Here is what I am responding to (also keep in mind I was using indel to mean "indels and substitutions", ie whatever may be counted as an error during NHEJ): >

Here is what I am responding to (also keep in mind I was using indel to mean "indels and substitutions", ie whatever may be counted as an error during NHEJ): > "There's no way cells survive with indels at 10% of their base positions, that's not possible." > "How is the per-base indel rate not 10% if 10% of cells carry an indel at any given locus?" I figured you were referring to per base within each cell. Your overall "per base" rate is getting the average (across cells) number of mutated sites. The survival of a cell is determined by its own genome, not the average of the population its been grouped into. However, it is the case that if x% of cells have a mutation at any given site then there must be at least some cells in this group that contain x% or greater mutated sites. Is that what you meant? Because that's not a bad point. I don't know where that 10% value came from and have no attachment to it, just assume that one is measurement noise for now, but even cells with 0.1% of sites mutated seems like a lot. There doesn't seem to be many whole genome single cell sequencing results available yet, which is what I think is needed here. Here is one that reports ~ 15k SNVs, 50-100 "micro-CNVs" (ie 10-100 kb copy number variants, fig S4), and 290 indels: >"We call an SNV if there is a called NR allele and: (a) the total read depth in the bulk sample is above 15; (b) no bulk read has the NR allele; (c) if two SNVs are within 100bp from each other, both are discarded. With this procedure, we called 15,940 SNVs on the autosome of sample BJ1...We called 294 putative INDELs from the BJ1-BJ2 pair, the negative control" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538131/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538131/ So taking the smallest and biggest numbers of possible here gives: 100%*(15e3 + 50*10e3 + 290*1)/3e9 = 0.02% of bases affected 100%*(15e3 + 100*100e3 + 290*10e3)/3e9 = 0.4% of bases affected This seems to ignore any very small or large mutations that may affect a given site, and not all the mutations will simulate the effect of NHEJ... but this makes me think it isnt impossible for 0.001-1% to happen, especially in vitro.