3329 results for "*geneti*"

in 60.32 milliseconds.

• Accurate Genome-Wide Germline DNA Profiling from Decade-Old Archival Tissue Specimens

  We evaluate the validity of repurposing archival tissue specimens for germline genetic studies. We performed lc-WGS and imputed genotypes on 10 pairs of matching blood and tumor tissue and benchmarked the accuracy of genome-wide genotypes, HLA haplotypes, and several polygenic risk scores (PRSs). The reported results indicate the high accuracy of germline genotypes and haplotypes obtained from archival tissue DNA. Using this methodology, we estimate breast cancer PRS in 36 Ductal carcinoma in situ (DCIS) patients and demonstrate its association with breast cancer subsequent event (BCSE).  

  Study phs002865

• CTN - 0051: Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT)

  The overarching goal of CTN-0051 is to foster adoption of new relapse-prevention pharmacotherapies in community-based treatment programs (CTPs) where these could have a substantial public health impact. To this end CTN-0051 will assess the comparative effectiveness of extended-release injectable naltrexone (XR-NTX, Vivitrol®), an opioid antagonist recently approved and indicated for the prevention of relapse to opioid dependence, versus buprenorphine-naloxone (BUP-NX, Suboxone®), a high affinity partial agonist indicated for maintenance treatment of opioid dependence, as pharmacotherapeutic aids to recovery. The study is conducted in 8 CTN-affiliated CTPs that provide or partner with detoxification services (inpatient/residential) which have the capacity to maintain participants opioid-free for approximately 3-7 days, have the capacity to provide medication-assisted therapy, and can provide a minimum of one group or individual counseling session per week during the 24-week treatment period. Up to 600 eligible participants will be randomized to treatment with XR-NTX or BUP-NX for 24 weeks (sufficient to include 350 participants who are randomized more than 72 hours after their last opioid). To maximize generalizability, the point of randomization is flexible, from shortly after program admission until just prior to program discharge. The primary goal of the study is to estimate the difference, if one exists, between XR-NTX and BUP-NX in the distribution of the time to relapse (i.e., loss of persistent abstinence) during the 6-month trial. The primary outcome measure is the time to the event, with the event called relapse. Secondary objectives are to: (1) compare outcome on XR-NTX versus BUP-NX across a range of clinical safety and secondary efficacy domains, (2) explore demographic, clinical, and genetic predictors of successful treatment and moderators of differential effectiveness (i.e., what variables may help clinicians choose which of these treatments is best for a given patient), and (3) collect a limited dataset to permit analyses of economic costs and benefits of the two treatments.

  Study phs002876

• Vulnerabilities of Midbrain Dopaminergic Neurons to Parkinson's Disease Revealed by Single-Cell Genomics

  We developed a novel protocol for the enrichment of midbrain DA neurons from frozen tissue. We subsequently performed single-nuclei RNA-sequencing on enriched samples from postmortem midbrain tissue from human, macaque, tree shrew, rat, and mouse. We identified vulnerable and resistant populations from these data and associated genetic enrichments and differential expression changes.

  Study phs002879

• The Pathogenesis and Genetics of Disseminated Coccidioidomycosis

  Whole exome sequencing on patients > 2 years of age with confirmed disseminated coccidioidomycosis, not undergoing active immunosuppressive therapy, negative HIV status. 

  Study phs002881

• The Role of CDX2 in Controlling ABCB1 Expression and Chemosensitivity in Human Colon Cancer

  This study reports the results of RNA sequencing (RNA-seq) experiments performed on two human colon cancer cell lines (HT-29, DLD-1) that were genetically engineered to achieve either the constitutive expression (in HT-29 cells) or the selective inactivation (in DLD-1 cells) of the transcription factor CDX2, a master regulator of embryonic gut development and a key regulator of multi-lineage differentiation in adult colon epithelial cells. Our previous studies had identified lack of CDX2 expression as a prognostic biomarker of poor prognosis and a predictive biomarker of benefit from adjuvant chemotherapy in Stage-II and Stage-III colon cancer patients (Dalerba et al., NEJM, 374:211-222, 2016; PMID: 26789870). The molecular basis of these associations, however, remained poorly understood. The present study was designed to identify which genes are under the transcriptional control of CDX2, in order to clarify their role in shaping colon cancer resistance to chemotherapy. Of the two lines included in this study, the first (HT-29) is CDX2-negative at baseline, and was infected with a lentivirus vector encoding for the cDNA of the human CDX2 gene under the control of a constitutive promoter (CMV). The second line (DLD-1) is CDX2-positive at baseline, and was infected with a series of lentivirus vectors encoding for CRISPR/Cas9 constructs designed to selectively inactivate the CDX2 gene. In both cases, infected cells were purified by fluorescence-activated cell sorting (FACS), based on the differential expression of a green fluorescent reporter (EGFP) that was also encoded by the lentivirus vectors, and transcribed in tandem with either the CDX2 cDNA (HT-29) or CRISPR/Cas9 gRNAs targeting CDX2 (DLD-1). The experiments were designed to include 3 experimental replicates per condition, and to compare the transcriptional profile of genetically engineered cells with that of autologous controls (i.e., HT-29 cells infected with an "empty" version of the same lentivirus vector used to over-express CDX2, DLD-1 cells engineered with a "non-targeting" CRISPR/Cas9 gRNA). In the specific case of DLD-1 cells engineered with CRIPSR-Cas9 constructs targeting CDX2, infected cells were sorted based on the differential expression of EGFP and then plated as single-cells, in order to sub-culture three isogenic clones, all of which were genetically sequenced to confirm bi-allelic knock-out of the CDX2 gene, and confirmed to lack CDX2 protein expression by Western blot. The results of our experiments demonstrate that, in human colon epithelial cells, CDX2 controls the expression of the ABCB1 efflux pump, by positively regulating the transcription of the corresponding gene.

