Summary |
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Variant origin |
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Variant description |
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Notes |
Mapping and Phenotype information for this QTL, its variants and associated markersJ:203040Linkage analysis was performed on 293 (129S6/SvEvTac-Scn1atm1Kea x C57BL/6J)F1 x 129S6/SvEvTac-Scn1atm1Kea 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. |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 08/02/2024 MGI 6.24 |
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