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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

#111

Post by wolfgke »

Someone1234 wrote: post #53
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 It is often cited as exactly the reason, and appears to be the scientific consensus. In fact you can see large swings in diagnosis numbers based on socioeconomic factors[0], which definitely hints at diagnostic bias. > The reported increase is largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, an…

> It is often cited as exactly the reason, and appears to be the scientific consensus. In fact you can see large swings in diagnosis numbers based on socioeconomic factors[0], which definitely hints at diagnostic bias.

A counterthesis based on personal observations: let us assume that there exists a genetic reason for ASD (plausible), assume that ASD people tend to work in specific jobs in specific branch of the economy (think software development and/or research) - also very plausible. Now, additionally, assume (again very plausibly) that people look for potential partners in their social milieu and finally assume that people with similar (also slightly autistic) traits fit better together in a relationship.

This, in my opinion, explains quite well why there is a lot of inbreeding between people with a slight Asperger bias which, by genetics, leads to an increase of autism presence (and thus diagnoses) in specific socioeconomic milieus without any diagnosis bias.

Re: New Causes of Autism Found in Noncoding DNA

#112

Post by tleonardi »

klmr wrote: post #92
dnautics wrote: post #75

Earlier quoted context omitted.

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.

I broadly agree with your point but careful when saying “no obvious phenotype”. As my former boss likes to say about work in C. elegans : “Worms can’t talk. They seem healthy but maybe they’re extremely unhappy.” Less flippantly, we know that biological systems in general have huge plasticity to buffer environmental changes. The environment is controlled under lab conditions, so loss of robustness due to genetic chan…

I couldn't agree more. Many knock-out mice for protein coding genes don't have an "obvious phenotype", but they are conserved across species. When studied in detail they often reveal an effect, be it in the response to environmental stress or subtle behavioural alterations. I can't find an updated reference, but results published in 2012 by the Mouse Genetics Project and the International Mouse Phenotyping Consortium indicate that ~20% of coding gene knock-out lines examined don't have an "obvious phenotype" [1]. The most likely explanation for their conservation is that they do have a function and a phenotype: we just don't know what to look for.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463797/

Re: New Causes of Autism Found in Noncoding DNA

#113

Post by NoahNedz »

arkades wrote: post #104
hannob wrote: post #82

Earlier quoted context omitted.

> 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.

I’m also unfamiliar with any data to suggest the increase in rates is anything but a change in diagnostic criteria. And it’s my field, so I’d OP has data to share, I’d be very appreciative of a link.

https://www.cdc.gov/ncbddd/autism/data.html

Re: New Causes of Autism Found in Noncoding DNA

#114

Post by spraak »

Toine wrote: post #80
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…

I'll put in out there (at the risk of being downvoted) : an extremely destructive/insensitive world around a developing child, as a fetus or later, is to me one of the root causes of autism. See Bruno Bettleheim's theories (refrigerator mother, The Emtpy Fortress, etc). "Autistic people have the conviction that their efforts have no influence on the world, because in the past they were convinced that the world is ins…

> an extremely destructive/insensitive world around a developing child, as a fetus or later

Are you saying i.e. an emotional and social cause? In contrast to e.g. a gene or chemical (physical) cause?

Re: New Causes of Autism Found in Noncoding DNA

#115

Post by najarvg »

NoahNedz wrote: post #113
arkades wrote: post #104

Earlier quoted context omitted.

I’m also unfamiliar with any data to suggest the increase in rates is anything but a change in diagnostic criteria. And it’s my field, so I’d OP has data to share, I’d be very appreciative of a link.

https://www.cdc.gov/ncbddd/autism/data.html

This link talks about prevalence rates. I don't see anything talking about an increase in autism rates that is not just explained by increase in diagnoses as the OP claimed

Re: New Causes of Autism Found in Noncoding DNA

#116

Post by dkoston »

klmr wrote: post #109
dkoston wrote: post #108

Earlier quoted context omitted.

Whole genome sequencing on humans has only existed for 16 years (1). In 2003, the cost was prohibitive until NGS (next generation sequencing) techniques became commercialized. We can definitely disagree here as 15 years of research which in my worldview is focused mostly on coding DNA and karyotyping doesn’t seem like much to draw this conclusion. There’s plenty of decades old science that has shifted or been rewritt…

Junk DNA has already been studied before whole-genome sequencing existed, and evidence from NGS not only hasn’t overturned that research, it has largely corroborated it. And as for personal biases, I’m a staunch defender of the ENCODE research so I’m certainly not biased in favour of the concept of junk DNA.

Interesting. I may be biased in the other direction after reading "The Epigenetics Revolution" and "Junk DNA" by Nessa Carey.

ENCODE is such an amazing project! Also, thanks for your research on non coding DNA.

Re: New Causes of Autism Found in Noncoding DNA

#117

Post by arkades »

NoahNedz wrote: post #113
arkades wrote: post #104

Earlier quoted context omitted.

I’m also unfamiliar with any data to suggest the increase in rates is anything but a change in diagnostic criteria. And it’s my field, so I’d OP has data to share, I’d be very appreciative of a link.

https://www.cdc.gov/ncbddd/autism/data.html

Right. These are the precise prevalence numbers that have been addressed in multiple studies showing that the change is attributable to increases in public awareness / detection efforts, and broadened diagnostic criteria.

Thank you for digging up a link.

Re: New Causes of Autism Found in Noncoding DNA

#118

Post by astazangasta »

klmr wrote: post #89
astazangasta wrote: post #51

Earlier quoted context omitted.

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.

Eh, I graduated in 2008. ENCODE was only a pilot yet. We didn't know about lincRNAs. My estimate was based on multi-species sequence alignments so it is pretty conservative. At the time it was not, however; it was doubling the amount of functional sequence. To be honest i am not sure what the current best estimates are based on (i switched fields). 8% seems absurdly high to me, but there is a ton more evidence now than i had.

Re: New Causes of Autism Found in Noncoding DNA

#119

Post by empath75 »

wolfgke wrote: post #111
Someone1234 wrote: post #53

Earlier quoted context omitted.

> which improved or over diagnosis cannot account for It is often cited as exactly the reason, and appears to be the scientific consensus. In fact you can see large swings in diagnosis numbers based on socioeconomic factors[0], which definitely hints at diagnostic bias. > The reported increase is largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, an…

> It is often cited as exactly the reason, and appears to be the scientific consensus. In fact you can see large swings in diagnosis numbers based on socioeconomic factors[0], which definitely hints at diagnostic bias. A counterthesis based on personal observations: let us assume that there exists a genetic reason for ASD (plausible), assume that ASD people tend to work in specific jobs in specific branch of the econ…

This is the kind of thing you could test without just spinning out a just-so story.

Re: New Causes of Autism Found in Noncoding DNA

#120

Post by alexandercrohde »

efa wrote: post #105
hannob wrote: post #82

Earlier quoted context omitted.

> 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.

Yes, I'd like to know where you are getting that the actual rates are increasing. My wife and I (parent's of a daughter with autism) laugh how every year they claim the numbers increase - 1/100, then 1/50, etc. These are numbers marketed by Autism Speaks and other organizations to make autism appear more wide spread and increase their funding. This does nothing but hurt people with more severe autism. Widening the ne…

Let's separate facts from feelings. At the end of the day it really is irrelevant what indirect emotional consequences the facts have, all that matters is that we get the ones that happen to be true so that we can make the best choices going forward.

I'll try to find the sources and post them on parent.

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