MOLECULAR CYTOGENETIC EVIDENCE FOR A COMMON BREAKPOINT IN THE LARGESTINVERTED DUPLICATIONS OF CHROMOSOME-15

Chromosomes from 20 patients were used to delineate the breakpoints of inverted duplications of chromosome 15 (inv dup[15]) that include the Prader-Willi syndrome/Angelman syndrome (PWS/AS) chromosomal region ( 15q11-q13), YAC and cosmid clones from 15q11-q14 were used for FISH an alysis, to detect the presence or absence of material on each inv dup( 15). We describe two types of inv dup(15): those that break between D1 5S12 and D15S24, near the distal boundary of the PWS/AS chromosomal re gion, and those that share a breakpoint immediately proximal to D15S10 10. Among the latter group, no breakpoint heterogeneity could be detec ted with the available probes, and one YAC (810f11) showed a reduced s ignal on each inv dup(15), compared with that on normal chromosomes 15 . The lack of breakpoint heterogeneity may be the result of a U-type e xchange involving particular sequences on either homologous chromosome s or sister chromatids. Parent-of-origin studies revealed that, in all the cases analyzed, the inv dup(15) was maternal in origin.