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Transformação genética de laranjeira doce com genes da via biossintética de carotenoides; Functional analysis of genes of the carotenoid biosynthetic pathway in sweet orange

Pinheiro, Thaísa Tessutti
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 03/06/2014 PT
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Plantas de Citrus regeneradas de tecidos juvenis demandam um longo período para a análise do fenótipo resultante em flores ou frutos. Este trabalho apresenta o mutante espontâneo de florescimento precoce de laranja doce, denominado 'x11', como modelo para estudos de genômica funcional de Citrus. As frutas cítricas são ricas em carotenoides, pigmentos que possuem grande valor nutricional, como pró-vitamina A (?- ou ?-caroteno). Estudos de genômica funcional envolvendo genes da via biossintética dos carotenoides terão resultados rapidamente obtidos utilizando-se variedades com florescimento e frutificação precoce, como a laranjeira doce mutante 'x11'. A laranjeira doce 'Sanguínea-de-Mombuca' (SM) é uma variedade de polpa vermelha que acumula licopeno na polpa dos frutos, podendo ser considerada uma importante ferramenta no estudo da acumulação de carotenoides nos frutos de laranjeiras. Desta maneira, o objetivo deste estudo foi estabelecer a laranjeira 'x11' como planta-modelo em experimentos de transformação genética visando estudos de genômica funcional dos genes PSY (fitoeno sintase), PDS (fitoeno desaturase), CRTISO (carotenoide isomerase), LCY-b (licpeno ?-ciclase) e ?-caroteno hidroxilase (HYb), envolvidos na biossíntese de carotenoides e utilizar a laranjeira SM como ferramenta no entendimento da acumulação dos carotenoides nos frutos de Citrus. Plantas de laranjeira 'x11' foram transformadas com promotor de expressão preferencial para órgãos reprodutivos de Citrus controlando a expressão de gene repórter (gusA) para a análise da tecido especificidade. Foi realizada a otimização do protocolo de transformação genética de segmentos de epicótilo de laranjeira 'x11' via Agrobacterium. A eficiência de transformação média foi de 18...

Sequenciamento de DNA de nova geração e suas aplicações na genômica de plantas

Carvalho, Mayra Costa da Cruz Gallo de; Silva, Danielle Cristina Gregorio da
Fonte: Universidade Federal de Santa Maria (UFSM) Publicador: Universidade Federal de Santa Maria (UFSM)
Tipo: Artigo de Revista Científica Formato: 735-744
POR
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As plataformas de sequenciamento de nova geração são uma alternativa poderosa para estudos de genômica estrutural e funcional. Na genômica de plantas, os trabalhos com as novas plataformas têm sido destinados ao sequenciamento de transcritos, ressequenciamento ou sequenciamento de novo de genomas plastidiais. Neste trabalho, são detalhadas as tecnologias das plataformas mais utilizadas atualmente, bem como é revisada a aplicação dessas tecnologias na genômica estrutural e funcional de plantas.; The next-generation DNA sequencing technologies are a powerful alternative to studies in structural and functional genomics. In plant genomics studies, the work with these new platforms has been used for the sequencing of transcripts, re-sequencing, and the de novo sequencing of plastid genomes. This research details the technological principles of the next-generation DNA sequencing platforms most used and reviews its application in structural and functional plant genomics.

Phytophthora functional genomics database (PFGD): functional genomics of phytophthora–plant interactions

Gajendran, Kamal; Gonzales, Michael D.; Farmer, Andrew; Archuleta, Eric; Win, Joe; Waugh, Mark E.; Kamoun, Sophien
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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The Phytophthora Functional Genomics Database (PFGD; ), developed by the National Center for Genome Resources in collaboration with The Ohio State University-Ohio Agricultural Research and Development Center (OSU-OARDC), is a publicly accessible information resource for Phytophthora–plant interaction research. PFGD contains transcript, genomic, gene expression and functional assay data for Phytophthora infestans, which causes late blight of potato, and Phytophthora sojae, which affects soybeans. Automated analyses are performed on all sequence data, including consensus sequences derived from clustered and assembled expressed sequence tags. The PFGD search filter interface allows intuitive navigation of transcript and genomic data organized by library and derived queries using modifiers, annotation keywords or sequence names. BLAST services are provided for libraries built from the transcript and genomic sequences. Transcript data visualization tools include Quality Screening, Multiple Sequence Alignment and Features and Annotations viewers. A genomic browser that supports comparative analysis via novel dynamic functional annotation comparisons is also provided. PFGD is integrated with the Solanaceae Genomics Database (SolGD; ) to help provide insight into the mechanisms of infection and resistance...

