3901 results for "*geneti*"

in 38.15 milliseconds.

• Autozygosity pilot - British-Pakistani from Birmingham 2

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 20-50%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consists of low coverage whole exome sequencing on these samples.

  Dataset EGAD00001001026

• Exome sequencing of a Novel Primary T Cell Immunodeficiency Kindred (2019-08-19)

  Primary T cell immunodeficiency disorders have a heterogeneous genetic basis. This study will focus on one case characterised by severe T cell lymphopenia in the index case. We aim to sequence the complete exomes of this individual, her three unaffected siblings and parents in an effort to identify the causative genetic mutation responsible for this disorder. We will perform exome capture using Agilent SureSelect system, followed by sequencing on the HiSeq platform. Our study has the potential to uncover genes important for T cell development and novel therapeutic strategies to treat T cell immunodeficiencies. . This dataset contains all the data available for this study on 2019-08-19.

  Dataset EGAD00001005263

• Genetic landscape of SMM

  Identifying high risk smoldering myeloma patients and progression mechanism is a prerequisite to implement effective inception strategies and curve myeloma related morbidity and mortality. We hypothesize that genomics may help identify determinants of progression that may help predict outcome and offer effective chemo preventive targets. Eighty-two patients underwent a custom targeted panel sequencing with an additional capture for the translocation loci. These results were compared to 223 newly diagnosed patients (EGAS00001003223 and EGAD00001004117) and 17 MGUS and 10 early myeloma patients. DNA was obtained from either CD138+ cells from the bone marrow of multiple myeloma patients (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using the HyperPlus kit (KAPA Biosystems). After PCR amplification the libraries were hybridized with probes against either a targeted panel consisting of 140 genes and chromosomal regions (Nimblegen) using SeqCap reagents (Nimblegen). Hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads. Overall, these data highlight the importance of dysregulation of the MAPK pathway in the progression to MM.

  Dataset EGAD00001005285

• Germline genome sequencing samples from the Hereditary Cancer Syndromes (ICCon) Cancer Flagship

  A prospective study of individuals with suspicion of a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or was not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing and a comprehensive cancer virtual gene panel analysis were undertaken.

  Dataset EGAD00001011260

• Genetic background for cardio vascular disorders in the general Finnish population

  Low coverage (4-6x) sequencing on samples from population cohorts (Finrisk, Health2000) will be done at Wellcome Trust Sanger Institute (WTSI) using Illumina HiSeq sequencing technology. We will produce 100bp paired end reads. Variants will be called using the 1000 Genomes Project pipeline. The samples have been selected from a national representative set of approximately 30,300 samples and comprises 500 individuals of each gender in the extreme tail of high density lipoprotein (HDL) concentrations. Included individuals were between 25 and 65 years of age. Individuals with a diagnosis of diabetes or BMI>30 were excluded from the study.

  Dataset EGAD00001001251

• CyTOF of 27 DLBCLs

  Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma and is notorious for its clinical heterogeneity. Patient outcomes can be predicted by cell-of-origin (COO) classification, demonstrating that the underlying transcriptional signature of malignant B-cells informs biological behavior in the context of standard combination chemotherapy regimens. In the current study, we used mass cytometry (CyTOF) to examine tumor phenotypes at the protein level with single cell resolution in a collection of 27 diagnostic DLBCL biopsy specimens from treatment naïve patients. We found that malignant B-cells from each patient occupied unique regions in 37-dimensional phenotypic space with no apparent clustering of samples into discrete subtypes. Interestingly, variable MHC class II expression was found to be the greatest contributor to phenotypic diversity. Within individual tumors, a subset of cases showed multiple phenotypic subpopulations, and in one case we were able to demonstrate direct correspondence between protein-level phenotypic subsets and DNA mutation-defined subclones. In summary, CyTOF analysis can resolve both inter- and intra-tumoral heterogeneity among primary samples, and reveals that each case of DLBCL is unique and may be comprised of multiple, genetically distinct subclones.

