Alternative titles; symbols
HGNC Approved Gene Symbol: IGH
Cytogenetic location: 14q32.33 Genomic coordinates (GRCh38): 14:105,586,437-106,879,844 (from NCBI)
Immunoglobulins (Ig) are the antigen recognition molecules of B cells. An Ig molecule is made up of 2 identical heavy chains and 2 identical light chains (see 147200) joined by disulfide bonds so that each heavy chain is linked to a light chain and the 2 heavy chains are linked together. Each Ig heavy chain has an N-terminal variable (V) region containing the antigen-binding site and a C-terminal constant (C) region, encoded by a C region gene (e.g., IGHG1; 147100), that provides effector or signaling functions. The heavy chain V region is encoded by 3 types of genes: V genes (see 147070), joining (J) genes (see 147010), and diversity (D) genes. Random selection of just 1 gene of each type to assemble a V region accounts for the great diversity of V regions among Ig molecules. The heavy chain locus on chromosome 14 contains approximately 40 functional V genes, followed by approximately 25 functional D genes and approximately 6 functional J genes. Due to polymorphism, the numbers of functional V, J, and D genes differ among individuals (Janeway et al., 2005).
Siebenlist et al. (1981) determined that human D genes belonging to the same family are encoded at regular 9-kb intervals. By sequencing a 15-kb DNA fragment containing more than 1 and a half of these 9-kb repeating units, Ichihara et al. (1988) identified 12 different D genes that could be classified into 6 different D gene families. They estimated the total number of D genes to be 30.
The Ig heavy chain D gene cluster is located within the Ig heavy chain locus on chromosome 14q32.33 (Kirsch et al., 1982).
Ichihara, Y., Matsuoka, H., Kurosawa, Y. Organization of human immunoglobulin heavy chain diversity gene loci. EMBO J. 7: 4141-4150, 1988. [PubMed: 3243276] [Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb03309.x]
Janeway, C. A., Jr., Travers, P., Walport, M., Shlomchik, M. J. Immunobiology: The Immune System in Health and Disease. (6th ed.) New York: Garland Science Publishing (pub.) 2005. Pp. 103-106, and 135-139.
Kirsch, I. R., Morton, C. C., Nakahara, K., Leder, P. Human immunoglobulin heavy chain genes map to a region frequently involved in chromosomal translocations in malignant B-lymphocytes. Science 216: 301-302, 1982. [PubMed: 6801764] [Full Text: https://doi.org/10.1126/science.6801764]
Siebenlist, U., Ravetch, J. V., Korsmeyer, S., Waldmann, T., Leder, P. Human immunoglobulin D segments encoded in tandem multigenic families. Nature 294: 631-635, 1981. [PubMed: 7312051] [Full Text: https://doi.org/10.1038/294631a0]