Rice functional genomics research in China

Han, Bin; Xue, Yongbiao; Li, Jiayang; Deng, Xing-Wang; Zhang, Qifa
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
EN
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Rice functional genomics is a scientific approach that seeks to identify and define the function of rice genes, and uncover when and how genes work together to produce phenotypic traits. Rapid progress in rice genome sequencing has facilitated research in rice functional genomics in China. The Ministry of Science and Technology of China has funded two major rice functional genomics research programmes for building up the infrastructures of the functional genomics study such as developing rice functional genomics tools and resources. The programmes were also aimed at cloning and functional analyses of a number of genes controlling important agronomic traits from rice. National and international collaborations on rice functional genomics study are accelerating rice gene discovery and application.

Xenogenomics: Genomic Bioprospecting in Indigenous and Exotic Plants Through EST Discovery, cDNA Microarray-Based Expression Profiling and Functional Genomics

John, Ulrik P.; Spangenberg, German C.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em /06/2005 EN
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To date, the overwhelming majority of genomics programs in plants have been directed at model or crop plant species, meaning that very little of the naturally occurring sequence diversity found in plants is available for characterization and exploitation. In contrast, ‘xenogenomics’ refers to the discovery and functional analysis of novel genes and alleles from indigenous and exotic species, permitting bioprospecting of biodiversity using high-throughput genomics experimental approaches. Such a program has been initiated to bioprospect for genetic determinants of abiotic stress tolerance in indigenous Australian flora and native Antarctic plants. Uniquely adapted Poaceae and Fabaceae species with enhanced tolerance to salt, drought, elevated soil aluminium concentration, and freezing stress have been identified, based primarily on their eco-physiology, and have been subjected to structural and functional genomics analyses. For each species, EST collections have been derived from plants subjected to appropriate abiotic stresses. Transcript profiling with spotted unigene cDNA micro-arrays has been used to identify genes that are transcriptionally modulated in response to abiotic stress. Candidate genes identified on the basis of sequence annotation or transcript profiling have been assayed in planta and other in vivo systems for their capacity to confer novel phenotypes. Comparative genomics analysis of novel genes and alleles identified in the xenogenomics target plant species has subsequently been undertaken with reference to key model and crop plants.

Re-Annotation Is an Essential Step in Systems Biology Modeling of Functional Genomics Data

van den Berg, Bart H. J.; McCarthy, Fiona M.; Lamont, Susan J.; Burgess, Shane C.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 14/05/2010 EN
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One motivation of systems biology research is to understand gene functions and interactions from functional genomics data such as that derived from microarrays. Up-to-date structural and functional annotations of genes are an essential foundation of systems biology modeling. We propose that the first essential step in any systems biology modeling of functional genomics data, especially for species with recently sequenced genomes, is gene structural and functional re-annotation. To demonstrate the impact of such re-annotation, we structurally and functionally re-annotated a microarray developed, and previously used, as a tool for disease research. We quantified the impact of this re-annotation on the array based on the total numbers of structural- and functional-annotations, the Gene Annotation Quality (GAQ) score, and canonical pathway coverage. We next quantified the impact of re-annotation on systems biology modeling using a previously published experiment that used this microarray. We show that re-annotation improves the quantity and quality of structural- and functional-annotations, allows a more comprehensive Gene Ontology based modeling, and improves pathway coverage for both the whole array and a differentially expressed mRNA subset. Our results also demonstrate that re-annotation can result in a different knowledge outcome derived from previous published research findings. We propose that...

