Search Results - EGA European Genome-Phenome Archive

Congenital diaphragmatic hernia (CDH) is a common and severe birth defect characterized by structural defects of the diaphragm and by pulmonary hypoplasia. Congenital diaphragmatic hernia patient may present either as an isolated phenotype or together with other congenital anomalies in a complex phenotype. Despite the clinical significance of CDH, the underlying genetic and developmental pathways are incompletely understood. In order to establish a catalog of human genetic variation for this condition, we performed whole exome sequencing (WES) on 275 carefully phenotyped individuals with CDH in the Pediatric Surgical Research Laboratories at the Massachusetts General Hospital (Boston, MA, USA) and Boston Children's Hospital (Boston, MA, USA). The exome data generated are valuable for comparison of candidate genes derived from WES of other CDH cohorts or affected kindreds, and to provide ideal candidates for further functional studies with the ultimate goal of enhancing our understanding of the heterogeneous and, possibly, oligogenic molecular etiology of CDH. While familial clustering has been reported in rare kindreds, the majority of probands with CDH have no family history of CDH leading to the hypothesis that de novo variants are an important and relatively frequent etiological mechanism. In the second version of the study, we performed WES analysis on 87 trios, to assess the contribution of de novo mutations in the etiology of diaphragmatic and pulmonary defects and to identify previously unknown candidate genes. This dbGaP submission includes WES data on: (a) 20 new probands, (b) 9 probands also reported in the previous version (dbGaP accession no. phs000783.v1.p1), (c) 174 unaffected parents, including the parents of 67 previously reported probands. Combined analysis with other available cohorts of congenital diaphragmatic hernia revealed a genome-wide enrichment of likely gene-disrupting de novo variants (i.e., nonsense, frameshift or splice site), and missense de novo variants predicted in silico to be damaging.

Study phs000783

NINDS-Genome-Wide Genotyping in Parkinson's Disease: First Stage Analysis and Public Release of Data

Epidemiological studies have estimated a cumulative prevalence of PD of greater than 1 per thousand. When prevalence is limited to senior populations, this proportion increases nearly 10-fold. The estimated genetic risk ratio for PD is approximately 1.7 (70% increased risk for PD if a sibling has PD) for all ages, and increases over 7-fold for those under age 66 years. The role for genes contributing to the risk of PD is therefore significant. This study utilized the well characterized collection of North American Caucasians with Parkinson's disease, and neurologically normal controls from the sample population which are banked in the National Institute of Neurological Disorders and Stroke (NINDS Repository) collection for a first stage whole genome analysis. Genome-wide, single nucleotide polymorphism (SNP) genotyping of these publicly available samples was originally done in 267 Parkinson's disease patients and 270 controls, and this has been extended to include genome wide genotyping in 939 Parkinson's disease cases and 802 controls. The NINDS repository was established in 10-2001 towards the goal of developing standardized, broadly useful diagnostic and other clinical data and a collection of DNA and cell line samples to further advances in gene discovery of neurological disorders. All samples, phenotypic, and genotypic data are available to the research community including to academics and industry scientists. In addition, well characterized neurologically normal control subjects are a part of the collection. This collection formed the basis of this first stage study by Fung et al., and the expanded study by Simon-Sanchez et al. The genotyping data was generated and provided by the laboratory of Dr. Andrew Singleton NIA, and Dr. John Hardy NIA (NIH Intramural, funding from NIA and NINDS). Important links to apply for individual-level data Data Use Certification Requirements (DUC) Apply here for controlled access to individual level data Participant Protection Policy FAQ

Study phs000089

WES Elucidation of Pathogenetic Mechanisms for Immune System Disorders and NIAID Pilot of Genetic Incidental Finding Management

