New evidence for genetic basis of autism found

New evidence for genetic basis of autism found
Three-dimensional representation of the mouse brain highlights eight regions (shown with different colors) affected by 16.p11.2 deletion. Credit: Image courtesy of Mills@CSHL

Scientists at Cold Spring Harbor Laboratory (CSHL) have discovered that one of the most common genetic alterations in autism -- deletion of a 27-gene cluster on chromosome 16 -- causes autism-like features. By generating mouse models of autism using a technique known as chromosome engineering, CSHL Professor Alea Mills and colleagues provide the first functional evidence that inheriting fewer copies of these genes leads to features resembling those used to diagnose children with autism. The study appears in the Proceedings of the National Academy of Sciences in the early online edition during the week of October 3.

"Children normally inherit one copy of a gene from each parent. We had the tools to see whether copy number changes found in kids with autism were causing the syndrome," explains Mills. In 2007, Professor Michael Wigler, also at CSHL, revealed that some children with autism have a small deletion on chromosome 16, affecting 27 genes in a region of our genomes referred to as 16p11.2. The deletion -- which causes children to inherit only a single copy of the 27-gene cluster -- is one of the most common copy number variations (CNVs) associated with autism.

"The idea that this deletion might be causing autism was exciting," says Mills. "So we asked whether clipping out the same set of genes in mice would have any effect."

After engineering mice that had a chromosome defect corresponding to the human 16p11.2 deletion found in autism, Mills and her team analyzed these models for a variety of behaviors, as the clinical features of autism often vary widely from patient to patient, even within the same family.

Climbing episodes of wild type mice (right) and mice with 16p11.2 deletion (left) during the first 10 hours of the experiment. At the beginning of the trial, both mice climb to the lower part of the cage ceiling, returning to the floor with their hindlimbs leading. Later on in the trial, wild type mice progress until they reach the highest point of the ceiling of the cage, returning to the floor from different ceiling areas with their forelimbs leading. In contrast, 16p11.2 deletion mice lack this progressive behavior, exhibiting the same behavior as earlier in the trial. Credit: Image courtesy of Horev@CSHL

"Mice with the deletion acted completely different from normal mice," explains Guy Horev, a Postdoctoral Fellow in the Mills laboratory and first author of the study. These mice had a number of behaviors characteristic of autism: , difficulty adapting to a new environment, sleeping deficits, and restricted, .

Interestingly, mice that had been engineered to carry an extra copy, or duplication, of the 16p11.2 region did not have these characteristics, but instead, had the reciprocal behaviors. For each behavior, the deletion had a more dire consequence than the duplication, indicating that gene loss was more severe. This might explain why 16p11.2 duplications are detected much more frequently than deletions within the human population, and why patients with 16p11.2 deletions tend to be diagnosed earlier than those with duplications.

The mouse models also revealed a potential link between 16p11.2 deletion and survival, as about half the mice died following birth. Whether these findings extend to the human population might be answered by future studies that investigate the link between this deletion and unexplained cases of infant death.

The researchers also used MRI to identify specific regions of the brain that were altered in the autism models, revealing that eight different parts of the brain were affected. The group is now working to identify which gene or group of genes among the 27 that are located within the deleted region is responsible for the behaviors and brain alterations observed.

"Alea Mills has created a valuable resource for everyone engaged in autism research. The technical skill is extraordinary in creating mouse models bearing a human genetic variant that has been associated with autism," says Dr. Gerald Fischbach, Director of Life Sciences and Simons Foundation Autism Research Initiative (SFARI).

These mice will be invaluable for pinpointing the genetic basis of autism and for elucidating how these alterations affect the brain. They could also be used for inventing ways to diagnose children with before they develop the full-blown syndrome, as well as for designing clinical interventions.

More information: Guy Horev, et al., "Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism," Proceedings of the National Academy of Sciences, October 3, 2011.
Citation: New evidence for genetic basis of autism found (2011, October 3) retrieved 21 October 2019 from
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Oct 03, 2011
'Autism' is not a single condition. It is a crude group name applied to several conditions that are more properly termed "autistic spectrum disorders." This specific deletion will cause a specific condition which may ba classified as a single autistic spectrum disorder. Faiure to distinguish this condition from other disorders in the same crude classification is irresponsible.
Exactly *WHICH* form of autism is the consequence of this deletion?

Oct 03, 2011
for more than ten years now i've been marveling at the amount of money spent on 'autism' research in the where in the world is there such a large amount of money spent on this fake area of research.

it's been well over ten years i've been watching this.

if you read about the history of mass delusions, and the social trends that last for years if not decades, if you read and know that people believed the earth was flat for thousands of years, you will not sheepishly and automatically ignore the evidence that the explosion of autism research as well as 'ADD' research ( but lesso) is a really not a discrete phenomena that could legitimately be the subject of so much funding for scrutiny that simply can have no answer.

the skeptic will point out that big pharma is behind it. the realist will say, as long as there is science being funded, even if the results are irrelevant, funding the process overall is a good thing over the long run. i would agree--but funding is limited

Oct 03, 2011
Man, you're a heartless ASS Jed...

They do this research because they want to be able to try to help people with the negative aspects of some of these disorders.

Oct 04, 2011
To Jeddy:

To start, I have worked with children with disabilities for the past 7 years. During this time I have worked with a wide variety of disabilities, including Autism. I understand the vagueness of the criteria for categorizing a person as "Autistic" and while i have my issues with it, I feel that we currently have no better way to categorize it.

What bothers me about what you posted is that you seem to argue that the condition is simply smoke in mirrors, an illusion that some organization wants us to believe. I can tell you that this is not true at all. My clients who have autism are vastly different from ALL of the others. They seem to suffer from sensory/perceptive issues and the subsequent interpretation of those perceptions rather than slow cognition which I see more commonly. I have seen the entire spectrum from nonverbal/nonfunctional to functional aspergers syndrome.

Oct 04, 2011
Damn the limit on characters ...

Anyway, you seem to have a problem with the fact that Autism is "on the rise" and that we are spending so much on it. My opinion is that it is not increasing, but rather is being diagnosed more. However, it is still a real condition that deserves research.

Oct 04, 2011
if you read and know that people believed the earth was flat for thousands of years, you will not sheepishly and automatically ignore the evidence...

Actually, the evidence I'm more interested in is that some people are not that smart, or are very ignorant. For example, have you "read" and do you "know" that people believed the earth was flat? Because it's just not true. People have known since at least the times of ancient Greece that the world is round. The myth that people thought it was flat up to Columbus' time was started by a fictional story by Washington Irving. Read "the flat earth error" for more information. My point is not that people knew the earth was round, but that you will never see how wrong you really are. As with most people who are wrong, they simply won't ever be able to see themselves as somebody who is wrong about what they believe. Get over yourself and leave the thinking to the experts.

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