Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  7
• Reference
  J:203040 Miller AR, et al., Mapping genetic modifiers of survival in a mouse model of Dravet syndrome. Genes Brain Behav. 2014 Feb;13(2):163-72
• ID
  MGI:5697813

Genes

Gene	Assay Type
Dsm2	visible phenotype

Notes

• Experiment
  Linkage analysis was performed on 293 (129S6/SvEvTac-Scn1a^tm1Kea x C57BL/6J)F1 x 129S6/SvEvTac-Scn1a^tm1Kea backcross mice to identify QTL associated with premature lethality in a Dravet syndrome model (Scn1a^+/- mice). Phenotype severity in Scn1a^+/- mice is strongly dependent on strain background; Scn1a^+/- mice exhibit no overt phenotype on the 129S6/SvEvTac background but exhibit spontaneous seizures and early lethality when bred onto a (C57BL/6J x 129S6/SvEvTac)F1 background.
  
  Analysis of the backcross using a two-part model, which allows for separate effects on penetrance (live/die) and severity (age at time of early death), found significant or suggestive evidence for linkage on chromosomes 5 (Dsm1), 7 (Dsm2), and 8 (Dsm3). In this analysis, penetrance indicates whether a mouse died during the 12-week observation period, while severity is represented by age at the time of early death. The locus on chromosome 5 affects penetrance of the lethal phenotype, whereas loci on chr 7 and 8 primarily affect the age at time of death. There is no evidence for interacting loci from a two-dimensional genome scan with a two-QTL model.
  
  QTL Dsm1 maps to Chromosome 5 (27.3 - 41.3 cM) with peak LOD scores at 34 cM in linkage with the lethality model as follows:
  Premature lethality: peak LOD score of 3.02 (suggestive)
  Lethality penetrance: peak LOD score of 3.01 (significant)
  Lethality severity: peak LOD score of 0.001 (not significant)
  The C57BL/6J allele confers increased risk of early death at the Dsm1 locus.
  
  QTL Dsm2 maps to Chromosome 7 (7.5 - 39.5 cM) with peak LOD scores at 27.5 cM in linkage with the lethality model as follows:
  Premature lethality: peak LOD score of 4.08 (significant)
  Lethality penetrance: peak LOD score of 0.78 (not significant)
  Lethality severity: peak LOD score of 3.34 (significant)
  The 129S6/SvEvTac allele confers increased risk of early death at the Dsm2 locus.
  
  QTL Dsm3 maps to Chromosome 8 (28.4 - 64.4 cM) with peak LOD scores at 41.6 cM in linkage with the lethality model as follows:
  Premature lethality: peak LOD score of 3.35 (suggestive)
  Lethality penetrance: peak LOD score of 0.38 (not significant)
  Lethality severity: peak LOD score of 2.96 (suggestive)
  The C57BL/6J allele confers increased risk of early death at the Dsm3 locus.