3613 results for "*geneti*"

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• Detecting and Subtyping Lung Cancer Through Analysis of Circulating Tumor DNA

  Small cell lung cancer (SCLC) is among the most aggressive tumors with poor clinical outcomes. Tumors are rarely resected, which is a major barrier to molecular profiling of tumor tissue; therefore, non-invasive approaches using circulating tumor DNA (ctDNA) from liquid biopsies are needed to help advance research and clinical care for patients with SCLC. We developed a targeted capture panel that profiles SCLC genes and transcriptional regulation sites, including transcription start sites (TSS) and transcription factor binding sites (TFBS). This is a single assay that detects genomic mutations and transcriptional regulation activity based on ctDNA fragment patterns reflecting epigenetic nucleosomal positions. We applied this assay to sequence patient-derived xenograft (PDX) and patient plasma samples. We also performed whole genome sequencing (WGS) for a subset of the PDX plasma samples to validate the capture data. We developed new algorithms to quantify activity of key SCLC marker genes of ASCL1, NEUROD1, POU2F3, and ATOH1 and to classify SCLC subtypes based on activity of these markers. Furthermore, we developed a model to classify SCLC from non-small cell lung cancer (NSCLC), which has potential important applications for monitoring transdifferentiation and tumor plasticity.

  Study phs003570

• Parkinson Cell Atlas in 5D (PD5D)

  Genome-wide association studies (GWAS) have unequivocally linked thousands of noncoding variants to Parkinson's disease (PD). Why have these breakthroughs not uncovered the mechanism(s) of common, genetically complex PD? We do not know how GWAS variants cause neurodegeneration, which variants are causal, and why they impair some brain cells but not others. Overwhelming evidence shows that cis regulation of transcription is the most likely mediator of disease risk, and that it is finely tuned by cellular and dynamic context.Here we will pinpoint the causal gene(s) through which GWAS loci function in spatially barcoded, single brain cells and, dynamically over pseudotime (Stage) using single-nucleus expression Quantitative Trait Locus (eQTL) analysis. Putative causal genes will be tested mechanistically in cell- and stage-specific analyses in vivo in Drosophila avatars and in vitro in human pluripotent stem cells. Moreover, we will identify the corresponding causal GWAS variants (eSNP) through allele-specific expression (ASE) and CRISPR/Cas9-variant editing in single brain cells. Our collaborative and highly integrated project will begin to reveal the complex human genetics of PD through a dynamic five-dimensional view of proximal cellular mechanisms across brain cells (1D), brain space (3D), and disease stage (1D).

  Study phs004421

• NCTN: Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome (AAML1531)

  Study ID: AAML1531 NCT Number: NCT02521493 Children's Oncology Group (COG) Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome (AAML1531) Trial Description: This phase III trial studies response-based chemotherapy in treating newly diagnosed acute myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Response-based chemotherapy separates patients into different risk groups and treats them according to how they respond to the first course of treatment (Induction I). Response-based treatment may be effective in treating acute myeloid leukemia or myelodysplastic syndrome in younger patients with Down syndrome while reducing the side effects. Clinical data presented in the following publication(s): • PMID 34320162 Disease type(s): • Hematopoietic Neoplasm/Leukemia - Acute Myeloid Leukemia • Hematopoietic Neoplasm/Leukemia - Myelodysplastic Syndrome Clinical Dataset(s) included:• NCT02521493-D1 (PMID 34320162): There are 2 datasets associated with PMID 34320162, NCT02521493-D1 through NCT02521493-D2. The NCT02521493-D1 dataset is a patient level dataset (single row per patient) containing patient characteristics, laboratory findings (hemoglobin, peripheral WBC, peripheral platelet), cytogenetics, outcome (overall survival and event-free survival), neutrophil recovery, ICU admission, select toxicity data, and targeted sequencing data for eligible myeloid leukemia in children with Down syndrome (ML-DS) enrolled on the AAML1531 clinical trial. • NCT02521493-D2 (PMID 34320162): There are 2 datasets associated with PMID 34320162, NCT02521493-D1 through NCT02521493-D2. The NCT02521493-D2 dataset is an adverse event level dataset (single row per adverse event, period, and patient) containing information of the micro-organisms associated with adverse events by period in the AAML1531 clinical trial. Additional genomic data are available for this trial under phs002187.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004081

