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  • 201.
    Virtanen, Anders
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Pettersson, U.
    Le Moullec, J.M.
    Tiollais, P.
    Perricaudet, M.
    Different mRNAs from the transforming region (EIB) of highly- and non-oncogenic human adenoviruses1982Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 295, nr 5851, s. 705-707Artikkel i tidsskrift (Fagfellevurdert)
  • 202.
    Wahl, Simone
    et al.
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Alexandria, Med Res Inst, Clin & Expt Surg Dept, Hadara, Alexandria 21561, Egypt..
    Drong, Alexander
    Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England..
    Lehne, Benjamin
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England..
    Loh, Marie
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Inst Hlth Sci, POB 5000, FI-90014 Oulu, Finland.;Translat Lab Genet Med TLGM, Agcy Sci, Technol & Res ASTAR, 8A Biomed Grove, Singapore 138648, Singapore..
    Scott, William R.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England..
    Kunze, Sonja
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany..
    Tsai, Pei-Chien
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England..
    Yang, Youwen
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England..
    Tan, Sili
    Fiorito, Giovanni
    Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy..
    Franke, Lude
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Guarrera, Simonetta
    Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy..
    Kasela, Silva
    Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Riia 23, EE-51010 Tartu, Estonia..
    Kriebel, Jennifer
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Richmond, Rebecca C.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Adamo, Marco
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England..
    Afzal, Uzma
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England..
    Ala-Korpela, Mika
    Univ Oulu & Biocenter Oulu, Computat Med, Fac Med, Oulu, Finland.;Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Kuopio, Finland.;Univ Bristol & Med Res Council Integrat Epidemiol, Univ Bristol, Sch Social & Community Med, Computat Med, Bristol, Avon, England..
    Albetti, Benedetta
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Ammerpohl, Ole
    Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel Campus, Kiel, Germany..
    Apperley, Jane F.
    Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England..
    Beekman, Marian
    Leiden Univ Med Ctr, Mol Epidemiol, NL-2333 ZC Leiden, Netherlands..
    Bertazzi, Pier Alberto
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Black, S. Lucas
    Imperial Coll London, Dept Med, Sect Infect Dis & Immun, London W12 0NN, England..
    Blancher, Christine
    Bonder, Marc-Jan
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Brosch, Mario
    Univ Oxford, High Throughput Genom Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Tech Univ Dresden, Univ Hosp, Med Dept 1, Dresden, Germany..
    Carstensen-Kirberg, Maren
    Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany..
    de Craen, Anton J. M.
    Leiden Univ Med Ctr, Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands..
    de Lusignan, Simon
    Univ Surrey, Dept Clin & Expt Med, Guildford GU2 7PX, Surrey, England..
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Elkalaawy, Mohamed
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.;Univ Alexandria, Med Res Inst, Clin & Expt Surg Dept, Hadara, Alexandria 21561, Egypt..
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Gaunt, Tom R.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Hampe, Jochen
    Univ Oxford, High Throughput Genom Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Hashemi, Majid
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England..
    Isaacs, Aaron
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Jenkinson, Andrew
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England..
    Jha, Sujeet
    Dept Endocrinol, Diabet & Obes, Max Healthcare, New Delhi 110017, India..
    Kato, Norihiro
    Res Inst, Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Tokyo 1628655, Japan..
    Krogh, Vittorio
    Epidemiol & Prevent Unit, Fondazione IRCSS Ist Nazl Tumori, Milan, Italy..
    Laffan, Michael
    Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England..
    Meisinger, Christa
    Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany..
    Meitinger, Thomas
    German Res Ctr Environm Hlth, Int Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Mok, Zuan Yu
    Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore..
    Motta, Valeria
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Ng, Hong Kiat
    Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore..
    Nikolakopoulou, Zacharoula
    Natl Heart & Lung Inst, London SW3 6LY, England..
    Nteliopoulos, Georgios
    Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England..
    Panico, Salvatore
    Dipartmento Med Clin Chirurgia Federio II Univ, Naples, Italy..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Riia 23, EE-51010 Tartu, Estonia..
    Prokisch, Holger
    Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Rathmann, Wolfgang
    Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Biometr & Epidemiol, Dusseldorf, Germany..
    Roden, Michael
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.;Heinrich Heine Univ Hosp Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Rota, Federica
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Rozario, Michelle Ann
    Sandling, Johanna K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England..
    Schafmayer, Clemens
    Univ Hosp Schleswig Holstein, Dept Visceral & Thorac Surg, Kiel Campus, Kiel, Germany..
    Schramm, Katharina
    Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Siebert, Reiner
    Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel Campus, Kiel, Germany.;Univ Hosp Ulm, Inst Human Genet, Albert Einstein Allee 11, D-89081 Ulm, Germany..
    Slagboom, P. Eline
    Leiden Univ Med Ctr, Mol Epidemiol, NL-2333 ZC Leiden, Netherlands..
    Soininen, Pasi
    Univ Oulu & Biocenter Oulu, Computat Med, Fac Med, Oulu, Finland.;Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Kuopio, Finland..
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat, Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany..
    Tai, E-Shyong
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119228, Singapore.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.;Duke Natl Univ, Singapore Grad Med Sch, Singapore 169857, Singapore..
    Tarantini, Letizia
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Thorand, Barbara
    Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Tigchelaar, Ettje F.
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Tumino, Rosario
    Cancer Registry & Histopathol Unit, Civile MP Arezzo Hosp, ASP 7, Ragusa, Italy..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands..
    van Duijn, Cornelia
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    van Meurs, Joyce B. J.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Vineis, Paolo
    Imperial Coll London, Epidemiol & Publ Hlth, London, England..
    Wickremasinghe, Ananda Rajitha
    Univ Kelaniya, Dept Publ Hlth, Fac Med, Box 6,Thalagolla Rd, Ragama 11010, Sri Lanka..
    Wijmenga, Cisca
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Yang, Tsun-Po
    Yuan, Wei
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.;Inst Canc Res, Surrey SM2 5NG, England..
    Zhernakova, Alexandra
    Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands..
    Batterham, Rachel L.
    Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.;UCL, Rayne Inst, Dept Med, Ctr Obes Res, London WC1E 6JJ, England..
    Smith, George Davey
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Jawhara Brahim Ctr Excellence Res Heredi, Jeddah 21589, Saudi Arabia..
    Heijmans, Bastiaan T.
    Herder, Christian
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Lindgren, Cecilia M.
    Broad Inst, Massachusetts Inst Technol & Harvard Univ, Cambridge, MA 02142 USA..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia..
    van der Harst, Pim
    Univ Med Ctr Groningen, Dept Cardiol, Univ Groningen, NL-9700 RB Groningen, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, NL-3511 GC Utrecht, Netherlands..
    Peters, Annette
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Illig, Thomas
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Feodor Lynen St 15, Hannover, Germany.;Hannover Med Sch, Inst Human Genet, Carl Neuberg St 1, Hannover, Germany..
    Relton, Caroline L.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Waldenberger, Melanie
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany..
    Jaervelin, Marjo-Riitta
    Imperial Coll London, Sch Publ Hlth, MRC Hlth Protect Agcy HPE Ctr Environm & Hlth, Dept Epidemiol & Biostatist, London, England.;Univ Oulu, Bioctr Oulu, POB 5000, Oulu, Finland.;Univ Oulu, Ctr Life Course Epidemiol, Fac Med, POB 5000, Oulu 90014, Finland.;Oulu Univ Hosp, Unit Primary Care, Kajaanintie 50,Box 20, Oulu, Finland..
    Bollati, Valentina
    Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy..
    Soong, Richie
    Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore.;Natl Univ Singapore Hosp, Dept Pathol, Singapore, Singapore..
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Scott, James
    Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England..
    McCarthy, Mark I.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford NIHR Biomed Res Ctr, Churchill Hosp, Oxford OX3 7LJ, England..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England..
    Bell, Jordana T.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Matullo, Giuseppe
    Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy..
    Gieger, Christian
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany..
    Kooner, Jaspal S.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England.;Imperial Coll Healthcare NHS Trust, London W12 0HS, England..
    Grallert, Harald
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England.;Imperial Coll Healthcare NHS Trust, London W12 0HS, England.;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore..
    Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity2017Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 541, nr 7635, s. 81-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type (2) diabetes, cardiovascular disease and related metabolic and inflammatory disturbances(1,2). Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation(3-6), a key regulator of gene expression and molecular phenotype(7). Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 x 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.

