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. 2022 Feb 28;12(3):381.
doi: 10.3390/biom12030381.

IMGT®Homo sapiens IG and TR Loci, Gene Order, CNV and Haplotypes: New Concepts as a Paradigm for Jawed Vertebrates Genome Assemblies

Marie-Paule Lefranc  1 , Gérard Lefranc  1
Affiliations

IMGT®Homo sapiens IG and TR Loci, Gene Order, CNV and Haplotypes: New Concepts as a Paradigm for Jawed Vertebrates Genome Assemblies

Marie-Paule Lefranc et al. Biomolecules. .

Abstract

IMGT®, the international ImMunoGeneTics information system®, created in 1989, by Marie-Paule Lefranc (Université de Montpellier and CNRS), marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics for the study of the adaptive immune responses. IMGT® is based on a standardized nomenclature of the immunoglobulin (IG) and T cell receptor (TR) genes and alleles from fish to humans and on the IMGT unique numbering for the variable (V) and constant (C) domains of the immunoglobulin superfamily (IgSF) of vertebrates and invertebrates, and for the groove (G) domain of the major histocompatibility (MH) and MH superfamily (MhSF) proteins. IMGT® comprises 7 databases, 17 tools and more than 25,000 pages of web resources for sequences, genes and structures, based on the IMGT Scientific chart rules generated from the IMGT-ONTOLOGY axioms and concepts. IMGT® reference directories are used for the analysis of the NGS high-throughput expressed IG and TR repertoires (natural, synthetic and/or bioengineered) and for bridging sequences, two-dimensional (2D) and three-dimensional (3D) structures. This manuscript focuses on the IMGT®Homo sapiens IG and TR loci, gene order, copy number variation (CNV) and haplotypes new concepts, as a paradigm for jawed vertebrates genome assemblies.