  Dataset EGAD00001005419

• Autozygosity pilot - British-Pakistani from Birmingham

  The offspring of first cousin marriages have ~6% of their genome autozygous, i.e. homozygous identical by descent, or even more if there was further consanguinity in their ancestry. In the UK there are large populations with very high first cousin marriage rates of 50-80%. Sequencing the exomes of a sample of these individuals has the potential both to support genetic health programmes in these populations, and to provide genetic research information about rare loss of function mutations. This pilot study based on existing British-Pakistani cohort samples from Birmingham will identify homozygous individuals for almost all variants down to an allele frequency around 1%, plus individuals carrying hundreds of new homozygous rare loss-of-function variants, and will support development of community relations and ethics for a wider study currently being designed. The data deposited in the EGA consist of low coverage whole exome sequencing on these samples.

  Dataset EGAD00001001025

• Oxidative phosphorylation is a key ontogenetic feature of monocyte immunometabolism promoting myeloid differentiation after birth

  The dataset consists of 12 samples of monocytes, which were analyzed using RNA-sequencing (RNA-seq). These samples were categorized into four distinct groups, each comprising three samples. The dataset was designed to investigate the transcriptomic and metabolic profiles of monocytes across different age groups and stimulation conditions. 3 neonatal controls, 3 neonatal LPS stimulated, 3 adult controls and 3 adult LPS stimulated samples.

  Dataset EGAD00001011340

• Mechanisms of patient response to Dabrafenib in Melanoma

  Samples will be from the BRF113683 (BREAK-3) study which is a Phase III Randomized, Open-label Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma (n=250 enrolled)*NGS [Agilent capture (Sanger V2 panel): 360 genes and 20 gene fusions; Illumina HiSEQ Sequencing]*CNV: [via NGS or Affy SNP 6.0 or Illumina Omni (TBD)]Bioinformatics: Analysis will be performed using core Sanger informatics pipelines similar to those previously described (Papaemmanuil E et al. (2013) Blood. 22:3616 -3627). Briefly, copy number analysis will be performed using the ASCAT algorithm, and base substitutions, small insertions and deletions using the CAVEMAN and Pindel algorithms, respectively. Statistical approaches including generalized linear models will be used to predict clinical variables such as maximum clinical response and duration of response using genetic data. Sanger and EBI to conduct analysis; Raw data and correlation with clinical endpoints to be analyzed by both EBI/Sanger and GSK (unique pipeline analyses to increase call confidence)

  Dataset EGAD00001001375

• Genetic architecture of male infertility in India

  The dataset consists of whole exome and genome sequencing data from infertile males and his parent(s) and/or sibling(s)

  Dataset EGAD00001015606

• MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

  Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long non-coding RNAs (lncRNAs), on the way MYC is able to influence cellular transcriptome. To this aim we have intersected RNA-sequencing data from two MYC-inducible cell lines and from a cohort of 91 mature B-cell lymphomas carrying, or not carrying, genetic variants resulting in MYC over-expression. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, for MYC-Induced long Non-Coding RNA, showing a strong correlation with MYC expression in MYC-positive lymphomas and also in pancreatic ductal adenocarcinomas. To understand its cellular role we performed RNA interference (RNAi) experiments and found that MINCR knock-down is associated with a reduction in cellular viability, due to an impairment in cell cycle progression. Differential gene expression analysis following RNAi showed a strongly significant enrichment of cell cycle genes among the genes down-regulate following MINCR knock-down. Interestingly these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of MYC transcriptional program. Accordingly, following MINCR knock-down, we observed a reduction in the binding of MYC to the promoters of selected cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes.

  Dataset EGAD00001001441

• 33 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS)

  Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma (MM) with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about molecular mechanism of malignant transformation. We have performed whole exome sequencing together with SNP array analysis in 33 flow-cytometry separated abnormal PC samples of MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations (NS-SNVs) and copy number alterations (CNAs) were present in 97.0% and in 63.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to MM (p<10-4) and we have identified 6 myeloma significantly mutated genes which are KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB in the MGUS dataset. We also found a positive correlation with increasing chromosome changes and somatic mutations. IGH translocations were present in 27.3% of cases comprising t(4;14), t(11;14), t(14;16) or t(14;20) and were in a similar frequency to MM, which corresponded with primary lesion hypothesis. Data from this study showed MGUS is a genetically comprehensive disease, however overall genetic instability is significantly lower compared to MM.

