Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model.

Abstract

Loci linked to sensitivity to dietary obesity were identified by Quantitative Trait Locus (QTL) analysis of two mapping populations derived from a cross between AKR/J and SWR/J mice. AKR/J mice are sensitive to dietary obesity when fed a high fat diet while SWR/J mice are resistant. Intercrosses between these strains segregate the phenotype of sensitivity to dietary obesity. Using an F2 mapping population of 931 male mice we found significant linkage with a QTL on chromosome 9 (Likelihood of the Odds [LOD] ratio of 4.85) and another QTL on chromosome 15 (LOD = 3.93). The presence of a QTL on chromosome 15 was confirmed in a separate mapping population of 375 male F1 x SWR/J mice (LOD = 3.82). These two loci are designated dietary obese 2 (Do2) and dietary obese 3 (Do3) for the chromosome 9 and 15 loci, respectively. Both of these chromosomal regions contain candidate genes which may contribute to variation in the phenotype. These loci also exert a significant control over individual adipose depot weights. (J. Clin. Invest. 1994. 94:1410-1416

Enhanced insulin secretion and cholesterol metabolism in congenic strains of the spontaneously diabetic (Type 2) Goto Kakizaki rat are controlled by independent genetic loci in rat chromosome 8

“…Comparative genome analysis data showed that Ins/gk1 and Chol/gk1 are conserved with a region of mouse chromosome 9, previously characterised for the obesity QTL Dob2 and Mob8 [23,24,25], and human chromosomes 11q22.3-24.3, 15q21.2-25.1 and 6p21.1-q14.1. The region of human 15q, which contains the locus LIPC and is associated with variations in HDL-C concentrations in Mexican Americans [26], seems to be homologous to Chol/gk1.…”

A meta-analysis of quantitative trait loci associated with body weight and adiposity in mice

“…4 In fact, for at least 13 QTL, evidence for linkage of body weight and body fat percentage was found within the same study, including Adip2, Adip3, Adip4a, Adip8, Bfq1, Bwnd5wk6, Do2, Do3, Do7, Kcal3, Nob1, Nzoq2, and Obq5. [51][52][53][54][55][56][57][58][59][60] It appears that most of these QTL involved cross-breeding experiments with parental mouse strains that show a relatively high (AKR, NZO, KK) and low (CAST, SM, SJL) body weight and (Figures 2 and 3). The contribution of QTL to certain consensus regions apparently correlates with the parental mouse strain.…”

Genetic modifiers of the insulin resistance phenotype in mice.

“…This finding is not unprecedented. In studies of genetic modifiers of the L e p r f a mutation, Chung et al (29) found that the susceptibility alleles to L e p r f a -associated diabetes are not always derived from the susceptible strain, a phenomenon known as "transgression" that has also been seen in studies of QTL controlling body fat and diet (46,47). A possible explanation is that these alleles are silenced by more dominant alleles in the context of the resistant strain but are active in the context of the susceptible strain.…”