Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A long noncoding RNA, LOC157273, is the effector transcript at the chromosome 8p23.1-PPP1R3B metabolic traits and type 2 diabetes risk locus

ABSTRACT: A long noncoding RNA, LOC157273, is the effector transcript at the chromosome 8p23.1-PPP1R3B metabolic traits and type 2 diabetes risk locus

PROVIDER: PRJNA596788 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR10742000_1.fastq.gz	Fastqsanger.gz
	SRR10742000_2.fastq.gz	Fastqsanger.gz
	SRR10741989_1.fastq.gz	Fastqsanger.gz
	SRR10741989_2.fastq.gz	Fastqsanger.gz
	SRR10741990_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

A long noncoding RNA, LOC157273, is the effector transcript at the chromosome 8p23.1-PPP1R3B metabolic traits and type 2 diabetes risk locus

Project description:Genome wide association studies (GWAS) identified a chromosome 8 locus associated with fasting glucose (FG), insulin (FI) and lipid levels that is located near PPP1R3B (a gene which encodes the catalytic subunit of a serine/threonine protein phosphatase that promotes hepatic glycogen storage upon insulin signaling). The lead SNP rs4841132 lies in a long non-coding RNA (lncRNA) LOC157273, 175 kb away and is not in linkage disequilibrium with PPP1R3B. Our analysis of the FANTOM consortium data shows LOC157273 is expressed only in hepatocytes. We hypothesized that LOC157273 is the causal candidate that acts upstream of PPP1R3B to regulate FG and FI. Human whole transcriptome sequencing was performed to understand which other genes undergo changes in expression levels upon silencing of LOC157273.

2020-04-01 | GSE142385 | GEO

A Long Non-coding RNA, LOC157273, Is an Effector Transcript at the Chromosome 8p23.1-PPP1R3B Metabolic Traits and Type 2 Diabetes Risk Locus.

Project description:Aims:Causal transcripts at genomic loci associated with type 2 diabetes (T2D) are mostly unknown. The chr8p23.1 variant rs4841132, associated with an insulin-resistant diabetes risk phenotype, lies in the second exon of a long non-coding RNA (lncRNA) gene, LOC157273, located 175 kilobases from PPP1R3B, which encodes a key protein regulating insulin-mediated hepatic glycogen storage in humans. We hypothesized that LOC157273 regulates expression of PPP1R3B in human hepatocytes. Methods:We tested our hypothesis using Stellaris fluorescent in situ hybridization to assess subcellular localization of LOC157273; small interfering RNA (siRNA) knockdown of LOC157273, followed by RT-PCR to quantify LOC157273 and PPP1R3B expression; RNA-seq to quantify the whole-transcriptome gene expression response to LOC157273 knockdown; and an insulin-stimulated assay to measure hepatocyte glycogen deposition before and after knockdown. Results:We found that siRNA knockdown decreased LOC157273 transcript levels by approximately 80%, increased PPP1R3B mRNA levels by 1.7-fold, and increased glycogen deposition by >50% in primary human hepatocytes. An A/G heterozygous carrier (vs. three G/G carriers) had reduced LOC157273 abundance due to reduced transcription of the A allele and increased PPP1R3B expression and glycogen deposition. Conclusion:We show that the lncRNA LOC157273 is a negative regulator of PPP1R3B expression and glycogen deposition in human hepatocytes and a causal transcript at an insulin-resistant T2D risk locus.

| S-EPMC7367044 | biostudies-literature

Assessment Of Long Noncoding RNA CCAT1 In Colorectal Cancer Patients

Project description:1. Evaluate the diagnostic value of long noncoding RNA (CCAT1) expression by RT-PCR in peripheral blood in colorectal cancer patients versus normal healthy control personal. 2. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in diagnosis of colorectal cancer patients & its relation to tumor staging. 3. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in precancerous colorectal diseases. 4. Compare long noncoding RNA (CCAT1) expression with traditional marker; carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) in diagnosis of colorectal cancer.

| 2330122 | ecrin-mdr-crc

Nascent transcript O-MAP reveals the molecular architecture a single-locus subnuclear compartment built by RBM20 and the TTN noncoding RNA

