Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.
Potential candidate genes for Iba4 (20 cM) on mouse Chromosome 19 as identified by ExQuest are Aldh1a1 (12 cM), Aldh1a7, Vldlr (20 cM), and Plce1. Vldlr exhibits 15.6-fold increased expression in the liver of Tally Ho compared to C57BL/6 animals. For QTL Afw8 (26 cM), potential candidate genes Pi4k2a, Cpn1, and Elovl3 (47 cM) were identified. For QTLs Nobq2 (47 cM) and Bglq13 (51 cM), potential candidate genes Ins1 (49 cM), Gpam (52 cM), and Acsl5 were identified. For QTLs Tanidd1 (50 cM) and T2dm2 (53 cM), potential candidate genes Gfra1, Pnlip (29 cM), Pnliprp1 (29 cM), and Pnliprp2 were identified. Pnliprp2 exhibits 21.8-fold decreased expression in the pancreas of Tally Ho animals in response to a 4% fat diet.