Yi Nengjun, Zinniel Denise K, Kim Kyoungmi, Eisen Eugene J, Bartolucci Alfred, Allison David B, Pomp Daniel
Department of Biostatistics, Section on Statistical Genetics, University of Alabama, Birmingham, AL 35294, USA.
Genet Res. 2006 Feb;87(1):45-60. doi: 10.1017/S0016672306007944.
To comprehensively investigate the genetic architecture of growth and obesity, we performed Bayesian analyses of multiple epistatic quantitative trait locus (QTL) models for body weights at five ages (12 days, 3, 6, 9 and 12 weeks) and body composition traits (weights of two fat pads and five organs) in mice produced from a cross of the F1 between M16i (selected for rapid growth rate) and CAST/Ei (wild-derived strain of small and lean mice) back to M16i. Bayesian model selection revealed a temporally regulated network of multiple QTL for body weight, involving both strong main effects and epistatic effects. No QTL had strong support for both early and late growth, although overlapping combinations of main and epistatic effects were observed at adjacent ages. Most main effects and epistatic interactions had an opposite effect on early and late growth. The contribution of epistasis was more pronounced for body weights at older ages. Body composition traits were also influenced by an interacting network of multiple QTLs. Several main and epistatic effects were shared by the body composition and body weight traits, suggesting that pleiotropy plays an important role in growth and obesity.
为了全面研究生长和肥胖的遗传结构,我们对由M16i(选作快速生长品系)和CAST/Ei(野生来源的小型瘦型小鼠品系)杂交产生的F1代回交至M16i的小鼠,在五个年龄阶段(12天、3周、6周、9周和12周)的体重以及身体组成性状(两个脂肪垫和五个器官的重量)进行了多个上位性数量性状位点(QTL)模型的贝叶斯分析。贝叶斯模型选择揭示了一个体重的多QTL时间调控网络,涉及强大的主效应和上位效应。没有QTL对早期和晚期生长都有强有力的支持,尽管在相邻年龄观察到主效应和上位效应的重叠组合。大多数主效应和上位相互作用对早期和晚期生长有相反的影响。上位性对较老年龄的体重贡献更为明显。身体组成性状也受到多个QTL相互作用网络的影响。身体组成和体重性状共享了一些主效应和上位效应,表明基因多效性在生长和肥胖中起重要作用。