17281 results for "the best way to get coins in fc 26 Navštivte Buyfc26coins.com Společnost známá transparentními transakcemi..CQ2q"

in 16.46 milliseconds.

• Kids First: Genetics of Pediatric Germ Cell Tumors

  The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the genomic and phenotypic data from this study are accessible through dbGaP. The data is also available at the Kids First Portal, where other Kids First datasets can also be accessed in the cloud for data analysis, data visualization, collaboration and interoperability, open to all researchers and developers.Pediatric malignant germ cell tumors (GCTs) represent approximately 6% of childhood cancers, including 3% of tumors in children aged 0-14 years and 15% of tumors in adolescents. GCTs are heterogeneous and grouped together due to the presumed common cell of origin, the primordial germ cell (PGC). GCTs typically occur in the testes or ovaries; however, extragonadal GCTs can occur and are likely a result of abnormal germ cell migration during development. Evidence suggests that GCTs, including those diagnosed in adults, are initiated in utero. Thus, alterations in normal embryonic development are likely to be especially relevant to GCT etiology. Germline susceptibility has not been evaluated in an agnostic fashion in pediatric GCT, mainly due to a lack of an adequate number of samples; however, emerging evidence supports a genetic etiology.In the two Kids First GCT projects, we will evaluate genetic susceptibility to intracranial and extracranial GCT by sequencing probands and their unaffected parents. The goals of the project are to: 1) evaluate the contribution of rare genetic variants in GCT through the use of aggregate burden tests, focusing on genes and established regulatory regions; 2) identify de novo SNVs and CNVs in pediatric GCT using a case-parent triad design; and 3) identify molecular signatures in GCT tumor specimens, overall and by age group and tumor characteristics. Whole Genome Sequencing (WGS) data generated through the Gabriella Miller Kids First Pediatric Research Program will provide an opportunity to investigate the genetic origins of GCT in a diverse set of samples. Given the limited knowledge of GCT etiology and biology, the results of the proposed analyses are likely to have a big impact on the field.

  Study phs002322

• WES_of_adult_intellectual_disabilities_with_co_morbid_psychiatric_disorders

  ost adults with intellectual disabilities (ID) do not undergo genetic diagnostic investigation as part of their clinical care and have 'missed the boat' with regard to the WES and WGS genetic testing that is now being provided for children with ID. There is a dramatically increased risk of psychistric disorders in adults with ID, e.g. the risk of psychoses is 10X higher than in the general population. It remains an open question as to how much of adult ID is genetic in origin and how similar the genetic forms of adult ID are to those being diagnosed in children, in part due to survivor bias. There is also the opportunity to identify adults with treatable forms of ID, of which over 80 have been described, thus improving their clinical management. Furthermore, analysis of medical records of adults with genetic forms of ID can help to characterise the 'natural history' of individual disorders, resulting in more accurate prognoses for diagnosed children and identifying opportunities for improved management and possibly therapeutic intervention (e.g. optimal anti-epileptic therapy). Here we propose to exome sequence (to ~50X coverage) 200 adults with ID and co-morbid psychiatric disorders. This cohort has previously been assayed with chromosomal microarrays (Wolfe et al 2017 EJHG, 25, 66–72) identifying a diagnostic yield of ~11% which is comparable to the CNV diagnostic yield in various child ID cohorts (10-15%). The authors observed no substantive biases in diagnostic yield between different psychiatric diagnostic classes. The WES data will be analysed using the diagnostic workflows developed in the DDD study to ensure comparability between child and adult ID datasets. This study is intended as a pilot study to demonstrate the value of WES in adults with ID. 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 EGAS00001002962

• Whole genome sequencing of colon organoid cultures with artificially induced oncogenic mutations

  Using the CRISPR-Cas9 genome editing system, various oncogenic mutations were introduced in the genome of normal adult stem cells derived from the colon. The resulting clonal cultures were subjected to whole genome sequencing. In addition, the cultures were transplanted in a mouse and the resulting primary and metastatic tumors were also subjected to whole genome sequencing. The initial bulk culture, which was used to generate the mutations, was also whole genome sequenced and served as a reference sample to filter germline variants.

  Study EGAS00001001969

• 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

• Circulating RNAs in Acute Heart Failure (CRUCIAL)

  The purpose of this American Heart Association-funded and NIH-funded study is to examine circulating RNAs in the acute congestive heart failure (CHF) setting, and how they change with decongestive therapy, and their function in vitro and in vivo. The investigators are testing the hypothesis that ex-RNA levels change significantly during decongestion therapy and can be used as a marker of those individuals who respond to CHF therapy (in terms of cardiac structure or outcome). Additionally, the translational research design allows the investigators to assay the effects of these RNAs on tissue phenotypes in vitro.

  Study phs003403

• Ulcerative Colitis Human Microbiome Project (UCHMP)

  The aims of the multi-center Ulcerative Colitis Human Microbiome Project (UCHMP) are to examine the role of the enteric microbiome in causing human ulcerative colitis, specifically the development of pouchitis. Pouchitis is an inflammatory condition of the surgically-created ileoanal pouch that serves as a pseudo-rectum in patients with ulcerative colitis who have undergone a total colectomy. It is a condition unique to ulcerative colitis (UC), as it rarely occurs in non-UC patients who have the same procedure. Within one year, about 50% of patients will develop pouchitis. The condition is almost certainly due to aspects of the pouch microbiota on a background of genetic susceptibility, as most patients respond to treatment with antibiotics. While there have been reports on the microbiota in pouchitis patients, all have been performed after the inflammatory process is initiated, rendering interpretation of the results difficult, as the inflammatory process itself will change the microbiota. Our project is therefore unique and possibly the only opportunity in the role of the enteric microbiome in IBD in a prospective manner, thereby establishing potentially important causal relationships between microbiota structure or function and development of UC.The studies also offer two additional advantages. First, the development of the pouch microbiota can be observed prospectively. Second, the cause of antibiotic treatment failure in some patients with pouchitis may be revealed. The two aims are (1) to identify causal factors in the structure and/or function of the enteric microbiota in the development of pouchitis, and (2) to determine the basis of treatment failure in UC pouchitis patients. Our analyses will include serial measurements of enteric microbial structure (16S rRNA gene-based), function (metagenomics and functional candidate genes), and cultivation, the latter to enhance interpretation of gene sequences derived from metagenomes and targeted gene surveys (either functional or 16S genes). The insights gained from these studies will help us understand the fundamental and causative roles of the enteric microbiome in human inflammatory bowel diseases (IBD). This information will be the basis for developing strategies to restore host-microbial relationships to prevent and treat IBD.

  Study phs000262

• Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer

  Background: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited. Objective: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC by tumour RNA sequencing, and to determine their association with overall survival (OS).

  Study EGAS50000001269

• The Genetic History of Greenlandic-European contact

  The Inuit ancestors of the Greenlandic people arrived in Greenland close to 1000 years ago. Since then, Europeans from many different countries have been present in Greenland. Consequently, the present-day Greenlandic population has ~25% of its genetic ancestry from Europe. In this study, we investigated to what extent different European countries have contributed to this genetic ancestry.

  Study EGAS00001004933

• CSER: South-Seq: DNA Sequencing for Newborn Nurseries in the South

  SouthSeq, part of the Clinical Sequencing Evidence-Generating Research (CSER2) effort, aims to perform genome sequencing for infants in nurseries at hospitals in Alabama, Mississippi, Louisiana, and Kentucky. SouthSeq aims to sequence 600 newborn babies presenting with congenital anomalies, or other signs of a rare genetic disorder. The primary goals of SouthSeq are to provide early diagnoses to children with rare genetic conditions, to demonstrate the utility of genome sequencing as a frontline test with potential to improve intermediate and long-term clinical outcomes, and to equip non-genetics providers to deliver test results in order to facilitate the conduction of genome sequencing outside of major medical centers where patients may not have access to a genetics provider. SouthSeq also aims to ensure that genomic testing is applied across diverse communities; recruitment efforts focus on patients from rural and minority populations that have been historically under-represented in both medicine and genomics research. Sequencing and analysis for SouthSeq are being conducted at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama (https://www.hudsonalpha.org/). Enrollment of infants with signs of genetic disease is approved at five clinical sites, including nurseries at the University of Alabama at Birmingham, the University of Mississippi Medical Center, Woman's Hospital in Baton Rouge, Children's Hospital in New Orleans, and the University of Louisville. Both biological parents are enrolled when available so that follow-up testing can be performed to determine inheritance. Further, participant families may choose to opt-into return of secondary findings identified in the proband, which focus on pathogenic and likely pathogenic variation identified within ACMG SFv3.0 genes.

  Study phs002307

• Renal_Follow_Up_Series

  This study's purpose is to use data generated in Renal whole genome and exome Cancer sequencing to target specific areas in multiple other Renal Cancer samples. These areas will then be subjected to bespoke pull downs, tagged and then pool the resultant amplicons. These amplicons will then be sequenced. This is hoped to show the prevalence of previous findings in multiple individuals in a high throughput method.

  Study EGAS00001000095