Résumé :
|
The development of new genotype based therapeutic approaches has reinforced the interest about Locus Specific Databases (LSDB). This field is a crossroad of bioinformatics, genetics, clinics and research and many initiatives have been developed worldwide. After almost 15 years, it has now come to maturity thanks to the efforts of the Human Genome Variation Society that played a major role to organize and define standards such as the international nomenclature of mutations, and recommendations. Despite these efforts there is still heterogeneity between LSDB ranging from simple flat files accessible through the web to the most advanced models that integrate many analysis tools. These later are known as knowledgebases because the user can not only extract information (mutations, phenotypes…) but can also extract knowledge from the data. Thus the UMD® generic tool available to set-up such knowledgebases was recently chosen to build patient's registries at the European level by the TREAT-NMD network. This initiative has rapidly been joined by many other countries and supported by patients' organizations. It has led to a major change in the LSDB field. Because updated phenotypic information have to be collected and updated, the IRB approval as well as the patient's written consent have to be obtained. A global network has been established to transfer data from national LSDB into the global registries (one per gene) that will be accessible to the public, the partners and the industry. It will thus be useful to: 1) rapidly evaluate therapeutic approaches; 2) select a cohort of patients for clinical trials; 3) validate therapeutic hypothesis and, because it is a knowledgebase system, make predictions to facilitate the design of new therapeutic approaches. This option has been used for the exon-skipping approach in various diseases (prediction of the best multi-skipping approach based on patients' phenotypes, best targets for AONs…) 1)INSERM U827, Montpellier, F-34000 France, 2) CHU Montpellier, Laboratoire de Génétique Moléculaire, Montpellier, F-34000 France, 3) Université Montpellier 1, UFR Médecine, Montpellier, F-34000 France
|