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    New gene functions in megakaryopoiesis and platelet formation


    Gieger, Christian, Radhakrishnan, Aparna, Cvejic, Ana, Tang, Weihong, Porcu, Eleonora, Pistis, Giorgio, Serbanovic-Canic, Jovana, Elling, Ulrich, Goodall, Alison H., Labrune, Yann, Lopez, Lorna M., Mägi, Reedik, Meacham, Stuart, Okada, Yukinori, Pirastu, Nicola, Sorice, Rossella, Teumer, Alexander, Voss, Katrin, Zhang, Weihua, Ramirez-Solis, Ramiro, Bis, Joshua C., Ellinghaus, David, Gögele, Martin, Hottenga, Jouke-Jan, Langenberg, Claudia, Kovacs, Peter, O’Reilly, Paul F., Shin, So-Youn, Esko, Tõnu, Hartiala, Jaana, Kanoni, Stavroula, Murgia, Federico, Parsa, Afshin, Stephens, Jonathan, van der Harst, Pim, Ellen van der Schoot, C., Allayee, Hooman, Attwood, Antony, Balkau, Beverley, Bastardot, François, Basu, Saonli, Baumeister, Sebastian E., Biino, Ginevra, Bomba, Lorenzo, Bonnefond, Amélie, Cambien, François, Chambers, John C., Cucca, Francesco, D’Adamo, Pio, Davies, Gail, de Boer, Rudolf A., de Geus, Eco J. C., Döring, Angela, Elliott, Paul, Erdmann, Jeanette, Evans, David M., Falchi, Mario, Feng, Wei, Folsom, Aaron R., Frazer, Ian H., Gibson, Quince D., Glazer, Nicole L., Hammond, Chris, Hartikainen, Anna-Liisa, Heckbert, Susan R., Hengstenberg, Christian, Hersch, Micha, Illig, Thomas, Loos, Ruth J. F., Jolley, Jennifer, Khaw, Kay-Tee, Kühnel, Brigitte, Kyrtsonis, Marie-Christine, Lagou, Vasiliki, Lloyd-Jones, Heather, Lumley, Thomas, Mangino, Massimo, Maschio, Andrea, Mateo Leach, Irene, McKnight, Barbara, Memari, Yasin, Mitchell, Braxton D., Montgomery, Grant W., Nakamura, Yusuke, Nauck, Matthias, Navis, Gerjan, Nöthlings, Ute, Nolte, Ilja M., Porteous, David J., Pouta, Anneli, Pramstaller, Peter P., Pullat, Janne, Ring, Susan M., Rotter, Jerome I., Ruggiero, Daniela, Ruokonen, Aimo, Sala, Cinzia, Samani, Nilesh J., Sambrook, Jennifer, Schlessinger, David, Schreiber, Stefan, Schunkert, Heribert, Scott, James, Smith, Nicholas L., Snieder, Harold, Starr, John M., Stumvoll, Michael, Takahashi, Atsushi, Wilson Tang, W. H., Taylor, Kent, Tenesa, Albert, Lay Thein, Swee, Tönjes, Anke, Uda, Manuela, Ulivi, Sheila, van Veldhuisen, Dirk J., Visscher, Peter M., Völker, Uwe, Wichmann, H.-Erich, Wiggins, Kerri L., Willemsen, Gonneke, Yang, Tsun-Po, Hua Zhao, Jing, Zitting, Paavo, Bradley, John R., Dedoussis, George V., Gasparini, Paolo, Hazen, Stanley L., Metspalu, Andres, Pirastu, Mario, Shuldiner, Alan R., Joost van Pelt, L., Zwaginga, Jaap-Jan, Boomsma, Dorret I., Deary, Ian J., Franke, Andre, Froguel, Philippe, Ganesh, Santhi K., Jarvelin, Marjo-Riitta, Martin, Nicholas G., Meisinger, Christa, Psaty, Bruce M., Spector, Timothy D., Wareham, Nicholas J., Akkerman, Jan-Willem N., Ciullo, Marina, Deloukas, Panos, Greinacher, Andreas, Jupe, Steve, Kamatani, Naoyuki, Khadake, Jyoti, Kooner, Jaspal S., Penninger, Josef, Prokopenko, Inga, Stemple, Derek, Toniolo, Daniela, Wernisch, Lorenz, Sanna, Serena, Hicks, Andrew A., Rendon, Augusto, Ferreira, Manuel A., Ouwehand, Willem H. and Soranzo, Nicole (2011) New gene functions in megakaryopoiesis and platelet formation. Nature, 480 (7376). pp. 201-208. ISSN 0028-0836

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    Abstract

    Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.
    Item Type: Article
    Keywords: New gene; functions; megakaryopoiesis; platelet formation;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17401
    Identification Number: 10.1038/nature10659
    Depositing User: Lorna Lopez
    Date Deposited: 10 Jul 2023 16:12
    Journal or Publication Title: Nature
    Publisher: Nature Research
    Refereed: Yes
    Related URLs:
    URI: https://mural.maynoothuniversity.ie/id/eprint/17401
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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