title: Restriction fragment analysis of duplication of the fourth component of complement (C4A).
abstract: The two genes encoding the fourth component of complement (C4A and C4B) reside between HLA-B and HLA-DR on human chromosome 6. Two kilobases downstream from each C4 gene lies a 21-hydroxylase gene (CA21HA and CA21HB, respectively). Utilizing the method of Southern blotting and a 5'-end 2.4-kb BamHI/KpnI fragment of the C4 cDNA, we have analyzed TaqI-digested DNA from four pedigrees with one or more extended haplotypes containing a C4A duplication, as demonstrated by protein electrophoresis and segregation analysis. Two C4A protein duplications (C4A*2,A*3,C4B*QO and C4A*3,A*5,C4B*QO) segregated with two large TaqI DNA restriction fragments (7.0 and 6.0). In pedigree Fi, one individual homozygous for HLA-A3,B35,C4,DR1,DQ1,BFF,C2C,-C4A2,3,C4BQO had TaqI 7.0- and 6.0-kb restriction fragments with equal hybridization intensities as measured by two-dimensional densitometry (7.0/6.0 kb = 0.83, SD = 0.12, N = 7). A hybridization probe for the 21-hydroxylase gene also demonstrated equal gene dosage (CA21HA/CA21HB = 1.01). DNA from another individual (Ma I-2) with a different C4A gene duplication (C4A*3,A*5,C4B*QO) also had equal densitometry measurements (7.0/6.0 kb = 1.07). We conclude that two extended haplotypes from unrelated pedigrees have two C4 genes and both C4 genes encode separate C4A alleles. These findings are compatible with a gene conversion event of C4B to C4A.
authors.affiliation: Department of Pediatrics, Johns Hopkins Hospital, Baltimore, Maryland 21205.
authors.forename: R H
authors.initials: RH
authors.lastname: McLean
authors.forename: P A
authors.initials: PA
authors.lastname: Donohoue
authors.forename: N
authors.initials: N
authors.lastname: Jospe
authors.forename: W B
authors.initials: WB
authors.lastname: Bias
authors.forename: C
authors.initials: C
authors.lastname: Van Dop
authors.forename: C J
authors.initials: CJ
authors.lastname: Migeon
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics; D002648:Child; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D003181:Complement C4 / Q000235:genetics*; D015934:Complement C4a; D004262:DNA Restriction Enzymes; D005260:Female; D005796:Genes; D005921:Glomerulonephritis / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008285:Major Histocompatibility Complex; D008297:Male; D010375:Pedigree
chemical_list: D003181:Complement C4; D006680:HLA Antigens; D015934:Complement C4a; D004262:DNA Restriction Enzymes