Project description:We here adapt Oligonucleotide-mediated proximity-interactome mapping (O-MAP), a novel RNA-targeted microenvironment-mapping method, to biochemically characterize the molecular neighborhoods near individual genomic loci. By targeting O-MAP to introns within the TTN pre-mRNA, we have systematically mapped the chromatin loci, RNAs, and proteins within a cardiomyocyte-specific "RNA factory" nucleated on these TTN-derived noncoding transcripts. This revealed an unanticipated compartmental architecture that organizes trans-chromosomal domains into a hub of transcriptionally silenced chromatin, and which recruits dozens of unique RNA-binding and chromatin-scaffolding factors, including QKI and SAFB, along with their target transcripts. Loss of the cardiac-specific splicing factor RBM20, a master regulator of TTN splicing, remodels nearly every facet of factor architecture, suggesting new mechanisms in RBM20-driven dilated cardiomyopathy. This establishes O-MAP as a pioneering method for probing single-locus, microcompartment-level interactions that are opaque to conventional tools, and suggests new mechanisms by which coding genes can "moonlight" as nuclear-architectural noncoding RNAs.

2024-10-08 | MSV000096046 | MassIVE

Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

Project description:Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

| S-EPMC4307976 | biostudies-literature

High-resolution physical and transcript map of human chromosome 2p21 containing the sitosterolaemia locus.

Project description:Sitosterolaemia (phytosterolaemia) is an autosomal recessive disorder characterised by the presence of tendon xanthomas in the face of normal or mildly elevated plasma cholesterol levels, premature atherosclerotic disease and has diagnostically elevated plasma and tissue plant sterol concentrations. Affected individuals show an increased absorption of both cholesterol and sitosterol from the diet, decreased bile clearance of these sterols and their metabolites resulting in markedly expanded whole body cholesterol and sitosterol pools. The defective gene is therefore hypothesised to play a crucial role in regulating dietary cholesterol absorption, and its elucidation may shed light on these molecular processes. We have previously localised the defective gene to human chromosome 2p21, between microsatellite markers D2S1788 and D2S1352, a distance of approximately 15 cM. Recently, the disease locus interval has been narrowed to lie between D2S2294 and D2S2291/D2S2174. We have constructed a high-resolution YAC and BAC contigs by using known STSs and generating novel STSs from the minimal interval. Eight previously identified genes and 60 ESTs were mapped to these contigs. The BAC contig contains 60 BAC clones and 108 STSs and encompasses a physical distance of approximately 2.0 cM between microsatellite markers D2S2294 and D2S2291. These results will not only facilitate cloning of the sitosterolaemia gene, but also other disease genes located in this region, and accelerate sequencing of the corresponding genomic clones.

| S-EPMC1350990 | biostudies-literature

Epigenome-wide association in the METSIM cohort identifies 22 novel loci for diabetes and metabolic syndrome traits

Project description:In this study, we examined the association of DNA methylation with metabolic traits in humans using adipose tissue samples from the Metabolic Syndrome in Men (METSIM) cohort. The METSIM cohort has been thoroughly characterized for longitudinal clinical data of metabolic traits including a 3-point oral glucose tolerance test, cardiovascular disorders, diabetes complications, drug and diet questionnaire, as well as high density genotyping, and genome-wide expression in adipose. We performed epigenome-wide association studies on clinical traits using reduced representation bisulfite sequencing data and identified 61 signifiant associations for metabolic syndrome traits, corresponding to 25 unique loci. These associations include previously known genes, FASN, RXRA, MSH2, and MSH6, as well as 22 loci harboring 18 new candidate genes for diabetes and obesity in humans.

2017-01-01 | GSE87893 | GEO

The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression (ChIP-Seq)

Project description:The long noncoding RNA Malat1 impacts the differentiation of effector and memory CD8+ T cell subsets by virtue of preferential epigenetic repression of memory-associated genes in terminal effector cells through an interaction with Ezh2

2022-05-18 | GSE203090 | GEO