Objective
The overall aim of this proposal is to understand how individual genetic and epigenetic variation in the Major Histocompatibility Complex (MHC) on chromosome 6p21 may determine susceptibility to autoimmune, infectious and inflammatory disease. The human MHC is a paradigm for genomics, showing remarkable polymorphism and striking association with disease, but causal genetic variants remain largely unresolved. The identification of specific disease risk variants is particularly challenging in the MHC due to the extent of genetic diversity now recognised, the complexity of coinheritance between genetic markers and the difficulty of resolving specific regulatory variants modulating gene expression. We have previously established the importance of allele-specific gene expression in the MHC at specific loci including the TNF, HSP70 and HLA-DRB1 genes. We now propose a comprehensive global analysis for the MHC addressing the following specific objectives: (1) to define allele-specific transcription across the classical MHC for disease associated haplotypes in specific peripheral blood cells using RNA sequencing; (2) to compliment this by identifying allelic differences in gene regulation at the level of chromatin structure and histone modifications; (3) to resolve DNA sequence variants associated with differences in MHC gene expression by quantitative trait mapping in healthy volunteers; (4) to investigate the extent and consequences of allele-specific DNA methylation in the MHC; (5) to functionally characterise specific gene loci showing evidence of allele-specific gene expression in the context of reported disease associations. The proposal is scientifically ambitious, using cutting edge genomic technologies to address in innovative ways a major roadblock in this field of scientific research. The work is of significant translational importance as we apply genomic medicine to improve care for the individual patient and advance our understanding of disease pathogenesis.
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.
- medical and health sciences health sciences inflammatory diseases
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences biological sciences genetics chromosomes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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.
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.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2011-StG_20101109
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Funding Scheme
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.
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.
Host institution
OX1 2JD Oxford
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.