Researchers examining gene coexpression and brain connectivity in females with ASD

Allison Jack, Assistant Professor, Psychology, is examining gene coexpression and brain connectivity in females with autism spectrum disorder (ASD).

To do this, Jack is conducting a secondary analysis of de-identified data from a National Database for Autism Research collection called "Multimodal Developmental Neurogenetics of Females with Autism."

During preliminary work with this dataset, Jack and her colleague, Abha Gupta, Assistant Professor of Pediatrics at Yale School of Medicine, found that girls with ASD showed a profile distinct from both typically developing girls and boys with ASD, one which was characterized by motor (M1) and striatal (STR) underactivation to social stimuli, and greater size of rare copy number variants (CNVs) affecting genes expressed in those brain regions. On the other hand, typically developing girls (but not typically developing boys or autistic girls) recruited regions of the brain's executive control network while viewing social stimuli, suggesting that executive engagement could contribute to female resilience to autism. Together, these findings suggest that the striatomotor-cortical system may be implicated in female-specific processes of ASD risk and protection, but do not fully delineate the biological mechanisms by which such effects operate.

For this project, Jack and Gupta are working to further specify these mechanisms. First, they plan to examine sex- and diagnosis-specific differences in functional connectivity between striatal and motor/frontal regions, and degree of coexpression of M1-, STR-, and frontal-expressed genes. Second, they will assess coexpression of genes impacting striatomotor-cortical system development.

The researchers will also explore how functional connectivity and genetic load in the striatomotor-cortical system are associated with phenotypic characteristics including social behavior, restricted/ repetitive patterns of behavior and interests, and executive function.

Jack received $93,375 from the U.S. Department of Health and Human Services (Eunice Kennedy Shriver National Institute of Child Health and Human Development) for this project. This funding began in March 2020 and will conclude in late February 2022.