Background: - There are many types of immune disorders. These range from rare immune deficiencies to allergies to autoimmune disease like rheumatoid arthritis. Genes are the instructions our body uses to work and develop. A new technology called whole exome sequencing may help find the cause of these disorders. Whole exome sequencing is a way to look at many genes at once for errors. Researchers hope to find new gene changes that lead to immune disorders. Additionally, researchers are interested in finding the best way to manage unexpected but important findings by whole exome sequencing. Objectives: - To better understand genetic causes of immune system disorders. Also, to better understand people s thoughts and feelings about immune system disorders and new genomic testing. Eligibility: - People ages 0 100 with an immune disorder or a relative with an immune disorder. People must be at least 2 to be evaluated at the NIH clinical center. People must be at least 12 to do the survey/interview portion of the study. Design: Participants will have their genes sequenced. They may be asked for a new sample of blood. If participants cannot come for a study visit, they can have a blood sample collected by their local lab or doctor and sent by mail. Researchers may or may not find the cause of the participant s immune disorder. Participants will learn that information. Some participants may be asked to return to NIH to get results and have more tests. Researchers may share information with other studies. The data will be anonymous. For the survey part of the study, participants will answer questions about their or their relative s immune disorder. They will also answer about their thoughts and feelings about genomic testing. Some participants will be asked for a brief interview to ask more about the survey topics. There may be more follow-up after several months. From clinicaltrials.gov

Study phs001561

NEI CIDR Methylation Profiling of Primary Open Angle Glaucoma in GLAUGEN Samples

This is a case-control study of Primary Open Angle Glaucoma (POAG). POAG is a progressive optic neuropathy that eventually leads to blindness. More than 30 million people worldwide have Primary Open Angle Glaucoma (POAG), of which greater than 3 million are blind. Gene expression changes in the retina have been observed for POAG. Several recent studies, including the GLAUGEN (Glaucoma Gene Environment) initiative have used GWAS to identify correlative regions of the genome. Despite this, the genetic basis of Glaucoma is not well understood. Epigenetic variation may account for low heritability and environmental effects on human disease. Despite the significant advances being made in understanding the role of epigenetics in gene regulation in other fields, little is known about the relationship between DNA methylation patterns, retinal gene expression, and retinal disease. The goal of this study is to identify differentially methylated regions in the peripheral blood of patients with POAG. The case identification is as per the GLAUGEN description: Cases and controls were recruited from ophthalmology clinics and were examined by ophthalmologists. For cases the clinical exam included intraocular pressure measurements, optic nerve assessment and visual field evaluation. Controls had no family history of glaucoma, normal intraocular pressure and normal optic nerves. POAG and control samples come from Massachusetts Eye and Ear Infirmary (MEEI). These samples were collected and genotyped as part of the GLAUGEN study. From the MEEI, 50 patients were selected from POAG pedigrees, to include all the probands genotyped by CIDR and are currently undergoing exome sequencing, and to include additional genotyped probands who belong to pedigrees of sufficient size and structure that parent of origin effects could be evaluated. Additional individual-level phenotype and genotype data may be obtained through the authorized access portal of phs000308 (Geneva - Glaugen GWAS Study).

Study phs000461

Optimizing Primary Stroke Prevention in Children with Sickle Cell Anemia (STOP II)

The STOP II trial evaluated whether prophylactic transfusion in patients with sickle cell disease and high risk of stroke can be safely halted after 30 months of treatment during which patients became low risk for stroke.Stroke causes substantial morbidity in children with sickle cell disease. To prevent first strokes, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) used prophylactic transfusions in children who were identified by transcranial Doppler (TCD) ultrasonography as being at high risk for stroke. This strategy reduced the incidence of stroke among such children from 10% per year to less than 1% per year, leading to recommendations for TCD screening and prophylactic transfusion for children with abnormal velocities on ultrasonography. Despite the reduced risk of stroke, long-term use of transfusions can cause adverse side effects, such as iron overload or alloimmunization. However, cessation of transfusions is associated with recurrence of stroke, and at the time of the STOP II trial, there were no clinical or laboratory indicators to guide the duration of prophylaxis. Therefore the STOP II trial was initiated to determine whether transfusions could be limited by monitoring patients with TCD examinations after transfusions were halted and resuming transfusions if the examination indicated a high risk of stroke.The trial was halted for safety concerns after 79 of a planned 100 children were randomized. Discontinuation of transfusion for the prevention of stroke in children with sickle cell disease resulted in a high rate of reversion to abnormal blood-flow velocities on Doppler studies and stroke incidence.Instructions for requesting individual-level data are available on BioData Catalyst at https://biodatacatalyst.nhlbi.nih.gov/resources/data/. Apply for data access in dbGaP. Upon approval, users may begin accessing requested data in BioData Catalyst. For questions about availability, you may contact the BioData Catalyst team at https://biodatacatalyst.nhlbi.nih.gov/contact.

