Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features (human)

ABSTRACT: Spliceosome malfunction causes neurodevelopmental disorders with overlapping features (human)

PROVIDER: PRJNA1031628 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR26499829_1.fastq.gz	Fastqsanger.gz
	SRR26499829_2.fastq.gz	Fastqsanger.gz
	SRR26499830_1.fastq.gz	Fastqsanger.gz
	SRR26499830_2.fastq.gz	Fastqsanger.gz
	SRR26499831_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 48

Similar Datasets

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Project description:Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

| PRJNA1031622 | ENA

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features (fly)

Project description:Spliceosome malfunction causes neurodevelopmental disorders with overlapping features (fly)

| PRJNA1031629 | ENA

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Project description:Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50-deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function.

2023-10-24 | GSE246137 | GEO

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features (fly)

Project description:Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including seven recurrent variants in 30 individuals) and six individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function of the Drosophila orthologs, U2af50 and Prp19, led to lethality, abnormal mushroom body (MB) patterning, and social deficits, differentially rescued by wild- type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50 deficient flies. Upon re-analysis of negative clinical exomes followed by data sharing, we further identified six NDD patients carrying RBFOX1 missense variants which, by in vitro testing, showed loss of function. Our study implicates three splicing factors as NDD causative genes and establishes a genetic network with hierarchy underlying human brain development and function.

2023-10-25 | GSE246136 | GEO

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features (human)

Project description:Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including seven recurrent variants in 30 individuals) and six individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function of the Drosophila orthologs, U2af50 and Prp19, led to lethality, abnormal mushroom body (MB) patterning, and social deficits, differentially rescued by wild- type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50 deficient flies. Upon re-analysis of negative clinical exomes followed by data sharing, we further identified six NDD patients carrying RBFOX1 missense variants which, by in vitro testing, showed loss of function. Our study implicates three splicing factors as NDD causative genes and establishes a genetic network with hierarchy underlying human brain development and function.

2023-10-25 | GSE246135 | GEO

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features.

| S-EPMC10760965 | biostudies-literature

Gain and loss of function variants in EZH1 disrupt neurogenesis and cause overlapping neurodevelopmental disorders.

Project description:Gain and loss of function variants in EZH1 disrupt neurogenesis and cause overlapping neurodevelopmental disorders.

| PRJNA942909 | ENA

Gene dosage imbalance in neurodevelopmental disorders

Project description:Gene dosage imbalance in neurodevelopmental disorders

| PRJNA287736 | ENA

GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders Mice

Project description:Mice experiment for GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders

2024-03-28 | E-MTAB-13475 | biostudies-arrayexpress

GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders Organoid

Project description:Mice experiment for GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders

2024-04-15 | E-MTAB-13477 | biostudies-arrayexpress

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