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New Causes of Autism Found in Noncoding DNA

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Re: New Causes of Autism Found in Noncoding DNA

#41

Post by cyphar »

dkoston wrote: post #36
stevenjohns wrote: post #27

Earlier quoted context omitted.

What is the benefit of having an arch in the nose vs not having one? Or the benefit in light brown hair vs dark brown hair? Or the benefit in light brown eyes vs dark brown eyes? How about the benefits in male pattern baldness where some of the hair on the scalp is affected by high levels of DHT and some aren't? How about diffused baldness where the way in which a person balds isn't in one particular place and is all…

I can absolutely appreciate that we are a series of mutations. To say that there is no benefit or detriment to having an arched nose or not also seems naive. It’s likely that the shape of your nose can affect how much air passes to your lungs, how likely it is to be sun burnt or not, and many other things. Just because the values or benefits might be minuscule compared to other things doesn’t mean they do not exist.…

Evolution is not a process of finding a global optimum, just a local one. And traits which have no impact on the chance for a species to reproduce just get carried along for the ride.

An obvious example of this is the Laryngeal nerve. Fish evolved with this nerve being a simple straight line between the brain and larynx. However, in animals which evolved from fish and have necks, we see that the nerve is "trapped" under the aortic arch in the thorax. So this nerve ends up looping through your neck to reach your thorax. Giraffes have this nerve going all the way down their neck and back up again. But this inefficiency has no impact on the survival chances of a species (if your neck is severed you're dead regardless of whether you have an additional nerve running through it) so it's stuck around.

So, there definitely are traits which objectively have no benefit or detriment and have just stuck around. You could argue even some late-life conditions which are detrimental also "stuck around for the ride" because people late in life don't reproduce and thus there is no evolutionary mechanism to affect such traits.

Re: New Causes of Autism Found in Noncoding DNA

#42

Post by alexandercrohde »

toomuchtodo wrote: post #32
dnautics wrote: post #25

Earlier quoted context omitted.

assortative mating - a certain 'type' of person going to college and meeting people they reproduce with - is also implicated.

Was this the polite way of saying "older, smart people"? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927579/ (Autism As a Disorder of High Intelligence [2016]) > The hypothesis that autism risk in offspring is positively associated with high parental intelligence, and high socioeconomic status, traces to Kanner (1943, p. 248), who stated, referring to autistic children, that “they all come of highly intelligent fam…

I guess what I'd like to know is (and I'm specifically asking you because you seem to be knowledgeable):

1. It sounds like de-novo mutations are the best theory for 70%+ of autism cases per this paper, right?

2. Does anybody track the "base rate" of de-novo mutations / generation in humans? If so, how many generations back do we have data for, and how many regions?

3. Aren't we seeing an increase in autism is developed nations even within poor uneducated families with young parents?

Re: New Causes of Autism Found in Noncoding DNA

#43

Post by cyphar »

dkoston wrote: post #12

How naive or arrogant do scientists have to be to think that we have “junk” DNA that doesn’t affect how we develop? Wouldn’t it be much more useful to classify things we don’t understand as “unknown purpose X” so that more people are inclined to study them? /end venting

Personally I think it's both naive and arrogant to assume that because something is called "junk DNA", that means that the scientific community as a whole have decided to never consider whether it has any impact. There are all sorts of weird terms-of-art in science and I find it quite frustrating that armchair-scientists think they know better purely based on the words that happen to be used.

Re: New Causes of Autism Found in Noncoding DNA

#44

Post by reilly3000 »

Non-biologist here. It would seem to reason that since non-coding DNA has a role in RNA manufacturing, it would be susceptible to resonance from specific energy signals that would invoke its expression, effectively appending new information to RNA. Once propagated that information made be difficult to subdue.

Maybe an analogy is an unexpected object being written to a pubsub topic. Each consumer may have different side-effects based on that object depending on how well they validate the message. Some will properly ignore it or throw an error, but others may yield a proper side effect where one should be, or even a malformed side effect. In any case, once it’s in the log it’s really hard to get rid of, short of replaying the topic to a new stream that filters out that data.

This is truly clueless conjecture. This noncoding DNA stuff is fascinating; a rare bit of unexplored territory in science that seems to be coming into focus. I think as scientific methods mature around system dynamics and emergence these types of complex behaviors are finally going to be better understood.

Re: New Causes of Autism Found in Noncoding DNA

#45

Post by dkoston »

cyphar wrote: post #41
dkoston wrote: post #36

Earlier quoted context omitted.

I can absolutely appreciate that we are a series of mutations. To say that there is no benefit or detriment to having an arched nose or not also seems naive. It’s likely that the shape of your nose can affect how much air passes to your lungs, how likely it is to be sun burnt or not, and many other things. Just because the values or benefits might be minuscule compared to other things doesn’t mean they do not exist.…

Evolution is not a process of finding a global optimum, just a local one. And traits which have no impact on the chance for a species to reproduce just get carried along for the ride. An obvious example of this is the Laryngeal nerve. Fish evolved with this nerve being a simple straight line between the brain and larynx. However, in animals which evolved from fish and have necks, we see that the nerve is "trapped" un…

Sure, I even made this point when I pointed out that the appendix has gotten carried along for the ride in another comment.

