G0 and G1 mosquito samples were chosen randomly, and samples from G7 through G10 were all individuals carrying NHEJ alleles selected by phenotype (white-eyed/DsRed-negative). (A) G0: ‘Founder’ individuals show the baseline for the IDAA profile. Both males and females present a WT sequence at the target site shown by a yellow peak (because all female G0s are WT, whereas even though G0 males were a combination of transgenic and WT males only WT [and NHEJ alleles, if there were any] were amplified by PCR). G1: First-generation offspring display expected low frequency of indels in sample pools of WT and low-frequency NHEJ individuals. Red-dotted line zoom-in inserts display the rarely occurring NHEJ indel events in the population (<0.8%), and the black and gray triangles indicate spectra peaks of indels. Two types of indels, -11 and -4, were identified in G1. IDAA and ddPCR allowed the analysis of a large number of samples from G0 and G1, which was required to determine NHEJ allele-generated frequency. G7–G10: White-eyed phenotype mosquitoes with homozygous NHEJ alleles were selected from different generations. Although phenotypically similar, the variable peak heights indicate that G7 individuals represent a heterogeneous population, with different types of indels, whereas G9 (near equal peak heights) and G10 (single peak) represent a homogeneous population with only one indel (-4) selectively carried to subsequence generations. WT alleles are distinguished by yellow peaks when present in the spectra; when absent, yellow triangles above the spectra panels are used to reference the WT location. Frameshift-causing indels are indicated with peaks color-coded in blue. (B) Sanger sequencing in mosquitoes from G7 (11 individuals), G9 (5 individuals) and G10 (16 individuals) show results comparable with the IDAA findings. Three types of indels (-4, +1, +8) were identified in G7 mosquitoes, whereas only one type of indel (-4) was present in G9 and G10 (Supplementary Table 3).
ddPCR: Droplet Digital PCR; IDAA: Indel detection by amplicon analysis; Indel: Insertions or deletion; NHEJ: Nonhomologous end joining; WT: Wild-type.