DNA METHYLATION AND THE ORIGIN OF COMPLEMENT FACTOR-B POLYMORPHISM

BF is a polymorphic complement component encoded in the MHC. In each o f two frequent alleles of BF, BFFA and BF*FB, the difference in relat ion to the major allele BFS has been shown to consist in the nonsynon ymous substitution of only one base of the coding sequence. Both subst itutions occur within the same codon and affect contiguous positions, corresponding to the dinucleotide CpG in BFS. We propose here that BF FA and BF*FB arose independently from BF*S by the frequently describe d transition mutations associated with cytosine methylation at CpG sit es. By probing sperm DNA with methylation-sensitive restriction enzyme s, we obtained experimental evidence of germ line methylation of the C pG site considered. The dinucleotide of the BF gene probably constitut es a site for recurrent mutation, and this is of relevance for the use of BF as a genetic marker, and the origin of forms of the protein wit h altered functional properties.