Atlas of Genetics and Cytogenetics in Oncology and Haematology

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IGH (Immunoglobulin Heavy)

Identity

HGNC (Hugo) IGH@
Location 14q32.33
Location_base_pair Starts at 105180450 and ends at 105997769 bp from pter ( according to hg18-Mar_2006)
 
  for complete Figure, see: chromosome 14, IMGT (The International ImMunoGeneTics information system ®) © Copyright 1995-2003 IMGT, IMGT is a CNRS trademark
Note The human IGH locus is located on the chromosome 14 at band 14q32.33, at the telomeric extremity of the long arm; the orientation of the locus has been determined by the analysis of translocations, involving the IGH locus, in leukemia and lymphoma

DNA/RNA

 
  IGH
V-GENE: Green box: Functional; Yellow box: Open reading frame; Red: Pseudogene; Grey triangle: Not sequenced, not found.
D-GENE: Blue: Functional; Blue open box: Open reading frame.
J-GENE: Grey: Functional .
C-GENE: Blue: Functional; Blue dashed box: Open reading frame; Blue open box: Pseudogene.
GENES NOT RELATED: Purple open box: Pseudogene.
for compete Figure, see: locus IGH, IMGT (The International ImMunoGeneTics information system ®) © Copyright 1995-2003 IMGT, IMGT is a CNRS trademark
Description
  • The human IGH locus at 14q32.33 spans 1250 kilobases (kb). It consists of 123 to 129 IGHV genes, depending from the haplotypes, 27 IGHD segments belonging to 7 subgroups, 9 IGHJ segments, and 11 IGHC genes.
  • Eighty-two to 88 IGHV genes belong to 7 subgroups, whereas 41 pseudogenes, which are too divergent to be assigned to subgroups, have been assigned to 4 clans. Seven non-mapped IGHV genes have been described as insertion/deletion polymorphism but have not yet been precisely located.
  • The most 5' IGHV genes occupy a position very close to the chromosome 14q telomere whereas the IGHC genes are in a more centromeric position.
  • The potentiel genomic IGH repertoire is more limited since it comprises 38-46 functional IGHV genes belonging to 6 or 7 subgroups depending from the haplotypes 23 IGHD, 6 IGHJ, and 9 IGHC genes.
  • Thirty-five IGH genes have been found outside the main locus in other chromosomal localizations. These genes designated as orphons cannot contribute to the synthesis of the immunoglobulin chains, even if they have an Open Reading Frame (ORF). 9 IGHV orphons and 10 IGHD orphons have been described on chromosome 15 (15q11.2), and 16 IGHV orphons on chromosome 16 (16p11.2). In addition, one IGHC processed gene, IGHEP2 is localised on chromosome 9 (9p24.2-p24.1)
  • This is so far the only processed Ig gene described. The total number of human IGH genes per haploid genome is 170 to 176 (206 to 212 genes, if the orphons and the processed gene are included) of which 77 to 84 genes are functional. List of the human IGH genes

    • Protein

    Description
  • Proteins encoded by the IGH locus are the immunoglobulin heavy chains. They result from the recombination (or rearrangement), at the DNA level, of three genes: IGHV, IGHD and IGHJ, with deletion of the intermediary DNA to create a rearranged IGHV-D-J gene.
  • The rearranged IGHV-D-J gene is transcribed with the IGHM gene and translated into an immunoglobulin mu chain. The gamma, alpha or epsilon heavy chains, result from a new recombination (or switch), again at the DNA level, between sequences designated as "Switch" and localized upstream of the IGHM and of each of the functional IGHG, IGHA and IGHE constant genes.
  • This recombination, accompanied by the deletion of the intermediary DNA, allows the IGHV-D-J initially transcribed with the IGHM, to be now transcribed with a IGHG, IGHA or IGHE gene, and translated into a gamma, alpha or epsilon chain.
  • Translation of the variable germline genes involved in the IGHV-D-J rearrangements are available at IMGT Repertoire Protein displays. Compared to the germline genes, the rearranged variable genes will acquire somatic mutations during the B cell differentiation in the lymph nodes, which will considerably increase their diversity. These somatic mutations can be analysed using IMGT/V-QUEST tool

