Projet de séquençage de génome 3061767 30861848 2008-06-21T21:00:40Z Tooony 196117 /* Assemblage génomique */ Les '''projets de séquençage de génome''' sont des projets scientifiques qui ont pour but d'obtenir les séquences complètes des [[génome]]s de différents organismes: [[bactérie]]s, [[plante]]s, [[champignon]]s, [[animaux]], et humain. Ce travail nécessite la séquence de l'[[ADN]] de chacun des chromosomes de l'espèce. Pour une bactérie, il n'y a qu'un seul chromosome à séquencer. Pour l'espèce humaine , qui possède 22 paires de chromosomes et 2 chromosomes sexuels ( X et Y), il y a 24 chromosomes à séquencer. Le [[projet génome humain]] est abouti depuis 2003. ==Assemblage génomique== L'assemblage génomique consiste à prendre un grand nombre de séquences d'ADN, qui ont été obtenues par la méthode ''Whole Genome Shotgun'' , pour les remettre ensemble et recréer le chromosome original. Dans la méthode ''Whole Genome Shotgun'' , l'ADN d'un seul organisme est fragmenté en millions de morceaux. Ceux-ci sont lus par des [[séquençage de l'ADN|séquenceurs d'ADN]] automatiques ( qui peuvent déerminer 900 bases par minutes). Les quatre bases sont [[adénine]], [[guanine]], [[cytosine]], et [[thymine]], abrégées AGCT. Un logiciel d'[[algorithme]] d'assemblage génomique analyse chaque fragment et les aligne tous les uns derrières les autres, en détectant les zones de chevauchement entre les fragments. Si deux séquences se correspondent elles sont considérées comme étant identiques ce qui relie les fragments. L'assemblage génomique peut être problématique pour les informaticiens, car les génomes contiennent des séquences qui se répètent, et ces répétitions peuvent être longues de plusieurs milliers de [[nucléotide]]s ( ou bases) et sur plusieurs endroit du génome. C'est surtout le cas pour les grands génomes des [[plante]]s et des [[animaux]]. <!-- ===Assembly software=== Originally, most large-scale DNA sequencing centers developed their own software for assembling the sequences that they produced. However, this has changed as the software has grown more complex and as the number of sequencing centers has increased. Some well known assembly programs include: [http://www.phrap.org/ Phred/Phrap] by Phil Green was one of the first successful assemblers, widely used in the 1990s and early 2000s, especially for smaller genomes. '''AMOS''' (A Modular, Open-Source assembler) is a well-known [[open source]] effort to bring together the efforts of leading genome assembly code developers. The home of AMOS is currently http://amos.sourceforge.net. AMOS was initiated at [[The Institute for Genomic Research]] by Steven Salzberg, Mihai Pop, and Art Delcher, who are now the [[The University of Maryland]]. The '''Celera Assembler''' was the assembler developed by [[Gene Myers]], [[Granger Sutton]], [[Art Delcher]], and others at [[Celera Genomics]] from 1998 until approximately 2002. It was moved to [[SourceForge]] and continues to be developed by the original scientists and others, at http://sourceforge.net/projects/wgs-assembler. The '''Arachne''' assembler began in 2000 as the doctoral thesis of [[Serafim Batzoglou]], now at [[Stanford University]]. Since that time, it has been developed by a team lead by [[David B. Jaffe]] at the [[Broad Institute]], formerly part of the [[Whitehead Institute]]. It is available for download at http://www.broad.mit.edu/wga/arachnewiki/. ==Genome annotation== '''Genome annotation''' is the process of attaching biological information to [[DNA sequence|sequences]]. It consists of two main steps: # identifying elements on the [[genome]], a process called [[Gene Finding]], and # attaching biological information to these elements. Automatic annotation tools try to perform all this by computer analysis, as opposed to manual annotation (a.k.a. curation) which involves human expertise. Ideally, these approaches co-exist and complement each other in the same annotation [[Pipeline (computing)|pipeline]]. The basic level of annotation is using [[BLAST]] for finding similarities, and then annotating genomes based on that. However, nowadays more and more additional information is added to the annotation platform. The additional information allows manual annotators to deconvolute discrepancies between genes that are given the same annotation. For example, the [http://www.theseed.org SEED] database uses genome context information, similarity scores, experimental data, and integrations of other resources to provide the most accurate genome annotations through their Subsystems approach. The [[Ensembl]] database relies on both curated data sources as well as a range of different software tools in their automated genome annotation pipeline.