Characterization of two hybrid C4 allotypes (C4A*12 and C4B*3) by electrophoretic, serological and restriction fragment length polymorphism analyses.
Informative pedigree analysis of two rare C4 allotypes is reported. One proband was C4A deficient as a consequence of having one haplotype with a deleted C4A gene, and the second haplotype with two C4B genes--one encoding the common C4B*1 and one encoding a unique hybrid gene product C4B*3. C4B*3 had approximately normal C4B hemolytic activity, a single alpha-chain of MR 94,000 by SDS-PAGE but was positive for Rg:1,2 by hemagglutination inhibition (HAI) and for Rg:1 by Western blotting. The hybrid nature was confirmed by RFLP analysis with a Rg:1-associated fragment by Eco0109 digestion but no C4A-associated fragments by N1aIV digestion were identified. A gene conversion at Locus I which included just the C4 isotype region could explain the structure of C4B*3. The second pedigree had a Rodgers negative C4A*12 allotype. This C4A gene, which segregated with a single 7.0 kb TaqI fragment, encoded a C4A alpha-chain, which was negative for Rg:1 epitope. The affected haplotype lacked the Rg:1-associated fragment by Eco0109 digestion yet had the C4A specific N1aIV digestion fragment. These studies successfully employed RFLP analyses to confirm serologic and electrophoretic observations.
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
R H
RH
McLean
W B
WB
Bias
C
C
Giles
C Y
CY
Yu
R D
RD
Campbell
D000293:Adolescent; D002648:Child; D002874:Chromosome Mapping; D015934:Complement C4a / Q000235:genetics* / Q000276:immunology; D015935:Complement C4b / Q000235:genetics* / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005785:Gene Conversion; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000235:genetics* / Q000276:immunology; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011233:Precipitin Tests
D000939:Epitopes; D007126:Immunoglobulin Allotypes; D015934:Complement C4a; D015935:Complement C4b