  Study phs002903

• Genomic Analysis of Extra-Nodal Natural Killer/T-Cell Lymphoma (ENKTCL)

  In this study, we performed extensive genetic profiling on 209 extra-nodal natural killer/T-cell lymphoma (ENKTCL) nasal-type cases, including 174 Chinese from four hospitals in China, and 31 Hispanic and 4 Caucasian patients from City of Hope and Eberhard Karls University of Tübingen. All of the cases were reviewed by experienced hematopathologists to confirm diagnosis. Written informed consents from patients were reviewed and approved by the institutional review board of each institution. We deposited targeted exon sequencing data of a selected 333-gene panel on the ENKTCL cases in dbGaP. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissues with an AllPrep DNA/RNA FFPE Kit. A custom platform (Agilent SureSelect) was used to capture target exons from genomic DNA of ENKTCL tumors. DNA was fragmented to 200bp using a Covaris S220 Focused-ultrasonicator and was end-repaired and ligated to Illumina adaptors with a KAPA Hyper Prep Kit. Ligated products were purified and amplified with a 7-cycle PCR. Exome capture from the PCR products was performed using a SureSelect Target Enrichment Kit. The captured exomes were further amplified with an 8-cycle PCR and purified for cluster generation using the cBot cluster generation system with a HiSeq PE Cluster Kit V4. 100bp paired-end reads were generated from an Illumina HiSeq 2500 system with a HiSeq SBS Kit V4.

  Study phs002925

• The Genetic Basis of Progression in Multiple Sclerosis

  This study examined the genetic determinants of multiple sclerosis (MS) severity in an international cohort of people with MS assembled by the International Multiple Sclerosis Genetics Consortium (IMSGC) and the MultipleMS Consortium. A total of 12,584 people with MS of European ancestry were included in the main genome-wide association study (GWAS). Participants were enriched for older individuals with longer disease duration (mean age 51.7 years and mean disease duration 18.2 years). All individuals were whole-genome genotyped on the Illumina Global Screen Array (GSAMD-24v2-0). Imputation was performed using the Haplotype Reference Consortium reference panel. The primary outcome was the age-related MS severity score. All individuals had at least 1 expanded disability status scale (EDSS) measure. When multiple EDSS scores were available, the last one was selected to calculate the age-related MS severity score.Of those 12,584 people with MS, this data release includes 4,623 participants recruited from non-European sites in the US, Canada and Australia. This release includes individual-level genotype and phenotype files necessary to replicate our GWAS of MS severity, including covariates.

  Study phs002929

• Molecular Biomarkers of Obesity and Metformin Response in Endometrial Cancer: Analysis of GOG-0286B

  The primary endpoint for the phase 2 study was progression free survival (PFS), and the primary endpoint for the phase 3 study was overall survival (OS). Data from phase 2 were included in the phase 3 analysis. Tissue was collected from patients with endometrial cancer who participated in the study (NCT02065687). The tissue will be analyzed for genetic data and combined with the clinical data to see if some gene variants are associated with longer PFS or OS, particularly on the metformin arm of the study.

  Study phs002934

• Exploring the Genomic Dark Matter of Neurodevelopmental Disorders

  Neurodevelopmental Disorders (NDDs) are a group of disorders that typically manifest early in development and may give rise to impaired cognition, communication, adaptive behavior, and psychomotor skills. This study aims to take a more comprehensive view into the genomic landscape of structural variants implicated in NDDs with intellectual disability (ID). We have evaluated the genome of families with a genetically unsolved severe NDD via optical genome mapping. This study identified likely pathogenic or pathogenic structural variants in known NDD genes, including BCL11A, OPHN1, PHF8, SON, and NFIA. Data is available in VCF format, following the standard filtering settings in Bionano Access and available as "variants_combine_filters_inMoleRefine1.vcf" files.

  Study phs002937

• NCI-Maryland Prostate Cancer Case-Control Study

  The study seeks to examine the genetic and ancestral basis of prostate cancer-associated inflammation using a genome-wide association approach. The study population are the participants of the NCI Maryland Prostate Cancer Case-Control study. This study recruited both African American and European American men, and investigated the causes for the excessive burden of prostate cancer among African American men in more general terms. We measured 82 blood-based immune-oncology markers, and genotyped the participants using the HumanOmni5-Quad BeadChip, which provides a significant genome coverage for genetically-admixed and diverse populations, to evaluate the genetic basis and evidence for causality of any immune-inflammation marker that is associated with prostate cancer risk. We want to assess how germline genetics influence the abundance levels of these 82 markers in African American and European American men, which may contribute to differences between them.

  Study phs002939