A subgroup of Tourette's patients overexpress specific natural killer cell genes in blood: A preliminary report

Lit, Lisa; Gilbert, Donald L.; Walker, Wynn L.; Sharp, Frank R.

doi:10.1002/ajmg.b.30550

Cited by 40 publications

(50 citation statements)

References 51 publications

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“…As in the previous study (Lit et al, 2007), these genes showed increased expression for TS compared to NC (Figure 6; Table 4). A genes (Pearson correlation, p ≥ 0.95)-by-samples (smooth correlation, p ≥ 0.95) unsupervised cluster using these 7 probes demonstrates good separation of TS from NC ( Figure 7A).…”

Section: Presence Of Previously Identified Genessupporting

confidence: 83%

“…Expression of 7 probes, representing 6 genes analogous to those previously found differentially expressed in TS compared to controls (Lit et al, 2007), was also significantly different in this study between TS and NC for the 10-12 age group (Table 4). As in the previous study (Lit et al, 2007), these genes showed increased expression for TS compared to NC (Figure 6; Table 4).…”

Section: Presence Of Previously Identified Genessupporting

confidence: 60%

“…Although previous analyses by our groups utilized a fold change cutoff in conjunction with a p-value subjected to a multiple comparison correction (e.g., Lit et al, 2007;Tang et al, 2005), we adopted an alternate analysis strategy in this report in part because vast age heterogeneity of the current sample and increased number of probes examined contributed to difficulty surpassing the resulting FDR. We also were interested in considering as broadly as possible how changes in gene expression across age groups differed in TS compared to controls.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, using the Affymetrix U95A expression microarray, we identified a group of genes that separated a subgroup of TS patients from age-matched subjects with other neurological disorders (Lit et al, 2007;Tang et al, 2005). Analogous probes for the current study using the Affymetrix U133-Plus 2 expression microarray were identified using the Affymetrix Netaffx analysis webtool (https://www.affymetrix.com/site/login/login.affx).…”

Section: Analysis Of Previously Identified Genesmentioning

confidence: 99%

“…In a previous pilot study of children and adults with TS compared to agematched controls, using two types of statistical analyses, we assessed whole blood gene expression and found altered expression of immune-related genes primarily associated with Natural Killer Cells (NK), the major cell type involved in the rapid, innate immune response to viral and other infections (Lit et al, 2007;Tang et al, 2005). Previous studies were limited by 1) use of older gene expression technology, 2) small sample size, and 3) use of a healthy control group that was not specifically recruited to match for age, sex, and race.…”

Section: Introductionmentioning

confidence: 99%

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Age-related gene expression in Tourette syndrome

Lit

Enstrom

Sharp

et al. 2009

Journal of Psychiatric Research

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Because infection and immune responses have been implicated in the pathogenesis of Tourette Syndrome (TS), we hypothesized that children with TS would have altered gene expression in blood compared to controls. In addition, because TS symptoms in childhood vary with age, we tested whether gene expression changes that occur with age in TS differ from normal control children. Whole blood was obtained from 30 children and adolescents with TS and 28 healthy children and adolescents matched for age, race and gender. Gene expression (RNA) was assessed using whole genome Affymetrix microarrays. Age was analyzed as a continuous covariate and also stratified into three groups: 5-9 (common age for tic onset), 10-12 (when tics often peak), and 13-16 (tics may begin to wane). No global differences were found between TS and controls. However, expression of many genes and multiple pathways differed between TS and controls within each age group (5-9, 10-12, and 13-16), including genes involved in the immune-synapse, and proteasome-and ubiquitinmediated proteolysis pathways. Notably, across age strata, expression of interferon response, viral processing, Natural Killer and cytotoxic T-lymphocyte cell genes differed. Our findings suggest agerelated interferon, immune and protein degradation gene expression differences between TS and controls.

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Section: Presence Of Previously Identified Genessupporting

confidence: 83%

Section: Presence Of Previously Identified Genessupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Previously Identified Genesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Age-related gene expression in Tourette syndrome

Lit

Enstrom

Sharp

et al. 2009

Journal of Psychiatric Research

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Tic disorders

Thapar

Pine

Leckman

et al. 2015

Rutter's Child and Adolescent Psychiatry

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Exon expression and alternatively spliced genes in tourette syndrome

Tian

Liao

Zhan

et al. 2010

American J of Med Genetics Pt B

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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 healthy controls (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. 376 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. 90 genes (transcripts) had differential expression of one 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.

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A subgroup of Tourette's patients overexpress specific natural killer cell genes in blood: A preliminary report

Cited by 40 publications

References 51 publications

Age-related gene expression in Tourette syndrome

Age-related gene expression in Tourette syndrome

Tic disorders

Exon expression and alternatively spliced genes in tourette syndrome

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