Figure 3.

An interstitial deletion within the IGH locus variable domain of the DB cell line. The deletion involves a 41 kb segment flanked by two RSS sequences with 23 bp spacers (filled arrows). The deletion was likely mediated through V replacement, although this allele has not undergone prior rearrangement at this locus. The deletion is initiated through recognition of an oppositely oriented cryptic heptamer (shown as a small downward facing, open triangle) within IGHV3-52 by the RSS of IGHV4-59. The deletion was detected by sequencing of the RSS-V4-59 junction (lower right panel); blue reads denote sequences with read pairs mapping across the junction. The rearrangement was confirmed by Sanger sequencing, with the recovered sequence matching the junction spanning sequence found with a split-reads (left lower panel, middle sequence). The split-reads sequence is shown aligned to the two sequences present in the reference genome (hg19). Nucleotides aligning to the reference regions are shown in gray, N-region nucleotides are white, and the reverse complement of the retained heptamer and nonamer of IGHV3-52 are shown in black.