New gene functions in megakaryopoiesis and platelet formation.

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

Nature 2011 Nov 30;480(7376):201-8. Epub 2011 Nov 30.

Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr 1, 85764 Neuherberg, Germany.

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.

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http://dx.doi.org/10.1038/nature10659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335296PMC
November 2011
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