Tomato Functional Genomics Database: a comprehensive resource and analysis package for tomato functional genomics

Fei, Zhangjun; Joung, Je-Gun; Tang, Xuemei; Zheng, Yi; Huang, Mingyun; Lee, Je Min; McQuinn, Ryan; Tieman, Denise M.; Alba, Rob; Klee, Harry J.; Giovannoni, James J.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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Tomato Functional Genomics Database (TFGD) provides a comprehensive resource to store, query, mine, analyze, visualize and integrate large-scale tomato functional genomics data sets. The database is functionally expanded from the previously described Tomato Expression Database by including metabolite profiles as well as large-scale tomato small RNA (sRNA) data sets. Computational pipelines have been developed to process microarray, metabolite and sRNA data sets archived in the database, respectively, and TFGD provides downloads of all the analyzed results. TFGD is also designed to enable users to easily retrieve biologically important information through a set of efficient query interfaces and analysis tools, including improved array probe annotations as well as tools to identify co-expressed genes, significantly affected biological processes and biochemical pathways from gene expression data sets and miRNA targets, and to integrate transcript and metabolite profiles, and sRNA and mRNA sequences. The suite of tools and interfaces in TFGD allow intelligent data mining of recently released and continually expanding large-scale tomato functional genomics data sets. TFGD is available at http://ted.bti.cornell.edu.

Recent Progress in Development of Tnt1 Functional Genomics Platform for Medicago truncatula and Lotus japonicus in Bulgaria

Revalska, Miglena; Vassileva, Valya; Goormachtig, Sofie; Van Hautegem, Tom; Ratet, Pascal; Iantcheva, Anelia
Fonte: Bentham Science Publishers Ltd Publicador: Bentham Science Publishers Ltd
Tipo: Artigo de Revista Científica
Publicado em /04/2011 EN
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Legumes, as protein-rich crops, are widely used for human food, animal feed and vegetable oil production. Over the past decade, two legume species, Medicago truncatula and Lotus japonicus, have been adopted as model legumes for genomics and physiological studies. The tobacco transposable element, Tnt1, is a powerful tool for insertional mutagenesis and gene inactivation in plants. A large collection of Tnt1-tagged lines of M. truncatula cv. Jemalong was generated during the course of the project ‘GLIP’: Grain Legumes Integrated Project, funded by the European Union (www.eugrainlegumes.org). In the project ‘IFCOSMO’: Integrated Functional and COmparative genomics Studies on the MOdel Legumes Medicago truncatula and Lotus japonicus, supported by a grant from the Ministry of Education, Youth and Science, Bulgaria, these lines are used for development of functional genomics platform of legumes in Bulgaria. This review presents recent advances in the evaluation of the M. truncatula Tnt1 mutant collection and outlines the steps that are taken in using the Tnt1-tagging for generation of a mutant collection of the second model legume L. japonicus. Both collections will provide a number of legume-specific mutants and serve as a resource for functional and comparative genomics research on legumes. Genomics technologies are expected to advance genetics and breeding of important legume crops (pea...

Tetrahymena Functional Genomics Database (TetraFGD): an integrated resource for Tetrahymena functional genomics

Xiong, Jie; Lu, Yuming; Feng, Jinmei; Yuan, Dongxia; Tian, Miao; Chang, Yue; Fu, Chengjie; Wang, Guangying; Zeng, Honghui; Miao, Wei
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 12/03/2013 EN
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The ciliated protozoan Tetrahymena thermophila is a useful unicellular model organism for studies of eukaryotic cellular and molecular biology. Researches on T. thermophila have contributed to a series of remarkable basic biological principles. After the macronuclear genome was sequenced, substantial progress has been made in functional genomics research on T. thermophila, including genome-wide microarray analysis of the T. thermophila life cycle, a T. thermophila gene network analysis based on the microarray data and transcriptome analysis by deep RNA sequencing. To meet the growing demands for the Tetrahymena research community, we integrated these data to provide a public access database: Tetrahymena functional genomics database (TetraFGD). TetraFGD contains three major resources, including the RNA-Seq transcriptome, microarray and gene networks. The RNA-Seq data define gene structures and transcriptome, with special emphasis on exon–intron boundaries; the microarray data describe gene expression of 20 time points during three major stages of the T. thermophila life cycle; the gene network data identify potential gene–gene interactions of 15 049 genes. The TetraFGD provides user-friendly search functions that assist researchers in accessing gene models...

