Positional cloning of a sequence from the breakpoint of chromosome 9 commonly associated with the loss of...

Isolates of Plasmodium falciparum commonly undergo a large, subtelomeric deletion of the right end of chromosome 9 during in-vitro cultivation. This deletion is usually accompanied by loss of ability to cytoadhere to melanoma cells, loss of a var-gene product from the red-cell surface and a reduction in gametocyte production. However, cytoadherence is stable in the isolate ItG2, remaining after many generations in culture. Deletions in all the non-cytoadherent clones examined have breakpoints within or delete a novel open-reading frame, called the breakpoint open-reading frame (BPORF), that is a unique sequence in the genome. In ItG2, surprisingly, BPORF has been removed by a 15-kb deletion, internal in chromosome 9. These results indicate mechanisms to explain why the deletion of chromosome 9 occurs so frequently and why cytoadherence is stable in ItG2.