Abstract
In the human, the order of the immunoglobulin heavy chain constant region (Ig CH) genes is the following: 5′-M-D-G3-G1-EP1-A1-GP-G2-G4-E-A2-3′. Extensive multigene deletions have been described in the Ig CH locus, some of these encompassing up to 160 kb. To date six different multigene deletion haplotypes have been identified, designated I to VI according to the chronological order of their being found: deletion I (del G1-EP1-A1-GP-G2-G4), II (del EP1-A1-GP), III (del A1-GP-G2-G4-E), IV (del EP1-A1-GP-G2-G4), V (del GP-G2-G4-E-A2), VI (del G1-EP1-A1-GP-G2). Individuals were found either homozygous for one type of deletion or heterozygous for two different deletions, mainly (17 cases out of 18) in the Mediterranean area. So far, deletions I and II have been found in Tunisia, deletions III, IV and V in Italy, and deletion VI in Sweden. In this paper, we show that a Tunisian, T17, previously reported as being homozygous for a deletion of type IV, is, in fact, homozygous for a deletion that encompasses A1-GP-G2-G4-E. Therefore T17 is the first case of a deletion of type III reported in the Tunisian population. Molecular analysis demonstrates that the T17 deletion occurred between highly homologous regions located downstream of IGHEP1 and IGHE, respectively. In contrast to the EZZ deletion, the recombination occurred near or in the switch regions, since the homologous regions involved in the deletion extend over 4.5 kb of DNA and encompass the Iα1-Sα1 and Iα2-Sα2 regions, respectively.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bernard F, Ducret F, Buresi C, Lefranc G, Lefranc M-P (1991) HindIII/EcoRI RFLP of the human immunoglobulin IGHE gene detected with a Cɛ probe in the French and Tunisian populations. Hum Genet 87:101
Bottaro A, Marchi M de, Lange G de, Boccazzi C, Caldesi F, Gallina R, Carbonara AO (1989) New types of multiple and single gene deletions in the human IgCH locus. Immunogenetics 29:44–48
Chaabani H, Bech-Hansen TU, Cox DW (1985) A multigene deletion within the immunoglobulin heavy-chain region. Am J Hum Genet 37:1164–1171
Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13
Flanagan JG, Rabbitts TH (1982a) Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing γ, ɛ and α genes. Nature 300:709–713
Flanagan JG, Rabbitts TH (1982b) The sequence of a human immunoglobulin epsilon heavy chain constant region gene, and evidence for three non-allelic genes. EMBO J 1:655–659
Ghanem N, Lefranc M-P, Lefranc G (1988a) Definition of the RFLP alleles in the human immunoglobulin IGHG gene locus. Eur J Immunol 18:1059–1065
Ghanem N, Dugoujon JM, Bensmana M, Huck S, Lefranc M-P, Lefranc G (1988b) Restriction fragment haplotypes in the human immunoglobulin IGHG locus and their correlation with the Gm polymorphism. Eur J Immunol 18:1067–1072
Ghanem N, Bensmana M, Dugoujon JM, Constans J, Lefranc MP, Lefranc G (1989) BamHI and SacI RFLPs of the human immunoglobulin IGHG genes with reference to the Gm polymorphism in African people: evidence for a major polymorphism. Hum Genet 83:37–44
Hofker MH, Walter MA, Cox DW (1989) Complete physical map of the human immunoglobulin heavy chain constant region gene complex. Proc Natl Acad Sci USA 86:5567–5571
Huck S, Fort P, Crawford DH, Lefranc M-P, Lefranc G (1986a) Sequence of human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human Cγ genes. Nucleic Acids Res 14:1779–1789
Huck S, Keyeux G, Ghanem N, Lefranc M-P, Lefranc G (1986b) A gamma 3 hinge region probe: first specific human immunoglobulin subclass probe. FEBS Lett 208:221–230
