Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pericentrin in health and disease: Exploring the patchwork of Pericentrin splice variants.

ABSTRACT: Researchers around the world perform large-scale screens to identify disease-related gene defects in humans. One of the genes of interest is Pericentrin (PCNT), a gene which codes for a large coiled-coil protein with multiple functions in the cell. Recently, we showed that different Pericentrin (Pcnt) splice variants are differentially distributed among sensory tissues of the mouse, emphasizing the importance of a protein's spliceome for the function of a cell.

SUBMITTER: Muhlhans J

PROVIDER: S-EPMC3460829 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Pericentrin in health and disease: Exploring the patchwork of Pericentrin splice variants.

Mühlhans Johanna J Gießl Andreas A

Communicative & integrative biology 20120701 4

Researchers around the world perform large-scale screens to identify disease-related gene defects in humans. One of the genes of interest is Pericentrin (PCNT), a gene which codes for a large coiled-coil protein with multiple functions in the cell. Recently, we showed that different Pericentrin (Pcnt) splice variants are differentially distributed among sensory tissues of the mouse, emphasizing the importance of a protein's spliceome for the function of a cell. ...[more]

PMID: 23060948

Similar Datasets

ABO splice site variants

Project description:ABO*A1-like allele (c.29-5T>C)

| PRJEB82660 | ENA

Xeroderma Pigmentosum: Gene Variants and Splice Variants.

Project description:The nucleotide excision repair (NER) is essential for the repair of ultraviolet (UV)-induced DNA damage, such as cyclobutane pyrimidine dimers (CPDs) and 6,4-pyrimidine-pyrimidone dimers (6,4-PPs). Alterations in genes of the NER can lead to DNA damage repair disorders such as Xeroderma pigmentosum (XP). XP is a rare autosomal recessive genetic disorder associated with UV-sensitivity and early onset of skin cancer. Recently, extensive research has been conducted on the functional relevance of splice variants and their relation to cancer. Here, we focus on the functional relevance of alternative splice variants of XP genes.

| S-EPMC8391564 | biostudies-literature

Contribution of Previously Unrecognized RNA Splice-Altering Variants to Congenital Heart Disease.

Project description:BackgroundKnown genetic causes of congenital heart disease (CHD) explain <40% of CHD cases, and interpreting the clinical significance of variants with uncertain functional impact remains challenging. We aim to improve diagnostic classification of variants in patients with CHD by assessing the impact of noncanonical splice region variants on RNA splicing.MethodsWe tested de novo variants from trio studies of 2649 CHD probands and their parents, as well as rare (allele frequency, <2×10-6) variants from 4472 CHD probands in the Pediatric Cardiac Genetics Consortium through a combined computational and in vitro approach.ResultsWe identified 53 de novo and 74 rare variants in CHD cases that alter splicing and thus are loss of function. Of these, 77 variants are in known dominant, recessive, and candidate CHD genes, including KMT2D and RBFOX2. In 1 case, we confirmed the variant's predicted impact on RNA splicing in RNA transcripts from the proband's cardiac tissue. Two probands were found to have 2 loss-of-function variants for recessive CHD genes HECTD1 and DYNC2H1. In addition, SpliceAI-a predictive algorithm for altered RNA splicing-has a positive predictive value of ≈93% in our cohort.ConclusionsThrough assessment of RNA splicing, we identified a new loss-of-function variant within a CHD gene in 78 probands, of whom 69 (1.5%; n=4472) did not have a previously established genetic explanation for CHD. Identification of splice-altering variants improves diagnostic classification and genetic diagnoses for CHD.RegistrationURL: https://clinicaltrials.gov; Unique identifier: NCT01196182.

| S-EPMC10404383 | biostudies-literature

<i>ABCA4</i> midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease.

