387

Knowledge discovery from data?  

Microsoft Academic Search

The knowledge discovery and data mining (KDD) field draws on findings from statistics, databases, and artificial intelligence to construct tools that let users gain insight from massive data sets. People in business, science, medicine, academia, and government collect such data sets, and several commercial packages now offer general-purpose KDD tools. An important KDD goal is to “turn data into knowledge”.

M. J. Pazzani; Marti A. Hearst

2000-01-01

388

Historian's Discovery of Childhood  

ERIC Educational Resources Information Center

|The "discovery of childhood" is a tricky notion because childhood is as much a fact of a biological and psychological nature as a cultural notion that through the centuries has been the object of changing perceptions, definitions, and images. Children barely speak in history; virtually everything we know about them is mediated by adults. Then how…

Frijhoff, Willem

2012-01-01

389

SeaDiscovery.com  

NSDL National Science Digital Library

SeaDiscovery.com is an online source for "underwater tech and ocean science news." The site presents not only news, but information about maritime technology employment which includes featured jobs and resumes. It also allows access to the Maritime Technology Reporter magazine and provides links to a number of important directories.

2013-07-05

390

Frequent Subgraph Discovery  

Microsoft Academic Search

Over the years, frequent itemset discovery algorithms have been used to solve various interesting problems. As data mining techniques are being increasingly applied to non-traditional domains, existing approaches for finding frequent itemsets cannot be used as they cannot model the requirement of these domains. An alternate way of modeling the objects in these data sets, is to use a graph

Michihiro Kuramochi; George Karypis

2001-01-01

391

Internet Resource Discovery Services  

Microsoft Academic Search

The exponentially growing global Internet is a virtual infinite fountain of information, yet it can seem like aninformation labyrinth when you try to find any specific fact. Recently, a number of tools have been developedto assist users in finding information of interest. These resource discovery tools specialize in browsing, searching,and organizing information distributed throughout the Internet. In this paper we

Katia Obraczka; Peter B. Danzig; Shih-hao Li

1993-01-01

392

New Pleading, New Discovery  

Microsoft Academic Search

Pleading in federal court has a new narrative. The old narrative was one of notice, with the goal of broad access to the civil justice system. New Pleading, after the landmark Supreme Court cases of Twombly and Iqbal, is focused on factual sufficiency, with the purpose of screening out meritless cases that otherwise might impose discovery costs on defendants. The

Scott Dodson

2010-01-01

393

Takeda's Oncology Discovery Strategy.  

PubMed

Takeda's Oncology Discovery Strategy is tightly integrated and focused on first and fast-best-in-class products and product combinations. Core areas of expertise include hormones, protein homeostasis, biotherapeutics and signal transduction. Strategic imperatives for research success are understanding of unmet needs, focus on biological expertise in foundational areas of leadership and flexibility to adapt to new information. PMID:23493743

DeSchuytner, Brian; Kuvalanka, Kyle; Hibner, Barbara; Bolen, Joseph

2013-03-14

394

False Discovery Rate Control With Groups.  

PubMed

In the context of large-scale multiple hypothesis testing, the hypotheses often possess certain group structures based on additional information such as Gene Ontology in gene expression data and phenotypes in genome-wide association studies. It is hence desirable to incorporate such information when dealing with multiplicity problems to increase statistical power. In this article, we demonstrate the benefit of considering group structure by presenting a p-value weighting procedure which utilizes the relative importance of each group while controlling the false discovery rate under weak conditions. The procedure is easy to implement and shown to be more powerful than the classical Benjamini-Hochberg procedure in both theoretical and simulation studies. By estimating the proportion of true null hypotheses, the data-driven procedure controls the false discovery rate asymptotically. Our analysis on one breast cancer dataset confirms that the procedure performs favorably compared with the classical method. PMID:21931466

Hu, James X; Zhao, Hongyu; Zhou, Harrison H

2010-09-01

395

False Discovery Rate Control With Groups  

PubMed Central

In the context of large-scale multiple hypothesis testing, the hypotheses often possess certain group structures based on additional information such as Gene Ontology in gene expression data and phenotypes in genome-wide association studies. It is hence desirable to incorporate such information when dealing with multiplicity problems to increase statistical power. In this article, we demonstrate the benefit of considering group structure by presenting a p-value weighting procedure which utilizes the relative importance of each group while controlling the false discovery rate under weak conditions. The procedure is easy to implement and shown to be more powerful than the classical Benjamini–Hochberg procedure in both theoretical and simulation studies. By estimating the proportion of true null hypotheses, the data-driven procedure controls the false discovery rate asymptotically. Our analysis on one breast cancer dataset confirms that the procedure performs favorably compared with the classical method.