Study phs002386

National Institute of General Medical Sciences (NIGMS) Human Genetic Cell Repository Human Variation Panels including 100 African-Americans (HD100AA), 100 Caucasians (HD100CAU), 100 Han People of Los Angeles (HD100CHI) and 100 Mexican American Community of Los Angeles (HD100MEX)

The Human Genetic Cell Repository is sponsored by the National Institute of General Medical Sciences (NIGMS) with the mission of supplying scientists with the materials for accelerating disease gene discovery and functional studies. The resources available include highly-characterized, contaminant-free cell cultures and high quality, well-characterized DNA samples derived from these cultures, both subjected to rigorous quality control. The Repository was established in 1972 at Coriell and contains more than 9,500 cell lines, primarily fibroblasts and transformed lymphoblasts. The Repository has a major emphasis on inherited diseases and chromosomally aberrant cell lines. In addition, it contains a large collection dedicated to understanding human variation that includes samples from populations around the world, the CEPH collection, the Polymorphism Discovery Resource, Human Variation and many apparently healthy controls. The Human Variation collection provides cell lines and DNA samples from a variety of populations. The panels of African-Americans (HD100AA) and Caucasians (100CAU) used for this study are comprised of samples present in the Repository that were originally collected over the years from apparently healthy people to be used as "controls", for example, unaffected family members of persons with identified mono-genetic diseases. The samples for the Han people of Los Angeles (HD100CHI) and the Mexican American Community of Los Angeles (HD100MEX), however, were collected relatively recently from volunteers, identified as member of these communities, specifically for use in these panels. The Coriell Genotyping and Microarray Center in conjunction with the NIGMS repository used the Affymetrix Genome-Wide Human SNP 6.0 platform to genotype 400 samples from the NIGMS human variation panels. The populations genotyped included Americans of African, Caucasian, Mexican, and Han Chinese ancestry. The Affymetrix SNP 6.0 array detects approximately 940,000 SNPs and provides copy number information for more than 900,000 additional locations across the genome.

Study phs000211

National Institute of Neurological Disorders and Stroke (NINDS), Family Study of Essential Tremor (FASET), Identification of Susceptibility Genes for Essential Tremor

The Familial Study of Essential Tremor (FASET) was designed to identify susceptibility genes for Essential Tremor. ET is among the most common neurological diseases with a prevalence (age > 40 years) estimated to be 4.0% and prevalence in advanced age (> 90 years) exceeding 20%. ET, often referred to as "familial tremor", is generally regarded as a highly genetic disorder with families, with affected members over multiple generations, and twin studies show high concordance among monozygotic twins. Probands (affected with ET) and relatives were enrolled in a family study of ET at Columbia University, New York between 2011 - 2014. The study was approved by the Institutional Review Board at Columbia University and written informed consent was obtained from all enrollees. The criteria for enrollment were: 1) the proband had early-onset ET with age at onset < 50 years, 2) the proband had a diagnosis of definite or probable ET, 3) in addition to the proband, there were at least two affected relatives in the family, 4) additional affected and unaffected family members were willing to participate in the study, and 5) the families contained more than two affected individuals in different generations. Blood samples were also collected for genetic research. For the genetic analyses, we excluded enrollees that we or others had diagnosed with Parkinson's disease (PD) or dystonia. The final sample includes 52 families (52 probands [affected with ET]) and 155 relatives). The number of affected individuals enrolled per family ranged from 3 - 7 (mean = 4.1). Genetic samples from FASET were analyzed with whole genome SNP genotyping (for linkage analyses) and whole exome sequencing. It is hoped that this resource will better help researchers to understand the genetic causes of ET and underlying disease pathogenesis.

