title: Structural and immunologic analysis of gene triplications in the Ig heavy chain constant region locus.
abstract: The Ig H chain C region is a multigene family often involved in genomic rearrangements leading to deleted and duplicated haplotypes, most probably through unequal crossing over between homologous regions within the locus. The frequency of these haplotypes in Italy is around 2.7% each. Using PFGE analysis in two unrelated Italian families we found an abnormal high m.w. band, inherited in a Mendelian fashion. To assess the extension of the haplotype we performed Southern blot analysis using several specific Ig H chain C probes. In both cases, the haplotype turned out to be triplicated, with three copies of the genes from A1 to E. In one family segregation of a duplication from EP to G4 was also observed. Analysis of polymorphic loci suggests that the two triplications are of independent origin. Serological detection of IgA2 allotypes demonstrated the functional activity of the genes at the 3' end of the triplicated locus, ruling out any major effect of these large genomic rearrangements on Ig class switching. Furthermore, the triplicated haplotype does not seem to give rise to any clinically significant immunological impairment or increase in Ig serum concentrations.
authors.affiliation: Dipartimento di Genetica, Biologia e Chimica Medica, Università di Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Brusco
authors.forename: U
authors.initials: U
authors.lastname: Cariota
authors.forename: A
authors.initials: A
authors.lastname: Bottaro
authors.forename: C
authors.initials: C
authors.lastname: Boccazzi
authors.forename: A
authors.initials: A
authors.lastname: Plebani
authors.forename: A G
authors.initials: AG
authors.lastname: Ugazio
authors.forename: R
authors.initials: R
authors.lastname: Galanello
authors.forename: A M
authors.initials: AM
authors.lastname: van Leeuwen
authors.forename: G G
authors.initials: GG
authors.lastname: DeLange
authors.forename: S
authors.initials: S
authors.lastname: Depelchin
mesh_terms: D017353:Gene Deletion; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D017578:Immunoglobulin Class Switching; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D005810:Multigene Family; D010375:Pedigree
chemical_list: D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains