Ontology highlight
ABSTRACT:
PROVIDER: PRJNA802806 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17860476_1.fastq.gz | Fastqsanger.gz | |||
| SRR17860476_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:Cellular models of propionic acidemia were generated using HepG2 cells that were edited by CRISPR gene editing to introduce the pathogenic PCCA c.1285-1416A>G variant associated with propionic acidemia, and a 7 bp deletion of a predicted hnRNP A1 binding motif (c.1285-1411delTAGAACA), which causes complete and partial activation of an 84 bp pseudoexon from intron 14 in the PCCA gene, respectively. Treatment by transfection of splice-switching antisense oligonucleotides (SSO) to block inclusion of the PCCA pseudoexon in mRNA, was used to investigate this as a potential therapeutic strategy.
2023-12-10 | E-MTAB-13549 | biostudies-arrayexpress
Project description:The dataset comprises of seven samples described below
1. Muscle samples from three patients with late-onset PEO caused by compound heterozygous POLG variants
M0305 POLG W748S/R1096C
M1105 POLG A467T/T251I+P587L
M1804 POLG A467T/X1240G+35aa
2. Muscle sample from a patient with adPEO with heterozygous TWNK variants
M0230 TWNK p.Arg357Pro
3. Blood control samples from two patients with late-onset PEO caused by compound heterozygous POLG variants
DNA2012-1630_S1 POLG W748S/R1096C
DNA2018-0168_S2 POLG A467T/T251I+P587L
4. Muscle samples from healthy control individuals
DNA2018-0172_S4 Healthy control 2
DNA2018-0173_S5 Healthy control 1
| EGAD00001004271 | EGA
Project description:Similar to human patients, mice with the compound heterozygous mutation podocin R231Q/A268V, develop a late onset FSGS. Here, we did a proteomics anaylsis of kidney glomeruli before the onset of disease (mice at 3 weeks of age). Analysis of the data reveals that there are no developmental changes in the proteome of compund heterozygous mice.
2020-05-15 | PXD018326 | Pride
Project description:Human fibroblasts from a control or a patient with compound heterozygous variants in KIAA0753 treated with SAG or WNT3A to test responses within canonical Hedgehog or WNT signaling.
2021-08-24 | GSE182286 | GEO
Project description:Novel Compound Heterozygous Variants in LTBP2 Associated with Relative Anterior Microphthalmia
| PRJNA846598 | ENA
Project description:The SLC25A26 gene encodes a mitochondrial inner membrane carrier that transports S-adenosylmethionine (SAM) into the mitochondrial matrix in exchange for S-adenosylhomocysteine (SAH). SAM is the predominant methyl-group donor for most cellular methylation processes, of which SAH is produced as a by-product. Pathogenic, bi-allelic SLC25A26 variants are a recognized cause of mitochondrial disease in children, with a severe neonatal-onset caused by decreased SAM transport activity. We describe two, unrelated adult cases presenting with exercise intolerance and mitochondrial myopathy associated with bi-allelic variants in SLC25A26 which lead to marked respiratory chain deficiencies and mitochondrial histopathological abnormalities in skeletal muscle that are comparable to the early-onset cases. We demonstrate using both mouse and fruit fly models that impairment of SAH, rather than SAM, transport across the mitochondrial membrane is the cause of this milder, later onset clinical phenotype. In this submission, the total larval proteome was assessed at two, three and four days after egg laying in mutants expressing a SAMC.R166Q mutation versus wDah genetic background controls. Our finding of a novel pathomechanism associated with a known disease-causing protein highlights the potential of precision medicine in clinical decision making.
2022-01-19 | PXD026900 | Pride
Project description:Genes involved in distinct diabetes types suggest shared disease mechanisms. We show that rare ONECUT1 coding variants cause monogenic recessive diabetes (neonatal or very early-onset, syndromic) in two unrelated patients, and monogenic dominant diabetes (early adult-onset) in heterozygous relatives of these and 13 additional unrelated cases. Patients heterozygous for rare ONECUT1 coding variants define a subgroup of T2D with early-onset diabetes and other features. In addition, common regulatory ONECUT1 variants are associated with multifactorial T2D. Directed differentiation of human pluripotent stem cells to the pancreatic lineage revealed that loss of ONECUT1 impairs pancreatic progenitor formation and a subsequent endocrine program. We uncovered that ONECUT1 activates the pro-endocrine genes NKX6.1 and NKX2.2 through binding to their cis-regulatory elements. Globally, ONECUT1-directed gene transcription occurs in association with major islet transcription factors, at clusters of pancreas- and endocrine-specific enhancers within open chromatin. ONECUT1 regulates a transcriptional and epigenetic machinery critical for proper endocrine pancreatic development, involved in a spectrum of diabetes, monogenic recessive and dominant, and multifactorial.
2021-11-03 | PXD018887 | Pride
Project description:Complex genetic inheritance is thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human congenital heart defect, left ventricular non-compaction (LVNC), can be caused by a combination of rare, inherited heterozygous missense single nucleotide variants. Whole exome sequencing of a nuclear family revealed novel single nucleotide variants of MYH7 and MKL2 in an asymptomatic father while the offspring with severe childhood-onset LVNC harbored an additional missense variant in the cardiac transcription factor, NKX2-5, inherited from an unaffected mother. Mice bred to compound heterozygosity for the orthologous missense variants in Myh7 and Mkl2 had mild cardiac pathology; the additional inheritance of the Nkx2-5 variant yielded a more severe LVNC-like phenotype in triple compound heterozygotes. RNA sequencing identified genes associated with endothelial and myocardial development that were dysregulated in hearts from triple heterozygote mice and human induced pluripotent stem cell–derived cardiomyocytes harboring the three variants, with evidence for NKX2-5’s contribution as a modifier on the molecular level. These studies demonstrate that the deployment of efficient gene editing tools can provide experimental evidence for complex inheritance of human disease.
2019-05-31 | GSE111394 | GEO
Project description:Complex genetic inheritance is thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human congenital heart defect, left ventricular non-compaction (LVNC), can be caused by a combination of rare, inherited heterozygous missense single nucleotide variants. Whole exome sequencing of a nuclear family revealed novel single nucleotide variants of MYH7 and MKL2 in an asymptomatic father while the offspring with severe childhood-onset LVNC harbored an additional missense variant in the cardiac transcription factor, NKX2-5, inherited from an unaffected mother. Mice bred to compound heterozygosity for the orthologous missense variants in Myh7 and Mkl2 had mild cardiac pathology; the additional inheritance of the Nkx2-5 variant yielded a more severe LVNC-like phenotype in triple compound heterozygotes. RNA sequencing identified genes associated with endothelial and myocardial development that were dysregulated in hearts from triple heterozygote mice and human induced pluripotent stem cell–derived cardiomyocytes harboring the three variants, with evidence for NKX2-5’s contribution as a modifier on the molecular level. These studies demonstrate that the deployment of efficient gene editing tools can provide experimental evidence for complex inheritance of human disease.
2019-05-31 | GSE131322 | GEO
Project description:TEFM variants impair mitochondrial transcription elongation causing childhood-onset neurological disease
| PRJNA768394 | ENA