Mutatis Mutandis: Genetic Mutations and Being at High Risk
July 25, 2007 by Kristina Chew, PhD
Filed under Health
Spontaneous gene mutations may account for half of all cases of autism in males: By now you’ve probably heard about this finding, and about a new model of autism genetics published in Proceedings of the National Academy of Sciences. For a cogent overview, see John Timmer’s July 24th post on Ars Technica. The title of the post, Autism may all be in the genes contains a hidden polemic: Most people take the view that a person has a “genetic predisposition to autism which is “triggered by environmental factors” and shy away from saying that autism is wholly genetic.
Timmer notes that
“genetics can accurately model much of the incidence of autism if you make some very specific assumptions about modes of inheritance”—assumptions which are based on “suggested by what’s already known about the disease.”
More specifically:
Under geneticist Michael Wigler of Cold Spring Harbor Laboratory in Long Island, NY, researchers studied families who have two or more autistic children and considered what the chances were for families whose first two children were autistic to have a third autistic child. In 86 families with two autistic children and with a third, male child, 42 of the third-born children had autistic symptoms. Notes the July 24th Nature.com:
This suggests that parents had a one-in-two chance of passing on a mutation to their offspring, matching a dominant inheritance pattern……
Using mathematical models, Wigler’s team found that the simplest way to describe the patterns of autism inheritance was to divide parents into two risk classes: those who carry a pre-existing autism-causing mutation, and those who do not.
The models suggest that about half of autistic children are born to parents with no previous genetic predisposition to autism, suggesting that the cases are caused by spontaneous mutations.
According to Wigler and his research team, mothers spontaneously acquire genetic mutations that are specific for autism. While the mothers themselves do not have autism, there is a 50% chance that they will transit the autism-related mutations to their children. There are, therefore, families who are at a “low risk” to have an autistic child, and families who are “high risk” (in which the mother carries the mutations but does not show autistic symptoms).
The July 24th Scientific American also brings up the notion of families who are at a “high risk” of having an autistic child in New Theory about Autism’s Roots:
The team determined that most cases of autism arise from novel, spontaneous mutations passed down from one or both parents, resulting in large gaps in a person’s genome often encompassing several genes, which are then disrupted or inactivated. (This loss of genetic code—known as copy number variation—results in an offspring receiving only one of the standard two copies of a gene, which could cause an insufficient amount of protein to be produced by those genes.) In most instances, this mutation will result in an autistic child. However, in some cases—more likely in girls than boys—the recipient of this mutation will not produce any symptoms.
“When that child matures and becomes a parent, they have a 50 percent chance of transmitting … [their mutation] … to a child that might not be as lucky as they were, especially if … [its] … a boy,” Wigler says. “So, they will be transmitting this with close to a 50 percent frequency—and that is the source of the high-risk families.”
Some might respond to these findings by saying that mercury or some environmental toxin created the genetic mutations. My response—my very personal, autism-mother-on-her-soapbox response—is to ask: Ok, spontaneous genetic mutations——–so, are we—-am I—-in the “high risk” 50%?
I am going to posit that I am. As I review my extended family, many members of which are engineers or work in computers or write software or are in IT—some members of which could be placed on some spectrum of quirky geekitude0000I find it perhaps notable that I (who have always written and loved poetry, and don’t do math), have an autistic child (and very happily so, after yet another afternoon passed at the swimming pool praising Charlie for not minding too much that the water slide was closed, an ABA session during which he kept running straightways out the garage door and struggled to say the /ch/ in his own name, and trying to show him how to push the shopping cart s-l-o-w-l-y and not into other shoppers). Some have suggested that there is a sort of “autism cluster” in Silicon Valley; the Valley is where many of my cousins live and work, while here I have been away on the East Coast teaching Latin and Greek and the Classics and teaching college students how to write a good essay.
Maybe those autism genes skipped around and settled in me, who find more and more of Charlie in me and of me in Charlie with each passing day.
