Mapping of human immunoglobulin heavy chain variable gene segments outside the major IGH locus

Physical mapping of the human immunoglobulin heavy chain gene cluster (IGH) on chromosome 14 has previously shown that the locus includes at least 63 variable region (VH) gene segments. Fifteen VH gene segments are located on six NotI DNA restriction fragments that are not within the mapped region of IGH. We have used human/rodent somatic cell hybrid lines to map these gene segments, as it was previously not proven that they are located in the chromosome 14 IGH locus. Four gene segments map to human chromosome 16 and two to chromosome 15. Apparently, four of the six NotI fragments, representing 11 VH gene segments, are not located within the chromosome 14 IGH locus. In addition, we have demonstrated that a YAC containing a functional human telomere, and mapping to 14qter, is located at the telomeric end of the IGH gene cluster physical map and contains at least four VH gene segments. This YAC is collinear with the existing physical map of genomic DNA. We conclude that our original physical map of IGH represents almost the entire locus on chromosome 14 and that the 11 gene segments newly mapped are not part of the functional IGH locus.