New gene functions in megakaryopoiesis and platelet formation.
New gene functions in megakaryopoiesis and platelet formation.
复制标题
DOI：
10.1038/nature10659
复制
发表时间：
2011-11-30
期刊：
影响因子：
64.8
通讯作者：
Soranzo, Nicole
中科院分区：
文献类型：
--
作者：
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.;Maegi, Reedik;Meacham, Stuart;Okada, Yukinori;Pirastu, Nicola;Sorice, Rossella;Teumer, Alexander;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;van der Harst, Pim;van der Schoot, C. Ellen;Allayee, Hooman;Attwood, Antony;Balkau, Beverley;Bastardot, Francois;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;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;Kuehnel, Brigitte;Kyrtsonis, Marie-Christine;Lagou, Vasiliki;Lloyd-Jones, Heather;Lumley, Thomas;Mangino, Massimo;Maschio, Andrea;Leach, Irene Mateo;McKnight, Barbara;Memari, Yasin;Mitchell, Braxton D.;Montgomery, Grant W.;Nakamura, Yusuke;Nauck, Matthias;Navis, Gerjan;Noethlings, 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;Tang, W. H. Wilson;Taylor, Kent;Tenesa, Albert;Thein, Swee Lay;Toenjes, Anke;Uda, Manuela;Ulivi, Sheila;van Veldhuisen, Dirk J.;Visscher, Peter M.;Voelker, Uwe;Wichmann, H-Erich;Wiggins, Kerri L.;Willemsen, Gonneke;Yang, Tsun-Po;Zhao, Jing Hua;Zitting, Paavo;Bradley, John R.;Dedoussis, George V.;Gasparini, Paolo;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;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.;Soranzo, Nicole
血小板是血液中第二丰富的细胞类型，对维持止血至关重要。它们的数量和体积被严格控制在狭窄的生理范围内，但对控制这两种性状的分子过程的理解有限。在这里，我们对多达66，867名欧洲血统的个体进行了全基因组关联研究（GWAS）的高性能荟萃分析，随后进行了广泛的生物学和功能评估。我们确定了68个与血小板计数和体积映射可靠相关的基因组位点，以确定和推定的巨核细胞生成和血小板形成的新调节因子。这些基因显示出巨核细胞特异性的基因表达模式和广泛的网络连接性。利用斑马鱼和果蝇的基因沉默，我们确定了11个基因作为血细胞形成的新调节因子。总之，我们的研究结果推进了对巨核细胞生成和血小板形成过程中控制命运决定事件的新基因功能的理解，为GWAS成功翻译功能提供了一个新的例子。
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.
登录
查看更多内容
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
5.3
作者：
Lo KS;Wilson JG;Lange LA;Folsom AR;Galarneau G;Ganesh SK;Grant SF;Keating BJ;McCarroll SA;Mohler ER 3rd;O'Donnell CJ;Palmas W;Tang W;Tracy RP;Reiner AP;Lettre G
通讯作者：
Lettre G
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
9.8
作者：
Meisinger, Christa;Prokisch, Holger;Doering, Angela
通讯作者：
Doering, Angela
影响因子：
11.8
作者：
Lu, Jun;Guo, Shangqin;Golub, Todd R.
通讯作者：
Golub, Todd R.