IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc, Laboratoire d'ImmunoGénétique Moléculaire LIGM (Université Montpellier 2 and CNRS) at Montpellier, France, in order to standardize and manage the complexity of immunogenetics data. The building of a unique ontology, IMGT-ONTOLOGY, has made IMGT® the global reference in immunogenetics and immunoinformatics. IMGT® is a high-quality integrated knowledge resource specialized in the immunoglobulins or antibodies, T cell receptors, major histocompatibility complex, of human and other vertebrate species, proteins of the IgSF and MhcSF, and related proteins of the immune systems of any species. IMGT® provides a common access to standardized data from genome, proteome, genetics and 3D structures. IMGT® consists of five databases (IMGT/LIGM-DB, IMGT/GENE-DB, IMGT/3Dstructure-DB, etc.), fifteen interactive online tools for sequence, genome and 3D structure analysis, and more than 10 000 HTML pages of synthesis and knowledge. IMGT® is used in medical research (autoimmune diseases, infectious diseases, AIDS, leukemias, lymphomas and myelomas), veterinary research, biotechnology related to antibody engineering (phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (clonalities, detection and follow-up of residual diseases) and therapeutical approaches (graft, immunotherapy, vaccinology). IMGT is freely available at http://www.imgt.org.
Background: Adaptative immune repertoire diversity in vertebrate species is generated by recombination of variable (V), diversity (D) and joining (J) genes in the immunoglobulin (IG) loci of B lymphocytes and in the T cell receptor (TR) loci of T lymphocytes. These V-J and V-D-J gene rearrangements at the DNA level involve recombination signal sequences (RSS). Whereas many data exist, they are scattered in non specialized resources with different nomenclatures (eg. flat files) and are difficult to extract.Description: IMGT/GeneInfo is an online information system that provides, through a user-friendly interface, exhaustive information resulting from the complex mechanisms of T cell receptor V-J and V-D-J recombinations. T cells comprise two populations which express the αβ and γδ TR, respectively. The first version of the system dealt with the Homo sapiens and Mus musculus TRA and TRB loci whose gene rearrangements allow the synthesis of the αβ TR chains. In this paper, we present the second version of IMGT/GeneInfo where we complete the database for the Homo sapiens and Mus musculus TRG and TRD loci along with the introduction of a quality control procedure for existing and new data. We also include new functionalities to the four loci analysis, giving, to date, a very informative tool which allows to work on V(D)J genes of all TR loci in both human and mouse species. IMGT/GeneInfo provides more than 59,000 rearrangement combinations with a full gene description which is freely available at http://imgt.cines.fr/ GeneInfo. Conclusion:IMGT/GeneInfo allows all TR information sequences to be in the same spot, and are now available within two computer-mouse clicks. This is useful for biologists and bioinformaticians for the study of T lymphocyte V(D)J gene rearrangements and their applications in immune response analysis.
The cDNA sequences of immunoglobulins (IG) and T cell receptors (TR) represent more than one half of the sequences in the IMGT^®^ nucleotide database IMGT/LIGM-DB^1^ and 75% of them are from human and mouse. A few cDNA are germline but the great majority results from a V-D-J or V-J gene rearrangement, spliced to a C gene. The IG and TR genes have been studied extensively in IMGT^®^ ("http://www.imgt.org":http://www.imgt.org) ^2^, which allowed to set up their nomenclature and the corresponding germline reference sequences. These standardized reference directory sets (one for each group of each locus) and the IMGT-ONTOLOGY axioms and derived concepts^3^ are the key elements indispensable to perform the annotation of IG and TR cDNA sequences. A Java program, IMGT/Automat^4^, was developed by IMGT^®^, to automatically annotate the IG and TR cDNA sequences and to produce a totally automatic and complete annotation. More than 9,000 human and mouse cDNA have already been successfully automatically annotated. The quality of the cDNA automatic annotation is equivalent to the quality of the annotation achieved by a human expert. The IMGT^®^ strategy is currently the only way, in the field of immunogenetics, to guarantee the annotation quality and the management of an always increasing number of IG and TR cDNA nucleotide sequences.
