4210 results for "*geneti*"

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• NHLBI TOPMed: Heart and Vascular Health Study (HVH)

  Objectives The Heart and Vascular Health Study (HVH) is a case-control study of risk factors for the development of myocardial infarction (MI), stroke, venous thrombosis (VT), and atrial fibrillation (AF). The study setting is Group Health, an integrated health care delivery system in Washington State. Only VT cases and early-onset AF cases are included as part of TOPMed. Background The HVH study originated in 1988 with the examination of risk factors for MI. Over the ensuing years, the study has been funded by a series of grants which have added case subjects with stroke, VT, and AF. Study aims focused on the associations of medication use with cardiovascular events, and starting in 1997, the study aims expanded to include genetic associations with cardiovascular disease. Participants recruited in 2009 or later who provided blood samples for genetic analysis were asked for consent to deposit genetic and phenotypic data in dbGaP. Design As part of the HVH study, case subjects were identified by searching for ICD-9 codes consistent with MI, stroke, VT, or AF, and medical records were reviewed to confirm the diagnosis. Control subjects were identified at random from the Group Health enrollment and were matched to MI cases. All subjects have an index date. For cases, the index date was assigned as the date that the cardiovascular event (MI, stroke, VT, or AF) came to clinical attention. For controls, the index date was a random date within the range of the case index dates. For both cases and controls, information was collected from the inpatient and outpatient medical record, by telephone interview with consenting survivors, and from the Group Health pharmacy and laboratory databases. Consenting participants provided a blood specimen. Subjects Only VT and early-onset AF cases from HVH are included in TOPMed. Within the HVH study, VT and AF cases were diagnosed in both inpatient and outpatient settings, and only incident cases are eligible for inclusion in TOPMed. Genetic Research Genetic factors underlying cardiovascular disease are studied using DNA isolated from the blood samples. Phenotype data for HVH study participants are available through dbGaP phs001013.

  Study phs000993

• Assembling the Genetic Architecture of X-Linked Dystonia-Parkinsonism

  X-linked Dystonia-Parkinsonism (XDP, DYT3) is a long-standing quandary in human disease genetics. XDP is predominantly observed on Panay island in the Philippines. This study is one of the first of its kind to interrogate an unsolved Mendelian disorder by integrating genome and transcriptome assembly methods using Illumina, 10X Genomics, Pacific Biosciences, and Agilent genome targeting technologies. These data provide strong evidence for a pathogenic link between a noncoding SVA retrotransposon and XDP. We demonstrate that this Mendelian disorder is associated with a sine-VNTR-Alu (SVA) retrotransposon that inserted into the TAF1 gene and is shared by all XDP probands, yet never observed in controls from worldwide populations. Transcriptome assembly in iPSC-derived neural stem cells (NSCs) and neurons revealed that this SVA caused aberrant splicing and significant intron retention, which was negatively correlated with TAF1 expression. Remarkably, CRISPR/Cas9 excision of the SVA rescued the aberrant transcriptional signature and normalized expression of TAF1 in patient-derived NSCs. We have also interrogated iPSC-derived microglia to investigate the contribution of glial components to the cellular and molecular deficit, effect of TNF treatment on XDP transcriptional signatures. Disease signatures in brain were further interrogated using postmortem brain samples from the prefrontal cortex, caudate, cerebellum, and occipital cortex. To understand what XDP may have in common with other hereditary dystonias (such as DYT6), we are further comparing these signatures to ones associated with dystonia-specific variants in proteins that, like TAF1, are also involved in regulating transcription, i.e. THAP1.

  Study phs001525

• NHLBI TOPMed: Australian Familial Atrial Fibrillation Study

  In the Australian Familial AF Study, a cohort of probands with familial AF was recruited for genetics studies at the Victor Chang Cardiac Research Institute. Familial AF cases were identified from in-patient and out-patient populations at St. Vincent's Hospital and by referral from collaborating physicians throughout Australia. Study subjects underwent clinical evaluation with history, ECG and echocardiogram, and informed consent was obtained from all participants. 151 probands aged In the current TOPMed study, we have performed whole genome sequencing in European Ancestry cases with early-onset atrial fibrillation (defined as atrial fibrillation onset prior to 61 years).