A scoring strategy combining statistics and functional genomics supports a possible role for common polygenic variation in autism

Carayol, Jérôme; Schellenberg, Gerard D.; Dombroski, Beth; Amiet, Claire; Génin, Bérengère; Fontaine, Karine; Rousseau, Francis; Vazart, Céline; Cohen, David; Frazier, Thomas W.; Hardan, Antonio Y.; Dawson, Geraldine; Rio Frio, Thomas
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 18/02/2014 EN
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Autism spectrum disorders (ASD) are highly heritable complex neurodevelopmental disorders with a 4:1 male: female ratio. Common genetic variation could explain 40–60% of the variance in liability to autism. Because of their small effect, genome-wide association studies (GWASs) have only identified a small number of individual single-nucleotide polymorphisms (SNPs). To increase the power of GWASs in complex disorders, methods like convergent functional genomics (CFG) have emerged to extract true association signals from noise and to identify and prioritize genes from SNPs using a scoring strategy combining statistics and functional genomics. We adapted and applied this approach to analyze data from a GWAS performed on families with multiple children affected with autism from Autism Speaks Autism Genetic Resource Exchange (AGRE). We identified a set of 133 candidate markers that were localized in or close to genes with functional relevance in ASD from a discovery population (545 multiplex families); a gender specific genetic score (GS) based on these common variants explained 1% (P = 0.01 in males) and 5% (P = 8.7 × 10−7 in females) of genetic variance in an independent sample of multiplex families. Overall, our work demonstrates that prioritization of GWAS data based on functional genomics identified common variants associated with autism and provided additional support for a common polygenic background in autism.

Integrative functional genomics identifies RINT1 as a novel GBM oncogene

Quayle, Steven N.; Chheda, Milan G.; Shukla, Sachet A.; Wiedemeyer, Ruprecht; Tamayo, Pablo; Dewan, Robert W.; Zhuang, Li; Huang-Hobbs, Emmet; Haidar, Sam; Xiao, Yonghong; Ligon, Keith L.; Hahn, William C.; Chin, Lynda
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN_US
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Large-scale cancer genomics efforts are identifying hundreds of somatic genomic alterations in glioblastoma (GBM). Distinguishing between active driver and neutral passenger alterations requires functional assessment of each gene; therefore, integrating biological weight of evidence with statistical significance for each genomic alteration will enable better prioritization for downstream studies. Here, we demonstrate the feasibility and potential of in vitro functional genomic screens to rapidly and systematically prioritize high-probability candidate genes for in vivo validation. Integration of low-complexity gain- and loss-of-function screens designed on the basis of genomic data identified 6 candidate GBM oncogenes, and RINT1 was validated as a novel GBM oncogene based on its ability to confer tumorigenicity to primary nontransformed murine astrocytes in vivo. Cancer genomics-guided low-complexity genomic screens can quickly provide a functional filter to prioritize high-value targets for further downstream mechanistic and translational studies.

Mapped Ds/T-DNA launch pads for functional genomics in barley

Zhao, T.; Palotta, M.; Langridge, P.; Prasad, M.; Graner, A.; Schulze-Lefert, P.; Koprek, T.
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em //2006 EN
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A system for targeted gene tagging and local saturation mutagenesis based on maize transposable elements (Ac/Ds) was developed in barley (Hordeum vulgare L.). We generated large numbers of transgenic barley lines carrying a single copy of the non-autonomous maize Ds element at defined positions in the genome. Independent Ds lines were either generated by activating Ds elements in existing single-copy lines after crossing with AcTPase-expressing plants or by Agrobacterium-mediated transformation. Genomic DNA flanking Ds and T-DNA insertion sites from over 200 independent lines was isolated and sequenced, and was used for a sequence based mapping strategy in a barley reference population. More than 100 independent Ds insertion sites were mapped and can be used as launch pads for future targeted tagging of genes in the vicinity of the insertion sites. Sequence analysis of Ds and T-DNA flanking regions revealed a sevenfold preference of both mutagens for insertion into non-redundant, gene-containing regions of the barley genome. However, whilst transposed Ds elements preferentially inserted adjacent to regions with a high number of predicted and experimentally validated matrix attachment regions (nuclear MARs), this was not the case for T-DNA integration sites. These findings and an observed high transposition frequency from mapped launch pads demonstrate the future potential of gene tagging for functional genomics and gene discovery in barley.; Tiehan Zhao...

