Human IGHC locus restriction fragment length polymorphisms in IgG4 deficiency: evidence for a structural IGHC defect. 1989

A Bottaro, and M DeMarchi, and G G DeLange, and C Boccazzi, and L Fubini, and C Borra, and N Cappello, and A O Carbonara
Dipartimento di Genetica, Biologia e Chimica Medica, Università di Torino, Italy.

In man, IgG4 is the least abundant of the four IgG subclasses, and its serum levels vary considerably from one subject to another. Its deficiency has been thought to lead to recurrent infections; nevertheless, it is also commonly found in healthy individuals (1/400 in the Italian population). In 39 subjects with IgG4 serum levels less than 1 microgram/ml, we used 4 different probes (described in the accompanying study, Bottaro et al., Eur. J. Immunol. 1989. 19: 2151) to examine 13 loci within the IGHC region and analyzed the RFLP for 7 of them. No aberrant restriction patterns were identified in any of the subjects, showing the absence of major IGHC structural alterations. The allele frequency of some loci, however, was significantly different from that of a control group of 95 random subjects. This variation was shown to depend on a selective increase in the number of homozygotes for the associated alleles, that reached significant levels for the IGHGP, G2, PG2, PG4 and SG4 loci, but not for SG1 and A2T. The highest value was reached for alleles in the PG4 region, just 5' of SG4. These data indicate that a minor structural IGHC defect is probably the cause of a significant fraction of IgG4 deficiencies. Moreover, the different association levels of the PG4 and SG4 regions suggest that this defect is likely to lie in an upstream regulatory region rather than in the structural G4 gene.

UI MeSH Term Description Entries
D007127 Immunoglobulin Constant Regions The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the C-terminus half of the IMMUNOGLOBULIN FAB FRAGMENT and two or three of them make up the rest of the heavy chains (all of the IMMUNOGLOBULIN FC FRAGMENT) Ig Constant Regions,Immunoglobulin Constant Region,Constant Region, Ig,Constant Region, Immunoglobulin,Constant Regions, Ig,Constant Regions, Immunoglobulin,Regions, Ig Constant
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D007153 Immunologic Deficiency Syndromes Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral. Antibody Deficiency Syndrome,Deficiency Syndrome, Immunologic,Deficiency Syndromes, Antibody,Deficiency Syndromes, Immunologic,Immunologic Deficiency Syndrome,Immunological Deficiency Syndromes,Antibody Deficiency Syndromes,Deficiency Syndrome, Antibody,Deficiency Syndrome, Immunological,Deficiency Syndromes, Immunological,Immunological Deficiency Syndrome,Syndrome, Antibody Deficiency,Syndrome, Immunologic Deficiency,Syndrome, Immunological Deficiency,Syndromes, Antibody Deficiency,Syndromes, Immunologic Deficiency,Syndromes, Immunological Deficiency
D008040 Genetic Linkage The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME. Genetic Linkage Analysis,Linkage, Genetic,Analyses, Genetic Linkage,Analysis, Genetic Linkage,Genetic Linkage Analyses,Linkage Analyses, Genetic,Linkage Analysis, Genetic
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D005787 Gene Frequency The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION. Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D005803 Genes, Immunoglobulin Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity). Genes, Ig,Immunoglobulin Genes,Gene, Ig,Gene, Immunoglobulin,Ig Gene,Ig Genes,Immunoglobulin Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017099 IgG Deficiency A dysgammaglobulinemia characterized by a deficiency of IMMUNOGLOBULIN G. Deficiency, IgG,Deficiencies, IgG,IgG Deficiencies

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