  • 203. Wang, Yingdi
    et al.
    Nakayama, Masanori
    Pitulescu, Mara E
    Schmidt, Tim S
    Bochenek, Magdalena L
    Sakakibara, Akira
    Adams, Susanne
    Davy, Alice
    Deutsch, Urban
    Lüthi, Urs
    Barberis, Alcide
    Benjamin, Laura E
    Mäkinen, Taija
    Nobes, Catherine D
    Adams, Ralf H
    Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis.2010Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 465, nr 7297Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells, acquires motile, invasive behaviour and extends filopodial protrusions. Although it is already appreciated that angiogenesis is triggered by tissue-derived signals, such as vascular endothelial growth factor (VEGF) family growth factors, the resulting signalling processes in endothelial cells are only partly understood. Here we show with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium. We link this pro-angiogenic function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalization of VEGFR3 in cultured cells and mutant mice is defective, which compromises downstream signal transduction by the small GTPase Rac1, Akt and the mitogen-activated protein kinase Erk. Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth.

  • 204. Warren, Wesley C
    et al.
    Clayton, David F
    Ellegren, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Evolutionsbiologi.
    Arnold, Arthur P
    Hillier, Ladeana W
    Künstner, Axel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Searle, Steve
    White, Simon
    Vilella, Albert J
    Fairley, Susan
    Heger, Andreas
    Kong, Lesheng
    Ponting, Chris P
    Jarvis, Erich D
    Mello, Claudio V
    Minx, Pat
    Lovell, Peter
    Velho, Tarciso A F
    Ferris, Margaret
    Balakrishnan, Christopher N
    Sinha, Saurabh
    Blatti, Charles
    London, Sarah E
    Li, Yun
    Lin, Ya-Chi
    George, Julia
    Sweedler, Jonathan
    Southey, Bruce
    Gunaratne, Preethi
    Watson, Michael
    Nam, Kiwoong
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Backström, Niclas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Smeds, Linnea
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Nabholz, Benoit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik.
    Itoh, Yuichiro
    Whitney, Osceola
    Pfenning, Andreas R
    Howard, Jason
    Völker, Martin
    Skinner, Bejamin M
    Griffin, Darren K
    Ye, Liang
    McLaren, William M
    Flicek, Paul
    Quesada, Victor
    Velasco, Gloria
    Lopez-Otin, Carlos
    Puente, Xose S
    Olender, Tsviya
    Lancet, Doron
    Smit, Arian F A
    Hubley, Robert
    Konkel, Miriam K
    Walker, Jerilyn A
    Batzer, Mark A
    Gu, Wanjun
    Pollock, David D
    Chen, Lin
    Cheng, Ze
    Eichler, Evan E
    Stapley, Jessica
    Slate, Jon
    Ekblom, Robert
    Birkhead, Tim
    Burke, Terry
    Burt, David
    Scharff, Constance
    Adam, Iris
    Richard, Hugues
    Sultan, Marc
    Soldatov, Alexey
    Lehrach, Hans
    Edwards, Scott V
    Yang, Shiaw-Pyng
    Li, Xiaoching
    Graves, Tina
    Fulton, Lucinda
    Nelson, Joanne
    Chinwalla, Asif
    Hou, Shunfeng
    Mardis, Elaine R
    Wilson, Richard K
    The genome of a songbird2010Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, nr 7289, s. 757-762Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.

  • 205. Wedemeyer-Bohm, Sven
    et al.
    Scullion, Eamon
    Steiner, Oskar
    van der Voort, Luc Rouppe
    de la Cruz Rodriguez, Jaime
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Teoretisk astrofysik.
    Fedun, Viktor
    Erdelyi, Robert
    Magnetic tornadoes as energy channels into the solar corona2012Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 486, nr 7404, s. 505-508Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heating the outer layers of the magnetically quiet solar atmosphere to more than one million kelvin and accelerating the solar wind requires an energy flux of approximately 100 to 300 watts per square metre(1-6), but how this energy is transferred and dissipated there is a puzzle and several alternative solutions have been proposed. Braiding and twisting of magnetic field structures, which is caused by the convective flows at the solar surface, was suggested as an efficient mechanism for atmospheric heating(7). Convectively driven vortex flows that harbour magnetic fields are observed(8-10) to be abundant in the photosphere (the visible surface of the Sun). Recently, corresponding swirling motions have been discovered(11) in the chromosphere, the atmospheric layer sandwiched between the photosphere and the corona. Here we report the imprints of these chromospheric swirls in the transition region and low corona, and identify them as observational signatures of rapidly rotating magnetic structures. These ubiquitous structures, which resemble super-tornadoes under solar conditions, reach from the convection zone into the upper solar atmosphere and provide an alternative mechanism for channelling energy from the lower into the upper solar atmosphere.

  • 206.
    Willem, Michael
    et al.
    Univ Munich, Biomed Ctr BMC, D-81377 Munich, Germany..
    Tahirovic, Sabina
    German Ctr Neurodegenerat Dis DZNE Munich, D-81377 Munich, Germany..
    Busche, Marc Aurel
    Tech Univ Munich, Dept Psychiat & Psychotherapy, D-81675 Munich, Germany.;Tech Univ Munich, Inst Neurosci, D-80802 Munich, Germany.;Univ Munich, Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany..
    Ovsepian, Saak V.
    German Ctr Neurodegenerat Dis DZNE Munich, D-81377 Munich, Germany..
    Chafai, Magda
    Univ Nice Sophia Antipolis, UMR 7275, CNRS, IPMC, F-06560 Valbonne, France..
    Kootar, Scherazad
    Univ Nice Sophia Antipolis, UMR 7275, CNRS, IPMC, F-06560 Valbonne, France..
    Hornburg, Daniel
    Max Planck Inst Biochem, D-82152 Martinsried, Germany..
    Evans, Lewis D. B.
    Univ Cambridge, Gurdon Inst, Cambridge Stem Cell Inst, Cambridge CB2 1QN, England.;Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England..
    Moore, Steven
    Univ Cambridge, Gurdon Inst, Cambridge Stem Cell Inst, Cambridge CB2 1QN, England.;Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England..
    Daria, Anna
    Univ Munich, Biomed Ctr BMC, D-81377 Munich, Germany..
    Hampel, Heike
    Univ Munich, Biomed Ctr BMC, D-81377 Munich, Germany..
    Mueller, Veronika
    Univ Munich, Biomed Ctr BMC, D-81377 Munich, Germany..
    Giudici, Camilla
    Univ Munich, Biomed Ctr BMC, D-81377 Munich, Germany..
    Nuscher, Brigitte
    Univ Munich, Biomed Ctr BMC, D-81377 Munich, Germany..
    Wenninger-Weinzierl, Andrea
    German Ctr Neurodegenerat Dis DZNE Munich, D-81377 Munich, Germany..
    Kremmer, Elisabeth
    German Ctr Neurodegenerat Dis DZNE Munich, D-81377 Munich, Germany.;Univ Munich, Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany.;German Res Ctr Environm Hlth, Inst Mol Immunol, D-81377 Munich, Germany..
    Heneka, Michael T.
    Univ Bonn, Clin Neurosci Unit, Dept Neurol, D-53127 Bonn, Germany.;German Ctr Neurodegenerat Dis DZNE Bonn, D-53175 Bonn, Germany..
    Thal, Dietmar R.
    Univ Ulm, Inst Pathol, Neuropathol Lab, D-89081 Ulm, Germany..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Mueller, Ulrike
    Heidelberg Univ, Funct Genom, Inst Pharm & Mol Biotechnol IPMB, D-69120 Heidelberg, Germany..
    Livesey, Frederick J.
    Univ Cambridge, Gurdon Inst, Cambridge Stem Cell Inst, Cambridge CB2 1QN, England.;Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England..
    Meissner, Felix
    Max Planck Inst Biochem, D-82152 Martinsried, Germany..
    Herms, Jochen
    German Ctr Neurodegenerat Dis DZNE Munich, D-81377 Munich, Germany..
    Konnerth, Arthur
    Tech Univ Munich, Inst Neurosci, D-80802 Munich, Germany.;Univ Munich, Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany..
    Marie, Helene
    Univ Nice Sophia Antipolis, UMR 7275, CNRS, IPMC, F-06560 Valbonne, France..
    Haass, Christian
    Univ Munich, Biomed Ctr BMC, D-81377 Munich, Germany.;German Ctr Neurodegenerat Dis DZNE Munich, D-81377 Munich, Germany.;Univ Munich, Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany..
    eta-Secretase processing of APP inhibits neuronal activity in the hippocampus2015Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, nr 7573, s. 443-447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimer disease (AD) is characterized by the accumulation of amyloid plaques, which are predominantly composed of amyloid-beta peptide(1). Two principal physiological pathways either prevent or promote amyloid-beta generation from its precursor, beta-amyloid precursor protein (APP), in a competitive manne(r)1. Although APP processing has been studied in great detail, unknown proteolytic events seem to hinder stoichiometric analyses of APP metabolism in vivo(2). Here we describe a new physiological APP processing pathway, which generates proteolytic fragments capable of inhibiting neuronal activity within the hippocampus. We identify higher molecular mass carboxy-terminal fragments (CTFs) of APP, termed CTF-eta, in addition to the long-known CTF-alpha and CTF-beta fragments generated by the alpha- and beta-secretases ADAM10 (a disintegrin and metalloproteinase 10) and BACE1 (beta-site APP cleaving enzyme 1), respectively. CTF-eta generation is mediated in part by membrane-bound matrix metalloproteinases such as MT5-MMP, referred to as g-secretase activity. g-Secretase cleavage occurs primarily at amino acids 504-505 of APP(695), releasing a truncated ectodomain. After shedding of this ectodomain, CTF-eta is further processed by ADAM10 and BACE1 to release long and short A eta peptides (termed A eta-alpha and A eta-beta). CTFs produced by g-secretase are enriched in dystrophic neurites in an AD mouse model and in human AD brains. Genetic and pharmacological inhibition of BACE1 activity results in robust accumulation of CTF-eta and A eta-alpha. In mice treated with a potent BACE1 inhibitor, hippocampal long-term potentiation was reduced. Notably, when recombinant or synthetic A eta-alpha was applied on hippocampal slices ex vivo, long-term potentiation was lowered. Furthermore, in vivo single-cell two-photon calcium imaging showed that hippocampal neuronal activity was attenuated by A eta-alpha. These findings not only demonstrate a major functionally relevant APP processing pathway, but may also indicate potential translational relevance for therapeutic strategies targeting APP processing.

