Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  5
• Reference
  J:203042 Hoover-Plow J, et al., Genetic dissection of quantitative trait Loci for hemostasis and thrombosis on mouse chromosomes 11 and 5 using congenic and subcongenic strains. PLoS One. 2013;8(10):e77539
• ID
  MGI:5792168

Genes

Gene	Assay Type
Hmtb4	visible phenotype
Hmtb5	visible phenotype
D5Mit320	PCR amplified length variant
D5Mit338	PCR amplified length variant
D5Mit394	PCR amplified length variant
D5Mit197	PCR amplified length variant
Hmtb10	visible phenotype
Hmtb11	visible phenotype

Notes

• Experiment
  QTL for hemostasis and thrombosis, Hmtb4, Hmtb5 and Hmtb6, were previoulsy identified using F2 progeny from a cross of (C57BL/6J-Chr 11^A/J/NaJ [CSS11] x C57BL/6J) mice and a cross of (C57BL/6J-Chr 5^A/J/NaJ [CSS5] x C57BL/6J) mice in J:139651 [pmid:18787898].
  
  The goal of this study was to fine map the previoulsy identified QTL using congenic and subcongenic mouse strains.
  
  Congenic and subcongenic strains were constructed from a cross of C57BL/6J-Chr 5^A/J/NaJ x C57BL/6J mice to verify the overlapping QTL on Chr 5, Hmtb4 and Hmtb5 for clot stability and bleeding.
  
  Congenic strain 3A-2, B6.A(rs6297441-D5Mit320)/NaJ and subcongenic strain 2A-1, B6.A(D5Mit338-D5Mit320)/NaJ were constructed for the distal region of Chr 5 containing the Hmtb4 and Hmtb5 QTL peak markers.
  In the proximal region of Chr 5, subcongenic strains 4A-1, B6.A(D5Mit394-D5Mit338)/NaJ, 4A-2, B6.A(rs16809655-D5Mit197)/NaJ, and 3A-1, B6.A(rs16809655-D5Mit394)/NaJ were constructed from the congenic strain 6A-1, B6.A(rs16809655-D5Mit338)/NaJ of Chr 5. [Fig 2.]
  
  Bleeding time in the CSS5 mice was significantly shorter than for B6 mice. The bleeding time of the subcongenic 2A-1 strain was the same as the time for the B6 mice. The bleeding time for the 3A-2 strain was shorter, the same as for the CSS5 mice. The A/J fragment of the 3A-2 strain was slightly longer than the 2A-1. Text suggests that this narrow region may be the site for the CSS5 short bleeding time phenotype and the Hmtb5 locus previously identified. For the Hmtb5 locus, the minimum A/J interval on the 3A-2 strain, 100.2-108.6 Mbp, that did not overlap with 2A-1 there were 78 protein coding genes (Table S4), and functional analysis revealed 11 relevant genes (Table 2).
  
  In the proximal region of Chr 5 the 3A-1 mice, carrying the A/J interval from the proximal end to the marker D5Mit394 had a bleeding time that was 2-fold longer than A/J or B6 mice, p<0.01. This locus, mapped in the B6.A(rs16809655-D5Mit394)/NaJ fragment between 5-29.8 Mbp was named Hmbt10. There were 266 protein coding genes [Table S5] in the interval, and annotation analysis identified 15 relevent genes [Table 2].
  
  The subcongenic strain 2A-1 (B6.A(D5Mit338-D5Mit320)/NaJ) had significantly prolonged clot stability time comparable to the CSS5 parental strain suggesting confirmation of the Hmbt4 locus on Chr5. In the subcongenic region of the A/J fragment, between 108.6 and 126.8 Mbp, there were 272 protein coding genes [Table S6]. Functional annotation analysis identified 18 relevant genes [Table 2].
  
  To further characterize the phenotype of the Hmbt4, Hmbt5, and Hmbt10 loci, carotid occulsion time after FeCl3 injury and aortic aneurysm formation after CaCl2 injury were assessed in the congeneic strains. The 4A-2 (B6.A(rs16809655-D5Mit197)/NaJ) had a prolonged occulsion time that was 4-fold longer than B6 mice, p<0.01, and similar to the CSS5 strain. This strain also had the lowest response to the CaCl2 injury. The results of these two models revealed another locus related to thrombosis modification, Hmbt11.
  Compared with 3A-1 (B6.A(rs16809655-D5Mit394)/NaJ) the 4A-2 congenic had only a 10 Mbp difference; within that region there were 10 additional protein coding genes and they did not associate with the annotation criteria [Table S7].