Characterization of chromosome 15q11-q13.1 duplication ( Dup15q) induced pluripotent stem cell (iPSCs) . (a) Map of the 15q11-q13.1 region. Boxes indicate genes (grey = biallelically expressed, red = maternally expressed, blue = paternally expressed) and lines indicate small nucleolar RNAs (snoRNAs). The striped boxes for ATP10A signify its variable imprinting status. The UBE3A anti-sense transcript is represented by the dotted line beginning at SNURF-SNRPN. Pink and blue shaded regions demarcate the Angelman Syndrome and Prader-Willi Syndrome imprinting centers (AS-IC and PWS-IC), respectively. Open circles represent unmethylated CpG islands, while the corresponding black circles on the maternal allele represent methylated CpG islands in silenced genes (black boxes). Breakpoints (BP1-BP5) are indicated. The regions deleted or duplicated in iPSC lines used in this study as well as their respective maternal (M) or paternal (P) allele copy numbers are indicated below the map. (b-d) Immunocytochemistry for the pluripotency markers TRA-1-60, Nanog, and SSEA-4 on idic(15) iPSC colonies (Idic1-8). Nuclei are counterstained with DAPI (blue). (e) Karyogram of idic(15) iPSCs shows a karyotype of 47,XX,+idic(15).ish15q12 SNRPN x 4, 15qter X2. Red box indicates the supernumerary isodicentric chromosome 15. (f, g) DNA FISH on metaphase idic(15) iPSCs (F) and interphase int dup(15) iPSCs (G) with a probe for SNRPN (red) and a control probe on the distal long arm of chromosome 15 (green). Two normal chromosomes 15 are indicated by white arrows (F). The isodicentric chromosome 15 (highlighted in white box and inset) shows four signals for SNRPN and no signal for the control probe (F). Three signals for SNRPN and two control signals indicate the presence of the interstitial duplication of 15q11-q13.1 on one chromosome 15 (G). Scale bars in (B) and (D) are 200 μm, in (C) is 100 μm, in (F) is 5 μm and in (G) is 10 μm.