The folks at Cold Spring Harbor Genetics Lab apparently have found an association between certain genetic mutations and the diagnosis of ASD (in particular, autism, PDD and Aspergers Syndrome).
Specifically, researchers report that they have found the existence of rare “gene copy number variations (CNV)” (duplicated or deleted genome segments that result in extra, or missing, copies of one or more genes) that appear at some 250 to 300 locations in the human genome. While this study does not state what role these genes have with respect to brain development, and thus, how those genes would actually lead to autism, a related study, employed a new form of analysis called NETBAG to identify “the large biological network of genes affected by [these] rare de novo CNVs in autism.” This related study noted that this large biological network is “strongly related to genes previously implicated in studies of autism and intellectual disability.” And they specify that the genes in question relate primarily to the development of synapses, the junctions between brain cells where the transmission of neurotransmitters takes place, axonal fibers, and the ability of young neurons to migrate -- essential aspects of brain development.
Of particular interest was the finding of what the researchers referred to as “de novo” genetic mutations in affected children. These are mutations that did not appear in either parent.
This is potentially good news. I mean, anything that helps us to better understand ASD must be good, right? If they have found certain mutated genes, perhaps this will give us an inkling as to what is causing the problem in the first place.
So, why am I writing, and what has this to do with the “Misleading Headline?”
Well, despite the very specific findings of these studies, as set forth above, the researchers have made some pretty giant, hypothetical leaps which are not founded in any factual findings derived from their research. As such, a couple of “theories” have been thrown about as a result of this research, which, if taken as true, can have very serious repercussions when it comes to treating ASDs.
Specifically, Newsday reports:
New research adds weight to a growing body of evidence that autism is caused by scores of rare genetic mutations, most of which occur spontaneously at conception and aren't passed from parent to child.
"This [study] solidifies that autism is a genetic disease. This suggests that the environment plays a limited role, but that needs to be researched in more depth," said Michael Ronemus, a researcher from Cold Spring Harbor Laboratory and an author of two papers published Thursday in the journal Neuron.
“The studies build on previous research. Wigler has proposed in the past that inherited cases of autism account for about a quarter of all cases; more than half, he and his colleagues have proposed, are the result of spontaneous mutations. How the rest of the cases are derived is unclear, Ronemus said.”
I’m sorry, but the fact of the matter is this study said ABSOLUTELY NOTHING regarding the actual cause of autism – let alone that it is a “genetic disease” in which “environment plays a limited role.” Yet, the genetic researchers seem to think it proves that autism is the result of a spontaneous genetic mutation that takes place in affected individuals at the time of conception. Indeed, they are bold enough to state that autism is inherited 25% of the time, results from these theorized “de novo mutations that occur at conception 50% of the time, but have no idea about the other 25%. How do they know all this?
They don’t. It’s just their best guess . . .
Now, I’m not even going to pretend that I fully understand the study (which I read, but discovered employed lingo that was completely foreign to me (and people complain about “legalese”)), so, I tapped into a pair of sources that can speak with far more knowledge about these topics – my wife, Catherine, and Mark Blaxill.
Here’s just some of what they had to say:
To begin with, the study’s methodologies are somewhat questionable. In particular, Blaxill is not convinced that the test subjects were a properly representative field of candidates. But, even assuming the study’s methodologies were appropriate, what the study actually found and what the headlines report are two entirely different things.
First, the findings are severely limited. According to Blaxill, the study itself, indicates that at best, these purported gene mutations are connected to only two (2) to three (3) percent of autism cases!
Second, and perhaps more importantly, “association is not the same as causation.” In other words, even assuming the researchers found a pattern of gene mutations, it does not mean such mutations cause autism.
While it may be safe to say that the “affected” children in this study did not inherit the gene mutations from the parents, jumping to the conclusion that such mutation occurred without any external catalyst at the time of conception is quite the leap of logic – and one the is not supported with any factual findings. Assuming such mutations are, indeed, linked to autism, what caused such mutations? This is a very important question that is left purely to speculation.
Moreover, even assuming such mutations are linked to autism and such mutations did occur spontaneously without any external catalyst whatsoever, does the mere presence of such mutations inexorably lead to autism or must there still be some external trigger? Do the mutations merely make you susceptible to an environmental insult, and that such externally triggered susceptibility cause autism? Again, another very important question that remains unanswered.
Also, even assuming the existence of such spontaneous genetic mutations taking place at conception, and such mutations “cause” autism, gaping questions would still exist. First, how could such a mutation take place on such a large scale? We’re talking about autism rates that could be as high as 1 in 38 (or even 1 in 10 if you include ADD/ADHD in the spectrum).
Really, we can experience a “rare” genetic mutation that “just happens” that can affect 1 in 10 people? Really??
And, again, if it’s something that “just happens” without any external trigger, then it’s something that always should have been happening. So, where are the 1 in 10 thirty, forty, fifty, sixty, seventy, and eighty year olds that are on the spectrum? How do you account for the meteoric rise in ASD diagnoses just over the past twenty years? If the genes mutations have always been there, but autism has not, then what was the trigger over the past two decades?