Study phs000966

GATA2 Deficiency and the MonoMAC Syndrome

The aim of this study was to identify the germline mutation(s) in an extended family with individuals having MonoMAC Syndrome/GATA2 deficiency but lacking a canonical GATA2 mutation. GATA2 deficiency patients develop bone marrow failure, severe immunodeficiency and may progress to myeloid malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The definitive treatment for GATA2 deficiency is a bone marrow transplant. Approximately 90% of GATA2 deficiency patients have a known de novo or inherited germline mutation in the GATA2 gene, but ~10% have no identified mutation. The study was initiated with the first patient and her second cousin, both of whom were treated for MonoMAC Syndrome and received bone marrow transplants at the NIH. Pedigree analysis and clinical evaluation identified the individuals in several generations of these patients' near and distant relatives who are/were presenting or carrying the disease manifestations of GATA2 deficiency. Whole Genome Sequencing (WGS) was employed on these patients' two related nuclear families to identify variants that segregated with the disease trait and carrier status of their families. Genotyping was confirmed with direct DNA sequencing of these and other family members within the extended family across generations. A single base adenine-to-thymidine change was identified in a highly conserved enhancer element ~117,000 bp upstream of the GATA2 gene. It creates a new Composite Element, a DNA motif known to be critical in the regulation of hematopoiesis. This variant is unique to this family and is not present in dbSNP or other variant databases. It segregates with the disease trait and obligate carriers throughout a large pedigree. In vitro studies show that this variant drives allele-specific overexpression of the GATA2 gene in cultured cells and luciferase assays. The WGS sequence from the nuclear families will be shared on dbGaP.

Study phs003269

UK10K COHORT ALSPAC

The UK10K project proposes a series of complementary genetic approaches to find new low-frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome-wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein-coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will directly analyse quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a two-generation prospective study. Pregnant women living in one of three health districts in the former county of Avon with an expected delivery date between April 1991 and December 1992 were eligible to be enrolled in the study, and this formed the initial point of contact for the development of a large, family based resource. Information has been collected on the children and the mothers through retrieval of biological materials (e.g. antenatal blood samples, placentas), biological sampling (e.g. collection of cord blood, umbilical cord, milk teeth, hair, toenails, blood and urine), self-administered questionnaires, data extraction from medical notes, linkage to routine information systems and at repeat research clinics.

Study EGAS00001000090

Genetic_Heterogeneity_of_the_familial_gastric_neuroendocrine_tumors

Gastric neuroendocrine tumors (gNETs) occur with an estimated frequency of 2 per 100,000 in the general population. Type I gastric neuroendocrine tumors (NETs) represent the 75% of gNTEs and arise from gastric enterochromaffin-like (ECL) cells. They have late age of onset and usually benigh course. Classically, hypergastrinemia in patients who have autoimmune atrophic gastritis, causes hyperplasia of gastric ECL cells that progresses into type I gastric NETs and parietal cell (PC) destruction. The genetic bases in families with this disease are unknown. We performed an exome sequencing study of an atypical aggressive familial gNETs case (with early age onset, nodal infiltrations and gastric adenocarcinomas) that followed a recessive model. We identified a deleterious mutation in homozygosis in the ATP4A gene, which encodes the proton pump responsible for acid secretion by gastric parietal cells. This mutation lead to achlorhydria first, and hypergastrinemia and gNET developing as consequence (Calvete et al. 2014). Recently, two more families with gNETs, classical clinical traits and recessive model have been studies by WES but we didn't find any mutation in the ATP4a gene. However, putative mutations affecting genes that contribute to the development and the integrity of PC have been found suggesting that genetic alterations associated to this disorder target to a unique cell type (parietal cells). In order to cinfirm this hypothesis, it is necessary the search for new genes implicated in the gNETs, more familial cases are needed to be studied. We have identified four more new familial gNETs cases. Here, we propose their study by WES. The first family is formed by thress siblings with gNETs. The other families include two siblings with gNETs. 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/

Study EGAS00001002273

15120 results for "cancer studies using rna-seq"

in 22.30 milliseconds.

A renal cell carcinoma tumorgraft platform to advance precision medicine

Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia (HIPO, H005)

FFPE_whole_genome_pilot

Angiosarcoma_whole_exome

Angiosarcoma_RNA_sequencing

Angiosarcoma_targeted_pulldown_cancer_gene_panel

Deep_sequencing_of_melanoma_for_driver_mutations

NECC WXS

PPCG UK BAMs

Angiosarcoma targeted pulldown cancer gene panel

Whole Exome Sequencing of Congenital Diaphragmatic Hernia Patients and Trios