Autism spectrum disorder (ASD) is a highly variable neurodevelopmental disorder. The main hallmarks of individuals with ASD are social communication impairments and repetitive sensory-motor behaviors, and they may present with additional comorbidities such as intellectual disability, epilepsy, anxiety, and/or attention-deficit/hyperactivity disorder.
The underlying cause of ASD is similarly heterogeneous. More than a thousand associated genetic variants including chromosomal abnormalities and de novo rare genetic variants have been identified to be associated with ASD. However, there is a general lack of understanding of how genetic variants contribute to the fetal development of ASD.
One interesting idea between the biological mechanism and ASD centers around immune associations and neurodevelopment. Many studies have found that a subset of genes are connected to immune pathways that converge on associated mechanisms of ASD. This work interrogates this idea by examining single cell expression of highly associated ASD genes in non-diseased human fetal thymus and brain. The high resolution of single cell expression highlights potential associations between specific cell types or pathways to ASD at a time point that is critical for neurodevelopment. Additionally, gene expression analysis has largely been focused on the brain, and this work investigates the thymus, a transient organ responsible for T cell development and a central component of the immune system.
By analyzing highly associated ASD genes in non-diseased tissues of the fetal brain and thymus, the finding that a subset of genes are enriched in thymus tissue substantiates the reason for further interrogation of the possible associations of the thymus and ASD. This analysis also offers a baseline to compare to upon similar analyses of affected tissues of fetal brain and thymus from individuals with ASD