<ref>{{cite web | url=http://www.ensembl.org/info/about/docs/index.html | title= Ensembl's genome annotation pipeline online documentation}}</ref> ''Structural annotation'' consists in the identification of genomic elements. * ORFs and their localisation * gene structure * coding regions * location of regulatory motifs ''Functional annotation'' consists in attaching biological information to genomic elements. * biochemical function * biological function * involved regulation and interactions * expression These steps may involve both biological experiments and ''[[in silico]]'' analysis. A variety of software tools have been developed to permit scientists to [http://openwetware.org/wiki/Wikiomics:Viewing_and_sharing_genome_annotations view and share genome annotations]. Genome annotation is the next major challenge for the [[Human Genome Project]], now that the genome sequences of human and several [[model organisms]] are largely complete. Identifying the locations of genes and other genetic control elements is often described as defining the biological "parts list" for the assembly and normal operation of an organism. Scientists are still at an early stage in the process of delineating this parts list and in understanding how all the parts "fit together".{{Fact|date=June 2008}} Genome annotation is an active area of investigation and involves a number of different organizations in the life science community which publish the results of their efforts in publicly available [[biological databases]] accessible via the web and other electronic means. Here is an alphabetical listing of on-going projects relevant to genome annotation: * [[ENCODE| ENCyclopedia Of DNA Elements (ENCODE)]] * [[Ensembl]] * [[Gene ontology|Gene Ontology Consortium]] * [[RefSeq]] * [[Uniprot]] * [[Vertebrate and Genome Annotation Project|Vertebrate and Genome Annotation Project (Vega)]] == When is a genome project finished? == When [[Genome sequencing|sequencing]] a genome, there are usually regions that are difficult to sequence (often regions with highly [[repetitive DNA]]). Thus, 'completed' genome sequences are rarely ever complete, and terms such as 'working draft' or 'essentially complete' have been used to more accurately describe the status of such genome projects. Even when every [[base pair]] of a genome sequence has been determined, there are still likely to be errors present because DNA sequencing is not a completely accurate process. It could also be argued that a complete genome project should include the sequences of [[mitochondria]] and (for plants) [[chloroplasts]] as these [[organelles]] have their own genomes. It is often reported that the goal of sequencing a genome is to obtain information about the complete set of [[genes]] in that particular genome sequence. The proportion of a genome that encodes for genes may be very small (particularly in [[eukaryotes]] such as humans, where [[coding region|coding DNA]] may only account for a few percent of the entire sequence). However, it is not always possible (or desirable) to only sequence the [[coding region]]s separately. Also, as scientists understand more about the role of this [[noncoding DNA]] (often referred to as [[junk DNA]]), it will become more important to have a complete genome sequence as a background to understanding the genetics and biology of any given organism. In many ways genome projects do not confine themselves to only determining a DNA sequence of an organism. Such projects may also include [[gene prediction]] to find out where the genes are in a genome, and what those genes do. There may also be related projects to sequence [[Expressed sequence tag|ESTs]] or [[mRNA]]s to help find out where the genes actually are. ==Historical and Technological Perspectives== Historically, when sequencing eukaryotic genomes (such as the worm ''[[Caenorhabditis elegans]]'') it was common to first [[Gene mapping|map]] the genome to provide a series of landmarks across the genome. Rather than sequence a chromosome in one go, it would be sequenced piece by piece (with the prior knowledge of approximately where that piece is located on the larger chromosome). Changes in technology and in particular improvements to the processing power of computers, means that genomes can now