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 t ranslocation in humans, having been reported in more than 160 unrelated fam ilies, Balanced carriers are at risk of having offspring with the derivativ e 22 syndrome owing to 3:1 meiotic non-disjunction event, Clinical features of the der(22) syndrome include mental retardation, craniofacial abnormali ties and congenital heart defects. The breakpoints for the t(11;22) translo cation have been mapped to specific Alu repeats on chromosomes 11 and 22, i ndicating that this event is due to an Alu-Alu recombination, Remarkably, i n five samples derived from individuals with no apparent common ancestry th e der(11) and der(22) breakpoints appear to be almost identical at the geno mic sequence level. The small number of base differences between the sample s indicates some variation in the position of the breakpoints, although thi s appears to be quite limited. Indeed, the der(11) breakpoints are all loca ted within a region of just 32 bp and the der(22) break-points within 21 bp . If, as suggested by current data, the widespread occurrence of this trans location is due to multiple independent events, our results suggest that th is particular Alu-Alu recombination is subject to an unprecedented degree o f selection.