The distribution of human C4 DNA variants in relation to major histocompatibility complex alleles and extended haplotypes

A C4 DNA polymorphism that can subdivide C4 allotypes and major histocompatibility complex-linked complement gene cluster allele combinations (complotypes) that are not distinguishable by standard electrophoretic means was used to assess further the distribution and linkage association of C4 variants. Segregation of the DNA polymorphism in family studies allowed assignment of particular variants to particular major histocompatibility complex haplotypes. These studies revealed that some complotypes were exclusively correlated with a particular C4 DNA variant, whereas others were not and could be subdivided according to which particular C4 DNA variant was observed. When complotypes that could be subdivided at the DNA level were considered in relation to flanking major histocompatibility complex markers, it was apparent that complotypes associated with major histocompatibility complex “extended haplotypes” had an exclusive correlation with a particular C4 DNA variant. This finding supports the hypothesis that “extended haplotypes” are unique associations of major histocompatibility complex allele combinations and are genetically similar, stably inherited units.