Obq4^C57L/J
QTL Variant Detail

Summary

• QTL variant: Obq4^C57L/J
• Name: obesity QTL 4; C57L/J
• MGI ID: MGI:2429751
• QTL: Obq4 Location: unknown Genetic Position: Chr17, cM position of peak correlated region/allele: 4.92 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57L/J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased adiposity in male animals compared to AKR/J, and accounts for 11.7% of the phenotypic variance in male inguinal fat pad weight (percentage). (J:39947)
• Inheritance: Recessive

Notes

Obq4 may also be consistent with an additive mode of inheritance.

Candidate Genes

J:91835

The correlation between gene expression and dietary interaction was examined in a population of (BALB/cStCrlfC3H/Nctr x VY/WffC3Hf/Nctr-A(vy)/a)F1 animals. A/a and A/A^vy animals were placed on a 70% (calorie restricted) or 100% (non-restricted) diet andliver mRNA levels were assessed for over 18,000 genes using DNA microarrays. Twenty-eight known genes showing statistically significant differential expression between the 70% and 100% calorie diets and A/a and A/A^vy genotypes mapped near known diabesity QTLs. These genes may be considered further for candidate genes.

On mouse Chromosome 17, Tbp (8.25 cM) shows differential expression between A/a and A/A^vy animals on the unrestricted diet. Diabesity QTL Obq4 (4 cM) maps near candidate gene Tbp. Vegfa (28 cM) shows differential expression between A/a and A/A^vy animals on the restricted diet. Diabesity QTL Trbv4c1 (23 cM) maps near candidate gene Vegfa. Ppm1b (50.8 cM) shows differential expression between the restricted and unrestricted diets on the A/A^vy background. Diabesity QTL Insq5 (56.7 cM) maps near candidate gene Ppm1b.

J:99477

Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.

Potential candidate genes for Hdl4 (32.3 cM) on mouse Chromosome 17 as identified by ExQuest are Gnmt, Lrg1, and Sepx1 (10 cM). For QTL Insq5 (56.7 cM), potential candidate gene Abcg5 (54.5 cM) was identified. For QTL Obq4 (4 cM) and Wta4 (17 cM), potential candidate genes Plg (7.3 cM), Acat2 (7.55 cM), Acat3 (7.55 cM), Hagh (11 cM), Igfals, Decr2, Clps (17.1 cM), Tff1 (17 cM), Tff2 (17 cM), Tff3 (17 cM), and Apom were identified. Tff3 exhibits almost undetectable levels of transcription in the liver of Tally Ho animals compared C57BL/6J.

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

J:39947

Statistical analysis of 93 individual genotypes (up to 339 for select markers) from (AKR/J x C57L/J)F2 fat and lean pool mice indicated the presence of a QTL locus on mouse Chromosome 17 affecting the adiposity index. A LOD peak score of 4.6 occurred at a position 5 cM distal to D17Mit143. A broad 1-LOD support interval extended from the centromere to 2 cM distal to D17Mit173. Gene order and percentage of recombination between markers is reported as: D17Mit143 - 5.8 - D17Mit173 - 5.2 - D17Mit28 - 3.4 - D17Mit11 - 3.4 - D17Mit66 - D17Mit117 - 12.3 - D17Mit20. This QTL is reported to account for 6.1% of the phenotypic variance,and is demonstrated to affect males much more than females (LOD = 4.0 vs. LOD = 1.6 respectively.

References

• Original: J:39947 Taylor BA, et al., Obesity QTLs on mouse chromosomes 2 and 17. Genomics. 1997 Aug 1;43(3):249-57
• All: 1 reference(s)