Whole genome expression as a quantitative trait

2009 ◽  
Vol 37 (6) ◽  
pp. 1276-1277 ◽  
Author(s):  
John Hardy ◽  
Danyah Trabzuni ◽  
Mina Ryten
Keyword(s):  
Gene Expression ◽  
Genetic Variability ◽  
Disease Risk ◽  
Neurological Diseases ◽  
Whole Genome ◽  
Genome Expression ◽  
Genome Analyses ◽  
Whole Genome Expression ◽  
Influence Gene Expression ◽  
Gene Expression Levels

Surprisingly, whole genome analyses of complex human neurological and psychiatric disorders have revealed that many genetic risk factors are likely to influence gene expression rather than alter protein sequences. Previous analyses of neurological diseases have shown that genetic variability in gene expression levels of deposited proteins influence disease risk. With this background, we have embarked on a comprehensive project to determine the effects of common genetic variability on whole genome gene expression.

scholarly journals Temporal genomewide expression profiling of DSS colitis reveals novel inflammatory and angiogenesis genes similar to ulcerative colitis

2011 ◽  
Vol 43 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Kai Fang ◽  
Megan Bruce ◽  
Christopher B. Pattillo ◽  
Songlin Zhang ◽  
Randolph Stone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Expression Profiling ◽  
Profile Analysis ◽  
Whole Genome ◽  
Qrt Pcr ◽  
Dss Colitis ◽  
Genome Expression ◽  
Expression Profile Analysis ◽  
Whole Genome Expression

Dextran sodium sulfate (DSS)-induced colitis is widely used to study pathological mechanisms and potential treatments of inflammatory bowel disease. Because temporal changes in genome expression profiles remain unknown in this model, we performed whole genome expression profile analysis during the development of DSS colitis in comparison with ulcerative colitis (UC) specimens to identify novel and common responses during disease. Colon tissue from DSS-treated mice was collected at days 0, 2, 4, and 6. Half of each specimen was used for histopathological analysis and half for Affymetrix whole genome expression profiling and qRT-PCR validation. Genesifter and Ingenuity software analysis was used to identify differentially expressed genes and perform interactive network analysis. Identified DSS-associated genes in mice were also compared with UC patient data. We identified 1,609 genes that were significantly altered during DSS colitis; the majority were functionally related to inflammation, angiogenesis, metabolism, biological adhesion, cellular growth and proliferation, and cell-to-cell signaling responses. Five hundred and one genes were progressively upregulated, while one hundred seventy-three genes were progressively downregulated. Changes in gene expression were validated in a subset of 33 genes by qRT-PCR, with r2 = 0.925. Ingenuity gene interaction network analysis revealed novel relationships among antigen presentation, cell morphology, and other biological functions in the DSS mouse. Finally, DSS colitis gene array data were compared with UC patient array data: 152 genes were similarly upregulated, and 22 genes were downregulated. Temporal genomewide expression profile analysis of DSS-induced colitis revealed novel associations with various immune responses and tissue remodeling events such as angiogenesis similar to those in UC patients. This study provides a comprehensive view of DSS colitis changes in colon gene expression and identifies common molecules with clinical specimens that are interesting targets for further investigation.

scholarly journals Sum1 and Ndt80 Proteins Compete for Binding to Middle Sporulation Element Sequences That Control Meiotic Gene Expression

2003 ◽  
Vol 23 (14) ◽  
pp. 4814-4825 ◽  
Author(s):  
Michael Pierce ◽  
Kirsten R. Benjamin ◽  
Sherwin P. Montano ◽  
Millie M. Georgiadis ◽  
Edward Winter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Dna Sequence ◽  
Whole Genome ◽  
Sequence Element ◽  
Genome Expression ◽  
Distinct Sequence ◽  
Whole Genome Expression ◽  
Sequence Requirements ◽  
Sporulation Genes

ABSTRACT A key transition in meiosis is the exit from prophase and entry into the nuclear divisions, which in the yeast Saccharomyces cerevisiae depends upon induction of the middle sporulation genes. Ndt80 is the primary transcriptional activator of the middle sporulation genes and binds to a DNA sequence element termed the middle sporulation element (MSE). Sum1 is a transcriptional repressor that binds to MSEs and represses middle sporulation genes during mitosis and early sporulation. We demonstrate that Sum1 and Ndt80 have overlapping yet distinct sequence requirements for binding to and acting at variant MSEs. Whole-genome expression analysis identified a subset of middle sporulation genes that was derepressed in a sum1 mutant. A comparison of the MSEs in the Sum1-repressible promoters and MSEs from other middle sporulation genes revealed that there are distinct classes of MSEs. We show that Sum1 and Ndt80 compete for binding to MSEs and that small changes in the sequence of an MSE can yield large differences in which protein is bound. Our results provide a mechanism for differentially regulating the expression of middle sporulation genes through the competition between the Sum1 repressor and the Ndt80 activator.

