Unlocking the genetic secrets of autism

[Guest guest]

Unlocking the genetic secrets of autism

Henry I. and Whelan, Forbes.com

Date: Saturday Jul. 31, 2010 7:24 AM ET

Intense and even fanatical resistance to vaccination against childhood diseases

is itself a significant public health problem. Opponents have blamed vaccines

for everything from allergies and diabetes to cancer and autism.

A recent study of abnormalities in the DNA of children with autism spectrum

disorders (ASDs) should finally put to rest the claims of some activists, mainly

parents of affected children, that vaccines cause these conditions.

An international group of scientists reported in June in the journal Nature that

patients suffering from ASDs had in their genes a higher incidence of mutations

in the form of deletions, insertions or duplications of segments of DNA than

unaffected control subjects. These findings offer the possibility of both early

detection and the development of drugs to target and neutralize the specific

biochemical abnormalities caused by the mutations.

Autism is a developmental disorder characterized by deficits in social

interaction and communication; a limited range of activities and interests; and

often the presence of repetitive, stereotyped behaviors. Cognitive development

can range from above-average to profound intellectual disability. Autism

disorders are diagnosed in 1 in 110 children in the U.S. and are found in four

times as many boys as girls.

Although it has been known that ASDs run in families the underlying genetic

determinants have been elusive, but the Nature article offers some new insights.

Drawing on data from 60 research institutions in 12 countries, the researchers

analyzed the genes of 996 children with ASDs and 1,287 children without the

condition. They found that each affected individual carried his or her own

unique assortment of mutations.

This contrasts with the situation in sickle-cell anemia, for example, where the

disease is most commonly caused by a unique mutation -- a change in one specific

nucleotide of DNA, which in turn causes a single amino acid change -- in a gene

that codes for the protein of hemoglobin. (Genes comprise DNA, which is a

template that, after an intermediate step, directs the ordering of various amino

acids into proteins.)

Where and when do these ASD mutations arise? Professor Geschwind, chief

of human genetics and director of the Center for Autism Research and Treatment

at the UCLA School of Medicine, said the findings suggest that the " tiny genetic

errors may occur during formation of the parents' eggs and sperm, " and that

these mutations are conveyed into the DNA of offspring. " The autistic child is

the first in their family to carry that variant. The parents do not have it. "

If ASDs arise spontaneously in this way, still unresolved is why they appear to

be so heritable: The occurrence of ASDs in siblings is about 100 times greater

than the rate at which the disorders affect unrelated people in the population.

Perhaps there is a predilection in some people toward the tiny genetic errors in

eggs and sperm that give rise to ASDs and that would tend to affect all their

offspring.

It is unclear how the beleaguered parents of autistic children will react to

this new information about the genetic basis of autism spectrum disorders. In

the past many have resisted such explanations, preferring instead to blame

adverse reactions to vaccines as the cause in spite of persuasive evidence to

the contrary.

The basis for this misapprehension is a 1998 article by a British physician that

claimed a link between the measles-mumps-rubella (MMR) vaccine and the autistic

symptoms. However, the findings were never duplicated and were subsequently

discredited in the medical community worldwide, and the article was withdrawn by

the journal that had published it.

Last month's article in Nature offers important new scientific insights into the

molecular basis of autism spectrum disorders. One of the lead researchers

predicted, " Just knowing about these genetic changes can help the families come

to terms with why their child has autism. " That remains to be seen. But equally

important are the broader implications of this research -- namely, the

alleviation of misplaced concerns in the broader community about childhood

vaccines, and greater awareness of the public health benefits of wider

immunization.

Dr. Henry , a physician and molecular biologist, is a fellow at Stanford

University's Hoover Institution. Dr. Whelan is president of the

American Council on Science and Health.