Figure 3

Genome-wide linkage mapping of body weight and adiposity index identifies diet specific genetic control independent of NAFLD. Linkages to body weight (A) and adiposity index (B) were calculated in (129S6xBALB/c) F2mice fed control diet (CHD) (black lines) or high fat diet (HFD) (red lines). LOD scores are plotted against map distances (centimorgans). Horizontal lines (A,B) indicate statistically significant LOD thresholds (P = 0.001). The two QTLs on chromosomes 6 and 11 in CHD-fed mice explain a high proportion of the phenotypic variances of BW (10.4–10.7%) and AI (8.8–12.3%). In HFD-fed F2 mice, the QTLs linked to BW explained 13.1–13.7% of the phenotypic variance of BW in the cross. Phenotypic effects of genotypes at markers exhibiting the strongest evidence of linkage are illustrated by phenotype means (±SEM) calculated according to the genotype homozygous for the 129S6 green) or BALB/c allele (red), or heterozygous (orange) at the loci (C–F). In CHD-fed mice, BALB/c alleles were associated with increased BW and AI on chromosome 6, and decreased BW and AI on chromosome 11 (C,D), indicating balancing effects of 129S6 and BALB/c alleles at these loci to maintain these phenotypes within similar ranges as observed in the parental strains. In contrast in HFD-fed mice, 129S6 alleles at the QTLs controlling BW (chromosomes 3 and 4) and AI (chromosome 4) were systematically associated with increased BW and AI (E,F).