Characterization of deletions of the HBB locus by array comparative genomic hybridization
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Daniel Sabath
PROVIDER: E-GEOD-68587 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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 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:Array-CGH used to characterize HBB deletions causing beta thalassemia and HPFH
2015-05-06 | GSE68587 | GEO
Project description:Epidemiological data have suggested that African Americans (AA) are twice as likely to be diagnosed with multiple myeloma (MM) as compared to European Americans (EA). Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from three studies and EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs. 52%; p=0.032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based upon gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients. This submission contains 27 of the 45 African American cases analyzed by aCGH. In addition, 196 samples from European American myeloma patients were also analyzed and compared to the 45 African American patients.
2013-02-25 | E-GEOD-44271 | biostudies-arrayexpress
Project description:β-hemoglobinopathies are the most common genetic disorders worldwide. In sickle cell disease (SCD) a single mutation (E6V) in the b-globin (HBB) gene results in dysfunctional hemoglobin protein, while in β-thalassemia, over 300 mutations distributed across the HBB gene are known to reduce the production of β-globin and cause severe anemia. A genetic engineering approach that replaces the whole HBB gene is an ideal strategy to rescue HBB expression for most genotypes but is technically challenging as the insert cannot be homologous to the endogenous gene and codon-optimized, intron-less sequences may not reconstitute adequate HBB levels. Here, we developed a novel approach for a “one-size-fits-all" HBB gene repair strategy using CRISPR-Cas9 which successfully addresses these problems. First, our DNA donor design avoids sequence homology through a diverged HBB coding sequence and second, incorporates heterologous introns from the fetal g-globin gene, further reducing homology to endogenous HBB while mimicking its intron composition. Screening DNA donors with various heterologous globin introns, polyadenylation signals and truncated sequences, identified a heterologous intron DNA donor that highly expresses β-globin and rescued β-globin expression in two in vitro hemoglobinopathy models in hematopoietic stem and progenitor cells (HSPCs). Furthermore, healthy donor HSPCs modified with this HBB gene replacement approach showed successful engraftment in immunodeficient mice at 16 weeks. In summary, we developed a universal HBB gene replacement strategy that results in physiological b-globin production, offering a potential differentiated approach for treating patients with β-thalassemia, SCD or compound heterozygous individuals.
2024-04-01 | GSE229212 | 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.
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Project description:The genomic DNA sample of monkey PG-haESCs were compared to the female adipose cells by comparative genomic hybridization. The data confirmed that these haploid cells sustained genome integrity. The analysis was performed on a Agilent aCGH G3 Rhesus Macaque 4x180K array to analyse the copy number variations in monkey PG-haESCs, and the genomic DNA of femal monkey adipose was used as control, which had the same background with haploid ESCs.
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2015-01-21 | E-GEOD-52641 | biostudies-arrayexpress
Project description:In this study, we investigated CNAs of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC) by 44k oligonucleotide-based array comparative genomic hybridization (array CGH). 23 mucosal portion of SMGC vs 23 paired submucosal (SM) portion of SMGC, 9 SM portion vs 9 paired lymph node (LN) metastasis, 12 SMGC with LN metastasis vs 15 SMGC without LN metastasis
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2012-03-24 | E-GEOD-28601 | biostudies-arrayexpress