Chromosome duplications and deletions and their mechanisms of origin

Duplications and deletions of the same gene loci or chromosome regions are known to produce different clinical manifestations and are significant fact ors in human morbidity and mortality. Extensive cytogenetic and molecular c ytogenetic studies with cosmid and YAC probes in two patients with unique m osaicism for reciprocal duplication-deletion allowed us to further understa nd the origin of these abnormalities. The first patient's mosaic karyotype was 46,XX,inv dup(ll) (q23q13)/46,XX,del(11)(q13q23). The second patient ha d a 46,XY,dup(7)(p11.2p13)/46,XY, del(7)(p 11.2p13)146,XY karyotype. Fluore scence in situ hybridization studies on the first patient placed the two br eakpoints near the folate-sensitive fragile sites FRA11A and FRA11B. The pr esence of repeated sequences responsible for these fragile sites may have b een involved in the patient's duplication-deletion. Our investigation leads us to conclude that, in addition to known mechanisms (such as unequal cros sovers between homologs, unequal sister chromatid exchanges, excision of in trachromatid loops, and meiotic recombination within a single chromatid), d uplication-deletion can also arise by the formation of an overlying loop fo llowed by an uneven crossover at the level of the DNA strand.