scholarly journals mTOR complex 1 pathway activation in severe keratoconus; the functional implications of GWAS identified loci

2018 ◽  
Author(s):  
Robert PL Wisse ◽  
Jonas JW Kuiper ◽  
Gijsbert M de Veij Mestdagh ◽  
Catharina GK Wichers ◽  
Sanne Hiddingh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vision Loss ◽  
Expression Profiles ◽  
Association Studies ◽  
Corneal Thickness ◽  
Corneal Tissue ◽  
Genome Wide Association Studies ◽  
Corneal Grafting ◽  
Functional Implications ◽  
Mtorc1 Pathway

AbstractPurposeKeratoconus (KC) is an eye condition that can lead to a severe vision loss and may warrant a corneal grafting procedure. Meta-analyses of genome wide association studies have identified several genes that confer risks for differences in corneal curvature, corneal thickness, and developing keratoconus. Currently, there is limited evidence of a functional role for the identified loci in the affected corneal tissues.MethodsWe investigated the gene expression profiles of 4 GWAS confirmed risk loci and several related pathways that function in cellular ageing and cell cycle control in corneal tissue of a discovery and replication cohort comprising in total 27 keratoconus patients, 16 healthy controls, and 21 diseased controls (failed corneal grafts).ResultsWe confirmed the MTOR gene locus as differentially expressed in KC corneas in a discovery cohort Next, we replicated these results in a second cohort and found evidence of increased expression of various mTORC1 pathway signature genes, namely MTOR itself (P=0.040), AKT1 (P=0.028), IGF1R (P=0.022) and RAPTOR (P=0.007).ConclusionsGene expression profiling in cornea tissues revealed robust up-regulation of the mTORC1 pathway in KC and substantiates a potential role for this pathway in its pathogenesis. Functional implications should be further studied since biomarkers for disease activity are needed and selective targeting of the mTOR pathway is a promising treatment concept.

scholarly journals Genome-wide association studies and gene expression profiles of rheumatoid arthritis

2016 ◽  
Vol 5 (7) ◽  
pp. 314-319 ◽  
Author(s):  
X. Xiao ◽  
J. Hao ◽  
Y. Wen ◽  
W. Wang ◽  
X. Guo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Expression Profiles ◽  
Association Studies ◽  
Gene Expression Profiles ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

The HaemAtlas: Characterising Gene Expression in Differentiated Human Blood Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2453-2453
Author(s):  
Nicholas A. Watkins ◽  
Marloes R. Tijssen ◽  
Arief Gusnanto ◽  
Bernard de Bono ◽  
Subhajyoti De ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factors ◽  
Cell Function ◽  
Expression Profiles ◽  
Association Studies ◽  
Cytotoxic T Cells ◽  
Expression Patterns ◽  
Immunoglobulin Superfamily ◽  
Genome Wide Association Studies

Abstract Haematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell surface receptors. In order to further understand haematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B-cells, cytotoxic and helper T-cells, Natural Killer cells, granulocytes and monocytes using whole genome microarrays. A bioinformatics analysis of this data was performed focusing on transcription factors, immunoglobulin superfamily members and lineage specific transcripts. We observed that the numbers of lineage specific genes varies by two orders of magnitude, ranging from five for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel co-expression patterns for key transcription factors involved in haematopoiesis (eg. GATA3–GFI1 and GATA2–KLF1). This study represents the most comprehensive analysis of gene expression in haematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which is freely accessible, will be invaluable for future studies on haematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.

scholarly journals Proteomics as a Potential Tool for Identifying Biomarkers for Host Resistance to Cattle Tick

Proceedings ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 131
Author(s):  
Ali Raza ◽  
Peter James ◽  
Ala Tabor
Keyword(s):  
Gene Expression ◽  
Host Resistance ◽  
Serum Proteins ◽  
Expression Profiles ◽  
Association Studies ◽  
Gene Expression Profiles ◽  
Economic Losses ◽  
Effective Vaccine ◽  
Cattle Tick ◽  
Genome Wide Association Studies

