Many algorithms, including BreakDancer, Hydra, PEMer, and VariationHunter, for the detection of structural variation rely on the presence of discordant paired reads (24–27). In the case of interchromosomal translocations, one member of the pair maps to one chromosome and its mate to another (Figure 1). In the case of inversions or intrachromosomal translocations, the two ends map to the same chromosome but in the wrong orientation or the wrong distance apart. These algorithms are generally quite sensitive in detecting translocations and inversions in mappable areas of the genome; however, in general, they can detect breakpoints only with low resolution and often suffer from low specificity, particularly when one member of the pair maps to a repetitive region or to a region that shares homology with other areas of the genome. Furthermore, translocations, because of the mechanisms by which they are generated, tend to occur in regions with repetitive elements, such as tandem duplications and transposons (26). Thus, true positives exist in these regions and are difficult to discern from the many false positives. The Hydra and VariationHunter software packages attempt
