Saturday, May 16, 2009

Why is it so difficult to find the "autism gene"?

There was media coverage recently about the discovery of the "first common" set of autism gene variants. The alleles are apparently found in 65% of autistic people. What's interesting is that they also occur in about 50% of non-autistic people. (Some sources say 60%.)

That doesn't sound like a finding that, by itself, could be practically applied to the genetic screening of autistic people. I'm not too worried about that. Additionally, autism-related studies of this sort don't replicate a lot of times.

It seems to be a very difficult problem. Why is that? I'm sure different people have different views about this.

What I was wondering is whether experts dealing with a similarly elusive problem could provide some insights of note. The problem I'm referring to is that of finding the "race gene." The following are the recommendations regarding race and genetics by the National Human Genome Center of Howard University.

1. When the human species is viewed as a whole, underlying genetic variation and expressed physical traits exhibit gradients of differentiation, not discrete units. Therefore, modern extant humans do not fracture into races (subspecies) based on the modern phylogenetic criteria of molecular systematics.
2. The biological “boundaries” between any human divisions (groups, populations, nationalities) are circumstantial and largely dependent on what traits are chosen for emphasis.
3. The demographic units of human societies (and of the U.S. census) are the products of social or political rules, not the forces of biological evolution. The names and characteristics of demographic groups can change and have changed over time.
4. Group differences in health parameters are not encoded in the human genome as part of an evolutionary pattern of divergence. Thus, differences in health or disease cannot be treated as causally related to ethnoancestral groups.
5. Genotype-environment interactions are more important in explaining group differences in health than genotype, environment, or a factor called “race”.
6. The non-existence of human races (subspecies) does not mean the non-existence of racism. Racism is the structured systematic oppression against individuals and groups defined based on physical traits that reflect an extremely limited fraction of the human genome. Racism must be addressed.
7. Individuals cannot be treated as representative for all those who physically resemble them, or have some of the same ethnohistorical ancestry. Ancestries of individuals and groups should be ascertained in order to evaluate differential expression of genetic effects.


I thought that sounded quite pertinent.

I'm not saying that it won't ever be possible to fairly accurately distinguish an autistic person from a non-autistic one by simply looking at a genome sequence. As someone with a Computer Science background, I can theoretically speculate that someone will figure out a method eventually. I just don't think it will get done by simply looking for alleles that represent statistically significant "risk" factors.

See also: Race and Genetics at Wikipedia.


  1. I think it is impossible because first you have to get a handle on what autism is, before you find any genes for it.

    That is something that science has not been able to do.

  2. Autism, Dyslexia, Attention Deficit Disorder are all potential pitfalls when a child doesn't have proper child development. I think all families should be wary of this.

  3. I think it will be impossible even in principle. Autism is a property of a phenotype, not a genotype.

    Just like body size is a property of a phenotype. There are genetic components to body size, but any individual can have a small body phenotype depending on the environment they developed in. You can't make assumptions about body size from a genotype unless you make assumptions about development conditions.

    I see ASDs as similar, but a lot more complex. Many of the development conditions that are important are in utero and completely opaque and unavailable for measurement or analysis.

  4. There's probably no genotype that exactly matches what we call autism. But the phenotype is highly heritable, apparently, so in principle it should be possible to find a genotype->phenotype mapping that is more convincing, e.g. 60% matches and 5% false positives. When they come up with a gap of this size, they'll probably start seriously talking about genetic screening.

    There's a technological problem, though. If the genotype is complex, exhaustively scanning for it might be an intractable problem, computationally.

  5. I fundamentally disagree. There is no "gene" for tallness. You can't have a genetic test for "tallness" because everyone has the property of height, they are just on a spectrum.

    Tallness is highly heritable. Tallness does run in families. If you did try to eliminate "tallness" from the human genome, you would be unsuccessful because having a height is an inherent property of being a human.

    Dogs have been bred to accentuate different properties of "dogness", but all dogs have a height, even though some breeds are very different than others. Height is a property of a phenotype, not a genotype. So is autism.

