Exon expression and alternatively spliced genes in tourette syndrome

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2011-01, Vol.156B (1), p.72-78
• Main Authors: Tian, Yingfang, Liao, Isaac H., Zhan, Xinhua, Gunther, Joan R., Ander, Bradley P., Liu, Dazhi, Lit, Lisa, Jickling, Glen C., Corbett, Blythe A., Bos-Veneman, Netty G.P., Hoekstra, Pieter J., Sharp, Frank R.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult and adolescent clinical studies; Age; Alternative splicing; Alternative Splicing - genetics; Biological and medical sciences; biomarkers; Blood; blood biomarker; Case-Control Studies; Child; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Demography; DNA probes; exon expression profiles; Exons; Exons - genetics; Female; gene expression profiling; Gilles de la Tourette syndrome; Humans; Male; Medical genetics; Medical sciences; Neurology; Oligonucleotide Array Sequence Analysis; Organic mental disorders. Neuropsychology; Polymerase chain reaction; Principal components analysis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tourette Syndrome; Tourette Syndrome - drug therapy; Tourette Syndrome - genetics
• ISSN: 1552-4841; 1552-485X; 1552-485X
• DOI: 10.1002/ajmg.b.31140

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 |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