MicroRNA array studies in Hirschsprung disease
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ABSTRACT:
ORGANISM(S): Merkel cell polyomavirus Human gammaherpesvirus 8 Human alphaherpesvirus 1 JC polyomavirus Human betaherpesvirus 6B Homo sapiens Human immunodeficiency virus 1 Herpesvirus saimiri (strain 11) Human betaherpesvirus 5
PROVIDER: GSE200369 | GEO | 2024/05/02
REPOSITORIES: GEO
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Project description:MicroRNA array studies in Hirschsprung disease
| PRJNA824332 | ENA
Project description:Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a functional association study (pathway-based analysis) has been conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung's disease that have been further validated in a larger population of 146 trios. The study revealed a strong association of 10 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes to the disease. A total of 10 new loci among the preselected candidates were found to be significantly associated to HSCR. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.
2012-03-18 | GSE33732 | GEO
Project description:Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a functional association study (pathway-based analysis) has been conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung's disease that have been further validated in a larger population of 146 trios. The study revealed a strong association of 10 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes to the disease. A total of 10 new loci among the preselected candidates were found to be significantly associated to HSCR. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases. DNA derived from peripheral blood was hybridized to Affymetrix GeneChip® 500K mapping arrays. In total, 53 trios were analyzed consisting of affected child and their unaffected parents.
2012-03-18 | E-GEOD-33732 | biostudies-arrayexpress
Project description:Hirschsprung disease (HSCR) is a neurocristopathy characterized by absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. The HSCR phenotype is highly variable with respect to gender, segment length of aganglionosis, familiality and the presence of additional anomalies. By molecular genetic analysis, a minimum of 11 neuro-developmental genes (RET, GDNF, NRTN, SOX10, EDNRB, EDN3, ECE1, ZFHX1B, PHOX2B, KIAA1279, TCF4) are known to harbor rare high-penetrance mutations that confer a large risk to the bearer. In addition, two other genes (RET, NRG1) harbor common low-penetrance polymorphisms that contribute only partially to risk and act as genetic modifiers. To broaden this search, we examined whether a set of 67 proven and candidate HSCR genes harbored additional modifier alleles. In this pilot study, we utilized a custom-designed array CGH with ~33,000 test probes at an average resolution of ~185bp to detect gene-sized or smaller copy number variants (CNVs) within these 67 genes in 18 heterogeneous HSCR patients. Using stringent criteria, we identified CNVs at three loci (MAPK10, ZFHX1B, SOX2) that are novel, involve regulatory and coding sequences of these neuro-developmental genes and show association with HSCR in combination with other congenital anomalies. Two-condition experiment: Patient vs. Control. Sex-matched controls. Technical replicates: 4 were examined twice and 3 were studied in triplicate. Technical replicates: 408.3.1, 408.3.2 Technical replicates: 300.3.1, 300.3.2 Technical replicates: 354.3.1, 354.3.2 Technical replicates: 355.3.1, 355.3.2 Technical replicates: 63.3.1, 63.3.2, 63.3.3 Technical replicates: 122.7.1, 122.7.2, 122.7.3 Technical replicates: 413.3.1, 413.3.2, 413.3.3
2011-05-06 | E-GEOD-29051 | biostudies-arrayexpress
Project description:Hirschsprung disease (HSCR) is a neurocristopathy characterized by absence of intramural ganglion cells along variable lengths of the gastrointestinal tract. The HSCR phenotype is highly variable with respect to gender, segment length of aganglionosis, familiality and the presence of additional anomalies. By molecular genetic analysis, a minimum of 11 neuro-developmental genes (RET, GDNF, NRTN, SOX10, EDNRB, EDN3, ECE1, ZFHX1B, PHOX2B, KIAA1279, TCF4) are known to harbor rare high-penetrance mutations that confer a large risk to the bearer. In addition, two other genes (RET, NRG1) harbor common low-penetrance polymorphisms that contribute only partially to risk and act as genetic modifiers. To broaden this search, we examined whether a set of 67 proven and candidate HSCR genes harbored additional modifier alleles. In this pilot study, we utilized a custom-designed array CGH with ~33,000 test probes at an average resolution of ~185bp to detect gene-sized or smaller copy number variants (CNVs) within these 67 genes in 18 heterogeneous HSCR patients. Using stringent criteria, we identified CNVs at three loci (MAPK10, ZFHX1B, SOX2) that are novel, involve regulatory and coding sequences of these neuro-developmental genes and show association with HSCR in combination with other congenital anomalies.
