Brockmann G A, Kratzsch J, Haley C S, Renne U, Schwerin M, Karle S
Research Institute for the Biology of Farm Animals, 18196 Dummerstorf, Germany.
Genome Res. 2000 Dec;10(12):1941-57. doi: 10.1101/gr.gr1499r.
Genes influencing body weight and composition and serum concentrations of leptin, insulin, and insulin-like growth factor I (IGF-I) in nonfasting animals were mapped in an intercross of the extreme high-growth mouse line DU6i and the inbred line DBA/2. Significant loci with major effects (F > 7.07) for body weight, obesity, and muscle weight were found on chromosomes 1, 4, 5, 7, 11, 12, 13, and 17, for leptin on chromosome 14, for insulin on chromosome 4, and for IGF-I on chromosome 10 at the Igf1 gene locus itself and on chromosome 18. Significant interaction between different quantitative trait loci (QTL) positions was observed (P < 0.01). Evidence was found that loci having small direct effect on growth or obesity contribute to the obese phenotype by gene-gene interaction. The effects of QTLs, epistasis, and pleiotropy account for 64% and 63% of the phenotypic variance of body weight and fat accumulation and for over 32% of muscle weight and serum concentrations of leptin, and IGF-I in the F(2) population of DU6i x DBA/2 mice. [The quantitative trait loci described in this paper have been submitted to the Mouse Genome Database.]
在极端高生长小鼠品系DU6i与近交系DBA/2的杂交后代中，对非禁食动物影响体重、身体组成以及瘦素、胰岛素和胰岛素样生长因子I（IGF-I）血清浓度的基因进行了定位。在1、4、5、7、11、12、13和17号染色体上发现了对体重、肥胖和肌肉重量有主要影响（F>7.07）的显著位点，在14号染色体上发现了对瘦素有影响的显著位点，在4号染色体上发现了对胰岛素有影响的显著位点，在10号染色体上的Igf1基因位点本身以及18号染色体上发现了对IGF-I有影响的显著位点。观察到不同数量性状位点（QTL）位置之间存在显著相互作用（P<0.01）。有证据表明，对生长或肥胖有小的直接影响的位点通过基因-基因相互作用导致肥胖表型。在DU6i×DBA/2小鼠的F(2)群体中，QTL、上位性和多效性效应分别占体重和脂肪积累表型变异的64%和63%，占肌肉重量以及瘦素和IGF-I血清浓度表型变异的32%以上。[本文描述的数量性状位点已提交至小鼠基因组数据库。]
