3241 results for "*geneti*"

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• Rare germline sequence variants, copy number variations, expression alterations, methylation variations and disease susceptibility in familial melanoma

  Although a number of high-risk melanoma genes have been identified, they account for melanoma risk in less than 40% of melanoma-prone families. The major goals of our research are to identify novel high-penetrance genes for familial melanoma in melanoma-prone families without known mutations and to identify modifier factors, including genetic and epigenetic, in melanoma-prone families with and without known major mutations. We are using whole exome sequencing to identify additional high-risk susceptibility genes and using targeted sequencing to follow up on the top genes in additional family members and in population-based melanoma cases and controls. We are also using RNASeq to investigate genome-wide allele-specific expression and eQTLs in these families to identify genes with expression alteration, which will provide additional information for gene discovery. In addition, we also conducted genome-wide copy number variation (CNV), methylation, and miRNA expression profiling analyses in our melanoma families with the goal of identifying genetic and epigenetic factors as disease modifiers.

  Study phs001177

• Disorders/Differences of Sex Development (DSD) Study Performed at UCLA in Collaboration with the DSD-Translational Research Network (DSD-TRN), with the Support of the Gabriella Miller Kids First Pediatric Research Program

  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). Both childhood cancers and structural birth defects are critical and costly conditions associated with substantial morbidity and mortality. Elucidating the underlying genetic etiology of these diseases has the potential to profoundly improve preventative measures, diagnostics, and therapeutic interventions. Whole Genome Sequence (WGS) and phenotypic data from this study are accessible through dbGaP and kidsfirstdrc.org, where other Kids First datasets can also be accessed. Disorders/Differences of Sex Development (DSD) are congenital conditions in which development of chromosomal, gonadal, or anatomic sex is atypical. DSD are chronic medical conditions collectively affecting ~1% of the population, frequently requiring life-long care by multiple specialists, and carrying a significant public health burden. Some are associated with life-threatening events, such as adrenal crises in Congenital Adrenal Hyperplasia (CAH). DSD are also associated with increased infertility, cancer, gender dysphoria risks, psychosocial distress and pervasive challenges to health-related quality of life (HRQoL) for patients and families. DSD are broadly classified into three categories: sex chromosome DSD, 46,XY DSD and 46,XX DSD, and further classified according to the type of gonad found in the patient (ovary, testis, ovotestis). We were able to increase significantly the diagnostic success for DSD using Whole Exome Sequencing (WES), with the identification of disease-causing and likely pathogenic variants in a third of a cohort of 46,XY patients. We have therefore proposed a shift in the diagnostic approach to DSD to use next-gen sequencing as a first-line clinical test, which could lead to faster and more accurate diagnosis, and orient further clinical management, limiting unnecessary, costly, and often invasive endocrine testing and imaging. However many remain unexplained (over half of the XY cases, a significant minority of XX cases, including most ovotesticular DSD, and most syndromic cases). In addition, the very large phenotypic variability in cases with known variants in the same gene is unexplained. We here propose to use Whole-Genome Sequencing (WGS), which dramatically improves upon exome sequencing, covering both coding and non-coding parts of the genome more uniformly, as an approach to not only improve diagnostic yield, but also to identify novel genes and regulatory elements involved in DSD.

  Study phs001178

• Genes-Environments and Admixture in Latino Asthmatics (GALA II) Study

  A case-control pharmacogenetic study of bronchodilator drug response among racially admixed Latino children with asthma. Each participant had two spirometry measurements using the KoKo PFT System. With the first spirometry test, participant was administered with 4 puffs of HFA Albuterol. The second albuterol measurement was based on age, for participants under 16 years of age, additional 2 puffs were administered and for those over 16 years of age, additional 4 puffs were administered. The overall goal is to identify genetic factors which are predictive of drug response in children with asthma. The principal tools include a questionnaire and biological specimen collection. Participants are 8-21 years old at time of recruitment. Children with asthma have physician-diagnosed asthma, symptoms and medications. The GALAII Study is utilized in the following dbGaP substudies. To view genotypes, analysis, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs001180 GALAII Study. phs001274phs001274 GALAII GWAS

