HPCX1 linked prostate cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Henna Mattila
PROVIDER: E-GEOD-24205 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene.
Mattila Henna H Schindler Martin M Isotalo Jarkko J Ikonen Tarja T Vihinen Mauno M Oja Hannu H Tammela Teuvo L J TL Wahlfors Tiina T Schleutker Johanna J
BMC cancer 20110802
<h4>Background</h4>Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPCX1 at Xq27-q28, but due to the complex structure of the region, the susceptibility gene has not yet been identified.<h4>Methods</h4>In this study, nonsense-mediated mRNA decay (NMD) inhibition was used for the discovery of truncating mutations. Six prostate cancer (PC) patients and their healthy brothers were selected from a group of HPCX1-linked families. Expression analyses wer ...[more]
Similar Datasets
Project description:MicroRNA expression levels in the lymphoblastic cells of prostate cancer patients and their healthy brothers from HPCX1 linked prostate cancer families were analyzed to trace variants that might alter miRNA expression and explain partly an inherited genetic predisposion to prostate cancer. MicroRNA expression levels in lymphoblastoid cell lines were detected using an Agilent Human miRNA V2 Oligo Microarray Kit (Agilent Technologies).100 ng of total RNA was used as a starting material, and miRNAs were labeled using the Agilent miRNA Labeling Kit. Labeled RNA was hybridized to Agilent miRNA arrays with eight identical arrays per slide, with each array containing probes directed against 723 human and 76 human viral miRNAs. Slides were scanned (Agilent microarray scanner) after hybridization and data was extracted using Feature Extraction software, version 9.5.1. (Agilent Technologies). Altogether 14 cancer patients and 15 healthy brothers from 11 families were included with no replicates.
2011-12-31 | E-GEOD-24201 | biostudies-arrayexpress
Project description:As a non-invasive blood testing, the detection of cell-free DNA (cfDNA) methylation in plasma is raising increasing interest due to its diagnostic and biology applications. Although extensively used in cfDNA methylation analysis, bisulfite sequencing is less cost-effective. Through enriching methylated cfDNA fragments with MeDIP followed by deep sequencing, we aimed to characterize cfDNA methylome in cancer patients. In this study, we investigated the cfDNA methylation patterns in lung cancer patients by MeDIP-seq. MEDIPS package was used for the identification of differentially methylated regions (DMRs) between patients and normal ones. Overall, we identified 330 differentially methylated regions (DMRs) in gene promoter regions, 33 hypermethylation and 297 hypomethylation respectively, by comparing lung cancer patients and healthy individuals as controls. The 33 hypermethylation regions represent 32 genes. Some of the genes had been previously reported to be associated with lung cancers, such as GAS7, AQP10, HLF, CHRNA9 and HOPX. Taken together, our study provided an alternative method of cfDNA methylation analysis in lung cancer patients with potential clinical applications.
2019-03-31 | E-MTAB-7163 | biostudies-arrayexpress
Project description:BACKGROUND Familial diarrheas are mostly severe recessive diseases. Here we describe the clinical picture and dominant genetic cause of a novel disease in 32 members of a Norwegian family. The chronic diarrhea is of early onset, relatively mild, and is combined with increased susceptibility to intestinal inflammation, ileus and oesophagitis. METHODS Whole genome SNP-analysis was used to identify a single candidate locus for dominant diarrhea on chromosome 12, followed by sequencing of the GU2CY gene. This encodes guanylyl cyclase 2C, an intestinal receptor for bacterial heat-stable enterotoxins and the peptides uroguanylin and guanylin. Functional studies of a missense mutation were performed after heterologous expression of the mutant receptor in HEK293T cells. The therapeutic response to metformin, an inhibitor of the cystic fibrosis transmembrane regulator (CFTR), was investigated in 5 patients. RESULTS We identified heterozygosity for the first described pathogenic human mutation (c.2519G>T ) in the GUCY2C gene. The mutant receptor showed increased cGMP production in response to its ligands. This may cause hyperactivation of the CFTR and consequent increased chloride and water secretion from the enterocytes, resulting in chronic diarrhea. Treatment with the CFTR-inhibitor metformin significantly reduced the frequency of stools in affected individuals by 34-45%. CONCLUSIONS Increased GC-C signaling disturbs normal bowel function, as shown by the diverse symptoms in our patients, and seems to have a pro-inflammatory effect, either through increased Cl- secretion or additional effects of elevated cellular cGMP. The importance of genetic variants in the GC-C-CFTR-pathway for conditions like Crohn’s disease and IBS should be further explored. Linkage analysis was performed (Allegro v 2.0) using Affymetrix 250K SNP arrays according to the manufacturer's directions on DNA extracted from peripheral blood samples. This accession number contains the data for 25 individuals of family branch A in the article.
