Exon expression and alternatively spliced genes in Tourette Syndrome.
Exon expression and alternatively spliced genes in Tourette Syndrome.
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DOI：
10.1002/ajmg.b.31140
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发表时间：
2011-01
影响因子：
2.8
通讯作者：
Sharp, Frank R.
中科院分区：
文献类型：
--
作者：
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.
关键词：
抽动秽语综合征（TS）的诊断是基于临床标准，包括运动和声音抽搐。我们假设外显子表达和剪接的差异可能对病理生理和诊断有用。为了证明TS患者与健康对照（HC）血液中外显子表达和选择性剪接基因的差异，从26名未服药的TS受试者和23名健康对照（HC）的血液中分离出RNA。每个样品在Affymetrix Human Exon 1.0 ST （HuExon）阵列和3 '偏置U133 Plus 2.0 （HuU133）阵列上运行。为了研究差异表达的外显子和转录本，进行了协方差分析（ANCOVA），控制了年龄、性别和批次。利用Partek的方差分析（ANOVA）模型确定了TS和HC之间不同的选择性剪接模式。376个外显子探针集在TS和HC之间差异表达（原始p<0.005，折叠变化>|1.2|），使用分层聚类和主成分分析将TS和HC受试者分开。通过10倍交叉验证，与HC相比，该探针组预测TS的灵敏度和特异性为90%。与HC相比，TS中有90个基因（转录本）有1个外显子的差异表达（p<0.005），并且被预测为选择性剪接（p<0.05）。这些初步发现可能有助于深入了解TS的病理生理学，并可能提供预后和诊断的生物标志物。然而，这些发现由于样本量小和多次比较而受到影响，需要使用PCR或深度RNA测序和更大的患者群体来证实。
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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影响因子：
14.5
作者：
Baym, C. L.;Corbett, B. A.;Bunge, S. A.
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
Martino, Davide;Dale, Russell C.;Gilbert, Donald L.;Giovannoni, Gavin;Leckman, James F.
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影响因子：
4.4
作者：
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通讯作者：
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DOI：
10.1002/ajmg.b.30550
发表时间：
2007-10-05
影响因子：
2.8
作者：
Lit, Lisa;Gilbert, Donald L.;Sharp, Frank R.
通讯作者：
Sharp, Frank R.