genetic polymorphism in C8 β-chains: evidence for two unlinked genetic loci for the eighth component of human complement

• Published in: The Journal of clinical investigation 1983-11, Vol.72 (5), p.1526-1531
• Main Authors: ALPER, C. A, MARCUS, D, RAUM, D, PETERSEN, B. H, SPIRA, T. J
• Format: Article
• Language: English
• Subjects: Alleles; Biological and medical sciences; Complement C8 - deficiency; Complement C8 - genetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetics of the immune response; Hemolytic Plaque Technique; Humans; Immunobiology; Immunodiffusion; Isoelectric Focusing; Macromolecular Substances; Polymorphism, Genetic
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI111111

Genetic polymorphism in the beta-subunit of the eighth component of human complement, C8, was defined by isoelectric focusing of serum in polyacrylamide gel in the presence of urea and development of specific patterns of hemolysis in an overlay gel containing antibody-sensitized erythrocytes and C8 beta-chain-deficient serum. Bands of hemolysis induced by serum from unrelated Caucasians suggested autosomal codominant inheritance of three structural alleles at a single locus, C82: C82 degrees A (acidic), C82 degrees B (basic), and C82 degrees A1 (very acidic) with frequencies of 0.952, 0.044, and 0.004, as well as the probable null allele C82 degrees Q0. The distribution of phenotypes agreed with the Hardy-Weinberg equilibrium. The previously described genetic polymorphism in human C8 defined with the use of "complete" C8 (C8 alpha-gamma-chain)-deficient serum was distinct from and independent of the inherited structural variation at C82. Therefore, the locus for C8 alpha-gamma-chains has been redesignated C81, and has the alleles C81 degrees A, C81 degrees A1, and C81 Q0. Linkage studies failed to show close linkage between the two loci for C8, C81, and C82, and between C82 and the major histocompatibility complex or C6.