Figure 5

Observed and expected read-depth signals for a two-copy duplication on chromosome 1. There are breakpoints 155,184,704 and 155,205,331 for two individuals. The mediating LCRs have coordinates [155180173,155190755] and [155200767,155213257]. For perspective, the observed and expected read depths are shown for an additional 100 kb flanking the breakpoints. The expected read-depth signal appears as a dotted line; red for the called NAHR two-copy duplication, blue for no NAHR event. The solid green line is the inferred observed read-depth signal in repetitive regions (see Section ‘False discovery rate via read depth’). The solid black line is the observed read-depth signal in the unique region of this locus. Vertical thin black lines mark the called breakpoints. Read-depth curves are calculated as sliding 1,250-bp window sums for presentation. The expected read-depth signals are highly non-uniform due to the GC-bias in fragment distribution (see Section ‘Read depth’). (a) Read depth in unique and repeat regions for NA19129. Notice that the observed read-depth signal for the unique sequence in between the mediating LCRs follows the expected read-depth signal of a two-copy NAHR duplication (red dotted line) much closer than the expected read-depth signal if there was no NAHR event (blue dotted line). We also see the inferred observed read-depth signal transition from closely following the expected no-event signal (blue) to the expected duplication signal (red) and back again at approximately the location of the breakpoints. Together, the observed read-depth signal in the unique regions and the inferred observed read-depth signal in the repetitive regions give an fdr =1.3×10⁻³; strong support for the proposed two-copy NAHR duplication. (b) Unique read depth and inferred repeat read depth is shown at the same locus for European individual NA07051. Our model determined there was not an NAHR event for this individual at this locus. The fdr at this locus for NA07051 is >0.99. chr, chromosome.