Genetic control of the eighth component of complement.

Abstract

A B S T R A C T Using isoelectric focusing in polyacrylamide gel and a hemolytic assay for development of patterns, extensive structural polymorphism in human C8 has been delineated. Two C8 allotypes have been determined for two previously studied familes, each with a homozygous C8-deficient propositus. This study suggests that C8 deficiency is a silent or null allele of the C8 structural locus, and that half normal levels of C8 cannot be used as a single criterion for the establishment of heterozygous C8 deficiency. C8 allotypes, as well as 18 other autosomal markers, were also determined for 24 familes. The C8 structural locus is not closely linked to these markers, including the human histocompatibility loci complex.

Genetic regulation of a structural polymorphism of human C3b receptor.

“…The structural polymorphism of the C3bR is unusual, because it can be detected by SDS-PAGE, whereas the demonstration of the polymorphic forms of the human serum complement proteins, C4, C2, C3, C6, C8, and factor B require procedures that separate proteins according to net charge rather than size (28)(29)(30)(31)(32)(33). Two forms of human C4 differing in their M, have been described, but they represent products of two separate loci, C4A and C4B (34).…”

Genetic polymorphism in C8 beta-chains. Evidence for two unlinked genetic loci for the eighth component of human complement (C8).

“…The a-and 'y-subunits are bound covalently Received for publication 12 April 1983 and in revised form 11 July 1983. 1 Abbreviations used in this paper: BF, properdin factor B; C, complement.…”

“…Using serum from a patient with C8 deficiency of the complete type (C8 a-y-chain deficient) as a functional reagent, extensive inherited structural polymorphism in human C8 was demonstrated (12). Patterns given by human sera after isoelectric focusing in polyacrylamide gels consisted of major clear-cut bands of hemolysis that constituted the polymorphism and a poorly defined cathodal zone of hemolysis.…”

“…Patterns given by human sera after isoelectric focusing in polyacrylamide gels consisted of major clear-cut bands of hemolysis that constituted the polymorphism and a poorly defined cathodal zone of hemolysis. Although no explanation for this second zone of hemolysis was at hand, it was suggested that protein-protein complexes containing C8 were involved (12). The C8 genetic types of members of the families of two unrelated homozygous deficient subjects provided clearcut evidence that the deficiency was determined by a null allele (QO) at a structural C8 genetic locus (12 The present study utilizes serum from patients with deficiency of the 13-subunit of C8 to define a second common genetic polymorphism in this protein, to show that this variation is distinct from and independent of the previously described C8 polymorphism and therefore controlled by a separate genetic locus for C8, to show that the C8 ,3-deficiency state may represent a null allele at the structural locus for the ,8-subunit, to demonstrate the absence of close linkage between the C8 13-locus and the C8 a--y-locus or the loci for the major histocompatibility complex or C6 and to provide evidence that the ill-defined zone of hemolysis observed in C8 a-y-subunit typing may represent complete C8 molecules undergoing association and/or dissociation during isoelectric focusing.…”

Genetic analysis of C4 deficiency.

“…As deduced from the C4 levels in the plasma of these two individuals, they were assigned the C4 types shown. (14), and C8 (15) have been previously shown to be the result of inheritance of null or "blank" alleles at the respective structural loci for these complement proteins. Such null alleles at single structural loci are demonstrated by the inheritance in heterozygous carriers (preferably parents or children of markedly deficient subjects) of no more than one structural allele present in only one of the carrier's parents.…”