The molecular genetics of components of complement

Adv Immunol. 1986;38:203-44. doi: 10.1016/s0065-2776(08)60007-3.


Rapid progress has been made in establishing linkages and in chromosome allocation of the genes of some 9 complement components. In the MHC, C2, Factor B, and two C4 or C4 related genes have been placed in some detail in both man and mouse. The gene coding for the cytochrome P-450 21-hydroxylase has been shown to be duplicated and immediately 3' to the two C4 genes, though it appears to be functionally and structurally unrelated to the complement components. Thus six genes have been mapped to this region where particular haplotypes are associated with increased susceptibility to a number of diseases, some of which are autoimmune in character. The complete gene structure of Factor B has been solved in man and rapid progress is being made with the C2 and C4 genes. The structural basis of the polymorphisms of these genes is being established. In C4, the polymorphism is exceptionally complex with varying numbers of loci and probably more than 50 allotypes occurring in man. A structural basis has also been found for the big differences in the biological activity of some of the C4 allotypes in man. Apart from the genes in the MHC, linkage has been found between the genes coding for C4bp, CR1, and Factor H. Remarkably there are sequence homologies between these proteins and C2 and Factor B, probably related to the ability to bind to one or other of the structurally similar proteins C3b and C4b. The complete cDNA sequences of C3 and C4 in mouse and man have given much information on the many posttranslational modifications of these proteins. A partial structure has been obtained for the C3 gene and the homology shown between C3, C4, C5, alpha 2-macroglobulin, and pregnancy zone protein. Although the amount of detailed information in the molecular genetics of complement components is accumulating rapidly, there appears to be a reasonable prospect that linkages and homologies will classify the data into a comprehensible form.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Animals
  • Carrier Proteins / genetics
  • Chromosome Mapping
  • Cloning, Molecular
  • Complement Activating Enzymes / genetics
  • Complement Activation
  • Complement C1q
  • Complement C2 / genetics
  • Complement C3 / genetics
  • Complement C4 / genetics
  • Complement C5 / genetics
  • Complement C9 / genetics
  • Complement Factor B / genetics
  • Complement Inactivator Proteins*
  • Complement System Proteins / genetics*
  • DNA / genetics
  • DNA Restriction Enzymes / genetics
  • Genetic Linkage
  • Glycoproteins*
  • Humans
  • Major Histocompatibility Complex
  • Polymorphism, Genetic


  • Carrier Proteins
  • Complement C2
  • Complement C3
  • Complement C4
  • Complement C5
  • Complement C9
  • Complement Inactivator Proteins
  • Glycoproteins
  • Complement C1q
  • Complement System Proteins
  • DNA
  • Complement Activating Enzymes
  • DNA Restriction Enzymes
  • Complement Factor B