  • 207.
    Winkler, K
    et al.
    Institute for Experimental Physics, University of Innsbruck, A-6020 Innsbruck, Austria.
    Thalhammer, G
    Institute for Experimental Physics, University of Innsbruck, A-6020 Innsbruck, Austria.
    Lang, F
    Institute for Experimental Physics, University of Innsbruck, A-6020 Innsbruck, Austria.
    Grimm, R
    Institute for Experimental Physics, University of Innsbruck, A-6020 Innsbruck, Austria;Institute for Quantum Optics and Quantum Information of the Austrian Academy of Sciences, A-6020 Innsbruck, Austria.
    Denschlag, J Hecker
    Institute for Experimental Physics, University of Innsbruck, A-6020 Innsbruck, Austria.
    Daley, A J
    Institute for Theoretical Physics, University of Innsbruck, A-6020 Innsbruck, Austria;Institute for Quantum Optics and Quantum Information of the Austrian Academy of Sciences, A-6020 Innsbruck, Austria.
    Kantian, A.
    Institute for Theoretical Physics, University of Innsbruck, A-6020 Innsbruck, Austria;Institute for Quantum Optics and Quantum Information of the Austrian Academy of Sciences, A-6020 Innsbruck, Austria.
    Büchler, H P
    Institute for Theoretical Physics, University of Innsbruck, A-6020 Innsbruck, Austria;Institute for Quantum Optics and Quantum Information of the Austrian Academy of Sciences, A-6020 Innsbruck, Austria.
    Zoller, P
    Institute for Theoretical Physics, University of Innsbruck, A-6020 Innsbruck, Austria;Institute for Quantum Optics and Quantum Information of the Austrian Academy of Sciences, A-6020 Innsbruck, Austria.
    Repulsively bound atom pairs in an optical lattice.2006Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 441, nr 7095, s. 853-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Throughout physics, stable composite objects are usually formed by way of attractive forces, which allow the constituents to lower their energy by binding together. Repulsive forces separate particles in free space. However, in a structured environment such as a periodic potential and in the absence of dissipation, stable composite objects can exist even for repulsive interactions. Here we report the observation of such an exotic bound state, which comprises a pair of ultracold rubidium atoms in an optical lattice. Consistent with our theoretical analysis, these repulsively bound pairs exhibit long lifetimes, even under conditions when they collide with one another. Signatures of the pairs are also recognized in the characteristic momentum distribution and through spectroscopic measurements. There is no analogue in traditional condensed matter systems of such repulsively bound pairs, owing to the presence of strong decay channels. Our results exemplify the strong correspondence between the optical lattice physics of ultracold bosonic atoms and the Bose-Hubbard model-a link that is vital for future applications of these systems to the study of strongly correlated condensed matter and to quantum information.

  • 208. Yang, Jian
    et al.
    Loos, Ruth J F
    Powell, Joseph E
    Medland, Sarah E
    Speliotes, Elizabeth K
    Chasman, Daniel I
    Rose, Lynda M
    Thorleifsson, Gudmar
    Steinthorsdottir, Valgerdur
    Mägi, Reedik
    Waite, Lindsay
    Smith, Albert Vernon
    Yerges-Armstrong, Laura M
    Monda, Keri L
    Hadley, David
    Mahajan, Anubha
    Li, Guo
    Kapur, Karen
    Vitart, Veronique
    Huffman, Jennifer E
    Wang, Sophie R
    Palmer, Cameron
    Esko, Tõnu
    Fischer, Krista
    Zhao, Jing Hua
    Demirkan, Ayşe
    Isaacs, Aaron
    Feitosa, Mary F
    Luan, Jian'an
    Heard-Costa, Nancy L
    White, Charles
    Jackson, Anne U
    Preuss, Michael
    Ziegler, Andreas
    Eriksson, Joel
    Kutalik, Zoltán
    Frau, Francesca
    Nolte, Ilja M
    Van Vliet-Ostaptchouk, Jana V
    Hottenga, Jouke-Jan
    Jacobs, Kevin B
    Verweij, Niek
    Goel, Anuj
    Medina-Gomez, Carolina
    Estrada, Karol
    Bragg-Gresham, Jennifer Lynn
    Sanna, Serena
    Sidore, Carlo
    Tyrer, Jonathan
    Teumer, Alexander
    Prokopenko, Inga
    Mangino, Massimo
    Lindgren, Cecilia M
    Assimes, Themistocles L
    Shuldiner, Alan R
    Hui, Jennie
    Beilby, John P
    McArdle, Wendy L
    Hall, Per
    Haritunians, Talin
    Zgaga, Lina
    Kolcic, Ivana
    Polasek, Ozren
    Zemunik, Tatijana
    Oostra, Ben A
    Junttila, M Juhani
    Grönberg, Henrik
    Schreiber, Stefan
    Peters, Annette
    Hicks, Andrew A
    Stephens, Jonathan
    Foad, Nicola S
    Laitinen, Jaana
    Pouta, Anneli
    Kaakinen, Marika
    Willemsen, Gonneke
    Vink, Jacqueline M
    Wild, Sarah H
    Navis, Gerjan
    Asselbergs, Folkert W
    Homuth, Georg
    John, Ulrich
    Iribarren, Carlos
    Harris, Tamara
    Launer, Lenore
    Gudnason, Vilmundur
    O'Connell, Jeffrey R
    Boerwinkle, Eric
    Cadby, Gemma
    Palmer, Lyle J
    James, Alan L
    Musk, Arthur W
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Psaty, Bruce M
    Beckmann, Jacques S
    Waeber, Gerard
    Vollenweider, Peter
    Hayward, Caroline
    Wright, Alan F
    Rudan, Igor
    Groop, Leif C
    Metspalu, Andres
    Khaw, Kay Tee
    van Duijn, Cornelia M
    Borecki, Ingrid B
    Province, Michael A
    Wareham, Nicholas J
    Tardif, Jean-Claude
    Huikuri, Heikki V
    Cupples, L Adrienne
    Atwood, Larry D
    Fox, Caroline S
    Boehnke, Michael
    Collins, Francis S
    Mohlke, Karen L
    Erdmann, Jeanette
    Schunkert, Heribert
    Hengstenberg, Christian
    Stark, Klaus
    Lorentzon, Mattias
    Ohlsson, Claes
    Cusi, Daniele
    Staessen, Jan A
    Van der Klauw, Melanie M
    Pramstaller, Peter P
    Kathiresan, Sekar
    Jolley, Jennifer D
    Ripatti, Samuli
    Jarvelin, Marjo-Riitta
    de Geus, Eco J C
    Boomsma, Dorret I
    Penninx, Brenda
    Wilson, James F
    Campbell, Harry
    Chanock, Stephen J
    van der Harst, Pim
    Hamsten, Anders
    Watkins, Hugh
    Hofman, Albert
    Witteman, Jacqueline C
    Zillikens, M Carola
    Uitterlinden, André G
    Rivadeneira, Fernando
    Zillikens, M Carola
    Kiemeney, Lambertus A
    Vermeulen, Sita H
    Abecasis, Goncalo R
    Schlessinger, David
    Schipf, Sabine
    Stumvoll, Michael
    Tönjes, Anke
    Spector, Tim D
    North, Kari E
    Lettre, Guillaume
    McCarthy, Mark I
    Berndt, Sonja I
    Heath, Andrew C
    Madden, Pamela A F
    Nyholt, Dale R
    Montgomery, Grant W
    Martin, Nicholas G
    McKnight, Barbara
    Strachan, David P
    Hill, William G
    Snieder, Harold
    Ridker, Paul M
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    Frayling, Timothy M
    Hirschhorn, Joel N
    Goddard, Michael E
    Visscher, Peter M
    FTO genotype is associated with phenotypic variability of body mass index2012Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 490, nr 7419, s. 267-272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ∼0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

