A report published in the April 2004 issue of the American Journal of Psychiatry highlights the identification of two gene variants on the short arm of chromosome 2 (2q), which showed a strong association with autism in a set of over 400 families.
Researchers at the Mount Sinai School of Medicine, led by Dr. Joseph Buxbaum, examined the DNA of over 400 families, most of which was collected by the Autism Genetic Resource Exchange (AGRE). The researchers screened families that showed some evidence for an association of autism with chromosome 2q. This region is especially interesting to scientists because it is most associated with deficits in language development.
Several changes in the DNA (DNA variants) were identified as a result of a screening of 10 genes on chromosome 2q of individuals with autism compared with individuals without autism. These genes were selected based on several criteria, namely their location within the region and existing evidence of the gene's activity in the brain.
After an initial screening of 38 unrelated individuals with autism and 50 unaffected controls, the DNA variants were tested in the entire set of families. The test looks for the DNA variant that has the highest association rate within a particular disorder. When DNA variants are not associated with any disorder, they are transmitted from parent to child about 50% of the time. While subtle fluctuations are common, transmission of a particular DNA variant in 69% of 147 individuals with autism is statistically unusual. To geneticists such as Dr. Buxbaum, this anomaly suggests that this gene is likely involved in autism.
The AGC1 gene that contains the DNA variants is involved in energy production within the mitochondria, a cellular structure that serves as the powerhouse of the cell. AGC1 is especially active during neuronal development so even subtle fluctuations in the activity of this gene can have serious consequences on brain development.
As with many scientific discoveries, it is important to wait until researchers have a chance to duplicate these findings before making any conclusive statements. Nevertheless, the discovery of these AGC1 gene variants is an important milestone in the identification of susceptibility genes for autism. Autism is thought to result from the interaction of multiple genes and environmental factors. AGC1 appears to be one of the genes which may play a significant role in an individual's susceptibility to autism.
Vlad Kustanovich, Ph.D. is the Autism Genetic Resource Exchange's Researcher Liaison. He holds a doctorate in Human Genetics from UCLA.