New mutations implicated in half of autism cases

news@nature.com ^ | 24 July 2007 | Heidi Ledford

[neverdem]

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Published online: 24 July 2007; | doi:10.1038/news070723-1

New mutations implicated in half of autism cases

Disorder linked to genetic differences between parent and offspring.

Heidi Ledford

Autistic children display a wide range of different symptoms.HENNY ALLIS / SCIENCE PHOTO LIBRARY

Half of all cases of male autism may be caused by spontaneous genetic mutations, say researchers who have studied the genetic patterns of the condition. Offspring who inherit such mutations are at a greater risk of having an autistic child themselves.

Autistic people have difficulty relating socially with others and tend to focus obsessively on a narrow set of interests. Three to six out of every 1,000 people are expected to have the condition; its cause is unknown but there is thought to be a strong genetic component.

"That genetics plays a major role in autism has been obvious now for 20 years or more," says Isabelle Rapin, a neurologist at Albert Einstein College of Medicine in New York, who was not affiliated with the study. "The evidence for genetics is not controversial."

But determining how genes affect autism has been difficult. Autism is a complex disease with a wide range of symptoms and severity. It also affects four times more males than females, for unknown reasons.

Spontaneous mutation

Earlier this year, a genome-wide scan linked some cases of autism with mutations in the number of copies of certain genes. Ten per cent of autistic patients had copy-number mutations that were not present in either parent, showing that the mutations were spontaneous¹.

But Michael Wigler, a geneticist at Cold Spring Harbor Laboratory in New York and a lead author on the study, says that the study probably missed some copy-number mutations. "We were sure that 10% was an underestimate," he says.

So Wigler and his colleagues turned to a database containing pedigrees of families with two or more autistic children and asked: if the family's first two children were autistic, what were the chances that the third was autistic as well?

In 86 families with two autistic children and a third, male child, 42 of the third-born children showed autistic symptoms, the researchers report in Proceedings of the National Academies of Sciences².

This suggests that parents had a one-in-two chance of passing on a mutation to their offspring, matching a dominant inheritance pattern. Another database gave the same result.

Handed down

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.

Older mothers, who are more likely to have autistic children, could fall into this class, notes Wigler. Such mothers' eggs have had more time to accumulate mutations.

Once those spontaneous mutations have been passed on, the offspring — particularly women, who can carry the mutation without showing symptoms — have a high risk of having an autistic child. Males with the mutation would also bear this risk, but are also likely to be autistic and therefore less likely to have children.

The researchers' model suggested that about a quarter of autistic children have inherited a copy-number mutation from their parents.

"It's a new way of looking at the data," says Rapin. Future studies using data from other family members are needed to further test the new models, she says. Other factors, such as complications during pregnancy, and the influence of multiple genes, may also be important in causing autism.

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References

1. Sebat, J. et al. Science 316, 445-449 (2007). | Article | PubMed | ISI | ChemPort |
2. Zhao, X. et al. Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.0705803104 (2007).

[neverdem]

Human genome more variable than previously thought

Global variation in copy number in the human genome We had Mendelian genetics, epigenetics and now copy number variation, i.e. non-Mendelian genetics. The Nature article is still free access. Just register.

[neverdem]

Ping

[neverdem]

The end of the plug? Scientists invent wireless device that beams electricity through your home Check the links in comments# 25 & 26.

Albert Ellis, Influential Psychotherapist, Dies at 93

FReepmail me if you want on or off my health and science ping list.

[pieceofthepuzzle]

Thanks for posting this. It’s absolutely amazing how little we know. It’s also amazing that with all the complexity during development and growth anyone turns out ‘normal’. When one considers all the factors beyond the genomic base sequence (e.g. copy number, imprinting, other epigenetic contributions, micro-RNA etc.) it’s just astounding, and exciting. I wonder what we will know in 20 years that we have no clue about currently?

[Mr Inviso]

Wait.. that can’t possibly be it.. it has to be the vaccines.. made by those evil greedy Big Pharma corporations.John Edwards and Mikey Moore-on told me so!!!

/need I?

[CarrotAndStick]

Evolution in action, now?

Lol!

[AdmSmith]

A good background on Sebat's research:

http://www.autismconnect.org/news.asp?section=00010001&itemtype=news&id=6101

[Rennes Templar]

“Spontaeous mutation” is simply a theory of causation, based om mathematical models. They need to look for the cause of “spontaneous mutation”. This is a classic case of confusing an effect with cause, like saying the cause of colds is sneezing.

[randita]

I’ve talked to several teachers and families about autism and they say that no one knows what causes it really. The teachers say that during the time they have taught, 20-25 years for some, the incidence of autism has skyrocketed. But whether that is from an increase in the occurrence of autism or a fine tuning of its diagnosis, they can’t say.

[AppyPappy]

When I was young, they evaluated me to see if I was mildly autistic. I have met a lot of good programmers who show the same traits (ie mild Aspergers)

[Hot Tabasco]

I wonder what we will know in 20 years that we have no clue about currently?

How the sock disappeared from the dryer and where it ended up.......

[pieceofthepuzzle]

“How the sock disappeared from the dryer and where it ended up.......”

Always check your backside in the mirror before leaving for work....

[SunkenCiv]

Thanks neverdem. 15 minutes to Wapner.

To all -- please ping me to other topics which are appropriate for the GGG list. Thanks.

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[Incorrigible]

It's hard to have an exponential increase in Autism if genetics is the only cause.

There may be some genetic predispositions but it's Auto-Immune disease that causes Autism.

 

[Monkey Face]

...those who carry a pre-existing autism-causing mutation, and those who do not....

There are only two kinds of people in the world. Those who put everything into groups, and those who do not. ;o]

[CholeraJoe]

But the greenies kept saying it was due to mercury in fish and vaccines.

[bannie]

I read that the socks get lost in the washer...they get sucked with the water through the water-leaving-the-machine hose.

I haven’t done any personal research, but they definitely leave sometime between the time they go in the washer and come out of the dryer.

[bannie]

What’s tweeking our DNA to mutate?

[Grammy]

"How the sock disappeared from the dryer and where it ended up......."

That's easy. They turn into hangars.

[Chickensoup]

So are these children EVOLVING?