Plant cell wall biosynthesis: genetic, biochemical and functional genomics approaches to the identification of key genes

Farrokhi, N.; Burton, R.; Brownfield, L.; Hrmova, M.; Wilson, S.; Bacic, A.; Fincher, G.
Fonte: Blackwell Publishing Ltd. Publicador: Blackwell Publishing Ltd.
Tipo: Artigo de Revista Científica
Publicado em //2006 EN
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Cell walls are dynamic structures that represent key determinants of overall plant form, plant growth and development, and the responses of plants to environmental and pathogen-induced stresses. Walls play centrally important roles in the quality and processing of plant-based foods for both human and animal consumption, and in the production of fibres during pulp and paper manufacture. In the future, wall material that constitutes the major proportion of cereal straws and other crop residues will find increasing application as a source of renewable fuel and composite manufacture. Although the chemical structures of most wall constituents have been defined in detail, the enzymes involved in their synthesis and remodelling remain largely undefined, particularly those involved in polysaccharide biosynthesis. There have been real recent advances in our understanding of cellulose biosynthesis in plants, but, with few exceptions, the identities and modes of action of polysaccharide synthases and other glycosyltransferases that mediate the biosynthesis of the major non-cellulosic wall polysaccharides are not known. Nevertheless, emerging functional genomics and molecular genetics technologies are now allowing us to re-examine the central questions related to wall biosynthesis. The availability of the rice...

Functional genomics: tools for improving farm animal health and welfare

Hiendleder, S.; Bauersachs, S.; Boulesteix, A.; Blum, H.; Arnold, G.; Frohlich, T.; Wolf, E.
Fonte: Office Int Epizooties Publicador: Office Int Epizooties
Tipo: Artigo de Revista Científica
Publicado em //2005 EN
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The first genome sequence assemblies of farm animal species are now accessible through public domain databases, and further sequencing projects are in rapid progress. In addition, large collections of expressed sequences have been obtained, which will aid in constructing annotated transcript maps for many economically important species. Thus, the breeding of farm animals is entering the post-genome era. Functional genomics, defined as applying global experimental approaches to assess gene function, by using the information and reagents provided by structural genomics (i.e. mapping and sequencing), has become the focus of interest. Combining a holistic view of phenotypes at the molecular level with genetic marker data seems a particularly promising approach for improving health and welfare traits in farm animals. These traits are often difficult to define. They suffer from low heritabilities and a corresponding lack of genetic gain in conventional selection and breeding programmes. At the same time, genomic information from micro-organisms and parasites offers the potential for new vaccines and therapeutics. This review describes major functional genomics tools, lists genomic resources available for farm animals and discusses the prospects and challenges of functional genomics in improving the health and welfare of farm animals.

Functional Genomics in the Productivity and End-Use Quality of Barley

Newbigin, E.; Bacic, A.; Langridge, P.; Fincher, G.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Conference paper
Publicado em //2004 EN
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Functional genomics is a technology through which large sets of genes that influence a particular biological process are identified. Functional genomics comprises several sub-disciplines, including genomics, proteomics and metabolomics. The total number of genes in plant genomes lies somewhere in the range of 25,000 to 40,000. Thus, functional genomics technologies must be geared to high throughput data collection and high throughput analyses of gene structure and function. Additional specialised resources, including barley mutant libraries, barley DNA microarrays and high-density genetic maps of barley, represent critical support technologies. The technologies will be illustrated by reference to specific applications relating to malting and brewing performance, such as the biosynthesis of cell wall polysaccharides, and to productivity, where tolerance to a range of abiotic stresses is a key determinant of yield. Finally, the potential impacts and benefits of functional genomics research for the barley industry will be addressed. Where a gene controlling an important trait has been isolated, a diagnostic marker that is 100% accurate in predicting the phenotype of the plants for the target trait could be used in high throughput screening of germplasm in breeding programs.; http://www.ibgs.cz/; http://www.ibgs.cz/photos/book_of_abstracts/Session_6.htm; Session 6 : Barley protein...

