Polymorphism and utilization of human VH Genes

Abstract

The human VH germline repertoire comprises approximately 100 elements, which can be grouped into seven families based on nucleotide sequence similarity. Members of different families are interspersed throughout the complex, with limited sets of alleles identified for most loci. Linkage disequilibrium between most elements is weak. Variation within the population can be attributed to differences in nucleotide sequence between allelic genes as well as to differences in the number of genes present. Gene number per haplotype varies as a result of the common occurrence of insertion/deletion polymorphisms, which may be small, involving a single element, or may be extensive, involving four or five elements. In some cases, such polymorphisms may involve duplication of a functional VH gene segment on some haplotypes and deletion of the gene on others. The resulting variation in germline composition of the VH locus may have profound effects on VH gene utilization.