  • 209.
    Yang, Zhenlin
    et al.
    Chinese Acad Sci, Shanghai Inst Mat Medica, Key Lab Receptor Res, Shanghai, Peoples R China;Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China.
    Han, Shuo
    Chinese Acad Sci, Shanghai Inst Mat Medica, Key Lab Receptor Res, Shanghai, Peoples R China;Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China.
    Keller, Max
    Univ Regensburg, Inst Pharm, Pharmaceut Med Chem 2, Regensburg, Germany.
    Kaiser, Anette
    Bender, Brian J.
    Vanderbilt Univ, Dept Pharmacol, Struct Biol Ctr, Nashville, TN USA.
    Bosse, Mathias
    Univ Leipzig, Inst Med Phys & Biophys, Leipzig, Germany.
    Burkert, Kerstin
    Univ Leipzig, Inst Biochem, Fac Life Sci, Leipzig, Germany.
    Koegler, Lisa M.
    Univ Leipzig, Inst Biochem, Fac Life Sci, Leipzig, Germany.
    Wifling, David
    Univ Regensburg, Inst Pharm, Pharmaceut Med Chem 2, Regensburg, Germany.
    Bernhardt, Guenther
    Univ Regensburg, Inst Pharm, Pharmaceut Med Chem 2, Regensburg, Germany.
    Plank, Nicole
    Univ Regensburg, Inst Pharm, Pharmaceut Med Chem 2, Regensburg, Germany.
    Littmann, Timo
    Univ Regensburg, Inst Pharm, Pharmaceut Med Chem 2, Regensburg, Germany.
    Schmidt, Peter
    Univ Leipzig, Inst Med Phys & Biophys, Leipzig, Germany.
    Yi, Cuiying
    Chinese Acad Sci, Shanghai Inst Mat Medica, Key Lab Receptor Res, Shanghai, Peoples R China.
    Li, Beibei
    Chinese Acad Sci, Shanghai Inst Mat Medica, Key Lab Receptor Res, Shanghai, Peoples R China;Univ Chinese Acad Sci, Beijing, Peoples R China.
    Ye, Sheng
    Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China.
    Zhang, Rongguang
    Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China;Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Shanghai, Peoples R China.
    Xu, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Larhammar, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Stevens, Raymond C.
    ShanghaiTech Univ, Human Inst, Shanghai, Peoples R China;ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China.
    Huster, Daniel
    Univ Leipzig, Inst Med Phys & Biophys, Leipzig, Germany.
    Meiler, Jens
    Vanderbilt Univ, Dept Pharmacol, Struct Biol Ctr, Nashville, TN USA;Vanderbilt Univ, Struct Biol Ctr, Dept Chem, 221 Kirkland Hall, Nashville, TN 37235 USA;Vanderbilt Univ, Dept Bioinformat, Struct Biol Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Zhao, Qiang
    Chinese Acad Sci, Shanghai Inst Mat Medica, Key Lab Receptor Res, Shanghai, Peoples R China;Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China;Univ Chinese Acad Sci, Beijing, Peoples R China;Chinese Acad Sci, Ctr Excellence Biomacromol, Beijing, Peoples R China.
    Beck-Sickinger, Annette G.
    Univ Leipzig, Inst Biochem, Fac Life Sci, Leipzig, Germany.
    Buschauer, Armin
    Univ Regensburg, Inst Pharm, Pharmaceut Med Chem 2, Regensburg, Germany.
    Wu, Beili
    Chinese Acad Sci, Shanghai Inst Mat Medica, Key Lab Receptor Res, Shanghai, Peoples R China;Univ Chinese Acad Sci, Beijing, Peoples R China;ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China;Chinese Acad Sci, Ctr Excellence Biomacromol, Beijing, Peoples R China.
    Structural basis of ligand binding modes at the neuropeptide Y Y-1 receptor2018Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 556, nr 7702, s. 520-524Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor superfamily and have important roles in food intake, anxiety and cancer biology(1,2). The NPY-Y receptor system has emerged as one of the most complex networks with three peptide ligands (NPY, peptide YY and pancreatic polypeptide) binding to four receptors in most mammals, namely the Y-1, Y-2, Y-4 and Y-5 receptors, with different affinity and selectivity(3). NPY is the most powerful stimulant of food intake and this effect is primarily mediated by the Y-1 receptor (Y1R)(4). A number of peptides and small-molecule compounds have been characterized as Y1R antagonists and have shown clinical potential in the treatment of obesity(4), tumour(1) and bone loss(5). However, their clinical usage has been hampered by low potency and selectivity, poor brain penetration ability or lack of oral bioavailability(6). Here we report crystal structures of the human Y1R bound to the two selective antagonists UR-MK299 and BMS-193885 at 2.7 and 3.0 angstrom resolution, respectively. The structures combined with mutagenesis studies reveal the binding modes of Y1R to several structurally diverse antagonists and the determinants of ligand selectivity. The Y1R structure and molecular docking of the endogenous agonist NPY, together with nuclear magnetic resonance, photo-crosslinking and functional studies, provide insights into the binding behaviour of the agonist and for the first time, to our knowledge, determine the interaction of its N terminus with the receptor. These insights into Y1R can enable structure-based drug discovery that targets NPY receptors.

  • 210.
    Yeung, Maggie S. Y.
    et al.
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
    Djelloul, Mehdi
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
    Steiner, Embla
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
    Bernard, Samuel
    Univ Lyon, CNRS, UMR 5208, Inst Camille Jordan, Villeurbanne, France.
    Salehpour, Mehran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Tillämpad kärnfysik.
    Possnert, Göran
    Brundin, Lou
    Karolinska Inst, Karolinska Univ Hosp, Div Neurol, Dept Clin Neurosci, Stockholm, Sweden.
    Frisen, Jonas
    Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
    Dynamics of oligodendrocyte generation in multiple sclerosis2019Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 566, nr 7745, s. 538-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Oligodendrocytes wrap nerve fibres in the central nervous system with layers of specialized cell membrane to form myelin sheaths(1). Myelin is destroyed by the immune system in multiple sclerosis, but myelin is thought to regenerate and neurological function can be recovered. In animal models of demyelinating disease, myelin is regenerated by newly generated oligodendrocytes, and remaining mature oligodendrocytes do not seem to contribute to this process(2-4). Given the major differences in the dynamics of oligodendrocyte generation and adaptive myelination between rodents and humans(5-9), it is not clear how well experimental animal models reflect the situation in multiple sclerosis. Here, by measuring the integration of C-14 derived from nuclear testing in genomic DNA(10), we assess the dynamics of oligodendrocyte generation in patients with multiple sclerosis. The generation of new oligodendrocytes was increased several-fold in normal-appearing white matter in a subset of individuals with very aggressive multiple sclerosis, but not in most subjects with the disease, demonstrating an inherent potential to substantially increase oligodendrocyte generation that fails in most patients. Oligodendrocytes in shadow plaques-thinly myelinated lesions that are thought to represent remyelinated areas-were old in patients with multiple sclerosis. The absence of new oligodendrocytes in shadow plaques suggests that remyelination of lesions occurs transiently or not at all, or that myelin is regenerated by pre-existing, and not new, oligodendrocytes in multiple sclerosis. We report unexpected oligodendrocyte generation dynamics in multiple sclerosis, and this should guide the use of current, and the development of new, therapies.

