Affymetrix SNP array data for short-segment Hirschsprung trios
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33732 | GEO | 2012/03/18
SECONDARY ACCESSION(S): PRJNA148445
REPOSITORIES: GEO
Similar Datasets
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:To address the role of miRNAs in Hirschsprund disease (HSCR), we carried out microRNA (miRNA) array analysis by using human intestinal samples obtained from HSCR patients and controls, and identified dysregulated miRNAs involved in the pathogenesis of HSCR.
2024-05-02 | GSE200369 | 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:Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features. high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. Only 21 samples with potentially pathogenic CNVs are included in this records
2014-04-02 | E-GEOD-56422 | biostudies-arrayexpress
Project description:Purpose: Hirschsprung’s disease (HSCR, OMIM 142623) represents one of the main causes of neonatal intestinal obstruction. It is caused by dysfunction of neural crest cells (NCCs) and their progeny during development of the enteric nervous system (ENS). HSCR is considered a multifactorial disorder, however, associated risk genes only account for a minority of cases. Consequently, defining disease-relevant variants is still a demanding task. Methods: To reduce the number of candidate genes identified by Whole Exome Sequencing (WES) and to examine their disease-causing relevance, we established a complementary study pipeline including transcriptome data of murine embryonic ENS-relevant tissues, literature and database searches, in silico network analyses as well as functional assays using genome-edited candidate-specific cell clones. Results: Applying this strategy on a pilot set of two HSCR patients and their non-affected parents led to the identification of four novel HSCR candidate genes: ATP7A, SREBF1, ABCD1 and PIAS2. This candidate gene selection was corroborated by the discovery of further rare variants in additional HSCR cases. Moreover, expression analyses revealed that all four genes are expressed in embryonic murine gastrointestinal tissues. Functional analyses using candidate gene-specific, neuronal-like CRISPR/Cas9-edited knockout cell clones demonstrated impaired differentiation, proliferation and/or cell survival capacity. Conclusions: Taken together, the presented study pipeline was proven to be suitable for the selection and validation of candidate genes as well as to gain insight into underlying pathomechanisms of HSCR.
2020-10-12 | GSE144442 | GEO
Project description:Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features.
2014-04-02 | GSE56422 | GEO
Project description:Long non-coding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only, to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC), using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA-expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes, and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2= 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR=1.25 per log2 expression unit, 95%CI 1.04-1.52, p value = 0.02).
2022-01-17 | E-MTAB-11367 | biostudies-arrayexpress