    If you had 100 clones of an individual, they would have 100 different positions along the autism spectrum, just as they would have 100 different heights. Some of those heights might be very similar, but none would be identical. The more diverse the conditions during development, the more diverse the different phenotypes would be.

    Development is a consequence of hundreds of thousands of non-linear coupled parameters. The result (the phenotype) is fundamentally a result of chaos (in a mathematical sense). It is fundamentally unpredictable.

  6. I'm sure there's no gene for tallness, but if tallness is highly heritable, I'm saying it should be possible to find a function f such that

    height ≈ f(genome)

    Or, in statistical terms, the association between observed height (at some age) and f(genome) should have a high correlation coefficient.

    If such a function cannot be found, it's simply because of computational complexity.

    Unless the heritability of height is explained by something other than DNA, I don't see how this could be incorrect.

  7. What you said is correct, but height is f(gene DNA, non-gene DNA, epigenetic modifications to DNA, environment, imprinting of DNA, unknown). The output is a non-linear function of the inputs.

    There likely would be a statistical correlation between the genotype and the phenotype, but the environment can change that correlation in ways that are completely unpredictable from the genome.

    We know that there are monozygous twins that are discordant for ASDs. That is proof that there can be no precise diagnosis of autism from genes alone.

    It is like the weather, why can't the weather be predicted months in advance? It can't be because the parameters that are involved are non-linear and coupled. The weather is inherently chaotic. The weather is pretty simple, the fluid flow is understood, so is the heat and mass transfer. The weather can’t be predicted because the coupling is non-linear. Development is inherently chaotic too. There are simply too many details to make deterministic predictions.

    What the curebies want for autism is a test with a very low false negative rate. Liability will force the providers of any such test to ensure that the number of false negatives is very low because the liability associated with a false negative will be high. The only way you can decrease the false negative rate is by increasing the false positive rate. If you call every test positive, there are no false negatives and no liability to support an ASD individual their entire life. If we (arbitrarily) assign a cost of $1 million to each false negative and charge $1000 for each test, then there can be no more than 1 false negative per 1000 tests.

  8. Joseph,

    This is completely off topic, but is there a way to contact you via email privately?

  9. Joseph, see for a response to your testing comment.

  10. @Alexander: I've left a comment in your blog.

    joe, this is not meant to be a comment...i cant figure out how to send this to you as a personal message.
    Please read the links contents i sent you and i would appreciate if you would give me your opinion on it.
    also, please delete this as a message or comment that others can see.

  12. A very interesting blog and discussion. I am not an expert in genetics but I wonder if anyone is testing non-coding regions of the human genome to determine if AS/autism constitutes a discreet population.

    Joseph - would you be interested in placing a link to my website on your blog? My url is , and the topic is a possible reason for the evolution of AS/autism.


  13. Autism is definitely controlled by more than one gene. It is not just a Mendelian trait with only two or three phenotypes. The reason it comes in such a broad spectrum is because it is polygenic, like height or skin color. Polygenic traits can be influenced by the environment as well. The argument against autism being genetic is the fact that sometimes only one identical twin develops it. It is the same principle as if one twin grows taller than the other, because he drinks milk while the other drinks soda. Whether one may develop autism or not is probably more complicated. It might not necessarily be triggered by chemical intake (from food or vaccines).


  14. Hello,

    Please help us spread the word! There are workshops once a week and many other programs to help families.
    Please give them a call.



    Advanced Behavior Management

    Presented by: Jennifer Styzens, M.S., BCBA

    For those who have a basic knowledge of ABA strategies, this workshop will expand your ability to utilize more advanced behavioral terminology and develop intervention plans with comprehensive reactive and proactive strategies.

    This 2-day workshop will include

    *Didactic and experiential format
    *Behavioral scenarios to demonstrate ABA strategies and techniques
    *Functional assessment issues
    *Development of intervention plans designed to reduce disruptive behavior
    *Development of intervention plans designed to teach replacement behaviors.

