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Genetics of human C4 polymorphism: Detection and segregation of rare and duplicated haplotypes

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Abstract

Applying a combined technology for the detection of allotypec variation of the fourth component of human complement (C4), including immunofixation with anti-C4 and C4-dependent lysis after agarose electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of C4 to separate the C4A and B α-chains, and the determination of Rodgers (Rg) and Chido (Ch) determinants of C4 in serum and at the blotted C4 α-chains, we detected rare human C4 allotypes and studied the genetic linkage. Partial inhibitors (p. i.) of anti-Rg and anti-Ch sera were found; the C4A51 allotype characterized as Rg p. i. and the C4A1 and C4B51 allotypes as Ch p. i. were genetically inherited. The C4A1 allotype has a unique Rg- Ch+ C4A α-chain. Duplicated C4A loci, A *3, A *2, and A *5, A *2 were both associated with a C4BQO and the HLA haplotype A3-Cw4-Bw35-DR1. These additions to the already known extensive C4 polymorphism may help to sort out their significance for the biological functions of human C4.

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Abbreviations

BF:

Factor B polymorphism of the alternative pathway of complement activation

C2:

second component of complement

C4:

fourth component of complement

C4D:

C4-deficient (C4*QO/QO)

Ch:

Chido determinant on C4B* products

EDTA:

ethylendiaminetetraacetic acid

GLO I:

glyoxalase I

HLA:

human leucocyte antigens, A, B, C and DR (D =related) loci

PAGE:

polyacrylamide gel electrophoresis

PGM3:

phosphoglucomutase, third locus

p. i.:

partial inhibitor = serological inhibition of some, but not all anti-Ch and anti-Rg sera at selected dilutions

SDS:

sodium dodecyl sulphate; 94k/96k, 94 000 and 96 000 dalton molecular weight

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Authors and Affiliations

  1. Institute of Legal Medicine, University of Bonn, Bonn, Germany

    Christian Rittner & Eva Mollenhauer

  2. Department of Immunology, Royal Postgraduate School of Medicine, Hammersmith Hospital, London, UK

    Carolyn M. Giles

  3. Division of Genetics, Antoni van Leewenhoekhuis, Amsterdam, The Netherlands

    Marleen H. Roos & Peter Démant

Authors
  1. Christian Rittner
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  2. Carolyn M. Giles
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  3. Marleen H. Roos
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  4. Peter Démant
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  5. Eva Mollenhauer
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Rittner, C., Giles, C.M., Roos, M.H. et al. Genetics of human C4 polymorphism: Detection and segregation of rare and duplicated haplotypes. Immunogenetics 19, 321–333 (1984). https://doi.org/10.1007/BF00345405

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  • DOI: https://doi.org/10.1007/BF00345405

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