Keywords: IMGT; T cell receptor (TR); antibody; bioengineering; copy number variation (CNV); haplotype; immunogenetics; immunoglobulin (IG); immunoinformatics; system biology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
IMGT®, the international ImMunoGenetics information system®, http://www.imgt.org (accessed on 22 February 2022) [1,5]. IMGT® comprises seven IMGT databases (shown as cylinders), seventeen online IMGT tools (shown as rectangles) and the IMGT Web resources (more than 25,000 pages, the ‘IMGT Marie-Paule page’) (not shown), for genes (in yellow), sequences (in green) and structures (in blue), all available from the IMGT® Home page. IMGT/mAb-DB has been online since 4 December 2009. IMGT/HighV-QUEST for next-generation sequencing (NGS) high-throughput sequence analysis, created in October 2010, has been available on the web since 22 November 2010. (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 22 February 2022).
Figure 2
Figure 2
Prototypes with IMGT standardized labels. (A) L-V-GENE-UNIT. This label describes gDNA of an IG or TR V-GENE unit, in germline configuration, that comprises L-PART1, V-INTRON, V-EXON and V-RS. (B) D-GENE-UNIT. This label describes gDNA of an IG or TR D-GENE unit, in germline configuration, that comprises 5′D-RS, D-REGION and 3′D-RS. (C) J-GENE-UNIT. This label describes gDNA of an IG or TR J-GENE unit, in germline configuration, that comprises 5′J-RS and J-REGION. Definitions of the IMGT standardized labels are available at https://www.imgt.org/ligmdb/label# (accessed on 22 February 2022). Abbreviations: L: leader, RS: recombination signal (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®).
Figure 3
Figure 3
Locus in genome assembly: Rhesus monkey (Macaca mulatta) IGL IMGT® http://www.imgt.org (accessed on 20 February 2022), IMGT Web resources > IMGT Repertoire (IG and TR) 1. Locus and genes. >3. Locus descriptions > Locus in genome assembly > IGL: Rhesus monkey http://www.imgt.org/IMGTrepertoire/index.php?section=LocusGenes&repertoire=locusAssembly&species=rhesus_monkey&group=IGL (accessed on 20 February 2022) Only the last annotated locus in genome assembly is shown in the figure, annotated loci of previous assemblies are available online on the right of the displayed locus. (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
Figure 4
Figure 4
IMGT/GENE-DB Localization in genome assemblies. (A) Query for Macaca mulatta|AG07107 (Species, AG07107 isolate) and IGH (Locus) showing the availability of IMGT/GENE-DB biocurated genes for the assembly ‘Mmul_10, NCBI’. (B) Top of the results page for the query. IMGT alleles of a given gene are defined by the number which follows the asterisk (i.e., *01) (With permission from M–P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
Figure 4
Figure 4
IMGT/GENE-DB Localization in genome assemblies. (A) Query for Macaca mulatta|AG07107 (Species, AG07107 isolate) and IGH (Locus) showing the availability of IMGT/GENE-DB biocurated genes for the assembly ‘Mmul_10, NCBI’. (B) Top of the results page for the query. IMGT alleles of a given gene are defined by the number which follows the asterisk (i.e., *01) (With permission from M–P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
Figure 5
Figure 5
Representation of the human IGH locus at 14q32.33 (REV orientation on the chromosome) [2,5]. The boxes representing the genes are not to scale. Exons are not shown. Switch sequences are represented by a filled circle upstream of the IGHC genes. Pseudogenes that could not be assigned to subgroups with functional genes are designated by a Roman numeral between parentheses, corresponding to the clans, followed by a hyphen, and a number for the localization from 3′ to 5′ in the locus [2]. IMGT® http://www.imgt.org (accessed on 20 February 2022), IMGT Repertoire (IG and TR) 1. Locus and genes > 2. Locus representations > IGH: Human (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
Figure 6
Figure 6
Haplotypes A to G of the Homo sapiens IGH CNV7 IGHC(203-211)9(7F,1OP,1P) of the IGH locus on chromosome 14 (14q32.33) [2,5]. The top line corresponds to haplotype A. The multigene deletions I to VI [142,143,144,145,146,147,148] correspond to the CNV7 haplotypes B to G (Table 4). (IMGT® http://www.imgt.org (accessed on 20 February 2022), IMGT Web resources > IMGT Repertoire (IG and TR) > 1. Locus and genes > 2. Locus representation > IGH: > Human IGHC multigene deletions in healthy individuals http://www.imgt.org/IMGTrepertoire/LocusGenes/locus/human/IGH/multigeneIGHC.html (accessed on 20 February 2022). (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
Figure 7
Figure 7
Representation of the human IGK locus at 2p12 (REV orientation on the chromosome) [2,5]. The boxes representing the genes are not to scale. Exons are not shown. The IGKV genes of the proximal V-CLUSTER are designated by a number for the subgroup, followed by a hyphen and a number for the localization from 3′ to 5′ in the locus. The IGKV genes of the distal duplicated V-CLUSTER are designated by the same numbers as the corresponding genes in the proximal V-CLUSTER, with the letter D added. Arrows show the IGKV genes polarity which is opposite to that of the J-C-CLUSTER [2]. IMGT® http://www.imgt.org (accessed on 20 February 2022), IMGT Repertoire (IG and TR) 1. Locus and genes > 2. Locus representations > IGK: Human (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
Figure 8
Figure 8
Representation of the human IGL locus at 22q11.2 (FWD orientation on the chromosome) [2,5]. The boxes representing the genes are not to scale. Exons are not shown. (A–C) refer to three distinct V-CLUSTER based on the IGLV gene subgroup content [149]. Pseudogenes that could not be assigned to subgroups with functional genes are designated by a Roman numeral between parentheses, corresponding to the clans, followed by a hyphen, and a number for the localization from 3′ to 5′ in the locus. IMGT® http://www.imgt.org (Accessed on 20 February 2022), IMGT Repertoire (IG and TR) 1. Locus and genes > 2. Locus representations > IGL: Human (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
Figure 9
Figure 9
Representation of the human TRB locus at 7q34 (FWD orientation on the chromosome). The boxes representing the genes are not to scale. Exons are not shown. The TRBV genes are designated by a number for the subgroup followed, whenever there are several genes belonging to the same subgroup, by a hyphen and a number for their relative localization in the locus. Numbers increase from 5′ to 3′ in the locus. T3 to T8 indicate trypsinogen or trypsinogen-like genes. T3 (PRSS3P3, TRY3) is at 7.4 kb upstream of TRBV1. Single arrows show genes whose polarity is opposite to that of the D-J-C-CLUSTER. Double arrows indicate insertion/deletion polymorphisms. IMGT® http://www.imgt.org (accessed on 20 February 2022), IMGT Repertoire (IG and TR) 1. Locus and genes > 2. Locus representations > TRB: Human (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
Figure 10
Figure 10
Representation of the human TRA locus at 14q11.2 (FWD orientation on the chromosome) [3]. The boxes representing the genes are not to scale. Exons are not shown. The TRAV genes are designated by a number for the subgroup, followed, whenever there are several genes belonging to the same subgroup, by a hyphen and a number for their relative localization in the locus. Numbers increase from 5′ to 3′ in the locus. The TRD genes are nestled in the TRA locus [3]. IMGT® http://www.imgt.org (accessed on 20 February 2020), IMGT Repertoire (IG and TR) 1. Locus and genes > 2. Locus representations > TRA: Human (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2020).
Figure 11
Figure 11
Representation of the human TRG locus at 7p14 (REV orientation on the chromosome) [3]. The boxes representing the genes are not to scale. Exons are not shown. A double arrow indicates an insertion/deletion polymorphism. The TRGV3P gene, a polymorphic gene by insertion has been identified by Southern hybridization in a rare haplotype but has not been sequenced. IMGT® http://www.imgt.org (accessed on 20 February 2022), IMGT Repertoire (IG and TR) 1. Locus and genes > 2. Locus representations > TRG: Human (With permission from M-P. Lefranc and G. Lefranc, LIGM, Founders and Authors of IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org) (accessed on 20 February 2022).
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References

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