The cattle tick, Rhiphicephalus microplus, and the diseases it transmits lead to massive economic losses to cattle industries in tropical and subtropical countries. The emergence of widespread resistance to acaricide drugs and the absence of an effective vaccine for tick control had led to genetic selection of host resistance as a method of choice for non-chemical control of cattle tick. Research to identify host genetic markers associated with tick susceptibility or resistance has been limited to the comparison of local breeds in specific geographic regions. Previous studies have also focused on gene expression profiles, localizing cellular and humoral immune responses, and genome-wide association studies (GWAS) to identify functional genetic variants associated with tick resistance/susceptibility. Given the fact that gene expression results and actual dynamics occurring at the protein level often do not correlate due to post-transcriptional, post-translational and degradation regulation, host proteomics may provide reliable biomarkers to assist in selection to support traditional breeding programs. The present study aims to investigate the variation in protein profiles among tick resistant and susceptible cattle following tick infestation. Preliminary findings suggest that different serum proteins exist between tick resistant and susceptible Santa Gertrudis cattle. This research is supported by Meat & Livestock Australia.

scholarly journals EW_dmGWAS: edge-weighted dense module search for genome-wide association studies and gene expression profiles

2015 ◽  
Vol 31 (15) ◽  
pp. 2591-2594 ◽  
Author(s):  
Quan Wang ◽  
Hui Yu ◽  
Zhongming Zhao ◽  
Peilin Jia
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Association Studies ◽  
Gene Expression Profiles ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals TWENTY-FOUR GENES ARE UPREGULATED IN PATIENTS WITH HYPOSPADIAS

2013 ◽  
Vol 16 (2) ◽  
pp. 39-43 ◽  
Author(s):  
R. Karabulut ◽  
Z. Turkyilmaz ◽  
K. Sonmez ◽  
G. Kumas ◽  
Sg. Ergun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Association Studies ◽  
Gene Expression Profiles ◽  
Ventral Surface ◽  
Genome Wide Association Studies ◽  
Expression Array ◽  
Large Patient ◽  
Expression Studies ◽  
Genome Wide

ABSTRACT Hypospadias is a congenital hypoplasia of the penis, with displacement of the urethral opening along the ventral surface, and has been reported to be one of the most common congenital anomalies, occurring in approximately 1:250 to 1:300 live births. As hypospadias is reported to be an easily diagnosed malformation at the crossroads of genetics and environment, it is important to study the genetic component in order to elucidate its etiology. In this study, the gene expression profiles both in human hypospadias tissues and normal penile tissues were studied by Human Gene Expression Array. Twentyfour genes were found to be upregulated. Among these, ATF3 and CYR61 have been reported previously. Other genes that have not been previously reported were also found to be upregulated: BTG2, CD69, CD9, DUSP1, EGR1, EIF4A1, FOS, FOSB, HBEGF, HNRNPUL1, IER2, JUN, JUNB, KLF2, NR4A1, NR4A2, PTGS2, RGS1, RTN4, SLC25A25, SOCS3 and ZFP36 (p <0.05). Further studies including genome-wide association studies (GWAS) with expression studies in a large patient group will help us for identifiying the candidate gene(s) in the etiology of hypospadias

scholarly journals Insights from GWAS into the quantitative genetics of transcription in humans

2010 ◽  
Vol 92 (5-6) ◽  
pp. 361-369 ◽  
Author(s):  
JINHEE KIM ◽  
GREG GIBSON
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Association Studies ◽  
Gene Expression Profiles ◽  
Transcript Abundance ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetic Traits ◽  
Genome Wide ◽  
Ready Availability

