Search results for " Sequence analysis"
showing 10 items of 294 documents
CAF-like state in primary skin fibroblasts with constitutional BRCA1 epimutation sheds new light on tumor suppressor deficiency-related changes in he…
2016
Constitutive epimutations of tumor suppressor genes are increasingly considered as cancer predisposing factors equally to sequence mutations. In light of the emerging role of the microenvironment for cancer predisposition, initiation, and progression, we aimed to characterize the consequences of a BRCA1 epimutation in cells of mesenchymal origin. We performed a comprehensive molecular and cellular comparison of primary dermal fibroblasts taken from a monozygous twin pair discordant for recurrent cancers and BRCA1 epimutation, whose exceptional clinical case we previously reported in this journal. Comparative transcriptome analysis identified differential expression of extracellular matrix-r…
iGEMS: an integrated model for identification of alternative exon usage events.
2016
Abstract DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with (n = 9) or without (n = 8) the anti-diabe…
The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity.
2007
Epithelial to mesenchymal transition (EMT) is implicated in the progression of primary tumours towards metastasis and is likely caused by a pathological activation of transcription factors regulating EMT in embryonic development. To analyse EMT-causing pathways in tumouri-genesis, we identified transcriptional targets of the E-cadherin repressor ZEB1 in invasive human cancer cells. We show that ZEB1 repressed multiple key determinants of epithelial differentiation and cell–cell adhesion, including the cell polarity genes Crumbs3, HUGL2 and Pals1-associated tight junction protein. ZEB1 associated with their endogenous promoters in vivo, and strongly repressed promotor activities in reporter …
CD40 activation in human pancreatic islets and ductal cells.
2008
Aims/hypothesis: CD40 expression on non-haematopoietic cells is linked to inflammation. We previously reported that CD40 is expressed on isolated human and non-human primate islets and its activation results in secretion of IL-8, macrophage inflammatory protein 1-beta (MIP-1β) and monocyte chemoattractant protein-1 (MCP-1) through nuclear factor-κB and extracellularly regulated kinases 1/2 pathways. The objective of this study was to identify the pattern of gene expression, and to study viability and functionality affected by CD40-CD40 ligand (CD40L) interaction in human islets. Furthermore, we have studied the CD40-mediated cytokine/chemokine profile in pancreatic ductal cells, as they are…
A 588-gene microarray analysis of the peripheral blood mononuclear cells of spondyloarthropathy patients
2002
OBJECTIVES: To identify genes which are more highly expressed in the peripheral blood mononuclear cells (PBMC) of patients with spondyloarthropathy (SpA), rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in comparison to normal subjects. METHODS: A 588-gene microarray was used as a screening tool to select a panel of such genes from PBMC of these subjects and of normal subjects. Results were then validated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The following genes were more highly expressed in arthritis patients than in normal subjects: macrophage differentiation marker MNDA (myeloid nuclear differentiation antigen), MRP8 and MRP14 (migratory inhibitor…
Endometrial gene expression analysis at the time of embryo implantation in women with unexplained infertility
2009
Successful embryo implantation depends on the quality of the embryo, as well as on the receptivity of the endometrium. The aim of this study was to investigate the endometrial gene expression profile in women with unexplained infertility in comparison with fertile controls at the time of embryo implantation in order to find potential predictive markers of uterine receptivity and to identify the molecular mechanisms of infertility. High-density oligonucleotide gene arrays, comprising 44 000 gene targets, were used to define the endometrial gene expression profile in infertile (n = 4) and fertile (n = 5) women during the mid-secretory phase (day LH + 7). Microarray results were validated usin…
Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome
2010
Objective To determine whether luteal phase endometrial transcriptome is altered in obese women during the window of implantation (WOI), considering the presence of infertility, fat distribution and association with polycystic ovary syndrome (PCOS). Design Prospective study. Setting University-affiliated infertility clinic, between May 2007 and March 2009. Patient(s) One control group of women with normal weight (n = 4), and four study groups of obese women (n = 6 each one) according to the association with infertility, PCOS, and ovarian stimulation. Intervention(s) The endometrium was biopsied 7 days after LH surge or hCG administration in 28 women. Main Outcome Measure(s) Endometrial gene…
Single-Nucleotide Polymorphism Array-Based Characterization of Ring Chromosome 18
2012
Objective To study genotype–phenotype correlation of ring chromosome 18 [r(18)] in 9 patients with 46,XN karyotype. Study design In 9 patients with a de novo 46,XN,r(18) karyotype (7 females, 2 males), we performed high-resolution single-nucleotide polymorphism array analysis (Illumina Human Omni1-QuadV1 array in 6 patients, Affymetrix 6.0 array in 3 patients), investigation of parental origin, and genotype–phenotype correlation. Results No breakpoint was recurrent. Single metaphases with loss of the ring, double rings, or secondarily rearranged rings were found in some cases, but true mosaicism was present in none of these cases. In 3 patients, additional duplications in 18p (of 1.4 Mb, 2 …
Array comparative genomic hybridization analysis of chromosomal imbalances and their target genes in gastrointestinal stromal tumors.
2007
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The tumors characteristically harbor KIT or PDGFRA mutations, and mutant tumors respond to imatinib mesylate (Glivectrade mark). Chromosomal imbalances resulting in altered gene dosage are known to have a role in the molecular pathogenesis of these tumors, but the target genes remain to be identified. The present study aimed to identify some of these genes. In total, 35 GIST samples were screened for chromosomal imbalances by array-based comparative genomic hybridization. A cDNA array was used to define the minimal common overlapping areas of DNA copy number change. Eight confirmative, …
Genome-wide analysis for micro-aberrations in familial exstrophy of the bladder using array-based comparative genomic hybridization
2007
OBJECTIVE: Exstrophy of the bladder (EB) is part of the bladder-exstrophy-epispadias complex (BEEC). Because familial occurrence of BEEC is rare, exogenous factors are thought to play a major role in the etiology of most BEEC cases. We aimed to investigate a possible genetic basis of BEEC in a consanguineous kindred of Moroccan origin with three members showing the same phenotypic expression of BEEC. PATIENTS AND METHODS: The three affected males (two cousins and their maternal uncle) all presenting with nonsyndromic classic EB, were born in Morocco or The Netherlands. One Moroccan patient had an open bladder surface for 22 years due to late surgical reconstruction, avoided upright posture …