    • Mutations

    Note Mutations which correspond to allelic polymorphisms of the functional germline IGHV, IGHD, IGHJ and IGHC genes are described in the IMGT database: (IMGT Repertoire>Alignments of alleles)

    Implicated in

    Entity Translocations which frequently result from errors of the recombinase enzyme complexe (RAG1, RAG2, etc.), responsable of the Immunoglobulin and T cell receptor V-J and V-D-J rearrangements, or from errors of the switch enzyme. IGHV, IGHD or IGHJ recombination signals or isolated heptamer (first case) or switch sequences (second case) are observed at the breakpoints
     
    c-Immunoglobulin genes IgH at 14q32.33, in normal cells: PAC 998D24 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are wellcome: contact M Rocchi
      
    Entity t(1;14)(p21;q32); involve BCL10 in 1p21
    Disease marginal zone B-cell lymphoma
      
    Entity t(3;14)(q27;q32); involve BCL6 in 3q27
    Disease B-cell non-Hodgkin lymphomas (NHL), mainly diffuse large cell lymphoma; adult aggressive lymphoma
    Prognosis controversial
      
    Entity t(4;14)(p16;q32); involve FGFR3 in 4p16
    Disease plasma cell leukaemia and multiple myeloma
    Prognosis yet poorly described
      
    Entity t(5;14)(q31;q32); involve IL3 in 5q31
    Disease B-cell acute lymphoblastic leukemia (ALL) with hypereosinophilia
    Prognosis prognosis appears to be poor
      
    Entity t(8;14)(q11;q32)
    Disease B-cell acute lymphoblastic leukemia (ALL); chronic myelogenous leukemia (CML)
    Prognosis still unknown
      
    Entity t(8;14)(q24;q32) ; involve C-MYC in 8q24
    Disease B-cell acute lymphoblastic leukemia (ALL3) and non-Hodgkin lymphomas (NHL), especially in the Burkitt lymphoma
    Prognosis the prognosis has evolved with new treatments
      
    Entity t(9;14)(p13;q32); involve PAX5 in 9p13
    Disease lymphoplasmatic lymphoma
      
    Entity t(10;14)(q24;q32); involve HOX 11 in 10q24
    Disease B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL)
    Prognosis not unfavourable
      
    Entity t(11;14)(q13;q32); involve BCL1 in 11q13
    Disease t(11;14) is mainly found in mantle cell lymphoma; B-prolymphocytic leukaemia, chronic lymphocytic leukaemia, splenic lymphoma with villous lymphocytes , and multiple myeloma other B-cell lymphoproliferations
      
    Entity t(14;18)(q32;q21); involve BCL2 in 18q21
    Disease follicle centre cell lymphoma mainly, and also diffuse large cell lyphoma; rarely in other B-cell lymphoproliferations
    Prognosis the t(14;18) may have little or no prognostic significance
      
    Entity t(14;19)(q32;q13.1); involve BCL3 in 19q13
    Disease chronic lymphocytic leukaemia (CLL) mainly, and other B-cell lymphoproliferations
    Prognosis t(14;19) is an adverse prognostic factor in CLL, compared to the usual prognosis in CLL
      

    Breakpoints

     