  • 211.
    Young, Iris D.
    et al.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Ibrahim, Mohamed
    Humboldt Univ, Inst Biol, D-10099 Berlin, Germany..
    Chatterjee, Ruchira
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Gul, Sheraz
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Fuller, Franklin D.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Koroidov, Sergey
    Umea Univ, Inst Kemi, Kemiskt Biol Ctr, S-90187 Umea, Sweden..
    Brewster, Aaron S.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Tran, Rosalie
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Alonso-Mori, Roberto
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Kroll, Thomas
    SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA.;SLAC Natl Accelerator Lab, SSRL, Menlo Pk, CA 94025 USA..
    Michels-Clark, Tara
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Laksmono, Hartawan
    SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA..
    Sierra, Raymond G.
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA.;SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA..
    Stan, Claudiu A.
    SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA..
    Hussein, Rana
    Humboldt Univ, Inst Biol, D-10099 Berlin, Germany..
    Zhang, Miao
    Humboldt Univ, Inst Biol, D-10099 Berlin, Germany..
    Douthit, Lacey
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Kubin, Markus
    Helmholtz Zentrum, Inst Methods & Instrumentat Synchrotron Radiat Re, D-14109 Berlin, Germany..
    de Lichtenberg, Casper
    Umea Univ, Inst Kemi, Kemiskt Biol Ctr, S-90187 Umea, Sweden..
    Pham, Long Vo
    Nilsson, Hakan
    Umea Univ, Inst Kemi, Kemiskt Biol Ctr, S-90187 Umea, Sweden..
    Cheah, Mun Hon
    Umea Univ, Inst Kemi, Kemiskt Biol Ctr, S-90187 Umea, Sweden..
    Shevela, Dmitriy
    Umea Univ, Inst Kemi, Kemiskt Biol Ctr, S-90187 Umea, Sweden..
    Saracini, Claudio
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Bean, Mackenzie A.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Seuffert, Ina
    Humboldt Univ, Inst Biol, D-10099 Berlin, Germany..
    Sokaras, Dimosthenis
    SLAC Natl Accelerator Lab, SSRL, Menlo Pk, CA 94025 USA..
    Weng, Tsu-Chien
    SLAC Natl Accelerator Lab, SSRL, Menlo Pk, CA 94025 USA.;Ctr High Pressure Sci & Technol Adv Res, Shanghai 201203, Peoples R China..
    Pastor, Ernest
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Weninger, Clemens
    SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA..
    Fransson, Thomas
    SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA..
    Lassalle, Louise
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Braeuer, Philipp
    Univ Oxford, Dept Biochem, S Parks Rd, Oxford OX1 3QU, England.;Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England..
    Aller, Pierre
    Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England..
    Docker, Peter T.
    Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England..
    Andi, Babak
    Brookhaven Natl Lab, Natl Synchrotron Light Source 2, Upton, NY 11973 USA..
    Orville, Allen M.
    Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England..
    Glownia, James M.
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Nelson, Silke
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Sikorski, Marcin
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Zhu, Diling
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Hunter, Mark S.
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Lane, Thomas J.
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Aquila, Andy
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Koglin, Jason E.
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Robinson, Joseph
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Liang, Mengning
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Boutet, Sebastien
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Lyubimov, Artem Y.
    Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.;Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA..
    Uervirojnangkoorn, Monarin
    Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.;Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA..
    Moriarty, Nigel W.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Liebschner, Dorothee
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Afonine, Pavel V.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Waterman, David G.
    STFC Rutherford Appleton Lab, Didcot OX11 0QX, Oxon, England.;Rutherford Appleton Lab, CCP4,Res Complex Harwell, Didcot OX11 0FA, Oxon, England..
    Evans, Gwyndaf
    Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon, England..
    Wernet, Philippe
    Helmholtz Zentrum, Inst Methods & Instrumentat Synchrotron Radiat Re, D-14109 Berlin, Germany..
    Dobbek, Holger
    Humboldt Univ, Inst Biol, D-10099 Berlin, Germany..
    Weis, William I.
    Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.;Stanford Univ, Dept Photon Sci, Stanford, CA 94305 USA.;Stanford Univ, Dept Struct Biol, Stanford, CA 94305 USA..
    Brunger, Axel T.
    Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.;Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.;Stanford Univ, Dept Photon Sci, Stanford, CA 94305 USA.;Stanford Univ, Dept Struct Biol, Stanford, CA 94305 USA..
    Zwart, Petrus H.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Adams, Paul D.
    Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA..
    Zouni, Athina
    Humboldt Univ, Inst Biol, D-10099 Berlin, Germany..
    Messinger, Johannes
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik. Umea Univ, Inst Kemi, Kemiskt Biol Ctr, S-90187 Umea, Sweden..
    Bergmann, Uwe
    SLAC Natl Accelerator Lab, Stanford PULSE Inst, Menlo Pk, CA 94025 USA..
    Sauter, Nicholas K.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Kern, Jan
    SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA..
    Yachandra, Vittal K.
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Yano, Junko
    Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging Div, Berkeley, CA 94720 USA..
    Structure of photosystem II and substrate binding at room temperature2016Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 540, nr 7633, s. 453-457Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment protein complex, couples the one-electron photochemistry at the reaction centre with the four-electron redox chemistry of water oxidation at the Mn4CaO5 cluster in the oxygen-evolving complex (OEC). Under illumination, the OEC cycles through five intermediate S-states (S-0 to S-4)(1), in which S-1 is the dark-stable state and S-3 is the last semi-stable state before O-O bond formation and O-2 evolution(2,3). A detailed understanding of the O-O bond formation mechanism remains a challenge, and will require elucidation of both the structures of the OEC in the different S-states and the binding of the two substrate waters to the catalytic site(4-6). Here we report the use of femtosecond pulses from an X-ray free electron laser (XFEL) to obtain damage-free, room temperature structures of dark-adapted (S-1), two-flash illuminated (2F; S-3-enriched), and ammonia-bound two-flash illuminated (2F-NH3; S-3-enriched) PS II. Although the recent 1.95 angstrom resolution structure of PS II at cryogenic temperature using an XFEL7 provided a damage-free view of the S-1 state, measurements at room temperature are required to study the structural landscape of proteins under functional conditions(8,9), and also for in situ advancement of the S-states. To investigate the water-binding site(s), ammonia, a water analogue, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S-2 and S-3 states(10). Since the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate water site(10-13). This approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O-O bond formation mechanisms.

  • 212. Yvon-Durocher, Gabriel
    et al.
    Allen, Andrew P.
    Bastviken, David
    Conrad, Ralf
    Gudasz, Cristian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi.
    St-Pierre, Annick
    Thanh-Duc, Nguyen
    del Giorgio, Paul A.
    Methane fluxes show consistent temperature dependence across microbial to ecosystem scales2014Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 507, nr 7493, s. 488-491Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Methane (CH4) is an important greenhouse gas because it has 25 times the global warming potential of carbon dioxide (CO2) by mass over a century(1). Recent calculations suggest that atmospheric CH4 emissions have been responsible for approximately 20% of Earth's warming since pre-industrial times(2). Understanding how CH4 emissions from ecosystems will respond to expected increases in global temperature is therefore fundamental to predicting whether the carbon cycle will mitigate or accelerate climate change. Methanogenesis is the terminal step in the remineralization of organic matter and is carried out by strictly anaerobic Archaea(3). Like most other forms of metabolism, methanogenesis is temperature-dependent(4,5). However, it is not yet known how this physiological response combines with other biotic processes (for example, methanotrophy(6), substrate supply(3,7), microbial community composition(8)) and abiotic processes (for example, water-table depth(9,10)) to determine the temperature dependence of ecosystem-level CH4 emissions. It is also not known whether CH4 emissions at the ecosystem level have a fundamentally different temperature dependence than other key fluxes in the carbon cycle, such as photosynthesis and respiration. Here we use meta-analyses to show that seasonal variations in CH4 emissions from a wide range of ecosystems exhibit an average temperature dependence similar to that of CH4 production derived from pure cultures of methanogens and anaerobic microbial communities. This average temperature dependence (0.96 electron volts (eV)), which corresponds to a 57-fold increase between 0 and 30 degrees C, is considerably higher than previously observed for respiration (approximately 0.65 eV)(11) and photosynthesis (approximately 0.3 eV)(12). As a result, we show that both the emission of CH4 and the ratio of CH4 to CO2 emissions increase markedly with seasonal increases in temperature. Our findings suggest that global warming may have a large impact on the relative contributions of CO2 and CH4 to total greenhouse gas emissions from aquatic ecosystems, terrestrial wetlands and rice paddies.

