Anatomy of normal and translocated IgH and cyclin D3 loci.

(A) The 1-Mb IgH locus 14q32 includes boxed coding regions, gamma-4 switch region (Sγ4), plus the Eμ and 3′ Εα enhancers (shaded ovals). Vertical arrows indicate HindIII restriction sites. Thick horizontal lines indicate VH cosmid located near the telomere (black dot) and CH BAC probes, plus 5′ and 3′ probes that flank all Sγ regions. For the cyclin D3 gene at 6p21, thick horizontal lines indicate the approximate positions of cosmid and BAC cyclin D3 probes. The anatomy of the KMM-1 der(14) t(6;14)(p21;q32) translocation breakpoint and 6.4-kb HindIII breakpoint clone are also depicted, with horizontal arrows indicating regions that were sequenced (see “Materials and methods”). The diagram is not to scale, and in all cases telomeric sequences are located to the left. (B) Southern blot of the KMM-1 genomic DNA digested withHindIII. The 5′ or 3′ Sγ probes flanking the Sγ regions are indicated at the top of the lanes. The 6.4-kb fragment that uniquely hybridizes with the 3′Sγ probe (*) represents an illegitimate switch recombination fragment that is the translocation breakpoint fragment.