Thread by @ekverstania

[THREAD] HERITABILITY AND CAUSES OF AUTISM

This is going to become one of my long and rambling threads, and I am starting it simply because many #ActuallyAutistic people seem to misunderstand genetics and heritability not only in autism, but in general. This results in...

...arguments being made based on these false assumptions.

I've in fact just been blocked by someone who said that I should use the word 'debate' instead of 'argument', when I specifically meant 'argument' in the academic sense, so I shared my definition of 'argument' in the context, to clarify. academicguides.waldenu.edu/writingcenter/…

This was interpreted as 'treating them as a child'. Unfortunately, I only know how to make academic arguments using elements such as assumptions, definitions, evidence and logic, so... sigh.

OK, moving along...

I will add to this thread over time, but its goal is not to delve into the causes of autism quite as much as it is to ensure that we (#ActuallyAutistic people) don't use a lot of nonfacts in our (academic or other) arguments about eugenics or other hot topics.

I don't know whether these are a common beliefs among #ActuallyAutistic people, but I will detail some of the statements that I disputed, based on current science.

The proponent said that "you need at least one or both parents to develop autism [in order to be autistic yourself], that’s literally how that works".

This is not evidenced in current science, though.

They further argued that the reason we are not currently seeing at least one autistic parent in every family that has an autistic kid, is because autism is underdiagnosed, and if the system was all working like clockwork, we'd see that there's always at least one autistic parent.

This is not in line with current science either.

Now, heritability. We will need to differentiate terms like 'genetic factors' from the notion of 'genes that cause autism'. We will also have to talk about 'epigenetics', and we will further have to talk about what 'autism' is, to be able to talk about what causes 'autism'.

If you didn't like me sharing that definition of 'argument' and you feel like you are being patronised by me doing so, then we've already lost each other, and you may as well block me now, because I will probably share more definitions of commonly used terms.

This practice of defining terminology to understand the basis of someone's argument is not an unusual practice in legal documents, business proposals or academic papers.

In fact, a similar practice is used in mathematics and programming to be able to keep the code short.

Also, when I refer you to research literature, you will be confonted with pervasive pathology language, because the majority of scientists who work in autism biology frame it that way. They talk about autism as a disease, a disorder, they talk about autism risk.

You need to be ready to translate this to your own paradigm in your head if you think it's going to make you feel miserable having to read it framed that way all the time.

I have a tip for how to do that, and I will get to it later. But now, I need to go to work.

Here's a lovely old machine which I photographed in a secret location in Pretoria in 2019.

First, some recommended reading for noobs to genetics, and in particular people like me who glaze over when confronted with lots of dense text. I learn best with chunks, humour and pictures. 'Introducing Genetics - A Graphic Guide)' has all that.

Suggestion: Make notes. Keep a list of terms (a personal glossary). This will help you when you are reading about genes and autism later.

The book also has an index. The Eugenics Society is mentioned on page 27...

Now, this book is just an introduction. It doesn't contain all the words you will need to understand discussions about autism and the role of genes. For example, it doesn't contain anything about epigenetics, a useful concept to learn about when talking about our health.

But it helps me contextually understand some of the difficult but fundamental concepts I read about in medical journals, and it explains how scientists came to their conclusions about these things.

I'm not going to summarise the book, or give you the fundamental concepts of genetics, genomics and epigenetics (partly because it's labour, and partly because I'd do it badly).

But I am going to give you a few factoids, and I will also elucidate a few concepts relevant to the topic.

First: Scientists are not looking for "the autism gene".

There isn't a thing called "the autism gene" or "the gene for autism".

I know, I know... when I was first diagnosed, I assumed that "autism is genetic so there must be an autism gene" and I didn't even question that assumption.

I also (with great confidence and much to my embarassment now) told other people complete nonsense about autism, based on my non-understanding of the genetics of autism. Businesspeople even. My clients. (Blush.)

I wouldn't say that I know a great deal now, I would just say that my Dunning-Kruger beliefs are not as terrible as they used to be.

A gene is a small bitty of a beeeeg molecule called DNA. DNA is a sort of recipe book for making other molecules, mainly proteins. So, usually a gene is a recipe for a specific protein.

Recipes have variations. Like, your zucchini soup maybe doesn't taste like my zucchini soup, because you make yours with garlic, and my recipe has onions; and that other dude's zucchini soup has hardly any zucchini!

So, similarly, we may have different variants of the same genes, and because these 'recipes' are different, the proteins made based on their instructions are slightly different from one another.

Fun fact: Many people think that "DNA is found in the nucleus of our cells" and that a person's DNA is the same throughout all the cells of their body. This is not an accurate reflection of the real state of affairs.