SummaryHuman gene expression profiles have emerged as an effective model system for the dissection of quantitative genetic traits. Peripheral blood and transformed lymphoblasts are particularly attractive for their ready availability and repeatability, respectively, and the advent of relatively inexpensive genotyping and microarray analysis technologies has facilitated genome-wide association for transcript abundance in numerous settings. Thousands of genes have been shown to harbour regulatory polymorphisms that have large local effects on transcription, explaining 20% or more of the variance in many cases, but the focus on such results obscures the reality that the vast majority of the genetic component of transcriptional variance remains to be ascertained. This mini-review surveys the inferences derived from genome-wide association studies (GWAS) for gene expression to date, and discusses some of the issues we face in finding the remainder of the heritability and understanding how environmental and genetic regulatory factors orchestrate the highly structured architecture of transcriptional variation.

scholarly journals The Colon Transcriptome Explorer (CoTrEx) 2.0: a Reference Web-Based Resource for Exploring Population-Based Normal Colon Gene Expression

2021 ◽  
Author(s):  
Virginia Díez-Obrero ◽  
Ferran Moratalla-Navarro ◽  
Christopher Dampier ◽  
Matthew Devall ◽  
Robert Carreras-Torres ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prediction Models ◽  
Expression Profiles ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Normal Colon ◽  
Colon Tissue ◽  
Web Based ◽  
Normal Colon Tissue ◽  
High Interest

Gene expression data is key for the functional annotation of single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS). Expression and splicing quantitative trait loci (e/sQTLs) in normal colon tissue, such as those from the University of Barcelona and University of Virginia RNA sequencing project (BarcUVa-Seq) and the Genotype-Tissue Expression project (GTEx), are required to gain biological insight of colon-related diseases risk loci. Moreover, transcriptome-wide association studies (TWAS) rely on reference gene expression imputation panels in the tissue of interest to nominate susceptibility genes. Also, it is of high interest to study the relationships between genes in a network framework. For facilitating these analyses, we have updated and expanded the scope of the Colon Transcriptome Explorer (CoTrEx) to the version 2.0. This web-based resource provides exhaustive visualization and analysis of transcriptome-wide gene expression profiles of normal colon tissue from BarcUVa-Seq and GTEx. In addition to the integration of new datasets, CoTrEx 2.0 provides additional e/sQTLs sets, as well as gene expression prediction models and regulatory and co-expression networks. It is freely available at https://barcuvaseq.org/cotrex/. Overall, it is of high interest for researchers aiming to investigate the genetic susceptibility to colon-related complex traits and diseases.

scholarly journals A HaemAtlas: characterizing gene expression in differentiated human blood cells

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. e1-e9 ◽  
Author(s):  
Nicholas A. Watkins ◽  
Arief Gusnanto ◽  
Bernard de Bono ◽  
Subhajyoti De ◽  
Diego Miranda-Saavedra ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factors ◽  
Cell Function ◽  
Expression Profiles ◽  
Association Studies ◽  
Cytotoxic T Cells ◽  
Gene Expression Profiles ◽  
Immunoglobulin Superfamily ◽  
Genome Wide Association Studies

Abstract Hematopoiesis is a carefully controlled process that is regulated by complex networks of transcription factors that are, in part, controlled by signals resulting from ligand binding to cell-surface receptors. To further understand hematopoiesis, we have compared gene expression profiles of human erythroblasts, megakaryocytes, B cells, cytotoxic and helper T cells, natural killer cells, granulocytes, and monocytes using whole genome microarrays. A bioinformatics analysis of these data was performed focusing on transcription factors, immunoglobulin superfamily members, and lineage-specific transcripts. We observed that the numbers of lineage-specific genes varies by 2 orders of magnitude, ranging from 5 for cytotoxic T cells to 878 for granulocytes. In addition, we have identified novel coexpression patterns for key transcription factors involved in hematopoiesis (eg, GATA3-GFI1 and GATA2-KLF1). This study represents the most comprehensive analysis of gene expression in hematopoietic cells to date and has identified genes that play key roles in lineage commitment and cell function. The data, which are freely accessible, will be invaluable for future studies on hematopoiesis and the role of specific genes and will also aid the understanding of the recent genome-wide association studies.

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