3874 results for "*geneti*"

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• SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors

  Malignant rhabdoid tumor (MRT) is a highly malignant and often lethal childhood cancer. MRTs are genetically defined by bi-allelic inactivating mutations in SMARCB1, a member of the BRG1/BRM-associated factors (BAF) chromatin remodeling complex. Mutations in BAF complex members are common in human cancer, yet their contribution to tumorigenesis remains in many cases poorly understood. Here, we studied derailed regulatory landscapes as a consequence of SMARCB1 loss in the context of MRT. Our multi-omics approach on patient-derived MRT organoids revealed a dramatic reshaping of the regulatory landscape upon SMARCB1 reconstitution. Chromosome conformation capture experiments subsequently revealed patient-specific looping of distal enhancer regions with the promoter of the MYC oncogene. This intertumoral heterogeneity in MYC enhancer utilization is also present in patient MRT tissues as shown by combined single-cell RNA-seq and ATAC-seq. We show that loss of SMARCB1 drives patient-specific epigenetic reprogramming underlying MRT tumorigenesis.

  Study EGAS00001007590

• Genome-wide association study identifies common variants associated with breast cancer in South African Black women

  Genome-wide association studies (GWAS) have characterized the contribution of common variants to the development of breast cancer (BC) in populations of European descent, however no GWAS have been reported in resident African populations. This GWAS included 2,485 resident African BC cases and 1,101 population matched controls. Two risk loci were identified, one on chromosome 15, located between UNC13C and RAB27A (rs7181788, p = 1.01x10-08) and a second in an intron of USP22 on chromosome 17 (rs899342, p = 4.62x10-08). RAB27A is a member of the RAS oncogene family associated with invasive growth and metastasis, and UNC13C is involved in tumor progression. The rs899342 SNP is an eQTL for expression of USP22 in a wide range of tissues. Several genome-wide significant signals were detected in a hormone receptor subtype analysis. Comparison of a meta-analysis of other African ancestry BC GWAS datasets predominantly of West African ancestry with our South African data showed limited evidence of shared risk loci, suggesting potential heterogeneity in genetic risk factors for breast cancer in different African populations. A European ancestry derived polygenic risk model for BC was applied to our data, explaining only 0.79% of variance, with an area under the curve of 0.56. This study identified genetic risk factors for BC in a resident African population, but larger studies in this and other African populations are needed to further define the contribution of common variants to BC risk.

  Study EGAS00001008032

• Solid_WXS_MET-XEN

  Whole-exome sequencing on AB 5500xl Genetic Analyzer of Patient-derived xenograft derived from colorectal cancer metastasis sample

  Dataset EGAD00001002106

• Blueprint: A human variation panel of genetic influences on epigenomes and transcriptomes in three immune cell types, (ChIP-Seq for mature neutrophil, on genome GRCh37)

  ChIP-Seq data for 182 mature neutrophil sample(s). 2847 run(s), 366 experiment(s), 355 analysis(s) on human genome GRCh37. Analysis documentation available at http://ftp.ebi.ac.uk/pub/databases/blueprint/blueprint_Epivar/protocols/README_chipseq_analysis_ebi_20160816

  Dataset EGAD00001002670

• Genetics of stroke outcome exome sequencing

  Exome sequencing performed on DNA from 94 anterior ischemic stroke cases

  Dataset EGAD00001004808

• Mapping genetic variants underlying gene regulation in healthy intestinal cell types to identify novel IBD drug targets (2020-05-12)

  Biopsies from the terminal ileum and rectum of healthy individuals are digested on ice to single cells and processed for single-cell RNA-sequencing (10X Genomics and Illumina) This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ . This dataset contains all the data available for this study on 2020-05-12.

  Dataset EGAD00001006139

• IBD Whole Genome Sequencing (2019-04-01)

  We will sequence at 15X coverage the genomes of 1536 IBD patients. These samples are currently onsite at Sanger and made available for sequencing via our collaboration with the UK IBD Genetics consortium. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ . This dataset contains all the data available for this study on 2019-04-01.

  Dataset EGAD00001004880

• Investigation of mutational signatures associated with DNMT3A deficiency (2019-04-03)

  Mutational signatures have been shown to be attributable to specific genetic contexts, such as mutations in DNA repair genes. DNMT3A is a DNA methyltransferase that helps maintain the DNA methylation pattern in a site-specific manner and may participate in DNA repair or the stress response. We have identified an adult individual who is a germline mosaic for a DNMT3A mutation. We have obtained clonal lymphoblastoid cells (LCLs) from the subject representing both WT and mutant lines grown in the same individual for >50 years. These clones represent a unique opportunity to examine the mutational impact of the DNMT3A mutation in a well-controlled setting. Our goal is to perform WGS on whole blood, representing the pool, as well as several WT and several mutant clones, in order to investigate the contribution of DNMT3A to mutation rates and signatures. . This dataset contains all the data available for this study on 2019-04-03.

  Dataset EGAD00001004889

• The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization

  To elucidate the epigenetic changes which occur when human long-term hematopoietic stem cells (LT-HSC) become activated we performed Bulk ATAC-Seq on 13 sorted bulk hematopoietic populations from cord bloodas well as single-cell ATAC-Seq upon CD34+CD38-CD45RA- cells enriched for HSC as well as CD34+/CD38+ progenitor cells both from cord blood. These studies revealed gains of chromatin accessibility around CTCF binding sites during HSPC activation, as such we additionally performed Low-C to directly profile the 3D conformation of human cord-blood derived LT-HSC and Short-term hematopoietic stem cells (ST-HSC), as well as Hi-C , ATAC-Seq and CTCF ChIP-Seq upon the OCIAML-2 cell line in which CTCF sites gained during LT-HSC activation are enriched. Finally we transduced human cord-blood LT-HSC with an shCTCF vector; in-vitro cultured LT-HSC cells harbouring shCTCF were used to perform RNA-Seq, and scATAC-Seq was performed on CD34+/CD38- human CB cells transduced with shCTCF, four weeks post xeno-transplantation into mice. Collectively these studies have helped us demonstrate the role of 3D chromatin conformation changes during human LT-HSC activation.

  Dataset EGAD00001006447

• Impact of genetic variants in clinical outcome of a cohort of patients with oropharyngeal squamous cell carcinoma

  Caracterization of somatic variants in patients with OpSCC

  Dataset EGAD00001006151