A deletion insertion leading to the generation of a direct repeat as a result of slipped mispairing and intragenic recombination in the faster VIII gene

A deletion/insertion in the human factor VIII gene was found in a patient w ith severe hemophilia A; 316 bp were removed, viz., those enclosing part of intron 15 and the first 7 bp of exon 16. In addition to the deletion, 6 bp were added to the deletion breakpoints; this resulted in the duplication o f an existing 13-bp unit. Thus, an overlapping 13-bp direct repeat was gene rated at the deletion junction. Moreover, the deleted fragment itself was f lanked by two homologous 6-bp sequences, one unit being lost by the deletio n. A combination of slipped mispairing during replication and an intragenic recombination is discussed to describe this deletion/insertion process.