Example of electropherograms and primer schematic. A–F: Capillary electropherograms for a sample without (A, C, E) and with (B, D, F) a C9orf72 G4C2 repeat expansion using Penn-C9 sizing reaction (A and B), Penn-C9 repeat-primed PCR (RP-PCR) assays (C and D), and AmplideX-C9 (E and F). PCR products were separated on an ABI 3130xl Genetic Analyzer and visualized by GeneMapper software version 3.7. The vertical pink bars indicate off-scale peaks (in relative fluorescence units). The sample that is negative for an expansion is heterozygous for two and five repeat alleles, seen as peaks in A and E. Using the Penn-C9 RP-PCR method (which does not contain gene-specific primers, unlike AmplideX-C9, which does), peaks begin at three repeats because the primer incorporates three repeats into the product and then additional peaks are present at a periodicity of 6 bp up to the peak at the size of the second allele (in this case, five repeats). B: When a sample with a large G4C2 repeat expansion is amplified using the Penn-C9 sizing reaction, it only shows the normal allele (two repeats in this example). D and F: With both the Penn-C9 RP-PCR and AmplideX-C9, an expansion-containing sample demonstrates a characteristic saw-tooth pattern of peaks at 6-bp intervals that can be individually counted, up to 70 repeats (Penn-C9) or 140 repeats (AmplideX-C9). The horizontal red arrows label the four-repeat peak amplitude comparing the sensitivity of assay between AmplideX-C9 and Penn-C9 RP-PCR. A high-molecular-weight pile-up peak is highlighted by a red oval. G: Schematic diagram of the PCR primer binding sites in the intron between exons 1a and 1b of Penn-C9 and AmplideX-C9 assays relative to the C9orf72 hexanucleotide repeat region, (GGGGCC)n. A 22-bp region with frequent sequence variation downstream of the repeat region is shown (red boxed area). C9DR, downstream reverse primer; C9DRP, downstream repeat primer that contains an adapter primer tail (not shown); C9SF, sizing forward primer; C9SR, sizing reverse primer; C9UF, upstream forward primer; C9URP, upstream repeat primer that contains an adapter primer tail (not shown); GSF, gene-specific forward primer; GSR, gene-specific reverse primer; RP, AmplideX-C9 repeat primer; rpt, repeats; RvRP-PCR, reverse RP-PCR.