The immunoglobulin (IG) and T cell receptor (TR) major loci span about 6 Megabases (Mb) of the human genome on chromosomes 2, 7, 14 and 22, and 9 Mb in mouse on chromosomes 6, 12, 13, 14 and 16. There are seven major loci: three IG loci (IGH, IGK, IGL) and four TR loci (TRA, TRB, TRG, TRD), with a distinct repartition of the variable (V), diversity (D), joining (J) and constant (C) genes. The human genome comprises a total number of 608-665 IG and TR genes (371-422 IG and 237-243 TR), depending on the haplotypes, per haploid genome ^1, 2^ of which 531-588 genes are located in the major loci (distributed in 369-418 V, 32 D, 105-109 J and 25-29 C genes). There are also 77 orphons (68 IG and 9 TR) including two processed IG genes, outside the major loci. The number of functional IG and TR genes is 308-356 (136-171 IG and 172-185 TR) per haploid genome. The mouse genome comprises an approximate number of 876 IG and TR genes (624 IG and 252 TR). All these genomic data are available in the IMGT® gene database, IMGT/GENE-DB ^3^. The major contribution of IMGT/GENE-DB has been to establish, for the first time, a standardized nomenclature of the IG and TR genes and alleles of humans and other vertebrates. In April 2009, IMGT/GENE-DB manages 1999 genes and 3026 alleles. [1] Lefranc M.-P. and Lefranc G., The Immunoglobulin FactsBook, Academic Press, London, 458 pages (2001).[2] Lefranc M.-P. and Lefranc G., The T cell receptor FactsBook, Academic Press, London, 398 pages (2001).[3] Giudicelli V. et al. Nucleic Acids Res., 33, D256-261 (2005).
IMGT/LIGM-DB^1^ is the first and the largest IMGT^®^ database^2^ in which are managed, analysed and annotated more than 136,000 immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences from human and 235 other vertebrate species (April 2009). The expert annotation of these sequences and the added standardized knowledge are based on IMGT-ONTOLOGY, the first ontology developed in the field of immunogenetics and immunoinformatics.^3^ The annotation of immunogenetic sequences requires important expertise, owing to the unusual structure (non-classical exon/intron structure) of the IG and TR genes and characteristic chain synthesis owing to DNA V-J and V-D-J rearrangements. The way to annotate these sequences depends on the molecular type (gDNA, mRNA, cDNA or protein) and the configuration type (germline or rearranged), and if sequences from the concerned species are present or not in the IMGT reference directory sets. IMGT/V-QUEST^5^ and internal tools (IMGT/Automat, IMGT/LIGMotif, IMGT/BLAST and IMGT/DomainGapAlign) were developed. The first step in annotation allows to identify the chain type (for instance IG-Heavy) and to assign standardized keywords (IDENTIFICATION axiom). The second step is the classification of IG and TR genes and alleles (CLASSIFICATION axiom). The third step is the description (DESCRIPTION axiom) of the V, D, J and C genes and alleles with specific standardized labels. There are more than 590 IMGT standardized labels from which 64 have been entered in Sequence Ontology (SO). The delimitation of the FR-IMGT and CDR-IMGT lengths and the positions of conserved amino acids based on the IMGT unique numbering (NUMEROTATION axiom) allow to bridge the gap between sequences and 3D structures.^6^ The complete annotation of immunogenetic germline (V, D, J) and C sequences is followed by the update of the IMGT Repertoire (IMGT Gene tables, Alignments of alleles, Protein displays, Colliers de Perles, etc.), IMGT® gene database (IMGT/GENE-DB) and IMGT reference directory sets of the IMGT® tools (IMGT/V-QUEST, IMGT/JunctionAnalysis and IMGT/DomainGapAlign).
