Mvwf3^CASA/RkJ
QTL Variant Detail

Summary

• QTL variant: Mvwf3^CASA/RkJ
• Name: modifier of von Willebrand factor 3; CASA/RkJ
• MGI ID: MGI:3796078
• QTL: Mvwf3 Location: Chr4:14010457-117072206 bp Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: CASA/RkJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased plasma von Willebrand factor levels compared to A/J in conjunction with CASA/RkJ-derived alleles at Mvwf2. (J:135941)

Notes

Mvwf3 interacts epsistatically with Mvwf2. Homozygosity for CASA/RkJ alleles at both Mvwf3 and Mvwf2 increases plasma von Willebrand factor levels.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:135941

Linkage analysis was performed on 198 animals from a (A/J x CASA/RkJ)F2 intercross to identify genetic loci influencing plasma Von Willebrand factor levels. Parental strains A/J and CASA/RkJ plasma von Willebrand factor levels differ by >8-fold. Genome scan was performed using 174 polymorphic markers at a resolution of 8.7 cM.

The Vwf locus at approximately 60 cM shows strong linkage to von Willebrand factor levels with LOD=11.12 at D6Mit12. This locus, named Mvwf2 (modifier of von Willebrand factor 2), accounts for 18% of the phenotypic variance and was detected in a previous study. The QTL interval spans 14 cM between D6Mit63 (49.7 cM) and D6Mit14 (71.2 cM). Controlling for Mvwf2 led to the identification two additional loci named Mvwf3 and Mvwf4. These loci appear to interact epistatically with homozygous CASA/RkJ alleles at Mvwf2. Together, Mvwf2, Mvwf3 and Mvwf4 account for 29% of the phenotypic variance.

Mvwf3 maps to 35.6 cM on mouse Chromosome 4 with LOD=4.45 at D4Mit132. The QTL interval spans approximately 48 cM from D4Mit18 (5.2 cM) to D4Mit37 (56 cM). Homozygosity for CASA/RkJ-derived alleles at Mvwf2 and Mvwf3 confer increased levels of plasma von Willebrand factor. A syntenic human locus (1p36.13) associated with variation in von Willebrand factor levels maps distal to Mvwf3. The human locus was identified by the Genetic Analysis of Idiopathic Thrombophilia (GAIT) study.

Mvwf4 maps to 68 cM on mouse Chromosome 13 with LOD=4.23 at D13Mit196. This locus spans approximately 25 cM between D13mit16 (10 cM) and D13Mit314 (45 cM). Homozygosity for CASA/RkJ-derived alleles at Mvwf2 and Mvwf4 confer increased levels of plasma von Willebrand factor. Mvwf4 may have a small effect independent of Mvwf2 and possibly represents 2 distinct QTLs on chromosome 13. The Mvwf4 interval is syntenic to two human loci (6p22.3 and 5q31.1) associated with variation in von Willebrand factor levels that were identified by the GAIT study.

Initially, a locus on mouse Chromosome X near DXMit19 (43.2 cM) displayed significant linkage to plasma von Willebrand factor levels. This locus disappeared when the effect of Mvwf2 was taken into account. However, authors do not rule out the possibility of an X-linked modifier of plasma von Willebrand factor concentrations.

References

• Original: J:135941 Lemmerhirt HL, et al., Genetic regulation of plasma von Willebrand factor levels: quantitative trait loci analysis in a mouse model. J Thromb Haemost. 2007 Feb;5(2):329-35
• All: 1 reference(s)