Extended Data Table 3:
Repair of eight pathogenic microduplication alleles in individual cellular experiments.
| Pathogenic allele | LDLRdup1 | LDLRdup2 | LDLRdup2 | LDLRdup3 | LDLRdup4 | LDLRdup5 | PORCNdup | GAAdup | GAAdup | GLB1dup |
|---|---|---|---|---|---|---|---|---|---|---|
| #AlleleID | 245617 | 245706 | 245706 | 245709 | 245715 | 246266 | 25739 | 354180 | 354180 | 98805 |
| Predicted frequency of deletions restoring frame (%) | 79 | 98 | 96 | 95 | 86 | 94 | 90 | 76 | 93 | 95 |
| Flow cytometric frameshift frequency (%) | 57 | 95 | 57 | 90 | 72 | 87 | ND | 79 | 74 | 85 |
| Predicted frequency of repair to wild-type genotype among all major editing products (%) | 72 | 90 | 83 | 94 | 85 | 86 | 89 | 74 | 91 | 79 |
| Flow cytometric phenotypic repair frequency, mESC (%) | 36 | 69 | 30 | 53 | 33 | 78 | ND | ND | ND | ND |
| Observed frequency of repair to wild-type genotype among all edited products in HTS, mESC (%) | ND | 67 | 39 | 25 | 15 | 65 | 48 | 76 | 59 | 42 |
| Observed frequency of repair to wild-type genotype among all edited products in HTS, U2OS (%) | 100 | 88 | ND | ND | ND | 77 | ND | ND | ND | ND |
| Observed frequency of repair to wild-type genotype among all edited products in HTS, HCT116 (%) | ND | ND | ND | 24 | ND | 89 | ND | ND | ND | ND |
| Observed frequency of repair to wild-type genotype among all edited products in Lib-B, mESCs (%) | ND | ND | ND | ND | ND | 58 | 42 | ND | 63 | 41 |
| CTGCGAA | TGCAAGG | TTCCTCG | ACTGCAA | TTTTCCT | GACATCT | GCTGTCC | CAGCTGC | GCTGCAG | GTGTGAA | |
| GATGGCT | ACAAATC | TCAGATT | GGACAAA | CGTCAGA | ACTCGCT | CTGGCTT | AGAAGGT | AAGGTGA | CTATGGT | |
| CGGAGGC | TGACAGG | TGTCCTG | TCTGAGG | TTTGTCG | GGTGAGC | TTATCCC | GACTGCA | CTGCAGA | GCATATA | |
| gRNA + PAM sequence | TCGGAT | ACAAAT | TCAGAT | ACAAAT | TCAGAT | TGG | TGG | GAAGGT | AGG | TGG |
| KKH | KKH | KKH | KKH | KKH | KKH | |||||
| Cas9 Type | SaCas9 | SaCas9 | SaCas9 | SaCas9 | SaCas9 | SpCas9 | SpCas9 | SaCas9 | SpCas9 | SpCas9 |
ND, not determined. LDLRdup1, LDLR:c.526_533dupGGCTCGGA. LDLRdup2, LDLR:c.668_681dupAGGACAAATCTGAC. LDLRdup3, LDLR:c.669_680dupGGACAAATCTGA. LDLRdup4, LDLR:c.672_683dupCAAATCTGACGA. LDLRdup5, LDLR:c.1662_1669dupGCTGGTGA. PORCNdup, PORCN:c.1059_1071dupCCTGGCTTTTATC. GAAdup, GAA:c.2704_2716dupCAGAAGGTGACTG. GLB1dup, GLB1:c.1456_1466dupGGTGCATATAT.