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.
McLean
R H
RH
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Bias
W B
WB
Giles
C
C
Yu
C Y
CY
Campbell
R D
RD
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