title: Exon expression and alternatively spliced genes in Tourette Syndrome.
abstract: Tourette Syndrome (TS) is diagnosed based upon clinical criteria including motor and vocal tics. We hypothesized that differences in exon expression and splicing might be useful for pathophysiology and diagnosis. To demonstrate exon expression and alternatively spliced gene differences in blood of individuals with TS compared to healthy controls (HC), RNA was isolated from the blood of 26 un-medicated TS subjects and 23 HC. Each sample was run on Affymetrix Human Exon 1.0 ST (HuExon) arrays and on 3' biased U133 Plus 2.0 (HuU133) arrays. To investigate the differentially expressed exons and transcripts, analyses of covariance (ANCOVA) were performed, controlling for age, gender, and batch. Differential alternative splicing patterns between TS and HC were identified using analyses of variance (ANOVA) models in Partek. Three hundred and seventy-six exon probe sets were differentially expressed between TS and HC (raw P < 0.005, fold change >|1.2|) that separated TS and HC subjects using hierarchical clustering and Principal Components Analysis. The probe sets predicted TS compared to HC with a >90% sensitivity and specificity using a 10-fold cross-validation. Ninety genes (transcripts) had differential expression of a single exon (raw P < 0.005) and were predicted to be alternatively spliced (raw P < 0.05) in TS compared to HC. These preliminary findings might provide insight into the pathophysiology of TS and potentially provide prognostic and diagnostic biomarkers. However, the findings are tempered by the small sample size and multiple comparisons and require confirmation using PCR or deep RNA sequencing and a much larger patient population.
authors.affiliation: M.I.N.D. Institute, Department of Neurology, University of California at Davis, Sacramento, 95817, USA. yftian@ucdavis.edu.
authors.forename: Yingfang
authors.initials: Y
authors.lastname: Tian
authors.forename: Isaac H
authors.initials: IH
authors.lastname: Liao
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhan
authors.forename: Joan R
authors.initials: JR
authors.lastname: Gunther
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Ander
authors.forename: Dazhi
authors.initials: D
authors.lastname: Liu
authors.forename: Lisa
authors.initials: L
authors.lastname: Lit
authors.forename: Glen C
authors.initials: GC
authors.lastname: Jickling
authors.forename: Blythe A
authors.initials: BA
authors.lastname: Corbett
authors.forename: Netty G P
authors.initials: NG
authors.lastname: Bos-Veneman
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Hoekstra
authors.forename: Frank R
authors.initials: FR
authors.lastname: Sharp
mesh_terms: D000293:Adolescent; D017398:Alternative Splicing / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D003710:Demography; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D005879:Tourette Syndrome / Q000188:drug therapy / Q000235:genetics*
chemical_list: D012333:RNA, Messenger