    Who Should Attend:

    Clinicians, parents and teachers with sufficient knowledge of autism

    Tues/Wed, August 18-19, 2009
    8:30AM – 3:30PM

    Autism Partnership
    200 Marina Drive, Seal Beach CA 90740
    Questions can be directed to or 1-800-816-9293, press “0”.

  15. You make an interesting point here. My husband and I assume there must be some genetic link to autism, because both of us have many autistic traits (and score high on the autism quiz) and the three children we've had together have diagnoses of autism spectrum disorder. Whereas my stepson, who has a very NT mom, doesn't place on the spectrum.

    Yet, I don't expect a single genetic cause to ever be found. A single cause would not explain the range of functioning or differences between genetic twins.

    And the racial comparison was spot on for its many implications!

  16. Why is no-one looking for the N/T gene? Given that N/Ts exhibit all of the neotenous characteristics of a domesticated species, and are thus more likely to actually be the "mutation", it'd probably be easier to find...

  17. This comment has been removed by a blog administrator.

  18. Mary,

    That website is a pretty blatant scam.

  19. Mary's comment is spam. I saw the same exact comment at LB/RB.

  20. Joseph,

    To be fair, she could just be asking around... and even if she isn't, noting that it is a scam benefits any naive readers who may be going through these comments.

  21. Here are the facts:
    -I have Asperger Syndrome
    -I am a 22 year old guy
    -I am in my last year of undergrad college doing an internship.
    -I had a strong interest in many natural sciences as a younger child.
    -I am an Eagle Scout.
    -I was frequently bullied by others in middle school.
    -I started my first year of college as a biology major.

    I am NOT a Rocket Scientist and
    I am NOT a Zookeeper;
    I am a Social Worker.
    I don't technically have a career or license yet, but since my first year of college I have experienced many emotional changes, and I realized that my place in society is to give direct help to those who cannot help themselves. It is my job in society to prevent young and innocent lives from being lost and destroyed. I have volunteered and worked for several different afterschool programs, helping agencies, and day camps. I now have and internship with child services in my home state, and even though so far it's been emotionally hardcore, I have no intentions of turning back.
    My point is there may be some genetics involved in this disorder, but I really believe that people with Asperger syndrome and other forms of autism on the high functioning end can do things that many people believe they can't or deliberately don't do. Don't get me wrong, my own family, as well as many close others were shaming me into going back to the science field, and it made me feel very useless, but I simply refused to go back. Their resistance and my own deficits together were just no match for my passion.

    I'm not advising those out there to enter this field or not enter it, but if you feel passionate about a cause of some kind, there has got to be a way.

  22. Southeast and main Asian pandora jewelry countries have twisted rubies for centuries, cheap pandora bracelets but research as to where, and how to find more deposits is Pandora charms spare, and production has figured out how and mining companies,” Pandora beads Giuliani says, to look at exactly the right time and place.” pandora set Farther investigation of claret formation, based on tectonic scenery, cheap pandora geochemistry, fluid inclusions and isotopic ratios, allowed discount pandora Giuliani’s lineup to remodel a new prototype for the French Institute pandora 2010 of Research for Development (IRD) and the National Scientific pandora sale Center of Research, two government-sponsored knowledge Pandora Bangles and technology research institutes that aim to aid in the sustainable cheap pandora bracelets development of developing countries. Before the collision pandora bracelets prices of the Eurasian and Indian plates, lagoons or deltas sat in the regions where marble is giant, pandora bracelets and charms he says, “and there is the brains to expect that the new pandora bracelets sale thoughts should help development of the artless capital.” discount pandora bracelets Virginie Garnier, Gaston Giuliani and Daniel Pandora necklace Ohnenstetter urban the shape to do just that. They work for the garnet cheap pandora charms genesis. While studying the bedrock in Vietnam in 1998, the discount pandora charms French players found rubies, which detained traces of aluminum, chromium pandora charms sale and vanadium from universities, international corporations, governments pandora charms 2010 and why the rubies got there, and has created a paradigm Pandora beads to help these evaporites, Garnier says, when the Eurasian cheap pandora beads and Indian plates collided, raising the Himalaya Mountains.