A human immunoglobulinIGHG3 allele (Gmb0, b1, c3, c5, u) with anIGHG4 converted region and three hinge exons

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The five human IGHG genes consist of three constant domain exons plus one of or four hinge exon(s), the quadruplicated hinge region being characteristic of the IGHG3 gene. Besides this structural difference, the IGHG genes are polymorphic, as demonstrated by the restriction fragment length polymorphism and, at the protein level, by the Gm allotypic antigenic determinants. In this paper, we report the sequence of the G3m(b0, b1, c3, c5,u) IGHG3 allele, typical of the Black African populations and of populations with Negroid admixture, found in a homozygous Tunisian designated as LAT. We demonstrate that this G3 allele contains only three hinge exons instead of four (the probable result of an unequal crossing over) and that IGHG3 genes with triplicated hinge exons (and therefore encoding shorter gamma 3 chains) are present in healthy individuals from different populations. Moreover, we show that the LAT G3m (b0, b1, c3, c5, u) coding sequence results from the conversion, in the CH3 exon, of the G3m (b0, b1, b3, b4, b5, u, v) allele, the most frequent IGHG3 gene in the Negroid populations, by the homologous region of a IGHG4 gene. The structural features of the LAT IGHG3 allele, which are the lack of one hinge exon and its conversion by the IGHG4 gene, demonstrate that both crossing-over and gene conversion events occur in the evolution of the human IGHG genes.