2012-04-09 | E-GEOD-31260 | biostudies-arrayexpress
Project description:Splenectomy improves clinical parameters of patients with hereditary spherocytosis but its potential benefit to red blood cell (RBC) morphology and deformability and the mechanism behind remain unknown. We here compared 7 non-splenectomized and 12 splenectomized patients with mutations in the β-spectrin (SPTB) or the ankyrin (ANK1) gene. We showed that hematological parameters, spherocyte abundance, osmotic fragility, intracellular calcium and extracellular vesicle release were largely restored by splenectomy, but cryohemolysis was not. To elucidate the only partial improvement of RBC morphology and deformability by splenectomy, we performed a quantative proteomic analysis and cytoskeleton characterization. Patients exhibited decreased ankyrin and/or β-spectrin contents but the extent of RBC alteration only slightly and negatively correlated with the ankyrin and not with β-spectrin content nor membrane association. In contrast, patients exhibited increased abundance of septins, small GTP-binding cytoskeletal proteins involved in cytokinesis. Among the four septins detected, septins-2,7 and 8 but not 11 were less abundant upon splenectomy and correlated with the disease severity. The septin increase was accompanied by exacerbated oxidative stress especially in the non splenectomized patients. Except cryohemolysis, all the RBC morphology and deformability alterations and oxidative stress correlated with septin content. Impairments can result from RBC maturation defects since endoplasmic reticulum remnants were found in RBCs from non-splenectomized patients and lysosomal and mitochondrial remnants in splenectomised patients. The correlation between septin abundance and disease severity opens the way towards using septins as disease biomarkers. Moreover, the absence of restoration of septin-independent cryohemolysis by splenectomy could question its systematic recommendation
2023-02-13 | PXD034588 | Pride
Project description:In this study, nonsense-mediated mRNA decay (NMD) inhibition was used for the discovery of truncating mutations. Six prostate cancer (PRCA) patients and their healthy brothers were selected from a group of HPCX1-linked families. mRNA was isolated from their lymphoblastic cells after pharmacological treatment. Expression analyses were done using Agilent 44K oligoarrays, and selected genes were screened for mutations by sequencing. In order to identify genes containing inactivating mutations in the Xq27-q28 region, an NMD microarray analysis with Agilent 44K Whole Human Genome oligonucleotide microarrays was performed in the families showing the strongest linkage to HPCX1. Five families were chosen with 6 affected and 6 healthy controls. Lymphoblastoid cell lines were derived from whole blood and treated with emetine to block NMD pathway. Total RNA was extracted from harvested cells (treated and untreated) and labeled with Cy5 and Cy3. Labeled samples were hybridized to the Agilent 44K Whole Human Genome Oligonucleotide Microarrays. After hybridization microarrays were scanned and data was extracted using Feature Extraction software. The candidate genes (n=17) for subsequent sequence analysis were selected according to the microarray analysis.
2011-12-31 | E-GEOD-24204 | biostudies-arrayexpress
Project description:Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2,112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters, and enrichment of co-localised functional elements. We found eQTLs for about 85% of analysed genes, 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 MB to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might often be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels, and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. We show for strongly heritable transcripts that a considerable gap still exists between total heritability resulting from all trans-chromosomes and explained variance of all identified trans-eSNPs. In contrast, the vast majority of most cis-heritability of these genes is already explained. Dissection of co-localised functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene-expression, pathways and disease related processes. Gene expression from human blood mononuclear cells from individuals of the Leipzig LIFE Heart Study was analyzed applying Illumina HT-12 v4 Expression BeadChips. After preprocessing, 28,295 expression probes for 2,112 individuals remained for analysis. In a population-based analysis, we identified associations between DNA variants and RNA expression levels and characterized these findings.
