Prevalence and polymorphism of human VH3 genes

Abstract

To better understand heterogeneity of human VH genes, we have studied polymorphism among three homologous genes from VH3, the most complex human VH gene family. Sequence-specific oligonucleotide probes were used to identify the germ-line source of each gene. The fetally expressed gene 56p1, and the germ-line VH element 1.9III, were identified and shown to be distinct. Also identified was T5M10, a VH element that resembles 56p1 and 1.9III, and likely corresponds to the previously described germ-line gene, hv3005. The elements 56p1, 1.9III, and T5M10 were each polymorphic, and in 52 unrelated individuals, their prevalences were 62%, 92%, and 35%, respectively. Among individuals lacking the hybridization bands characteristic of 56p1, 1.9III, or T5M10, alternative RFLP or coding region sequence variants were not found. In the population studied, these three VH elements were present in five different combinations, and at least three haplotypes. The distribution of these VH elements indicated they are not alleles of a single locus, and 56p1 and 1.9III are probably not alleles of each other. These results suggest that polymorphism is commonplace among human VH3 genes, but that a limited number of conserved alleles dominate each locus. We conclude that heterogeneity in the VH germ-line repertoire may derive more from diversity of haplotypes than from diversity of alleles.