Ath9^FVB/NCr
QTL Variant Detail

Summary

• QTL variant: Ath9^FVB/NCr
• Name: atherosclerosis 9; FVB/NCr
• MGI ID: MGI:2386542
• QTL: Ath9 Location: Chr1:177112768-177112883 bp Genetic Position: Chr1, cM position of peak correlated region/allele: 81.08 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: FVB/NCr

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased HDL cholesterol compared to C57BL/6J. (J:76127)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Ath9 exhibits additive inheritance.

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

J:76127

Two independent strain intercosses that carry atherosclerosis phenotype-sensitizing Apoe deficiency were performed to reveal artherosclerosis susceptibility loci that are distinct from loci linked to lipoprotein levels.

Animals from a C57BL/6J-derived background are susceptible to atherosclerosis and yield several-fold higher aortic lesion scores compared to animals from an FVB/NCr-derived background.

In the first cross, referred to as cross 1, B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres F1 mice were crossed and the F1 offspring were intercrossed to create 197 (B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres) F2 mice for the QTL analysis. Interval mapping was done with 194 markers at a distance of no more than 10cM.

In the second, confirmatory cross, B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres F1 mice were crossed and the F1 offspring were intercrossed to create 186 (B6.129P2-Apoe^tm1Unc x FVB.129P2-Apoe^tm1Bres)F2 mice for QTL analysis. This cross was referred to as cross 2; these mice were genotyped using 127 markers at no more than 10cM intervals.

Interval mapping of chromosome 1, in cross 1, revealed a peak at D1Mit359, this QTL was associated with total cholesterol, HDL and LDL with LOD scores exceeding 3.5 in the combined gender groups. A peak LOD score of 6.0 was also detected at D1Mit359 for HDL in male specific data. This QTL was named Ath9. A possible candidate gene for Ath9 is Apoa2

Unexpectedly, cross 2 also revealed a suggestive linkage (LOD 3.3) for lesion formation atD1Mit359 where cross 1 did not.

The interval from 60-90 cM on mouse chromosome 1 is homologous to human 1q21-32.

References

• Original: J:76127 Dansky HM, et al., A phenotype-sensitizing apoe-deficient genetic background reveals novel atherosclerosis predisposition Loci in the mouse. Genetics. 2002 Apr;160(4):1599-608
• All: 1 reference(s)