NONHOMOLOGOUS RECOMBINATION BETWEEN THE CYTOCHROME B(558) HEAVY-CHAINGENE (CYBB) AND LINE-1 CAUSES AN X-LINKED CHRONIC GRANULOMATOUS-DISEASE

We cloned and characterized a genomic DNA fragment including the delet ion junction of a chronic granulomatous disease patient with a 25-kb d eletion extending to the 5' two-thirds of CYBB. The 3' breakpoint of t he deletion exists in exon 7 of CYBB. A LINE-1 element lies at 5 kb up stream of CYBB in normal persons, and the 5' breakpoint of the deletio n in the patient is in the LINE-1 element. There are no significant ho mologies between corresponding normal 5' and 3' regions flanking the b reakpoint of the patient, so a nonhomologous recombination is the most possible mechanism for this 25-kb deletion. The analysis also reveals that the patient has a novel 30-bp duplication in the 5' flanking reg ion of the deletion point, which was transmitted by his mother with th e deletion. Furthermore we suggest that the deletion occurred in his g randfather. (C) 1998 Academic Press.