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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 26, 2008 Accepted October 30, 2008 Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes Maria Diamandis, Andrew D Paterson, Johanna M Rommens, D Kika Veljkovic, Jessica Blavignac, Dennis E Bulman, John S Waye, Francine Derome, Georges E Rivard, and Catherine P.M. Hayward* Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada Molecular Genetics, University of Toronto, Toronto, ON, Canada Regenerative Medicine, Ottawa Health Research Institute, Ottawa, ON, Canada Hematology/Oncology, Centre Hospitalier Universitaire Sainte Justine, Montreal, QC, Canada * Corresponding author; email: haywrdc{at}mcmaster.ca. 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 Megabase region on chromosome 10q containing PLAU with a maximum multi-point LOD score= 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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