And, if such mutations take place at conception, and such mutations affect those genes that are involved in critical brain development, how do you explain cases of “autistic regression,” that is cases where the child is developing normally until about the age of 2 ½ to 3 years of age and then suddenly, and without warning, descends into autism? If the genetic mutations are present from the time of conception, wouldn’t there have been some signs of a problem from the date of birth?
Additionally, I am concerned by yet another theory tossed out by the researchers (again, asserted with no factual support) that points to an inconsistency in the “spontaneous mutation” theory.
According to the researchers, themselves, boys and girls are equally susceptible to these mutations, thus, boys and girls should each have about the same number of CNVs. Presuming this is the case, why do more boys than girls develop ASD? And why are the observed CNVs in girls larger?
The researchers guess that girls are in some manner “resistant” to autism based upon the fact that female brains “have an accelerated timescale for a number of cognitive milestones, for example, their first words at an earlier age. A quicker pace of development might reflect a robustness that offers females protection.” As the researchers put it, “this apparent female resistance to comparatively small genetic hits remains one of autism’s mysteries.”
I’m no geneticist, but isn’t it also possible that if the mutations occur at the time of conception, and the mutations adversely affect brain development, and the female brain develops faster – with the mutations already in place (it’s not as if the female brain can outrun the mutations) – wouldn’t the girls possibly be worse off?
Moreover, if we’re talking about “female robustness,” the same can be said of the arguments that point to vaccines as a cause of autism. Female immune systems are stronger than boys. Testosterone inhibits the immune systems’ ability to detoxify the body, estrogen enhances that ability.
Also, a stronger immune system makes the girls less prone to chronic infections often treated with antibiotics. Another theory regarding a cause of autism is the disruption of the mind-gut connection. Antibiotics have been proven to cause such disruption. Is it possible that girls get sick less, therefore, take fewer antibiotics, and therefore, do not experience gut dysfunction as often as boys?
So, is it the female’s more robust brain or their more robust immune system?
As anyone who has followed this blog knows, I sit firmly in the camp of those who believe ASD (including ADD/ADHD) are caused by something in our environment that affects those genetically predisposed to harm. The theory that ASD is an environmental disorder, and I admit, it is just a theory, is completely compatible with the findings of these studies.
First, it is a given that environmental factors can, in fact, affect our genes. Indeed, even the makeup of your gut flora (the bacteria inhabiting your digestive system) affects your genes and how they work. Second, as is the case with certain diseases like breast cancer, one may have the gene associated with a particular disease, but never actually contract that disease absent some external trigger.
I’m sorry, but I simply do not see how this study and the hypotheses thrown about by the genetic researchers discounts environment as a cause of autism.
Or, as Mr. Blaxill put it:
“What does that mean for the interpretation of autism-CNV research? The one glaringly obvious possibility that none of the genetic researchers can bring themselves to admit is that their painstaking genetic findings could simply be an effect and not a cause. Indeed, why wouldn’t it be the case that a population of pregnant women and infants that is under higher environmental stress than a control population would have a higher rate of DNA damage? Isn’t it more likely that the environmental exposures that have provoked the autism epidemic are also mutagenic in their own right?”
Indeed, Andy Shih, vice president of scientific affairs for the advocacy group Autism Speaks, said the studies don't "eliminate the role of the environment at all."
“Even the possible role of vaccines in triggering autism -- a controversial theory -- cannot be dismissed based on the new studies, he said. It's possible, [Shih] added, that people with certain genetic mutations are more susceptible to vaccines.”
In addition, the research does little to explain the vast majority of autism cases. Prior research has shown that about 5 percent to 7 percent of autism cases can be explained by a single gene disorder. Another 5 percent seems to be caused by metabolic conditions that affect brain function.
De novo copy number variants explain anywhere from 7 percent to 20 percent of autism cases with no known cause. But for the other 70-plus percent, there is no genetic explanation.
“It doesn’t mean we’ll [never] know the risk factors for the other 70 percent. Some could be environmental, some could be other genetic mechanism not yet discovered or that our current technology doesn’t allow us to identify,” Shih said.
So, here we are again, looking for the car keys, “not where we lost them, but where the light is better.” http://sparkdevelopment.blogspot.com/2010/12/autism-and-genetics.html.
Sources:
Stephan J. Sanders, A. Gulhan Ercan-Sencicek, et al., “Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism,” Neuron 70, 863–885 (June 9, 2011).
Sarah R. Gilman,Ivan Iossifov, et al., “Rare De Novo Variants Associated with Autism Implicate a Large Functional Network of Genes Involved in Formation and Function of Synapses,” Neuron 70, 898–907 (June 9, 2011)
Ridgely Ochs, “Research ‘solidifies’ autism, genetic link,” Newsday (June 8, 2011).
Young Shin Kim, Bennett L. Leventhal, et al., “Prevalence of Autism Spectrum Disorders in a Total Population Sample,” Am J Psychiatry, first published on May 9, 2011 as doi: doi:10.1176/appi.ajp.2011.10101532)
Jenifer Goodwin, “Girls May Be More Resistant to Autism Than Boys: Study,” HealthDay (June 8, 2011
David Kirby, Evidence of Harm, (St. Martin’s Press 2005)
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