The human immunoglobulin V sub(H)7 gene family consists of a small, polymorphic group of six to eight gene segments dispersed throughout the V sub(H) locus

In this report we describe the analysis and mapping of members of the human immunoglobulin V sub(H)7 gene family. V sub(H)7 and V sub(H)1 gene segments are closely related, with individual gene segments sharing between 78% and 82% sequence identity. Divergence from V sub(H)1 gene sequence occurs as an abrupt event at the boundary between framework region (FR) 2 and complementarity-determining region (CDR) 2 and continues through a major portion of FR 3. We used polymerase chain reaction amplification to create a 162-base pair probe spanning the family-specific region of CDR 2 and FR 3 that proved suitable for standard Southern analysis of genomic DNA. The V sub(H)7 gene family was found to be a small but discrete V sub(H) gene family consisting of five to eight germ-line elements, of which at least three are polymorphic. Four different V sub(H)7 gene segments were cloned from the germ line of a single individual, and assigned to specific restriction fragments by sequence-specific hybridization. Two of the four V sub(H)7 elements were pseudogenes. The pattern of sequence variation in these and other known pseudogenes suggests that these nonfunctional elements may play a role in the evolution of novel V sub(H) families. A combination of one and two-dimensional pulsed field gel electrophoresis was employed to map the chromosomal location of all of these V sub(H)7 elements. Individual V sub(H)7 gene segments were found to be dispersed over a region of at least 940 kb of DNA, and interspersed with members from other V sub(H) gene families. The polymorphism of the V sub(H)7 gene segments and their scattered location throughout the V sub(H) locus makes them potentially useful markers for mapping and linkage studies.