Mammalian Genome

, 19:406

Quantitative trait locus analysis for hemostasis and thrombosis

  • Qila Sa
  • Erika Hart
  • Annie E. Hill
  • Joseph H. Nadeau
  • Jane L. Hoover-Plow
Article

DOI: 10.1007/s00335-008-9122-0

Cite this article as:
Sa, Q., Hart, E., Hill, A.E. et al. Mamm Genome (2008) 19: 406. doi:10.1007/s00335-008-9122-0

Abstract

Susceptibility to thrombosis varies in human populations as well as many in inbred mouse strains. The objective of this study was to characterize the genetic control of thrombotic risk on three chromosomes. Previously, utilizing a tail-bleeding/rebleeding assay as a surrogate of hemostasis and thrombosis function, three mouse chromosome substitution strains (CSS) (B6-Chr5A/J, Chr11A/J, Chr17A/J) were identified (Hmtb1, Hmtb2, Hmtb3). The tail-bleeding/rebleeding assay is widely used and distinguishes mice with genetic defects in blood clot formation or dissolution. In the present study, quantitative trait locus (QTL) analysis revealed a significant locus for rebleeding (clot stability) time (time between cessation of initial bleeding and start of the second bleeding) on chromosome 5, suggestive loci for bleeding time (time between start of bleeding and cessation of bleeding) also on chromosomes 5, and two suggestive loci for clot stability on chromosome 17 and one on chromosome 11. The three CSS and the parent A/J had elevated clot stability time. There was no interaction of genes on chromosome 11 with genes on chromosome 5 or chromosome 17. On chromosome 17, twenty-three candidate genes were identified in synteny with previously identified loci for thrombotic risk on human chromosome 18. Thus, we have identified new QTLs and candidate genes not previously known to influence thrombotic risk.

Supplementary material

335_2008_9122_MOESM1_ESM.tif (5.5 mb)
Bleeding and rebleeding time in the CSS backcrosses. Panel A: Bleeding Time (seconds) and Panel B: Rebleeding Time (seconds) were tested in heterosomic mice, (B6xCSS-5)F1 (5F1) and (B6xCSS-17)F1 (17F1) and doubly heterosomic mice for chromosomes 5 and 17 (5x17). Bars are the mean ± SEM of 5–28 mice. Statistical differences between B6 mice and the CSS were determined with a t-test, and a Bonferroni correction was made to determine significance value (P < 0.01). Symbols indicate a significant difference between B6 values. *P < 0.01. (Figure 5 from Hoover- Plow, J., Shchurin, A., Hart, E., Sha, J., Hill, A.E., Singer, J.B., Nadeau, J.H. Genetic background determines response to haemostasis and thrombosis. BMC Blood Disord. 6:6, 2006.) (tif 5.54 Mb)

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Qila Sa
    • 1
    • 2
  • Erika Hart
    • 1
    • 2
  • Annie E. Hill
    • 3
  • Joseph H. Nadeau
    • 3
  • Jane L. Hoover-Plow
    • 1
    • 2
    • 4
  1. 1.Department of Molecular CardiologyJoseph J. Jacobs Center for Thrombosis and Vascular BiologyClevelandUSA
  2. 2.Department of Cardiovascular MedicineCleveland Clinic Lerner Research InstituteClevelandUSA
  3. 3.Department of GeneticsCase Western Reserve University School of MedicineClevelandUSA
  4. 4.Department of Molecular Cardiology, NB50Cleveland Clinic Lerner Research InstituteClevelandUSA

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