Objetivo First, I propose to identify all imprinted loci in humans. I will perform a whole-genome screen using high-density oligonucleotide microarrays coupled with immunoprecipitation of methylated DNA to compare the methylation patterns in rare uniparental tissues. I have obtained samples from complete hydatidiform moles, which have an exclusively paternal genetic contribution, and ovarian teratomas, which have an exclusively maternal genetic contribution. I demonstrate that the study of genomic methylation in these two tissues enables the direct comparison of a maternally methylated genome versus a paternally methylated genome, representing an optimized system for the detection of novel imprinted loci. Second, I will use this imprinting map to perform a preliminary investigation of the role of epigenetic defects in disorders of human development. I hypothesise that the study of genomic methylation patterns in connection with human disease represents a rich and largely untapped area of genetic research. I will investigate methylation patterns in a cohort of monozygotic twins who show discordant developmental phenotypes. As monozygotic twins are genetically identical, the study of twin pairs who present with phenotypic differences represents a highly sensitized population for the identification of epigenetic errors associated with human disease. This proposal harnesses a new generation of high-density oligonucleotide arrays which allow for the first time the entire human genome to be investigated at the necessary resolution to systematically uncover novel imprinted genes. The proposal will give ample opportunity to acquire new experimental, theoretical and computational knowledge, and also to develop the novel research area of ‘Methylomics’ in human genetics. Ámbito científico natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesbasic medicinemedical geneticsnatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Palabras clave Epigenetics Genome Imprinting Methylation Microarray Programa(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Convocatoria de propuestas FP7-PEOPLE-2007-2-1-IEF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IEF - Intra-European Fellowships (IEF) Coordinador UNIVERSITE DE GENEVE Aportación de la UE € 259 642,64 Dirección RUE DU GENERAL DUFOUR 24 1211 Geneve Suiza Ver en el mapa Región Schweiz/Suisse/Svizzera Région lémanique Genève Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Stylianos Antonarakis (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
