PEERING THROUGH THE MUTATIONS: Researchers have now collected enough rare mutations associated with autism to begin finding patterns of common disrupted pathways and networks.
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The underpinnings of autism are turning out to be even more varied than the disease's diverse manifestations. In four new studies and an analysis published June 8 researchers have added some major landmarks in the complex landscape of the disease, uncovering clues as to why the disease is so much more prevalent in male children and how such varied genetic mutations can lead to similar symptoms.
Large genetic studies have ruled out the idea that the malfunction of a universal gene or set of genes causes autism. And the new papers, which assessed the genomes of about 1,000 families that had only one autistic child, revealed that the genetic mutations that are likely responsible for the disorder are exceedingly rare—sometimes almost unique to an individual patient. Even some of the most common point of mutations were found in only about 1 percent of autistic children.
This finding means that the number of genes lurking behind autism spectrum disorder (ASD) is at least "in the hundreds," says Matthew State of Yale University's Program on Neurogenetics and co-author of one of the new studies. "That's a significant change from the '90s when it was [thought to be] five to 15." And getting a handle on such rare genetic mutations—even in the growing autistic population—is challenging.
Despite the rarity of these genetic code errors, researchers could detect some important patterns in the disparate data. One aberrant gene has already been linked to other social disorders. And by analyzing the role of these genes in neural development, one team of researchers suggests different genetic mutations might often disturb an entire common network.
Down the road, these developments might benefit treatment, too. "It sets the stage to think about it in a new way," says State, whose group's work appears in Neuron.
These large studies are "a good step forward," says Simon Gregory, an associate professor of molecular genetics and microbiology at Duke University, who was not involved in any of the new research. They "enable us to confirm what we'd thought about genetic rearrangements" and are "very important" in having pinpointed new relevant pathways, he notes.
Family patterns
Although autism has been established as a genetically based disease, it does not seem to be passed along in families in the same way that Huntington's disease is. Because those with ASD rarely end up having children of their own, mutations are unlikely to become widespread in populations.
Studies of twins and other families in which more than one child has ASD have shown that autism does have strong genetic roots, but the new studies sought to get past the commonalities and search instead families in which only one child has the disease.
"You see clearly that if you compare the autistic kids with their [unaffected] siblings, they have more of these mutations," says Dennis Vitkup of the Department of Biomedical Informatics at Columbia University and co-author of one of the new studies published in Neuron.
In assessing such a large and diverse data set several of the studies all alighted on a genetic explanation for one of the most striking patterns in ADS: why at least four times as many boys than girls are diagnosed with the disease.
Girls, it seems, might better resist the development of autistic signs: Bigger genetic disruptions are necessary to cause ASD to manifest in girls than in boys, according to the new analyses. Girls might be better protected against autism-causing genetic anomalies, Vitkup suggests, because they tend to have stronger social inclinations than boys.
Although the ability of girls to withstand genetic mayhem might seem to predispose them to become silent carriers of autism, the new analysis shows that mothers were no more likely than fathers to pass on harmful mutations.
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36 Comments
Add CommentWhen do you give up on genetics and say that something else is causing Autism? Isn't there enough evidence already suggesting that in most children something in the environment is causing Autism?
Reply | Report Abuse | Link to thisNo, There is no question that it's genetic. The denial some parents have stands in the way of the reality.
Reply | Report Abuse | Link to thisThere was a good article about "Why Smart People Believe Weird Things".
It maybe a book too. I'm sure you can find it in the search here.
Denial is the real problem. Years of environmental proof is just not there. I'm sorry, it's the truth.
Bops, I agree its largely genetic. However, nothing in the world is absolute (except the US's poor soccer), but I wonder to what degree epigenetics play a part in autism.
Reply | Report Abuse | Link to thisEver since studying epigenetics in college, I've found myself frustrated by its lack of mention. With all genetic issues, epigenetics is something worthy of consideration, and it never seems mentioned in these type of articles.
Could this be the first sign of human beings mutating right before our eyes?
Reply | Report Abuse | Link to thisYou got that right Cool! My Asperger's has made life for me challenging but very rewarding. It's evolution at work, sometimes you get the Rainman and sometimes you get a Green Beret with an IQ of 138.
