3311 results for "*geneti*"

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• Dataset that contains runs of submission 163

  Description of runs dataset of submission 163

  Dataset EGAD50000000257

• Human genomic and phenotypic synthetic data for the study of rare diseases

  The purpose of this dataset is to facilitate development of technical implementations for rare disease data integration, analysis, discovery, and federated access. This synthetic dataset includes clinical and genomic data from 6 rare disease cases. It consists of 18 whole genomes (6 index cases with their parents) which have genetic background based on public human data sequenced in the context of the Illumina Platinum initiative (Eberle, MA et al. (2017)) and made available by the HapMap project (https://www.genome.gov/10001688/international-hapmap-project). In each of the cases, real causative variants correlating with the phenotypic data provided were spiked-in. The cases included in this synthetic dataset correspond to the following type of disorders: CASE 1- Congenital myasthenic syndrome (Autosomal Dominant -de novo variant) CASE 2- Macular dystrophy (Autosomal Dominant) CASE 3- Muscular dystrophy (Autosomal Recessive-compound heterozygous variants) CASE 4- Mitochondrial disorder (Autosomal Recessive-consanguineous case - homozygous variant) CASE 5- Breast cancer (Autosomal Dominant) CASE 6- Similar as case 1 for patient matchmaking tests: Congenital myasthenic syndrome (Autosomal Dominant-de novo variant) For each case you will be able to download the following data: clinical information (phenopackets per individual and pedigree per family), raw genomic data (FASTQ and BAMs) and processed genomic data (vcfs). When using the data, the following should be acknowledged: the RD-Connect GPAP (https://platform.rd-connect.eu/), EC H2020 project EJP-RD (grant # 825575), EC H2020 project B1MG (grant # 951724) and Generalitat de Catalunya VEIS project (grant # 001-P-001647).

  Study EGAS00001005702

• Structural variant analysis of homologous recombination-deficient genomes

  Homologous recombination (HR) deficiency causes DNA breaks and cytogenetic aberrations. Paradoxically, the types of DNA rearrangements specifically associated with HR-deficient cancers only minimally impact chromosomal structure. Addressing this, we combined a genome graph analysis of short-read whole genome sequencing (WGS) profiles across thousands of tumors with deep linked-read (LR) WGS of 46 BRCA1 or BRCA2 mutant breast cancers to discover a distinct class of HR deficiency-enriched rearrangements called reciprocal pairs. LR WGS showed that reciprocal pairs with identical rearrangement orientations gave rise to one of two distinct chromosomal outcomes, distinguishable only with long molecule data. While one (cis) outcome corresponded to the copy and pasting of a small segment to a distant site, a second (trans) outcome was a quasi-balanced translocation or multi-megabase inversion with substantial (10kb) duplications at each junction. The full spectrum of reciprocal pair outcomes could be explained by an HR-independent replication restart repair mechanism. LR WGS additionally identified single-strand annealing (SSA) as a BRCA2-deficiency specific repair pathway in human cancers. Replication restart- and SSA-associated SVs improved BRCA1- vs. BRCA2- deficiency classification and identified metastatic cancer cases with favorable chemotherapy responses. Our data reveal classes of BRCA1- and BRCA2-deficiency specific rearrangements as drivers of cytogenetic aberrations in HR deficient cells.

  Study EGAS00001007186

• Population_dynamics_in_abnormal_haematopoiesis

  Background: Our recent study has made direct insight into the clonal dynamics of blood cell production in an unperturbed setting in a human. Using whole genome sequencing to track acquired somatic mutations, we were able to construct a phylogenetic tree of different stem and progenitor cells and used this tree to determine the dynamics of mature blood cell production in longitudinal samples. These data set the baseline for understanding population dynamics in abnormal haematopoiesis, and how malignant clones outcompete their normal counterparts to drive haematological malignancies. Aim: This study will measure population dynamics in abnormal human haematopoiesis in patients with clonal blood stem cell disorders. Methods: From patient bone marrow or peripheral blood, we have isolated colonies grown from single blood stem cells/progenitors. Colony DNA will be analysed by whole-genome sequencing to build (or populate) a phylogenetic tree to determine clonal relationships and track stem cell contribution to mature blood cell production. These data will also reveal disease-associated genomic features (mutational burden and mutational signatures) in haematopoietic cells.

