Detection and verification of inversions. (A) Inversion with discordant fosmid data spanning both breakpoints. Multiple chimpanzee fosmids that are discrepant by orientation (blue lines) demarcate the two ends of a hypothetical inversion breakpoint on chromosome 3. (B) A large (44-Mb) inversion on human chromosome 12 identified by our analysis. Orange lines correspond to a known pericentric inversion (ideogram in C) (Yunis et al. 1980; Yunis and Prakash 1982). The breakpoints depicted map within 40 kb of recently characterized sequence breakpoints (Kehrer-Sawatzki et al. 2005b). A second “putative” inversion shown on chromosome 12 is due to a lineage-specific transposition of a segmental duplication in the chimpanzee genome. (C) A schematic of FISH probe design using three BAC probes, one distal to a putative inversion breakpoint (green box, RP11–1007O22F), one spanning the breakpoint (red box RP11–348G10), and one proximal to the breakpoint (blue box, RP11–959B13C5). The expected pattern of probe colors in chimpanzee should split the red probe into two hybridization signals on either side of the centromere. (D) The tricolor FISH results confirm the presence of an inversion on chimpanzee chromosome 12.