title: Characterization of a de novo conversion in human complement C4 gene producing a C4B5-like protein.
abstract: Complement C4 is a highly polymorphic protein essential for the activation of the classical complement pathway. Most of the allelic variation of C4 resides in the C4d region. Four polymorphic amino acid residues specify the isotype and an additional four specify the Rodgers and Chido determinants of the protein. Rare C4 allotypes have been postulated to originate from recombination between highly homologous C4 genes through gene conversions. Here we describe the development of a de novo C4 hybrid protein with allotypic and antigenic diversity resulting from nonhomologous intra or interchromosomal recombination of the maternal chromosomes. A conversion was observed between maternal C4A3a and C4B1b genes producing a functional hybrid gene in one of the children. The codons determining the isotype, Asp(1054), Leu(1101), Ser(1102), Ile(1105) and His(1106), were characteristic of C4B gene, whereas the polymorphic sites in exon and intron 28 were indicative of C4A3a sequence. The protein produced by this hybrid gene was electrophoretically similar to C4B5 allotype. It also possesses reversed antigenicity being Rodgers 1, 2, 3 and Chido-1, -2, -3, 4, -5, and -6. Our case describes the development of a rare bimodular C4B-C4B haplotype containing a functional de novo C4 hybrid gene arisen through gene conversion from C4A to C4B. Overall the data supports the hypothesis of gene conversions as an ongoing process increasing allelic diversity in the C4 locus.
authors.affiliation: Department of Tissue Typing, Finnish Red Cross Blood Transfusion Service, Helsinki, Finland. Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Jaatinen
authors.forename: Miia
authors.initials: M
authors.lastname: Eholuoto
authors.forename: Tarja
authors.initials: T
authors.lastname: Laitinen
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Lokki
mesh_terms: D015934:Complement C4a / Q000235:genetics*; D015935:Complement C4b / Q000235:genetics*; D005785:Gene Conversion; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008285:Major Histocompatibility Complex
chemical_list: D015934:Complement C4a; D015935:Complement C4b