Project description:Congenital Heart Disease (CHD) accounts for 1% of birth defects, and while large-scale genetic studies have uncovered genes associated with CHDs, identifying causal mutations remains a challenge. We hypothesized that genetic determinants for CHDs could be found in the protein interactomes of GATA4 and TBX5, two cardiac transcription factors (TFs) associated with CHDs. Defining their interactomes in human cardiac progenitors via affinity purification-mass spectrometry and integrating the results with genetic data from the Pediatric Cardiac Genomic Consortium (PCGC) revealed an enrichment of de novo variants among proteins that interact with GATA4 or TBX5. A consolidative score designed to prioritize TF interactome members based on distinctive variant, gene and proband features identified numerous likely CHD-causing genes, including the epigenetic reader GLYR1. GLYR1 and GATA4 widely co-occupied cardiac developmental genes resulting in co-activation and the GLYR1 variant associated with CHD disrupted interaction with GATA4. This integrative proteomic and genetic approach provides a framework for prioritizing and interrogating the contribution of genetic variants in CHD and can be extended to other genetic diseases.

2022-07-05 | PXD022091 | Pride

Identification of Copy Number Variants in Patients with Hypoplastic Left Heart Syndrome and Other Congenital Heart Defects

Project description:Hypoplastic left heart syndrome (HLHS) is a heterogeneous, lethal combination of congenital malformations that result in a heart unable to sustain systemic circulation. The genetic determinants of this disorder are largely unknown. Evidence of copy number variants (CNVs) contributing to the genetic etiology of HLHS and other congenital heart defects (CHDs) has been mounting. However, the functional effects of such CNVs have not been examined, particularly in cases where the variant of interest is found in only a single patient. Initially whole-genome SNP microarrays were employed to detect CNVs in two patient cohorts (N = 70 total) predominantly diagnosed with some form of nonsyndromic HLHS. We discovered 16 rare variants adjacent to or overlapping 20 genes associated with cardiovascular or premature lethality phenotypes in mouse knockout models. Fifteen of the 16 variants were identified in separate patients, suggestive of a private mutation model of disease. We evaluated the impact of selected variants on the expression of nine of these genes through quantitative PCR on cDNA derived from patient heart tissue. Four genes displayed significantly altered expression in patients with an overlapping or proximal CNV verses patients without such CNVs. Thus, rare and private genomic imbalances perturb transcription of genes affecting cardiogenesis in a subset of nonsyndromic HLHS patients. Some of these genes influence extracellular matrix structure, cardiac neural crest development, and coronary vascularization. A total of 70 samples from CHD patients, mostly with nonsyndromic HLHS, yielded SNP genotypes and probe intensity ratios of sufficient quality for CNV identification. Two classes of CNV detection algorithms (HMM and CBS) were employed. After identification, concordant entries were subjected to selection criteria based on rarity and gene content, which produced putative candidate genes for follow-up experiments.

2015-12-10 | E-GEOD-66032 | biostudies-arrayexpress

Expression data of osteosarcoma 143B and metastatic variants

Project description:Expression data of osteosarcoma 143B and metastatic variants

| PRJNA780937 | ENA

Expression data from SETD5-expressing 3T3-L1 cells.

Project description:Expression data from SETD5-expressing 3T3-L1 cells.

| PRJNA762098 | ENA

Expression data from second oncogene expressing Melanoma Cells.

Project description:Expression data from second oncogene expressing Melanoma Cells.

| PRJNA506456 | ENA

Expression data from heart expressing cofilin-1(Th25) variants

Project description:We used microarrays to detail the global programme of gene expression underlying cardiac dysfunction and identified distinct classes of up-regulated genes during this process.

2022-12-07 | GSE218891 | GEO

Abcg2 expressing VESC in adult heart

Project description:Abcg2 expressing vascular endothelial stem cells (AbcVESC) in adult murine heart promote vessel regeneration after cardiac infarction injury. Here we compared H3.3 K4Me3, K27Me3 modifications between AbcVESC and mature EC

2023-05-31 | GSE225987 | GEO

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