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“Penn is poised to make genetic discoveries that will significantly improve how the medical community approaches Asperger syndrome,” said Daniel J. Rader, MD, chair of Genetics and ASPE director. “ASPE will draw on our strength in genetics and psychiatry to push the field ahead to create new options for individuals and families. We are fortunate to be partnering with a truly forward-thinking philanthropist.”

“Leveraging advanced technologies in genomic medicine and improved methods of behavioral assessment, we aim to identify genes that contribute to Asperger syndrome, to unveil how these genes function biologically, and to use this information to improve how we diagnose and treat Asperger syndrome,” said Maja Bucan, PhD, a professor of Genetics, and the program’s co-director with Edward Brodkin, MD, an associate professor of Psychiatry and director of the Adult Autism Spectrum Program at Penn.

“While most genetic studies of ASD have focused on more severely affected individuals with intellectual disability, the efforts of our program will be one of the first large-scale genetic studies to recruit individuals with Asperger syndrome and their family members, including family members with AS, ASD, or without either diagnosis. This approach holds promise for revealing as-yet-undiscovered genetic mechanisms that may be involved in both AS and ASD, as a whole,” Brodkin said.

ASPE will take a two-pronged approach by conducting a pioneering family-based genetic study and simultaneously developing model systems to investigate specific mutations in genes found in earlier genome-wide association studies associated with AS and ASD. A major focus will be on the NRXN1 gene, which codes for the protein neurexin 1 and has been associated with ASD and other psychiatric and neurodevelopmental disorders. The team will compare the genomes of individuals with and without mutations in the NRXN1 gene and individuals with AS and their family members who may or may not have been diagnosed with AS.

“One of the exciting features of ASPE is that we will be going beyond diagnoses to look at the whole individual, measuring variation in many different aspects of functioning,” said Laura Almasy, PhD, a professor of Genetics who will direct statistical genetic analyses for the project. “This should help us both to identify genes and to understand their role in vulnerability and also in resilience.”

The ASPE team will use model systems to study exactly how mutations in the NRXN1 gene and newly discovered genes affect the biology and function of the brain in individuals with Asperger syndrome. Model systems include fruit flies, mice, and stem cells that have been genetically engineered to closely resemble specific human characteristics of ASD. The team will also develop new mouse and fruit fly models to recreate other mutations identified in families in the study.

“Building on our expertise in ASD, with such conditions as Rett syndrome, Fragile X syndrome, and CDKL5, we plan to significantly improve our understanding of how NRXN1 and other genes affect patients with Asperger syndrome,” said Zhaolan (Joe) Zhou, PhD, an associate professor of Genetics, who along with Tom Jongens, PhD, also an associate professor of Genetics, will lead ASPE’s model system work.

“The overall goal of ASPE is to uncover the full picture of how NRXN1 mutations interact with other gene variants to contribute to Asperger syndrome and other neurodevelopmental conditions,” Rader said. “Guided by these discoveries, the team will explore precise new treatments to improve the lives of individuals affected by Aspergers.”