Experiment
Over 200 (C57BL/6J x CAST/Ei)F2 intercross animals were typed for 116 polymorphic markers on all mouse chromosomes (except the Y chromosome) at an average marker density of 10 cM to identify QTLs associated with body fat. Inbred parental strain CAST/Ei is very lean (~8% body fat) compared to inbred parental strain C57BL/6J (~18% body fat). (CAST/Ei x C57BL/6J)F1 hybrids exhibit an intermediate phenotype. Mob5 (multigenic obesity) mapped to distal Chromosome 2 from approximately 75 cM - 109 cM with a peakLOD = 5.8 near D2Mit50. Mob5 is also linked to QTL peaks for hepatic lipase activity, HDL cholesterol levels on chow diet, and insulin levels. Mob6 mapped to central mouse Chromosome 2 from approximately 35 cM - 85 cM with a peak LOD = 7.4 near D2Mit14. Mob6 is also linked to QTL peaks for hepatic lipase activity, HDL cholesterol levels on atherogenic diet, and insulin levels. Mob7 mapped to proximal mouse Chromosome 2 from approximately 25 cM - 35 cM with a peak LOD = 5.8 near D2Mit9. Mob7 is also linked to QTL peaks for HDL levels on atherogenic diet and insulin levels. Mob8 mapped to mouse Chromosome 9 with a peak LOD = 4.7 at D9Mit8. A suggestive QTL for body fat mapped to mouse chromosome 8 with peak LOD = 3.2 near D8Mit12. Mob5, Mob6, and Mob7 appear to affect body fat inheritance in a codominant fashion with CAST-derived alleles conferring reduction in body fat. In contrast, Mob8 appears to be dominantly inherited with CAST-derived alleles conferring increased body fat. Candidate genes in the region of Mob5 and Mob6 are Mc3r, Tnfrsf5 (Cd40), Cebpb, Pltp, agouti, Ghrh, Ahcy, Pcsk2, Adra2b, Sgne1, Lrp2 (Gp330), and a candidate gene in the region of Mob7 is Ptgds. Candidate genes in the region of Mob8 include Ldlr, Il10ra, Apoa1, Apoa4, Apoc3, Acat1,Cyp11a1, and Lipc (Hlp). A QTL associated with body length and body weight, Bdln2, mapped to mouse Chromosome 15 from 7.8 cM - 10.6 cM with a maximum LOD = 4.3 at D15Mit54. A candidate gene near Bldn2 is Ghr, growth hormone receptor.
Analysis Tools