Control vs. Th3 beta thalassemia kidney
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE36312 | GEO | 2012/03/07
SECONDARY ACCESSION(S): PRJNA153349
REPOSITORIES: GEO
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Project description:a comparison of a control and a mutant condition (Th3) of the Hemoglobin Beta major and minor chain, used as Beta Thalassemia mouse model. 4 controls and 4 mutants
2012-03-07 | E-GEOD-36312 | biostudies-arrayexpress
Project description:Delta-Beta thalassemia is an unusual variant of thalassemia caused by large deletions in the β globin gene cluster involving δ- and β-globin genes. The mutations are characterized by high fetal hemoglobin with significant phenotypic diversity. Routinely used diagnostic tests targeting point mutations and small insertions, deletions of the β-globin gene are not suitable for detection of large deletion mutations. This is overcome by either direct globin chain synthesis analysis or beta-cluster gene analysis using different methods. In the current study, we use direct globin chain analysis to diagnose a family with δβ-thalassemia using high resolution mass spectrometry.
2024-08-09 | PXD044775 | Pride
Project description:β-thalassemia major can be caused by homozygous mutations of the HBB gene, most of the cases are inherited from parents who both have β-thalassemia minor. Herein, we show that a mosaic paternal uniparental isodisomy of chromosome 11p14.3-15.5 is associated with β-thalassemia major in a patient with β-thalassemia minor-that evolved to β-thalassemia major. From this case, we suggest that analysis of HBB gene for non-hematopoietic tissues should be performed in late-onset β-thalassemia major patients. Keywords: genomic
2007-05-22 | GSE7847 | GEO
Project description:β-hemoglobin disorders, such as sickle cell disease (SCD) and β-thalassemia (BT), are the most common inherited monogenic blood disorders globally. Despite decades of research, there are only four FDA-approved medications available for the management of SCD with hydroxyurea (HU) being the most widely used drug that partially benefits patients by inducing fetal hemoglobin (HbF) production. On the other hand, there are no approved oral drugs currently available for β-thalassemia patients. To our knowledge, there are currently no well-characterized erythroid progenitor cell lines available that can accurately replicate the pathophysiology of SCD and BT while also having the same genetic background apart from the disease mutation enabling consistency and reproducibility. Our novel, physiologically relevant cellular systems provide a plethora of avenues for researchers to investigate various applications related to parasite invasion, drug validation, and genome-editing in the context of SCD and BT.
2024-02-07 | PXD044642 | Pride
Project description:β-thalassemia major can be caused by homozygous mutations of the HBB gene, most of the cases are inherited from parents who both have β-thalassemia minor. Herein, we show that a mosaic paternal uniparental isodisomy of chromosome 11p14.3-15.5 is associated with β-thalassemia major in a patient with β-thalassemia minor-that evolved to β-thalassemia major. From this case, we suggest that analysis of HBB gene for non-hematopoietic tissues should be performed in late-onset β-thalassemia major patients. Experiment Overall Design: This study is to evaluate the cause of delay-onset β-thalassemia major in our patient. Patients peripheral blood, hair follicle, and oral mucosa, and her parents pripheral blood samples were analyzed.
2008-06-15 | E-GEOD-7847 | biostudies-arrayexpress
Project description:β-thalassemia cell lines were generated via CRISPR-Cas9 genome editing of Bristol Erythroid Line Adult (BEL-A) and differentiated to the basophilic and polychromatic erythroid cell stage. TMT comparative proteomics was then performed on stage matched WT and β-thalassemia cells isolated by FACS.
2023-10-24 | PXD044730 | Pride
Project description:To explore the role of circRNAs in the regulation of β-thalassemia and provide new evidence and targets for the treatment of β-thalassemia, circRNAs expression profiling was analyzed from patients with β-thalassemia intermedia and major.
