Summary
Extensive genetic polymorphism of complement component C8 was demonstrated by isoelectric focusing of serum or plasma samples followed by immunoblotting procedures. Using these methods, we could detect both α-γ (C81) and β (C82) chain polymorphisms in the same gel. Two-dimensional (2D) electrophoresis of C8 immunoprecipitates was used to obtain further information of the C8 patterns. Evidence was obtained that the C81 polymorphism resides in the structural gene of the C8 α chain. Both C8 systems show autosomal, chiefly codominant inheritance, and the distribution of phenotypes agrees with the Hardy-Weinberg equilibrium. Our findings suggest at least five different alleles in the C81 system; the gene frequencies of the two most common ones, C81 *A and C81 *B being 0.59 and 0.39, respectively. In C82 we found evidence for at least three codominant alleles, the gene frequencies for the two most common ones, C82 *B and C82 *A being 0.94 and 0.05, respectively. In addition, family studies disclosed the existence of a null allele, C82 * Q0.
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Alper CA, Marcus D, Raum D, Petersen BH, Spira TJ (1983) Genetic polymorphism in C8 β-chains. J Clin Invest 72:1526–1531
Anderson L, Anderson NG (1977) High resolution two-dimensional electrophoresis of human plasma proteins. Proc Natl Acad Sci USA 74:5421–5425
Giraldo G, Degos L, Beth E, Sasportes M, Marcelli A, Gharbi R, Day NK (1977) C8 deficiency in a family with xeroderma pigmentosum. Clin Immunol Immunopathol 8:377–384
Hawkes R, Niday E, Gordon J (1982) A dot-immunobinding assay for monoclonal and other antibodies. Anal Biochem 119:142–147
Jasin HE (1977) Absence of the eight component of complement in association with systemic lupus crythematosus-like disease. J Clin Invest 60:709–715
Kolb WP, Müller-Eberhard HJ (1976) The membrane attack mechanism of complement: The three polypeptide chain structure of the eighth component (C8). J Exp Med 143:1131–1139
Marcus D, Spira TJ, Petersen BH, Raum D, Alper CA (1982) There are two unlinked genetic loci for human C8 (Abstract). Mol Immunol 19:1385a
Merritt AD, Petersen BH, Biegel AA, Meyers DA, Brooks GF, Hodes ME (1976) Chromosome 6: Linkage of the eighth component of complement (C8) to the histocompatibility region (HLA). Birth Defects 12:331–334
Mevåg B, Olaisen B, Teisberg P (1981) Electrophoretic polymorphism of human C4 is due to charge differences in the α-chain, presumably in the C4d fragment. Scand J Immunol 14:303–307
Mevåg B, Rogde S, Olaisen B, Gedde-Dahl T Jr, Teisberg P, Tedesco F (1984) Genetic polymorphism of complement component C8. Proceedings, 10th International Congress of the Society for Forensic Haemogenetics, Munich, pp 361–365
Petersen BH, Graham JA, Brooks GF (1976) Human deficiency of the eighth component of complement. J Clin Invest 57:283–290
Raum D, Spence A, Balavitch D, Tideman S, Merritt AD, Taggart RT, Petersen BH, Day NK, Alper CA (1979) Genetic control of the eighth component of complement. J Clin Invest 64:858–865
Rittner C, Hargesheimer W, Mollenhauer E (1984) Population and formal genetics of the human C81 (α-γ) polymorphism. Hum Genet 67:166–169
Rogde S, Mevåg B, Olaisen B, Gedde-Dahl T Jr, Teisberg P (1984) Structural gene(s) for complement factor C8 (C8) on chromosome 1 (Abstract). VIIth Human Gene Mapping Conference Los Angeles 1983. Cytogenet Cell Genet 37:571
Steckel EW, York RG, Monahan JB, Sodetz JM (1980) The eighth component of human complement. J Biol Chem 255:11997–12005
Tedesco F, Bardare M, Giovanetti AM, Sirchia G (1980) A familial dysfunction of the eighth component of complement (C8). Clin Immunol Immunopathol 16:180–191
Tedesco F, Densen P, Sirchia G (1982) Reconstitution of C8 hemolytic activity from the mixture of sera from two groups of C8 deficient subjects (Abstract). Mol Immunol 19:1405a
Tedesco F, Densen P, Villa MA, Petersen BH, Sirchia G (1983a) Two types of dysfunctional eighth component of complement (C8) molecules in C8 deficiency in man. J Clin Invest 71:183–191
Tedesco F, Villa MA, Densen P, Sirchia G (1983b) β Chain deficiency in three patients with dysfunctional C8 molecules. Mol Immunol 20:47–51
Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354
Tschopp J, Esser AF, Spira TJ, Müller-Eberhard HJ (1981) Occurrence of an incomplete C8 molecule in homozygous C8 deficiency in man. J Exp Med 154:1599–1607
Whitehouse DB, Putt W (1983) Immunological detection of the sixth complement component (C6) following flat bed polyacrylamide gel isoelectric focusing and electrophoretic transfer to nitrocellulose filters. Ann Hum Genet 47:1–8
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Rogde, S., Mevåg, B., Teisberg, P. et al. Genetic polymorphism of complement component C8. Hum Genet 70, 211–216 (1985). https://doi.org/10.1007/BF00273444
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DOI: https://doi.org/10.1007/BF00273444