Experiment
Linkage analysis was performed on (DBA/2J x AKR/J)F1 x DBA/2J and (129P3/J x SJL/J)F1 x 129P3/J backcross populations and 21 AKXD (AK=AKR/J; D=DBA2/J) recombinant inbred (RI) strains to identify QTLs associated with intestinal cholesterol absorption. TheAKR/J parental strain exhibits high cholesterol absorption whereas DBA/2J exhibits low cholesterol absorption. In the the (DBA/2J x AKR/J)F1 x DBA/2J backcross population, linkage was detected on mouse Chromosome 2 (Chab1; LOD=4.0 at D2Mit305) and mouse Chromosome 10 (Chab2; LOD=3.5 at D10Mit6) assuming an additive mode of inheritance. Nr1h3 (previously Lxra) is a possible candidate gene for Chab1. In the AKXD RI strains, three loci contributing to intestinal cholesterol absorption (Chab3, Chab4, and Chab5) were identified. Chab3 is linked to the rhodopsin gene (Rho) on mouse Chromosome 6 with a LOD score of 2.0 at 51.5 cM. Pparg was identified as a candidate gene for Chab3. Chab4 is linked to salivary protein 2 (Spt2) on mouse Chromsome 15 with a LOD score of 2.0 at 58.1 cM, and Acat2 was identified as a candidate gene. *Note-MGD currently places Acat2 at 7.55cM on mouse Chromosome 17* Chab5 maps to 16 cM on mouse Chromosome 19 with a LOD score of 1.6 at D19Mit41 with Vldlr and Osbp identified as candidate genes. In the (129P3/J x SJL/J)F1 x 129P3/J backcross population two loci (Chab6 and Chab7) were detected. 129P3/J is a high-absorbing strain whereas SJL/J is a low-absorbing strain. Assuming an additive mode of inheritance, Chab6 maps to 63.1 cM onmouse Chromosome 1 with a LOD score of 2.9 at D1Mit90, and Chab7 maps to 61 cM on mouse Chromosome 5 with a LOD score of 4.3 at D5Mit317. Cyp27 and Hdlbp were identified as candidate genes for Chab6, and Srb1 was identified as a candidate gene for Chab7.
Analysis Tools