  Dataset EGAD00001001901

• March 2016 update of Whole genome bisulfite sequencing assay data (bams) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  March 2016 update of Whole genome bisulfite sequencing assay data (bams) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001001987

• Chromatin accessibility maps of chronic lymphocytic leukemia identify subtype-specific epigenome signatures and transcription regulatory networks

  Chronic lymphocytic leukemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, we established genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients using the ATAC-seq assay, and we also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting dataset, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status – which distinguishes the two major subtypes of CLL – was accurately predicted by the chromatin profiles, and gene regulatory networks inferred for IGHV-mutated vs. IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we discovered widespread heterogeneity in the chromatin landscape of CLL, established a community resource for studying epigenome deregulation in leukemia, and demonstrated the feasibility of chromatin accessibility mapping in cancer cohorts and clinical research.

  Dataset EGAD00001002110

• Determination of cell specific regulatory enhancers in hematopoetic models

  The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The human variation workpackage (WP10, led by NS) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise "experimental noise" and therefore enhance the power to discover modest effects. Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose. The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively. Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers. Units of 475 ml of AB will be obtained from consenting volunteers of the Cambridge BioResource (CBR), a panel of 10,000 healthy volunteers local to Cambridge who have already consented to participate in biomedical research and of whom biological samples (DNA, plasma, serum) and lifestyle data have been deposited in a repository and database, respectively. We are requesting funding from the Human Diversity project to sequence the genomes of the 200 CBR volunteers at low pass (6x coverage). Nuclei, DNA and RNA will be recovered from the purified cells and made available for RNA-seq, DNA-seq and ChIP-seq and genomic DNA for entire genome sequencing will be recovered from the DNA repository.

  Dataset EGAD00001002205

• GoT2D: Genetics of Type 2 Diabetes, a study of the the genetic architecture of type 2 diabetes

  The GoT2D study includes ~2800 samples, half T2D cases and half T2D controls, of Northern European ancestry sequenced over 3 three technologies: deep whole exome sequencing, low-pass (4x) whole genome sequencing, and OMNI 2.5M genotyping. Samples were ascertained to be phenotypically "extreme" (e.g. leaner, younger cases and older, more obese controls). Genotypes (SNVs, INDELs, and SVs) were called separately for each technology and then integrated via genotype refinement into a single phased reference panel; samples and variants were then excluded based on QC procedures described in Fuchsberger et al. Please note that 2 of the samples in the GoT2D vcf do not have phenotype data.

  Dataset EGAD00001002247

• PSCP_mutation analysis in hESCs

  Many studies over the past 10 years, culminating in the recent report of the International Stem Cell Initiative (ISCI, 2011) have shown that hPSC acquire genetic and epigenetic changes during their time in culture. Many of the genetic changes are non-random and recurrent, probably because they provide a selective growth advantage to the undifferentiated cells. Some are shared by embryonal carcinoma cells, the malignant counterparts of ES cells. The origins of these growth advantages are poorly understood, but may come from altered cell cycle dynamics, resistance to apoptosis or altered patterns of differentiation. Less is known about the nature and consequences of epigenetic changes, but it is likely that these similarly affect hPSC behaviour; e.g., enhanced expression of DLK1, an imprinted gene, is associated with altered hPSC growth (Enver et al 2005). Inevitably, these genetic and epigenetic changes will impact on our ability to use hPSC for regenerative medicine, either because malignant transformation of the undifferentiated cells or their differentiated derivatives to be used for transplantation compromises safety, or because they impede the function of those differentiated derivatives, or because they affect the efficiency with which the undifferentiated cells can be expanded and differentiated into desired cell types. Focusing initially upon the existing clinical grade hESC lines, later moving to iPSC, we will Consolidate and extend knowledge of the rate, type and functional impact of the genetic variations that occur during hPSC culture. We will use whole genome and exome sequencing as well as SNP arrays, together with clonal analysis and other cytogenetics techniques. Common changes will be compared with those found in the normal human population, at low frequency in the original cell population or observed during iPSC generation in the HIPSCI project currently based at the WTSI. These studies will provide a better understanding of the range of genetic changes that occur in hPSC beyond the CNVs already identified. In conjunction with cancer genome resources and expertise at WTSI, bioinformatic analyses of these hPSC data will allow us to assess potential impact on hPSC behaviour pertinent to applications in regenerative medicine, notably the likelihood that specific changes arising in undifferentiated PSC cultures may be associated with potential malignant transformation of differentiated progeny. This data is part of a pre-publication release. For information on the proper use of pre-publication data shred by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001002231

• Exome Atlas in HCC tumors

  The atlas provides a comprehensive exploration of genetic and transcriptomic landscapes within HCC, offering insights into key genomic alterations and gene expression patterns. The integration of exome sequencing and RNAseq data enhances our understanding of the molecular complexity underlying HCC, potentially paving the way for targeted therapeutic strategies and biomarker discovery in the context of hepatocellular carcinoma.

