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Aug 1, 2010 (Vol. 30, No. 14)

Unlocking the Genetic Secrets of Autism

Recent Study Offers Important New Scientific Insights into the Molecular Basis of ASDs

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    New findings that dispel the "vaccines cause autism" myth open the door for early detection as well as the development of effective drugs. [Tramper2/Fotolia.com]

    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 the conditions. An international group of scientists reported in June in the journal Nature that patients suffering from ASDs had a higher incidence of “rare genic copy number variants” in their genes—mutations that cause deletions, insertions, or duplications of segments of DNA—than unaffected control subjects.

    These findings offer the possibility of both early detection and the possibility of developing drugs that target and neutralize the specific biochemical abnormalities that result from 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 United States and are found in four times as many boys as girls.

    Although ASDs are known (largely from studies on identical and fraternal twins) to be highly heritable, the underlying genetic determinants have been largely unknown, 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 affected individuals carried a 19% “higher global burden of rare, genic copy number variants,” especially for sites on DNA “previously implicated in either ASD and/or intellectual disability,” at which the burden was 69% higher. They also found that among these copy number variants, there were “numerous de novo and inherited events, sometimes in combination in a given family.”

    Because copy number variants result from mutations that disrupt or rearrange DNA, it is not surprising that the genetic errors appear to cause the disease if they occur in DNA sequences that correspond to genes, as opposed to the long stretches of DNA that separate genes. Each patient carried his or her own unique assortment of copy number variants.

    This contrasts with the situation in sickle-cell anemia, for example, where the disease is most commonly caused by a unique mutation—a substitution in one nucleotide of DNA, which in turn causes a single amino acid change—in one of the genes that code for the protein of hemoglobin. (DNA is, in effect, a template that, after an intermediate step, specifies the ordering of various amino acids into proteins.)

    Where and when do these ASD mutations arise? Professor Daniel 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. He added, “The autistic child is the first in their family to carry that variant. The parents do not have it.”

    It is unclear how the 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 seize on 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 British doctor Andrew Wakefield and colleagues that claimed a link between the measles-mumps-rubella (MMR) vaccine and the autistic symptoms, which supposedly occurred within days of the inoculation. The findings were never duplicated and were subsequently universally discredited in the medical community worldwide, and the article was withdrawn by The Lancet, which had published it. 

    Dr. Wakefield was eventually censured by the U.K.’s General Medical Council, the regulator of medical practice, which ruled that in conducting the study he had acted “dishonestly and irresponsibly” by failing to disclose financial conflicts of interest and that he had shown “callous disregard” for his patients by subjecting them to unnecessary invasive procedures.

    The recent study in Nature offers important new scientific insights into the molecular basis of autism spectrum disorders. One of the lead researchers predicted that, “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—the alleviation of misplaced concerns in the broader community about childhood vaccines and the public health benefits of wider immunization.


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