New gene functions in megakaryopoiesis and platelet formation

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3151620 60 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
New gene functions in megakaryopoiesis and platelet formation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Έτος δημοσίευσης:
2011
Συγγραφείς:
Gieger, Christian
Radhakrishnan, Aparna
Cvejic, Ana
Tang,
Weihong
Porcu, Eleonora
Pistis, Giorgio
Serbanovic-Canic,
Jovana
Elling, Ulrich
Goodall, Alison H.
Labrune, Yann and
Lopez, Lorna M.
Maegi, Reedik
Meacham, Stuart
Okada,
Yukinori
Pirastu, Nicola
Sorice, Rossella
Teumer, Alexander
and Voss, Katrin
Zhang, Weihua
Ramirez-Solis, Ramiro
Bis,
Joshua C.
Ellinghaus, David
Goegele, Martin
Hottenga,
Jouke-Jan
Langenberg, Claudia
Kovacs, Peter
O'Reilly, Paul
F.
Shin, So-Youn
Esko, Toenu
Hartiala, Jaana
Kanoni,
Stavroula
Murgia, Federico
Parsa, Afshin
Stephens, Jonathan
and van der Harst, Pim
van der Schoot, C. Ellen
Allayee, Hooman
and Attwood, Antony
Balkau, Beverley
Bastardot, Francois and
Basu, Saonli
Baumeister, Sebastian E.
Biino, Ginevra
Bomba,
Lorenzo
Bonnefond, Amelie
Cambien, Francois
Chambers, John
C.
Cucca, Francesco
D'Adamo, Pio
Davies, Gail
de Boer,
Rudolf A.
de Geus, Eco J. C.
Doering, Angela
Elliott, Paul
and Erdmann, Jeanette
Evans, David M.
Falchi, Mario
Feng,
Wei
Folsom, Aaron R.
Frazer, Ian H.
Gibson, Quince D. and
Glazer, Nicole L.
Hammond, Chris
Hartikainen, Anna-Liisa and
Heckbert, Susan R.
Hengstenberg, Christian
Hersch, Micha and
Illig, Thomas
Loos, Ruth J. F.
Jolley, Jennifer
Khaw, Kay
Tee
Kuehnel, Brigitte
Kyrtsonis, Marie-Christine
Lagou,
Vasiliki
Lloyd-Jones, Heather
Lumley, Thomas
Mangino,
Massimo
Maschio, Andrea
Leach, Irene Mateo
McKnight, Barbara
and Memari, Yasin
Mitchell, Braxton D.
Montgomery, Grant W. and
Nakamura, Yusuke
Nauck, Matthias
Navis, Gerjan
Noethlings,
Ute
Nolte, Ilja M.
Porteous, David J.
Pouta, Anneli and
Pramstaller, Peter P.
Pullat, Janne
Ring, Susan M.
Rotter,
Jerome I.
Ruggiero, Daniela
Ruokonen, Aimo
Sala, Cinzia and
Samani, Nilesh J.
Sambrook, Jennifer
Schlessinger, David and
Schreiber, Stefan
Schunkert, Heribert
Scott, James
Smith,
Nicholas L.
Snieder, Harold
Starr, John M.
Stumvoll, Michael
and Takahashi, Atsushi
Tang, W. H. Wilson
Taylor, Kent and
Tenesa, Albert
Thein, Swee Lay
Toenjes, Anke
Uda, Manuela
and Ulivi, Sheila
van Veldhuisen, Dirk J.
Visscher, Peter M. and
Voelker, Uwe
Wichmann, H-Erich
Wiggins, Kerri L.
Willemsen,
Gonneke
Yang, Tsun-Po
Zhao, Jing Hua
Zitting, Paavo and
Bradley, John R.
Dedoussis, George V.
Gasparini, Paolo and
Hazen, Stanley L.
Metspalu, Andres
Pirastu, Mario
Shuldiner,
Alan R.
van Pelt, L. Joost
Zwaginga, Jaap-Jan
Boomsma,
Dorret I.
Deary, Ian J.
Franke, Andre
Froguel, Philippe and
Ganesh, Santhi K.
Jarvelin, Marjo-Riitta
Martin, Nicholas G. and
Meisinger, Christa
Psaty, Bruce M.
Spector, Timothy D. and
Wareham, Nicholas J.
Akkerman, Jan-Willem N.
Ciullo, Marina and
Deloukas, Panos
Greinacher, Andreas
Jupe, Steve
Kamatani,
Naoyuki
Khadake, Jyoti
Kooner, Jaspal S.
Penninger, Josef
and Prokopenko, Inga
Stemple, Derek
Toniolo, Daniela and
Wernisch, Lorenz
Sanna, Serena
Hicks, Andrew A.
Rendon,
Augusto
Ferreira, Manuel A.
Ouwehand, Willem H.
Soranzo,
Nicole
Περιοδικό:
Nature Metabolism
Εκδότης:
Nature Publishing Group
Τόμος:
480
Αριθμός / τεύχος:
7376
Σελίδες:
201-208
Επίσημο URL (Εκδότης):
DOI:
10.1038/nature10659
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