  Dataset EGAD00001015342

• Comprehensive Deep Sequencing Atlas in HCC tumors

  The atlas aims to unravel the intricate genetic landscape of HCC, providing a detailed characterization of genomic alterations, transcriptomic profiles, and key mutations associated with liver tumors. The integration of WGS, RNAseq, and WES data offers a holistic perspective, facilitating a deeper understanding of the molecular mechanisms driving HCC pathogenesis. The resulting atlas serves as a valuable resource for researchers, clinicians, and the broader scientific community, contributing to advancements in HCC diagnostics, prognostics, and therapeutic interventions.

  Dataset EGAD00001015343

• Non-ADT METs ICGC Prostate UK

  To characterize the subclonal genomic architecture of non-androgen-deprived metastatic prostate cancer, we performed whole-genome sequencing (WGS) of pelvic lymph node metastases and matching noncancerous blood from 10 patients to an average sequencing depth of 55x. The patients are part of PELICAN (Project to ELIminate Lethal Cancer) study led by G. Steven Bova at Johns Hopkins University (USA) and Tampere University (Finland). As of September 2020, study using these data is: Wedge et al, Nature Genetics 2018 (PMID: 29662167)

  Dataset EGAD00001002002

• Characterisation of the genomic landscape of CRLF2-d ALL

  To determine the clinical and genetic landscape of CRLF2 deregulated acute lymphoblastic leukaemia (CRLF2-d ALL). We identified 172 patients with a CRLF2 rearrangement treated on either the UKALL2003 trial for children and adolescents (1-24 years) or the UKALLXII trial for adolescents and adults (15-59 years). Genomic technologies from conventional karyotyping, and FISH through to whole genome and exome sequencing were used to characterise the genomes of patients with CRLF2-d ALL. This is the largest study to date to investigate the genomic landscape of CRLF2-d ALL and define CRLF2-d as a unique subgroup of B-other ALL. We have confirmed the high incidence of CRLF2-d in Down syndrome-ALL and demonstrated the co-existence of CRLF2-d with other primary chromosomal rearrangements, suggesting that in these patients CRLF2-d can be a secondary genetic abnormality. Other defining features included enrichment of IKZF1, BTG1 and ADD3 deletions in IGH-CRLF2 patients and specific chromosomal gains seen at much higher frequencies than B-other ALL . We report recurrent established and new co-operating abnormalities and the novel involvement of USP9X and DDX3X in CRLF2-d ALL. It is clear from these data that CRLF2-d ALL is heterogenoeus, requiring a combination of genetic abnormalities in functionally relevent genes, to work alongside the deregulated expression of CRLF2 in order to initiate and drive leukaemogenesis in this subtype. Although the functional relevance of many of the abnormalities presented here are currently unknown, many are likely to activate alternate pathways or sensitize patients to current therapies.

  Dataset EGAD00001002007

• Characterisation of the genomic landscape of CRLF2-d ALL

  To determine the clinical and genetic landscape of CRLF2 deregulated acute lymphoblastic leukaemia (CRLF2-d ALL). We identified 172 patients with a CRLF2 rearrangement treated on either the UKALL2003 trial for children and adolescents (1-24 years) or the UKALLXII trial for adolescents and adults (15-59 years). Genomic technologies from conventional karyotyping, and FISH through to whole genome and exome sequencing were used to characterise the genomes of patients with CRLF2-d ALL. This is the largest study to date to investigate the genomic landscape of CRLF2-d ALL and define CRLF2-d as a unique subgroup of B-other ALL. We have confirmed the high incidence of CRLF2-d in Down syndrome-ALL and demonstrated the co-existence of CRLF2-d with other primary chromosomal rearrangements, suggesting that in these patients CRLF2-d can be a secondary genetic abnormality. Other defining features included enrichment of IKZF1, BTG1 and ADD3 deletions in IGH-CRLF2 patients and specific chromosomal gains seen at much higher frequencies than B-other ALL . We report recurrent established and new co-operating abnormalities and the novel involvement of USP9X and DDX3X in CRLF2-d ALL. It is clear from these data that CRLF2-d ALL is heterogenoeus, requiring a combination of genetic abnormalities in functionally relevent genes, to work alongside the deregulated expression of CRLF2 in order to initiate and drive leukaemogenesis in this subtype. Although the functional relevance of many of the abnormalities presented here are currently unknown, many are likely to activate alternate pathways or sensitize patients to current therapies.

