International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 48 - USING THE MOUSE TO IDENTIFY CANDIDATE MODIFIERS FOR HUMAN VON WILLEBRAND DISEASE (VWD)

Miss Heidi Rottschafer
The University of Michigan Medical Center
Dept of Human Genetics
MSRB I, Room 4520
1150 West Medical Center Drive
Ann Arbor, MI 48109-0650
USA

Co-Authors: 1) Levy G, 2) Ginsburg D.
Institutions: 1) The University of Michigan, 2) Howard Hughes Medical Institute at The University of Michigan

Deficiencies in von Willebrand factor (VWF) result in the common human bleeding disorder VWD.  A number of genetic factors contribute to the incomplete penetrance and variable expressivity of VWD.  We previously described a modifier gene for plasma VWF levels in the mouse (Mvwf) which causes a switch in the lineage-specific expression of a glycosyltransferase (Galgt2).  This switch leads to altered post-translational processing and accelerated clearance of VWF from plasma.  To identify additional modifier genes, we have now extended this approach to an analysis of 200 F2 progeny from an A/J X CASA/Rk cross.  Plasma VWF levels in CASA/Rk are approximately seven times higher than those of the A/J strain, and are independent of the Galgt2 modification.  A whole genome scan demonstrated that F2 plasma VWF level strongly correlated with parental genotype at the D6Mit12 and D9Mit67 markers.  D6Mit12 is located ~1.2 cM from the murine VWF gene, suggesting that strain-specific differences in VWF expression may be a primary mechanism for variation in plasma VWF level among mouse strains.  Fine mapping at the D9Mit67 locus may identify an additional novel gene contributing to overall plasma VWF level.  Continued analysis of the molecular basis for genetic variation in plasma VWF levels in mice may provide new insight into the biology of VWF biosynthesis, and identify candidates for important genetic modifiers of bleeding and thrombosis in humans.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012