Experiment
A QTL linked to obesity on distal mouse Chromosome 2 was analyzed using a congenic line and recombinant progeny testing. Congenic line M16i.B6-(D2Mit306-D2Mit52) carries C57BL/6J-derived DNA from D2Mit306 (61.2 cM) to D2Mit52 (99 cM) on an M16i genetic background, which includes the chromosome 2 obesity locus. Donor strain C57BL/6J is relatively lean whereas background strain M16i is obese, hyperinsulinemic, and hyperglycemic.
1200 animals were produced from an F2 intercross between M16i and M16i.B6-(D2Mit306-D2Mit52). The intercross animals were assessed for a total of 18 obesity-related traits. The chromosome 2 obesity locus appears have several distinct components.
Significant linkage to body weight at different time points mapped to an interval between D2Mit194 and D2Mit343. Peak linkage is near D2Mit194 (81.4 cM). This QTL is designated Gnf1 (growth and fatness 1). The confidence interval of Gnf1 spans 78.1 cM - 82.4 cM (136.5 Mb - 147.5 Mb), and this locus explains 2.5% - 3.8% of the variance. Linkageto bone mineral density (BMD) and percent lean weight also peaks at D2Mit194. Gnf1 accounts for 8.5% of the BMD variance and 11.7% of the percent lean weight variance. Linkage to fatness traits overlap with this locus from 80.4 cM - 84.2 cM. Approximately 13% - 18% of the variance for fatness is explained by this locus. Gnf1 most likely represents a single QTL with pleiotropic effects. C57BL/6J-derived alleles at Gnf1 confer decreased body weight, fatness, and bone mineral density while increasing lean body mass. Previously identified body weight and fatness QTLs mapping near Gnf1 are W10q1 (79.6 cM), Epfq1 (84 cM), and Scfq1 (84 cM). A previously identified BMD QTL named Tbbmd3 (78.7 cM) also maps near Gnf1. Potential candidate genes for Gnf1 are Sstr4 (84 cM), Acas2l, and Dusp15.
A locus named Gnf2 (growth and fatness 2) mapped to an interval between D2Mit285 and D2Mit263. Gnf2 is linked to fatness, and the confidence interval spans 88.4 cM - 91.6 cM (157.3 Mb - 161.3 Mb). Gnf2 accounts for approximately 9% - 11% of the variance for fatness. C57BL/6J-derived alleles at Gnf2 confer decreased fatness. Previously identified fatness QTLs mapping near Gnf2 are Mob5 (95 cM) and Epfq2 (97.6 cM). Potential candidate genes for Gnf2 are Rem1, Id1 (84 cM), Bcl2l1(87.5 cM), Hck (86 cM), Gdf5 (90 cM), and Acss2.
A locus named Gnf3 (growth and fatness 3) mapped to an interval between D2Mit343 and D2Mit285. Gnf3 is linked to fatness, and the confidence interval spans 84.6 cM - 86.4 cM (154 Mb - 156.9 Mb). Thislocus accounts for approximately 8.3% of the variance in fatness. C57BL/6J-derived alleles at Gnf3 confer decreased fatness. Potential candidate genes for Gnf3 are Ndrg3, Ncoa6, Rbm12, Samhd1, and Lbp (83 cM).
Linkage to liver weight mapped to an intervalbetween D2Mit304 and D2Mit106. This locus is named Gnf4 (growth and fatness 4). Peak linkage to liver weight occurs at D2Mit106. The confidence interval of Gnf4 spans 73 cM - 76.6 cM (128.5 Mb - 134.5 Mb). This locus accounts for approximately 4% of thevariance for liver weight. Previously identified liver weight QTLs mapping near Gnf4 are Lvrq1 (59.7 cM) and Orgwq3 (65 cM). Potential candidate genes for Gnf4 are Slc20a1 (73 cM), Mertk, Pdyn (73.3 cM), and Cenpb (73.9 cM).
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