  Dataset EGAD00001002008

• Native American Ancient DNA sequencing

  The morphology of the first humans in the Americas (Paleoamericans) differs from that of Native Americans, and has raised the question of whether or not there are also differences in origin or genetics. A few populations who survived until relatively recently have been suggested to retain Paleoamerican morphology. One of these populations is from La Jolla. Here, we have generated genome sequence data from four La Jolla individuals in order to investigate these questions 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/

  Dataset EGAD00001002144

• An exome sequencing study of the HIV elite-long term non progressors and rapid progressors (CASCADE cohorts)

  Background: A rare subgroup of HIV infected individuals naturally controls infection without treatment. These ?elite controllers? constitute an important model for the natural control of HIV infection. Indeed, the study of these individuals may provide insights into strategies for the development of HIV vaccines. Although several HLA and chemokine alleles are known to be over-represented in elite controllers, only a small portion of HIV phenotypic variation is explained by known genetic variants. The elite controller phenotype is rare and distinct, representing the extreme of an infectious disease trait. As such, this phenotype may be partly explained by variation in host immune control, which may be characterized by differences in rare functional genetic variants. Genomic regions underlying elite control can be potentially identified by comparing the presence or frequency of variants in this group to that representing the opposite extreme. In this context, ?rapid progressors? is a group defined by its rapid immunological and clinical disease progression. Aim: To extend an existing study, in order to identify DNA sequence variants involved in the control of HIV infection with greater statistical resolution. Specifically, we aim to sequence up to 200 exomes from multiple cohort studies within the EuroCoord CASCADE collaboration (a collaboration of 25 HIV seroconversion cohort studies across Europe).

  Dataset EGAD00001002179

• Genome Diversity in Africa Project - ancient samples - standard libraries

  Given the central importance of Africa to studies of human origins, genetic diversity and disease susceptibility, large-scale and representative characterisation of genetic diversity in Africa is needed. Analyses of ancient DNA from Africa would complement sequencing of modern African populations and provide unique opportunities to transform our understanding of the pre-history of the region. This approach would greatly refine our understanding of population structure and gene flow in Africa and globally, including genetic signatures of ancient admixture. This low coverage sequencing experiment will allow us to test and refine our pipeline for ancient DNA sequencing. 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/

  Dataset EGAD00001002211

• PSCP_bisulphite analysis in hESCs

  Many studies over the past 10 years, culminating in the recent report of the International Stem Cell Initiative (ISCI, 2011) have shown that hPSC acquire genetic and epigenetic changes during their time in culture. Many of the genetic changes are non-random and recurrent, probably because they provide a selective growth advantage to the undifferentiated cells. Some are shared by embryonal carcinoma cells, the malignant counterparts of ES cells. The origins of these growth advantages are poorly understood, but may come from altered cell cycle dynamics, resistance to apoptosis or altered patterns of differentiation. Less is known about the nature and consequences of epigenetic changes, but it is likely that these similarly affect hPSC behaviour; e.g., enhanced expression of DLK1, an imprinted gene, is associated with altered hPSC growth (Enver et al 2005). Inevitably, these genetic and epigenetic changes will impact on our ability to use hPSC for regenerative medicine, either because malignant transformation of the undifferentiated cells or their differentiated derivatives to be used for transplantation compromises safety, or because they impede the function of those differentiated derivatives, or because they affect the efficiency with which the undifferentiated cells can be expanded and differentiated into desired cell types. Focusing initially upon the existing clinical grade hESC lines, later moving to iPSC, we will Consolidate and extend knowledge of the rate, type and functional impact of the genetic variations that occur during hPSC culture. We will use whole genome and exome sequencing as well as SNP arrays, together with clonal analysis and other cytogenetics techniques. Common changes will be compared with those found in the normal human population, at low frequency in the original cell population or observed during iPSC generation in the HIPSCI project currently based at the WTSI. These studies will provide a better understanding of the range of genetic changes that occur in hPSC beyond the CNVs already identified. In conjunction with cancer genome resources and expertise at WTSI, bioinformatic analyses of these hPSC data will allow us to assess potential impact on hPSC behaviour pertinent to applications in regenerative medicine, notably the likelihood that specific changes arising in undifferentiated PSC cultures may be associated with potential malignant transformation of differentiated progeny. 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/

  Dataset EGAD00001002235

• DERMATLAS: Hidradenoma papilliferum_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible.For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previously, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.

