Risky DNA: autism studies yield fresh genetic leads

Science News, Jan 12, 2008 by Bruce Bower

As scientists inch closer to unraveling autism's causes, this perplexing developmental condition increasingly shows its diverse roots. Consider two new genetic investigations.

One finds that spontaneous alterations to a tiny stretch of chromosome 16 contribute to about 1 percent of childhood autism cases. Either a deletion or a duplication of this DNA section raises a child's susceptibility to autism and related disorders, report geneticist Mark J. Daly of Massachusetts General Hospital in Boston and his colleagues.

The researchers plan to determine how tweaks to the DNA segment, which contains about 25 genes, promote autism. Their findings appear online and in an upcoming New England Journal of Medicine.

"This is one piece in the autism puzzle, but it's one of the few pieces that we have," Daly says.

The group of developmental disorders that includes autism affects as many as 1 in 150 children by age 3.

Daly's team used novel DNA-screening techniques to identify variations in the number of copies of each gene in the genomes of members of 751 families. Each family included two or more children diagnosed with autism or a related disorder, for a total of 1,441 affected youngsters.

Five individuals with autism displayed deletions of the key chromosome 16 segment. No such deletions appeared in their parents, leading the researchers to propose that these DNA alterations occurred during genetic recombination at or shortly after fertilization.

The researchers identified an additional five eases of the same DNA deletion among 512 children with autism or related disorders referred to Children's Hospital Boston. Four deletions had occurred spontaneously and one was inherited from a parent.

Finally, Daly's team detected the same chromosome 16 deletion in 3 of 299 residents of Iceland diagnosed with autism. Only 2 of 18,834, Icelanders without autism or a related ailment displayed the same deletion.

Moreover, seven individuals from the original sample and four youngsters from Children's Hospital, all with autism, possessed extra copies of genes within the crucial chromosome 16 area.

The second study indicates that inheriting one variant of a brain-related gene ups the chances that a child will develop autism. A team led by geneticist Aravinda Chakravarti of the Johns Hopkins University School of Medicine in Baltimore first identified DNA variations among 292 members of 72 families, including 145 children with autism. A small portion of chromosome 7 showed a link to the disorder.

A closer analysis indicated that children with autism tended to inherit a specific version of a gene within that area. Prior research suggests that this gene makes a protein that fosters the growth of nerve projections essential for neural communication. Comparable findings emerged in a DNA analysis of 1,295 children with autism and their healthy parents, the researchers report online Jan. 10 in the American Journal of Human Genetics.

As genetic evidence mounts, new data question the controversial contention that childhood vaccines have inflamed autism rates (SN: 9/29/07, p. 197). Autism's prevalence among California children continued to rise after vaccine manufacturers largely removed the mercury-containing preservative thimerosal from their products, according to a study directed by physician Robert Schechter of the California Department of Public Health in Richmond.

His analysis, published in the January Archives of General Psychiatry, covers children ages 3 to 12 receiving state services for autism between January 1995 and March 2007. Prevalence rates for the disorder increased gradually throughout that time for kids at each year of age. Manufacturers removed thimerosal from vaccines from 1999 to 2001.