The immunoglobulin (IG) and T cell receptor (TR) major loci span about 6 Megabases (Mb) of the human genome on chromosomes 2, 7, 14 and 22, and 9 Mb in mouse on chromosomes 6, 12, 13, 14 and 16. There are seven major loci: three IG loci (IGH, IGK, IGL) and four TR loci (TRA, TRB, TRG, TRD), with a distinct repartition of the variable (V), diversity (D), joining (J) and constant (C) genes. The human genome comprises a total number of , depending on the haplotypes, per haploid genome [1, 2] of which 531-588 genes are located in the major loci (distributed in 369-418 V, 32 D, 105-109 J and 25-29 C genes). There are also 77 orphons (68 IG and 9 TR) including two processed IG genes, outside the major loci. The number of functional IG and TR genes is 5-4 6-6 7-5 5-5 6-7 7-6 5-6 6-8 7-7 5-7 6-9 7-8 5-8 7-9 13 10-3 IMGT/GENE-DB entry for Mus musculus IGHV1-58Genomic The human genome comprises 371-422 IG genes (303-354 genes located in the 3 major IG loci and 68 orphons), per haploid genome.The functional IG genes (136-171 depending on the haplotypes) are located in the 3 major IG loci. Different molecular mechanisms (V-J and V-D-J rearrangements, N-diversity, and for IG, somatic hypermutations), unique to vertebrates, allow to create a huge repertoire of 2x10 12 IG (or antibodies) per individual.The human genome comprises 237-243 TR genes (228-234 genes located in the 4 major TR loci and 9 orphons), per haploid genome.The functional TR genes (172-185 depending on the haplotypes) are located in the 4 major TR loci. Different molecular mechanisms (V-J and V-D-J rearrangements, N-diversity), unique to vertebrates, allow to create a huge repertoire of 2x10 12 TR per individual.
Information system®IMGT/LIGM-DB [1] is the first and the largest IMGT® database [2] in which are managed, analysed and annotated more than 136,000 immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences from human and 235 other vertebrate species (April 2009). The expert annotation of these sequences and the added standardized knowledge are based on IMGT-ONTOLOGY, the first ontology developed in the field of immunogenetics and immunoinformatics [3]. The annotation of immunogenetic sequences requires important expertise, owing to the unusual structure (non-classical exon/intron structure) of the IG and TR genes and characteristic chain synthesis owing to DNA V-J and V-D-J rearrangements. The way to annotate these sequences depends on the molecular type (gDNA, mRNA, cDNA or protein) and the configuration type (germline or rearranged), and if sequences from the concerned species are present or not in the IMGT reference directory sets. IMGT/V-QUEST [5] and internal tools (IMGT/Automat, IMGT/LIGMotif, IMGT/BLAST and IMGT/DomainGapAlign) were developed. The first step in annotation allows to identify the chain type (for instance IG-Heavy) and to assign standardized keywords (IDENTIFICATION axiom). The second step is the classification of IG and TR genes and alleles (CLASSIFICATION axiom). The third step is the description (DESCRIPTION axiom) of the V, D, J and C genes and alleles with specific standardized labels. There are more than 590 IMGT standardized labels from which 64 have been entered in Sequence Ontology (SO). The delimitation of the FR-IMGT and CDR-IMGT lengths and the positions of conserved amino acids based on the IMGT unique numbering (NUMEROTATION axiom) allow to bridge the gap between sequences and 3D structures [6]. The complete annotation of immunogenetic germline (V, D, J) and C sequences is followed by the update of the IMGT Repertoire (IMGT Gene tables, Alignments of alleles, Protein displays, Colliers de Perles, etc.), IMGT® gene database (IMGT/GENE-DB) and IMGT reference directory sets of the IMGT® tools (IMGT/V-QUEST, IMGT/JunctionAnalysis and IMGT/DomainGapAlign). The NUMEROTATION axiom and the concepts of numerotation determine the principles of a unique numbering for a domain (sequences and 3D structures). The "IMGT_unique_numbering" concept is illustrated by the "IMGT_Collier_de_Perles" concept which allows graphical representation in two dimensions (2D) The NUMEROTATION axiom 4The CLASSIFICATION axiom generates the concepts of classification, they allow to classify and name the genes and their alleles. The genes which code the IG and TR belong to highly polymorphic multigenic families. A major contribution of IMGT-ONTOLOGY was to set the principles of their classification and to propose a standardized nomenclature [1,2]. IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org) is based on IMGT-ONTOLOGY, the first ontology for immunogenetics and immunoinformatics [1]. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets that rely on ...
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