  Dataset EGAD00001015481

• Whole-Genome Sequences from five human populations of Sudan

  This dataset provides the first high-coverage (~30X) whole-genome sequencing (WGS) data from Sudan, encompassing 125 individuals from five ethnolinguistic groups: Copts, Beja, Fulani, Fur, and Mahas. These populations represent three major linguistic families: Afro-Asiatic, Nilo-Saharan, and Niger-Congo, offering a detailed view of the country’s genetic diversity.

  Dataset EGAD00001015636

• Single cell transcriptional evolution of myeloid leukaemia of Down syndrome – WGS

  Abstract: Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS). Unusually for a childhood leukaemia, ML-DS arises from a preleukaemic state, termed transient abnormal myelopoiesis (TAM), and via a conserved sequence of mutations. Here, we examined the relationship between the genetic and transcriptional evolution of ML-DS from a rich collection of primary patient samples through single cell mRNA sequencing, complemented by phylogenetic analyses in progressive disease. We distilled the transcriptional consequence of each genetic step in the evolution of ML-DS, showing that TAM-defining GATA1 mutations account for most of the ML-DS transcriptome, including those of progressive disease. This transcriptional backbone may thus represent a common vulnerability in ML-DS. We extracted the transcriptional difference between TAM and ML-DS which, unexpectedly, reflected features shared across childhood leukaemia. Our approach delineates the transcriptional evolution of ML-DS and provides an analytical blueprint for distilling consequences of mutations directly from patient samples.

  Dataset EGAD00001015453

• A next-generation dual guide CRISPR system for genetic interaction library screening

  Raw sgRNA sequencing data from a pilot CRISPR screening library to test the dual guide vector system (8,914 guide pairs), and from a large scale genetic interaction screen (~100,136 guide pairs) in HT-29 cells. This data refers to Burgold et al. Nature Communications 2025.

  Dataset EGAD00001015754

• BIOCLOCK Phenotype Information Dataset

  This dataset contains phenotypic metadata from participants in the BIOCLOCK endurance exercise intervention and epigenetic aging study. It includes intervention status, cardiorespiratory fitness (VO2 max), body composition, estimated leukocyte proportions, and other relevant traits linked to epigenetic aging outcomes.

  Dataset EGAD00001015799

• Targeted-capture sequencing (bam files) of 81 samples of myxofibrosarcoma and 44 matched pairs

  Myxofibrosarcoma (MFS) is a rare subtype of sarcomas in the elderly, whose genetic basis is poorly understood. To elucidate it, the Targeted-capture sequencing was performed.

  Dataset EGAD00001007826

• Epigenetic profiles of neuroblastoma PDXs

  This dataset contains bam files for ChIP-seq experiments for 6 neuroblastoma PDXs (Patient Derived Xenograft). It includes the bam files for the H3K27ac mark as well as the bam files of the corresponding input DNA for each sample.

  Dataset EGAD00001003394

• GenomeDenmark Phase 2 - HLA validation sequencing data

  Validation of HLA variation of 8 individuals from the GenomeDenmark Phase 2 study. Validation is performed Sanger sequencing of selected amplicons (5-10 amplicons per sample).

  Dataset EGAD00001003454

• Gene Characterization in Carbohydrate metabolic alterations (neonatel diabetes & congenital hyperinsulinemic) in early childhood (2018-03-14)

  Whole Exome Sequencing of trios (proband + parents) or probands only with Neonatal Diabetes Mellitus (NDM) or Congenital Hyperinsulinism of Infancy (CHI) of unknown genetic origin. 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 2018-03-14.

  Dataset EGAD00001004040

• The contribution of POT1 variants to sporadic melanoma development (2018-06-06)

  A case-control series of melanoma cases from Leeds, UK have been sequenced in the Fluidigm platform to identify genetic variants associated with sporadic melanoma development. Samples in which potentially contributing variants have been detected are being sequenced in an orthogonal platform for variant confirmation. . This dataset contains all the data available for this study on 2018-06-06.

