Obq7^NZO/HlLt
QTL Variant Detail

Summary

• QTL variant: Obq7^NZO/HlLt
• Name: obesity QTL 7; NZO/HlLt
• MGI ID: MGI:2154252
• QTL: Obq7 Location: unknown Genetic Position: Chr1, cM position of peak correlated region/allele: 33.31 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: NZO/HlLt

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased adiposity compared to SM/J. (J:67838)
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Obq7 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 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:67838

QTL mapping was performed on 328 (SM/J x NZO/HlLt)F2 intercross animals to identify loci associated with obesity phenotypes. Parental strain SM/J is small and lean while parental strain NZO/HlLt is obese.

Three loci mapped to mouse Chromosome 1: Obq7, Obq8, and Obq9.

Obq7 is linked to gonadal fat percentage (LOD = 6.9, stronger effect in males), mesenteric fat percentage (LOD = 6.0), and retroperitoneal fat percentage (LOD = 2.4) at 28.7 cM. NZO-derived alleles confers increased gonadal fat percentagein a recessively or additively inherited fashion at Obq7.

Obq8 is linked to retroperitoneal fat percentage (LOD = 6.4) and adiposity index (LOD = 5.7) at 69.1 cM with the NZO-derived allele conferring increased adiposity in a dominantly or recessively inherited fashion.

Obq9 is linked to mesenteric fat percentage (LOD = 6.7), adiposity index (LOD = 6.2), and inguinal fat percentage (LOD = 2.5) at 88.4 cM with the NZO-derived allele conferring increased adiposity in an additive fashion.

Obq10 maps tomouse chromosome 2 and is linked to adiposity index (LOD = 5.4, stronger effect in males), gonadal fat percentage (LOD = 7.4, stronger effect in males), mesenteric fat percentage (LOD = 7.4), and retroperitoneal fat percentage (LOD = 3.0) at 58.1 cM withthe NZO-derived allele conferring increased adiposity in an additive fashion. Obq10 may also have an effect on body length.

On mouse Chromosome 5, Obq11 and Obq12 map to 10 cM and 29 cM, respectively.

Obq11 is linked to adiposity index (LOD = 3.1, inmales), mesenteric (LOD=4.4), gonadal (LOD = 4.1), retriperitoneal (LOD = 3.3), and inguinal (LOD = 1.7) fat percentages.

Obq12 is linked to adiposity index (LOD = 3.7, in males), mesenteric (LOD = 5.3), gonadal (LOD = 4.5), retriperitoneal (LOD = 2.0), and inguinal (LOD = 2.2) fat percentages. NZO-derived alleles confer increased adiposity at Obq11 and Obq12 in an additive fashion.

On mouse Chromosome 6, Obq13 and Obq14 map to 26.8 cM and 43.5 cM, respectively.

Obq13 is linked to adiposity index (LOD= 8.8), mesenteric (LOD = 9.3), gonadal (LOD = 6.0), inguinal (LOD = 6.2), and retroperitoneal (LOD = 5.1) fat percentages, and Obq14 is linked to adiposity index (LOD=6.4), mesenteric (LOD = 9.2), gonadal (LOD = 4.1), inguinal (LOD = 4.5), and retroperitoneal (LOD = 3.9) fat percentages. NZO-derived alleles confer increased adiposity in an additive fashion at Obq13 and Obq14. A candidate gene for Obq13 is neuropeptide Y (Npy). Analysis of Npy sequence revealed polymorphisms between SM/J and NZO/HlLt but does not appearto explain the phenotypic differences between the strains.

Obq15 maps to mouse Chromosome 7 at 51.4 cM and is linked to adiposity index (LOD = 6.3), gonadal (LOD = 8.1, stronger effect in males), inguinal (LOD = 4.2), mesenteric (LOD= 2.9), and retroperitoneal (LOD = 2.8) fat percentages with the NZO-derived allele contributing to increased adiposity in a dominant fashion.

A locus linked to adiposity index (LOD = 5.8), inguinal (LOD = 8.8, stronger in males), gonadal (LOD = 3.5), retroperitoneal (LOD = 3.1), and mesenteric (LOD = 3.0) fat percentages mapped to mouse Chromosome 17 at 8.7 and colocalizes with Obq4, a previously mapped obesity QTL (Taylor, J:39947).

11.20.2014 Curator's Note: Because the QTL cited here as colocalizing with Obq4 was originally mapped using a different cross we consider the current study a separate mapping study. We have named the QTL mapping here, to mouse Chromosome 17 at 8.7cM, Obq36. SM/J-derived alleles confer increased adiposity in a dominant or overdominant fashion at Obq36.

A suggestive locus mapped to mouse Chromosome X at 49 cM and is linked to adiposity index in males (LOD = 2.7) and gonadal fat percentage (LOD = 4.1). SM/J-derived alleles appear to increase gonadal fat percentages in males at this locus.

References

• Original: J:67838 Taylor BA, et al., Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains. Mamm Genome. 2001 Feb;12(2):95-103
• All: 1 reference(s)