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

Talebizadeh, Zohreha; Aldenderfer, Richarda; Wen Chen, Xueb

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.

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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

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Correspondence to Zohreh Talebizadeh, PhD, Children’s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA Tel: +1 816 983 6506; fax: +1 816 983 6501; e-mail:

Received July 3, 2012

Accepted March 7, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins