Autism spectrum disorders are devastating developmental disorders characterized by altered social interactions and behavior. Although genetic risks are known to contribute to the development of autism spectrum disorders, the genetic causes of the disease are not well understood. Now, three studies provide new insight into the diversity of the genetic abnormalities that contribute to autism and represent a step towards the future design of treatments specifically targeted to different kinds of autism.
Studies Provide New Insight into Genetics of Autism Spectrum Disorders
“We observed a higher incidence of de novo (new) CNVs in children with autism spectrum disorder than their unaffected siblings,” explains Dr. Michael Wigler, who led one of the studies. “The functions of the genes in the regions of de novo variation point to a great diversity of genetic causes, but also suggest functional convergence. In addition, our results show that, relative to males, females have a greater resistance to autism from genetic causes, which raises the question of the fate of female carriers.” In a companion study led by Dr. Dennis Vitkup, the CNVs identified in Dr. Wigler’s study were analyzed using a new method which revealed that the affected genes are part of a large network involved in the development of synapses, key sites of communication between neurons.
A separate collaborative and multi-site study led by Dr. Matthew W. State identified six rare recurrent de novo CNVs and, along with Dr. Wigler’s group, found a significant association of autism spectrum disorder with de novo duplications of a chromosomal region that, when deleted, causes Williams-Beuren syndrome, a rare neurodevelopmental disorder which is associated with a highly social personality. “Finding strong evidence that at one position in the genome increases in the genetic material lead to autism spectrum disorder, while losses at precisely the same region lead to a highly social personality, was particularly exciting. This relatively small genomic interval clearly holds important clues to understanding the social brain,” explains Dr. State.
Taken together, results from these studies highlight the importance of diverse rare genetic variations in autism. “The diversity implies that a treatment for one form of autism may have no value for the majority,” says Dr. Wigler. “Once the specific genes mutated in autism spectrum disorders are known with confidence, we can begin to think with clarity about problems specific to individuals within categories of causation rather than attempting to manage a conglomerate disorder.” Dr. State adds, “These studies represent a significant step forward in understanding the genomic architecture of autism spectrum disorders and provide important new points of traction in elaborating the molecular mechanisms and developmental neurobiology underlying autism spectrum disorders. This type of knowledge is a critical first step in developing novel treatment approaches.”
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