  • 213.
    Zaremba-Niedzwiedzka, Katarzyna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fernández Cáceres, Eva
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Saw, Jimmy Hser Wah
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bäckström, Disa
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Juzokaite, Lina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Vancaester, Emmelien
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Univ Ghent, Dept Plant Syst Biol, VIB, Technol Pk 927, B-9052 Ghent, Belgium.;Univ Ghent, Dept Plant Biotechnol & Bioinformat, Technol Pk 927, B-9052 Ghent, Belgium..
    Seitz, Kiley W.
    Univ Texas Austin, Inst Marine Sci, Dept Marine Sci, Port Aransas, TX 78373 USA..
    Anantharaman, Karthik
    Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.;Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA..
    Starnawski, Piotr
    Aarhus Univ, Sect Microbiol, DK-8000 Aarhus, Denmark.;Aarhus Univ, Ctr Geomicrobiol, Dept Biosci, DK-8000 Aarhus, Denmark..
    Kjeldsen, Kasper U.
    Aarhus Univ, Sect Microbiol, DK-8000 Aarhus, Denmark.;Aarhus Univ, Ctr Geomicrobiol, Dept Biosci, DK-8000 Aarhus, Denmark..
    Stott, Matthew B.
    Extremophile Res Grp, GNS Sci, Private Bag 2000, Taupo 3352, New Zealand..
    Nunoura, Takuro
    Japan Agcy Marine Earth Sci & Technol, Res & Dev Ctr Marine Biosci, Yokosuka, Kanagawa 2370061, Japan..
    Banfield, Jillian F.
    Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.;Univ Calif Berkeley, Dept Environm Sci Policy & Management, Berkeley, CA 94720 USA..
    Schramm, Andreas
    Aarhus Univ, Sect Microbiol, DK-8000 Aarhus, Denmark.;Aarhus Univ, Ctr Geomicrobiol, Dept Biosci, DK-8000 Aarhus, Denmark..
    Baker, Brett J.
    Univ Texas Austin, Inst Marine Sci, Dept Marine Sci, Port Aransas, TX 78373 USA..
    Spang, Anja
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ettema, Thijs J. G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Asgard archaea illuminate the origin of eukaryotic cellular complexity2017Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 541, nr 7637, s. 353-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The origin and cellular complexity of eukaryotes represent a major enigma in biology. Current data support scenarios in which an archaeal host cell and an alphaproteobacterial (mitochondrial) endosymbiont merged together, resulting in the first eukaryotic cell. The host cell is related to Lokiarchaeota, an archaeal phylum with many eukaryotic features. The emergence of the structural complexity that characterizes eukaryotic cells remains unclear. Here we describe the 'Asgard' superphylum, a group of uncultivated archaea that, as well as Lokiarchaeota, includes Thor-, Odin- and Heimdallarchaeota. Asgard archaea affiliate with eukaryotes in phylogenomic analyses, and their genomes are enriched for proteins formerly considered specific to eukaryotes. Notably, thorarchaeal genomes encode several homologues of eukaryotic membrane-trafficking machinery components, including Sec23/24 and TRAPP domains. Furthermore, we identify thorarchaeal proteins with similar features to eukaryotic coat proteins involved in vesicle biogenesis. Our results expand the known repertoire of 'eukaryote-specific' proteins in Archaea, indicating that the archaeal host cell already contained many key components that govern eukaryotic cellular complexity.

