Why don’t you do this in a mouse first? The whole cycle from birth to phenotype, including complex reasoning (e.g. bayesian inference, causality) can take 6 months.
Unfortunately our genetic predictors for mice are terrible. The way mouse research works is not at all like how one would want it to work if we planned to actually use them as a testbed for the efficacy of genetic engineering.
Mice are mostly clones. So we don’t have the kind of massive GWAS datasets on which genes are doing what and how large the effect sizes are.
Instead we have a few hundred studies mostly on the effects of gene knockouts to determine the function of particular proteins.
But we’re mostly not interested in knockouts for genetic engineering. 2/3rds of the disease related alleles in humans are purely single letter base pair changes.
We have very little idea which specific single letter base pair changes affect things like disease risk in mice.
MAYBE some of the human predictors translate. We haven’t actually explicitly tested this yet. And there’s at least SOME hope here; we know that (amazingly), educational attainment predictors actually predict trainability in dogs with non-zero efficacy. So perhaps there’s some chance some of our genetic predictors for human diseases would translate at least somewhat to mice.
We do need to do more thorough investigation of this but I’m not really that hopeful.
I think a far better test bed is in livestock, especially cows.
We have at least a few hundred thousand cow genomes sequenced and we have pretty well labelled phenotype data. It should be sufficient to get a pretty good idea of which alleles are causing changes in breed value, which is the main metric all the embryo selection programs are optimizing for.
Dogs would be interesting—super smart working dogs might even have a viable labour market, and it seems like the evidence of supercanine IQ would be obvious in a way that’s not true of any other species (just given how much exposure most people have to the range of normal canine intelligence).
Sort of analogous to what Loyal is doing for longevity research.
The lack of good population genetic information in animal models and deep phenotyping of complex behavioral traits is probably one of the biggest impediments to robust animal testing of this general approach.
Do we have it in any other animal besides cows? Dogs? Housecats? Fruit flies? Guinea pigs? Any other short-lived animal commonly used in laboratory research that still has a decent amount of genetic diversity?
Great write up!
Why don’t you do this in a mouse first? The whole cycle from birth to phenotype, including complex reasoning (e.g. bayesian inference, causality) can take 6 months.
I would love to try this in mice.
Unfortunately our genetic predictors for mice are terrible. The way mouse research works is not at all like how one would want it to work if we planned to actually use them as a testbed for the efficacy of genetic engineering.
Mice are mostly clones. So we don’t have the kind of massive GWAS datasets on which genes are doing what and how large the effect sizes are.
Instead we have a few hundred studies mostly on the effects of gene knockouts to determine the function of particular proteins.
But we’re mostly not interested in knockouts for genetic engineering. 2/3rds of the disease related alleles in humans are purely single letter base pair changes.
We have very little idea which specific single letter base pair changes affect things like disease risk in mice.
MAYBE some of the human predictors translate. We haven’t actually explicitly tested this yet. And there’s at least SOME hope here; we know that (amazingly), educational attainment predictors actually predict trainability in dogs with non-zero efficacy. So perhaps there’s some chance some of our genetic predictors for human diseases would translate at least somewhat to mice.
We do need to do more thorough investigation of this but I’m not really that hopeful.
I think a far better test bed is in livestock, especially cows.
We have at least a few hundred thousand cow genomes sequenced and we have pretty well labelled phenotype data. It should be sufficient to get a pretty good idea of which alleles are causing changes in breed value, which is the main metric all the embryo selection programs are optimizing for.
Dogs would be interesting—super smart working dogs might even have a viable labour market, and it seems like the evidence of supercanine IQ would be obvious in a way that’s not true of any other species (just given how much exposure most people have to the range of normal canine intelligence).
Sort of analogous to what Loyal is doing for longevity research.
The lack of good population genetic information in animal models and deep phenotyping of complex behavioral traits is probably one of the biggest impediments to robust animal testing of this general approach.
Well we have it in cows. Just not in mice.
Do we have it in any other animal besides cows? Dogs? Housecats? Fruit flies? Guinea pigs? Any other short-lived animal commonly used in laboratory research that still has a decent amount of genetic diversity?