POSITIONAL CLONING OF A SEQUENCE FROM THE BREAKPOINT OF CHROMOSOME-9 COMMONLY ASSOCIATED WITH THE LOSS OF CYTOADHERENCE

Isolates of Plasmodium falciparum commonly undergo a large, subtelomer ic deletion of the right end of chromosome 9 during in-vitro cultivati on. This deletion is usually accompanied by loss of ability to cytoadh ere to melanoma cells, loss of a var-gene product from the red-cell su rface and a reduction in gametocyte production. However, cytoadherence is stable in the isolate ItG2, remaining after many generations in cu lture. Deletions in all the non-cytoadherent clones examined have brea kpoints within or delete a novel open-reading frame, called the breakp oint open-reading frame (BPORF), that is a unique sequence in the geno me. In ItG2, surprisingly, BPORF has been removed by a 15-kb deletion, internal in chromosome 9. These results indicate mechanisms to explai n why the deletion of chromosome 9 occurs so frequently and why cytoad herence is stable in ItG2.