Reply | Report Abuse | Link to thisWhy do we continue to think of environment and genetics as two discrete, non-interacting either/or spheres? Why for example, does this very article basically throw away without further comment the most concrete observation- that girls are 1/4th as likely to manifest autistic characteristics - because they are more "socially inclined" therefore more "resistant" to genetic variations? This "social inclination" is basically a learned phenomena based on how we treat and raise boys vs. girls and it gets no further discussion at all. Instead we go back to looking for genes we can manipulate by pharmacology. That may or may not have any future value, but the very article implies we need more more integrated focus on how/what learned behaviors give this increased "resistance" to the genetic variations we attempt to link to ASD.
Reply | Report Abuse | Link to thisI also suspect that I 'suffer' from Asperger's (my life has been an 'interesting' experience), but there was certainly no testing when I was a child in the 1050s. I do have a gifted grandson that has been diagnosed and two very interesting granddaughters.
Reply | Report Abuse | Link to thisAlso interesting is that the population of the world will soon have tripled in my lifetime while the rural populace has increasingly migrated to cities. While I think this is an extremely high risk strategy for humanity, it most certainly changes the demands for individual survival strategies in ways that are not completely understood. Everyone now seems to communicate most intimately with personal electronics devices and social networks... Perhaps 'normal' has already changed, leaving pseudo-psycho-science behind.
This article states:
"...To help sort out this increasingly urgent answer, Gregory advocates for a broad-spectrum approach. "It's not going to be one thing, it's going to be a collection," he says. "Between genetic, genomic and epigenetic, we'll identify what causes the spectrum.""
How could it be otherwise when such a broad spectrum of symptoms and varying degrees of disability have already been thrown together a single condition? There is almost no hope of finding a single solution for such a 'broad spectrum' of disorders. In fact, some of these symptoms could be beneficial adaptations to broadly changing conditions.
Not to say that many if not most of those affected with classical Autism symptoms are not profoundly disabled. But to make such generalizations as:
"Although autism has been established as a genetically based disease, it does not seem to be passed along in families in the same way that Huntington's disease is. Because those with ASD rarely end up having children of their own, mutations are unlikely to become widespread in populations."
is ludicrous. If you surveyed those with Asperger's I suspect you'd find that they are outliers in your sample population. My biggest fear for my grandson is that his diagnosis will lead to social and/or medical bureaucratic ostracization - or worse.
Who knows - perhaps it is those who can see the world differently that will be necessary to save it.
I've seen it argued that the apparent increasing incidence of ASD's could be due to more assortative mating taking place. In modern society, it could be that like is meeting like more often, and drawing consequences. If both sides have a disposition to ASD, the chances that offspring will have the overt syndrome are perhaps higher.
Reply | Report Abuse | Link to thisThere have been suggestions that ASD style traits are more common in sciency types. With access to college being easier nowadays, couples with that disposition are finding each other and producing kids with stronger versions of the trait.
Although you may be partially correct, it would be close to impossible to test for any kind of assortative mating with such a large populous. It may be more beneficial if we first isolated some epigenetic influences because it seems that is where most problems are occurring. By studying families and how they interact with their children who have autism may be a better start for the future of understanding this disease better. Then, maybe, if it becomes more possible you can then start testing for some kind of assortative mating influences. The current progress of understanding for this disease is in a very good spot. Rome wasn't built in one day.
Reply | Report Abuse | Link to thisHas anyone studied relation of sonograms performed during fetal development and later emergence of autism?
Reply | Report Abuse | Link to thisA really excellent article and some great comments. As I read it I could not help wondering about the one topic not mentioned. The categorisation of sufferers of ASD. I see no mention of how sophisticated they are categorised or if it done at all. It would seem to me that starting with well categorised sufferers DNA is critical to drawing conclusions from the DNA analysis.
Reply | Report Abuse | Link to thisHi! Yah i'd say you are correct Coolynn, a mutation. Would you like an explanation based on genetics, among other things? - visit www.jovianarchive.com.
Reply | Report Abuse | Link to thisA lot of "hunches" and contrived reasons here. Humans are generally not too intelligent or creative and it takes decades for a society to resolve anything, only to create another problem because of that lack of intelligence. It seems all advancements are cancelled by humans themselves. How long ago was it that humans knew blood circulated through the body? Not too long ago. Genetics,etc? What is not a part of genetics? Humans have not figured out what is "normal" genetics and yet they venture to define. The silly idea that autism can be cured through social intervention is incredibly primitive and just a sad act of desperation...otherwise autism would have been " cured" already. Behavioral,etc. intervention does have a degree of success, because it effects the symptom. Humans don't know much about how the brain operates, and until they do....autism and many other "defects" will not be treatable.