Mutatis mutandis goes the Latin: That which has been changed, had to be changed. There can be no doubt that my life has been profoundly changed and shaped by the experience of raising Charlie—-the change of a lifetime that I am grateful for. But what new and difficult choices might parents face if they are told that they are at “high risk” to have a child like him? What changes might happen in our world and among us human beings?
I’d be willing to speculate I have this mutation also… although I would be reluctant to say ‘no’ traits.
I hope the scientists at CSHLab are looking at all possibilities and not just hunting for The Gene.
Other conditions can cause someone to appear to have ‘autistic traits’.
How to determine why some children develop ‘typically’, reaching all milestones, age appropriate speech, socially aware and engaged, no ‘behaviors’, bright as a new penny and then something happens that results in a pervasive development diagnosis?
One often hears of families with more than one child ‘on the spectrum’ these days. Has this always been the case?
Did families years ago just go to ground and disappear from society if they had numerous offspring with autistic characteristics?
Caroline, you ask good questions, and if you immerse yourself in reading legitimate sources of scientific information about this issue you will find the answers.
I wonder if I have the mutation. As I’ve mentioned here and other places before, several of my family members are autistic. They just didn’t call it autism back then. Now I have a child on the spectrum, too. I have also been able to see oddities in myself — I didn’t speak clearly until I was 4, I have synathesia (sp?) — as part of a broader autistic phenotype.
If it’s a spontaneous mutation, you don’t inherit it — by definition, it happens “out of the blue.” It wouldn’t matter what your various family members were like, would it?
Arrgh! Caroline what is called autism now was never called autism years ago if anything.
I once read that a parent thought that this genetic basis was a new way to blame parents. (!) I must say as someone who embraced this view for years watching the science more and more come to agree with me, EMPHATICALLY states hogwash! It is not about blaming parents. It never was. The whole autistic rights movement was never about blaming parents. It was about empowering those on the spectrum which a lot of people find threatening.
Evolution is the random mutation that proves to be beneficial or least non fatal till reproduction that gets passed down.If we stop these random mutations are we curing autism or “curing” evolution? How will humanity be able to cope without the ability to adapt? I also read that the rate of mutations among the autistic population is greater. I remember reading something about rats and how they are evolving “fast”. But in autistics due to prejudice it is described in a negative way.
I always felt that autism is really the misidentification of the part of the human population that is launching pad of the next stage in human evolution.
Hey is that you, cousin Penny?
Uh, I dunno… I’m somebody’s cousin, so maybe I’m yours? There are a surprising number of Pennys in the world, though.
I’ve been fairly sure for quite a while now that, to the extent it is genetic (who knows about environmental contribution?), my son’s autism comes via me and my mother. Both of us, like him, have hyperlexia, as well as various shadow traits of ASDs. Moreover, his dad’s side of the family doesn’t fit the “geeky engineer” profile that some suggest lead to offspring with ASDs. (I’m also not sure whether hyperleixa-type autism might not be its own distinct subset, as few of the people I’ve encountered who are hyperlexic seem to be literal-minded scientific types of the Temple Grandin variety…)
I honestly do have a cousin named Penny who might be reading autism blogs. She’s the one who first pointed out Kassiane’s to me for instance. If that’s you, hey, you owe me email.
It may not be about blaming parents, but someone needs to tell that to the headline writers at Fox News online: Study Links Autism to Mothers.
Copy number variations occur throughout the human genome including the general population people. An association says nothing about the CNV actually does. The first report of a CNV that was associated with a condition was found in HIV patients. Different copy number variations were associated with either susceptibility or resistance to being infected.
Another study last year reported copy number variations in chromosome 11 was associated with adverse reaction to vaccines,
Like so many ‘breakthroughs’ in genetic research, this one has yet to be replicated.
The running count of autism specific genes that cause autism remains zero.
