title: A proof-of-concept study: exon-level expression profiling and alternative splicing in autism using lymphoblastoid cell lines.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aSection of Medical Genetics and Molecular Medicine, Children's Mercy Hospital and University of Missouri-Kansas City School of Medicine, Kansas City, Missouri bDepartment of Electrical Engineering and Computer Science, University of Kansas, Lawrence, Kansas, USA.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Talebizadeh
authors.forename: Richard
authors.initials: R
authors.lastname: Aldenderfer
authors.forename: Xue
authors.initials: X
authors.lastname: Wen Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D017398:Alternative Splicing; D001321:Autistic Disorder / Q000235:genetics*; D002460:Cell Line; D005091:Exons; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109916:CYFIP1 protein, human