2011-05-06 | GSE29051 | GEO
Project description:Objective Hirschsprung disease (HSCR) is a severe congenital disorder affecting 1:5000 live births. HSCR results from failure of enteric nervous system (ENS) progenitors to fully colonise the gastrointestinal tract during embryonic development. This leads to aganglionosis in the distal bowel, resulting in disrupted motor activity and impaired peristalsis. Currently, the only viable treatment option is surgical resection of the aganglionic bowel. However, patients frequently suffer debilitating, lifelong symptoms, with multiple surgical procedures often necessary. Hence, alternative treatment options are crucial. An attractive strategy involves the transplantation of ENS progenitors generated from human pluripotent stem cells (hPSCs). Design ENS progenitors were generated from hPSCs using an accelerated protocol and characterised, in detail, through a combination of single cell RNA-sequencing, protein expression analysis and calcium imaging. We tested ENS progenitors’ capacity to integrate and restore functional responses in HSCR colon, after ex vivo transplantation to organotypically cultured patient-derived colonic tissue, using organ bath contractility. Results We found that our protocol consistently gives rise to high yields of cell populations exhibiting transcriptional and functional hallmarks of early ENS progenitors. Following transplantation, hPSC-derived ENS progenitors integrate, migrate and form neurons within explanted human HSCR colon samples. Importantly, the transplanted HSCR tissue displayed increased basal contractile activity and increased responses to electrical stimulation compared to control tissue. Conclusion Our findings demonstrate, for the first time, the potential of hPSC-derived ENS progenitors to repopulate and restore functional responses in human HSCR patient colonic tissue.
2024-09-30 | GSE252061 | GEO
Project description:<p>Hirschsprung disease (HSCR) is a birth defect resulting from the absence of nerve (ganglion) cells in the gastrointestinal tract. Hirschsprung disease has a population incidence of 1/5,000 live births and most often occurs as an isolated condition. However, approximately 30% of HSCR cases are associated with other birth defects such as Down syndrome, deafness, hypopigmentation, and Congenital Central Hypoventilation syndrome (CCHS). Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described. The goal of the research study is to identify genes harboring causative HSCR mutations and to better understand the complex inheritance of HSCR in families using whole genome mapping and sequencing studies with functional follow-up of candidate genes and variants. We intend to ascertain the frequency with which mutations in any human gene lead to familial and isolated forms of HSCR. Clinical information is collected to allow investigation of possible genotype - phenotype correlations.</p> <p>The subject population consists of individuals diagnosed with HSCR and their unaffected relatives. Individuals/families are ascertained through support groups, web-based listings of research studies and genetic testing services, an educational study website, and referrals from genetic counselors and physicians. Blood, or tissue, samples are requested from affected individuals and their unaffected relatives.</p>
| phs000497.v1.p1 | EGA
Project description:<p>Hirschsprung disease (HSCR) is a birth defect resulting from the absence of nerve (ganglion) cells in the gastrointestinal tract. Hirschsprung disease has a population incidence of 1/5,000 live births and most often occurs as an isolated condition. However, approximately 30% of HSCR cases are associated with other birth defects such as Down syndrome, deafness, hypopigmentation, and Congenital Central Hypoventilation syndrome (CCHS). Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described. The goal of the research study is to identify genes harboring causative HSCR mutations and to better understand the complex inheritance of HSCR in families using whole genome mapping and sequencing studies with functional follow-up of candidate genes and variants. We intend to ascertain the frequency with which mutations in any human gene lead to familial and isolated forms of HSCR. Clinical information is collected to allow investigation of possible genotype - phenotype correlations.</p> <p>The subject population consists of individuals diagnosed with HSCR and their unaffected relatives. Individuals/families are ascertained through support groups, web-based listings of research studies and genetic testing services, an educational study website, and referrals from genetic counselors and physicians. Blood, or tissue, samples are requested from affected individuals and their unaffected relatives.</p>
| phs000497 | dbGaP
Project description:MicroRNAs are important regulators of cell-autonomous gene expression that influences many biological processes. They are also released from cells and are present in virtually all body fluids, including blood, urine, saliva, sweat, and milk. The functional role of extracellular miRNAs is controversial, and irrefutable demonstration of miRNA uptake by cells and canonical miRNA function is still lacking. Here we show that miRNAs are present at high levels in milk of lactating mice. To investigate intestinal uptake of miRNAs in newborn mice, we employed genetic models in which newborn miR-375 and miR-200c KO mice received milk from wildtype foster mothers. Analysis of intestinal epithelium, blood, liver and spleen revealed no evidence for miRNA uptake. miR-375 levels in hepatocytes were at the limit of detection and remained orders of magnitude below the threshold for target gene regulation (between 1000 and 10,000 copies/cell). Furthermore, our study revealed rapid degradation of milk miRNAs in the intestinal fluid. Together, our results indicate a nutritional rather than gene regulatory role of miRNAs in milk of newborn mice.
2015-08-19 | GSE70201 | GEO
Project description:We compared the profile of miRNAs expressed in HEK293 and MRC5 cells that overexpressed KRASG12V to those expressed in parental cells that harbored wild-type KRAS. The results indicated that a subset of miRNAs was significantly down-regulated in KRASG12V transfected two cells. To address the functional relevance of miRNAs in KRAS mutant cancers, we transfected exogenous KRASG12V into HEK293 and MRC5 cells with wild type KRAS genes, and we comprehensively profiled the dysregulated miRNAs.
2015-09-01 | E-GEOD-60370 | biostudies-arrayexpress