In summary, we directly demonstrate that the DUP4 variant has a complex structure involving a duplication of GYPE, deletion of GYPB, and generation of two GYPB/GYPA fusion genes. The evolution of this particular rearrangement remains unclear. A model involving three intermediates has been suggested but none of these putative intermediates have yet been found.5 Given the relatively limited numbers of individuals analyzed for glycophorin structural variation so far, it is possible that these intermediate variants are rare or have been lost from the population. Indeed, given the extensive structural variation seen already at this locus, it seems likely that a high rate of genomic rearrangement generates complex variants that are mostly lost by genetic drift, with a few, such as DUP4, increasing in frequency due to positive selection. Further studies on the extensive variation in Africa are needed to fully characterize the variation at this locus.