Project description:Stargardt disease is caused by variants in the ABCA4 gene, a significant part of which are noncanonical splice site (NCSS) variants. In case a gene of interest is not expressed in available somatic cells, small genomic fragments carrying potential disease-associated variants are tested for splice abnormalities using in vitro splice assays. We recently discovered that when using small minigenes lacking the proper genomic context, in vitro results do not correlate with splice defects observed in patient cells. We therefore devised a novel strategy in which a bacterial artificial chromosome was employed to generate midigenes, splice vectors of varying lengths (up to 11.7 kb) covering almost the entire ABCA4 gene. These midigenes were used to analyze the effect of all 44 reported and three novel NCSS variants on ABCA4 pre-mRNA splicing. Intriguingly, multi-exon skipping events were observed, as well as exon elongation and intron retention. The analysis of all reported NCSS variants in ABCA4 allowed us to reveal the nature of aberrant splicing events and to classify the severity of these mutations based on the residual fraction of wild-type mRNA. Our strategy to generate large overlapping splice vectors carrying multiple exons, creating a toolbox for robust and high-throughput analysis of splice variants, can be applied to all human genes.

| S-EPMC5749174 | biostudies-literature

Project description:The identifcation of alternatively spliced transcript variants specific to particular biological processes in tumours should increase our understanding of cancer. Hypoxia is an important factor in cancer biology and associated splice variants may present new markers to help with planning treatment. A method was developed to analyse alternative splicing in exon array data, using probeset multiplicity to identify genes with changes in expression across their loci, and a combination of the splicing index and a new metric based on the variation of reliability weighted fold changes to detect changes in the splicing patterns. The approach was validated on a cancer/normal sample dataset in which alternative splicing events had been confirmed using RT-PCR. We then analysed ten head and neck squamous cell carcinomas using exon arrays and identified differentially expressed splice variants in five samples with high versus five with low levels of hypoxia-associated genes (Winter et al, 2007; Cancer Res 67:3441-9). The analysis identified a splice variant of LAMA3 (Laminin 3), LAMA3-A, known to be involved in tumour cell invasion and progression. The full-length transcript of the gene (LAMA3-B) did not appear to be hypoxia-associated. The results were confirmed using qualitative real time PCR. In a series of 59 prospectively-collected head and neck tumours (Winter et al, 2007; Cancer Res 67:3441-9), expression of LAMA3-A had prognostic significance whereas LAMA3-B did not. This work illustrates the potential for alternatively spliced transcripts to act as biomarkers of disease prognosis with improved specificity for particular tissues or conditions over assays which do not discriminate between splice variants.

2009-10-07 | GSE18300 | GEO

Analysis of human macrophage splice variants

Project description:gene expression and alternative splicing analysis in human macrophages versus dorsal root ganglia and heart the focus was on alternatively spliced channel proteins in macrophages versus those expressed in excitable tissues

2018-06-30 | GSE112501 | GEO

Splice variants of RAS-translational significance.

Project description:One of the mechanisms potentially explaining the discrepancy between the number of human genes and the functional complexity of organisms is generating alternative splice variants, an attribute of the vast majority of multi-exon genes. Members of the RAS family, such as NRAS, KRAS and HRAS, all of which are of significant importance in cancer biology, are no exception. The structural and functional differences of these splice variants, particularly if they contain the canonical (and therefore routinely targeted for diagnostic purposes) hot spot mutations, pose a significant challenge for targeted therapies. We must therefore consider whether these alternative splice variants constitute a minor component as originally thought and how therapies targeting the canonical isoforms affect these alternative splice variants and their overall functions.

| S-EPMC7680328 | biostudies-literature

TRPV1 splice variants: structure and function.

