3854 results for "*geneti*"

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• Shallow Whole Genome Sequencing of Patient Derived Xenografts

  Chemotherapy is the standard-of-care treatment for metastatic colorectal cancer (mCRC) and benefits some patients, but what distinguishes responders from non-responders is unclear. In this study, we leveraged a comprehensive collection of 27 molecularly annotated patient-derived xenografts to uncover functional predictors of response to 5-FU and irinotecan combination therapy (FOLFIRI) in mCRC. Genetic analyses revealed that treatment sensitivity was marked by genomic scars indicative of BRCAness, suggesting homologous recombination (HR) deficiency as a key determinant. Accordingly, we surveyed a manually curated panel of 44 genes with a documented role in HR for the potential presence of pathogenic mutations. We did not observe a specific enrichment of HR gene mutations based on response to FOLFIRI. This result, combined with the absence of widespread biallelic inactivation of the analyzed genes and the predominance of mutations categorized as variants of unknown significance, suggests that FOLFIRI sensitivity is not primarily governed by underlying mutations in HR genes responsible for mitigating the genotoxic effects of this therapeutic regimen.

  Dataset EGAD50000000277

• Clonally heritable gene expression imparts a layer of diversity within cell types

  Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high coverage single cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo. We combined chromatin accessibility and RNA profiling on different lymphocyte clones to reveal thousands of regulatory regions exhibiting interclonal variation which could be directly linked to interclonal variation in gene expression. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging and disease.

  Study EGAS50000000161

• Data Access Committee of Biobank Lab, Department of Oncobiology and Epigenetics, University of Lodz

  Dac EGAC50000000080

• An isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn’s disease with defective antimicrobial activity

  Despite major advances in linking single genetic variants to single causal genes, the significance of genetic variation on transcript-level regulation of expression, transcript-specific functions, and relevance to human disease has been poorly investigated. Strawberry notch homolog 2 (SBNO2) is a candidate gene in a susceptibility locus with different variants associated with Crohn’s disease and bone mineral density. The SBNO2 locus is also differentially methylated in Crohn’s disease but the functional mechanisms are unknown. Here we show that the isoforms of SBNO2 are differentially regulated by lipopolysaccharide and IL-10. We identify Crohn’s disease associated isoform quantitative trait loci that negatively regulate the expression of the noncanonical isoform 2 corresponding with the methylation signals at the isoform 2 promoter in IBD and CD. The two isoforms of SBNO2 drive differential gene networks with isoform 2 dominantly impacting antimicrobial activity in macrophages. Our data highlight the role of isoform quantitative trait loci to understand disease susceptibility and resolve underlying mechanisms of disease. This dataset contains RNAseq raw data from CD14+ monocyte-derived macrophages and siRNA-mediated knockdown experiments, as well as RNAseq raw data from THP-1 monocytes-derived macrophages following ectopic expression of SBNO2 isoforms.

  Dataset EGAD50000000264

• DAC for the study molecular biomarkers associated with the diagnosis and severity of genetic and diseases from PAIDI-BIO354 GENYO-UGR)

  Dac EGAC00001003090

• NalaGenetics Data Access Committee

  Dac EGAC00001003475

• Whole genome sequencing of individuals from Latvia: the first step towards the population-specific reference of genetic variation

  Study EGAS00001007406

• Unraveling the genetics of transformed splenic marginal zone lymphoma

  Study EGAS00001006389

• Detection of rare mutations, copy number variation, and DNA methylation in the same template DNA molecules

  The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics in the future.

  Study EGAS00001006839

• Transcriptome Analysis Offers a Comprehensive Illustration of the Genetic Background of Pediatric Acute Myeloid Leukemia

  Study EGAS00001003701

• SNP Genotype Data: Subpopulations of Filipino, Malaysian, and Papua New Guinea

  In the context of the study 'Exploring Adaptive Phenotypes for the Human Calcium-Sensing Receptor Polymorphism R990G,' this repository contains 11 VCF files. Each file includes genetic data from 22 autosomes, representing distinct subpopulations. The subpopulations are as follows: Malaysian: Aeta (15 samples) Agta (11 samples) Batak (10 samples) Mamanwa (6 samples) Filipino: Jehai (13 samples) Kintaq (6 samples) Temiar (5 samples) Papua New Guinea: Highlands (2 samples) Koinambe (10 samples) Kosipe (10 samples) Sepik (2 samples) The numbers in parentheses indicate the sample size for each respective subpopulation.