If I don't run out of energy, I will eventually post something about mitochondrial DNA—DNA that is found inside the "energy centres" of our cells.

I think I'll post a video later about why mitochondrial DNA is not the same throughout the body, and why it's sometimes important to consider in health issues (and often neglected, because many doctors dunno about why it's relevant). Mitochondrial DNA comes only from mothers.

There are reasons why even nuclear DNA isn't always the same throughout the body, but let me not get sidetracked now, I am already off on a tangent here.

Let me get back to this and why it's important.

https://twitter.com/ekverstania/status/1445079275930009608

Genes don't just provide recipes for anatomical features, like the curliness of your hair or the size of your brain. They also provide recipes for the day to day running of your body.

For example, part of the day to day running of your body involves neurotransmission -- the sending of signals via your nerves. That's a sort of "electrical process" (or more accurately, "an electrochemical process").

Neurons (nerve cells) are very long (like electrical wires) and the long bits (called axons) are covered in a sheath (almost like copper wire is usually covered in a protective coating to isolate it).

But unlike copper wires, these long cells have a variety of little channels going through their membrane, along their length, that let ions (charged particicles) in and out of that cell.

Biologists, feel free to interrupt if I am explaining badly!

Everyone else, feel free to google for pics of any of these things: neurons, axons, etc.

It is because of these ion channels and the electrical charge which keeps changing along the length that a signal can move along the length of a nerve.

Those ion channels are not just empty passages. They are... proteins!

There are many kinds of ion channels with different purposes. For example, there are sodium channels, calcium channels, chloride channels... the channels are all different proteins, each 'designed' to give access to a specific type of ion (charged atom/molecule/particle).

It gets even more specific than that and I am tempted to go into more detail now, but I will attempt to resist the urge...

Let's just say, for now, that if your recipe for a specific ion channel is not optimal, you may have "biological issues".

For example, you could have an ion channel problem that makes it harder for your cells to retain their potassium, and so you often have sensory overload.

And your friend maybe has an ion channel problem that does the opposite, and they ALSO often have sensory overload, but for a different reason.

Or you may have an ion channel problem that leads to seizures, ataxia, and huge migraines.

Aaaaand so on!

This article contains lists of channelopathies (ion channel diseases) that affect the nervous system, the heart, the endocrine (hormone) system, the immune system, and the renal (kidney) system.

ncbi.nlm.nih.gov/pmc/articles/P…

It is possible to have a channelopathy that is not congenital (in other words, you weren't born with a gene that makes the proteins that way); but many channelopathies ARE linked to specific gene variants.

Now, genes also provide recipes for a whole lot of other things; this is just an example.

I used this example because certain channelopathies occur more frequently in autistic people than in other people, although not all autistic people have them; and not all autistic people who have channelopathies have the same ones.

Now, remember that genes provide recipes for the body to make the ion channels; and specific variants of the genes will make ion channels that are quite unusual and uncommon.

In some cases, you can be pretty sure that if someone has a specific gene variant, they WILL also be autistic—or at least 'autistic-like'; because it depends on how you define autism!

Here's an example:

Mutations in the CACNA1C gene are responsible for all reported cases of Timothy syndrome.

This gene provides the recipe for making an ion called CaV1.2 that transports positively charged calcium ions into cardiac cells (cardiomyocytes) and nerve cells (neurons) in the brain. People with Timothy syndrome have heart problems.

They also have autistic traits. Some people would say that it's the way those ion channels work when they have that recipe that is causing those autistic traits in people with Timothy syndrome.
link.springer.com/article/10.100…

Now, not everyone who is autistic has Timothy syndrome. Not every autistic person has an unusual CaV1.2 channel in their cells. Not every autistic person has a CACNA1C mutation.

So, is the CACNA1C gene "the autism gene"? Nah.

Is it "an autism gene"? Yeah, sometimes. If you have a relevant variant of that gene, you're gonna have autistic traits.

medlineplus.gov/genetics/gene/…

This is just one example. The people who collect information about autistic people's genes put them into databases and create graphs to show which gene variants and which combinations of gene variants occur most often in people who have autistic traits.

This enables them to say, "You have this and that, and your husband has the same, plus this other thing, so there's a strong possibility that if you have a baby, the baby will be autistic and will also have [whatever other traits associated with that]."

gene.sfari.org/database/gene-…

Now, one of my friends who has quite pronounced autistic traits, and a very autistic-like father, had genome testing done, and the geneticist found NO gene variants that are known to be associated with autism. When autism is of unknown origin, it is called "idiopathic autism".