be '[[Whole genome shotgun sequencing|shotgun sequenced]]' in one go (there are caveats to this approach though when compared to the traditional approach). Improvements in [[DNA sequencing]] technology has meant that the cost of sequencing a new genome sequence has steadily fallen (in terms of cost per [[base pair]]) and newer technology has also meant that genomes can be sequenced far more quickly. When research agencies decide what new genomes to sequence, the emphasis has been on species which have either a relevance to human health (e.g. pathogenic [[bacteria]] or [[vector (biology)|vectors]] of disease such as [[mosquito]]s) or species which have commercial importance (e.g. livestock and crop plants). Secondary emphasis is placed on species whose genomes will help answer important questions in molecular evolution (e.g. the [[chimpanzee|common chimpanzee]]). In the future, it is likely that it will become even cheaper and quicker to sequence a genome. This will allow for complete genome sequences to be determined from many different individuals of the same species. For humans, this will allow us to better understand aspects of [[Human Genome Diversity Project|human genetic diversity]]. --> ==Exemples de projets == [[Image:Drosophila melanogaster - side (aka).jpg|thumb|La [[Drosophila melanogaster|drosophile]], un des organismes supérieurs à voir son génome entier séquencé.]] [[Image:Zebrafisch.jpg|thumb|Le[[Zebra Danio|poisson zèbre]] , un autre [[organisme modèle]]]] [[Image:Pinot Gris close.JPG|thumb|Le ''[[International Grape Genome Program]]'' a pour but la maîtrise de la qualité des vins.]] De nombreux organismes sont le sujet de projet de séquençage de génome, déjà abouti ou sur le point de l'être: ===Invertébrés=== *L'oursin, ''[[Arbacia punctulata]]'' ; *Le vers [[nématode]] ''[[Caenorhabditis elegans]]''; *La [[drosophile]]; *L'abeille ''[[Apis mellifera]]''; ===Vertébrés=== *Le crapaud xénope, ''Xenopus laevis''; *Le poisson ''[[Oryzias latipes]]''; *Le poisson ''[[Fugu|Takifugu rubipres]]''; ====Mammifères==== *[[Humain]]s, ''Homo sapiens''; voir [[Projet génome humain]] abouti en 2003; *La [[souris]], ''Mus musculus''; *Le [[rat]], ''Rattus norvegicus''; *Le [[chimpanzé]] ''Pan troglodytes''; ; *Le [[Macaque rhésus]], ''Macaca mulatta''; *Le [[poulet]], ''Gallus gallus''; *Le [[chat]] domestique, ''Felis silvestris''; *L'ornithorynque [[Platypus]], ''Ornithorhynchus anatinus'' ===Plantes=== *L'arabette des dames ''[[Arabidopsis thaliana]]'', une [[organisme modèle|plante modèle]]; *Le riz ''[[Oryza sativa]]''; *Le blé, ''[[Triticum aestivum]]'; *Le maïs, ''[[Zea mays]]''; *Le peuplier, [[Populus trichocarpa]]; *La tomate ''Solanum lycopersicum''; *La patate ''Solanum tuberosum''; *La vigne, ''[[Vitis vinifera|Vitis vinifera L.]]''; ===Micro-organismes=== *''[[Haemophilus influenzae]]'', une bactérie (le premier mico-organisme non parasite à être séquencé); *La levure de boulanger ''[[Saccharomyces cerevisiae]]''; *La bactérie intestinale ''[[Escherichia coli]]''; *Le virus du [[SRAS]] ; *La moisissure ''[[Neurospora crassa]]''; ===Microbiome et Métagénome=== LE 11 janvier 2008, le [[National Institutes of Health]] lance dans le cadre du NIH Roadmap for Medical Research le [[:en:Human Microbiome Project]]. Le but de celui-ci est le séquençage, dans un délai de cinq ans, du [[génome]] d'un millier de [[microbiotes]] de l'homme et l'analyse de leurs rôles dans la [[santé]] et les maladies humaines<ref>[http://www.bulletins-electroniques.com/actualites/52538.htm Bulletin-electronique.com]</ref>. Le 11 avril 2008 est lancé le projet européen MetaHIT<ref>[http://www.metahit.eu/metahit/index.php?id=91 MetaHIT seventh framework programme]</ref>.Coordonné par l'[[INRA]], il a pour but d'étudier le [[génome]] de l'ensemble des [[bactéries]] constituant la [[flore intestinale]] humaine afin de caractériser ses fonctions et ses implications sur la [[santé]]<ref>[http://www.inra.fr/presse/sequencage_flore_intestinale_humaine_lancement_metahit INRA Séquençage de la flore intestinale humaine : lancement du projet européen MetaHIT coordonné par l'INRA]</ref>. ==Notes== <references /> ==Liens externes== * [http://www.bulletins-electroniques.com/actualites/52538.htm Bulletin-electronique.com Veille technologique internationale] * [http://bacterioblog.over-blog.com/article-5218606.html Le blog des bactéries et de l'évolution] {{portail biologie}} [[en:genome project]] [[nl:Genoomproject]] [[ja:ゲノムプロジェクト]] [[pt:Projeto Genoma]]