Specific Regional and Age-Related Small Noncoding RNA Expression Patterns Within Superior Temporal Gyrus of Typical Human Brains Are Less Distinct in Autism Brains

Stamova, Boryana; Ander, Bradley P.; Barger, Nicole; Sharp, Frank R.; Schumann, Cynthia M.

doi:10.1177/0883073815602067

Cited by 34 publications

(38 citation statements)

References 79 publications

(128 reference statements)

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“…Interestingly, data from the GTEx database (http://www.gtexportal.org/home/gene/mir4519) showed that miR‐4519 is expressed in higher levels in substantia nigra, the primary area of the brain that is affected by PD [Croisier et al., ]. In agreement with our findings, two recent studies have also demonstrated this miRNA to be expressed in the human brain tissues [Hong et al., ; Stamova et al., ].…”

Section: Discussionsupporting

confidence: 93%

Genetic Variants in MicroRNAs and Their Binding Sites Are Associated with the Risk of Parkinson Disease

et al. 2015

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MicroRNAs (miRNAs) are small noncoding RNAs that serve as key regulators of gene expression. They have been shown to be involved in a wide range of biological processes including neurodegenerative diseases. Genetic variants in miRNAs or miRNA-binding sites on their target genes could affect miRNA function and contribute to disease risk. Here, we investigated the association of miRNA-related genetic variants with Parkinson disease (PD) using data from the largest GWAS on PD. Of 243 miRNA variants, we identified rs897984:T>C in miR-4519 (P value = 1.3×10(-5) and OR = 0.93) and rs11651671:A>G in miR-548at-5p (P value = 1.1×10(-6) and OR = 1.09) to be associated with PD. We showed that the variant's mutant alleles change the secondary structure and decrease expression level of their related miRNAs. Subsequently, we highlighted target genes that might mediate the effects of miR-4519 and miR-548at-5p on PD. Among them, we experimentally showed that NSF is a direct target of miR-4519. Furthermore, among 48,844 miRNA-binding site variants, we found 32 variants (within 13 genes) that are associated with PD. Four of the host genes, CTSB, STX1B, IGSF9B, and HSD3B7, had not previously been reported to be associated with PD. We provide evidence supporting the potential impact of the identified miRNA-binding site variants on miRNA-mediated regulation of their host genes.

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Section: Discussionsupporting

confidence: 93%

Genetic Variants in MicroRNAs and Their Binding Sites Are Associated with the Risk of Parkinson Disease

et al. 2015

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“…As such the application of gene expression analysis, using unbiased application of mathematical cluster analysis to identify stroke subtypes offers promise. Studies of microarrays and NGS show the diagnostic potential of such an approach 5, 6, 7, 8, 10, 23, 24, 25. Using molecular technology, preliminary diagnostic discrimination following stroke is over 90% accurate, with similar high sensitivity and specificity.…”

Section: Discussionmentioning

confidence: 99%

Blood transcriptome changes after stroke in an African American population

Meller

Pearson

Hardy

et al. 2016

Ann Clin Transl Neurol

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ObjectiveMolecular diagnostic medicine holds much promise to change point of care treatment. An area where additional diagnostic tools are needed is in acute stroke care, to assist in diagnosis and prognosis. Previous studies using microarray‐based gene expression analysis of peripheral blood following stroke suggests this approach may be effective. Next‐generation sequencing (NGS) approaches have expanded genomic analysis and are not limited to previously identified genes on a microarray chip. Here, we report on a pilot NGS study to identify gene expression and exon expression patterns for the prediction of stroke diagnosis and prognosis.MethodsWe recruited 28 stroke patients and 28 age‐ and sex‐matched hypertensive controls. RNA was extracted from 3 mL blood samples, and RNA‐Seq libraries were assembled and sequenced.ResultsBioinformatical analysis of the aligned RNA data reveal exonic (30%), intronic (36%), and novel RNA components (not currently annotated: 33%). We focused our study on patients with confirmed middle cerebral artery occlusion ischemic stroke (n = 17). On the basis of our observation of differential splicing of gene transcripts, we used all exonic RNA expression rather than gene expression (combined exons) to build prediction models using support vector machine algorithms. Based on model building, these models have a high predicted accuracy rate >90% (spec. 88% sen. 92%). We further stratified outcome based on the improvement in NIHss scores at discharge; based on model building we observe a predicted 100% accuracy rate.Interpretation NGS‐based exon expression analysis approaches have a high potential for patient diagnosis and outcome prediction, with clear utility to aid in clinical patient care.

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“…The results were then overlapped to identify post-stroke sex-specific and common lncRNA expression. To eliminate those genes with very low expression and reduce noise, differentially expressed lncRNAs were considered significant with absolute fold change (FC)>1.2 and p<0.005 3, 32, 33 . Prior to visualization on principal components analysis (PCA) and hierarchical clustering, effects due to batch scan date and time since stroke were removed from both the derivation and validation sets.…”

Section: Methodsmentioning

confidence: 99%

Altered Expression of Long Noncoding RNAs in Blood After Ischemic Stroke and Proximity to Putative Stroke Risk Loci

Dykstra-Aiello

Jickling

Ander

et al. 2016

Stroke

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122

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Background and Purpose Though peripheral blood mRNA and microRNA change following ischemic stroke, any role for long noncoding RNA (lncRNA), which comprise most of the genome and have been implicated in various diseases, is unknown. Thus, we hypothesized that lncRNA expression also changes following stroke. Methods lncRNA expression was assessed in 266 whole-blood RNA samples drawn once per individual from ischemic stroke patients and matched vascular risk factor controls. Differential lncRNA expression was assessed by Analysis of Covariance (ANCOVA, p-value < 0.005; fold change > |1.2|), principal components analysis and hierarchical clustering on a derivation set (n=176) and confirmed on a validation set (n=90). Post-stroke temporal lncRNA expression changes were assessed using ANCOVA with confounding factor correction (p<0.005; partial correlation with time since event >|0.4|). Because sexual dimorphism exists in stroke, analyses were performed for each sex separately. Results 299 lncRNAs were differentially expressed between stroke and control males, whereas 97 lncRNAs were differentially expressed between stroke and control females. Significant changes of lncRNA expression with time after stroke were detected for 49 lncRNAs in males and 31 lncRNAs in females. Some differentially expressed lncRNAs mapped close to genomic locations of previously identified putative stroke-risk genes, including Lipoprotein, Lp(A)-Like 2, ABO blood group, Prostaglandin 12 Synthase, and α-Adducins. Conclusions This study provides evidence of altered and sexually dimorphic lncRNA expression in peripheral blood of stroke patients compared to controls and suggests lncRNAs have potential for stroke biomarker development. Some regulated lncRNA could regulate some previously identified putative stroke-risk genes.

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Specific Regional and Age-Related Small Noncoding RNA Expression Patterns Within Superior Temporal Gyrus of Typical Human Brains Are Less Distinct in Autism Brains

Cited by 34 publications

References 79 publications

Genetic Variants in MicroRNAs and Their Binding Sites Are Associated with the Risk of Parkinson Disease

Genetic Variants in MicroRNAs and Their Binding Sites Are Associated with the Risk of Parkinson Disease

Blood transcriptome changes after stroke in an African American population

Altered Expression of Long Noncoding RNAs in Blood After Ischemic Stroke and Proximity to Putative Stroke Risk Loci

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