  Study EGAS50000000044

• Multimodal epigenetic sequencing analysis for colon cancer

  Targeted methylation sequencing (enzymatic conversion) data of plasma samples collected from colon cancer patients and non-cancer subjects.

  Study EGAS50000000052

• Carboxylesterase 1 mediates a distinctive metabolic profile of dendritic cells to attain an inflammatory phenotype

  The metabolic profile of dendritic cells (DCs) shapes their phenotype and functions. Carboxylestrase 1 (CES1) enzyme is highly expressed in mononuclear myeloid cells however its exact role in DCs is elusive. We used a CES1 inhibitor (WWL113) and genetic overexpression to explore the role of CES1 in DCs differentiation in inflammatory models. CES1 expression was analyzed during CD14+ monocytes differentiation to DCs (MoDCs) using quantitative PCR. CES1 Inhibitor (WWL113) was applied during MoDCs differentiation. Surface markers, secreted cytokines, lactic acid production, phagocytic and T cell polarization capacity were analyzed. Transcriptomic and metabolic profile were assessed with RNA-sequencing and mass spectrometry. Cellular respiration was assessed with seahorse respirometry. Transgenic mice were used to assess CES1 overexpression in DCs in inflammatory models. CES1 expression peaks early during MoDCs differentiation. Pharmacological inhibition of CES1 led to higher expression of CD209, CD86 and MHCII. WWL113 treated MoDCs secreted higher quantities of IL6, IL8, TNF and IL10 and demonstrated stronger phagocytic ability and higher capacity to polarize Th17 differentiation in autologous DCs-T cells co-culture model. Transcriptomic profiling revealed enrichment of multiple inflammatory and metabolic pathways. Functional metabolic analysis shows impaired maximal mitochondrial respiration capacity, increased lactate production and decreased intracellular amino acids and TCA intermediates. Transgenic human CES1 overexpression in murine DCs generated less inflammatory phenotype and increased resistance to T cell mediated colitis. In conclusion, CES1 inhibition directs DCs differentiation towards more inflammatory phenotype, that shows stronger phagocytic capacity and supports Th17 skewing. This is associated with disrupted mitochondrial respiration and amino acids depletion.

  Study EGAS50000000230

• RNA-seq data for study 'Smoking-dependent expression alterations in nasal epithelium reveal immune impairment linked to germline variation and lung cancer risk.'

  RNA-seq data from nasal and bronchial tissues in 649 subjects, many with lung cancer. Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to lifestyle risk in the form of cigarette smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, often many years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk are unclear. CT screening of current and former smokers has been shown to reduce lung cancer mortality by up to 26%. To examine whether clinical risk stratification can be improved upon by the addition of genetic data, and to explore the mechanisms of the persisting risk in former smokers, we have analyzed transcriptomic data from accessible airway tissues of 487 subjects. We developed a model to assess smoking associated gene expression changes and their reversibility after smoking is stopped, in both healthy subjects and clinic patients. We find persistent smoking associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune and interferon related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. Our results provide initial evidence for germline-mediated personalised smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

  Dataset EGAD50000000333

• INTEGRATIVE MOLECULAR ANALYSIS OF SKIN TUMORS FROM CYLD CUTANEOUS SYNDROME PATIENTS

  CYLD cutaneous syndrome (CCS) is a rare autosomal dominant disorder characterized by germline CYLD mutations and by multiple benign skin tumors dependent on NF-kB pathway. We assembled a large cohort of CCS rare skin tumors that was profiled with whole exome or genome sequencing, RNA sequencing and methylation arrays to better understand genetic mechanisms of CCS tumorogenesis.

  Study EGAS50000000247

• INTEGRATIVE MOLECULAR ANALYSIS OF SKIN TUMORS FROM CYLD CUTANEOUS SYNDROME PATIENTS

  CYLD cutaneous syndrome (CCS) is a rare autosomal dominant disorder characterized by germline CYLD mutations and by multiple benign skin tumors dependent on NF-kB pathway. We assembled a large cohort of CCS rare skin tumors that was profiled with whole exome or genome sequencing, RNA sequencing and methylation arrays to better understand genetic mechanisms of CCS tumorogenesis.

