The Impact of the Williams Syndrome Mutations on Neural
James S. McDonnell Foundation Collaborative Activity Award:
The Genetic and Neural Basis of Social Cognition:
Evidence from Williams Syndrome and Non-Human Primates
Three genes, CYLN2, GTF2IRD1 and GTF2I, located in the Williams region of chromosome 7, may be responsible for the hypersociability that is so evident in the Williams syndrome phenotype. Little is known about the function of these genes and when or where these genes are expressed. To address these questions, in Projects 1 and 2 we will examine and parse out the social behavior of Williams individuals with full deletions compared to those with smaller deletions and to normal controls to examine what aspects of social behavior are affected, integrated with the molecular genetic analyses of these genes in Williams. In this proposal, we will use the nonhuman primate model to more effectively study direct links between these specific genes and social cognition. The expression of these genes will also provide presumptive evidence that the brain regions in which they are located have a role in the regulation of social cognition.
We will use metabolic and functional brain imaging technology in Project 4 to determine which brain regions are more activated to social stimuli in the classical Williams patient compared to the short form of the deletion as an indicator of brain regions associated with the hypersocial behavior of the typical Williams subject. We would predict that the brain regions preferentially activated in the full deletion Williams subject might be the same as the regions demonstrating differential expression for CYLN2, GTF2IRD1 or GTF2I in the monkey brain. As initial stages in developing a nonhuman primate model of Williams syndrome, in Projects 3 and 5, we will search for rhesus monkeys that naturally display either hypersocial or hyposocial behavior and examine their genetic composition. Finally, in Project 6 we will use a recently developed molecular/genetic technique to transiently and selectively deactivate selected populations of neurons in the rhesus monkey brain in an attempt to ultimately mimic more closely the neurogenetic basis of the human social behavior found in individuals with Williams syndrome.
In sum, through our James S. McDonnell Foundation Panel on Social Cognition, we have brought together a multidisciplinary team of scientists who are uniquely capable of moving between the Williams patient population and the appropriate animal model for social cognition, the rhesus monkey. This group of leading investigators is now proposing to take the exciting next steps forward in developing strategies for bridging genes to brain to cognition.
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