Advances in functional genomics for investigating salinity stress tolerance mechanisms in cereals

Shelden, M.; Roessner, U.
Fonte: Frontiers Research Foundation Publicador: Frontiers Research Foundation
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
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Abiotic stresses such as low water availability and high salinity are major causes of cereal crop yield losses and significantly impact on sustainability. Wheat and barley are two of the most important cereal crops (after maize and rice) and are grown in increasingly hostile environments with soil salinity and drought both expected to increase this century, reducing the availability of arable land. Barley and wheat are classified as glycophytes (salt-sensitive), yet they are more salt-tolerant than other cereal crops such as rice and so are good models for studying salt tolerance in cereals. The exploitation of genetic variation of phenotypic traits through plant breeding could significantly improve growth of cereals in salinity-affected regions, thus leading to improved crop yields. Genetic variation in phenotypic traits for abiotic stress tolerance have been identified in land races and wild germplasm but the molecular basis of these differences is often difficult to determine due to the complex genetic nature of these species. High-throughput functional genomics technologies, such as transcriptomics, metabolomics, proteomics, and ionomics are powerful tools for investigating the molecular responses of plants to abiotic stress. The advancement of these technologies has allowed for the identification and quantification of transcript/metabolites in specific cell types and/or tissues. Using these new technologies on plants will provide a powerful tool to uncovering genetic traits in more complex species such as wheat and barley and provide novel insights into the molecular mechanisms of salinity stress tolerance.; Megan C. Shelden and Ute Roessner

A Rapid and Efficient Method for Purifying High Quality Total RNA from Peaches (Prunus persica) for Functional Genomics Analyses

Meissel, Lee; Fonseca, Beatriz; Gonzalez, Susana; Baeza-Yates, Ricardo; Cambiazo, Veronica; Campos, Reinaldo; Gonzalez, Mauricio; Orellana, Ariel; Retamales, Julio; Silva, Herman
Fonte: Sociedad de Biología de Chile Publicador: Sociedad de Biología de Chile
Tipo: Artigo de Revista Científica
EN
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http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602005000100010&lng=es&nrm=iso; Prunus persica has been proposed as a genomic model for deciduous trees and the Rosaceae family. Optimized protocols for RNA isolation are necessary to further advance studies in this model species such that functional genomics analyses may be performed. Here we present an optimized protocol to rapidly and efficiently purify high quality total RNA from peach fruits (Prunus persica). Isolating high-quality RNA from fruit tissue is often difficult due to large quantities of polysaccharides and polyphenolic compounds that accumulate in this tissue and co-purify with the RNA. Here we demonstrate that a modified version of the method used to isolate RNA from pine trees and the woody plant Cinnamomun tenuipilum is ideal for isolating high quality RNA from the fruits of Prunus persica. This RNA may be used for many functional genomic based experiments such as RT-PCR and the construction of large-insert cDNA libraries.

A functional genomics catalogue of activated transcription factors during pathogenesis of pneumococcal disease

