Figure 3
Figure 3. Genealogic analysis of CLL-cell subgroups from CLL subject 012. The 14 subgroups labeled A-N from CLL subject 012 (Figure 1) were sequentially arranged based on the assumption that descendant CLL-cell groups lower in the tree would have more somatic mutations than predecessor subgroups, that it would be unlikely for already mutated bases within the heavy and light chain immunoglobulin sequences to revert back to germ line sequences, and that the same mutation would not occur twice independently. In some instances, these assumptions could not be followed (subject 012, heavy chain at position 69 reverts back to germ line from stage D to E; subject 012, light chain at position 51 reverts back to germ line from stage E to F; patient 151, lambda light chain at position 31b, the same mutation occurs twice independently); therefore, efforts were made to minimize instances where these assumptions were violated. The germ line sequence (GL) is indicated at the top of the tree, and each subgroup is designated with its respective letter (A-N). The number of sequences or CLL cells in each group is listed in Figure 1. For the sequence data in the figure, only the bases which indicated the positions of partially shared and unique mutations are shown. The germ line base positions for each chain are indicated in the grid. Sequence changes from each previous subgroup are indicated in bold and underlined. For simplicity, shared mutations are not shown and are listed in Figure 1. Sequence data subgroups shown in lowercase letters and with a dashed circle label are intermediates that were not identified but whose existence was postulated.

Genealogic analysis of CLL-cell subgroups from CLL subject 012. The 14 subgroups labeled A-N from CLL subject 012 (Figure 1) were sequentially arranged based on the assumption that descendant CLL-cell groups lower in the tree would have more somatic mutations than predecessor subgroups, that it would be unlikely for already mutated bases within the heavy and light chain immunoglobulin sequences to revert back to germ line sequences, and that the same mutation would not occur twice independently. In some instances, these assumptions could not be followed (subject 012, heavy chain at position 69 reverts back to germ line from stage D to E; subject 012, light chain at position 51 reverts back to germ line from stage E to F; patient 151, lambda light chain at position 31b, the same mutation occurs twice independently); therefore, efforts were made to minimize instances where these assumptions were violated. The germ line sequence (GL) is indicated at the top of the tree, and each subgroup is designated with its respective letter (A-N). The number of sequences or CLL cells in each group is listed in Figure 1. For the sequence data in the figure, only the bases which indicated the positions of partially shared and unique mutations are shown. The germ line base positions for each chain are indicated in the grid. Sequence changes from each previous subgroup are indicated in bold and underlined. For simplicity, shared mutations are not shown and are listed in Figure 1. Sequence data subgroups shown in lowercase letters and with a dashed circle label are intermediates that were not identified but whose existence was postulated.

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