    External links

    Nomenclature
    HGNC (Hugo)IGH@   5477
    Entrez_Gene (NCBI)IGH@  3492  immunoglobulin heavy locus
    Cards
    AtlasIgHID40
    GeneCards (Weizmann)IGH@
    Ensembl (Hinxton)ENSG00000142871 [Gene_View]  IGH@ [Vega]
    AceView (NCBI)IGH@
    Genatlas (Paris)IGH@
    euGene (Indiana)3492
    SOURCE (Stanford)
    Genomic and cartography
    GoldenPath (UCSC)IGH@  -  14q32.33   chr14:105180450-105997769 -  14q32.33   [Description]    (hg18-Mar_2006)
    EnsemblIGH@ - 14q32.33 [CytoView]
    Mapping of homologs : NCBIIGH@ [Mapview]
    OMIM
    Gene and transcription
    Gene : Genbank (Entrez)AK097306 AK128421 AK130609 AK130614 AK131045
    Reference sequence (RefSeq transcript) :SRS
    Reference transcript : Entrez
    RefSeq genomic : SRS
    RefSeq genomic : Entrez
    Consensus coding sequences : CCDS NCBIIGH@
    Cluster EST : UnigeneHs.700112 [ SRS ] Hs.700112 [ NCBI ]
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtQ0ZCI1 (SRS) Q0ZCI1 (Expasy) Q0ZCI1 (Uniprot)
    With graphics : InterProQ0ZCI1
    Splice isoforms : VarSplice FASTAQ0ZCI1(VarSplice FASTA)
    Domaine pattern : Prosite (SRS)IG_LIKE (PS50835)   
    Domain pattern : Prosite (Expaxy)IG_LIKE (PS50835)   
    Domains : Interpro (SRS)Ig-like    Ig-like_fold    Ig_V-set    Ig_V-set_sub   
    Domains : Interpro (EBI)Ig-like    Ig-like_fold    Ig_V-set    Ig_V-set_sub   
    Related proteins : CluSTrQ0ZCI1
    Domain families : Pfam SRSV-set (PF07686)   
    Domain families : Pfam SangerV-set (PF07686)   
    Domain families : Pfam NCBIpfam07686   
    Domain families : Smart EMBLIGv (SM00406)
    Blocks (Seattle)Q0ZCI1
    Crystal structure of protein : PDB SRS
    Crystal structure of protein : PDBSum
    Crystal structure of protein : IMB
    Crystal structure of protein : PDB RSDB
    Protein Interaction databases
    DIP (DOE-UCLA)Q0ZCI1
    IntAct (EBI)Q0ZCI1
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBIIGH@
    SNP : GeneSNP UtahIGH@
    SNP : HGBaseIGH@
    Genetic variants : HAPMAPIGH@
    Mutations and Diseases : HGMDIGH@
    Hereditary diseases : OMIM
    Hereditary diseases : GENETests
    Diseases : Genetic AssociationIGH@
    General knowledge
    Homologs : HomoloGeneIGH@
    Homology/Alignments : Family Browser UCSCIGH@
    Phylogenetic Trees/Animal Genes : TreeFamIGH@
    Chemical/Protein Interactions : CTD3492
    Keywords Ontology : AmiGO
    Keywords Ontology : EGO-EBI
    Pathways : BIOCARTA
    Pathways : KEGG
    Other databases
    Other databaseIGH@ - IMGT
    Probes
    ProbeProbes IMGT
    ProbeImmunoglobulin genes IgH at14q32.33, in normal cells (Bari)
    Probes : ImagenesIGH@ Related clones (RZPD - Berlin)
    Literature
    PubMed23 Pubmed reference(s) in Entrez
    PubGeneIGH@

    Bibliography

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    PMID 114999
     
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    Kirsch IR, Morton CC, Nakahara K, Leder P
    Science (New York, N.Y.). 1982 ; 216 (4543) : 301-303.
    PMID 6801764
     
    Localization of human variable and constant region immunoglobulin heavy chain genes on subtelomeric band q32 of chromosome 14.
    McBride OW, Battey J, Hollis GF, Swan DC, Siebenlist U, Leder P
    Nucleic acids research. 1982 ; 10 (24) : 8155-8170.
    PMID 6819544
     
    Physical map of the 3' region of the human immunoglobulin heavy chain locus: clustering of autoantibody-related variable segments in one haplotype.
    Shin EK, Matsuda F, Nagaoka H, Fukita Y, Imai T, Yokoyama K, Soeda E, Honjo T
    The EMBO journal. 1991 ; 10 (12) : 3641-3645.
    PMID 1935893
     
