THE PHYSICAL ORGANIZATION OF THE HUMAN-IMMUNOGLOBULIN HEAVY-CHAIN GENE-COMPLEX

Two dimensional DNA electrophoresis (2D-DE) was used to map the variable (V(H)) region of the human heavy chain immunoglobulin gene cluster. Seventy-six V(H) gene segments were mapped to specific SfiI, BssHI and NotI fragments by 2D-DE. We have determined that a common insertion/deletion polymorphism of 80 kb, involving three V(H) gene segments, occurs in the V(H) region. The physical map suggests that the evolution of the human IGH gene complex involved duplication of blocks containing different V(H) families. This physical map will allow comparison of the usage of V(H) loci in human ontogeny with their proximity to the C(H) region. Knowledge of the germline repertoire of a particular DNA source studied is essential as the number of the dispersed V(H) gene segments of V(H) families, especially of the V(H)5 family, is variable. 2D-DE, as illustrated here for the IGH gene cluster, has general application in the development of large scale physical maps of gene and repeat families.