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Factsbook IG
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The Immunoglobulin FactsBook

DNA

Overview

The human IGH locus is located on the chromosome 14 [1], at band 14q32.33, at the telomeric extremity of the long arm [2,3]. One processed gene has been localized on chromosome 9, and IGH orphons have been identified on chromosomes 15 and 16. The total number of IGH genes per haploid genome is 170 to 176 depending from the haplotypes (206 to 212, if the orphons and the processed gene are included) of which 77 to 84 genes are functional [4-6].

The list of human IGH genes is available at IMGT/GENE-DB.

Human IGH locus at 14q32.33

Orphons and processed gene

Thirty-five IGH genes have been found outside the main locus in other chromosomal localizations corresponding to 4 chromosomal orphon sets. These genes designated as orphons cannot contribute to the synthesis of the immunoglobulin chains, even if they have an Open Reading Frame (ORF). Nine IGHV orphons and 10 IGHD orphons have been described on chromosome 15 (15q11.2), and 16 IGHV orphons on chromosome 16 (16p11.2) [12,13]. In addition, one IGHC processed gene, IGHEP2 is localized on chromosome 9 (9p24.2-p24.1) [46]. This is so far the only processed Ig gene described.

Total number of human IGH genes

The total number of human IGH genes per haploid genome is 170 to 176 depending from the haplotypes (206 to 212, if the orphons and the processed gene are included) of which 76 to 84 genes are functional [47].

IG and TR number of genes: Human
Nomenclature and overview of the human immunoglobulin genes (IMGT Education)

Nomenclature

IGHV gene nomenclature

IMGT and HUGO gene nomenclatures

Links between IMGT, HGNC and NCBI Gene

The Complete list of the human immunoglobulin and T cell receptor IMGT gene names (symbols) provides the IMGT definition (full name), the gene functionality, the IMGT accession number of the reference sequence, the number of alleles per gene, and the and NCBI Gene accession ID. The table below reports entries which concern the IGH locus or groups and are found in the OMIM and NCBI Gene genome databases, and in HGNC:

IMGT name IMGT definition (a) OMIM NCBI Gene HGNC
IGH locus Immunoglobulin heavy locus - 3492 IGH
IGHC group Immunoglobulin heavy constant group (b) (b) (b)
IGHD group Immunoglobulin heavy diversity group 146910 50648 IGHD
IGHJ group Immunoglobulin heavy joining group 147010 3506 IGHJ
IGHV group Immunoglobulin heavy variable group 147070 3509 IGHV

(a) The locus definition is identical in IMGT, HGNC and NCBI Gene. The IMGT 'group' concept comprises genes of the major locus and of the chromosomal orphon sets, whereas the HGNC IG group symbols only refer to genes of the major locus.

(b) There is no entry for the IGHC group in the OMIM, NCBI Gene database and HGNC. The individual OMIM entries for the IGHC genes are the following: IGHA1: 146900, IGHA2: 147000, IGHD: 147170, IGHE: 147180, IGHG1: 147100, IGHG2: 147110, IGHG3: 147120, IGHG4: 147130, IGHM: 147020. Individual NCBI Gene entries are reported in the complete gene name list. HGNC symbols for the IGHC genes are identical to IMGT gene names.

Protein

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 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 the IMGT/V-QUEST tool. The junctions can be analysed with IMGT/JunctionAnalysis.

Alleles and mutation

Mutations which correspond to allelic polymorphisms of the functional germline IGHV, IGHD, IGHJ and IGHC genes are described in Alignments of alleles [47] and Tables of alleles.

Translocations

Translocations in which the human IGH locus is implicated frequently result from errors of the recombinase enzyme complexe (RAG1, RAG2, ...), 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.

t(3;14)(q27;q32)
t(4;14)(p16;q32)
t(5;14)(q31;q32)
t(8;14)(q11;q32)
t(8;14)(q24;q32)
t(10;14)(q24;q32)
t(11;14)(q13;q32)
t(14;18)(q32;q21)
t(14;19)(q32;q13.1)

References:
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Created:
21/09/2001
Last updated:
Friday, 27-May-2016 21:02:17 CEST
Editors:
Valérie Contet, Chantal Ginestoux