Wt6q1^MH
QTL Variant Detail

Summary

• QTL variant: Wt6q1^MH
• Name: body weight, 6 weeks, QTL 1; MH
• MGI ID: MGI:2154374
• QTL: Wt6q1 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: MH line

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased body weight at 6 weeks compared to C57BL/6J and ML. (J:55483)
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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 1, Idh1 (29.8 cM) showed differential expression between restricted and unrestricted diets on the A/a background. Diabesity QTLs mapping near Idh1 are Dbsty1 (21 cM),Insq2 (36 cM), Wt10q1 (25 cM), Wt6q1 (27 cM), Obq7 (28.7 cM), and Bw5 (36 cM). At another locus, Pea15 (93.8 cM) showed differential expression between restricted and unrestricted diets on the A/a background and F11r (93.3 cM) showed differential expression between A/a and A/A^vy animals on the restricted diet. Diabesity QTL Obq9 (88.4 cM) maps near Pea15 and F11r.

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.

A potential candidate gene for Obq2 at 15 cM on mouse Chromosome 1 as identified by ExQuest is Gsta3. For QTLs Obq7 (28.7 cM), Wt6q1 (27 cM), Insq2 (36cM), and Insq6 (37 cM), potential candidate genes Aox1 (23.2 cM), Fn1 (36.1 cM), Pecr, Igfbp2 (36.1 cM), Plcd4 (39.2 cM), Scg2 (43.6 cM), Irs1, and Inpp5d (57 cM) were identified. For QTL Nidd6 (77 cM), potential candidate gene Qscn6 was identified. For QTL Obq9 (88.4 cM), potential candidate genes Fmo1, Fmo3, and Apoa2 (92.6 cM) were identified. For QTL Wt6q2 (108 cM), potential candidate gene Hsd11b1 was identified.

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

J:55483

Authors used a composite base population from four outbred strains (NIH, ICR, CF-1 and CFW) to select for lines showing a difference in heat loss. After 15 generations of selection, the MH line showed higher heat loss, consumed more feed, were leaner and more active than the ML line of mice. C57BL/6J was chosen as the inbred line to create a resource population from a cross between a selection line and an inbred line. Average heat loss and feed intake of the C57BL/6J mice were similar to that of mice from the ML line but their body composition was similar to the MH line. To identify QTLs that are responsible for heat loss and other phenotypes related to energy balance, a complete genome wide scan was conducted in a (MH x C57BL/6J)F2 intercross (n = 560). Regions harboring QTL with the greatest effects were then evaluated in a (MH x ML)F2 intercross (n = 560). A QTL influencing body weight at 6 weeks, Wt6q1 (LOD = 4.02, 3.3% of residual variance explained) was identified with a peak at 27 cM on Chromosome 1 in the (MH x C57BL/6J)F2 intercross. The MH allele was responsible for increased body weight at 6 weeks for this QTL. Wt6q1 was confirmed in the (MH x ML)F2 intercross with a LOD score of 3.44, p<0.0001.

References

• Original: J:55483 Moody DE, et al., Identification of quantitative trait loci influencing traits related to energy balance in selection and inbred lines of mice. Genetics. 1999 Jun;152(2):699-711
• All: 1 reference(s)