Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome

ABSTRACT: Here we aimed to contribute to the description of the genetic architecture of Congenital heart defect (CHD) in Down syndrome (DS), and report the results of a genome-wide association study using samples from DS individuals with and without CHD. CHD is a common developmental defect of DS occurring in 40% of cases. This case-control GWAS includes 187 DS with CHD as cases, and 151 DS without CHD as controls.

PROVIDER: EGAS00000000129 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Publications

The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome.

Sailani M Reza MR Makrythanasis Periklis P Valsesia Armand A Santoni Federico A FA Deutsch Samuel S Popadin Konstantin K Borel Christelle C Migliavacca Eugenia E Sharp Andrew J AJ Duriaux Sail Genevieve G Falconnet Emilie E Rabionet Kelly K Serra-Juhé Clara C Vicari Stefano S Laux Daniela D Grattau Yann Y Dembour Guy G Megarbane Andre A Touraine Renaud R Stora Samantha S Kitsiou Sofia S Fryssira Helena H Chatzisevastou-Loukidou Chariklia C Kanavakis Emmanouel E Merla Giuseppe G Bonnet Damien D Pérez-Jurado Luis A LA Estivill Xavier X Delabar Jean M JM Antonarakis Stylianos E SE

Genome research 20130619 9

Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS with ...[more]

PMID: 23783273

Similar Datasets

Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines (congenital heart disease)

Project description:Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines. In this study, we want to identify genes and pathways specifically dysregulated in atrioventricular septal defect and /or atrial septal defect + ventricular septal defect in case of trisomy 21. Total RNA obtained from DS lymphoblastoid cell lines without congenital heart disease compared to cell lines from DS with congenital heart disease.

2012-08-14 | E-GEOD-34457 | biostudies-arrayexpress

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [ATAC-seq Heart]

Project description:Dysplasia of cardiac endothelial cells significantly contributes to congenital heart disease (CHD), the most common congenital disability. The regulatory role of miRNAs in this process remains elusive. This study identified elevated miR-187 expression in embryonic heart endothelial cells from CHD fetuses. Using a conditional knock-in model, we showed that increased miR-187 levels in embryonic endothelial cells induce CHD in homozygous fetal mice, closely mirroring human CHD. Mechanistically, miR-187 targets NIPBL, which is responsible for recruiting the cohesin complex and facilitating chromatin accessibility between enhancers and promoters. Consequently, the endothelial cell-specific upregulation of miR-187 inhibited NIPBL, leading to reduced chromatin accessibility and impaired gene expression, which hindered endothelial cell development and ultimately caused heart septal defects and reduced heart size both in vitro and in vivo. Importantly, exogenous miR-187 expression in human cardiac organoids mimicked developmental defects in the cardiac endothelial cells, reversible by NIPBL replenishment. Our findings establish the miR-187/NIPBL axis as a potent regulator that inhibits cardiac endothelial cell development by attenuating the transcription of numerous endothelial genes, with our mouse and human cardiac organoid models effectively replicating severe defects from minor perturbations.

2024-11-03 | GSE276222 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [ATAC-Seq]

2024-11-03 | GSE276221 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [CUT&Tag]

2024-11-03 | GSE275850 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL

2024-11-03 | GSE275951 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [Heart RNA-Seq]

2024-11-03 | GSE275950 | GEO

Elevated microRNA-187 causes cardiac endothelial dysplasia to promote congenital heart disease through inhibition of NIPBL [Endothelial cell RNA-seq]

2024-11-03 | GSE275849 | GEO

Chemical inhibition of immune signaling rescues defects during heart development in Down syndrome via regulating canonical Wnt pathway

Project description:Congenital heart defects (CHDs) are very frequent in children with Down syndrome (DS), the genetic condition caused by trisomy of chromosome 21 (T21). However, the mechanisms by which T21 causes susceptibility to CHDs are poorly understood. Here, using a combination of human induced pluripotent stem cell (iPSC)-based model and Dp(16)1Yey/+ (Dp16) a mouse model of DS, we identified downregulation of canonical Wnt signaling that is caused by increased dosage of interferon (IFN) receptors encoded on chromosome 21 (HSA21) as a causative factor of CHDs in DS. We differentiated human iPSCs derived from individuals with DS as well as CHDs (DS/CHD iPSCs), and controls (control iPSCs) into cardiac cells. We observed that T21 upregulates IFN signaling, downregulates the canonical WNT pathway, and impairs cardiac differentiation. Furthermore, genetic and pharmacological normalization of IFN pathways restored canonical WNT signaling and rescued defects during cardiac differentiation of DS/CHD iPSCs. Strikingly, treatment with an inhibitor of Janus kinase, which is activated by IFN receptor engagement normalized the canonical Wnt pathway and ameliorated CHDs in Dp16 embryos. Our findings provide new mechanisms underlying CHDs in DS, ultimately aiding the development of novel therapeutic strategies.

2023-06-28 | GSE217557 | GEO

Analysis of copy number variants on chromosome 21 in Down syndrome-associated congenital heart defects

Project description:One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2,000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: 1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and 2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 236 case individuals with DS+AVSD and 290 control individuals with DS and a normal heart using a custom microarray with dense probes tiled on chromosome 21 for array CGH. We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. Pathway analyses indicated copy number perturbtations of genes involved in protein heterotrimerization and histone methylating proteins. Finally, we showed that previously DS+AVSD-associated common CNVs on chromosome 21 are likely false positives. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population.

2017-01-30 | GSE93004 | GEO

Genomic profiling in Down syndrome pediatric acute lymphoblastic leukemia

Project description:Patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have distinct clinical and biological features. Whereas most DS-ALL cases lack the sentinel cytogenetic lesions that guide risk assignment in childhood ALL, JAK2 mutations and CRLF2 overexpression are highly enriched. To further characterize the unique biology of DS-ALL, we performed genome-wide profiling of 58 DS-ALL and 35 non-Down syndrome (NDS) ALL cases by DNA copy number, loss of heterozygosity, gene expression, and methylation analyses. We report novel deletions within the 6p22 histone gene cluster as significantly more frequent in DS-ALL, occurring in 12 DS (24%) and only a single NDS case (3%) (Fisher’s exact p = 0.013). Homozygous deletions yielded significantly lower histone expression levels, and were associated with higher methylation levels, distinct spatial localization of methylated promoters, and enrichment of highly methylated genes for specific pathways and transcription factor binding motifs. Gene expression profiling identified CRLF2 overexpression in nearly half DS-ALL cases, and supervised analysis identified an associated 39-gene signature. However, no expression signature was identified for DS-ALL overall, nor for histone status, suggesting that DS-ALL constitutes several, heterogeneous molecular entities. Characterization of pathways associated with histone deletions and high CRLF2 expression may identify opportunities for novel targeted interventions. This SuperSeries is composed of the SubSeries listed below.

2011-07-12 | GSE21094 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data