Fig. 3

Targeting pairs of allele-specific polymorphisms. a Common shared targetable variant pairs for SpCas9 and SaCas9 vary greatly by population, as demonstrated in the gene BEST1 including the 5-kb flanking regions in the five 1KGP superpopulations. b AlleleAnalyzer optimizes sgRNA pair combinations to best cover a cohort, which performs much better compared to the naïve approach of selecting the most highly shared pairs (top 5). c The pairs identified by the AlleleAnalyzer and the top 5 approaches demonstrate disparate patterns of sharing among the entire 1KGP population. The height of the arcs is only for visualization purposes and is not otherwise meaningful. d AlleleAnalyzer designs sgRNAs, colored by Cas variety, here with SpCas9 represented by purple and SaCas9 by green. e For each variant, or sgRNA site, multiple sgRNAs can be designed on both the reference and alternate alleles, depending which is to be targeted. Each sgRNA, then, has its own set of off-target sites, predicted using the incorporation of the CRISPOR tool in AlleleAnalyzer