A proof-of-concept study: exon-level expression profiling and alternative splicing in autism using lymphoblastoid cell lines

Psychiatr Genet. 2014 Feb;24(1):1-9. doi: 10.1097/YPG.0b013e3283635526.


Objective: Autism is a complex, heterogeneous neurobehavioral disorder with many causes and varying degrees of severity. Some genetic implications related to autism may involve gene-regulatory processes such as alternative splicing. Here, we assess the feasibility of profiling exon-level gene expression in autism using the Affymetrix Human exon 1.0 ST array.

Methods: We examined lymphoblastoid cell line-derived RNAs from five patients with autism compared with five controls.

Results: Analysis of variance and Bonferroni multiple test correction identified 57 genes exhibiting differential exon-level expression, suggesting potential changes in the resultant alternatively spliced transcripts in autism compared with controls. Genes with differentially expressed exons included CYFIP1, a previously reported autism susceptibility gene. Furthermore, several genes recently reported to have deregulated alternative splicing in autism brain samples showed differential exon expression in our autism group.

Conclusion: The paucity of autism brain samples and extensive phenotypic heterogeneity of autism demands finding ways to also identify autism-related genomic events in accessible nonbrain resources, which may contribute in biomarker identifications. This proof-of-concept study shows that the analysis of alternative splicing in lymphoblastoid cell line samples has a potential to reveal at least a subset of brain-related deregulation of splicing machinery that might be implicated in autism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Alternative Splicing*
  • Autistic Disorder / genetics*
  • Cell Line
  • Exons*
  • Gene Expression Profiling*
  • Genetic Predisposition to Disease
  • Humans
  • Reverse Transcriptase Polymerase Chain Reaction


  • Adaptor Proteins, Signal Transducing
  • CYFIP1 protein, human