Maverick against the mendalians

January 30, 2008

Maverick Against the Mendelians

By Nikhil Swaminathan

Ask Wigler about the genetic basis of autism, and he will tell

you

that the standard genetic methods of tracing disease-causing mutations in

families with multiple affected members are not working. Although most

scientists agree that environmental influences play a role in disease

onset, autism has a strong genetic component: among identical twins,

if one

is autistic, there is a 70 percent chance the other will show the

disease,

a risk factor nearly 10 times that observed in fraternal twins and

regular

siblings. Yet years of time and bags of money have been spent

unsuccessfully looking for genes linked to the condition.

To Wigler, a geneticist at Cold Spring Harbor Laboratory on Long Island,

the key to unlocking autism's genetic mystery lies in spontaneous

mutationsalteration

s in the parental germ line that are novel in

offspring. Last year he proved that spontaneous events contribute to some

cases of autism and then formed a controversial theory for the genetics

of the disorder. It suggests, among other things, that females, who

develop

autism with a quarter of the frequency with which males do, may carry the

genetic profile for the illness, which they then pass on to their

children.

As Wigler sees it, conventional genetic studies have failed because they

have corralled families that have more than one autistic child to search

for differences in one base along the genetic code. These differences,

which are presumed to affect neural connectivity, can be an addition, a

deletion or a substitution of a base and are known as single nucleotide

polymorphisms (SNPs). In autism research, uncovering SNPs shared by

affected people would enable scientists to determine who would have an

elevated risk for acquiring the disease or passing it on.

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