    A map of the human immunoglobulin VH locus completed by analysis of the telomeric region of chromosome 14q.
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    Nature genetics. 1994 ; 7 (2) : 162-168.
    PMID 7920635
     
    The human immunoglobulin VH repertoire.
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    Immunology today. 1995 ; 16 (5) : 237-242.
    PMID 7779254
     
    The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus.
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    The Journal of experimental medicine. 1998 ; 188 (11) : 2151-2162.
    PMID 9841928
     
    Organization of human immunoglobulin heavy chain diversity gene loci.
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    The EMBO journal. 1988 ; 7 (13) : 4141-4150.
    PMID 3243276
     
    The human immunoglobulin heavy variable genes.
    Pallarˆ®s N, Lefebvre S, Contet V, Matsuda F, Lefranc MP
    Experimental and clinical immunogenetics. 1999 ; 16 (1) : 36-60.
    PMID 10087405
     
    The use of chromosomal translocations to study human immunoglobulin gene organization: mapping DH segments within 35 kb of the C mu gene and identification of a new DH locus.
    Buluwela L, Albertson DG, Sherrington P, Rabbitts PH, Spurr N, Rabbitts TH
    The EMBO journal. 1988 ; 7 (7) : 2003-2010.
    PMID 3138112
     
    Sequence of the human immunoglobulin diversity (D) segment locus: a systematic analysis provides no evidence for the use of DIR segments, inverted D segments, minor D segments or D-D recombination.
    Corbett SJ, Tomlinson IM, Sonnhammer EL, Buck D, Winter G
    Journal of molecular biology. 1997 ; 270 (4) : 587-597.
    PMID 9245589
     
    The human immunoglobulin heavy diversity (IGHD) and joining (IGHJ) segments.
    Ruiz M, Pallarˆ®s N, Contet V, Barbi V, Lefranc MP
    Experimental and clinical immunogenetics. 1999 ; 16 (3) : 173-184.
    PMID 10394055
     
    Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.
    Ravetch JV, Siebenlist U, Korsmeyer S, Waldmann T, Leder P
    Cell. 1981 ; 27 (3 Pt 2) : 583-591.
    PMID 6101209
     
    The sequence of a human immunoglobulin epsilon heavy chain constant region gene, and evidence for three non-allelic genes.
    Flanagan JG, Rabbitts TH
    The EMBO journal. 1982 ; 1 (5) : 655-660.
    PMID 6234164
     
    Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions.
    Lefranc MP, Lefranc G, de Lange G, Out TA, van den Broek PJ, van Nieuwkoop J, Radl J, Helal AN, Chaabani H, van Loghem E
    Molecular biology & medicine. 1983 ; 1 (2) : 207-217.
    PMID 6438434
     
    Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions.
    Lefranc MP, Lefranc G, de Lange G, Out TA, van den Broek PJ, van Nieuwkoop J, Radl J, Helal AN, Chaabani H, van Loghem E
    Molecular biology & medicine. 1983 ; 1 (2) : 207-217.
    PMID 6438434
     
    Human immunoglobulin heavy chain genes: evolutionary comparisons of C mu, C delta and C gamma genes and associated switch sequences.
    Rabbitts TH, Forster A, Milstein CP
    Nucleic acids research. 1981 ; 9 (18) : 4509-4524.
    PMID 6795593
     
    Human immunoglobulin D: genomic sequence of the delta heavy chain.
    White MB, Shen AL, Word CJ, Tucker PW, Blattner FR
    Science (New York, N.Y.). 1985 ; 228 (4700) : 733-737.
    PMID 3922054
     
    Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes.
    Huck S, Fort P, Crawford DH, Lefranc MP, Lefranc G
    Nucleic acids research. 1986 ; 14 (4) : 1779-1789.
    PMID 3081877
     
