Fig 1: CRISPR-Cas9 can selectively target the PSEN1M146L allele in human fibroblasts(A and B) NGS analysis of the PSEN1 allele from CRISPR-Cas9-treated PSEN1M146L/WT and PSEN1WT/WT fibroblasts with CRISPResso2. Alignment and editing frequency of reads as determined by the percentage and number of sequence reads showing unmodified and modified PSEN1 alleles from CRISPR-Cas9-treated PSEN1M146L/WT and PSEN1WT/WT fibroblasts. The M146L gRNA resulted in indel formation in the PSEN1M146L but not in the PSEN1WT allele (indel formation is depicted separately for the different alleles of the PSEN1M146L/WT fibroblasts). (C) Visualization of the distribution of the 15 most frequently identified alleles around the cleavage site. Nucleotides are indicated by unique colors (A = green; C = red; G = yellow; T = purple). Red rectangles highlight inserted sequences. Horizontal dashed lines indicate deleted sequences. The vertical dashed line indicates the predicted cleavage site. The most common modification was a single base pair deletion. (D) Frameshift analysis of coding sequence reads affected by modifications (unmodified reads are excluded from this analysis). (E) Predicted impact on splice sites. Modified splice site refers to a read in which either of the two intronic positions adjacent to exon junctions is disrupted.