STRUCTURAL-ANALYSIS OF THE HUMAN-V(H) LOCUS USING NONREPETITIVE INTERGENIC PROBES AND REPETITIVE SEQUENCE PROBES - EVIDENCE FOR RECENT RESHUFFLING

The organization and evolution of the 0.8-Mb JH-proximal region in the human Ig V(H) locus were studied by mapping DNA fragments hybridized to non-repetitive intergenic probes and by determination of the conten t and distribution of repetitive sequences. Southern blot analysis of cloned DNA covering the 0.8-Mb region with intergenic probes allowed u s to map two to seven cross-hybridizing fragments by each probe. Clust ers of fragments detected by an identical set of probes appeared repea tedly within the 0.8-Mb J(H)-proximal region. Distantly located V(H) s egments flanked by a cluster of DNA fragments hybridized by the same s et of probes were highly homologous to each other, providing evidence for recent frequent duplication and translocation throughout the locus . DNA fragments detected by the same set of probes were orientated wit h the same 5' to 3' order within the cluster, suggesting little involv ement of inversion upon recombination in the locus. The content of int erspersed Alu and L1 sequences in the V(H) locus were not significantl y greater than the average in the genome.