EXPRESSED COPIES OF THE MN7 (D15F37) GENE FAMILY MAP CLOSE TO THE COMMON DELETION BREAKPOINTS IN THE PRADER-WILLI ANGELMAN-SYNDROMES/

Approximately 70 % of patients with Prader-Willi syndrome or Angelman syndrome have a similar sized de novo deletion of 3-4 Mb in the proxim al region of 15q. The distal breakpoints appear to cluster between the P gene (OCA2) and D15S24, whereas two deletion breakpoint clusters ha ve been identified on the proximal side tone centromeric to D15S541 an d one between D15S541 and D15S9). Based on the identification of a gen e family in 15q11-->q13 (MN7, D15F37), we have previously proposed tha t the presence of multiple copies of this sequence may be related to t he instability of this region. Using fluorescence in situ hybridizatio n and YAC mapping, we have found that at least one D15F37 locus is cen tromeric to D15S9 and at least two are between OCA2 and D15S24. As det ermined by cDNA cloning and sequence analysis, each of the individual loci is expressed. The close proximity of the D15F37 loci and the dele tion breakpoints suggests that the common deletions arise by unequal c rossover events at or near these loci.