Reply | Report Abuse | Link to thisAssortative mating is true for many issues, and thinking of it as the cause is ridiculous. It's virtually not worth mentioning. It certainly offers no cure. Thinking is certainly not taught enough in US schools.
Reply | Report Abuse | Link to thisWell, we don't continue to think about environment and genetics as separate spheres. That time has long since passed. I think the key issue is that it is still difficult to integrate genetic and environmental data on the broad scale seen in these kinds of studies. This isn't all that surprising, I mean GWAS didn't even exist >10 years ago. It will be interesting to see what happens when we start throwing in more environmental variables as well as gene expression data.
Reply | Report Abuse | Link to thisIf there is such a broad range of genetic mutations than can account for ASD, then why is it that 1 in 150 kids have it? That's just way too widespread for so may mutations to be necessary. I believe that it HAS to be something that virtually all kids are exposed to and means environmental, diet-related or common medical-related practices. May genetic mutations in so many people would be quite rare.
Reply | Report Abuse | Link to thisIf there is such a broad range of genetic mutations than can account for ASD, then why is it that 1 in 150 kids have it? That's just way too widespread for so may mutations to be necessary. I believe that it HAS to be something that virtually all kids are exposed to and means environmental, diet-related or common medical-related practices. May genetic mutations in so many people would be quite rare.
Reply | Report Abuse | Link to thisWhat if the, "many genetic mutations (occurring) in so many people" is actually an evolutionary change that as, a system change, in us started hundreds of years ago and is only now making it's way to the surface? A lot of the time Science is like trying to find a needle in a haystack. But i do enjoy the search.
Reply | Report Abuse | Link to this"If there is such a broad range of genetic mutations than can account for ASD, then why is it that 1 in 150 kids have it?"
Reply | Report Abuse | Link to thisWell, that's the whole point--ASD is not a "single" disease. It's a spectrum of behaviour which is thought to be produced by a wide variety of genetic mutations. Nobody with an ASD diagnosis has all of the possible mutations that are associated with ASD. Rather, each person just has a few specific mutations which may make them susceptible to developing this disorder. This probably isn't the whole story as it's likely that many factors interact with these mutations to produce ASD. However, there's no reason to believe that there is some sort of environmental toxin or dietary deficiency which is causing people to develop this disease.
I didn't go to a US school, and if I just went by your response I'd have to conclude that reading and manners aren't taught in the US either. Where did I say that assortative mating was the cause of ASD? I posited a possible partial explanation for the alleged increase in this condition. It wasn't my idea: it came from someone who has high post-grad qualifications in biology.
Reply | Report Abuse | Link to thisOne of the problems with girls/women and ASD is that many end up diagnosed wrongly, for example as borderline. How can you make decisions on genetics when the diagnoses is still in its infancy? Another question: might ASD be in fact a collection of different disorders?
Reply | Report Abuse | Link to thisThe world would be much poorer without the odd (!) Asperger gene combinations, which, by way of this marvelous Mendelian gene shuffling game, have led, and are leading, to the odd genius - think: Mozart & Beethoven and such ilk....
Reply | Report Abuse | Link to thisOne could possibly classify the majority of creative artists , if not as 'Aspi's' (on the widest possible spectrum) , then plain & simply as extreme introverts; and Comparative behaviorology gives us an evolutionary insight into this phenomenon, too: Every dog breeder knows full well that in each litter there are wide variations possible amongst its puppies regarding their aptitude towards sociability training;
cf. a wild wolf's behavior with a guide dog's 'empathy' into a blind person's needs...
Domestication-cum- civilization must have worked mighty changes in our H. S.S. prefrontal department, too!
The fact that autism has grown tenfold or more in the past three or four decades, however,clearly points to some environmental changes influencing babies' brain developments, apart from their 'given' genes cocktail.
Dietary influences are the most likely culprits.
I am constantly astounded that the role of dietary deficiencies is being almost always totally ignored or negated ( see under 19).
The role of essential fatty acids such as the omega3/omega6 ratio in brain health ( both in fetal neuronal development and, later, in Alzheimer's disease) is now clearly coming to the fore.
'Frankenstein' fats such as transfatty acids might have a lot to answer for, amongst many other dumb diet changes from natural to denatured. (youthevity.com)
If autism is genetic, where are all the 80-year old autism cases?
