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Blood, 12 February 2009, Vol. 113, No. 7, pp. 1543-1546. Prepublished online as a Blood First Edition Paper on November 6, 2008; DOI 10.1182/blood-2008-08-175216. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figure All Versions of this Article: blood-2008-08-175216v1 113/7/1543    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Diamandis, M. Articles by Hayward, C. P. M. Search for Related Content PubMed PubMed Citation Articles by Diamandis, M. Articles by Hayward, C. P. M. Related Collections Platelets and Thrombopoiesis Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes Maria Diamandis1, Andrew D. Paterson2,3, Johanna M. Rommens2,4, D. Kika Veljkovic1, Jessica Blavignac1, Dennis E. Bulman5, John S. Waye1, Francine Derome6, Georges E. Rivard6, and Catherine P. M. Hayward1,7 1 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON; 2 Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON; 3 Dalla Lana School of Public Health and Institute of Medical Sciences, University of Toronto, ON; 4 Department of Molecular Genetics, University of Toronto, ON; 5 Department of Regenerative Medicine, Ottawa Health Research Institute, Ottawa, ON; 6 Department of Hematology/Oncology, Centre Hôspitalier Universitaire Sainte Justine, Montreal, QC; and 7 Department of Medicine, McMaster University, Hamilton, ON Quebec platelet disorder (QPD) is an autosomal dominant disorder with high penetrance that is associated with increased risks for bleeding. The hallmark of QPD is a gain-of-function defect in fibrinolysis due to increased platelet content of urokinase plasminogen activator (uPA) without systemic fibrinolysis. We hypothesized that increased expression of uPA by differentiating QPD megakaryocytes is linked to PLAU. Genetic marker analyses indicated that QPD was significantly linked to a 2-Mb region on chromosome 10q containing PLAU with a maximum multipoint logarithm of the odds (LOD) score of +11 between markers D10S1432 and D10S1136. Analysis of PLAU by sequencing and Southern blotting excluded mutations within PLAU and its known regulatory elements as the cause of QPD. Analyses of uPA mRNA indicated that QPD distinctly increased transcript levels of the linked PLAU allele with megakaryocyte differentiation. These findings implicate a mutation in an uncharacterized cis element near PLAU as the cause of QPD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. K. Veljkovic, G. E. Rivard, M. Diamandis, J. Blavignac, E. M. Cramer-Borde, and C. P. M. Hayward Increased expression of urokinase plasminogen activator in Quebec platelet disorder is linked to megakaryocyte differentiation Blood, February 12, 2009; 113(7): 1535 - 1542. [Abstract] [Full Text] [PDF]

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