2023-08-20 | GSE241141 | GEO
Project description:The fetal-to-adult hemoglobin switch is regulated in a developmental stage-specific manner and reactivation of fetal hemoglobin (HbF) has therapeutic potential for β-hemoglobinopathies. Although BCL11A and ZBTB7A interact with their coregulators, reportedly mediating most γ-globin transcriptional silencing in erythroid in trans, and in cis, the molecular mechanism underlying the epigenetic dysregulation of the switch remains largely unclear. Here we showed that epigenetic inactivation of an ETS2 repressor factor (ERF) reactivates γ-globin expression during stress erythropoiesis, and ERF depletion elevates γ-globin in erythroid cells and in erythroid progenies from the edited HSPCs engrafted into immunodeficient mice. ERF represses γ-globin by directly binding to two motifs regulating HBG expression, independently of the major HbF repressors BCL11A and ZBTB7A. We further uncovered that an lncRNA, RP11-196G18.23 mediates ERF promoter hypermethylation resulting in reactivation of g-globin. Herein, the epigenetic alterations were identified as novel modulators ameliorating the severity of b-thalassemia, thus providing novel therapeutic targets for β-hemoglobinopathies.
2020-12-27 | GSE160601 | GEO
Project description:The fetal-to-adult hemoglobin switch is regulated in a developmental stage-specific manner and reactivation of fetal hemoglobin (HbF) has therapeutic potential for β-hemoglobinopathies. Although BCL11A and ZBTB7A interact with their coregulators, reportedly mediating most γ-globin transcriptional silencing in erythroid in trans, and in cis, the molecular mechanism underlying the epigenetic dysregulation of the switch remains largely unclear. Here we showed that epigenetic inactivation of an ETS2 repressor factor (ERF) reactivates γ-globin expression during stress erythropoiesis, and ERF depletion elevates γ-globin in erythroid cells and in erythroid progenies from the edited HSPCs engrafted into immunodeficient mice. ERF represses γ-globin by directly binding to two motifs regulating HBG expression, independently of the major HbF repressors BCL11A and ZBTB7A. We further uncovered that an lncRNA, RP11-196G18.23 mediates ERF promoter hypermethylation resulting in reactivation of g-globin. Herein, the epigenetic alterations were identified as novel modulators ameliorating the severity of b-thalassemia, thus providing novel therapeutic targets for β-hemoglobinopathies.
2020-12-27 | GSE160602 | GEO
Project description:Background: The thalassemias are highly diverse at both the molecular and clinical levels. Many of the HBB mutations that result in β-thalassemia are missense mutations in the coding region of the β-globin gene, but a few cause alternative splicing, and interfere with normal processing of the β-globin transcripts. Transcriptome profiling in individuals affected with β-thalassemia, especially in individuals who carry novel mutations in the HBB, may improve our understanding of the heterogeneity and molecular mechanisms of the disease. Methods: Members of a family with a daughter affected with thalassemia intermedia, although her mother was not clinically affected, were examined for physical characteristics, hematological parameters and β-globin gene sequences. We also characterized genome-wide gene expression in the family using RT-qPCR and high-throughput RNA-sequencing mRNA expression profiling of blood. Results: Clinical findings, hematological indices, DNA and RNA sequence analysis of individuals with β-thalassemia, including the description of a novel mutation in the β-globin gene, which introduces a cryptic donor splice site. More than 300 genes are differentially expressed in β-thalassemic blood with many of the DEGs involved in pathways relevant to the clinical management of β-thalassemia. β-thalassemia shows important similarities and differences with sickle cell disease at the transcriptome level. Conclusions: We described the down-regulation of the β-globin gene in β-thalassemia by RNA-sequencing analysis using a sample from an affected individual and her mother, who have a novel mutation in the HBB that creates a cryptic donor splice site. The daughter has a typical β-thalassemia allele as well, and an unexpectedly severe phenotype. The DEGs are enriched in pathways that are directly or indirectly related to β-thalassemia such as hemopoiesis, heme biosynthesis, response to oxidative stress, inflammatory responses, immune responses, control of circadian rhythm, apoptosis, and other cellular activities. We compare our findings with published results of RNA-Sequencing analysis of sickle cell disease (SCD) and erythroblasts from a KLF1-null neonate with hydrops fetalis, and recognize similarities and differences in their transcriptional expression patterns.
2019-03-09 | GSE96060 | GEO