Objectif
The aim of this program is to draw a detailed physical and genetic map of the major histocompatibility complex (MHC) located on the human genome in 6p21-23.
A detailed physical map and genetic map of the major histocompatibility complex (MHC) located on the human genome in 6p21-23 is being constructed. The human MHC is a chromosomal region of about 5000 kilobases (kb). 3 subregions can be distinguished: the class I region encodes the transplantation antigens; the class II region encodes products which are also implicated in immunological responses; the class III region codes for proteins of the complement cascade. Other genes are present within this region such as 21 OH, TNF and numerous other genes many of which were discovered during this study.
Substantial results were obtained corresponding to the preparation of a whole battery of reagents and probes which enabled the establishment of a physical and genetic map of the region to be pursued. The map is not yet complete.
In addition, several genes worth recalling were identified and more or less characterized such as:
RING 3, which is related to the Drosophila gene female sterile homeotic;
DM only distantly related to other class III products;
ABC transporter of TAPS and the proteasome component;
a gene sharing a substantial homology with SUP 45, a gene previously identified in yeast (this new gene has been identified and located in the class I regions);
several genes whose chromosomal deoxyribonucleic acid (cDNA) map to the class I region were also identified and sequenced (one of them corresponds to a gene previously identified in yeast and call SUP 45 and it appears very interesting and promising).
Important work still needs to be done before a complete knowledge of this very important region is gained.
The human MHC is a chromosomal region of about 5000 kb. Three sub-regions can be distinguished: the class I region encodes the transplantation antigens; the class II region encodes products which are also implicated in immunological responses; the class III region codes for proteins of the complement cascade. Other genes are present within this region such as 21 OH, TNF and numerous other genes many of which were discovered during this study.
The study of the MHC region has been chosen among many other regions of the human genome in view of:
1. its biological importance;
2. the availability of very good genetic studies of two multigenic families (important for studying the contraction-expansion phenomenon);
3. gene clustering with products implicated in different immunological processes, and with sometimes similarity in their regulation pathway (TNF and HLA-B) offers a good opportunity to understand the gene clustering within the genome (chromatin structure for example);
4. several associated diseases.
The genomic organization of the MHC region can be summarized as follows. Genes of class I are the more telomeric, genes of class II are centromeric, whereas genes of class III are in between. It is presently still difficult to give the exact number of genes encoded in this region and such knowledge will probably await complete sequencing of the whole region, since in addition to having many genes, the region also encodes many pseudogenes and genes with a high level of sequence analogy, which makes calculation through hybridization data more questionable. In fact, this sequencing strategy is one of the purposes of the following program.
The present study, which lasted two years, was initiated at the end of February 1992 and was split between seven laboratories. Three laboratories, those of Campbell-Papamatheakis and Trowsdale, are mainly working on the region encompassing class II and III genes, those of Galibert, Le Gall and Pontarotti on the region containing class I genes. Philippe Brulet, who has a large expertise in ES cells and homologous recombination, makes use of DNA fragments mapped by other contractants to search for the function of newly identified genes.
Champ scientifique (EuroSciVoc)
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CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN. Voir: Le vocabulaire scientifique européen.
- sciences naturelles sciences biologiques génétique ADN
- sciences naturelles sciences biologiques biochimie biomolécule protéines
- sciences médicales et de la santé médecine clinique transplantation
- sciences naturelles sciences biologiques génétique chromosome
- sciences naturelles sciences biologiques génétique génome
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35043 Rennes
France
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