Ig gamma restriction fragment length polymorphisms indicate an ancient separation of Caucasian haplotypes

Abstract

This investigation was undertaken to study genetic variation in the human immunoglobulin gamma heavy-chain (IgG) genes using Southern blot hybridization techniques to identify restriction fragment length polymorphisms (RFLPs). A genomic Ig gamma-1 clone was used as a probe, and variants were identified with two restriction enzymes (R.E.), each of which defined RFLPs at two separate IgG loci. Once alleles and haplotypes were determined, molecular localization of the alleles was made through genetic analysis of recombinant haplotypes and through the use of regional specific subclones. Linkage between the newly defined RFLPs and switch region variants as well as protein allotypic markers (Gm) was complete. This analysis included markers for Ig Mu, Alpha 1, Alpha 2, Gamma 1, Gamma 2, Gamma 3, and Pseudo Gamma. The picture that emerges from the molecular study of two common haplotypes, each with many rare variants resulting from recombination or mutation, confirms and extends the earlier immunological observations. The accumulated differences between the two major Caucasian IgG haplotypes indicate that their separation may be ancient and maintained through heterozygote advantage.