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is this useful beyond improved breeding for genetic experiments? I understand there is scientific value in being able to quickly and cheaply breed in fewer gene

is this useful beyond improved breeding for genetic experiments? I understand there is scientific value in being able to quickly and cheaply breed in fewer generations a mouse with specific sets of genes as a tool for downstream research. I have a hard time imagining gene drive is useful for improving some species: how does one determine the utility of one set of genes versus another? we can not accurately reflect the real world in a lab environment to determine if some change is a net advantage or net disadvantage over all environments, situations a species faces. I agree it will be possible to assess the performance of traits in a lab benchmark, but then it's obvious we are over fitting to the genetic fitness of pulling a lever, or running in a wheel etc, and disregarding the cost of the change on all other functions the organism would face in a representative test. The real world with millions or billions of creatures is a much faster and parallellized test, i.e. a lab with space for 1000 mice, could in theory face 1000 micedays per day of artificial selection, while those in the wild are performing giga micedays per day of natural selection over the whole challenge set without overfitting... Again, I do see the utility for breeding selective traits and downstream learning about the functions of the genome in a cheaper way compared to fifty fifty coin flip breeding...

mxwsn 8y ago
In some cases, genetic variation in humans has performed a natural experiment for us. It's absolutely crucial to understand the potential impact of a proposed genetic edit in the realm of messy reality. As an example, Ccr5 delta32 is present in a small fraction of Europeans, and noted for granting HIV immunity but potentially greater risk to West Nile virus. We don't know enough about all the real life consequences of Ccr5 delta32 at the moment, but natural experiments are a rich enough source of information to get us there, at least in theory.
wonderwonder 8y ago
There are quite a few useful applications. Sickle Cell anemia is caused by a recessive gene, "Recessive means that two copies of the gene are necessary to have the trait, one inherited from the mother, and one from the father." If we code the gene out, no more Sickle Cell. There are also a plethora of degenerative diseases such as Huntington's that are caused by a defect in a single gene that this could potentially help eliminate. I would think essentially any disease that can be genetically tested for could be potentially cured by the application of gene drives.
- DoctorOetker 8y ago
  what keeps sickle cell anemia in the gene pool? is there some rare beneficial aspect? or is it because natural selection acts largely on chromosomes instead of genes, and the other variants of the chromosomes have similar negative imperfections? or is it because the chromosome variants that propagate sickle cell anemia contain a different gene that is comparatively better than the equivalent gene on some of the non SCA carrying chromosomes? i.e. chromosome binding of genes forces natural selection to largely take the good with the bad genes, without cherry picking genes within chromosomes, and mostly operates on chromosome fitness as opposed to gene fitness?
  - pjscott 8y ago
    Being heterozygous for the sickle cell trait gives some protection against malaria, which explains why the two tend to be common in the same parts of the world: https://en.wikipedia.org/wiki/Heterozygote_advantage#Sickle-cell_anemia https://en.wikipedia.org/wiki/Heterozygote_advantage#Sickle-... (Nicely guessed, by the way!)
    - DoctorOetker 8y ago
      thanks for pointing this out! does this mene using gene drive to expell SCA alleles from the gene pool would result in a higher malaria rate? it would seem that if one could put both SCA and non-SCA alleles in the same chromosome the advantage would be unconditional?
- adrianN 8y ago
  How likely are these single-gene diseases to arise from a point mutation instead of being inherited?
  - wonderwonder 8y ago
    From my limited understanding, Sickle cell at least is always inherited.

mxwsn 8y ago

In some cases, genetic variation in humans has performed a natural experiment for us. It's absolutely crucial to understand the potential impact of a proposed genetic edit in the realm of messy reality. As an example, Ccr5 delta32 is present in a small fraction of Europeans, and noted for granting HIV immunity but potentially greater risk to West Nile virus. We don't know enough about all the real life consequences of Ccr5 delta32 at the moment, but natural experiments are a rich enough source of information to get us there, at least in theory.

wonderwonder 8y ago

There are quite a few useful applications. Sickle Cell anemia is caused by a recessive gene, "Recessive means that two copies of the gene are necessary to have the trait, one inherited from the mother, and one from the father." If we code the gene out, no more Sickle Cell. There are also a plethora of degenerative diseases such as Huntington's that are caused by a defect in a single gene that this could potentially help eliminate. I would think essentially any disease that can be genetically tested for could be potentially cured by the application of gene drives.

DoctorOetker 8y ago
what keeps sickle cell anemia in the gene pool? is there some rare beneficial aspect? or is it because natural selection acts largely on chromosomes instead of genes, and the other variants of the chromosomes have similar negative imperfections? or is it because the chromosome variants that propagate sickle cell anemia contain a different gene that is comparatively better than the equivalent gene on some of the non SCA carrying chromosomes? i.e. chromosome binding of genes forces natural selection to largely take the good with the bad genes, without cherry picking genes within chromosomes, and mostly operates on chromosome fitness as opposed to gene fitness?
- pjscott 8y ago
  Being heterozygous for the sickle cell trait gives some protection against malaria, which explains why the two tend to be common in the same parts of the world: https://en.wikipedia.org/wiki/Heterozygote_advantage#Sickle-cell_anemia https://en.wikipedia.org/wiki/Heterozygote_advantage#Sickle-... (Nicely guessed, by the way!)
  - DoctorOetker 8y ago
    thanks for pointing this out! does this mene using gene drive to expell SCA alleles from the gene pool would result in a higher malaria rate? it would seem that if one could put both SCA and non-SCA alleles in the same chromosome the advantage would be unconditional?
adrianN 8y ago
How likely are these single-gene diseases to arise from a point mutation instead of being inherited?
- wonderwonder 8y ago
  From my limited understanding, Sickle cell at least is always inherited.