  Dataset EGAD00001004151

• Genetic screening of GPI-anchor protein synthesis (2018-08-13)

  This study will analyse the guide sequence which were used for making mutations in the Cas9-expressing cells. We used GeCKO v2 library which were released by Feng Zhang, 2014. 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 2018-08-13.

  Dataset EGAD00001004294

• Open Targets 020 Epigenomes of Cell Lines (2018-10-23)

  There is currently a drive to establish cell based assay systems of greater human biological and disease relevance through the use of well characterised transformed cell lines, primary cells and complex cellular models (e.g. co-culture, 3D models). However, although the field is gaining valuable experience in running more non-standard & complex cell assays for target validation and compound pharmacology studies, there is the lack of a systematic approach to determine if this expansion in cell assay models is reflected in increased human biological and disease relevance. The increasing wealth of publically available transcriptomic, and epigenome (ENCODE and Epigenome Roadmap) data represents an ideal reference mechanism for determining the relationship between cell types used for target & compound studies to primary human cells and tissues from both healthy volunteers & patients. The CTTV020 epigenomes of cell line project aims to generate epigenetic and transcriptomic profiles of cell lines and compare these with existing and newly generated reference data sets from human tissue and cell types. The aim is to identify assay systems which will provide greater confidence in translating target biology and compound pharmacology to patients. Multiple cell types commonly used within research have been grouped according to biology. Examples include erythroid, lung epithelial, hepatocyte cell types and immortalised models of monocyte / macrophage biology. 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 2018-10-23.

  Dataset EGAD00001004414

• Exome sequencing of advanced hepatocellular carcinoma

  The aim of our project is to decipher the genomic of advanced hepatocellular carcinoma using whole exome sequencing. To this purpose, we aim to compare genetic landscape of advanced hepatocellular carcinoma with early tumor in order to understand the mechanisms of tumor progression. This work will also help to identify new therapeutic targets potentially useful to treat patients at advanced stage. This dataset contain whole exome sequencing aligned reads for 41 tumor with matched normal samples

  Dataset EGAD00001004555

• The mutational landscape of skin tumours in CYLD cutaneous syndrome determined

  Patients with germline mutations in CYLD can develop hundreds of benign skin tumours called cylindromas. The development of multiple tumours within a single patient at sun-protected and sun-exposed sites, varying tumour histological patterns and grades of malignancy allow for the testing of several genetic hypothesis in relation to cutaneous carcinogenesis. By adopting the unprecedented approach of whole genome sequencing of multiple benign skin tumours within individuals in multigenerational families, we set out to study the impact of mutational diversity on models such as multistep carcinogenesis as well as non-sequential carcinogenesis. Using non-negative matrix factorisation (NMF) to discover mutational signatures, we found distinct mutational signatures in identical benign tumours (N=2 patients; n=11 tumours) at sun exposed and sun protected skin tumours within a mother and her daughter. We found recurrent mutations in epigenetic modifying genes in CCS tumours which are known to have an oncogenic dependency on Wnt signalling. We also demonstrate that cutaneous tumours that metastasize to the lung carry a a UV signature, supporting the origin from the skin. Distinct malignant tumours, such as BCC and malignant spiradenocarcinoma carried unique driver mutations. These findings add new dimensions to the existing paradigms of UV-induced skin cancer and highlight the utility of studying rare disease to gain novel insights into genetic mechanisms of tumour formation.

  Dataset EGAD00001004573

• Balanced Brain Tumour Whole Genome Sequencing

  We propose to definitively characterise the somatic genetics of a number of pediatric malignant tumours including ependymoma, high grade glioma and central nervous system primitive neurectodermal tumours through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.

  Dataset EGAD00001000369

• Genetic factors underlying premature coronary heart disease in patients with normal coronary arteries

  The study will analyse by exome sequencing 42 Greek patients with premature MI and no vessel disease to identify genetic factors underlying this condition.