  Study phs001180

• National Institute of Environmental Health (NIEHS) Sciences Study of Somatic Mutation Load in Clones of Single Human Cells

  Accumulation of genetic changes with time and proliferation of cells is inevitable. We report here the genome-wide magnitude and spectra of mutations accrued in skin fibroblasts over the lifetime of healthy humans. We found that every cell contains at least one somatic chromosomal rearrangement and 600 - 13,000 base substitutions, similar to the median mutation load in human cancers. The mutation spectra and correlation of changes with epigenomic features also resemble many human cancers. Interestingly, the magnitude of ultraviolet light-characteristic mutations, representative of environmental mutagenesis, in sun-exposed skin was comparable to the number of mutations attributed to endogenous DNA damage estimated in unexposed cells. Our methodology allows delineating the precise contributions of environmental and endogenous factors to the accrual of genetic changes in the human body. This is fundamental to understanding the etiology, and improving the prognosis and prevention of cancers and other genetic diseases.

  Study phs001182

• Genome-Wide Scan for Genetic Variants Associated with Early-Onset Prostate Cancer

  This is a genome-wide association scan of 931 early-onset prostate cancer cases of European ancestry. The samples were selected from prostate cancer studies at the University of Michigan. Controls were previously genotyped individuals selected from the Cancer Genetics Markers of Susceptibility (CGEMS) and Illumina's iControlDB database.

  Study phs001185

• The Finland-United States Investigation of NIDDM Genetics (FUSION) Study - Islet Expression and Regulation by RNAseq and ATACseq

  This study evaluates gene expression and its regulation in human pancreatic islets, a tissue relevant in the study of genetic risk factors contributing to diabetes. We obtained islets from deceased donors and generated data from genome-wide SNP chip, bulk RNA-Seq, microRNA (miRNA)-Seq, whole genome sequence, DNA methylation (methyl)-Seq, transcription initiation profiles using cap analysis of gene expression (CAGE)-Seq, single cell RNA-seq, and single nuclei ATAC-seq. These data include ATAC-seq of two islet subjects, RNA-seq of 31 additional subjects, genome-wide chip genotypes, and imputed genotypes of the 33 subjects released with phs001188.v1. For genotyping, 500-1000 islet equivalents (IEQ) were cultured as in Gershengorn (Science, 2004, PMID: 15564314); genomic DNA isolated from islet cultures. For RNA analyses, 2500-5000 IEQ from each islet source were used for bulk or single-cell RNA isolation. Messenger RNA was isolated with trizol extraction and 12-plex libraries were generated using the Illumina TruSeq directional mRNA-seq library protocol. Bulk RNA sequencing was performed on HiSeq2000/HiSeq2500 sequencers using paired-end reads at the NIH Intramural Sequencing Center (NISC). miRNA libraries were prepared from total RNA from 68 samples, pooled and sequenced 50bp single-end reads on Illumina HiSeq2500. CAGE libraries were prepared from total RNA samples using the nAnT-iCAGE protocol at DNAFORM, Japan. CAGE libraries were sequenced at the NIH Intramural Sequencing Center (NISC) on the HiSeq2000 sequencer. Genotyping on the Illumina Omni2.5M array was performed at the NHGRI Genomics Core facility. Genotypes were imputed using the HRC.r1.1.2016 reference panel. In order to assess regions of open chromatin in islets, we performed bulk ATAC-seq on HiSeq2000 sequencers using paired-end reads at NISC. Single-nuclei ATAC-seq libraries were prepared using single-cell-combinatorial-indexing (sci-) ATAC-seq protocol and sequenced on Illumina NextSeq using paired-end reads. scRNA-seq libraries were generated using the 10X Genomics platform and sequenced on Illumina HiSeq3000 at the Genomics Technology Core of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Greater than 90% of the loci associated with T2D through genome-wide association studies occur in non-coding regions, suggesting a strong regulatory component to disease susceptibility. Therefore, there is a critical need to understand the full spectrum of genetic variation and regulatory element usage in T2D-relevant tissues. To that end, this study contains whole genome sequence and whole genome bisulfite sequence, and/or Illumina MethylationEPIC Array data, providing a comprehensive survey of both individual genetic variation as well as DNA methylation across different tissues from multiple individuals. In addition, we carried out sequencing of single cell RNAs (two subjects) and single cell nuclei (one subject) to characterize gene expression and chromatin accessibility of islets.

