EGAS00001000425-sc-20130206 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001000351 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:This pilot study aims to generate pilot data to inform future study designs by resequencing the whole exomes of 10 unrelated individuals diagnosed with Congenital Heart Disease (CHD).
| EGAS00001000425 | EGA
Project description:This pilot study aims to generate pilot data to inform future study designs by resequencing the whole exomes of 10 unrelated individuals diagnosed with Bilateral Anophthalmia.
| EGAS00001000356 | EGA
Project description:This pilot study aims to generate pilot data to inform future study designs by resequencing the whole exomes of 10 unrelated individuals diagnosed with Bilateral Anophthalmia.
| EGAD00001000348 | EGA
Project description:This pilot study aims to generate pilot data to inform future study designs in consanguineous families or inbred populations by resequencing the exome of six individuals from five families with neurodevelopmental diseases. For all of these families a single mapping interval containing the causal variant has previously been identified.
| EGAD00001000341 | EGA
Project description:This pilot study aims to generate pilot data to inform future study designs in consanguineous families or inbred populations by resequencing the exome of six individuals from five families with neurodevelopmental diseases. For all of these families a single mapping interval containing the causal variant has previously been identified.
| EGAS00001000024 | EGA
Project description:Congenital heart diseases (CHD) are a class of birth defects affecting ~1% of live births. These conditions are hallmarked by extreme genetic heterogeneity, and therefore, despite a strong genetic component, only a very handful of at-risk loci in CHD have been identified. We herein introduced systems analyses to uncover the hidden organization on biological networks of genomic mutations in CHD, and leveraged network analysis techniques to integrate the human interactome, large-scale patient exomes, the fetal heart spatial transcriptomes, and single-cell transcriptomes of clinical samples. We identified a highly connected network in CHD where most of the member proteins had previously uncharacterized functions in regulating fetal heart development. While genes on the network displayed strong enrichment for heart-specific functions, a sub-group, active specifically at early developmental stages, also regulates fetal brain development, thereby providing mechanistic insights into the clinical comorbidities between CHD and neurodevelopmental conditions. At a small scale, we experimentally verified previously uncharacterized cardiac functions of several novel proteins employing cellular assays and gene editing techniques. At a global scale, our study revealed developmental dynamics of the identified CHD network and observed the strongest enrichment for pathogenic mutations in the network specific to hypoplastic left heart syndrome (HLHS). Our single-cell transcriptome analysis further identified pervasive dysregulation of the network in cardiac endothelial cells and the conduction system in the HLHS left ventricle. Taken together, our systems analyses identified novel factors in CHD, revealed key molecular mechanisms in HLHS, and provides a generalizable framework readily applicable to studying many other complex diseases.
2022-09-26 | GSE197709 | GEO
Project description:Congenital heart disease (CHD) is the most frequent birth defect and affects nearly 1% of newborns. The etiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances have been identified in many forms of syndromic CHD, but next to nothing is known about the impact of DNA copy number changes in non-syndromic CHD. Here we present a sub-megabase resolution array CGH screen of a cohort with CHD as the sole abnormality at the time of diagnosis. Keywords: array CGH In this BAC array CGH study 104 patients with congenital heart disease and some of their parents were screened for DNA copy number changes at submegabase resolution. No dye swap was performed.
2008-05-11 | E-GEOD-7527 | biostudies-arrayexpress
Project description:The heart, the first organ to develop, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of CHD patients survive into adulthood but often suffer premature death from heart failure (HF) and non-cardiac causes 1. To gain insight into poorly understood disease progression, we performed single nuclear RNA sequencing (snRNA-seq) and analyzed more than 157,000 nuclei from donors and CHD patients, including hypoplastic left heart syndrome (HLHS) and Tetralogy of Fallot (TOF), two common forms of cyanotic CHD lesions, as well as, dilated (DCM) and hypertrophic (HCM) cardiomyopathies. We observed CHD specific cell states in cardiomyocytes (CMs) which had evidence of insulin resistance and increased FOXO and CRIM1 expression. Cardiac fibroblasts (CFs) in HLHS had enrichment for a low HIPPO and high YAP cell state characteristic of activated CFs. Imaging Mass Cytometry (IMC) uncovered the spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD in agreement with CHD predilection to infection and cancer 2. Our comprehensive CHD phenotyping provides a roadmap for future personalized medicine in CHD.
2022-06-22 | GSE203274 | GEO
Project description:The heart, the first organ to develop, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of CHD patients survive into adulthood but often suffer premature death from heart failure (HF) and non-cardiac causes 1. To gain insight into poorly understood disease progression, we performed single nuclear RNA sequencing (snRNA-seq) and analyzed more than 157,000 nuclei from donors and CHD patients, including hypoplastic left heart syndrome (HLHS) and Tetralogy of Fallot (TOF), two common forms of cyanotic CHD lesions, as well as, dilated (DCM) and hypertrophic (HCM) cardiomyopathies. We observed CHD specific cell states in cardiomyocytes (CMs) which had evidence of insulin resistance and increased FOXO and CRIM1 expression. Cardiac fibroblasts (CFs) in HLHS had enrichment for a low HIPPO and high YAP cell state characteristic of activated CFs. Imaging Mass Cytometry (IMC) uncovered the spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD in agreement with CHD predilection to infection and cancer 2. Our comprehensive CHD phenotyping provides a roadmap for future personalized medicine in CHD.
2022-06-22 | GSE203273 | GEO
Project description:Haploinsufficiency of transcriptional regulators causes human congenital heart disease (CHD), predicting gene regulatory network (GRN) imbalances. Here, we define transcriptional responses to reduced transcription factor dosage in human iPSCs heterozygous or homozygous for loss of the CHD gene TBX5.
2020-12-14 | GSE137871 | GEO