2015-06-29 | E-GEOD-65907 | biostudies-arrayexpress
Project description:Background & Aims: Since liver hepatocytes produce the majority of serum proteins, liver cirrhosis displays a massive alteration in serum proteome. The aim of the current study was to characterize these alterations and to study the prognostic usefulness of hepatocellular proteins available in routine clinical testing. Methods: Sera from 29 healthy controls and 43 cirrhotic subjects were subjected to untargeted proteomic analysis. The data were analyzed by Perseus program, R and unsupervised hierarchical clustering. The prognostic usefulness potential of selected biomarkers was tested in 61 controls and 285 cirrhotic individuals. Ingenuity pathway analysis (IPA) was employed to determine the upstream regulators that were further validated in 9 control and 9 cirrhotic livers. Results: Proteomics uncovered 65 down- and 16 upregulated hepatocellular serum proteins that are significantly down- respectively upregulated in cirrhotic subjects versus controls. Hierarchical clustering revealed two main clusters and 6 subclusters, while IPA identified HNF4α and IL6 as the two major upstream regulators that were confirmed in gene expression analyses. Pseudocholinesterase (AUROC 0.618; P=0.002), transferrin (AUROC 0.594; P=0.013), and transthyretin (TTR; AUROC 0.586; P=0.023) but not albumin serum levels discriminated between 90 days transplant-free survivors vs. non-survivors. Tree learning decision algorithm identified transthyretin as a biomarker that improved the prediction of death or transplant in the subset of patients with acute-on-chronic liver failure (ACLF). TTR≤58 mg/dl conferred an increased risk in both univariate (HR 1.75; 95% CI 1.14-2.67; P=0.01) and multivariable analysis (aHR 1.59; 95% CI 1.04-2.24; P=0.033). Conclusion: Our study uncovers the changes in hepatocellular serum proteins as well as the underlying transcriptional factors and suggest that transthyretin may constitute an useful prognostic adjunct in ACLF subjects.
2023-11-20 | PXD035024 | Pride
Project description:The immune response to SARS-CoV-2 varies among patients. We used proteomic analysis to study CD19+ lymphocytes, which are important for the immune response. By comparing the proteomes of CD19+ cells from healthy individuals and COVID-19 patients, we discovered proteins and signaling pathways involved in the immune response during COVID-19. This knowledge improves our understanding of immune dysregulation in COVID-19 and can help develop targeted therapies. Our research also explores the role of CD19+ lymphocytes in COVID-19 and identifies potential biomarkers. Overall, our findings contribute to understanding COVID-19 immunology and inform future research efforts.
2023-09-24 | PXD042938 | Pride
Project description:We wanted to explore the genomic regions 1p13, 1q41, 9p21 and 10q11, which are among the labeled âtop 12 golden lociâ linked to coronary artery disease (CAD) risk, in order to see whether their geographic variation could be explained by demographic effects. To do this, we have genotyped these risk regions in a set of Mediterranean populations. Genomic DNA was extracted from blood cells using a Blood Midi kit (Omega Biotek, USA) according to manufacturer's procedures. DNA samples were genotyped for a combined set of 366 SNPs using an Illumina Custom GoldenGate Panel. SNPs were selected as a representative set of the common variation in the four genomic regions, according to the following criteria: i) average coverage of 1 SNP every 1.5 kb, ii) minor allele frequency (MAF) higher than 0.05 in CEU and TSI HapMap populations, iii) given priority to markers not in linkage disequilibrium (LD) (r2<0.8) in European populations, and iv) prioritizing markers previously associated with CAD. These criteria were applied giving preference to tag SNPs.
2016-11-24 | E-MTAB-5265 | biostudies-arrayexpress
Project description:Citrullinated and unmodified peptides (>95% purity, ProImmune AB) were immobilized onto a chemically modified glass slide, sera from RA patients and healthy controls were applied into the reactions sites and fluorescence intensity after incubation with anti-human IgG antibody was acquired in a laser scanner. Final results for each citrullinated peptide were calculated by subtracting the intensity values of corresponding arginine containing control peptide from citrullinated peptide for all RA patients and controls.
2015-10-25 | E-MTAB-3606 | biostudies-arrayexpress