Hivan1^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Hivan1^CAST/EiJ
• Name: HIV-associated nephropathy 1; CAST/EiJ
• MGI ID: MGI:3037878
• QTL: Hivan1 Location: Chr3:7586174-68716946 bp Genetic Position: Chr3, cM position of peak correlated region/allele: 9.61 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased renal disease severity compared to FVB/N. (J:88645)

Notes

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

J:88645

Linkage analysis was performed on 185 animals from a (FVB/N-TgN(pNL43d14)26Lom x CAST/EiJ)F1 x FVB/N-TgN(pNL43d14)26Lom backcross population to identify QTLs associated with HIV-associated nephropathy. 139 polymorphic markers at an average spacing of 13 cM were used in the genome scan. All 185 animals were heterozygous for the HIV-1 transgene. Parental strain FVB/N-TgN(pNL43d14)26Lom exhibit severe renal disease compared to parental strain CAST/EiJ.

A major locus named Hivan1 mapped to 9.8 cM on mouse Chromosome 3 near D3Mit204 (multipoint LOD=4.9). Individual phenotype scores at Hivan1 are as follows: renal histology-LOD=3.5, cholesterol- LOD=3.1, blood urea nitrogen- LOD=2.4, and urinary protein- LOD=2.1. CAST/EiJ-derived alleles confer increased renal disease severity at Hivan1. The Hivan1 interval spans 30 cM from 2.4 cM (D3Mit164) to 33 cM (D3Mit154). Candidate genes mapping to this region include Agtr1b, Skil, Prkci, and Tnfsf10. This locus explains 15% of the variance in composite renal score, and explains 10% of the variance in histology and cholesterol levels. Hivan1 is syntenic to human Chromosome 3q25-27.

Suggestive loci mapped to 23 cM on mouse Chromosome 11 (LOD=2.2 at D11Mit138) and to 6.5 cM on mouse Chromsome 14 (LOD=2.1 at D14Mit138). FVB/N-derived alleles confer increased renal disease severity at both suggestive loci.

A locus associated with serum cholesterol levels was identified at approximately 36 cM on mouse Chromosome 9 (LOD=3.3). This locus spans from 23 cM (D9Mit286) to 48 cM(D9Mit9) and is named Schol (serum cholesterol level). Schol explains 10% of the phenotypic variance and does not affect the renal disease phenotype. The Apoa1, Apoc3, Apoa4, and Apoa5 gene cluster maps to this region.

References

• Original: J:88645 Gharavi AG, et al., Mapping a locus for susceptibility to HIV-1-associated nephropathy to mouse chromosome 3. Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2488-93
• All: 2 reference(s)