Hrtfm8^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Hrtfm8^DBA/2J
• Name: heart failure modifier 8; DBA/2J
• MGI ID: MGI:5636755
• QTL: Hrtfm8 Location: Chr3:148451045-152592311 bp Genetic Position: Chr3, Syntenic

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased survival and increased heart function compared to AKR/J. (J:100634)

Notes

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

J:100634

Linkage analysis was performed on 220 (DBA/2J-Tg(Myhca-Casq2)1Mord x AKR/J)F1 x DBA/2J backcross animals to identify QTL associated with heart function and survival. Transgenic parental strain DBA/2J-Tg(Myhca-Casq2)1Mord displays dilated cardiomyopathy and premature death (mean survival = 157 days). F1 hybrids display increased survival time (mean survival = 231 days), indicating the AKR/J genetic background contributes protective factors. 115 polymorphic markers at an average spacing of 15 cM were used for the genome scan.

Significant linkage to survival mapped to 84 cM on mouse Chromosome 3 near D3Mit220 (LOD=9.5). This locus also shows linkage to left ventricular end diastolic diameter (LVEDD), a measurement of heart function, with LOD=5.2, and is thought to be identical to a previously identified QTL named Hrtfm2 (heart failure modifier 2).

04.07.2015 Curators Note: Because Hrtfm2 was originally mapped in 2002 in J:76105 using 70 (C57BL/6J x DBA/2J-Tg(Myhca-Casq2)1Mord)F1 x C57BL/6J backcross animals, which differ from the cross used here, we consider a separate mapping experiment and have named this QTL Hrtfm8.

Fine map analysis localized Hrtfm8 to an interval between D3Mit147 (79.4 cM) and D3Mit322 (83.5 cM). Hrtfm8 accounts for 30% of the genetic variability for survival and 22.2% of the variability for LVEDD. DBA/2J-derived alleles at Hrtfm8 confer increased survival and decreased LVEDD (increased heart function) with recessive inheritance. Haplotype analysis identified potential candidate genes within the 2-LOD support interval- Pla2g2a (68 cM), Cryz, Lhx8, and Tnni3k. Potential candidate genes mapping 2 Mb distal of the 2-LOD support interval include Clca1 (72.5 cM), Hs2st1, Sep15, and Sh3glb1.

Significant linkage to LVEDD mapped to 8.7 cM on mouse Chromosome 18 near D18Mit22 (LOD=3.5). This locus is named Hrtfm7 (heart failure modifier 7) and accounts for 16% of the genetic variability for LVEDD. Although Hrtfm5 (35 cM) also maps to chromosome 18, it is separate and distinct from the newly identified Hrtfm7. AKR/J-derived alleles at Hrtfm7 confer decreased LVEDD (increased heart function).

References

• Original: J:100634 Wheeler FC, et al., QTL mapping in a mouse model of cardiomyopathy reveals an ancestral modifier allele affecting heart function and survival. Mamm Genome. 2005 Jun;16(6):414-23
• All: 1 reference(s)