Jurka J (1990) Novel families of interspersed repetitive elements from the human genome. Nucleic Acids Res 18:137–141
Keyeux G, Lefranc G, Lefranc M-P (1989a) A multigene deletion in the human IGH constant region locus involves highly homologous hot spots of recombination. Genomics 5:431–441
Keyeux G, Lefranc G, Lefranc M-P (1989b) A specific switch alpha probe of the human immunoglobulin IGHA locus. Nucleic Acids Res 17:3624
Lefranc G, Chaabani H, Loghem E van, Lefranc M-P, Lange G de, Helal A (1983) Simultaneous absence of the human IgG1, IgG2, IgG4 and IgA1 subclasses: immunological and immunogenetical considerations. Eur J Immunol 13:240–244
Lefranc M-P, Rabbitts TH (1984) Human immunoglobulin heavy chain A2 gene allotype determination by restriction fragment length polymorphism. Nucleic Acids Res 12:1303–1311
Lefranc M-P, Lefranc G (1987) Human immunoglobulin heavy-chain multigene deletions in healthy individuals. FEBS Lett 213:231–237
Lefranc M-P, Lefranc G, Rabbitts TH (1982) Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals. Nature 300:760–762
Lefranc M-P, Lefranc G, Lange G de, Out TA, Brock PJ van den, Nieuwkoop J van, Radj J, Helal AN, Chaabani H, Loghem E van, Rabbitts TH (1983) Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions. Mol Biol Med 1:207–217
Lefranc M-P, Hammarström L, Smith CIE, Lefranc G (1991) Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis. Immunodeficiency Rev 2:265–281
Migone N, Oliviero S, Lange G de, Delacroix DL, Boschis D, Altruda F, Silengo L, Marchi M de, Carbonara AO (1984) Multiple gene deletions within the human immunoglobulin heavy-chain cluster. Proc Natl Acad Sci USA 81:5811–5815
Milstein C, Deverson EV, Rabbitts TH (1984) The sequence of the human immunoglobulin μ-δ intron reveals possible vestigial switch segments. Nucleic Acids Res 12:6523–6535
Nilsson L, Islam KB; Olafsson O, Zalcberg I, Samakovlis C, Hammarström L, Smith CIE, Sideras P (1991) Structure of TGF-β 1-induced human immunoglobulin Cα1 and Cα2 germline transcripts. Int Immunol 3:1107–1115
Plebani A, Ugazio AG, Meini A, Ruggeri L, Negrini A, Albertini A, Leibovitz M, Duse M, Bottaro A, Brusco R, Cariota U, Boccazzi C, Carbonara AO (1993) Extensive deletion of immunoglobulin heavy chain constant region genes in the absence of recurrent infections: when is IgG subclass deficiency clinically relevant. Clin Immunol Immunopathol 68:46–50
Shows TB, McAlpine PJ, Boucheix C, Collins FS, Conneally PM, Frezal J, Gershowitz H, Goodfellow PN, Hall JG, Issitt P, Jones CA, Knowles BB, Lewis M, McKusick VA, Meisler M, Morton NE, Rubinstein P, Schanfield MS, Schmickel RD, Skolnick MH, Spence MA, Sutherland GR, Traver M, VanCong N, Williard HF (1987) Guidelines for human gene nomenclature ISGN:HGM9. Cytogenet Cell Genet 46:11–28
Smith CIE, Hammarström L, Henter JJ, Lange G de (1989) Moleular and serological analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions. J Immunol 142:4514–4519
Soua Z, Ghanem N, Ben Salem M, Lefranc G, Lefranc M-P (1989) Frequencies of the IGHA2*M1 and IGHA2*M2 alleles corresponding to the A2m(1) and A2m(2) allotypes in the French, Lebanese, Tunisian and Black African populations. Nucleic Acids Res 17:3625
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wiebe, V., Helal, A., Lefranc, MP. et al. Molecular analysis of the T17 immunoglobulin CH multigene deletion (del A1-GP-G2-G4-E). Hum Genet 93, 520–528 (1994). https://doi.org/10.1007/BF00202816
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00202816