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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

#81

Post by hannob »

asdf21 wrote: post #24
alexandercrohde wrote: post #23

Would this mean gene-therapy could potentially undo autism? Also, since I believe it's now actually agreed upon that autism rates actually ARE increasing, and not just increased diagnoses, is there any candidate theory as to why mutations would be higher in developed countries recently?

Older parents is the presumption.

This "older parents" hypothesis is thrown around very often, but it's entirely based on correlational studies (obviously, it wouldn't be ethically possible to do it in a controlled study).

And there's a very plausible alternative explanation for that correlation: Autism is probably at least partly genetic and autism impacts social interaction. It's very plausible to think that it simply takes people with autistic personality traits longer to find a partner to have children.

Re: New Causes of Autism Found in Noncoding DNA

#82

Post by hannob »

alexandercrohde wrote: post #23

Would this mean gene-therapy could potentially undo autism? Also, since I believe it's now actually agreed upon that autism rates actually ARE increasing, and not just increased diagnoses, is there any candidate theory as to why mutations would be higher in developed countries recently?

> since I believe it's now actually agreed upon that autism rates actually ARE increasing

why do you believe that? I'm not aware of any recent research that would point in that direction and disprove the very plausible hypothesis that the increase is an effect of changing diagnosis criteria and increased attention for the topic.

Re: New Causes of Autism Found in Noncoding DNA

#83

Post by hyperbovine »

dnautics wrote: post #75
gravelc wrote: post #67

Earlier quoted context omitted.

I'm going to disagree with go with 'sometimes yes and sometimes no'. Take a construct and transform it into a plant. Check the expression of the transgene from hundreds of different transformation events, and there'll be huge variation, from highly expressed to silenced, even though all inserted transgenes have the same promoter and terminator. Location matters. However, if the function of gene A is redundant, or it…

I would make a bet. Randomly generate 100 spots in the mouse genome, let's say maybe not in centromeric locations. Don't correct for being inside an ORF or a promoter. Pick 100 random translocations swapping these spots. 95 of them will be viable with no obvious phenotype.

In how many samples are you doing this? It’s all about effect size.

Re: New Causes of Autism Found in Noncoding DNA

#85

Post by patall »

alexandercrohde wrote: post #23

Would this mean gene-therapy could potentially undo autism? Also, since I believe it's now actually agreed upon that autism rates actually ARE increasing, and not just increased diagnoses, is there any candidate theory as to why mutations would be higher in developed countries recently?

> Also, since I believe it's now actually agreed upon that autism rates actually ARE increasing, and not just increased diagnoses, is there any candidate theory as to why mutations would be higher in developed countries recently?

This paper is mostly about the impact of de-novo mutations, i.e mutations that are found only in the child and not in its parents. One theory is that as paternal age is rising and a higher paternal age is linked to a higher number of de-novo mutations which leads to a higher chance of de-novo mutation related genetic diseases like in this case autism (and other mental disorders).

Note that the paternal age in developed countries has been at a historic low in the mid 20th century, which may have lead to a historically low rate of mental disorders in the last decades.

Re: New Causes of Autism Found in Noncoding DNA

#86

Post by patall »

hannob wrote: post #81
asdf21 wrote: post #24

Earlier quoted context omitted.

Older parents is the presumption.

This "older parents" hypothesis is thrown around very often, but it's entirely based on correlational studies (obviously, it wouldn't be ethically possible to do it in a controlled study). And there's a very plausible alternative explanation for that correlation: Autism is probably at least partly genetic and autism impacts social interaction. It's very plausible to think that it simply takes people with autistic per…

No, its also based on the fact that older parents (and especially fathers) lead to more de-novo mutations (which you can already see in sperm) and in this study now they show that especially de-novo mutations play a role.

If the older parents hypothesis was not true, you would not find higher autism rate is younger siblings or how do you account for that in your alternative explanation?

But sure, as they say in the paper, its most likely not a single large effect variant that causes autism but usually the combination of multiple rare variants. The genetically inherited part may also play a rule. For a complex disease such as this, its not a single cause that is responsible even for one patient. A tall basketball player can be tall due to some luck, tall parents and good nutrition all at the same time.

Re: New Causes of Autism Found in Noncoding DNA

#87

Post by faceplanted »

onetimemanytime wrote: post #79

My guess: older parents + environment. Granted people are having children later in life but that doesn't account for the increase in cases (Better detection and incentives in funding to label kids autistic is another possibility.) So something is now in the air, food or water supply that is making these changes. Maybe older parents are more prone to this?

The scientific consensus is that it's the better detection and also that many places have started diagnosing things as autism that were previously diagnosed as something else, there's not been any real evidence yet that it's actually more common in anything but diagnosis.

Re: New Causes of Autism Found in Noncoding DNA

#88

Post by klmr »

alexandercrohde wrote: post #23

Would this mean gene-therapy could potentially undo autism? Also, since I believe it's now actually agreed upon that autism rates actually ARE increasing, and not just increased diagnoses, is there any candidate theory as to why mutations would be higher in developed countries recently?

> Would this mean gene-therapy could potentially undo autism?

Almost certainly not. Autism is caused by developmental changes. This means that any gene therapy would have to start before the embryo development is even finished, i.e. in the mother’s womb. After that, it’s essentially too late. Think of it this way: Could gene therapy make an adult person taller or smaller? Despite the fact that height has a large genetic component the answer is obviously no, since skeletal growth stops after puberty.

> I believe it's now actually agreed upon that autism rates actually ARE increasing

You’re jumping the gun there. It’s plausible that there are factors that are causing an increase of autism rates (e.g. ageing parents) but so far there’s no positive evidence that this is indeed the case, or that diagnostic changes aren’t the sole reason (see https://en.wikipedia.org/wiki/Epidemiology_of_autism#Changes...).

Re: New Causes of Autism Found in Noncoding DNA

#89

Post by klmr »

astazangasta wrote: post #51
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…

This is what my thesis is about (I titled it "Rehabilitating Junk DNA"). It isn't that complicated. Your resonance comment is gibberish, sorry. The DNA is a giant tape in base 4 (ATGC). There are programs written at random places on the tape that in a 64 bit encoding (i.e. triplets of quaternary bits). This is "coding sequence", about 1% of the genome (itself 3 gigabases, so 30 Mbases of coding sequence). A tape head…

Nice explanation but you seem to be saying that at most 3% (being generous) of DNA would be functional (if the rest is “random noise”). This number is over twice as small as the lowest estimate (~ 8%) of even the most fervent critics of ENCODE’s number. I’d love to hear a brief break-down of your reasons, if possible.

Re: New Causes of Autism Found in Noncoding DNA

#90

Post by klmr »

PunchTornado wrote: post #84

are these in rna genes or outside of rna genes?

It seems this study focuses on regulatory regions of coding genes (i.e. regions of DNA that’s in proximity of coding genes, or in introns), rather than on noncoding RNAs. This doesn’t exclude the possibility of noncoding RNAs also having an effect though.
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