A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression

10.1038/79896 ◽  
2000 ◽  
Vol 26 (2) ◽  
pp. 183-186 ◽  
Author(s):  
Barak A. Cohen ◽  
Robi D. Mitra ◽  
Jason D. Hughes ◽  
George M. Church
Keyword(s):  
Gene Expression ◽  
Computational Analysis ◽  
Whole Genome ◽  
Expression Data ◽  
Genome Expression ◽  
Whole Genome Expression

Gene expression profiling of prostate tissue based on variable expression of 5-alpha reductase 2.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 143-143
Author(s):  
Keyan Salari ◽  
Seth Bechis ◽  
Rongbin Ge ◽  
Jian Hong ◽  
Aleksander Otsetov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hierarchical Clustering ◽  
Promoter Methylation ◽  
Expression Profiling ◽  
Molecular Subtypes ◽  
Prostatic Tissue ◽  
Whole Genome ◽  
Variable Expression ◽  
Genome Expression ◽  
Whole Genome Expression

143 Background: Androgen signaling plays a central role in the pathophysiology of both benign and malignant prostatic disease. We previously showed that some men carry epigenetic modifications of the 5-alpha reductase (AR) promoter that modulate gene expression, raising the hypothesis that there may be molecular heterogeneity underlying the variability in clinical response to 5-AR inhibitors for management of benign and malignant prostatic diseases. In this study, we performed whole-genome expression profiling of prostatic tissue based on variable expression of 5-AR2 to determine whether molecular subtypes of clinical relevance could be identified. Methods: Prostatic tissue specimens were obtained from 22 patients with symptomatic BPH undergoing prostate debulking surgery. 5-AR2 protein expression was measured by immunohistochemistry, and 5-AR2 promoter methylation determined by PCR. RNA was extracted from each specimen and whole-genome expression profiling was performed using Illumina Human BeadChip Arrays. Gene expression data was analyzed by unsupervised hierarchical clustering and Gene Set Enrichment Analysis. Results: Unsupervised hierarchical clustering identified two subtypes of patients with distinct gene expression signatures. Among the most differentially expressed genes were several notable androgen-regulated genes, including TMPRSS2, NKX3-1, AZGP1, KLK3 (encoding the PSA protein) and multiple other members of the kallikrein family of serine proteases (all P< 0.001, FDR < 0.02). Multiple gene sets composed of androgen-regulated genes and androgen receptor target genes were found to be significantly enriched in one of the two subtypes. Interestingly, patients from this Androgen-Up subtype were also noted to have a higher frequency of 5-AR2 promoter methylation (though not statistically significant). Conclusions: Our findings suggest that there are distinct molecular subtypes among prostatic tissues with variable expression of 5-AR2, driven by differences in androgen gene regulation. These differences may partially explain the variable response to 5-AR inhibitors and thereby inform clinical strategies for devising therapies for benign and malignant prostatic disease.

scholarly journals C.02 Whole genome expression profiling of blood-brain barrier endothelial cells after experimental subarachnoid hemorrhage

2016 ◽  
Vol 43 (S2) ◽  
pp. S11-S11
Author(s):  
MK Tso ◽  
P Turgeon ◽  
B Bosche ◽  
J Ai ◽  
P Marsden ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Subarachnoid Hemorrhage ◽  
Blood Brain Barrier ◽  
Expression Profiling ◽  
Brain Barrier ◽  
Whole Genome ◽  
Genome Expression ◽  
Blood Brain ◽  
Whole Genome Expression

Background: The pathophysiology of subarachnoid hemorrhage (SAH) is complex and includes disruption of the blood-brain barrier (BBB). We freshly isolated BBB endothelial cells (BECs) by 2 distinct methods after experimental SAH and then interrogated their gene expression profiles with the goal of uncovering new therapeutic targets. Methods: SAH was induced using the prechiasmatic blood injection mouse model. BBB permeability studies were performed by administering intraperitoneal cadaverine dye injections at 24h and 48h. BECs were isolated either by sequential magnetic-based sorting for CD45-CD31+ cells or by fluorescence-activated cell sorting (FACS) for Tie2+Pdgfrb- cells. Total RNA was extracted and analyzed using Affymetrix Mouse Gene 2.0 ST Arrays. Results: BBB impairment occurred at 24h and resolved by 48h after SAH. Analysis of gene expression patterns in BECs at 24h reveal clustering of SAH and sham samples. We identified 707 (2.8%) significant differentially-expressed genes (403 upregulated, 304 downregulated) out of 24,865 interrogated probe sets. Many significantly upregulated genes were involved in inflammatory pathways. These microarray results were validated with real-time polymerase chain reaction (RT-PCR). Conclusions: This study is the first to investigate in an unbiased manner, whole genome expression profiling of freshly-isolated BECs in an SAH animal model, yielding targets for novel therapeutic intervention.

scholarly journals Whole Genome Expression Profiles of Yeast RNA Polymerase II Core Subunit, Rpb4, in Stress and Nonstress Conditions

2002 ◽  
Vol 278 (5) ◽  
pp. 3339-3346 ◽  
Author(s):  
Beena Pillai ◽  
Jiyoti Verma ◽  
Anju Abraham ◽  
Princy Francis ◽  
Yadunanda Kumar ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Expression Profiles ◽  
Whole Genome ◽  
Genome Expression ◽  
Whole Genome Expression
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