Reply | Report Abuse | Link to thisVaccines exist for a reason.
They make drug companies rich, selling drugs to treat autoimmune diseases caused by vaccination.
The drug makers main source for info on the safety of thimerosal, Poul Thorsen, was recently indicted for fraud and grand larceny in connection with his thimerosal research. He was hired by drug companies to commit fraud so they could keep poisoning children. Eli Lilly Co. owns the patent on thimerosal. Who was head of Lilly after he left the CIA? George Herbert Walker Bush.
This vaccine/autoimmune illness link has been common knowledge in the medical research field since June, 2000, when the first Vaccine Safety Datalink Study results read at Simpsonwood, Ga. showed a tenfold increase in a wide array of neurological problems associated with infant vaccines. They saw increased reading delays, speech delays, autism, tics and mood disorders, which scared them so badly they immediately began discussing ways to bury the data and commit fraud.
What was the most common diagnosis? "Misery and Unhappiness Disorder." What is one the most common symptoms of mercury poisoning? Depression.
The mechanism is called a "Type IV Delayed Immune Hypersensitivity," and it can trigger immune attacks against healthy tissue, days or years after vaccination. The other adjuvants and preservatives in vaccines (aluminum, antibiotics, etc.) interact with lead and testosterone to cause even higher rates of damage to males, resulting in the 4-to-1 sex disparity in autism. But please, go on poisoning your children. Kids are FAR less important than drug company profits from causing childhood diabetes, autism, ADD, ADHD, depression, asthma and Guillain-Barre Syndrome, among others.
All of which increased among children after additions to the children's vaccine schedule, and skyrocketed since George H.W. Bush mandated the day of birth HepB shot in 1989.
One hilarious aspect of this public health disaster is the rate of autism in Atlanta, Ga. was discovered in 1996 to be far higher than the rest of the nation.
Reply | Report Abuse | Link to thishttp://www.medscape.com/viewarticle/447240
This is most likely the result of parents playing the role of good little cattle, herding their calves in to be vaccinated under the watchful eye of Atlanta's "Centers for Disease Control." Interesting name, that.
It's not the Centers for Disease PREVENTION, or the Centers for Disease ERADICATION. No, it's all about CONTROL. They want to control who gets sick. Judging from the one-in-six rate for neurological trouble in American kids, they're doin' a bang-up job.
"This "social inclination" is basically a learned phenomena based on how we treat and raise boys vs. girls and it gets no further discussion at all. Instead we go back to looking for genes we can manipulate by pharmacology."
Reply | Report Abuse | Link to thisI think a large part of the difference is the different sex hormone ratios in girls vs boys not purely environment.
Unusual conclusions require unusually strong proof. So, put up or shut up. How is anyone to know if your assertions are not just ravings of a paranoid personality?
Reply | Report Abuse | Link to thisIf people are still blind enough to think this epidemic is in the genes then i despair..wake up..its ALL vaccine damage/enviromental... playing on certain people with certain genes/predispositions ..god ..a monkey could work it out ..big pharma does not want anyone to catch onto this,and that is the truth..there is a rise in asd disorders that directly correlates to the rise in vaccine scedule...when will the general public wake up from the damn slumber and listen to the parents ,who have seen it all with their own eyes.!!!!
Reply | Report Abuse | Link to thisexactly...at least someone is awake here.
Reply | Report Abuse | Link to thistry talking to the thousands of parents that you just swept aside with those uneducated statements... ask them whether they saw their child disapear after vaccinations or not..ask them if their child has biological problems like gut issues,and then ask if they have solved them with certain interventions,,proving this is biological... try asking the parents for the truth smart arse.
Reply | Report Abuse | Link to thisfor goodness sake.!!! its an epidemic...there is no such thing as an genectic epidemic...im surrounded by fools..no wonder the poor parents of all these children are tearing their hair out...why wont anyone listen to them??? the vaccines are the most likely cause in this,,it is those which have gone up in number along with the rise in asd ,and it is those that give children the bodies full of toxic crap..the metals in the vaccines compromise the immune system ,and also they are causing encephalitis ... if you do not all listen to the parents soon,you will be listening to the crap science forever and in the meantime your children and grand children too will be injured..its only a matter of time
Reply | Report Abuse | Link to thisno,,because the children in poor countries do not get that,,but what they are now getting is more vaccines instead of help with better sanitation and clean water..and now watch, the asd rates climb.
