Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA185743 | ENA |
REPOSITORIES: ENA
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Project description:PAGE: CALiCo: Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
| PRJNA176954 | ENA
Project description:PAGE: CALiCo: Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
| PRJNA176953 | ENA
Project description:<p>PAGE II (2013-2017) seeks to expand understanding gained during PAGE I and similar studies of how ancestry-specific differences in allele frequencies and LD may explain differences in risks of common traits and conditions. Recent studies have identified rare genetic variants that are likely to contribute to common diseases and traits and observed that rare variants likely to be functional, such as those in coding and regulatory regions, tend to be population-specific. PAGE II has genotyped over 50,000 samples using MEGA, an Illumina high density custom exomechip array. The MEGA data is being imputed in PAGE to the 1000 Genomes panel. PAGE also sequenced 1,000 samples representative of 21 populations from the Americas. PAGE has harmonized phenotype data for ~300 trait variables. These datasets will be analyzed to continue emphasis on characterizing population-level disease risks in non-European-descent individuals. Cohorts in PAGE II are: CALiCo (Causal Variants Across the Life Course, a consortium of ARIC, CARDIA, HCHS/SOL, Strong Heart Studies), ISMMS (Mount Sinai BioMe Biobank), MEC (Multiethnic Cohort), WHI (Women's Health Initiative), and Stanford University (PAGE Global Reference Panel). Genotyping services were provided by the Center for Inherited Disease Research (CIDR) and sequence data were provided by the McDonnell Genome Institute at Washington University School of Medicine.</p> <p>PAGE I (2008-2013): The first phase of PAGE examined putative causal genetic variants across approximately 100,000 African Americans, Asian Americans, American Indians, European Americans, Hispanic Americans, and Native Hawaiians from four groups representing nine large U.S.-based cohorts. Two genotyping approaches were employed - targeted genotyping of selected SNPs identified in genome-wide association studies of common disease, and a large-scale effort focused on the Metabochip array, which facilitated trans-ethnic fine mapping of several diseases of public health importance. Cohorts in PAGE I were: CALiCo (Causal Variants Across the Life Course, a consortium of ARIC, CARDIA, CHS, HCHS/SOL, Strong Heart Cohort Study, Strong Heart Family Study), EAGLE (Epidemiologic Architecture for Genes Linked to Environment, based on 3 National Health and Nutrition Examination Surveys (NHANES)), MEC (Multiethnic Cohort) and WHI (Women's Health Initiative).</p> <p>Logistical and scientific support is provided by the PAGE Coordinating Center and the NHGRI Division of Genomic Medicine. PAGE II is funded by the NHGRI and the NIMHD.</p> <p>To access PAGE studies currently available in dbGaP, please click on the links below.Please note that some PAGE studies belong to larger cohorts and have been included as PAGE substudies. For those studies, there is an additional link to the parent study. <ul> <li><a href="study.cgi?study_id=phs000223">phs000223</a> PAGE-ARIC and <a href="study.cgi?study_id=phs000280">phs000280</a> ARIC Cohort</li> <li><a href="study.cgi?study_id=phs000236">phs000236</a> PAGE-CARDIA and <a href="study.cgi?study_id=phs000285">phs000285</a> CARDIA Cohort</li> <li><a href="study.cgi?study_id=phs000301">phs000301</a> PAGE-CHS and <a href="study.cgi?study_id=phs000287">phs000287</a> CHS Cohort</li> <li><a href="study.cgi?study_id=phs000559">phs000559</a> PAGE-EAGLE-BioVu</li> <li><a href="study.cgi?study_id=phs000208">phs000208</a> PAGE-EAGLE-NHANES</li> <li><a href="study.cgi?study_id=phs000555">phs000555</a> PAGE-HCHS/SOL and <a href="study.cgi?study_id=phs000810">phs000810</a> HCHS/SOL Cohort</li> <li><a href="study.cgi?study_id=phs000220">phs000220</a> PAGE-MEC</li> <li><a href="study.cgi?study_id=phs000580">phs000580</a> PAGE-SHS and SHFS</li> <li><a href="study.cgi?study_id=phs001033">phs001033</a> PAGE Global Reference Panel</li> <li><a href="study.cgi?study_id=phs000227">phs000227</a> PAGE-WHI and <a href="study.cgi?study_id=phs000200">phs000200</a> WHI Cohort</li> </ul> </p>
| phs000356 | dbGaP
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature