A convergent coexpression approach identifies novel genes associated with autism Autism SD genomics transcriptomics CRISPR coexpression convergence genetics exome genome CellGenomics mcgillu IcahnMountSinai MassGeneralNews
By Dr. Priyom Bose, Ph.D.Mar 14 2023Reviewed by Benedette Cuffari, M.Sc. Autism spectrum disorder is a developmental disability that causes difficulties in communication, learning, and social interactions. The high level of connectivity across ASD risk genes provides an opportunity to use their coexpression to better understand the molecular convergence in ASD.
Background ASD is a neuropsychiatric disorder that is a heritable genetic condition with a population prevalence of around 1%. Genetic sequencing studies have identified many genes that enhance the risk of ASD. Using Loss of function models, FOXP1 and CHD8 transcriptional regulators have been linked with ASD, with a possibility of more dysregulated genes potentially causing this condition. Several altered genes associated with ASD showed the absence of CHD8 and FOXP1 binding sites, thus suggesting that the manifestation of ASD is due to the perturbation of other downstream regulatory interactions.
Interestingly, the discovery of protein-protein interaction networks and coexpression modules of ASD risk genes have highlighted the existence of high and well-orchestrated connectivity and interactions. Furthermore, convergent gene expression was demonstrated in ASD risk genes linked to rare protein truncation variants. Additionally, ASD genes have been associated with significant copy number variants and common variations.
Study findings It was observed that coexpression could influence the regulatory consequences of CRISPR perturbation across common factors with the same correlation to replicate CRISPR experiments linked to a similar gene. A total of 993 human postmortem brains associated with the transcriptional consequences of CRISPR perturbations in human neurons were used to determine coexpression patterns.
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