AN ESTIMATE ON THE FREQUENCY OF DUPLICATED HAPLOTYPES AND SILENT ALLELES OF HUMAN C4 PROTEIN POLYMORPHISM .2. INVESTIGATIONS IN HEALTHY NEGRO FAMILIES

The first investigation of complete MHC marker data in South African N egroes by segregation analysis in 11 families with up to three generat ions is presented, including quantitative evaluation of C4 allotype pa tterns and C4 beta chain determinations according to Steuer et al. (1) . The frequency of homo- and heteroduplicated, hybrid, and non-express ed C4 alleles was determined from C4 protein phenotyping, including C4 alpha and beta chains, quantitative estimates of the relative electro phoretic C4 banding patterns by scanning densitometry, and from the ot her classical MHC markers by submitting all results to the family anal ysis program (FAP). From unrelated non-diseased individuals (n = 105) in these families with 62 haplotypes, the following frequencies were o bserved for non-expressed alleles: C4AQ0 0.1189, C4B*Q0 0.2552, and f or the total of heteroduplicated alleles: C4A 0.0645, C4B 0.0608. Appl ying additionally quantitative determinations of C4 banding patterns, homoduplications such as C4A3 A*3, C4B*1 B*1, C4B*3 B*3, and the hete roduplication C4A3 A*2 were assumed. In the investigated individuals the heteroduplications of C4A12 and C4A*3 with the A*91 allele and of C4B2 with C4B*92 were observed. It was concluded that not only allel e frequencies but also the frequency of heteroduplications seems to be of specific ethnic character. Furthermore, the prior hypothesis that deletion or non-expression at one C4 locus is accompanied by duplicati on at the other was only confirmed for non-expressed B-alleles with C4 A3 A*91 or C4A*12 A*91. For the correlation of C4 genes with other cl ass III markers no linkage disequilibria with p-values less than 0.001 as in Caucasoid populations were seen. The presented data may form a basis for further investigations in African Negroes on characteristic MHC haplotypes in defined diseases.