There the main bottleneck is the iteration of selection, or making synthetic genomes. Going for the most typical genome with the least amount of originality is not a technical challenge in itself, right?
Right.
If you are doing genome synthesis, you aren’t frustrated by the rare variant problems as much because you just aren’t putting them in in the first place; therefore, there is no need to either identify the specific ones you need to remove from a ‘wild’ genome nor make highly challenging edits. (This is the ‘modal genome’ baseline. I believe it has still not been statistically modeled at all.)
While if you are doing iterated embryo selection, you can similarly rely mostly on maximizing the common SNPs, which provide many SDs of possible improvement, and where you have poor statistical guidance on a variant, simply default to trying to select out against them and move towards a quasi-modal genome. (Essentially using rare-variant count as a tiebreaker and slowly washing out all of the rare variants from your embryo-line population. You will probably wind up with a lot in the final ones anyway, but oh well.)
Right.
If you are doing genome synthesis, you aren’t frustrated by the rare variant problems as much because you just aren’t putting them in in the first place; therefore, there is no need to either identify the specific ones you need to remove from a ‘wild’ genome nor make highly challenging edits. (This is the ‘modal genome’ baseline. I believe it has still not been statistically modeled at all.)
While if you are doing iterated embryo selection, you can similarly rely mostly on maximizing the common SNPs, which provide many SDs of possible improvement, and where you have poor statistical guidance on a variant, simply default to trying to select out against them and move towards a quasi-modal genome. (Essentially using rare-variant count as a tiebreaker and slowly washing out all of the rare variants from your embryo-line population. You will probably wind up with a lot in the final ones anyway, but oh well.)