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British Medical Bulletin 43:50-65 (1987)
© 1987 The British Council

research-article

Polymorphism and Molecular Genetics of Human C4

Michael C Carroll and Chester A Alper

Department of Pediatrics, Harvard Medical School Boston, Massachusetts

Abstract

There are two closely linked genetic loci for the fourth component of complement in man (C4A and C4B) and in some, but not all, other mammalian species. The protein products of human C4A differ from those of C4B in average net surface charge, haemolytic activity, alpha chain size and reactivity with anti-Chido and anti-Rodgers alloantisera. There is extraordinarily extensive inherited polymorphism at each of the C4 loci with duplicated C4 genes and common null alleles at each locus forming half-null C4A-C4B haplotypes. The double-null haplotype leading to C4 deficiency is rare.

Studies of C4 protein and cDNA have shown that C4A and C4B proteins differ by 14 nucleotides, mostly in the C4d region of the alpha chain near the internal thiolester. Allotypic and serologic differences appear to be largely the result of single amino acid substitutions. About half of C4 null genes are the result of DNA deletions, some of which also involve nearby steroid 21 -hydroxylase genes.


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