Reply | Report Abuse | Link to thisWell, you could try doing some research, the transcript of the Simpsonwood meeting where doctors and industry reps conspired to commit fraud is available online.
Reply | Report Abuse | Link to thishttp://www.autismhelpforyou.com/HG%20IN%20VACCINES%20-%20Simpsonwood%20-%20Internet%20File.pdf
How is anyone to know if your complacent platitudes are not the product of an industry hatchet man? The drug companies opinion that injecting aluminum, mercury and other toxins into babies is harmless is the unusual conclusion. Where's your proof it's safe? You have none.
"If autism is genetic, where are all the 80-year old autism cases?" My father an engineer [typical profession for one end of the spectrum] is in his 70s. I am officially diagnosed and I am 45. Then realize that many people diagnosed with "mental retardation" in the past are now more correctly diagnosed with an ASD.
Reply | Report Abuse | Link to thisIf vaccines are to make $$ then why do poor and developing countries do their best to manufacture their own vaccines? This includes communist and socialist countries who give them to their citizens for free. As a person who bought vaccines for an animal hospital I can tell you that they were no money maker for us or the manufacturer. The only expensive vaccines were the newer less used vaccines, for example the Lyme disease vaccines. The vaccine that was required by law, Rabies, was the least expensive and we did not overcharge for it.
Pediatricians will tell you the same sort of story, so unless they all lie, like the exciting plot of an X-files episode [this why you guys all believe this stuff, it is SO exciting, huh?], your idea is just plain incorrect.
If you are going to do proper research you need to cite original documents not an "autism for you" site, or at least from a neutral source. As far as this old canard about Simpsonwood, its supposed nefarious content has been debunked. See Wikipedia: "Salon magazine later corrected the article multiple times for factual errors and ultimately retracted the article." 2000 Simpsonwood CDC conference: Wikipedia. This mercury theory also has been debunked many times over. Now the latest X-files "episode" is about "Too many, Too soon". But watch out, "trust no one!"
Reply | Report Abuse | Link to thisBTW, Aluminum combines with mercury only if aluminum is in its "elemental" form, not when aluminum is in a salt form as it is in microgram amounts in some vaccine adjuvants.
Again, mercury poisoning is nothing like autism. I do not know any autistic person whose skin is pealing off whose skin is pink, who sweats profusely, who has high blood pressure from no other cause, who is losing teeth, hair and nails, who has kidney dz from no other cause etc. These ideas are fabrications grabbed desperately for those looking for a scapegoat. Just read up on mercury poisoning yourself, not from some one who has an axe to grind or money to make (like product liability lawyers).
Reply | Report Abuse | Link to this"This "social inclination" is basically a learned phenomena based on how we treat and raise boys vs. girls and it gets no further discussion at all."
Reply | Report Abuse | Link to thisHave you never thought of hormone differences? The idea that social inclination is mostly a "learned phenomena" has been proven false. Sure, our culture has stereotypes for men and women, but such powerful things like our hormones [ever feel the strong desire to get romantic when you were a teenager?] influence many systems in our bodies, thus at least one of these systems "gets though" to our social behavior.
As a female with an ASD I am a little different from my nephew with the same syndrome. He is quite a bit more interested in collecting things from vacuumes to records [without caring about the music on them] to crystals and many more objects. I was more interested in very few subjects in intense ways. Socially, I am different from my nephew, but we both have difficulties keeping friendships going if the other person is a person focusing on conformity to the majority society.
Just like many genetic traits the variation to extremes, like a very tall kid, can have advantages and sometimes disadvantages. If those around the person with one type of extreme act helpful and try to accommodate and help them learn to adapt, life can turn out better; but if the person is shunned or singled out and treated negatively the consequences can be difficulty for everyone.
Just because someones dose not speak does not mean they cannot hear; just because someone does not look at you does not mean they do not know that you are talking about them or reacting to them. The autistic child is NOT "gone"; they are merely thinking and behaving differently than you. Don't panic.
You need "The Hitchhiker's Guide to the Autistic Galaxy" and you may need a "Babel fish" [ See the book: The Hitchhiker's Guide to the Galaxy] to translate; but you are not in a situation where suicide or despair is the best course of action. In this book the protagonist is taken up away from earth and he relies on his host to help him out, thus similarly, you let them guide you as to how to act in this new world. Sure, you can help out your host and you may use aides to help conduct yourself here, but changing your host or your new world is not your primary job. Be gracious and DON'T PANIC.