I don’t think I have any cousins who use the name “Bink,” but I wouldn’t be all that surprised, either…
Sorry to hijack this comment thread with a round of “Are You My Cousin?” But it’s also kinda appropriate, in the thread about genetics and inheritance and whatnot, eh?
All in kind!
Thanks to RAJ for why this “breakthrough” is not exactly such.
On the recurring “let’s blame mom” thread is this headline from DailyIndia.com, Mums more likely to pass Autism to their kids—makes it sound like autism is “transmitted.”
RAJ is not quite right despite Dr chew’s endorsement. Nobody said there are not seen elsewhere. I made the point that a study said there is a greater number of mutations in the ASD population.
Also this notion of no single gene is misleading. Autism can be an effect of a set of genes without being “due to a gene”. So in fact no single gene doesnt make it not genetic. Autism can be in the various flavors due to more than one set of genes that can overlap.
Always glad to endorse you, Joe—-I do think that it is too simple to say that there is an “autism gene,” that there is a single gene for autism.
The root word of “mutation,” the Latin mutare, simply means to change without any of the pejorative associations in such English words as “mutant” or “mutation.” I wonder if those pejorative associations are in people’s minds in talking about genetic mutations.
While I’m intrigued by the arguments about autism being underpinned by a genetic mutation, I still wonder about the wide variety of ways autism appears to manifest itself — in some cases from birth, in others as a “regression” and a loss (or at least substantial modification) of skills. How would a single genetic configuration (rather than genetic-predisposition-plus-life/external-factors) account for this? (As you all can tell, I’m not a scientist…
I had a chance to read the paper and have a couple of thoughts:
In the discussion part of the paper, the authors state: “We must emphasize at the outset that our biological interpretation of the risk models assumes that risk is determined by genetic factors, and thus, except for their appealing simplicity, the risk models themselves should not be taken as evidence for genetic causation.”
In other words (my other words, anyway) – “We don’t know if autism is purely genetic in nature, but if it is we think this could explain how that works.”
The authors do offer an explanation of why boys are more affected than girls: “To explain greater penetrance in males, we need merely consider the hypothesis that autism involves loss of cognitive abilities related to social skills, language, and repetitive behavior that may already be targets of sexual dimorphism and hence these traits are already sensitive to perturbation.”
Treading on dangerous ground, especially if you bring this up to those who would like to believe the tabula rasa theory of the mind, that everyone – boys and girls alike – start off equal.
The paper does not mention any incidences of autistic men fathering children, or the impact that has on prevalence in children. I know it’s not because those cases don’t exist. Perhaps it is just statistically insignificant?
To add to Joe’s thoughts about “no single gene,” I’d like to share G.C. Williams definition of the term “gene” (from Adaptation and Natural Selection):
“I use the term gene to mean ‘that which segregates and recombines with appreciable frequency.’ … A gene could be defined as any hereditary information for which there is a favorable or unfavorable selection bias equal to several or many times its rate of endogenous change.”
If research can be funded to determine the genetic (and therefore prenatal screening test) difference between high functioning or savant autistics and people with autistic disorder then maybe science might be able to enable society to keep their genius in the human gene pool. however what i think is more to the point is the quality of life of the person with autism. My child spends a large proportion of the day self-mutilating and as far as we can judge because he is non-verbal and has virtually has no other communication, he is miserable and his life is not worth living. I hope he dies young for his sake but also for the sake of his siblings whom I know love him so much they feel the same way too. we hate to see him suffer. He is on medication but to no avail. At least Einsttein and Mozart may have been able to say if they were unhappy or in pain or sitting in their own faeces.may be society ise being selfish to want a genius at the expense of a child doomed to a lifetime of suffering?????????? I would have had an abortion at the drop of a hate to prevent the pain my child is going through now and I hope my other kids choose to adopt or have a surrogate.
Note to readers: 2 different commenters have posted as “Caroline” in this thread.
