Skip to main content
Fig. 6 | Genome Biology

Fig. 6

From: Identification of pathogenic variants in cancer genes using base editing screens with editing efficiency correction

Fig. 6

Identified loss-of-function variants were in both coding and noncoding regions of BRCA1/2 genes. a, b Fraction of identified loss-of-function variants among all the tested variants across the exons of BRCA1 (a) or BRCA2 (b). c Identified loss-of-function variants in the BRCT domains of BRCA1 (PDB code: 1 T29). Variant positions are shown in green. d Four loss-of-function variants viewed on the mouse BRCA2-DSS1-ssDNA (PDB code: 1MJE). Residues corresponding to positions of five variants in human are shown in green. e Schematic of the c.9502-1G>A variant disrupting the splicing acceptor site in exon 26. f, g Secondary RNA structures predicted by RNAfold for the 232 nucleotide in the 5′ UTR of BRCA1 (f) and the 228 nucleotides in the 5′ UTR region of BRCA2 (g). The structure is colored by base-pairing probabilities. For unpaired regions the color represents the probability of being unpaired. Variants identified as “loss-of-function” in our screen were indicated by arrows. h, i Gene expression analysis after base editing for 6 sites in 5′ UTR regions of BRCA1 (h) or BRCA2 (i). Expression levels of BRCA1 or BRCA2 in treated group were normalized to non-targeting control groups. Error bars represent SEMs from 3 independent quantitative PCR experiments and two-tailed Student’s t tests were used to determine P values. Detailed data for the figure is shown in Table S1

Back to article page