Mahdi, L.K.; Deihimi, T.; Zamansani, F.; Fruzangohar, M.; Adelson, D.L.; Paton, J.C.; Ogunniyi, A.D.; Ebrahimie, E.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em //2014 ENGLISH
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BACKGROUND: Streptococcus pneumoniae (the pneumococcus) is the world's foremost microbial pathogen, killing more people each year than HIV, TB or malaria. The capacity to penetrate deeper host tissues contributes substantially to the ability of this organism to cause disease. Here we investigated, for the first time, functional genomics modulation of 3 pneumococcal strains (serotype 2 [D39], serotype 4 [WCH43] and serotype 6A [WCH16]) during transition from the nasopharynx to lungs to blood and to brain of mice at both promoter and domain activation levels. RESULTS: We found 7 highly activated transcription factors (TFs) [argR, codY, hup, rpoD, rr02, scrR and smrC] capable of binding to a large number of up-regulated genes, potentially constituting the regulatory backbone of pneumococcal pathogenesis. Strain D39 showed a distinct profile in employing a large number of TFs during blood infection. Interestingly, the same highly activated TFs used by D39 in blood are also used by WCH16 and WCH43 during brain infection. This indicates that different pneumococcal strains might activate a similar set of TFs and regulatory elements depending on the final site of infection. Hierarchical clustering analysis showed that all the highly activated TFs...

Functional Genomics in Chickens: Development of Integrated-Systems Microarrays for Transcriptional Profiling and Discovery of Regulatory Pathways

Cogburn, L. A.; Wang, X.; Carre, W.; Rejto, L.; Aggrey, S. E.; Duclos, M. J.; Simon, J.; Porter, T. E.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em /04/2004 EN
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The genetic networks that govern the differentiation and growth of major tissues of economic importance in the chicken are largely unknown. Under a functional genomics project, our consortium has generated 30 609 expressed sequence tags (ESTs) and developed several chicken DNA microarrays, which represent the Chicken Metabolic/Somatic (10 K) and Neuroendocrine/Reproductive (8 K) Systems (http://udgenome.ags.udel.edu/cogburn/). One of the major challenges facing functional genomics is the development of mathematical models to reconstruct functional gene networks and regulatory pathways from vast volumes of microarray data. In initial studies with liver-specific microarrays (3.1 K), we have examined gene expression profiles in liver during the peri-hatch transition and during a strong metabolic perturbation—fasting and re-feeding—in divergently selected broiler chickens (fast vs. slow-growth lines). The expression of many genes controlling metabolic pathways is dramatically altered by these perturbations. Our analysis has revealed a large number of clusters of functionally related genes (mainly metabolic enzymes and transcription factors) that control major metabolic pathways. Currently, we are conducting transcriptional profiling studies of multiple tissues during development of two sets of divergently selected broiler chickens (fast vs. slow growing and fat vs. lean lines). Transcriptional profiling across multiple tissues should permit construction of a detailed genetic blueprint that illustrates the developmental events and hierarchy of genes that govern growth and development of chickens. This review will briefly describe the recent acquisition of chicken genomic resources (ESTs and microarrays) and our consortium's efforts to help launch the new era of functional genomics in the chicken.

Functional genomics studies of human brain development and implications for autism spectrum disorder

Ziats, Mark
Fonte: University of Cambridge; Department of Physiology, Development and Neuroscience Publicador: University of Cambridge; Department of Physiology, Development and Neuroscience
Tipo: Thesis; doctoral; PhD
EN_US
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Human neurodevelopment requires the coordinated expression of thousands of genes, exquisitely regulated in both spatial and temporal dimensions, to achieve the proper specialization and inter-connectivity of brain regions. Consequently, the dysregulation of complex gene networks in the developing brain is believed to underlie many neurodevelopmental disorders, such as autism spectrum disorders (ASD). Autism has a significant genetic etiology, but there are hundreds of genes implicated, and their functions are heterogeneous and complex. Therefore, an understanding of shared molecular and cellular pathways underlying the development ASD has remained elusive, hampering attempts to develop common diagnostic biomarkers or treatments for this disorder. I hypothesized that analyzing functional genomics relationships among ASD candidate genes during normal human brain development would provide insight into common cellular and molecular pathways that are affected in autistic individuals, and may help elucidate how hundreds of diverse genes can all be linked to a single clinical phenotype. This thesis describes a coordinated set of bioinformatics experiments that first (i) assessed for gene expression and co-expression properties among ASD candidates and other non-coding RNAs during normal human brain development to discover potential shared mechanisms; and then (ii) directly assessed for changes in these pathways in autistic post-mortem brain tissue. The results demonstrated that when examined in the context of normal human brain gene expression during early development...