RECENT TRANSLOCATION OF VARIABLE AND DIVERSITY SEGMENTS OF THE HUMAN-IMMUNOGLOBULIN HEAVY-CHAIN FROM CHROMOSOME-14 TO CHROMOSOME-15 AND CHROMOSOME-16

We studied the organization and origin of three orphon regions, V-H-F, D-5-a, and D-5-b, of the human immuno globulin heavy-chain gene using yeast artificial chromo somes. V-H-F and two D-5 regions were mapped to chromosome bands 16p11 and 15q11-q12, respectively, by using human/rodent somatic cell hybrids and fluorescence in situ hybridization. No D-5 segments were found on chromosome 14, in contradiction to previous reports. The V-H-F region consists of 7 V-H segments and encompasses 160 kb of DNA. A cluster of V-H segments homologous to the V-H-F region orphons was found in the region 245-430 kb (V2-26 to V3-11) upstream of the J(H) cluster on chromosome 14. Comparison of V-H sequences between the V-H-F and the chromosome 14 loci indicates that the translocation of the V-H-F region took place, at the earliest, 20 x 10(6) years ago. The D-5-a and D-5-b regions were obtained in two independent contigs. The former contains only D segments in 140 kb of DNA, while the latter carries 3 V-H segments downstream of D segments in 110 kb of DNA. V-54, one of these V-H orphon segments, is about 95% homologous to V1-18, which is located within the putative ancestor of the V-H-F region on chromosome 14. Furthermore, the region detected by two DNA probes flanking the V-54 Segment was found only in the proximity of V1-18 within the 0.8-Mb V-H region on chromosome 14. These results suggest that the two orphon loci on chromosomes 15 and 16 may have been translocated simultaneously. (C) 1994 Academic Press, Inc.