The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters

We have constructed a panel of Abelson murine leukemia virus-transformed pre-B cells to study the organization of the mouse VH gene families. Based on the analyses of VH gene deletions on 51 chromosomes with VH gene rearrangements, we have inferred a map order of the Igh locus that holds for both the Igha and Ighb haplotypes. We show that members of each VH gene family are generally clustered, although three family clusters (VHS107, VH36-60, VGAM3.8) are dispersed in two or three subregions of the locus. Members of two VH gene families, VHQ52 and VH7183, are extensively interspersed and map within the same subregion. An examination of the distribution of VH group members (VH II, I, and III) within the locus suggests that two major duplications may, in part, explain the dispersed pattern of VH family clusters. The relationship of VH organization and functional expression is discussed in terms of position-dependent and complexity-driven models.