The most frequent constitutional translocation in humans, the t(11;22)(q23;q11) is due to a highly specific alu-mediated recombination

The t(11;22) is the most common recurrent non-Robertsonian constitutional translocation in humans, having been reported in more than 160 unrelated families. Balanced carriers are at risk of having offspring with the derivative 22 syndrome owing to 3:1 meiotic non-disjunction event. Clinical features of the der(22) syndrome include mental retardation, craniofacial abnormalities and congenital heart defects. The breakpoints for the t(11;22) translocation have been mapped to specific Alu repeats on chromosomes 11 and 22, indicating that this event is due to an Alu-Alu recombination. Remarkably, in five samples derived from individuals with no apparent common ancestry the der(11) and der(22) breakpoints appear to be almost identical at the genomic sequence level. The small number of base differences between the samples indicates some variation in the position of the breakpoints, although this appears to be quite limited. Indeed, the der(11) breakpoints are all located within a region of just 32 bp and the der(22) breakpoints within 21 bp. If, as suggested by current data, the widespread occurrence of this translocation is due to multiple independent events, our results suggest that this particular Alu-Alu recombination is subject to an unprecedented degree of selection.