Hu, James X.; Zhao, Hongyu; Zhou, Harrison H.

2011-01-01

396

Genome projects and gene therapy: gateways to next generation biological weapons.  

PubMed

Genomic and gene therapy research promise important gains into the treatment of human, animal, and plant diseases. However, there is a military aspect to this research that must be recognized. This research enables a new form of biological warfare named genomic warfare. This is the first peer-reviewed scientific article to discuss this threat in-depth. This article advocates that we begin to deal with this threat. Despite that the United States and many signatories of previous bioweapons treaties have agreed not to use biological weapons, mankind has a track record of using all of the weapons at its disposal. This article has a review of the literature and a basic overview of genomic research and gene therapy, which is followed by a discussion of how this therapy can be weaponized. How genomic warfare weapons might be deployed, how deployment may be detected, and the policies and research that would reduce this threat will be described. It is the aim of this article to clearly articulate that this risk exists and to encourage public health, scientific, political, and military leaders to take action to deal with the risk. PMID:14680038

Black, John Logan

2003-11-01

397

Literature-Related Discovery (LRD).  

National Technical Information Service (NTIS)

Discovery in science is the generation of novel, interesting, plausible, and intelligible knowledge about the objects of study. Literature- related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked (i.e...

J. A. Block J. L. Solka M. B. Briggs R. L. Rushenberg R. N. Kostoff

2007-01-01

398

Serendipitous Science: An Unexpected Discovery  

NSDL National Science Digital Library

This article describes glaciologist Lonnie Thompson's discovery of an ancient plant in Peru. It also illustrates some important characteristics of good science that can be seen even in a serendipitous discovery.

Landis, Carol

399

Parents' Decisions to Screen Newborns for FMR1 Gene Expansions in a Pilot Research Project  

PubMed Central

OBJECTIVE: The goal of this study was to document rates of parental consent in a pilot study of newborn screening for FMR1 gene expansions, examine demographic characteristics of mothers who consented or declined, describe the reasons for their decision, and discuss ethical and social aspects of the consent process. METHODS: A brief survey was used to record basic demographic data from mothers and an open-ended question was used to elicit parents' reasons for accepting or declining screening. A descriptive analysis was conducted on the number of mothers who consented to or declined screening, and a logistic regression model predicted mothers' likelihood to agree to screening based on demographic characteristics. Reasons for decisions were analyzed using content analysis. The study was conducted at University of North Carolina Hospitals. A total of 2137 mothers were approached. RESULTS: The uptake rate for couples was 63%. Acceptance rates varied by race/ethnicity, with black respondents being less likely to accept screening. Primary reasons for accepting were “to know,” “belief in research,” and “the test was minimal/no risk.” Reasons for declining included not wanting to know or worry, not being a good time, and issues with testing children or with genetic tests. CONCLUSIONS: Findings demonstrate that a majority of parents accepted newborn screening for FMR1 gene expansions, but decision rates and reasons for accepting or declining varied in part as a function of race/ethnicity and in part as a function of what parents most valued or feared in their assessment of risks and benefits.

Choudhury, Summer; Sideris, John; Guarda, Sonia; Buansi, Allen; Roche, Myra; Powell, Cynthia; Bailey, Donald B.

2011-01-01

400

Rapid Annotation of Anonymous Sequences from Genome Projects Using Semantic Similarities and a Weighting Scheme in Gene Ontology  

PubMed Central

Background Large-scale sequencing projects have now become routine lab practice and this has led to the development of a new generation of tools involving function prediction methods, bringing the latter back to the fore. The advent of Gene Ontology, with its structured vocabulary and paradigm, has provided computational biologists with an appropriate means for this task. Methodology We present here a novel method called ARGOT (Annotation Retrieval of Gene Ontology Terms) that is able to process quickly thousands of sequences for functional inference. The tool exploits for the first time an integrated approach which combines clustering of GO terms, based on their semantic similarities, with a weighting scheme which assesses retrieved hits sharing a certain number of biological features with the sequence to be annotated. These hits may be obtained by different methods and in this work we have based ARGOT processing on BLAST results. Conclusions The extensive benchmark involved 10,000 protein sequences, the complete S. cerevisiae genome and a small subset of proteins for purposes of comparison with other available tools. The algorithm was proven to outperform existing methods and to be suitable for function prediction of single proteins due to its high degree of sensitivity, specificity and coverage.

Fontana, Paolo; Cestaro, Alessandro; Velasco, Riccardo; Formentin, Elide; Toppo, Stefano

2009-01-01