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New gene functions in megakaryopoiesis and platelet formation

机译：新基因在巨核细胞生成和血小板形成中的功能

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摘要

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.
机译：血小板是血液中第二丰富的细胞类型，对于维持止血至关重要。它们的数量和体积被严格控制在狭窄的生理范围内，但是对控制这两种性状的分子过程的了解有限。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）的高效荟萃分析，然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定位可靠相关的基因组位点，以建立和假定的新型巨核细胞生成和血小板形成调节剂。这些基因显示出巨核细胞特异性基因表达模式和广泛的网络连通性。使用丹尼奥里奥和果蝇果蝇中的基因沉默，我们确定了11个基因作为血细胞形成的新型调节剂。综上所述，我们的发现提高了对控制巨核细胞生成和血小板形成过程中决定命运的事件的新基因功能的理解，为GWAS成功翻译提供了新的例子。

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  • 来源
    《Nature》 |2011年第7376期|p.201-208|共8页
  • 作者

    Christian Gieger; Aparna Radhakrishnan; Ana Cvejic; Weihong Tang; Eleonora Porcu; et al;

  • 作者单位

    Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstadter Landstr.l, 85764 Neuherberg, Germany;

    Department of Haematology, University of Cambridge & NHS Blood and Transplant, Cambridge CB2 OPT, UK Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH/1SA, UK;

    rnDepartment of Haematology, University of Cambridge & NHS Blood and Transplant, Cambridge CB2 OPT, UK Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH/1SA, UK;

    rnDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota 55455-0354, USA;

    rnlstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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