Demaille Jacques.
2002. What comes next after the genome sequencing.
In : Second international symposium on Candidate Genes for Animal Health (C.G.A.H), Montpellier, France, August 16-18th 2002 : abstracts. CIRAD, INRA
Note générale : Session 1 : Present and future strategies and tools of the candidate gene approach
Résumé : The almost complete nucleotide sequence of several eukaryotic genomes is now available, including yeast, worm, fly and man, as well as a plant Arabidopsis thaliana, and adding to the knowledge gained from around sixty bacterial genomes, Archaea and Eubacteria. From this vast amount of raw information, general conclusions can be drawn: firstly, the complexity of a higher organism is not directly related to the number of genes found in its genome; for instance, the human genes are probably less than twice as numerous as the genes of the nematode made of less than one thousand cells. Secondly, alternative splicing is common in higher organisms, affecting a good half of the genes and giving rise to several gene products per gene that are tissue specific. Thirdly, roughly half of the genes are of unknown function, even within the limited number of eukaryotic orthologous genes, common for instance to man, fly and worm, and likely to belong to the cell basic machinery. Describing the function of all gene products is now the challenge of the post-sequencing era; presently, the function of a protein is not semantically well defined: the function may be molecular (enzymes are often defined this way), or derived from a phenotype (oncogenes cause cancer) or from a subcellular localization (nucleolin resides in the nucleole), hence the huge eforts carried out these days to define gene ontologies. More and more, biologists tend to talk about contextual function, that is to say all the interactions of the protein of interest with all other cell components, whether the interactions are physical (such as in a particle like the spliceosome) or only functional (metabolic pathways). This is of course a huge task, for which in silico methods can be used, such as the Rosetta stone, the phylogenetic profiles, or the chromosomal colocalizations, adding to experimental techniques, such as the mRNA coexpression observed for instance from microarrays experiments. When two of these tools are in agreement, confidence can be good that the two proteins have a functional interaction, resulting in the progressive building of the complex network of interactions within the living cell. The main avenues of research are now well visible, and they use techniques that are miniaturized, robotized and parallelized. The first one is the rapid expansion of the proteomics field which takes advantage of remarkable progress of mass spectrometry. The second one is the massive structural resolution of recombinant proteins, purified and crystallized on a micro scale, analyzed by synchrotron diffraction, and their structure solved with more and more powerful computation. Finally, frequent diseases benefit from a better knowledge of the genome polymorphisms (single nucleotide polymorphisms as well as microsatellites) in large studies similar to the one performed in Iceland by linking databases concerning the pedigrees of the whole population, the medical records, and the relative genotypes. These are the new avenues to drug discovery. (Texte intégral)
Mots-clés Agrovoc : génétique moléculaire, gène, génome, Arabidopsis thaliana
Mots-clés complémentaires : Séquencage
Classification Agris : L10 - Génétique et amélioration des animaux
Auteurs et affiliations
- Demaille Jacques, IGH (FRA)
Autres liens de la publication
Source : Cirad - Agritrop (https://agritrop.cirad.fr/512003/)
[ Page générée et mise en cache le 2024-01-28 ]
