So this is why if you read the CNV studies and you look at the hits they identify, and how many subjects are covered by the identified hits, you find that like, maybe 2% of the cohort will have one of those specific identified hits and lose 2 IQ points or gain 2 kg of fat etc. So you can see how that would work out in embryo selection: you’d be able to avoid that loss, which is meaningful! …in a tiny fraction of all embryos. On average, you’d just sequence them all, find no known pathogenic variant, and shrug, and use the SNP PGS like usual, having gained nothing.
Also, of course, WGS is substantially more expensive than SNP genotyping and more difficult to do on embryos.
That is relevant in pre-implantation diagnosis for parents and gene therapy at the population level. But for Qwisatz Haderach breeding purposes those costs are immaterial. 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? We would not be interested in the effect of the ugliness, only in getting it out.
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.)
Yeah, separate from both the proposal at top of this thread and GeneSmith’s proposal, there’s also the “make the median human genome” proposal—the idea being that, if most of the variance in human intelligence is due to mutational load (i.e. lots of individually-rare mutations which are nearly-all slightly detrimental), then a median human genome should result in very high intelligence. The big question there is whether the “mutational load” model is basically correct.
That is relevant in pre-implantation diagnosis for parents and gene therapy at the population level. But for Qwisatz Haderach breeding purposes those costs are immaterial. 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? We would not be interested in the effect of the ugliness, only in getting it out.
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.)
Yeah, separate from both the proposal at top of this thread and GeneSmith’s proposal, there’s also the “make the median human genome” proposal—the idea being that, if most of the variance in human intelligence is due to mutational load (i.e. lots of individually-rare mutations which are nearly-all slightly detrimental), then a median human genome should result in very high intelligence. The big question there is whether the “mutational load” model is basically correct.