Do you really believe that 75-98.8% of our DNA serves no purpose and is being carried along for the ride? That doesn't seem like a small inefficiency.

Re: New Causes of Autism Found in Noncoding DNA

#46

Post by refurb »

mikeash wrote: post #18
dkoston wrote: post #12

How naive or arrogant do scientists have to be to think that we have “junk” DNA that doesn’t affect how we develop? Wouldn’t it be much more useful to classify things we don’t understand as “unknown purpose X” so that more people are inclined to study them? /end venting

As far as I can tell, the preferred scientific term is "non-coding DNA," with "junk DNA" being a sensational term that gets more traction in the media.

I like the use of “junk” DNA only because it reminds people how much we don’t know. It wasn’t that long ago the term was used because that’s DNA was assumed to be useless.

Re: New Causes of Autism Found in Noncoding DNA

#47

Post by refurb »

reilly3000 wrote: post #44

Non-biologist here. It would seem to reason that since non-coding DNA has a role in RNA manufacturing, it would be susceptible to resonance from specific energy signals that would invoke its expression, effectively appending new information to RNA. Once propagated that information made be difficult to subdue. Maybe an analogy is an unexpected object being written to a pubsub topic. Each consumer may have different si…

resonance from specific energy signals

Did you have something more specific in mind?

Re: New Causes of Autism Found in Noncoding DNA

#48

Post by refurb »

cyphar wrote: post #43
dkoston wrote: post #12

How naive or arrogant do scientists have to be to think that we have “junk” DNA that doesn’t affect how we develop? Wouldn’t it be much more useful to classify things we don’t understand as “unknown purpose X” so that more people are inclined to study them? /end venting

Personally I think it's both naive and arrogant to assume that because something is called "junk DNA", that means that the scientific community as a whole have decided to never consider whether it has any impact. There are all sorts of weird terms-of-art in science and I find it quite frustrating that armchair-scientists think they know better purely based on the words that happen to be used.

Actually, “junk DNA” was assumed to have no function decades ago. That’s why it got the name. That’s what I was taught in college 15 years ago.

Subsequently it was discovered it does have a very important function.

Scientific understanding evolves.

Re: New Causes of Autism Found in Noncoding DNA

#49

Post by empath75 »

spraak wrote: post #31

With the drastically increased prevalence (which improved or over diagnosis cannot account for) we must look for environmental triggers or factors. Gene changes simply do not happen this quickly. To be clear, I am not dismissing looking for genes, but there are many diseases which are environmental in cause but can be exasperated by a wide variety of genes, i.e. for which we would not attribute the cause to genes/a s…

>(which improved or over diagnosis cannot account for)

Out of curiosity, why not?

Re: New Causes of Autism Found in Noncoding DNA

#50

Post by jballanc »

dnautics wrote: post #29
jballanc wrote: post #6

Earlier quoted context omitted.

Gene location is extremely consequential, especially in Eukaryotes (everything that's not bacteria or bugs living near hydrothemal vents). A couple of things that are influenced by position: * First, and most immediate, are promoter/suppressor sequences. These are the bits of non-coding DNA that regulate when a gene is turned on or off. If you move a gene away from its promoter, it will not turn on and off at the rig…

I'm going to go against this and say no. We swap gene locations, all the time wholesale in mice, and usually the effect is limited. That doesn't get you a paper, so of course you publish when something... more interesting crops up. It's just that there are many well-studied systems where where there are profound and severe effects that are singly extremely consequential, where you go "huh, wouldn't have guessed that"…

So, two quick points in response:

1. Yeah, I probably overstated the case. It's not as if it's impossible to move a gene somewhere else on a chromosome and have it function completely normally. As you point out, we do this all the time. That said...

2. Genetics is hard, and I'm of the school of thought that one reason it is so hard is because systems are more fragile in meaningful ways than we assume. That is to say, if you attempt a gene translocation 100 times and get 3 successes, most geneticists would be happy with that result and not question the 97 failures. And, indeed, it is entirely possible that the quality of the reagents, the stringency of the protocols, or any of an infinite number of other variables that have little or nothing to do with genetics could be the cause of those 97 failures...or, it could be that 97 times the translocation worked but the product wasn't viable. I know from experience that it is very hard to distinguish between these possibilities, and furthermore that in the publish-or-perish world of academia today there's not any motivation for navel gazing into the reason most genetic protocols are not more efficient. That said, I've seen hints in my past work that make me think location, gene dose, DNA secondary and tertiary structure, etc. are more consequential than the common wisdom would have you believe.

(Oh, and for anyone still reading, I'll share the brain teaser that was my light-bulb moment for the extent of gene dose effect in prokarya: it takes 40 min to replicate the E. coli genome, but during exponential growth E. coli can double in number every 20 min. How?)

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