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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of the American Chemical Society 80 (1958), S. 4732-4736 
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of materials science 15 (1996), S. 1895-1897 
    ISSN: 1573-4811
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2015-10-13
    Description: Journal of Chemical & Engineering Data DOI: 10.1021/acs.jced.5b00638
    Print ISSN: 0021-9568
    Electronic ISSN: 1520-5134
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 4
    Publication Date: 2015-01-18
    Description: Journal of Chemical & Engineering Data DOI: 10.1021/je500830a
    Print ISSN: 0021-9568
    Electronic ISSN: 1520-5134
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 5
    Publication Date: 2013-02-26
    Description: Poly(propylene)imine hexadecylamine dendrimer (DAB-Am-16) was anchored on the surface of 3-chloropropylsilyl silica gel and subsequently interacted with copper nitroprusside. The composite was characterized by infrared (FTIR), energy dispersive X-ray (EDX), and cyclic voltammetry. The above techniques confirmed the successful anchoring of the dendrimer on the silica gel modified surface and its interaction with copper nitroprusside. The cyclic voltammogram of CuNPSD was found to exhibit two redox couples with (Eθ′)1 = 0.30 V and (Eθ′)2 = 0.78 V versus Ag/AgCl (KCl=1.0 mol L−1;
    Print ISSN: 2090-3529
    Electronic ISSN: 2090-3537
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Published by Hindawi
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  • 6
    Publication Date: 2012-10-10
    Description: The Mmr multidrug efflux pump recognizes and actively extrudes a broad range of antimicrobial agents, and promotes the intrinsic resistance to these antimicrobials in Mycobacterium tuberculosis . The expression of Mmr is controlled by the TetR-like transcriptional regulator Rv3066, whose open reading frame is located downstream of the mmr operon. To understand the structural basis of Rv3066 regulation, we have determined the crystal structures of Rv3066, both in the absence and presence of bound ethidium, revealing an asymmetric homodimeric two-domain molecule with an entirely helical architecture. The structures underscore the flexibility and plasticity of the regulator essential for multidrug recognition. Comparison of the apo-Rv3066 and Rv3066–ethidium crystal structures suggests that the conformational changes leading to drug-mediated derepression is primarily due to a rigid body rotational motion within the dimer interface of the regulator. The Rv3066 regulator creates a multidrug-binding pocket, which contains five aromatic residues. The bound ethidium is found buried within the multidrug-binding site, where extensive aromatic stacking interactions seemingly govern the binding. In vitro studies reveal that the dimeric Rv3066 regulator binds to a 14-bp palindromic inverted repeat sequence in the nanomolar range. These findings provide new insight into the mechanisms of ligand binding and Rv3066 regulation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Publication Date: 2018-06-05
    Description: The Association of Young People of Alto Rio Preto (JUAP) and the Association of Children and Friends of São Benedito, Maranhão, Brasil (AFASB) develop the “Avante Camaradas” (Forward Comrades) Project and the “Alonga Vida” (Lenghten Life) Operation, for the maintenance of the Preto River and the Mocambo River, its main tributary. From these actions arose the necessity of technical study of the Preto River. In this research we carried out expeditions in the river, we verified its bed, tributaries, vegetation, number of households and riverside. The study area was from Tutanguira village to ETA CAEMA (Water Treatment Station of the Environmental Sanitation Company of Maranhão). Flora, with identification of 89 species and fauna, with identification of 101 bird species, 28 species of herpetofauna (amphibian and reptiles) and 11 species of mammals were studied. Environmental impacts such as cutting and burning vegetation, extraction of wood for sawmill, coal and fishing, sand extrac...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
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  • 8
    Publication Date: 2014-12-10
    Description: Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (〈/=50 years in males and 〈/=60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol 〉 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319990/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Do, Ron -- Stitziel, Nathan O -- Won, Hong-Hee -- Jorgensen, Anders Berg -- Duga, Stefano -- Angelica Merlini, Pier -- Kiezun, Adam -- Farrall, Martin -- Goel, Anuj -- Zuk, Or -- Guella, Illaria -- Asselta, Rosanna -- Lange, Leslie A -- Peloso, Gina M -- Auer, Paul L -- NHLBI Exome Sequencing Project -- Girelli, Domenico -- Martinelli, Nicola -- Farlow, Deborah N -- DePristo, Mark A -- Roberts, Robert -- Stewart, Alexander F R -- Saleheen, Danish -- Danesh, John -- Epstein, Stephen E -- Sivapalaratnam, Suthesh -- Hovingh, G Kees -- Kastelein, John J -- Samani, Nilesh J -- Schunkert, Heribert -- Erdmann, Jeanette -- Shah, Svati H -- Kraus, William E -- Davies, Robert -- Nikpay, Majid -- Johansen, Christopher T -- Wang, Jian -- Hegele, Robert A -- Hechter, Eliana -- Marz, Winfried -- Kleber, Marcus E -- Huang, Jie -- Johnson, Andrew D -- Li, Mingyao -- Burke, Greg L -- Gross, Myron -- Liu, Yongmei -- Assimes, Themistocles L -- Heiss, Gerardo -- Lange, Ethan