  Study phs001188

• NHLBI TOPMed: Cleveland Clinic Atrial Fibrillation (CCAF) Study

  The Cleveland Clinic Atrial Fibrillation Study consists of clinical and genetic data of patients with atrial fibrillation and control cohorts from the Cleveland Clinic CV/Arrhythmia Biobank, including the Cleveland Clinic Lone Atrial Fibrillation GeneBank. The Cleveland Clinic Lone AF GeneBank Study has enrolled patients with lone AF, defined as AF in the absence of significant structural heart disease. The CV/Arrhythmia Biobank has also enrolled participants with non-lone atrial fibrillation. All patients provided written informed consent.

  Study phs001189

• eMERGE: Northwestern (NUgene) WGS

  The NUgene Project is a biorepository with longitudinal medical information from participating patients at Northwestern Medicine affiliated hospitals and outpatient clinics. Participants' DNA samples are coupled with data from a self-reported questionnaire (2 versions were used, 1 before and 1 after February 2006, both are included) and continuously updated data from our Electronic Medical Record (EMR) representing actual clinical care events. Northwestern has a state-of-the art, comprehensive inpatient and outpatient EMR system of over 3 million patients. NUgene has broad access to participant data for all outpatient visits as well as inpatient data via a consolidated enterprise data warehouse. NUgene participants consent to distribution and use of their coded DNA samples and data for a broad range of genetic research by third-party investigators. The electronic MedicalRecords and Genomics (eMERGE) Network is a consortium of 9 clinical sites with EMR linked DNA biobanks, including Northwestern University and its NUgene biobank, funded by the NHGRI (National Human Genome Research Institute) to investigate the use of electronic medical record systems for genomic research. The goal of eMERGE is to conduct genome-wide association studies in approximately 100,000 individuals using EMR-derived phenotypes and DNA from linked biorepositories. Using electronic phenotyping methods, the consortium has been and is using DNA samples from all participating sites to explore the genetic determinants of approximately 80 phenotypes, including both diseases and traits, for which the electronic phenotyping algorithms have or are being published on PheKB.org. Thus, for the eMERGE network, ~900 NUgene subjects were selected, as described in the study inclusion/exclusion criteria section below, to be genotyped using whole genome sequencing (WGS), for use in the eMERGE network as eMERGE subjects. The criteria used below were selected so that these subjects will likely meet the criteria to be cases and/or controls, of diverse races and/or ethnicities, for at least 1 of the ~80 phenotypes being studied within eMERGE, and could be recontacted for future research if needed.

  Study phs001191

• National Cancer Institute (NCI) Adding Hispanics to Ongoing GWAS in Colorectal Cancer