  Study EGAS00001003181

• H3Africa - Genomic Characterization and Surveillance of Microbial Threats in West Africa

  Viral diseases are remarkably heterogeneous in their presentation and clinical course. Although diseases such as Lassa Fever and Ebola Virus Disease are thought to be severe and rapidly fatal, they can often present with mild symptoms or remain asymptomatic. Host genetic variability is likely an important mediator of this heterogeneity. Complete characterization of the clinical, laboratory, and host genetic features of these illnesses is not only imperative to rapid diagnosis and effective clinical care, but also important for further scientific study. In this project, we propose to address this need through deep characterization of the clinical and laboratory features of viral disease and through study of genetic mediators of resistance to Lassa Fever and Ebola Virus Disease. Will carry out deep clinical characterization and laboratory assessment of viral febrile cases at two West African Collaborative Centers, and will use this data to develop prognostic models using cutting-edge tools in exploratory data visualization and machine learning. Investigate host genetic factors of Lassa Fever and Ebola Virus Disease through genome-wide association studies. We will then develop field-deployable genotyping assays for the top-associated variants, and apply them in new cohorts to replicate our findings and investigate patterns of genetic resistance in clinical subgroups. This project can shed light on the clinical manifestations of viral illness and their host genetic mediators, leading to potential new insights in disease biology and pathophysiology. We will also create a rich resource of clinical, laboratory, and genetic data for these illnesses in two countries in West Africa, which will serve as a foundation for advancing the clinical care and scientific study of viral disease in the region.

  Study EGAS00001007250

• The Genetic Landscape of Ocular Adnexa MALT Lymphoma Reveals Frequent Aberrations in NFAT and MEF2B Signaling Pathways

  A comprehensive constellation of somatic non-silent mutations and copy number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NFkB, NOTCH and NFAT signaling pathways. One of the most commonly altered genes is CABIN1, a calcineurin inhibitor acting as a negative regulator of the NFAT and MEF2B transcriptional activity. CABIN1 deletions enhance BCR-stimulated NFAT and MEF2B transcriptional activity, while CABIN1 mutations enhance only MEF2B transcriptional activity by impairing binding of mSin3a to CABIN1. Our data provide an unbiased identification of genetically altered genes that may play a role in the molecular pathogenesis of OAMZL and serve as therapeutic targets.

  Study EGAS00001006631

• ATAC-seq/ChIP part

  Epigenetics: ATAC-seq and ChIP-seq data

  Study EGAS00001006520

• Duplexseq_of_the_interstrand_crosslinks_WGS

  One of the most dangerous forms of DNA damage are interstrand crosslinks (ICLs), which covalently crosslink the two strands of the DNA double helix. The repair of these lesions is crucial for cellular survival due to their ability to block transcription and DNA replication. Initially, the major pathway that has been described in ICL repair involves a network of 22 genes that are mutated in a severe human genetic disease known as Fanconi Anemia (FA). Using synthetic lethality screens in the near-haploid human HAP1 cell line, we recently identified two potentially novel regulators of ICL repair, C1orf112 and THAP12. Loss of C1orf112 and THAP12 causes hypersensitivity to ICL-inducing DNA damaging agents, such as Mitomycin C (MMC). Additionally, C1orf112-depleted cells show elevated levels of micronuclei and accumulation of DNA damage in S-phase. To better understand how C1orf112 and THAP12 mediate the repair of ICLs, we want to perform mutational signature analysis, using the BotSeq method. Therefore, WT, C1orf112 and THAP12 knockout cells were cultured in vehicle or MMC treated conditions for 10 days and the genomic DNA was isolated. FANCA and FANCD2 knockout cells are taken along as controls in this experimental setting.

  Study EGAS00001006545

• Genomic evolution and transcriptional changes in the evolution of prostate cancer into neuroendocrine and ductal carcinoma types (RNAseq)

  Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuro-endocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease and the former often arises on a background of androgen deprivation therapy, although it can al-so arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tis-sue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with 3 longitudinal samples over 5 years. Case 2 was a single time point after development of treatment related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all sam-ples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for the ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small cell neuroendocrine and ductal prostatic carcinoma can have a common an-cestry and the process of evolution over time. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.

  Study EGAS00001007428

• SudanMitoSeq: Sudanese mitochondrial sequencing

  In various contexts, mitochondrial function or dysfunction can be linked to mitochondrial genome variations. The use of mitochondrial genetics thus promises personalized diagnostics and treatments. In order to devise specific precision medicine approaches based on mitochondrial genetic variation and to test them within clinical studies, control data is indispensable. Such control data needs to comprehensively cover genetic variation commonly observed and thus expected. In the context of this study we assessed whether current, world-wide mitochondrial data sufficiently represents the region of North and East Africa, that is, whether current reference data is ready for precision medicine in this region. Towards this, we sequenced mitochondrial genomes of 159 Sudanese individuals provided as part of this EGA study and analyzed them together with various other, publicly available data concerning mitochondrial variation. For details, please refer to the publication.

  Study EGAS00001005669