Experiment
The Fob3 locus was identified at 34 cM on mouse Chromosome 15 by Horvat et al, 2000 (J:59227) in F-Line (fat) and L-Line (lean) mice. Stylianou et all, 2004 (J:9000) resolved the Fob3 interval into two separate regions using three Fob3 congenic lines created with the following L-Line-derived Chr15 intervals: A-congenic (D15Mit150 [12 cM] - D15Mit107 [49 cM]), B-congenic (D15Mit184 [25 cM] - D15Mit39 [56 cM]), and D-congenic (D15Mit184 [25 cM] - D15Mit107 [49 cM]) at approximately 27 cM and 68 cM. These loci were named Fob3a and Fob3b, respectively.
In the current study the congenic lines B and D were backcrossed to the recipient F line for another 5-7 generations. In this way the interval specific congenic lines used here were back crossed in 10-12 generations with additional marker assisted elimination of other QTL regions. The B line used in this study retained Lean line alleles between markers D15Mit26.1 and D15Mit70. A recombinant mouse found during the backcrossing was used to develop congenic line M. After another 5-12 generations of backcrossing, more recombinants within the Fob3b QTL region were identified from the D line that at the fifth backcross carried Lean line alleles between D15Mit184 and D17Mit73 to develope congenic lines D12, E, P, G and K. All congenic lines were eventually fixed for overlapping segments and used for fine mapping of the Fob3b QTL region.
Fine mapping analysis using F2 congenic intercrosses (congenic lines x F line) revealed that the Fob3b QTL was composed of at least two linked QTL:
Fob3b1, mapped between 71.38 - 76.36 Mb on Chr 15; Fob3b2 mapped between 75.25 - 82.93 Mb on the same Chr [NCBI36]. The effect of each QTL for adiposity index amounts were 1.22 and 0.77% in the Fob3b1 and Fob3b2 respectively. Alleles from the Lean line decrease obesity-related traits.
High priority candidate genes for Fob3b1 are Dgat1, Ly6a, Gpihpbp1 and Rhpn1.
Analysis Tools