DNA POLYMORPHISMS OF THE COMPLEMENT C6 AND C7 GENES

The linked C6 and C7 loci are rich in genetic markers, both at the pro tein and DNA levels. There are now seven common DNA polymorphisms dist ributed over about 300 kbp of chromosome 5p12-14. We report a new TaqI RFLP for C7 and a method for typing a C7 variant (T368S) hitherto kno wn only from cDNA clones. We have re-investigated the published RFLPs to provide information on their frequency in North European Caucasian (predominantly British and Irish) subjects and have revised some of th e published parameters, especially the sizes of polymorphic restrictio n fragments. Their precise locations within the genes are also reporte d : the three markers for CB are in exon 3, intron 3 and adjacent to e xon 17 and the four markers for C7 are in introns 15 and 13 and in exo ns 13 and 9. The gene frequencies of the second commonest allele of al l seven markers lie in the range 0.2 to 0.37, except C6 A/B in the Jap anese, where the frequencies of both common alleles are about 0.45. We have estimated the gene frequencies for the DNA polymorphisms which c orrelate with C7 M/N phenotype and for the C6 A/B phenotype and find t hem to be the same as the phenotypic estimates in Caucasians and in th e Japanese respectively. The markers provide the possibility of defini ng 128 haplotypes, many (28) of which have been observed. Allelic asso ciations in these genes are generally surprisingly weak.