Regions of genomic instability on 22q11 and 11q23 as the etiology for the recurrent constitutional t(11;22)

The constitutional t(11;22)(q23;q11) is the only known recurrent, non-Rober tsonian translocation. To analyze the genomic structure of the breakpoint, we have cloned the junction fragments from the der(11) and der(22) of a 1(1 1;22) balanced carrier. On chromosome 11 the translocation occurs within a short, palindromic AT-rich region (ATRR), Likewise, the breakpoint on chrom osome 22 has been localized within an ATRR that is part of a larger palindr ome. Interestingly, the 22q11 breakpoint falls within one of the 'unclonabl e' gaps in the genomic sequence. Further, a sequenced chromosome fl BAC clo ne, spanning the t(11;22) breakpoint in 11q23, is deleted within the palind romic ATRR, suggesting instability of this region in bacterial clones. Seve ral unrelated t(11;22) families demonstrate similar breakpoints on both chr omosomes, indicating that their translocations are within the same palindro me, It is likely that the palindromic ATRRs produce unstable DNA structures in 22q11 and 11q23 that are responsible for the recurrent t(11;22) translo cation.