  Dataset EGAD50000000362

• SAB demo study

  SAB demo

  Study EGAS50000000199

• UK Biobank whole cohort directly genotyped and imputed data (~500,000 participants)

  Genotype data is available for all 500,000 participants in the UK Biobank cohort. Genotyping has been performed using the Affymetrix UK BiLEVE Axiom array on an initial 50,000 participants and the remaining 450,000 participants have been genotyped using the Affymetrix UK Biobank Axiom® array. The two arrays are extremely similar (with over 95% common content).Quality control and imputation (to over 90 million SNPs, indels and large structural variants) has been performed by a collaborative group headed by the Wellcome Trust Centre for Human Genetics.The following data are available:* A clean set of QC’ed genotype calls* Confidence values that a genotype call is correct* Intensity data to generate cluster plots* Extensive QC information regarding SNPs and samples including SNP metrics, batch effects, population structure and relatedness* Imputed dataFor further information, please refer to the UK Biobank website

  Study EGAS00001002399

• Nurminen et al ("GP2Men") Study Primary and Metastatic Prostate Cancer Whole Genome Sequence Data

  We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones.

  Study EGAS50000000005

• Paired primary and recurrent patient GBM sample EZH2 binding profiles

  To ascertain the change in PRC2 occupancy at different promoter sets between primary and recurrent tumour, we performed EZH2 ChIPseq in longitudinal GBM samples from one Up and one Down responder from our cohort.

  Study EGAS50000000100

• High Density SNP Association Analysis of Melanoma: Case-Control and Outcomes Investigation

  This research builds upon an extensive resource of melanoma cases and hospital based controls collected over several years at the U.T. M.D. Anderson Cancer Center. The goal of this research is to identify novel susceptibility and outcome-related genes for melanoma using a systematic genome-wide association-based approach. Our goal is to conduct high-density SNP association and outcome studies. This dbGaP study contains samples from 2000 European ancestry cases and 1000 European ancestry controls using the Illumina OMNI1-Quad SNP chip. As a part of an ongoing R01 project, we have epidemiological data together with candidate gene results for 1000 of the melanoma cases and the controls. With regard to the outcome aspect of our design, as part of our melanoma Specialized Program of Research Excellence (SPORE) grant, our MelCore database contains comprehensive, prospectively maintained clinical information from all melanoma patients included in the study cohort, including primary tumor histopathology and staging information, standard and investigational blood tumor markers, details of surgical and systemic therapies, and extensive follow-up information, including time to relapse or recurrence, pattern of recurrence and survival duration. Finally, we intend to collaborate with the GenoMEL collaboration so we can jointly evaluate each other's findings. The goal of our analysis will be to identify novel genetic factors predisposing the development of melanoma, as well as genetic factors controlling melanoma stage at presentation, recurrence and progression. This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to melanoma through large-scale genome-wide association studies of 2000 European ancestry cases and 1000 European ancestry controls. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000187

• Better Outcomes for Children: GWAS from Cincinnati Children's Hospital Medical Center (CCHMC) - eMERGE Phase II data - (dbGaP Deposit 1)