• National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from GenTAC include Aorta Tissue, Buffy Coat, DNA, EBV Cell Line, Lymphocytes, Plasma, and Polymorphonuclear Cells/RBC Pellets. Please note that use of biospecimens in genetic research is subject to a tiered consent. Objectives: The overall objective of GenTAC was to establish a registry of patients with genetically induced thoracic aortic aneurysms and related cardiovascular conditions, and collect associated medical data, as well as blood and tissue samples and make them available to investigators to advance research in diagnosis and management of genetically induced thoracic aortic aneurysms.Background: Thoracic aortic aneurysms (TAAs) predispose individuals to life threatening aortic complications, including aortic dissection and rupture. The treatment of complications arising from TAAs is complex, with high rates of morbidity, mortality, and surgical procedures. TAAs are associated with loss of vascular smooth muscle cells and degeneration of extracellular matrix in the aortic wall. This degeneration may be caused by hypertension and inflammation, particularly in elderly individuals. Genetic mutations are the main cause of TAAs in many young or middle-aged individuals. Genetic disorders, such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome, have a high risk for TAA, and up to 20% of individuals with TAAs or dissection have a family history of TAAs without being affected by a known syndrome or known genetic mutation. While diagnostic and treatment advances have dramatically improved care for patients with genetically induced TAAs, many questions remain about how best to identify and treat these disorders. Thus, GenTAC was developed as a longitudinal registry for patients affected by genetically induced thoracic aortic conditions in order to facilitate ongoing and future investigations to improve the diagnosis and clinical management of patients with genetically induced TAAs. Information gained from studying the genetically induced TAAs is expected to benefit the clinical management of non-genetic TAAs, as well.Participants: Over 3,500 participants were enrolled.Design: GenTAC was a longitudinal observational cohort study of affected individuals with either known or suspected genetic mutation that predisposes them for thoracic aortic aneurysms and dissections (TAAD). There were no interventions planned, and all decisions regarding approaches to treatment were to be made by the patients and their care teams. Enrollment data were abstracted from medical records or obtained through patient interviews. The data collected include clinical evaluations (by several organ systems), historically diagnosed conditions and outcomes and drug treatment; patient reported quality of life, co-morbidities, family history, smoking, alcohol use, and pregnancy history; most recent imaging evaluations, genetic testing, blood chemistry, and surgical interventions. When blood could not be collected from participants, a saliva sample was obtained as a source of DNA. Excess aortic tissue was frozen from participants that underwent surgery. Follow-up data was collected at regular intervals for each participant enrolled, with the interval varying by the diagnosis. Follow-up data include outcomes, clinical and imaging evaluations and treatment and lifestyle changes since the enrollment visit. Images were read by the imaging core according to the study protocol. Diagnosis of each participant was confirmed by the phenotyping core.Conclusions: GenTAC established a vast biospecimen inventory and clinical database from over 3500 participants that is available to researchers with the ultimate goal of advancing the diagnosis and management of genetically induced thoracic aortic aneurysms and other cardiovascular complications. Some of the publications resulting from analysis of the GenTAC data and biospecimens can be found at https://www.nhlbi.nih.gov/research/resources/gentac/research.Publications: A list of GenTAC publications can be found on the GenTAC Alliance website: https://www.gentacalliance.org/publications/.

  Study phs004340

• Genome-Wide Association Study and Predictors of Neonatal Blood Cell Traits in Hispanic Newborns

  This study leverages cord blood samples from the NHLBI's Umbilical Cord Blood Unit Collection to conduct genome-wide association studies (GWAS) of neonatal blood cell traits in newborns of Hispanic ethnicity. Cord blood (CB) aliquots from 382 de-identified newborns of Hispanic ethnicity were obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) through Project Request #11595. The CB samples were originally collected between 1998-2001 as part of the COBLT (Cord Blood Transplantation) study. Briefly, the COBLT study primarily aimed to (i) build ethnically diverse public cord blood banks with standardized collection/processing protocols and (ii) to conduct a prospective phase II trial of unrelated cord-blood transplantation in pediatric and adult candidates for allogeneic hematopoietic stem cell transplantation. The collected CB units and aliquots are currently maintained by BioLINCC, with samples available from donors with diverse racial/ethnic background. All COBLT CB samples were red cell depleted, volume reduced and cryopreserved with DMSO/Dextran in 25 ml bags. Test aliquots were used by COBLT for flow cytometry to characterize predictors of time to engraftment for CB samples. Cell surface markers assessed included CD34, CD45, CD3, CD8, CD4, CD19, CD16, and CD56. CB aliquots were requested from subjects reported as Hispanic in the NHLBI Umbilical Cord Blood Unit Collection. Epidemiological data and cell-related indices were obtained from the Umbilical Cord Blood Unit Collection repository. To investigate genetic variation associated with blood cell traits measured in the Hispanic newborn samples, we isolated DNA from CB and conducted genome-wide SNP genotyping using the Axiom PangenomiX array (Thermo Fisher). Whole-genome imputation was performed using the TOPMed Imputation Server, and GWAS of 24 blood and immune cell traits were conducted in up to 382 Hispanic newborns for each trait.

  Study phs004758

• Health Effects of Arsenic Longitudinal Study

  The Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes. We applied array-based genotyping technologies to baseline DNA samples from a subset of the HEALS study and linked those genotypes to data on arsenic species measured in urine. We used these data to identify regions influencing arsenic metabolism (AS3MT and FTCD). We also applied array-based DNA methylation technologies to baseline DNA samples from a subset of individuals from HEALS. These data were linked to data on arsenic concentration (in both urine and drinking water) to identify regions of the genome where DNA methylation is impacted by arsenic exposure.

  Study phs003839

• Blood and Marrow Clinical Trials Network - A Multi-Center, Phase III, Randomized Trial of RIC, and Transplantation of (dUCB) Versus HLA-Haplo Related Bone Marrow for Patients with Hematologic Malignancies (BMT CTN-1101-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.ObjectivesTo compare double unrelated umbilical cord blood and HLA-mismatched (haploidentical) related donor transplantations for the treatment of leukemia and lymphoma in adults.BackgroundEarlier studies have shown that partially HLA-mismatched related bone marrow (haplo-BM) and unrelated double umbilical cord blood (dUCB) are valuable sources of donor cells for Reduced-Intensity Conditioning (RIC) hematopoietic cell transplants (HCT) in patients that do not have access to either an HLA-matched sibling or suitably HLA-matched unrelated donor. Both haplo-BM and dUCB grafts are more accessible for patients lacking an HLA-matched donor.This study assessed the hypothesis that progression-free survival at two years after haplo-BM transplantation is similar to the progression-free survival after dUCB transplantation.ParticipantsPatients aged 18 to 70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were assigned to undergo double unrelated umbilical cord blood (n = 186) or HLA-mismatched (haploidentical) related donor transplantation (n = 182). Of the 186 patients randomized to the dUCB arm, 172 received the treatment as assigned. Of the 182 patients randomized to the haplo-BM arm, 153 received the treatment as assigned.Enrolled patients had a Karnofsky score greater than or equal to 70% and adequate physical function of the cardiac, hepatic, renal, and pulmonary systems. Furthermore, subjects had one of the following: Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR); Acute Myelogenous Leukemia (AML) in CR1; Acute Leukemias in 2nd or subsequent CR; Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR; adult T-cell leukemia/lymphoma in first or subsequent CR; Burkitt's lymphoma: second or subsequent CR; chemotherapy-sensitive Lymphoma.DesignParticipants were enrolled in the study between June of 2012 and June 2018 and randomized 1:1 using random block sizes stratified by transplant centers (n=33). The primary end point was 2-year progression-free survival (PFS).The donor and recipient in the haplo-BM arm were HLA identical for at least one antigen (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1.Patients enrolled in the dUCB arm had to have two UCB units with a minimum of 1.5 x 10^7/kg pre-cryopreserved total nucleated cell dose. For non-red blood cell depleted units, the minimum pre-cryopreserved total nucleated cell dose of each unit was at least 2.0 x10^7/kg. Furthermore, units were HLA matched at a minimum of 4/6 to the recipient at HLA -A, HLA-B (at low resolution using DNA based typing), and HLA -DRB1 (at high resolution using DNA based typing).All participants received a conditioning regimen/preparative regimen prior to transplant as well as a GVHD prophylaxis regimen.Participants randomized to the dUCB arm received the following conditioning regimen: fludarabine cyclophosphamide, and either 200 or 300 cGy total-body irradiation (TBI). GVHD prophylaxis started 3 days prior to transplantation and included 15 mg/kg mycophenolate mofetil three times daily (with a maximum daily dose of 3 g) through day 35 and cyclosporine adjusted to maintain a trough level of 200 to 400 ng/mL through day 100 and tapered by 10% weekly until discontinued between days 180 and 200.Participants randomized to the haplo-BM received the following conditioning regimen: cyclophosphamide, fludarabine, and 200 cGy TBI. GVHD prophylaxis consisted of 50 mg/kg cyclophosphamide IV daily on days 3 and 4, 15 mg/kg mycophenolate mofetil three times daily from days 5 through 35, and tacrolimus adjusted to maintain a concentration of 5 to 15 ng/mL from day 5 through day 180.ConclusionsThere were no significant differences seen in progression-free survival between double unrelated umbilical cord blood and HLA-mismatched (haploidentical) related donor transplantations for leukemia or lymphoma. Analyses of secondary end points, including overall survival, favored haploidentical BM donors.Fuchs EJ, O'Donnell PV, Eapen M, et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021;137(3):420-428. doi:10.1182/blood.2020007535

