Theory Suggests That All Genes Affect Every Complex Trait • Hacker News Board

Re: Theory Suggests That All Genes Affect Every Complex Trait

#31

Post by meowface » Wed, Jun 20, 2018, 9:44 PM UTC

jcims wrote: post #22

I was hoping CRISPR/Cas9 (or some similar system) was going to answer many prayers. Maybe this means it's less likely?

I don't think this significantly changes expectations. CRISPR and similar systems will still be immensely beneficial for simple traits (e.g. traits determined by a very small number of genes). Some diseases can be eliminated by changing a single gene.

CRISPR and similar systems could someday be helpful for dealing with complex traits, but we first need to understand exactly what genes contribute to them and how, and for many traits, that will take a very long time. In some sense, CRISPR is just a dumb cutting tool. Knowing where to cut was always the hard part, and it always will be.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#32

Post by gwern » Wed, Jun 20, 2018, 9:44 PM UTC

toasterlovin wrote: post #15

gwern wrote: post #5

R.A. Fisher was right, as usual.

Off topic: I see you on here commenting on discussions related to evolution pretty frequently, so I figured I'd ask you: Are there any communities like HN, but focused on evolution, population genetics, etc. that you would recommend?

Not really, with the exception of genetics Twitter.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#33

Post by adjkant » Wed, Jun 20, 2018, 9:46 PM UTC

frgtpsswrdlame wrote: post #16

These kinds of strange findings are going to keep occurring because these researchers are too far invested into a mode of research (genetics) that won't actually find the determinism they desire. It's the environment not the genes.

That doesn't make it nondeterministic if the environment is also deterministic. The nature/nurture debate is independent of determinism.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#34

Post by jjeaff » Wed, Jun 20, 2018, 9:52 PM UTC

spruciefic399 wrote: post #8

This is a paper that I'm glad was published (maybe not Cell, but somewhere), because it presents an interesting and pretty clear theory. At the same time, it seems like it's fairly clearly falsifiable almost on its face, because there are many genetic disorders involving clear, substantial mutations (in a chromosomal topography sense) that are circumscribed in their effects, at least to one extent or another. I think…

The top comment on this post addresses the one gene, one trait evidence. In essence, just because changing one gene mutation fixes the problem, that doesn't mean that only one gene was responsible for the problem in the first place.

"The "one gene = one protein" dogma of molecular biology (expanded: "one trait selectable in breeding experiments = one compact locus of the chromosome") was a priori wrong, but it's taken us decades to undo the damage. We were led astray because there are traits that do map to a single locus, or single mutations that were found to be able to control a trait, which is not the same thing as the trait."

Re: Theory Suggests That All Genes Affect Every Complex Trait

#35

Post by politician » Wed, Jun 20, 2018, 9:53 PM UTC

bookofjoe wrote: post #21

aphextron wrote: post #19

Earlier quoted context omitted.

I literally can't understand a single word on that page. Care to explain?

"We describe our first patient treated with lentiviral vector–mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells."

"We describe our first patient treated with into . ."

Re: Theory Suggests That All Genes Affect Every Complex Trait

#36

Post by reptation » Wed, Jun 20, 2018, 9:56 PM UTC

One reason for this dependence could be that DNA exists within a confined space in the nucleus. The locations of the genes are not random. eg. https://www.sciencedirect.com/science/article/pii/S136759311...

Re: Theory Suggests That All Genes Affect Every Complex Trait

#37

Post by politician » Wed, Jun 20, 2018, 9:57 PM UTC

fizx wrote: post #12

onychomys wrote: post #11

Earlier quoted context omitted.

From an evolution point of view, it actually just means that selection happens at the organismal level, not the gene level.

You misunderstand my point... larger ratio of base pairs to behavior means that the behavior is likely more robust to noise, and the original evolution of the behavior would have been smoother (i.e. proceeded in less of a step-wise manner, because each step would be a much smaller fraction of the required change than previously thought).

Traits embedded into a dense vector space encoded as DNA base pairs is a pretty radical deviation from the one-hot vector approach we were taught in school. Wouldn't it be lovely if we found that vector addition worked similarly in this domain?

Re: Theory Suggests That All Genes Affect Every Complex Trait

#38

Post by speby » Wed, Jun 20, 2018, 10:02 PM UTC

ancorevard wrote: post #26

Two things: 1. The theory of "junk DNA" of which the authors received Nobel Price is increasingly looking like...well...junk. 2. The recent discovery of Epigenetics adds a whole other dimension for understanding traits and genetics. Lots of biological science needs to be rewritten/updated in the years to come.

#2 is perhaps one of the most confounding recent areas of research that really starts complicating the study of DNA and how changes to it map to an organism's outcome in the real world over time and in different environments.

As new studies emerge on identical twins/triplets/etc., it has become clear that even identical DNA does not at all have 100% clone of the person, even if they do in fact share the same DNA. Ranging from things like height differences, leg lengths, intelligence levels, and a host of other characteristics, "identical" DNA does not mean physically identical creatures that look and behave exactly the same, even if they are far more similar than different.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#39

Post by deegles » Wed, Jun 20, 2018, 10:07 PM UTC

api wrote: post #4

Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to varying degrees in parallel. They are nothing like the linear assemblies of modules that humans prefer to engineer.

I wonder if years from now we'll look back at the "selfish gene" the way we look at Freudian ideas about psychology.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#40

Post by woodandsteel » Wed, Jun 20, 2018, 10:08 PM UTC

A couple of comments from a non-biologist.

It seems to me that this is an example of a common pattern in biological research. A simple explanation is developed for a phenomena, but then as time goes on, it turns out that in at least some important ways things are much more complicated than originally thought.

Also, the article talks about the controversy between the view that all genes make tiny causal contributions versus some are core and other peripheral.

But perhaps it is, at least in some cases, a matter of what I would call complex conditionality. So for instance maybe disease X happens if there are mutations in genes A, B and C, or C, D and E, or G, H and I, but not any other combination. Certainly we find things like that in other areas of reality.