  This submission includes genotyping data from 6 separate cohorts (named A-E here), each is described in separate paragraphs below. Cohort A) Autism is a neurodevelopmental disorder that affects 1.5 million people in the United States, at an estimated lifetime cost of $4 million. It is part of Pervasive Developmental Disorder characterized by impairments in communication, language and reciprocal social interaction, and by unusual patterns of restricted and repetitive interests or behaviors. Autism, or autistic disorder, is the most severe form of the disease which has a wide range of symptom severity encompassed by the more inclusive term, Autism Spectrum Disorder (ASD). The prevalence of Autistic Disorder is currently estimated to be 4 per 1000, affecting 4 times more boys than girls. Susceptibility to autism is clearly attributable to genetic factors but the extensive clinical and genetic heterogeneity within the disorder have hindered efforts at genetic dissection. Identifying the genetic variants that contribute to this highly heritable disease is crucial to advancing research on autism. Reported concordance rates among monozygotic twins range from 60% − 90% and heritability of autism has been estimated to be 90% or greater. Identifying genetic variants that contribute to this highly heritable disease is crucial to advancing research on autism. Cohort B) The long-term objective of this research is to determine the molecular genetic basis of Cardiovascular (CV) disease in the young; this study seeks to identify gene mutations that cause "structural heart defects". Every year in the USA, 32,000 individuals are born with CV malformations; approximately 20% die during the first year of life. Another 30,000 young people develop a disturbance of cardiac rhythm or conduction. In addition, the life expectancy of another 40,000 young people is shortened by other forms of CV disease. It is becoming more apparent that in spite of the success in diagnosis and treatment, very little is known about the causes of CV disease in the young; understanding the causes will permit insight into the pathophysiologic basis of disease and allow definition of disease risk - two critical elements for disease prevention. Disease prevention and/or risk modification promises to be the new frontier in the management of CV disease in the young. Cohort C) Eosinophilic Esophagitis (EE) is one of the manifestations of eosinophilic gastrointestinal inflammation which have profound effects on a patient's health and development. Results of epidemiologic studies performed through our center demonstrate that eosinophil-associated gastrointestinal disease is not an uncommon entity. While the epidemiology of eosinophilic esophagitis has not been thoroughly studied until recently, there appears to be a significant increase in the diagnosis of EE in the last decade. Based on our research, this mainly reflects increased disease recognition, but there is also a bona-fide increase in disease incidence which coincides with the increasing incidence of asthma and allergic diseases in the industrialized world. In addition, many patients with intractable symptoms thought in the past to represent atypical GERD or other disorders are now being recognized as having EE. Diagnosis of EE requires endoscopy and biopsies to document the characteristic histologic findings of esophageal eosinophilia. In general, this study proposed to elucidate the mechanisms underlying eosinophil growth, survival, migration, and function, and to investigate and further characterize the pathophysiology of, clinical manifestations of, and spectrum of disease severity of eosinophilic esophagitis in humans. Cohort D) Juvenile idiopathic arthritis (JIA) is a debilitating complex genetic disorder characterized by inflammation of the joints and other tissues and shares histopathological features with other autoimmune diseases. It is considered a complex genetic disorder. There are more than 50,000 children with JIA in the USA, approximately 1 per 1000 births, which is about the same incidence as juvenile diabetes. It is believed that genes in the major histocompatibility complex (MHC) play a role in defining genetic risk, and it can be hypothesized that loci in other chromosomal regions are involved in conferring risk in JIA. These candidate chromosomal regions can be identified using genome wide association analyses. The long-term goal is a comprehensive understanding of the genetic basis of these disabling arthropathies for which the molecular basis is not presently understood. The results of recent GWAS for Caucasian JIA were recently published in Arthritis Rheum. 2012 Feb 21 (Published online, PMID=22354554). Cohort E) Childhood Absence Epilepsy (CAE) is characterized by very frequent (several to many per day) absence seizures in an otherwise normal child with an EEG usually demonstrating 3 Hz bilateral, synchronous, symmetrical spikewaves pattern with normal background activity. CAE occurs in 10% to 15% of all children with epilepsy with an annual incidence of 6.3 to 8/100,000 in children <15 years of age. Females are more affected than males. Epilepsy onset is typically between the ages of 4 to 8 years with a peak incidence of 6 to 7 years. CAE does not start after age 13 years. The primary objective of this study is: To identify the optimal anticonvulsant (i.e. the antiepileptic drug (AED) with highest rate of seizure control and lowest incidence of treatment limiting toxicity) used for the initial treatment of children with Childhood Absence Epilepsy (CAE). The secondary objectives are: To determine the pharmacogenetic and other non-heritable factors underlying the interindividual variation in anticonvulsant response efficacy and toxicity. To define and contrast the effects of ethosuximide, lamotrigine, and valproic acid monotherapy on cognition (attention), behavior and quality of life in children with Childhood Absence Epilepsy. Cohort F) Cincinnati Controls. These are local healthy children selected to be representative of the population of Cincinnati with respect to gender and ancestry. Cohort G) Cytogenetics cases are ascertained by the clinical request to obtain cytogenetic analysis. The platform used included genotyping data which are then available for genome wide association analysis

  Study phs000494

• National Institute of Dental and Craniofacial Research (NIDCR) Sjögren's International Collaborative Clinical Alliance (SICCA): Center for Inherited Disease Research (CIDR) Genome-Wide Genotyping