Caroline: What kinds of efforts have been made to help to teach your son other things to do besides the self-mutilating, if I may ask? My son used to head-bang regularly and on anything.
Caroline –
“My child spends a large proportion of the day self-mutilating and as far as we can judge because he is non-verbal and has virtually has no other communication, he is miserable and his life is not worth living.”
Watching my son hurt himself was easily the most difficult part of his regression into autism.
My son stopped head banging completely within two months of starting anti fungal treatments and introduction of friendly bacteria to his gut. If you have not investigated biomedical treatments, I urge you to do so. Likewise, others have reported success using behavior modification training.
Stay strong.
-pD
Hello friends –
Just the other night I saw an episode of Nova Science Now that went over epigenitics; the interaction of genetics and environment.
It was completely fascinating and I am willing to recommend it.
Nova Now Link
There is a three or four minute flash moive, ‘A tale of two mice’ that has shows the result of some interesting studies of genetically identical mice that look nothing alike.
Check it out!
-pD
Okay, so there is no confusion I will go by “Caroline L.” from now on. I often comment on Kristina’s beautifully written and informative posts.
It is the first time and only place I have ever commented on the issues that concern me most:
* all persons regardless of health conditions or differing abilities deserve respect and the non-patronising supports each individual requires. If for nothing else, then for good karma, because in the blink of an eye, we all could lose the ability to communicate and function independently.(dementia, stroke, accident, etc.)
SO, back to this post on CSHL, it does not matter to me about the possibility of a prenatal test. I would like to see more scientific research on this whole ‘regressive autism’ label because I do not think it is autism at all. The people who comment on AutismVox who can describe from personal experience what autism is describe something very different from what I have seen in the so – called ‘regressive autism’ subset.
* I believe autism spectrum disorders are being over-diagnosed. For those individuals and parents who feel it fits, and the services and therapies are appropriate, that is great. But some education professionals make snap judgements based on a child’s behavior at one point in time and the child can be trapped in a cycle of wildly inappropriate placements.
*I believe in properly supported inclusion. I do not believe in mandatory segregation.
*I believe in appropriate individualized education plans and transition plans for each individual – not just photocopying some random goals that fit the ‘diagnosis’.
* I believe in teachers and other education staff treating children in their care with respect and empathy, and working on the assumption that the child/adult understands everything, even if ‘non-verbal’.
To Caroline 2,
I can understand your despair for your child. Excellent behavior modification therapy delivered in a natural, loving, relaxed, empathetic way can perform miracles. PassionlessDrone makes a great suggestion as well – we have had great success (knock wood) from probiotics.
with best wishes, Caroline L.
(apologies for length)
Joe Mele accurately states that autism might be polygenic, the interactions of more than one gene that ’cause’ autism. Excluding genetic mental retardation syndromes (Tuberous Sclerosis, Fragile X) there is still not one autism specific gene that has been found. The polygenic theory remains unproven. Michael Rutter, perhaps the leading authority on autism and the child psychiatrist who originally developed the concept of the broad autism phenotype seems to opening up the door to gene-environment interactions as likely involved in at least part of autism etiology. A few years ago he actually referred to the scientists who deeply believe that autism is a genetic only condition as ‘genetic evangelists’.
Epigenetics a bit off topic. I saw this
http://www.pbs.org/wgbh/nova/sciencenow/
It talks about it. If there is truth to this then genes can turned on or off. While this does no the gluten free diet is proved. It does raise interesting possibilities about amelioration of the least desirable charateristics.
Eye on DNA has a recent post on Environment, Epigenetics, and DNA.
Caroline L—-the word autism definitely seems to have been overly endowed with many and multiple meaning!
I hope we can all find some common ground, despite this.
best wishes—
Hi,
Please consider visiting http://www.neoteny.org/?cat=7 to review a unique and unorthodox theory for the cause of autism.
Thank you,
Andrew Lehman