M -- Folsom, Aaron R -- Taylor, Herman A -- Olivieri, Oliviero -- Hamsten, Anders -- Clarke, Robert -- Reilly, Dermot F -- Yin, Wu -- Rivas, Manuel A -- Donnelly, Peter -- Rossouw, Jacques E -- Psaty, Bruce M -- Herrington, David M -- Wilson, James G -- Rich, Stephen S -- Bamshad, Michael J -- Tracy, Russell P -- Cupples, L Adrienne -- Rader, Daniel J -- Reilly, Muredach P -- Spertus, John A -- Cresci, Sharon -- Hartiala, Jaana -- Tang, W H Wilson -- Hazen, Stanley L -- Allayee, Hooman -- Reiner, Alex P -- Carlson, Christopher S -- Kooperberg, Charles -- Jackson, Rebecca D -- Boerwinkle, Eric -- Lander, Eric S -- Schwartz, Stephen M -- Siscovick, David S -- McPherson, Ruth -- Tybjaerg-Hansen, Anne -- Abecasis, Goncalo R -- Watkins, Hugh -- Nickerson, Deborah A -- Ardissino, Diego -- Sunyaev, Shamil R -- O'Donnell, Christopher J -- Altshuler, David -- Gabriel, Stacey -- Kathiresan, Sekar -- 090532/Wellcome Trust/United Kingdom -- 095552/Wellcome Trust/United Kingdom -- 5U54HG003067-11/HG/NHGRI NIH HHS/ -- G-0907/Parkinson's UK/United Kingdom -- K08 HL114642/HL/NHLBI NIH HHS/ -- K08HL114642/HL/NHLBI NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- R01 HL107816/HL/NHLBI NIH HHS/ -- R01HL107816/HL/NHLBI NIH HHS/ -- RC2 HL-102923/HL/NHLBI NIH HHS/ -- RC2 HL-102924/HL/NHLBI NIH HHS/ -- RC2 HL-102925/HL/NHLBI NIH HHS/ -- RC2 HL-102926/HL/NHLBI NIH HHS/ -- RC2 HL-103010/HL/NHLBI NIH HHS/ -- T32 HL007208/HL/NHLBI NIH HHS/ -- T32HL00720/HL/NHLBI NIH HHS/ -- T32HL007604/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Feb 5;518(7537):102-6. doi: 10.1038/nature13917. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA. [4] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; 1] Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Division of Statistical Genomics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Clinical Biochemistry KB3011, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen 1165, Denmark. ; Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universita degli Studi di Milano, Milano 20122, Italy. ; Division of Cardiology, Ospedale Niguarda, Milano 20162, Italy. ; Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK. ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; University of Verona School of Medicine, Department of Medicine, Verona 37129, Italy. ; John &Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada. ; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 1TN, UK. ; MedStar Health Research Institute, Cardiovascular Research Institute, Hyattsville, Maryland 20782, USA. ; Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands. ; Department of Cardiovascular Sciences, University of Leicester, and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK. ; DZHK (German Research Centre for Cardiovascular Research), Munich Heart Alliance, Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Berlin 13347, Germany. ; Medizinische Klinik II, University of Lubeck, Lubeck 23562, Germany. ; 1] Center for Human Genetics, Duke University, Durham, North Carolina 27708, USA. [2] Department of Cardiology and Center for Genomic Medicine, Duke University School of Medicine, Durham, North Carolina 27708, USA. ; Department of Cardiology and Center for Genomic Medicine, Duke University School of Medicine, Durham, North Carolina 27708, USA. ; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada. ; Department of Biochemistry, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. ; 1] Department of Biochemistry, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. [2] Department of Medicine, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. ; 1] Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, Mannheim D-68167, Germany. [2] Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. [3] Synlab Academy, Mannheim 68259, Germany. ; Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, Mannheim D-68167, Germany. ; The National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; National Heart, Lung, and Blood Institute Center for Population Studies, The Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; Department of Biostatistics and Epidemiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Epidemiology, University of Alabama-Birmingham, Birmingham, Alabama 35233, USA. ; Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27106, USA. ; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. [2] Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota 55455, USA. ; University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. ; Atherosclerosis Research Unit, Department of Medicine, and Center for Molecular Medicine, Karolinska Institutet, Stockholm 171 77, Sweden. ; Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford OX1 2JD, UK. ; Merck Sharp &Dohme Corporation, Rahway, New Jersey 08889, USA. ; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. ; 1] The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. [2] Department of Statistics, University of Oxford, Oxford OX1 2JD, UK. ; National Heart, Lung, and Blood Institute, Bethesda, Maryland 20824, USA. ; 1] Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington 98195, USA. [2] Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101, USA. ; Section on Cardiology, and Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27106, USA. ; Jackson Heart Study, University of Mississippi Medical Center, Jackson State University, Jackson, Mississippi 39217, USA. ; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22904, USA. ; 1] Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA. [2] Seattle Children's Hospital, Seattle, Washington 98105, USA. [3] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Biochemistry, University of Vermont, Burlington, Vermont 05405, USA. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; St Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri 64111, USA. ; 1] Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Department of Genetics, Washington University in St Louis, Missouri 63130, USA. ; Department of Preventive Medicine and Institute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. ; Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. ; 1] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA. ; Ohio State University, Columbus, Ohio 43210, USA. ; Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. ; 1] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA. [2] Department of Medicine, School of Medicine, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Clinical Biochemistry KB3011, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen 1165, Denmark. [2] Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Kobenhavn N, Denmark. ; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Missouri 48109, USA. ; 1] Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK. [2] The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Cardiology, Parma Hospital, Parma 43100, Italy. ; 1] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487149" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Age of Onset ; *Alleles ; Apolipoproteins A/*genetics ; Case-Control Studies ; Cholesterol, LDL/blood ; Coronary Artery Disease/genetics ; Exome/*genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Genetics, Population ; Heterozygote ; Humans ; Male ; Middle Aged ; Mutation/genetics ; Myocardial Infarction/blood/*genetics ; National Heart, Lung, and Blood Institute (U.S.) ; Receptors, LDL/*genetics ; Triglycerides/blood ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2012-09-01
    Description: We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30x) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617501/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617501/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, Matthias -- Kircher, Martin -- Gansauge, Marie-Theres -- Li, Heng -- Racimo, Fernando -- Mallick, Swapan -- Schraiber, Joshua G -- Jay, Flora -- Prufer, Kay -- de Filippo, Cesare -- Sudmant, Peter H -- Alkan, Can -- Fu, Qiaomei -- Do, Ron -- Rohland, Nadin -- Tandon, Arti -- Siebauer, Michael -- Green, Richard E -- Bryc, Katarzyna -- Briggs, Adrian W -- Stenzel, Udo -- Dabney, Jesse -- Shendure, Jay -- Kitzman, Jacob -- Hammer, Michael F -- Shunkov, Michael V -- Derevianko, Anatoli P -- Patterson, Nick -- Andres, Aida M -- Eichler, Evan E -- Slatkin, Montgomery -- Reich, David -- Kelso, Janet -- Paabo, Svante -- GM100233/GM/NIGMS NIH HHS/ -- R01 GM040282/GM/NIGMS NIH HHS/ -- R01 GM100233/GM/NIGMS NIH HHS/ -- R01-GM40282/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Oct 12;338(6104):222-6. doi: 10.1126/science.1224344. Epub 2012 Aug 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany. mmeyer@eva.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22936568" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Fossils ; Gene Flow ; Gene Library ; *Genetic Variation ; Genome, Human/*genetics ; *Heterozygote ; Humans ; Molecular Sequence Data ; Neanderthals/*genetics ; Sequence Analysis, DNA
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2012-05-19
    Description: As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111x in 2440 individuals of European (n = 1351) and African (n = 1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the majority of which were rare (86% with a minor allele frequency less than 0.5%), previously unknown (82%), and population-specific (82%). On average, 2.3% of the 13,595 SNVs each person carried were predicted to affect protein function of ~313 genes per genome, and ~95.7% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708544/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708544/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tennessen, Jacob A -- Bigham, Abigail W -- O'Connor, Timothy D -- Fu, Wenqing -- Kenny, Eimear E -- Gravel, Simon -- McGee, Sean -- Do, Ron -- Liu, Xiaoming -- Jun, Goo -- Kang, Hyun Min -- Jordan, Daniel -- Leal, Suzanne M -- Gabriel, Stacey -- Rieder, Mark J -- Abecasis, Goncalo -- Altshuler, David -- Nickerson, Deborah A -- Boerwinkle, Eric -- Sunyaev, Shamil -- Bustamante, Carlos D -- Bamshad, Michael J -- Akey, Joshua M -- Broad GO -- Seattle GO -- NHLBI Exome Sequencing Project -- R01 HG003229/HG/NHGRI NIH HHS/ -- RC2 HL-102923/HL/NHLBI NIH HHS/ -- RC2 HL-102924/HL/NHLBI NIH HHS/ -- RC2 HL-102925/HL/NHLBI NIH HHS/ -- RC2 HL-102926/HL/NHLBI NIH HHS/ -- RC2 HL-103010/HL/NHLBI NIH HHS/ -- RC2 HL102926/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2012 Jul 6;337(6090):64-9. doi: 10.1126/science.1219240. Epub 2012 May 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22604720" target="_blank"〉PubMed〈/a〉
    Keywords: African Americans/*genetics ; Disease/genetics ; European Continental Ancestry Group/*genetics ; *Evolution, Molecular ; *Exome ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; *Genetic Variation ; *Genome, Human ; *High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Polymorphism, Single Nucleotide ; Population Growth ; Selection, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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