  Study phs004698

• Lung Cancer Genetic Study Among Asian Never Smokers

  The Lung Cancer Genetic Study Among Asian Never Smokers includes data from four population-based studies conducted among Asian women: the Shanghai Women's Health Study (SWHS), the Hwasun Cancer Epidemiology Study (HCES1 and HCES2), the Female Lung Cancer Consortium in Asia (FLCCA, including sFLCA), and the Guangzhou Lung Cancer Study (GLCS). Shanghai Women's Health Study (SWHS): The SWHS is a population-based prospective cohort study of approximately 75,000 adult women who were recruited between 1997 and 2000. The cohort has been followed by a combination of record linkage and active follow-ups. Lung cancer patients identified in the SWHS and non-cases were included in the current study.Hwasun Cancer Epidemiology Study-Lung Cancer (HCES1 and HCES2): The HCES is a hospital-based case-control study whose goal is to identify factors of the cancer development and clinical progression in a Korean population. Included in this project were 299 female lung cancer cases from HCES2, who were diagnosed between April 2004 and February 2013 at Chonnam National University Hwasun Hospital, a cancer specified hospital in Jeollanam-do province, South Korea. Controls were randomly selected from women with no previous cancer diagnosis at enrollment in the Namwon Study and the Dong-gu study, ongoing community-based cohort studies in South Korea. A total of 1,103 controls (273 from HCES1 and 830 from HCES2) were genotyped by MEGA. Guangzhou Lung Cancer Study (GLCS): The GLCS is a case-control study including never-smoking women lung cancer cases and controls from Guangzhou, China.In this study, the DNA samples of 1,195 subjects from SWHS and GLCS were genotyped using whole exome sequencing (WES), and the DNA samples of 7,174 subjects from SWHS, HCES1, HCES2, FLCCA, and sFLCA were genotyped using the Multi-Ethnic Global Array (MEGA).

  Study phs002366

• Multi-Omics Study of Lung Cancer in Smokers From EAGLE

  EAGLE (Environment And Genetics in Lung cancer Etiology) is a population-based case-control study examining the full spectrum of lung cancer etiology from smoking initiation, smoking dependency to lung cancer development and outcome. It combines a traditional molecular epidemiology design with more integrative approaches by examining epidemiological, molecular, and clinical data together. To comprehensively investigate the effect of tobacco smoking behaviors on genomic or epigenomic alterations, we performed a multi-omics study including whole-genomic, transcriptomic, and epigenomic profiles in a total of 221 individuals from the EAGLE study.

  Study phs002992

• SCORCH: Revealing the Single Cell Determinants of Brain Relevant to Persistent HIV Infection and Opioid Use Disorder

  People living with HIV (PLWH) are at the higher risk for impaired cognitive functions such as HIV-Associated Neurocognitive Disorder or HAND. Further, higher use of legal and illegal opioids among PLWH could affect their immune functions and exacerbate CNS impairment. However, little is known about the HIV harboring cell types in brain, effect of ART on specific CNS cell types, and the modification of brain functions by opioid use. The human brain is composed of an enormous diversity of cell types defined by distinct gene expression, morphology, connectivity, and physiology. Single cell sequencing assays enable cell type-specific analysis of the role of these cell types in healthy brain function and disease. The overall objective of this proposal is to reveal the single cell determinants of opioid use disorder in the brain relevant to persistent HIV infection using snRNA-seq and snATAC-seq technologies, bioinformatics approaches, and validation studies. Single cell and spatial characterization of HIV and opioid use disorder across multiple regions of the human brain will be performed. These regions may include nucleus accumbens (NAc), prefrontal cortex (PFC), cerebellum, amygdala, and other accessible regions. These results will provide an unprecedented conceptual and experimental system to identify single cell determinants of opioid use disorder in the brain relevant to persistent HIV infection as well as potential opportunities to illuminate how genetic variation affects gene expression.

  Study phs004026