Objective
Idiopathic haemochromatosis, an autosomal recessive disorder of iron metabolism, is one of the most common genetic diseases in Europe. It is characterised by excessive iron absorption through the duodenal mucosa and progressive iron deposition in parenchymal organs, which results in the midlife onset of severe clinical complications, including cirrhosis, diabetes mellitus, cardiopathy, endocrine dysfunctions, and arthropathy. Patients who undergo early diagnosis and phlebotomy treatment before the development of organ damage have a normal life expectancy in contrast to those individuals who remain undiagnosed. A significant proportion of those latter individuals will indeed succumb to hepatocellular carcinoma or cardiac failure. The nature of the underlying defect is still unknown. HLA typing studies have shown an association between haemochromatosis and the HLA-A3 antigen. Subsequent analysis of affected pedigrees has demonstrated linkage between the putative haemochromatosis gene and HLA-class I genes on chromosome 6p. There is however no evidence that the gene lies close to HLA-A: recent work has suggested that allele 8 of the marker D6S105, subsequently mapped approximately 2000 kb telomeric to HLA-A, was a better marker for the disease than HLA-A3. Linkage disequilibrium data from Cardiff suggest that the gene may even lie telomeric to D6S105. With respect to physically localising the gene, investigators must still content with a candidate gene region spanning a total physical distance of at least 2000 kb.
The objectives of the proposed work are: i) to narrow the size of the haemochromatosis candidate region on chromosome 6p to about 200 kb by isolating and physically mapping microsatellite markers spanning the region between MOG and D6S105 (and beyond if necessary), producing high resolution haplotypes across the disease locus for linkage disequilibrium mapping, ascertaining significant chromosomal abnormalities such as deletions or insertions in patients, as well as recombination events in families with multiple affected individuals; ii) to identify the gene responsible for haemochromatosis in this narrowed region by creating a contig of cosmids, identifying coding sequences by exon trapping, cDNA selection, and/or zoo blot, characterising the genomic structure of candidate genes and carrying out mutation analyses in patients.
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 clinical medicine endocrinology diabetes
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine hepatology
- natural sciences biological sciences genetics chromosomes
You need to log in or register to use this function
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.
Data not available
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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.
Coordinator
31300 Toulouse
France
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.