Supplementing High-Density SNP Microarrays for Additional Coverage of Disease-Related Genes: Addiction as a Paradigm

Commercial SNP microarrays now provide comprehensive and affordable coverage of the human genome. However, some diseases have biologically relevant genomic regions that may require additional coverage. Addiction, for example, is thought to be influenced by complex interactions among many relevant genes and pathways. We have assembled a list of 486 biologically relevant genes nominated by a panel of experts on addiction. We then added 424 genes that showed evidence of association with addiction phenotypes through mouse QTL mappings and gene co-expression analysis. We demonstrate that there are a substantial number of SNPs in these genes that are not well represented by commercial SNP platforms. We address this problem by introducing a publicly available SNP database for addiction. The database is annotated using numeric prioritization scores indicating the extent of biological relevance. The scores incorporate a number of factors such as SNP/gene functional properties (including synonymy and promoter regions), data from mouse systems genetics and measures of human/mouse evolutionary conservation. We then used HapMap genotyping data to determine if a SNP is tagged by a commercial microarray through linkage disequilibrium. This combination of biological prioritization scores and LD tagging annotation will enable addiction researchers to supplement commercial SNP microarrays to ensure comprehensive coverage of biologically relevant regions

Ernest Hemingway

Interview. Hawks reminisces about his and news photographer Robert Capa’s relationships with Hemingway. Sheds light on Hemingway’s aversion to Hollywood

The Big Sleep (1946). Lobby card.

Lobby card for The Big Sleep, directed by Howard Hawks. Screenplay by William Faulkner, based on the book by Raymond Chandler. 1946.https://egrove.olemiss.edu/ms_mystery/1068/thumbnail.jp

Deedle-dee-dee go see Detroit take it from me say you\u27ll enjoy [first line of chorus]

Performers: Taylor, Macy and HawksPiano, Voice and Chord

Water Quality

This series of videos discusses water usage and the safety of drinking water. The material comes from two University Extension broadcasts

The Fe-only nitrogenase and the Mo nitrogenase from Rhodobacter capsulatus - A comparative study on the redox properties of the metal clusters present in the dinitrogenase components

Siemann S, Schneider K, Drottboom M, Müller A. The Fe-only nitrogenase and the Mo nitrogenase from Rhodobacter capsulatus - A comparative study on the redox properties of the metal clusters present in the dinitrogenase components. EUROPEAN JOURNAL OF BIOCHEMISTRY. 2002;269(6):1650-1661.The dinitrogenase component proteins of the conventional Mo nitrogenase (MoFe protein) and of the alternative Fe-only nitrogenase (FeFe protein) were both isolated and purified from Rhodobacter capsulatus, redox-titrated according to the same procedures and subjected to an EPR spectroscopic comparison. In the course of an oxidative titration of the MoFe protein (Rc1(Mo)) three significant S = 1/2 EPR signals deriving from oxidized states of the P-cluster were detected: (1) a rhombic signal (g = 2.07, 1.96 and 1.83), which showed a bell-shaped redox curve with midpoint potentials (E-m) of -195 mV (appearance) and -30 mV (disappearance), (2) an axial signal (g(ii) = 2.00, g(perpendicular to) = 1.90) with almost identical redox properties and (3) a second rhombic signal (g = 2.03, 2.00, 1.90) at higher redox potentials ( > 100 mV). While the 'low-potential' rhombic signal and the axial signal have been both attributed to the one-electron-oxidized P-cluster (P1+) present in two conformationally different proteins, the 'high-potential' rhombic signal has been suggested rather to derive from the P3+ state. Upon oxidation, the FeFe protein (Rc1(Fe)) exibited three significant S = 1/2 EPR signals as well. However, the Re I F, signals strongly deviated from the MoFe protein signals, suggesting that they cannot simply be assigned to different P-cluster states. (a) The most prominent feature is an unusually broad signal at g = 2.27 and 2.06, which proved to be fully reversible and to correlate with catalytic activity. The cluster giving rise to this signal appears to be involved in the transfer of two electrons. The midpoint potentials determined were: -80 mV (appearance) and 70 mV (disappearance). (b) Under weakly acidic conditions (pH 6.4) a slightly altered EPR signal occurred. It was characterized by a shift of the g values to 2.22 and 2.05 and by the appearance of an additional negative absorption-shaped peak at g = 1.86. (c) A very narrow rhombic EPR signal at g = 2.00, 1.98 and 1.96 appeared at positive redox potentials (E-m = 80 mV, intensity maximum at 160 mV). Another novel S = 1/2 signal at g = 1.96, 1.92 and 1.77 was observed on further, enzymatic reduction of the dithionite-reduced state of Rc1(Fe), with the dinitrogenase reductase component (Rc2(Fe)) of the same enzyme system (turnover conditions in the presence of N-2 and ATP). When the Rc1(Mo) protein was treated analogously. neither this 'turnover signal' nor any other S = 1/2 signal were detectable. All Rc1(Fe)-specific EPR signals detected are discussed and tentatively assigned with special consideration of the reference spectra obtained from Rc1(Mo) preparations

Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas.

Context.—The diagnosis and clinical management of patients with diffuse gliomas (DGs) have evolved rapidly over the past decade with the emergence of molecular biomarkers that are used to classify, stratify risk, and predict treatment response for optimal clinical care.Objective.—To develop evidence-based recommendations for informing molecular biomarker testing for pediatric and adult patients with DGs and provide guidance for appropriate laboratory test and biomarker selection for optimal diagnosis, risk stratification, and prediction.Design.—The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. A systematic review of literature was conducted to address the overarching question, "What ancillary tests are needed to classify DGs and sufficiently inform the clinical management of patients?" Recommendations were derived from quality of evidence, open comment feedback, and expert panel consensus.Results.—Thirteen recommendations and 3 good practice statements were established to guide pathologists and treating physicians on the most appropriate methods and molecular biomarkers to include in laboratory testing to inform clinical management of patients with DGs.Conclusions.—Evidence-based incorporation of laboratory results from molecular biomarker testing into integrated diagnoses of DGs provides reproducible and clinically meaningful information for patient management

Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas:Guideline from the College of American Pathologists in Collaboration with the American Association of Neuropathologists, Association for Molecular Pathology, and Society for Neuro-Oncology

Context.—The diagnosis and clinical management of patients with diffuse gliomas (DGs) have evolved rapidly over the past decade with the emergence of molecular biomarkers that are used to classify, stratify risk, and predict treatment response for optimal clinical care.  Objective.—To develop evidence-based recommendations for informing molecular biomarker testing for pediatric and adult patients with DGs and provide guidance for appropriate laboratory test and biomarker selection for optimal diagnosis, risk stratification, and prediction.  Design.—The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. A systematic review of literature was conducted to address the overarching question, ‘‘What ancillary tests are needed to classify DGs and sufficiently inform the clinical management of patients?’’ Recommendations were derived from quality of evidence, open comment feedback, and expert panel consensus.  Results.—Thirteen recommendations and 3 good practice statements were established to guide pathologists and treating physicians on the most appropriate methods and molecular biomarkers to include in laboratory testing to inform clinical management of patients with DGs.  Conclusions.—Evidence-based incorporation of laboratory results from molecular biomarker testing into integrated diagnoses of DGs provides reproducible and clinically meaningful information for patient management