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Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals

Naturevolume 300, pages760–762 (1982)Cite this article

Abstract

The existence of specific probes for human genes makes it feasible to study genetic abnormalities, both inherited and acquired, at the level of the genome. In this respect, the antibody genes of man are of particular interest as they represent a multigene family expressed in many leukaemias and immunodeficiency diseases. Furthermore, selective deficiency of immunoglobulins has been described in healthy individuals1. Normally, human adults express five types of immunoglobulin—IgM, IgD, IgG, IgE and IgA (defined by the class of heavy chain constant region). Subclasses are also known in IgG (IgG1, IgG2, IgG3 and IgG4) and IgA (IgA1 and IgA2) in which the immunoglobulins containγ1,γ2,γ3 orγ4 andα1 orα2 CH regions, respectively. Recently, a healthy Tunisian person was described who showed abnormal patterns of immunoglobulin expression2. The serum immunoglobulin of this individual, designated TAK3, was confined to IgM, IgD, IgG3, IgE and IgA2. We have now used cloned CH-gene probes to study the DNA of TAK3 as well as two brothers, also Tunisian but apparently unrelated to the individual TAK3, and who show a similar immunoglobulin abnormality. We found that in these cases there seems to have been a large chromosomal deletion which includes threeγ genes, anα gene and a pseudo-ε gene. This deletion accounts for the simultaneous absence of certain H-chain subclasses. These results illustrate that the human immunoglobulin gene locus is capable of undergoing rapid change, which is particularly apparent within small populations in which consanguinity is common.

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Author information

Author notes

  1. G. Lefranc: Faculté de Pharmacie, Monastir, Tunisia.

Authors and Affiliations

  1. Laboratory of Molecular Biology, The MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

    Marie-Paule Lefranc, G. Lefranc & T. H. Rabbitts

  2. Laboratoire d'Immunogénétique, Université des Sciences et Techniques du Languedoc, 34060, Montpellier, France

    Marie-Paule Lefranc & G. Lefranc

Authors
  1. Marie-Paule Lefranc
  2. G. Lefranc
  3. T. H. Rabbitts

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Lefranc, MP., Lefranc, G. & Rabbitts, T. Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals.Nature300, 760–762 (1982). https://doi.org/10.1038/300760a0

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