Figure 6—figure supplement 1.

Figure 6—figure supplement 1.

(a) Cartoon of ERG structure according to Wang and MacKinnon, 2017, highlighting the S4-6 domains. (b) Summary of mutations in the S4 domain in model systems studying ERG function in human (Hs ERG), medaka (Ol ERG) and zebrafish (Dr ERG) (Hassel et al., 2008; Nakajima et al., 1999; Ng et al., 2012; Sanguinetti and Xu, 1999; Zhang et al., 2011). (c) Workflow. Control injections only contained the sgRNA. (d) Phenotypes observed following editing of kcnh6a were grouped by being either isolated ‘cardiac’ phenotypes or with a ‘saturated’ outcome of ventricular asystole concomitant with additional unspecific developmental defects (‘global’). (e) Fraction of phenotype scores as a function of base editor generation. (f) Summary of editor type-specific C-to-T conversion efficiencies relative to the target C protospacer position for BE4-Gam (n = 5), ancBE4max (n = 4) and evoBE4max (n = 7). To highlight the dinucleotide context, the nucleotide preceding the target C is shown by red (A), green (T), blue (C) and yellow (G) squares below the respective C. (f') Example Sanger sequencing reads of single edited embryos with resulting missense and stop-gain mutations through editing at C3, C5, C7, and C8, respectively.