    A human immunoglobulin IGHG3 allele (Gmb0,b1,c3,c5,u) with an IGHG4 converted region and three hinge exons.
    Huck S, Lefranc G, Lefranc MP
    Immunogenetics. 1989 ; 30 (4) : 250-257.
    PMID 2571587
     
    The nucleotide sequence of a human immunoglobulin C gamma1 gene.
    Ellison JW, Berson BJ, Hood LE
    Nucleic acids research. 1982 ; 10 (13) : 4071-4079.
    PMID 6287432
     
    Duplication and deletion in the human immunoglobulin epsilon genes.
    Max EE, Battey J, Ney R, Kirsch IR, Leder P
    Cell. 1982 ; 29 (2) : 691-699.
    PMID 6288268
     
    The human immunoglobulin pseudo-gamma IGHGP gene shows no major structural defect.
    Bensmana M, Huck S, Lefranc G, Lefranc MP
    Nucleic acids research. 1988 ; 16 (7) : page 3108.
    PMID 3130612
     
    Linkage and sequence homology of two human immunoglobulin gamma heavy chain constant region genes.
    Ellison J, Hood L
    Proceedings of the National Academy of Sciences of the United States of America. 1982 ; 79 (6) : 1984-1988.
    PMID 6804948
     
    Nucleotide sequence of a human immunoglobulin C gamma 4 gene.
    Ellison J, Buxbaum J, Hood L
    DNA (Mary Ann Liebert, Inc.). 1981 ; 1 (1) : 11-18.
    PMID 6299662
     
    Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes.
    Flanagan JG, Rabbitts TH
    Nature. 1982 ; 300 (5894) : 709-713.
    PMID 6817141
     
    Sequence of the CH1 and hinge-CH2 exons of the human immunoglobulin IGHA2 A2m(2) allele: comparison with the nonallelic and allelic IGHA genes.
    Bensmana M, Chuchana P, Lefranc G, Lefranc MP
    Cytogenetics and cell genetics. 1991 ; 56 (2) : page 128.
    PMID 1901541
     
    Protein displays of the human immunoglobulin heavy, kappa and lambda variable and joining regions.
    Scaviner D, Barbiˆ© V, Ruiz M, Lefranc MP
    Experimental and clinical immunogenetics. 1999 ; 16 (4) : 234-240.
    PMID 10575277
     
    A processed human immunoglobulin epsilon gene has moved to chromosome 9.
    Battey J, Max EE, McBride WO, Swan D, Leder P
    Proceedings of the National Academy of Sciences of the United States of America. 1982 ; 79 (19) : 5956-5960.
    PMID 6964396
     
    Nomenclature of the human immunoglobulin genes (Review)
    Lefranc MP
    Current Protocols in Immunology. 2000.
     
    The Immunoglobulin FactsBook (Review)
    Lefranc MP and Lefranc G
    Academic Press, London, UK (. 1945.
     
    Locus Map and Genomic repertoire of the Human Immunoglobulin Genes (Review)
    Lefranc MP
    The immunologist. 2000.
     
    Nomenclature of the human immunoglobulin heavy (IGH) genes.
    Lefranc MP
    Experimental and clinical immunogenetics. 2001 ; 18 (2) : 100-116.
    PMID 11340299
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    Contributor(s)

    Written07-2000Marie-Paule Lefranc
    IMGT, LIGM, IGH, UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France
    Updated09-2003Marie-Paule Lefranc
    IMGT, LIGM, IGH, UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France

    Citation

    This paper should be referenced as such :
    Lefranc MP . IGH (Immunoglobulin Heavy). Atlas Genet Cytogenet Oncol Haematol. July 2000 .
    URL : http://AtlasGeneticsOncology.org/Genes/IgHID40.html
    Lefranc MP . IGH (Immunoglobulin Heavy). Atlas Genet Cytogenet Oncol Haematol. September 2003 .
    URL : http://AtlasGeneticsOncology.org/Genes/IgHID40.html

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    indexed on : Sat Jun 27 16:38:31 CEST 2009
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