  Study phs001435

• Experimental and Clinical Studies of Presbyacusis

  The Medical University of South Carolina (MUSC) Longitudinal Cohort Study of Age-related Hearing Loss is an ongoing (1988-current) community-based cohort study in Charleston, South Carolina, USA. The purpose of this study is to determine the audiological features of age-related hearing loss, identify genes and variants that cause or contribute to age-related hearing loss, a common and complex disease with a strong genetic component, and provide scientific bases for diagnosis, rehabilitation, and prevention. Participants are continuously enrolled and are recruited through community events, online and print advertisements, and participant referral. Recruitment, consenting, and study protocols are approved by the Institutional Review Board for Human Research at MUSC. Two to six visits are scheduled to complete a baseline examination that include, but are not limited to, pure-tone thresholds at conventional and extended high frequencies, middle-ear measures, speech recognition in quiet and noise, otoacoustic emissions, auditory brainstem responses, a battery of cognitive measures, and responses to self-report questionnaires including demographics, medical history, medications, hearing difficulties, hearing and hearing-aid history, and noise exposure history. Blood samples are obtained for clinical chemistries and DNA extraction for whole exome sequencing (WXS). Following completion of the baseline protocol, participants return annually to obtain an updated audiogram, health history, and hearing health history. Every 2 to 3 years after baseline, participants attend a comprehensive follow-up visit where most of the baseline measures are repeated. In 2026, the participant sample included 1,800 adults of 18 to >80 years of age at enrollment (mean age ~ 60 years) with longitudinal data spanning up to ~ 33 years (~ 57% female; ~ 17% Black). Exome sequencing is carried out using the Agilent SureSelect X2 Target Enrichment System (version 5) and the Agilent SureSelect Human All Exon V5 kit, which included 5' and 3' UTRs. DNA was sheared using the Covaris S220 focused ultrasonicator. Libraries were sequenced on the Illumina HiSeq 2500. Variant loads per gene are calculated and compared between groups with normal hearing and hearing loss. Individual variants affecting pure-tone thresholds are also identified. “Hearing phenotype”, based on audiometric results, is determined only for participants with genomic data. These participants are classified into one of the following five hearing phenotypes, Older-Normal, Metabolic, Sensory, Unclassified, and Unselected (see PMID: 30180840, PMID: 38011198). Analyses are also conducted in a second, independent cohort from a clinical sample.

  Study phs003327

• Gene Expression and Epigenetic Analyses of Human Myocytes from Different Muscles

  The study contains expression, DNA methylation data and genomic data of in vitro cultured primary myoblasts, immortalized control myoblast, and mutant myoblasts. The primary myoblasts were derived from biopsies of control, facioscapulohumeral dystrophy 1 (FSHD1) and FSHD2 patients from the tibialis anterior, quadricep, bicep and deltoid. FSHD is linked to DUX4 (Gene ID: 100288687) mRNA expression from the last copy of the D4Z4 repeats on chromosome 4q. The control myoblast cell line was derived from a quadricep biopsy of a healthy individual. The mutant cells, carrying either D4Z4 mutations, SMCHD1 (Gene ID: 23347) mutation or both, were generated from the control myoblast cells by CRISPR-mediated genome editing. Expression data is from bulk RNA-seq using the SmartSeq2 protocol for days 0 and 5 of differentiation of the primary myocytes from the bicep and deltoid of FSHD1 patients, and for days 0, 3/4/5 (early myotubes) and 12/13/14 (late myotubes) of differentiation of the immortalized control and mutant myocytes. DNA methylation data was produced using the TruSeq Methyl Capture EPIC kit (Illumina) for days 0, 3 and 12 of in vitro differentiation of primary myocytes from the tibialis anterior and quadricep of healthy individuals and FSHD2 patients. Genomic data for myoblasts was acquired by targeted, amplification-free DNA sequencing using CRISPR/Cas and the Nanopore sequencing platform. For Electrical Pulse Stimulation (EPS), immortalized control and FSHD patient myocytes were subjected to EPS on day 10 of differentiation using a C-Pace EM culture pacer. Cells with or without EPS stimulation were harvested 6 hours after completion of stimulation for RNA extraction.

  Study phs002554

• NSCCG CRC WES

  1006 Familial early onset gemrline CRC patients sequenced by the Molecular and Population Genetics group of the Institute of Cancer Research

  Dataset EGAD00001002204

• 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

• Sequencing data for ICGC Oesophageal Adenocarcinoma tissue samples - 129_cohort

  Sequencing data for ICGC Oesophageal Adenocarcinoma tissue samples - 129_cohort EAC whole genomic sequencing data - Publication Secrier & Li et al., 2016, Nature Genetics

  Dataset EGAD00001002218

• 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

• Congenital anosmia 1

  Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). To date, only a single recessive gene underlying complete anosmia has been identified. Here we sequenced the exomes of 10 individuals from a single family, including three with complete anosmia, across three generations to identify the genetic basis of congenital anosmia in this family. 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 EGAD00001002210