Analysis of Increased Functional Diversity by Alternative Splicing in Autism Candidate Genes

Background: Alternative pre-mRNA splicing generates multiple protein isoforms from a single gene, thereby contributing to functional and proteome diversity. Alternative splicing regulates gene expression. Its biological role in biomedical research can be dramatically amplified when the protein isoforms generated serve as potential biomarkers or therapeutic targets. While many studies have focused on alternative splicing prediction, its impact on protein function in candidate genes associated with common diseases, in particular neuropsychiatric disorders, such as autism have received little attention.

Objectives: Analyze the impact of alternative splicing on protein function in autism.

Methods: We performed computational analysis of alternative splicing in 238 autism candidate genes. We hypothesized that alternative splicing affects protein function and increases functional diversity.

Results: We have shown that more than 80% of autism candidate genes are alternatively spliced, and demonstrate that alternative splicing events involve structural deletions, insertions, and substitutions. The number of protein isoforms generated per candidate gene ranged from 1 to 17. About 40 genes had complete deletion of functional domains.

Conclusions: Knowledge discovery and comparative genomic analysis showed increased functional diversity, which could potentially contribute to phenotypic plasticity and diversity.