Cel Epigenetic control of gene expression by DNA methylation and chromatin mechanisms plays a crucial role in normal development, genetic disease, and cancer. It is therefore important to identify genetic factors that control methylation and chromatin structure, as these factors are likely to contribute to cancer susceptibility and to predisposition and expression of many genetic diseases, and are likely to play an important role in multifactorial causes of disease. The centres that are involved in this proposed Epigenetics Network have previously developed transgenic model systems in the mouse that show variable transgene expression and repression associated with DNA methylation and chromatin compaction which is controlled by genotype-specific modifier genes in the genome. Here it is proposed to use three different transgenic systems as well as endogenous gene targets of epigenetic control, to genetically characterise and map modifier genes which are responsible for this variable expression and methylation. The genetic fine mapping of these modifier genes will eventually lead to their isolation by positional cloning. The developmental and lineage-specific action of modifier genes will be analyzed, and embryonic stem (ES) cells will be isolated that carry transgenic targets. This will eventually establish a test system for candidate modifier genes. The sequence targets of modifier action will be defined using the already established transgenic mouse strains. Endogenous target sequences of modifier action will be isolated using RDA (Representational Difference Analysis). Mapping and characterisation of modifier genes will lead to a better understanding of the epigenetic mechanisms of gene regulation. Since these genes are likely to play a major role in multifactorial diseases that are characterised by variable expressivity, they are strong candidates for `risk alleles' in a number of genetic diseases and cancers. This research will therefore make an important future contribution to the molecular diagnosis, predictive testing and genetic counselling in a potentially large number of genetic disorders. Dziedzina nauki natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Program(-y) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Temat(-y) 5.2 - Analysis of gene function and interaction Zaproszenie do składania wniosków Data not available System finansowania CSC - Cost-sharing contracts Koordynator THE BABRAHAM INSTITUTE Wkład UE Brak danych Adres Babraham Hall CB2 4AT CAMBRIDGE Zjednoczone Królestwo Zobacz na mapie Koszt całkowity Brak danych Uczestnicy (3) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko CENTRE HOSPITALIER UNIVERSITAIRE DE NANTES Francja Wkład UE Brak danych Adres Boulevard Jean Monnet 30 44035 NANTES Zobacz na mapie Koszt całkowity Brak danych Max-Planck-Gesellschaft zur Förderungder Wissenschaften e.V. Niemcy Wkład UE Brak danych Adres 73,Ihnestrasse 14195 Berlin Zobacz na mapie Koszt całkowity Brak danych Universität Köln Niemcy Wkład UE Brak danych Adres 121,Weyertal 50931 Köln Zobacz na mapie Koszt całkowity Brak danych