  • 214.
    Zheng, Hou-Feng
    et al.
    McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada..
    Forgetta, Vincenzo
    McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada..
    Hsu, Yi-Hsiang
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA..
    Estrada, Karol
    Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA.;Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Rosello-Diez, Alberto
    Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA..
    Leo, Paul J.
    Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia..
    Dahia, Chitra L.
    Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA.;Hosp Special Surg, Tissue Engn Regenerat & Repair Program, New York, NY 10021 USA..
    Park-Min, Kyung Hyun
    Hosp Special Surg, Rheumatol Div, New York, NY 10021 USA..
    Tobias, Jonathan H.
    Univ Bristol, Sch Clin Sci, Bristol BS10 5NB, Avon, England.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA..
    Kleinman, Aaron
    23andMe, Res Dept, Mountain View, CA 94041 USA..
    Styrkarsdottir, Unnur
    deCODE Genet, Dept Populat Genom, IS-101 Reykjavik, Iceland..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Uggla, Charlotta
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden..
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94158 USA..
    Nielson, Carrie M.
    Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Bone Mineral Unit, Portland, OR 97239 USA..
    Walter, Klaudia
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Pettersson-Kymmer, Ulrika
    Umea Univ, Dept Pharmacol, S-90187 Umea, Sweden.;Umea Univ, Dept Clin Neurosci, S-90187 Umea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden..
    McCarthy, Shane
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Eriksson, Joel
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, S-41345 Gothenburg, Sweden..
    Kwan, Tony
    McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada..
    Jhamai, Mila
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Trajanoska, Katerina
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Memari, Yasin
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Min, Josine
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Huang, Jie
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Danecek, Petr
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Wilmot, Beth
    Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Dept Med & Clin Informat, Portland, OR 97239 USA..
    Li, Rui
    McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada..
    Chou, Wen-Chi
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA..
    Mokry, Lauren E.
    McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada..
    Moayyeri, Alireza
    UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Claussnitzer, Melina
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA.;Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA..
    Cheng, Chia-Ho
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA..
    Cheung, Warren
    McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands..
    Ge, Bing
    McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada..
    Chen, Shu-Huang
    McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada..
    Choi, Kwangbom
    Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14642 USA..
    Oei, Ling
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands..
    Fraser, James
    McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.;McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada..
    Kraaij, Robert
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands..
    Hibbs, Matthew A.
    Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14642 USA.;Trinity Univ, Dept Comp Sci, San Antonio, TX 78212 USA..
    Gregson, Celia L.
    Univ Bristol, Musculoskeletal Res Unit, Bristol BS10 5NB, Avon, England..
    Paquette, Denis
    McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.;McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands..
    Wibom, Carl
    Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Tranah, Gregory J.
    Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Bone Mineral Unit, Portland, OR 97239 USA..
    Marshall, Mhairi
    Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia..
    Gardiner, Brooke B.
    Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia..
    Cremin, Katie
    Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia..
    Auer, Paul
    Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53726 USA..
    Hsu, Li
    Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA..
    Ring, Sue
    Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England..
    Tung, Joyce Y.
    23andMe, Res Dept, Mountain View, CA 94041 USA..
    Thorleifsson, Gudmar
    deCODE Genet, Dept Stat, IS-101 Reykjavik, Iceland..
    Enneman, Anke W.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1007 MB Amsterdam, Netherlands..
    de Groot, Lisette C. P. G. M.
    Wageningen Univ, Dept Human Nutr, NL-6700 EV Wageningen, Netherlands..
    van der Velde, Nathalie
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Acad Med Ctr, Sect Geriatr, Dept Internal Med, NL-1105 Amsterdam, Netherlands..
    Melin, Beatrice
    Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Kemp, John P.
    Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Christiansen, Claus
    Nord Biosci, DK-2730 Herlev, Denmark..
    Sayers, Adrian
    Univ Bristol, Musculoskeletal Res Unit, Bristol BS10 5NB, Avon, England..
    Zhou, Yanhua
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Calderari, Sophie
    INSERM, UMRS 1138, Cordeliers Res Ctr, F-75006 Paris, France.;Univ Paris 06, Inst Cardiometab & Nutr, F-75013 Paris, France..
    van Rooij, Jeroen
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands..
    Carlson, Chris
    Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA..
    Peters, Ulrike
    Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA..
    Berlivet, Soizik
    McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.;McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada..
    Dostie, Josee
    McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.;McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands..
    Williams, Stephen R.
    Univ Virginia, Ctr Publ Hlth Genom, Dept Med, Charlottesville, VA 22908 USA.;Univ Virginia, Ctr Publ Hlth Genom, Dept Cardiovasc Med, Charlottesville, VA 22908 USA..
    Farber, Charles
    Univ Virginia, Ctr Publ Hlth Genom, Dept Med, Charlottesville, VA 22908 USA.;Univ Virginia, Ctr Publ Hlth Genom, Dept Cardiovasc Med, Charlottesville, VA 22908 USA..
    Grinberg, Daniel
    Univ Barcelona, Dept Genet, E-08028 Barcelona, Spain.;Ctr Biomed Network Res Rare Dis CIBERER, U720, Barcelona 28029, Spain.;Univ Barcelona, Inst Biomed, Dept Human Mol Genet, E-08028 Barcelona, Spain..
    LaCroix, Andrea Z.
    Univ Calif San Diego, Womens Hlth Ctr Excellence Family Med & Publ Hlth, San Diego, CA 92103 USA..
    Haessler, Jeff
    Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA..
    Chasman, Daniel I.
    Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA..
    Giulianini, Franco
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA..
    Ridker, Paul M.
    Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA..
    Eisman, John A.
    Garvan Inst Med Res, Osteoporosis & Bone Biol Program, Sydney, NSW 2010, Australia.;Univ Notre Dame Australia, Sch Med Sydney, Sydney, NSW 6959, Australia.;NSW Univ, St Vincents Hosp, Sydney, NSW 2010, Australia.;NSW Univ, Sch Clin, Sydney, NSW 2010, Australia..
    Nguyen, Tuan V.
    Garvan Inst Med Res, Osteoporosis & Bone Biol Program, Sydney, NSW 2010, Australia.;NSW Univ, St Vincents Hosp, Sydney, NSW 2010, Australia.;NSW Univ, Sch Clin, Sydney, NSW 2010, Australia..
    Center, Jacqueline R.
    Garvan Inst Med Res, Osteoporosis & Bone Biol Program, Sydney, NSW 2010, Australia.;NSW Univ, St Vincents Hosp, Sydney, NSW 2010, Australia.;NSW Univ, Sch Clin, Sydney, NSW 2010, Australia..
    Nogues, Xavier
    Univ Virginia, Ctr Publ Hlth Genom, Dept Med, Charlottesville, VA 22908 USA.;Univ Virginia, Ctr Publ Hlth Genom, Dept Cardiovasc Med, Charlottesville, VA 22908 USA.;Inst Hosp Mar Invest Med, Musculoskeletal Res Grp, Barcelona 08003, Spain.;Univ Autonoma Barcelona, Hosp Mar, Dept Internal Med, E-08193 Barcelona, Spain..
    Garcia-Giralt, Natalia
    Inst Hosp Mar Invest Med, Musculoskeletal Res Grp, Barcelona 08003, Spain.;Inst Hlth Carlos III, Cooperat Res Network Aging & Fragil RETICEF, Madrid 28029, Spain..
    Launer, Lenore L.
    NIA, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA..
    Gudnason, Vilmunder
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Mellstrom, Dan
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden..
    Vandenput, Liesbeth
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands..
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands..
    Karlsson, Magnus K.
    Skane Univ Hosp, Dept Orthopaed, S-20502 Malmo, Sweden..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Svensson, Olle
    Umea Univ, Dept Surg & Perioperat Sci, S-90185 Umea, Sweden..
    Hallmans, Goran
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden..
    Rousseau, Francois
    Univ Laval, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ G1V 0A6, Canada.;CHU Quebec, Ctr Rech, Axe Sante Populat & Prat Optimales Sante, Quebec City, PQ G1V 4G2, Canada..
    Giroux, Sylvie
    CHU Quebec, Ctr Rech, Axe Sante Populat & Prat Optimales Sante, Quebec City, PQ G1V 4G2, Canada..
    Bussiere, Johanne
    CHU Quebec, Ctr Rech, Axe Sante Populat & Prat Optimales Sante, Quebec City, PQ G1V 4G2, Canada..
    Arp, Pascal P.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Koromani, Fjorda
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Prince, Richard L.
    Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.;Univ Western Australia, Dept Med, Perth, WA 6009, Australia..
    Lewis, Joshua R.
    Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.;Univ Western Australia, Dept Med, Perth, WA 6009, Australia..
    Langdahl, Bente L.
    Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus C, Denmark..
    Hermann, A. Pernille
    Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense C, Denmark..
    Jensen, Jens-Erik B.
    Hvidovre Univ Hosp, Dept Endocrinol, DK-2650 Hvidovre, Denmark..
    Kaptoge, Stephen
    UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England..
    Khaw, Kay-Tee
    Univ Cambridge, Clin Gerontol Unit, Cambridge CB2 2QQ, England..
    Reeve, Jonathan
    Univ Cambridge, Med & Publ Hlth & Primary Care, Cambridge CB1 8RN, England.;Univ Oxford, Botnar Res Ctr, Inst Musculoskeletal Sci, Oxford OX3 7LD, England..
    Formosa, Melissa M.
    Univ Malta, Dept Appl Biomed Sci, Fac Hlth Sci, MSD-2080 Msida, Malta..
    Xuereb-Anastasi, Angela
    Univ Malta, Dept Appl Biomed Sci, Fac Hlth Sci, MSD-2080 Msida, Malta..
    Akesson, Kristina
    Skane Univ Hosp, Dept Orthopaed, S-20502 Malmo, Sweden.;Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden..
    McGuigan, Fiona E.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden..
    Garg, Gaurav
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden..
    Olmos, Jose M.
    Univ Cantabria, Dept Med & Psychiat, Santander 39011, Spain.;Hosp UM Valdecilla IDIVAL, Dept Internal Med, Santander 39008, Spain..
    Zarrabeitia, Maria T.
    Univ Cantabria, Dept Legal Med, Santander 39011, Spain..
    Riancho, Jose A.
    Univ Cantabria, Dept Med & Psychiat, Santander 39011, Spain.;Hosp UM Valdecilla IDIVAL, Dept Internal Med, Santander 39008, Spain..
    Ralston, Stuart H.
    Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Alonso, Nerea
    Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Jiang, Xi
    Univ Connecticut, Ctr Hlth, Coll Dent Med, Dept Reconstruct Sci, Farmington, CT 06030 USA..
    Goltzman, David
    McGill Univ, Dept Med & Physiol, Montreal, PQ H4A 3J1, Canada..
    Pastinen, Tomi
    McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada..
    Grundberg, Elin
    McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada..
    Gauguier, Dominique
    INSERM, UMRS 1138, Cordeliers Res Ctr, F-75006 Paris, France.;Univ Paris 06, Inst Cardiometab & Nutr, F-75013 Paris, France..
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Bone Mineral Unit, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA..
    Karasik, David
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Bar Ilan Univ, Fac Med Galilee, IL-13010 Safed, Israel..
    Davey-Smith, George
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Siggeirsdottir, Kristin
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Harris, Tamara B.
    NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA..
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    van Meurs, Joyce B. J.
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    Thorsteinsdottir, Unnur
    deCODE Genet, Dept Populat Genom, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Maurano, Matthew T.
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA..
    Timpson, Nicholas J.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Durbin, Richard
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Wilson, ScottG.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.;Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Med & Pharmacol, Crawley 6009, Australia..
    Ntzani, Evangelia E.
    Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.;Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02903 USA..
    Brown, Matthew A.
    Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia..
    Stefansson, Kari
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Hinds, David A.
    23andMe, Res Dept, Mountain View, CA 94041 USA..
    Spector, Tim
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Cupples, L. Adrienne
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA..
    Ohlsson, Claes
    Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden..
    Greenwood, Celia M. T.
    McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Gerald Bronfman Ctr, Dept Oncol, Montreal, PQ H2W 1S6, Canada..
    Jackson, Rebecca D.
    Ohio State Univ, Dept Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA..
    Rowe, David W.
    Univ Connecticut, Ctr Hlth, Coll Dent Med, Dept Reconstruct Sci, Farmington, CT 06030 USA..
    Loomis, Cynthia A.
    NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA.;NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA..
    Evans, David M.
    Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Ackert-Bicknell, Cheryl L.
    Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14642 USA..
    Joyner, Alexandra L.
    Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA..
    Duncan, Emma L.
    Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.;Royal Brisbane & Womens Hosp, Dept Diabet & Endocrinol, Brisbane, Qld 4029, Australia..
    Kiel, Douglas P.
    Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA.;Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA..
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands..
    Richards, J. Brent
    McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture2015Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, nr 7571, s. 112-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

  • 215. Zhu, M.
    et al.
    Ahlberg, Per E.
    Natural History Museum of London .
    Zhao, W.
    Jia , L.
    First Devonian tetrapod from Asia2002Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 420, s. 760-761Artikkel i tidsskrift (Fagfellevurdert)
  • 216. Zhu, M.
    et al.
    Yu, X.
    Ahlberg, Per E.
    Natural History Museum of London .
    A primitive sarcopterygian fish with an eyestalk.2001Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 410, s. 81-84Artikkel i tidsskrift (Fagfellevurdert)
  • 217. Zhu, Min
    et al.
    Ahlberg, Per E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Evolutionär organismbiologi.
    The origin of the internal nostril of tetrapods2004Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 432, nr 7013, s. 94-97Artikkel i tidsskrift (Fagfellevurdert)
  • 218. Zhu, Min
    et al.
    Yu, Xiaobo
    Ahlberg, Per Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Choo, Brian
    Lu, Jing
    Qiao, Tuo
    Qu, Qingming
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Zhao, Wenjin
    Jia, Liantao
    Blom, Henning
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Zhu, You'an
    A Silurian placoderm with osteichthyan-like marginal jaw bones2013Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 502, nr 7470, s. 188-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The gnathostome (jawed vertebrate) crown group comprises two extant clades with contrasting character complements. Notably, Chondrichthyes (cartilaginous fish) lack the large dermal bones that characterize Osteichthyes (bony fish and tetrapods). The polarities of these differences, and the morphology of the last common ancestor of crown gnathostomes, are the subject of continuing debate. Here we describe a three-dimensionally preserved 419-million-year-old placoderm fish from the Silurian of China that represents the first stem gnathostome with dermal marginal jaw bones (premaxilla, maxilla and dentary), features previously restricted to Osteichthyes. A phylogenetic analysis places the new form near the top of the gnathostome stem group but does not fully resolve its relationships to other placoderms. The analysis also assigns all acanthodians to the chondrichthyan stem group. These results suggest that the last common ancestor of Chondrichthyes and Osteichthyes had a macromeric dermal skeleton, and provide a new framework for studying crown gnathostome divergence.

