Monell Chemical Senses Center, Philadelphia Pennsylvania, USA.
PLoS One. 2013 Jul 29;8(7):e68776. doi: 10.1371/journal.pone.0068776. Print 2013.
Obesity is a heritable trait caused by complex interactions between genes and environment, including diet. Gene-by-diet interactions are difficult to study in humans because the human diet is hard to control. Here, we used mice to study dietary obesity genes, by four methods. First, we bred 213 F2 mice from strains that are susceptible [C57BL/6ByJ (B6)] or resistant [129P3/J (129)] to dietary obesity. Percent body fat was assessed after mice ate low-energy diet and again after the same mice ate high-energy diet for 8 weeks. Linkage analyses identified QTLs associated with dietary obesity. Three methods were used to filter candidate genes within the QTL regions: (a) association mapping was conducted using >40 strains; (b) differential gene expression and (c) comparison of genomic DNA sequence, using two strains closely related to the progenitor strains from Experiment 1. The QTL effects depended on whether the mice were male or female or which diet they were recently fed. After feeding a low-energy diet, percent body fat was linked to chr 7 (LOD=3.42). After feeding a high-energy diet, percent body fat was linked to chr 9 (Obq5; LOD=3.88), chr 12 (Obq34; LOD=3.88), and chr 17 (LOD=4.56). The Chr 7 and 12 QTLs were sex dependent and all QTL were diet-dependent. The combination of filtering methods highlighted seven candidate genes within the QTL locus boundaries: Crx, Dmpk, Ahr, Mrpl28, Glo1, Tubb5, and Mut. However, these filtering methods have limitations so gene identification will require alternative strategies, such as the construction of congenics with very small donor regions.
肥胖是一种遗传性特征，由基因和环境（包括饮食）之间的复杂相互作用引起。由于人类饮食难以控制，因此很难在人类中研究基因与饮食的相互作用。在这里，我们使用小鼠来研究饮食肥胖基因，采用了四种方法。首先，我们从容易肥胖的 [C57BL/6ByJ（B6）] 和不易肥胖的 [129P3/J（129）] 两个品系中繁殖了 213 只 F2 代小鼠。当这些小鼠吃低能量饮食和高能量饮食 8 周后，我们分别检测了它们的体脂百分比。连锁分析鉴定出与饮食肥胖相关的 QTL。我们使用三种方法在 QTL 区域内筛选候选基因：（a）使用 40 多个品系进行关联作图；（b）比较两种与实验 1 中亲本品系密切相关的品系的基因表达差异和（c）基因组 DNA 序列差异。QTL 效应取决于小鼠的性别、最近吃的饮食。当喂食低能量饮食时，体脂百分比与第 7 号染色体（LOD=3.42）相关。当喂食高能量饮食时，体脂百分比与第 9 号染色体（Obq5；LOD=3.88）、第 12 号染色体（Obq34；LOD=3.88）和第 17 号染色体（LOD=4.56）相关。第 7 号和 12 号染色体 QTL 依赖于性别，所有 QTL 都依赖于饮食。这些过滤方法的组合突出了 QTL 基因座边界内的七个候选基因：Crx、Dmpk、Ahr、Mrpl28、Glo1、Tubb5 和 Mut。然而，这些过滤方法存在局限性，因此基因鉴定将需要替代策略，例如构建具有非常小供体区域的同源染色体。
