Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences genetics epigenetics
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
CB2 4AT CAMBRIDGE
United Kingdom
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