Dsm2^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Dsm2^C57BL/6J
• Name: Dravet survival modifier 2; C57BL/6J
• MGI ID: MGI:5697819
• QTL: Dsm2 Location: unknown Genetic Position: Chr7, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

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

J:203040

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.

References

• Original: 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
• All: 1 reference(s)