New genetic technologies, like the one illustrated here that shows patterns of gene expression, enable scientists to better understand the causes of autism. Photo: Courtesy of Geschwind Lab
UCLA researchers have combined gene expression and the use of peripheral blood to help scientists pinpoint genes that play a role in autism and zero in on those that offer future therapeutic targets for the disorder.
"Technological advances now allow us to rapidly sequence the genome and uncover dozens of rare mutations," says Daniel Geschwind, M.D., Ph.D., UCLA's Gordon and Virginia MacDonald Distinguished Professor of Human Genetics. "But just because a particular genetic mutation is rare doesn't mean it's actually causing disease. We used a new approach to tease out potential precursors of autism from the occasional genetic glitch."
The study was published in the online edition of the American Journal of Human Genetics.
Dr. Geschwind and his colleagues studied DNA in blood samples from 244 families with one healthy child and one child on the autism spectrum. The team used a hybrid method that blended tests that read the order of DNA bases with those that analyze gene expression, the process by which genes make cellular proteins. Gene expression offers a molecular signpost pointing scientists in the right direction by narrowing the field and highlighting specific areas of the genome.
"We found that we can use gene expression to help understand if a rare mutation is causing disease or playing a role in disease development," says Dr. Geschwind. "A gene mutation accompanied by a change in expression clues us to a hot spot on the genome and directs us where to look next."
The researchers used the combined method to prioritize gene targets that merit closer investigation. Their search turned up new regions in the genome, where genetic variations showed strong links to autism and altered expression patterns. Genes in these regions were more likely to be mutated in the autistic children than in their unaffected siblings.
Finally, the research team discovered that the DNA contained in peripheral blood - the blood that flows and circulates through the body - can help shed light on diseases of the central nervous system. "Brain tissue from people with autism is not readily available for study, and some people are reluctant to use non-neural tissue in psychiatric disease," Dr. Geschwind explained. "But our study demonstrates that even peripheral blood can expand our knowledge of neurological disease."