Summary
Human immunoglobulin heavy chain constant region (IGHC) genes constitute a typical multigene family, usually comprising eleven genes on the telomere of chromosome 14 (14q32). In this region, deleted and duplicated haplotypes have been reported to exist with considerable frequency. Their origin is the result of either unequal crossing-over or looping out excision. In this paper, we report the characterization of a new type of deletion, involving the IGHG4 gene, in a subject who also carries a larger deletion of a previously described type on the second chromosome. Employment of several methods (polymerase chain reaction, standard Southern blot, pulsed field gel electrophoresis, serological techniques) to analyze these deleted haplotypes has resulted in a level of accuracy in their characterization that has not been achieved in previous cases. The site of recombination responsible for the IGHG4 deletion was restricted to a 2.5-kb region 3′ of the G4 gene; this rules out any possible involvement of the S regions in the recombination process. The usefulness of the various techniques in the characterization of the deletions is also discussed, together with possible future applications in the field.
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Baas F, Bikker H, Ommen GJB van, Vijlder JJM de (1984) Unusual scarcity of restriction site polymorphism in the human thyroglobulin gene. A linkage study suggesting autosomal dominance of a defective thyroglobulin allele. Hum Genet 67:301–305
Battey J, Max EE, McBride WO, Swan D, Leder P (1982) A processed human immunoglobulin ɛ gene has moved to chromosome 9. Proc Natl Acad Sci USA 79:5956–5960
Bech-Hansen NT, Cox DW (1986) Duplication of the human immunoglobulin heavy chain gamma-2 gene. Am J Hum Genet 38:67–74
Bottaro A, DeMarchi M, deLange GG, Carbonara AO (1989a) Gene deletions in the human immunoglobulin heavy chain constant region gene cluster. Exp Clin Immunogenet 6:55–59
Bottaro A, DeMarchi M, deLange GG, Boccazzi C, Caldesi F, Gallina R, Carbonara AO (1989b) New types of multiple and single gene deletions in the human IgCH locus. Immunogenetics 29:44–48
Bottaro A, DeMarchi M, Migone N, Carbonara AO (1989c) Pulsed field gel analysis of human immunoglobulin heavy chain constant region gene deletions reveals the extent of unmapped regions within the locus. Genomics 4:505–508
Bottaro A, Gallina R, DeMarchi M, Carbonara AO (1989d) Genetic analysis of new restriction fragment length polymorphisms (RFLP) in the human IgH constant gene locus. Eur J Immunol 19:2151–2157
Carbonara AO, Migone N, Oliviero S, DeMarchi M (1986) The molecular basis of Ig deficiencies. In: Aiuti F, Rosen F, Cooper MD (eds) Recent advances in primary and acquired immunodeficiencies, vol 28. Raven Press, New York, pp 219–225
Chaabani H, Bech-Hansen NT, Cox DW (1985) A multigene deletion within the immunoglobulin heavy chain region. Am J Hum Genet 37:1164–1171
Church GM, Gilbert W (1984) Genomic sequencing. Proc Natl Acad Sci USA 81:1991–1995
Ellison J, Hood L (1982) Linkage and sequence homology of two human immunoglobulin γ heavy chain constant region genes. Proc Natl Acad Sci USA 79:1984–1988
Flanagan JG, Rabbitts TH (1982) 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
Hendriks RW, Tol M van, deLange GG, Schuurman RKB (1989) Inheritance of a large deletion within the human immunoglobulin heavy chain constant region gene complex and immunological implications. Scand J Immunol 29:535–541
Hisajima H, Nishida Y, Nakai S, Takahashi N, Ueda S, Honjo T (1983) Structure of the human immunoglobulin Cɛ2 pseudogene: implications for its evolutionary origin. Proc Natl Acad Sci USA 80:2995–2999
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, Keyeux G, Ghanem N, Lefranc M-P, Lefranc G (1986) A gamma 3 hinge region probe: first specific human immunoglobulin subclass probe. FEBS Lett 208:221–230
Jefferis R, Reimer CB, Skvaril F, deLange GG, Ling NR, Lowe J, Walker MR, Phillips DJ, Aloisio CH, Wells TW, Vaerman JP, Magnusson CG, Kubagawa H, Cooper M, Vartdal F, Vandvik B, Haaijman JJ, Mákelá O, Sarnesto A, Lando Z, Gergely J, Rajnavólgyi E, Laszlo G, Radl J, Molinaro GA (1985) Evaluation of monoclonal antibodies having specificity for human IgG subclasses: results of an IUIS/WHO collaborative study. Immunol Lett 10:223–252
Johnson MJ, deLange GG, Cavalli-Sforza LL (1986) Ig gamma restriction fragment length polymorphisms indicate an ancient separation of Caucasian haplotypes. Am J Hum Genet 38:617–640
Keyeux G, Lefranc G, Lefranc M-P (1989) A multigene deletion in the human IGH constant region locus involves highly homologous hot spots of recombination. Genomics 5:431–441
Kirsch IR, Morton CC, Nakahara K, Leder P (1982) Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science 216:301–303
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, 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, deLange GG, Out TA, Broek PJ van den, Nieuwoop J van, Radl 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, Helal AN, deLange GG, Chaabani H, Loghem E van, Lefranc G (1986) Gene conversion in human immunoglobulin γ locus shown by unusual location of IgG allotypes. FEBS Lett 196:96–102
Max EE, Battey J, Ney R, Kirsch IL, Leder P (1982) Duplication and deletion in the human immunoglobulin ɛ genes. Cell 29:691–699
Migone N, Oliviero S, deLange GG, Delacroix DL, Boschis D, Altruda F, Silengo L, DeMarchi M, Carbonara AO (1984) Multiple gene deletions in the human immunoglobulin heavy chain cluster. Proc Natl Acad Sci USA 81:5811–5815
Poustka A, Pohl TM, Barlow DP, Frischauf AM, Lehrach H (1987) Construction and use of human chromosome jumping ibraries from NotI digested DNA. Nature 325:353–355
Ravetch JV, Siebenlist U, Korsmeyer S, Waldman T, Leder P (1981) Structure of the human immunoglobulin μ locus: characterization of embryonic and rearranged J and D genes. Cell 27:583–591
Reimer CB, Phillips DJ, Aloisio CH, Moore DD, Galland GG, Wells TW, Black CM, McDougal JS (1984) Evaluation of thirty-one mouse monoclonal antibodies to human IgG epitopes. Hybridoma 3:263–275
Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491
Schwartz DC, Cantor CR (1984) Separation of yeast chromosomesized DNAs by pulsed field gradient gel electrophoresis. Cell 37:67–75
Smith CIE, Hammarström L, Henter JI, Lange GG de (1989) Molecular and serologic analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions. J Immunol 142:4514–4519
Takahashi N, Ueda S, Obata M, Nikaido T, Nakai S, Honjo T (1982) Structure of human immunoglobulin gamma genes: implications for the evolution of a gene family. Cell 29:671–679
Vlug A, deBot AJ, Brouwer H, deLange GG, Leeuwen AM van, deRon EA, Eijk RVW van (1989) Monoclonal antibodies against IgG subclasses. In: Poulik MD (ed) Protides of the biological fluids, vol 36. Pergamon Press, Oxford, pp 39–47
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Bottaro, A., Cariota, U., deLange, G.G. et al. Multiple levels of analysis of an IGHG4 gene deletion. Hum Genet 86, 191–197 (1990). https://doi.org/10.1007/BF00197704
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DOI: https://doi.org/10.1007/BF00197704