  Genome-wide association studies (GWAS) of colorectal cancer (CRC) have been instrumental in identifying a number of common susceptibility loci in Non Hispanic (NH)-White populations, and a NCI priority is to extend GWAS findings to other populations to address racial/ethnic disparities in cancer susceptibility. Currently, GWA studies of CRC in NH-Whites, Japanese and African-Americans are ongoing. We propose a complementary study to address this critical research area in Hispanics. Hispanics represent the fastest growing ethnic population in the U.S. and have been largely understudied in terms of genetic susceptibility to cancer. There are noted differences in incidence, survival and mortality in CRC by ethnic/racial groups. Hispanics often present with CRC at a younger age and have a significantly greater incidence of stage IV tumors or metastatic disease compared to NH-Whites. We propose to conduct a large, cost-efficient, population-based GWAS in Hispanics by building upon existing NIH-funded resources, the Colon Cancer Family Registry (Colon CFR) and the Multiethnic Cohort Study (MEC). We plan to recruit 2,500 Hispanic men and women diagnosed with CRC between 01/2008 to present using cancer registries in California, physican referrals and familial referrals. Risk factor/diet questionnaires, pathology reports, Oragene saliva samples (for genotyping), optional blood samples (for genotyping and biometric analysis) and tumor blocks (for MSI testing) will be collected using methodologies developed in the Colon CFR/MEC. Cases of CRC in the MEC (currently 473; anticipated 600 at end) will also be included. Population-based Hispanic individuals without a diagnosis of CRC participating in other GWA studies in the MEC (n=3,900, U01HG004726, Haiman) will be used as controls. We will genotype all 3,100 cases using the Illumina 1M array and use available genotype and epidemiologic data collected on 3,900 controls. Our statistical analyses will include: single-SNP and haplotype effects, gene-environment interactions and heterogeneity by MSI, tumor subtype and family history of CRC. We will replicate findings in a second-stage using CRC cases and controls from Mexico (1,000 cases and 1,000 controls, EU FP7 funding, CHIBCHA, Carvajal-Carmona/Tomlinson). We will also examine heterogeneity of the risk estimates by ethnicity/race by leveraging GWA data on NH-Whites (2,142 cases, 1,909 controls, U01 CA122839, Casey), (4,000 cases, 6,000 NH-White controls, UK-CHIBCHA, Tomlinson), Colombians (2,000 cases and 2,000 controls, CHIBCHA), Japanese (1,000 cases and 1,000 controls) and African-Americans (1,500 cases and 1,500 controls, R01CA126895, Le Marchand). We will genotype replicated significant SNPs in our main and combined analysis in several Hispanic populations (note: studies funded by EU or NIH for data collection but not GWAS), including 800 Puerto Ricans, 2,000 Brazilians, 2,000 Argentineans and 3,000 Spanish/Portuguese, to assess generalizability of findings. We will examine the differences in inflammatory gene transcription dynamics in leukocytes (from blood sample collection) by fatigue level (as assessed from study questionnaire data). This study will have a high impact by addressing the key question of racial/ethnic disparities related to genetic susceptibility to CRC, will provide translational guidelines on biological mechanisms during the cancer survivorship period to increase quality of life among cancer survivors, and will enable further growth and investment into research among Hispanics by providing a resource of genetic data and biospecimens, which is lacking.

  Study phs001193

• National Heart, Lung, and Blood Institute (NHLBI) Bench to Bassinet Program: The Pediatric Cardiac Genetics Consortium (PCGC) Study

  Multi-center, prospective observational cohort study of individuals with congenital heart defects (CHD). Phenotypic data and source DNA derived from 10,000 probands, parents, and families of interest are being collected to investigate relationships between genetic factors and phenotypic and clinical outcomes in patients with CHD. The PCGC Cohort is utilized in the following dbGaP substudies. To view genotypes, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" section of this top-level study page phs001194 PCGC Cohort. phs000571 The Pediatric Cardiac Genetics Consortium (PCGC): whole exome sequences, targeted sequences, and SNP array data phs001843 PCGC-CMG Collaboration: whole genome sequences The Gabriella Miller Kids First Pediatric Research Program (Kids First) subset of the PCGC project (phs001194) is now accessible through a separate dbGaP study accession: phs001138. To access this dataset, please submit a Data Access Request (DAR) for phs001138. Approval of this DAR will be expedited for approved users of phs001194. To learn about other Kids First datasets visit https://kidsfirstdrc.org/.

  Study phs001194