We have previously demonstrated a genetic polymorphism of human C4. Modification of the methods employed in the separation and detection of C4 proteins has shown that further molecular variability exists in C4. By employing prolonged high voltage electrophoresis in agarose and a sensitive hemolytic detection system, three common C4 alleles and one less common have been detected. The following gene frequencies have been found in the Norwegian population: C4F: 0.46, C4F1: 0.20, C4S: 0.32, C4M: 0.02.

In 165 informative meioses not a single recombinant has been observed between C4 and HLA-B. In three known cross-over events between HLA-A and B, C4 in each instance follows B. The short map distance between C4 and HLA-B is further substantiated by haplotype association data. All 12 HLA-B8 chromosomes carry C4S. In seven out of eight instances HLA-B7 follows C4F1.

In 53 informative meioses no cross-over event has been observed between C4 and Bf (locus for factor B).

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