  Dataset EGAD00001000402

• ENGAGE - Amendment "500 genes exon sequencing"

  The ENGAGE project is a FP7 funded EU project aiming to combine genetic and phenotype information from European population based cohorts. In this sub-project we aim to do whole exome sequencing of individuals selected from Health 2000 and FINRISK cohorts. Individuals have been selected based on their metabolic trait phenotypes

  Dataset EGAD00001000403

• Identification of low frequency variants associated with ulcerative colitis using whole-genome sequencing

  2000 ulcerative colitis cases drawn from the UKIBD Genetics Consortium cohort and whole-genome sequenced at 2X depth. A case control association study using control samples whole-genome sequenced by UK10K will be undertaken to identify common, low-frequency and rare variants associated with ulcerative colitis. Data will be combined with similar data across 3000 Crohn's disease cases from the same cohort to identify inflammatory bowel disease (IBD) loci and better understand the genetic differences and similarities of the two common forms of IBD.

  Dataset EGAD00001000409

• RNA-Seq in Patients with Primordial Dwarfism

  Transcriptome studies in patients with rare genetic diseases can potentially aid in the interpretation of likely causal genetic variation through identification of altered transcript abundance and/or structure. RNA-Seq is the most sensitive assay for both investigating transcript structure and abundance The primary aim of this pilot project is to investigate to what degree integrating exome-Seq and RNA-Seq data on the same individual can accelerate the identification of causal alleles for rare genetic diseases. There are two main strands to this: (i) identifying which variants discovered in exome-seq appear to be having a functional impact on transcripts, and (ii) identifying transcript outliers, especially among known causal genes, that may not necessarily have a causal variant identified from exome sequencing. The latter may identify the presence of causal variants that lie far from coding regions (e.g. the formation of cryptic splice sites deep within introns, or loss of long range regulatory elements), which can be confirmed with further targeted genetic assays. Just over 50% of all disease-causing variants recorded in the Human Gene Mutation Database (HGMD) affect transcript structure and abundance (e.g. nonsense SNVs, essential splice site SNVs, frameshifting indels, CNVs). This pilot project will study RNA from lymphoblastoid cell-lines from 12 patients with primordial dwarfism syndromes, for 10 of these samples we have previously generate exome data as part of our collaboration with the group of Prof Andrew Jackson. The two remaining samples are positive controls where the causal mutation is known, and is known to affect transcript structure and/or abundance. Primordial dwarfism is a prime candidate for these RNA-seq studies because all known causal mutations to date have key roles in DNA replication and thus, unsurprisingly, the products of the causal genes are typically ubiquitously expressed. Each RNA will be sequenced, with two technical replicates (independent RT-PCR and libraries) per sample, and each replicate run in 1/2 of a HiSeq lane using 100bp paired reads. Samples preparation was as follows :The cells were grown to confluency, then pellets frozen at -80. RNA samples were prepared using the Qiagen RNeasy kit, then nanodropped and analyzed using the bioanalyzer to determine concentration and purity. 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/

  Dataset EGAD00001000640

• Triple Negative Breast Cancer Whole Genome Validations

  We propose to definitively characterise the somatic genetics of Triple negative breast cancer through generation of comprehensive catalogues of somatic mutations in 500 cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses. This study will use a bespoke bait set to pulldown regions of interest found in whole genome sequencing to validate mutations found.

  Dataset EGAD00001000662

• Whole genome sequencing of an individual's genomic DNA and that of its lymphoblastoid cell line.

  The genetic consequences of cellular transformation by Epstein-Barr-Virus were assessed by comparing whole genome sequences of the original genome (before transformation) and the genome after transformation.

  Dataset EGAD00001000693

• Sequencing probands and families with severe insulin resistance syndromes

  This is an ongoing project and continuation to all the sequencing we have been doing over the last few years. We have some additional families and probands with syndromes of insulin resistance not previously sequenced within uk10k or other core funded projects. We would like to complete the sequencing in all of the good quality families and probands we have, this would require another ~50 samples to be WES sequenced. This cohort has already proven to be a rich source of interesting findings with papers in Science and Nature genetics.

  Dataset EGAD00001000694

• Whole genome sequencing of Italian genetic isolates -Friuli Venezia Giulia

  Low coverage whole genome sequencing of samples from individuals from Friuli Venezia Giulia, an Italian genetic isolate population.

  Dataset EGAD00001000728

• RRBS data of 48 individuals of the Dutch Hunger Winter Families Study

  The dataset entails 48 RRBS libraries of 24 siblings. 24 individuals are conceived during the Dutch Famine, a severe 6 month famine at the end of World War 2. A same sex sibling was added as a control, allowing partial matching for (early) familial environment and genetics.

  Dataset EGAD00001000733