ANALYSIS OF GENETIC-VARIATION REVEALS HUMAN-IMMUNOGLOBULIN VH-REGION GENE ORGANIZATION
- 1 March 1988
- journal article
- research article
- Vol. 42 (3) , 446-451
Abstract
We have investigated the extent of genetic variation and the number of germ-line heavy-chain variable (VH) genes to obtain information on the organization and repertoire of the VH genes. Our studies revealed extensive genetic variation in this region, indicated by restriction-endonuclease site polymorphisms. Analysis of the distribution of selected polymorphic loci revealed evidence of linkage disequilibrium, particularly between VH2 and VH3 subclass loci, indicating that the subclasses are interdispersed in the human germ line chromosome. Absolute correlation was detected between alleles of a VH2 locus and the alleles of three VH3 loci, evidence for an extra set of VH genes, which are present in 48% of the Caucasian population. A preliminary estimate of the number of VH genes, approximately 50, indicates a smaller number of VH genes than suggested by the amount of protein variation. The extensive genetic variation we have observed may be associated with genetic differences in the immune response and potentially with variable susceptibility to autoimmune disorders.This publication has 18 references indexed in Scilit:
- Human immunoglobulin variable region genes: A new VH sequence used to detect polymorphismImmunogenetics, 1987
- One heavy chain variable region gene segment subfamily in the BALBc mouse contains 500–1000 or more membersCell, 1986
- High rate of somatic point mutation in vitro in and near the variable-region segment of an immunoglobulin heavy chain gene.Proceedings of the National Academy of Sciences, 1986
- Organization and evolution of variable region genes of the human immunoglobulin heavy chainJournal of Molecular Biology, 1986
- Polymorphisms of a human variable heavy chain gene show linkage with constant heavy chain genes.Proceedings of the National Academy of Sciences, 1984
- Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell linesNature, 1984
- The immunoglobulin heavy chain variable region (Igh‐V) locus in the mouse. I. One hundred Igh‐V genes comprise seven families of homologous genesEuropean Journal of Immunology, 1984
- Restriction fragment length polymorphisms associated with immunoglobulin C gamma genes reveal linkage disequilibrium and genomic organization.Proceedings of the National Academy of Sciences, 1983
- Analysis of a break in chromosome 14 mapping to the region of the immunoglobulin heavy chain locus.Proceedings of the National Academy of Sciences, 1983
- Somatic generation of antibody diversityNature, 1983