  • 219.
    Zody, Michael
    et al.
    Broad Institute.
    Garber, Manuel
    Broad Institute.
    Adams, David
    The Wellcome Trust Sanger Institute.
    Sharpe, Ted
    Broad Institute.
    Harrow, Jennifer
    The Wellcome Trust Sanger Institute.
    Lupski, James
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Nicholson, Christine
    The Wellcome Trust Sanger Institute.
    Searle, Steven
    The Wellcome Trust Sanger Institute.
    Wilming, Laurens
    The Wellcome Trust Sanger Institute.
    Young, Sarah
    Broad Institute.
    Abouelleil, Amr
    Broad Institute.
    Allen, Nicole
    Broad Institute.
    Bi, Weimin
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Bloom, Toby
    Broad Institute.
    Borowsky, Mark
    Broad Institute.
    Bugalter, Boris
    Broad Institute.
    Butler, Jonathan
    Broad Institute.
    Chang, Jean
    Broad Institute.
    Chen, Chao-Kung
    The Wellcome Trust Sanger Institute.
    Cook, April
    Broad Institute.
    Corum, Benjamin
    Broad Institute.
    Cuomo, Christina
    Broad Institute.
    de Jong, Pieter
    Children's Hospital Oakland Research Institute.
    DeCaprio, David
    Broad Institute.
    Dewar, Ken
    Broad Institute.
    FitzGerald, Michael
    Broad Institute.
    Gilbert, James
    The Wellcome Trust Sanger Institute.
    Gibson, Richard
    The Wellcome Trust Sanger Institute.
    Gnerre, Sante
    Broad Institute.
    Goldstein, Steven
    University of Wisconsin-Madison, Laboratory for Molecular and Computational Genomics.
    Grafham, Darren
    The Wellcome Trust Sanger Institute.
    Grocock, Russell
    The Wellcome Trust Sanger Institute.
    Hafez, Nabil
    Broad Institute.
    Hagopian, Daniel
    Broad Institute.
    Hart, Elizabeth
    The Wellcome Trust Sanger Institute.
    Hosage Norman, Catherine
    Broad Institute.
    Humphray, Sean
    The Wellcome Trust Sanger Institute.
    Jaffe, David
    Broad Institute.
    Jones, Matt
    The Wellcome Trust Sanger Institute.
    Kamal, Michael
    Broad Institute.
    Khodiyan, Varsha
    University College London, Department of Biology.
    LaButti, Kurt
    Broad Institute.
    Laird, Gavin
    The Wellcome Trust Sanger Institute.
    Lehoczky, Jessica
    Broad Institute.
    Liu, Xiaohong
    Broad Institute.
    Lokyitsang, Tashi
    Broad Institute.
    Loveland, Jane
    The Wellcome Trust Sanger Institute.
    Lui, Annie
    Broad Institute.
    Macdonald, Pendexter
    Broad Institute.
    Major, John
    Broad Institute.
    Matthews, Lucy
    The Wellcome Trust Sanger Institute.
    Mauceli, Evan
    Broad Institute.
    McCarroll, Steven
    Broad Institute.
    Mihalev, Atanas
    Broad Institute.
    Mudge, Jonathan
    The Wellcome Trust Sanger Institute.
    Nguyen, Cindy
    Broad Institute.
    Nicol, Robert
    Broad Institute.
    O'Leary, Sinéad
    Broad Institute.
    Osoegawa, Kazutoyo
    Children's Hospital Oakland Research Institute.
    Schwartz, David
    University of Wisconsin-Madison, Laboratory for Molecular and Computational Genomics.
    Shaw-Smith, Charles
    The Wellcome Trust Sanger Institute.
    Stankiewicz, Pawel
    Baylor College of Medicine, Department of Molecular and Human Genetics.
    Steward, Charles
    The Wellcome Trust Sanger Institute.
    Swarbreck, David
    The Wellcome Trust Sanger Institute.
    Venkataraman, Vijay
    Broad Institute.
    Whittaker, Charles
    Broad Institute.
    Yang, Xiaoping
    Broad Institute.
    Zimmer, Andrew
    Broad Institute.
    Bradley, Allan
    The Wellcome Trust Sanger Institute.
    Hubbard, Tim
    The Wellcome Trust Sanger Institute.
    Birren, Bruce
    Broad Institute.
    Rogers, Jane
    The Wellcome Trust Sanger Institute.
    Lander, Eric
    Broad Institute.
    Nusbaum, Chad
    Broad Institute.
    DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage2006Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 440, nr 7087, s. 1045-1049Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.

  • 220.
    Zody, Michael
    et al.
    Broad Institute.
    Garber, Manuel
    Broad Institute.
    Sharpe, Ted
    Broad Institute.
    Young, Sarah
    Broad Institute.
    Rowen, Lee
    Institute for Systems Biology.
    O'Neill, Keith
    Broad Institute.
    Whittaker, Charles
    Broad Institute.
    Kamal, Michael
    Broad Institute.
    Chang, Jean
    Broad Institute.
    Cuomo, Christina
    Broad Institute.
    Dewar, Ken
    Broad Institute.
    FitzGerald, Michael
    Broad Institute.
    Kodira, Chinnappa
    Broad Institute.
    Madan, Anup
    Institute for Systems Biology.
    Qin, Shizhen
    Institute for Systems Biology.
    Yang, Xiaoping
    Broad Institute.
    Abbasi, Nissa
    Institute for Systems Biology.
    Abouelleil, Amr
    Broad Institute.
    Arachchi, Harindra
    Broad Institute.
    Baradarani, Lida
    Institute for Systems Biology.
    Birditt, Brian
    Institute for Systems Biology.
    Bloom, Scott
    Institute for Systems Biology.
    Bloom, Toby
    Broad Institute.
    Borowsky, Mark
    Broad Institute.
    Burke, Jeremy
    Institute for Systems Biology.
    Butler, Jonathan
    Broad Institute.
    Cook, April
    Broad Institute.
    DeArellano, Kurt
    Broad Institute.
    DeCaprio, David
    Broad Institute.
    Dorris, Lester
    Broad Institute.
    Dors, Monica
    Institute for Systems Biology.
    Eichler, Evan
    University of Washington, Department of Genome Sciences.
    Engels, Reinhard
    Broad Institute.
    Fahey, Jessica
    Institute for Systems Biology.
    Fleetwood, Peter
    Institute for Systems Biology.
    Friedman, Cynthia
    Fred Hutchinson Cancer Research Center, Division of Human Biology.
    Gearin, Gary
    Broad Institute.
    Hall, Jennifer
    Broad Institute.
    Hensley, Grace
    Institute for Systems Biology.
    Johnson, Ericka
    Institute for Systems Biology.
    Jones, Charlien
    Broad Institute.
    Kamat, Asha
    Broad Institute.
    Kaur, Amardeep
    Institute for Systems Biology.
    Locke, Devin
    University of Washington, Department of Genome Sciences.
    Madan, Anuradha
    Institute for Systems Biology.
    Munson, Glen
    Broad Institute.
    Jaffe, David
    Broad Institute.
    Lui, Annie
    Broad Institute.
    Macdonald, Pendexter
    Broad Institute.
    Mauceli, Evan
    Broad Institute.
    Naylor, Jerome
    Broad Institute.
    Nesbitt, Ryan
    Institute for Systems Biology.
    Nicol, Robert
    Broad Institute.
    O'Leary, Sinéad
    Broad Institute.
    Ratcliffe, Amber
    Institute for Systems Biology.
    Rounsley, Steven
    Broad Institute.
    She, Xinwei
    University of Washington, Department of Genome Sciences.
    Sneddon, Katherine
    University College London, Department of Biology.
    Stewart, Sandra
    Institute for Systems Biology.
    Sougnez, Carrie
    Broad Institute.
    Stone, Sabrina
    Broad Institute.
    Topham, Kerri
    Broad Institute.
    Vincent, Dascena
    Institute for Systems Biology.
    Wang, Shunguang
    Broad Institute.
    Zimmer, Andrew
    Broad Institute.
    Birren, Bruce
    Broad Institute.
    Hood, Leroy
    Institute for Systems Biology.
    Lander, ic
    Broad Institute.
    Nusbaum, Chad
    Broad Institute.
    Analysis of the DNA sequence and duplication history of human chromosome 152006Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 440, nr 7084, s. 671-675Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplication in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.

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