Most cases of autism are considered to be idiopathic, in other words, "Yeah, doh... uh... OK, so you have this nerdy engineer dad, but by looking at your genes, we can't figure out why you're autistic."

frontiersin.org/research-topic…

So now... we will turn our attention to... epigenetics!

But this is where I get to take a break, so here is another picture which I took in that secret place in 2019.

Oh drat. I seem to have accidentally created one or two forks in my thread, which means that whichever path you followed, you would have had some missing bits in the explanation.

I don't have the stamina to go and tie up those loose ends now, but if I remember, I will reconnect them next time.

Sigh. I can't find the fork now, so let me just keep moving. Here is some reference material for the discussion on epigenetics, which comes next.

yourgenome.org/facts/what-is-…

You'll see that the page mentions mRNA, and if you are interested in a tangent, you may want to read up about how the Moderna and Pfizer vaccines for COVID-19 work, because they make use of mRNA. theconversation.com/how-mrna-vacci…

Some people who don't understand mRNA have been afraid that these vaccines can 'change your genes'. This is wrong. mRNA is not 'genes'. mRNA is like e-mail that someone sends with instructions to make soup BASED on a recipe. It is neither the recipe book nor a page in that book.

In the case of these vaccines, that e-mail is not based on your own recipe book. It's an external memo with instructions.

There is no way the e-mail memo is gonna bust out of your computer and grab the recipe book off the shelf and rewrite the pages.

Or if we want to use a digital recipe book (a .pdf or Kindle book) as our metaphor for our DNA, then the same thing applies: e-mail doesn't just go rogue and develop weird intelligent weapons and hunt for a specific .pdf and then go and rewrite recipes in it.

So, because I know what mRNA does, and that the mRNA vaccines don't actually include any concussed versions of the actual virus like many old-fashioned vaccines, I thought this was suuuuper clever and I was very excited to get this amazing vaccine.

Sorry, I got side-tracked. I think I should just pause also to thank @iXeno and other scientists who have been reading this thread, and who will stop me if I tell you to much nonsense. So it makes me more secure, knowing that I am not gonna mislead you too badly.

So, back to GENE EXPRESSION.

You know how you can have a recipe book, and you often bake the scones, but you neeeever make the the raspberry pudding that is in the same book?

Well, genes can be like that, some of them could just lie there and nothing really happens.

Your DNA is actually an heirloom recipe book. It contains two recipes for each dish, one from your biological father and one from your biological mother.

Sometimes they both give you the same recipe, and sometimes you get two different variants for the same dish, and one becomes your main recipe for that dish.

In other words, you have gene pairs, and if the variants of those genes differ from one another, one will be dominant and one will be recessive.

Why some genes are 'obeyed' by the body while others just sit there and watch the dominant ones do their thing is best understood from the perspective of evolutionary biology.

And if you're an aspie supremacist, you sit up and go wide-eyed now, because you think I am gonna talk wild ideas about how autism is the next stage in human perfectifying or something.

Sorry, nah, I wanna get to epigenetics, but if you're lucky, I may talk about biohacking when I get there, and you'll probably find that interesting.

Let me just try to stay on track, though, and say that gene expression means "actually using a recipe to make something".

Epigenetics is about how your environment and the things you do (plus things that get done to you) can cause changes that affect the way your genes work.

This won't change your actual genes, it just affects gene expression, so it definitely can affect how you feel and how your body works.

What's also interesting is that all this environment and experiences stuff can alter how genes are expressed in... your offspring!

People are suggesting, therefore, that not all autisms are strictly genetic in their aetiology. They're thinking that some autisms could be epigenetic. ncbi.nlm.nih.gov/pmc/articles/P…

Yeah, I used a plural there: autisms. It was intentional.

But now, I need to finish off a report for a client, so here is another machine scene for 2019.

PS: This is a reminder to myself to tell you how to 'translate' autism genetics into a more palatable form for yourself, because if you just keep reading words like 'pathology', 'missense genes', 'disorder', 'disease', etc. in every friggin' biology paper on autism...

...you may just start feeling like they reeeeeeaaally don't like your existence on the planet. (Well, you'd probably be right, the biologists mostly wanna either get rid of you or edit you, but it doesn't mean YOU have to go down into their mental dungeon.)

Argh, I left out a word!

The sentence should read,
"This gene provides the recipe for making an ion channel called CaV1.2..."

https://twitter.com/ekverstania/status/1445100760220459016

Coming up in future episodes: lots of -ome words! Genome! Microbiome! Human virome or viral metagenome! And just for fun (although not in the same category of -ome things): connectome! Shall we do things ending in -omics too? Adversomics? Yeah, lets do that too, for good measure.