  The Sjögren's International Collaborative Clinical Alliance (SICCA) is a multisite observational cohort study that recruited a large cohort of geographically diverse participants. Enrollment of participants began in late 2004 at five (one domestic and four international) sites, in which all groups used the same protocol-directed methods to provide uniform evaluations; collect oral, ocular, and rheumatologic data; and collect specimens. The sites were located at the University of Buenos Aires, Argentina; Peking Union Medical College, Beijing, China; Rigshopitalet (formerly at Glostrup Hospital), Copenhagen, Denmark; Kanazawa Medical University, Ishikawa, Japan; King's College, London, UK (joined in 2007); and the University of California, San Francisco (UCSF). In 2009, Aravind Eye Hospital, Madurai, India; Johns Hopkins University, Baltimore, MD; and University of Pennsylvania, Philadelphia, PA were added as additional SICCA sites. UCSF is the coordinating center for SICCA. All specimens and data collected for SICCA are housed at UCSF. To facilitate the research focused on understanding the genetics of Sjögren'sSjögren's syndrome, high-density SNP genotype data and SICCA clinical information are being made available to the research community. This includes participants recruited from all SICCA research groups (RG). These participants (3,382), blood relatives (439), and unrelated healthy controls (25) had their whole blood or saliva sample (Oragene) extracted for DNA for the GWAS at the UCSF DNA Bank. Eighty eight percent of the participants are women, most are of European or Asian ancestry and the median age is 55. To assess potential batch effects when doing case-control comparisons using planned external controls, 30 DNA samples from each of three studies were genotyped with SICCA DNA samples: The Genetic Architecture of Smoking and Smoking Cessation - Collaborative Genetic Study of Nicotine Dependence (COGEND) - PI: Laura Bierut. NEI-Age-related disease study (AREDS) - Genetic Variation in Refractive Error Substudy - PI: Dwight Stambolian. Controls from the National Institute of Mental Health's (NIMH's) Human Genetics Initiative. Genome-Wide Association Study of Schizophrenia - PI: Pablo V. Gejman. Molecular Genetics of Schizophrenia - nonGAIN Sample (MGS_nonGAIN) - PI: Pablo V. Gejman. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data quality control, dbGaP preparation and posting, and imputation to 1000 Genomes to increase SNP density was performed by the Center for Biomedical Statistics at the University of Washington. Data analysis was performed at UCSF using software PLINK, EIGENSOFT, and SNPTEST.

  Study phs000672

• Research Study into The Molecular Genetics of Hereditary Neuropathies

  Identification of genes implicated in inherited neuropathy through collecting and sequencing multiple generation families with inherited neuropathy. Patients in this study have been evaluated for demyelinating peripheral neuropathy as determined by decreased motor nerve conduction velocities in the sural nerve. Patients have also been screened for mutations in all genes implicated in demyelinating peripheral neuropathy and are expected to have previously unidentified mutations. Exome (WES) sequencing for two patients affected with inherited neuropathy. VCF files with called variants for each de-identified patient have been submitted.

  Study phs001351

• Genome-Wide Association Study of Sporadic and Familial Testicular Germ Cell Tumors

  Case-Control Study:Testicular germ cell cancer has been increasing among men during most of the 20th century. Despite this increase, the etiology of testicular cancer is poorly understood. To better understand the molecular epidemiology of testicular cancer, the National Cancer Institute and the Department of Defense are conducting a case-control study of testicular cancer among military servicemen. The project includes obtaining biosamples and questionnaire data from all participants. Pre-diagnostic serum samples are available from the approximately 1,000 cases and 1,000 controls enrolled in the study. Multiple-Case Family Study:In a parallel project, we are also studying families in which 2 or more testicular cancers have occurred. Among those men diagnosed with testicular cancer, about 1-3 percent report a family history of the disease (FTGCT). Brothers of affected individuals are 8 to 10 times more likely to develop testicular cancer, and men whose fathers had testicular cancer are four times more likely to develop testicular cancer, when compared with the relatives of men who have never had testicular cancer. Large-scale genetic linkage studies have failed to identify one or more rare, highly-penetrant testicular susceptibility genes. Rather, it appears that these familial clusters are due to the combined effects of multiple more common genes with low penetrance (so-called "polygenic inheritance"). Our cohort of FTGCT families was assembled to characterize this syndrome's clinical phenotype, and to discover the full range of cancer susceptibility loci that influence TGCT pathogenesis.

  Study phs001303