Fig. 1.
Fig. 1. The upper part is a fiber FISH map of the immunoglobulin CH region, based on the hybridization pattern of the probes indicated as red (biotin-labeled) and green (digoxigenin-labeled) bars. Although cosmid probes U2-2 and 3/64 each showed a single, continuous signal, cosmid cosIg6 hybidized to two stretches of genomic DNA, each twice as long as a normal cosmid and separated by a gap. These two stretches represent the two evolutionary duplication units of the human CH region, illustrating the high degree of homology between and within these units. The 16 kb C probe hybridized to both C genes and S regions and also gave a small signal at the site of Sμ, because Sμ is highly homologous to S. The Cγ4 probe hybridized to all Cγ genes as well as to the Cψγ gene. Below the scale bar a fiber representing the germline configuration of the most common haplotype (A) is shown. The second fiber is an allele that has undergone VDJ recombination, resulting in loss of almost the whole cosmid U2-2 probe signal. The four fibers below are alleles, derived from HCL cases that have also recombined their V, D, and J genes, but in addition have undergone class-switch deletion to, from top to bottom, the Cδ, Cγ3, Cγ1, and C1 genes. In each case this deletion has led to loss of all probe signals between VDJ and the target CH gene. In the case with Cδ switching this deletion is recognized by shortening of cosmid 3/64 signal combined with absence of the Sμ signal. The probe signals representing the remains of cosmids U2-2 and 3/64 containing the JH-5′ Sμ region are often too small to be observed. In the Cγ3-and Cγ1-switched fibers they are visible, however, as a red and a green dot at the left end of the fiber (arrow). To facilitate interpretation, only fibers of haplotype A were selected for this figure, and the lengths of the class-switched fibers were normalized to the germline fiber. This was only done for Fig 1, allowing the inclusion of a scale bar. In the other figures no scale bars were given because the fibers have different degrees of magnification and stretching.

The upper part is a fiber FISH map of the immunoglobulin CH region, based on the hybridization pattern of the probes indicated as red (biotin-labeled) and green (digoxigenin-labeled) bars. Although cosmid probes U2-2 and 3/64 each showed a single, continuous signal, cosmid cosIg6 hybidized to two stretches of genomic DNA, each twice as long as a normal cosmid and separated by a gap. These two stretches represent the two evolutionary duplication units of the human CH region, illustrating the high degree of homology between and within these units. The 16 kb C probe hybridized to both C genes and S regions and also gave a small signal at the site of Sμ, because Sμ is highly homologous to S. The Cγ4 probe hybridized to all Cγ genes as well as to the Cψγ gene. Below the scale bar a fiber representing the germline configuration of the most common haplotype (A) is shown. The second fiber is an allele that has undergone VDJ recombination, resulting in loss of almost the whole cosmid U2-2 probe signal. The four fibers below are alleles, derived from HCL cases that have also recombined their V, D, and J genes, but in addition have undergone class-switch deletion to, from top to bottom, the Cδ, Cγ3, Cγ1, and C1 genes. In each case this deletion has led to loss of all probe signals between VDJ and the target CH gene. In the case with Cδ switching this deletion is recognized by shortening of cosmid 3/64 signal combined with absence of the Sμ signal. The probe signals representing the remains of cosmids U2-2 and 3/64 containing the JH-5′ Sμ region are often too small to be observed. In the Cγ3-and Cγ1-switched fibers they are visible, however, as a red and a green dot at the left end of the fiber (arrow). To facilitate interpretation, only fibers of haplotype A were selected for this figure, and the lengths of the class-switched fibers were normalized to the germline fiber. This was only done for Fig 1, allowing the inclusion of a scale bar. In the other figures no scale bars were given because the fibers have different degrees of magnification and stretching.

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