Project description:The capsaicin receptor (TRPV1) is a non-selective cation channel predominantly expressed in specialized sensory neurons that detect painful stimuli. Although its many functional roles continue to be revealed, it has been confirmed to play a critical role in the perception of peripheral inflammatory hyperalgesia and pain. TRPV1 not only is sensitized and/or activated under a wide range of conditions including inflammation and nerve injury but also undergoes changes in expressed levels in response to these same pathologic conditions. Just as our understanding of the structural requirements of TRPV1 activation has grown, there is evidence that TRPV1 forms heteromeric channel complexes. This review is focused on the structural and functional consequence of TRPV1 splice variants: VR.5'sv, TRPV1b/beta and TRPV1var. Through their co-expression and formation of heteromeric complexes with TRPV1, they have been shown to modulate TRPV1 activation. Moreover, TRPV1 splice variant subunits may also contribute unique properties of activation such as the detection of hypertonic conditions.

| S-EPMC3888216 | biostudies-literature

Oxidative stress modulates KLF6Full and its splice variants.

Project description:Induction of reactive oxygen species (ROS) is a central mechanism in alcohol hepatotoxicity. Krüppel-like factor 6 (KLF6), a transcription factor and a tumor-suppressor gene, is an early-responsive gene to injury; however, the effect of ROS and alcohol on KLF6 induction is unknown. The aim of this study is to investigate the contribution of 2 sources of ROS, cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase (NQO1), and alcohol on the modulation of KLF6(Full) expression, splicing to KLF6_V1 and KLF6_V2, and the effect on TNF?, a downstream target.Endogenous ROS production in CYP2E1-expressing HepG2 cells induced mRNA and protein expression of KLF6(Full) and its splice variants compared to control cells. Incubation with pro-oxidants such as arachidonic acid (AA), ?-naphtoflavone, and H(2) O(2) further enhanced KLF6(Full) and its splice variants. The AA effects on KLF6(Full) and its splice forms were blocked by vitamin E-which prevents lipid peroxidation-and by diallylsulfide-a CYP2E1 inhibitor. Menadione and paraquat, 2 pro-oxidants metabolized via NQO1, induced KLF6(Full) mRNA in a thiol-dependent manner. Antioxidants and an NQO1 inhibitor suppressed the menadione-dependent increase in KLF6(Full) and its splice variants mRNA. Furthermore, primary hepatocytes and livers from chronic alcohol-fed rats, with elevated lipid peroxidation, H(2) O(2) and CYP2E1 but with low GSH, showed a ~2-fold increase in KLF6(Full) mRNA compared to controls. Inhibition of p38 phosphorylation further up-regulated the CYP2E1 and the AA effects on KLF6(Full) mRNA, whereas inhibition JNK and ERK1/2 phosphorylation decreased both. KLF6_V1 but not KLF6(Full) ablation markedly increased TNF? levels in macrophages; thus, TNF? emerges as a downstream target of KLF6_V1.The novel effect of ROS on modulating KLF6(Full) expression and its splice variants could play a relevant role in liver injury and in TNF? regulation.

| S-EPMC3396787 | biostudies-other

Desmin splice variants causing cardiac and skeletal myopathy.

Project description:Desmin myopathy is a hereditary or sporadic cardiac and skeletal myopathy characterised by intracytoplasmic accumulation of desmin reactive deposits in muscle cells. We have characterised novel splice site mutations in the gene desmin resulting in deletion of the entire exon 3 during the pre-mRNA splicing. Sequencing of cDNA and genomic DNA identified a heterozygous de novo A to G change at the +3 position of the splice donor site of intron 3 (IVS3+3A-->G) in a patient with sporadic skeletal and cardiac myopathy. A G to A transition at the highly conserved -1 nucleotide position of intron 2 affecting the splice acceptor site (IVS2-1G-->A) was found in an unrelated patient with a similar phenotype. Expression of genomic DNA fragments carrying the IVS3+3A-->G and IVS2-1G-->A mutations confirmed that these mutations cause exon 3 deletion. Aberrant splicing leads to an in frame deletion of 32 complete codons and is predicted to result in mutant desmin lacking 32 amino acids from the 1B segment of the alpha helical rod. Functional analysis of the mutant desmin in SW13 (vim-) cells showed aggregation of abnormal coarse clumps of desmin positive material dispersed throughout the cytoplasm. This is the first report on the pathogenic potentials of splice site mutations in the desmin gene.

| S-EPMC1734475 | biostudies-other

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