Detection of MAGEL2 peptides in Magel2 mutant rats and Schaaf-Yang syndrome (SYS) human induced pluripotent stem cell (hiPSC) lines. (A) Schematic diagram showing the expected full-length wild-type MAGEL2 protein compared to the truncated mutant MAGEL2 protein. Within each schematic, the white box indicates wild-type amino acid (aa) sequence; the yellow box indicates the mutant aa sequence. The anticipated detection of wild-type (blue boxes) and mutant (light-pink boxes) peptides are shown below each schematic diagram. (B) Representative image of SDS-PAGE gel containing wild-type (m+/p+), maternally inherited (m−/p+), paternally inherited (m+/p−) and homozygous Magel2 (m−/p−) hypothalamus samples with excisions from 93-170 kDa and 53-93 kDa. R corresponds to each biological replicate. (C) Ion scores (m/z) of detected wild-type and mutant peptides within each allelic combination. R corresponds to each biological replicate. Rat wild-type MAGEL2 aa sequence corresponding to n=1 wild-type peptide was detected in m+/p+ and m−/p+, and not detected in m+/p− or m−/p−, rat hypothalami. All three predicted mutant peptides were only detected within the novel region (p.132-728) in m+/p− and m−/p− rat hypothalami. n/d, not detected. (D) Schematic diagram showing expected full-length MAGEL2 protein in typical developing (TD) control hiPSC lines compared to predicted truncated mutant MAGEL2 protein in either c.1996dupC or c.1802delC hiPSC lines derived from SYS individuals. Boxes indicate wild-type aa sequence (white), mutant aa sequence for c.1996dupC (yellow), mutant aa sequence for c.1802delC (orange) and anticipated TD-detected peptides (green). (E) Representative image of SDS-PAGE gel containing TD control, c.1996dupC and c.1802delC samples. R indicates biological replicate number. Red boxes outline the excisions from 120-180 kDa (TD hiPSCs) and 65-100 kDa (SYS hiPSCs). (F) Ion scores of detected TD control and mutant peptides within each sample replicate. not detected (n/d); green, strong/confident peptide detection; red, poor/low confident peptide detection. Both TD control replicates had detectable MAGEL2 peptides; c.1996dupC and c.1802delC replicates did not display detectable control or mutant sequences.