(A) Position of USP18 within the block structure of the LCR22s. Each of the LCR22s are ordered with respect to the centromere of chromosome 22q11.2. The block structure of LCR22 was created using miropeats software to detect sequence relationships. The colors of the blocks were chosen to be coordinated with the genes within. The USP18 gene (red) is shown in its proper transcription orientation. The position of the functional USP18 locus (most centromeric copy in LCR22) and its unprocessed pseudogene copies within the LCR22 block structure are shown. (B) Duplication events for USP18. The exons (numbered red boxes) and high-copy repeating elements are shown (in a “+” orientation above the line and in a “-” orientation below the line. Alu elements are indicated by the subfamily. Mer elements (abbreviated as “M”) were drawn as tracked by RepeatMasker (UCSC browser; June 2002 assembly) in the vicinity of the USP18 functional locus as shown (11 exons; chr22:15573184-15600410). R/C, reverse and complement. The position of the breakpoints in the USP18 functional locus (substrate) and junctions in the duplicated copies (products) are indicated with a vertical line separating the juxtaposed intervals, shown in different colors depending on the LCR22 block to which they map. The Alu elements involved in the recombination events have black fill. The positions of the breakpoints in LCR22-2 that are shown are 15685023-15689864 (LCR22-2), 18244496-18249337 (LCR22-4), and 17418000-17420692 (LCR22-3a). A different breakpoint in the interval between exons 10 and 11 occurred, creating the copy in LCR22-2, shown at positions 15790288-15794241 and LCR22-4 at 18351456-18355409. For more details see Supplemental Figures 1-3.