title: Human C4 polymorphism: pedigree analysis of qualitative, quantitative, and functional parameters as a basis for phenotype interpretations.
abstract: Ten families with 82 members were investigated for C4A- and B polymorphism in a blind trial. Phenotyping was done on neuraminidase treated sera by immunofixation and simultaneously by hemolytic overlay electrophoresis. In addition Rg, Ch, BF, C2, HLA-A, B, C, DR, and GLO were determined. After decoding the samples the reliability of blind typing was found to be 84.4% according to segregation patterns. Inconsistencies occurred mostly when A4, A2, or A92 were present. The detection of silent A*Q0 and B*Q0 alleles was more critical than that of "difficult" allotypes. The quantitation of the C4A/B ratio by densitometry of stained gels or by conventional immunochemical measurements of serum C4 level could not substantially improve the identification of A*Q0 or B*Q0. C4 dependent activity in radial diffusion hemolysis showed satisfactory correspondence with the number of expressed C4B alleles. At least three haplotypes with two C4A genes (duplicated A genes) were observed as ascertained from offspring analysis in accordance with the MHC segregation pattern. Individuals with the duplicated C4A gene (C4A*3, A*2, in the absence of any other expressed A allele or together with C4A*92) showed only partial inhibition of Rodgers antisera. Partial inhibition of Chido antisera was seen in individuals with C4B 2 (in the absence of other B allotypes). The findings support the hypothesis of at least two structural C4 loci. They also demonstrate the inconsistency of quantitative data in the recognition of silent alleles.
mesh_terms: D000483:Alleles; D001789:Blood Group Antigens / Q000235:genetics*; D002874:Chromosome Mapping; D003175:Complement C2 / Q000235:genetics; D003181:Complement C4 / Q000235:genetics*; D015934:Complement C4a; D015935:Complement C4b; D011415:Complement Factor B / Q000235:genetics; D005802:Genes, MHC Class II; D005819:Genetic Markers; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D006461:Hemolysis; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000235:genetics; D009439:Neuraminidase / Q000032:analysis; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D001789:Blood Group Antigens; D003175:Complement C2; D003181:Complement C4; D005819:Genetic Markers; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D015934:Complement C4a; D015935:Complement C4b; D009439:Neuraminidase; D011415:Complement Factor B; D007791:Lactoylglutathione Lyase