Identification of novel non-insulin-dependent diabetes mellitus susceptibility loci in the Otsuka Long-Evans Tokushima Fatty rat by MQM-mapping method
Identification of novel non-insulin-dependent diabetes mellitus susceptibility loci in the Otsuka Long-Evans Tokushima Fatty rat by MQM-mapping method
复制标题
利用 MQM 作图方法鉴定大冢 Long-Evans 德岛脂肪大鼠中新型非胰岛素依赖型糖尿病易感位点
作者：
K. Sugiura;T. Miyake;Y. Taniguchi;Takahisa Yamada;D. Moralejo;Suwen Wei;K. Wei;Y. Sasaki;Kozo Matsumoto
抽象的。大冢Long-Evans Tokushima Fatty(OLETF)大鼠是人类肥胖型非胰岛素依赖型糖尿病(NIDDM)的动物模型。我们用区间作图的方法在160只OLETF和Fischer-344(F344)大鼠的F2代中发现了11个与NIDDM易感性相关的QTL，这些QTL位于第1、5、7、8、9、11、12、14和16号染色体(NIDD1-11/OLETF)(NIDD1-11/OF)上。MQM作图用于基于多QTL模型的QTL分析，被认为比区间作图更有效，因为在定位一个QTL的过程中，包含其他QTL的遗传背景受到控制。将MQM定位技术应用于F2代杂交，除在Nidd1-11/OF基因座外，还在大鼠CHR5(Nidd12/OF)、7(Nidd13/OF)和17(Nidd14/OF)上发现了3个新的QTL。这三个QTL与NIDD1-11/OF一起，分别解释了F2代空腹和餐后血糖水平遗传变异的∼70%和∼85%。虽然OLETF等位基因与Nidd12和14/Of的预期血糖水平升高相对应，但Nidd13/Of表现出杂种优势：杂合子的血糖水平显著高于OLETF或F344纯合子。Nidd2与14/OF之间存在上位性互作。此外，我们的结果表明，这些新的QTL与体重没有连锁关系，但Nidd12/OF与体重存在互作。
Abstract. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, non-insulin-dependent diabetes mellitus (NIDDM) in humans. We have previously identified 11 quantitative trait loci (QTLs) responsible for NIDDM susceptibility on Chromosomes (Chrs) 1, 5, 7, 8, 9, 11, 12, 14, and 16 (Nidd1–11/of for Non-insulin-dependent diabetes1–11/oletf) by using the interval mapping method in 160 F2 progenies obtained by mating the OLETF and the Fischer-344 (F344) rats. MQM-mapping, which was applied for QTL analysis based on multiple-QTL models, is reported to be more powerful than interval mapping, because in the process of mapping one QTL the genetic background, which contains the other QTLs, is controlled. Application of MQM-mapping in the F2 intercrosses has led to a revelation of three novel QTLs on rat Chrs 5 (Nidd12/of), 7 (Nidd13/of), and 17 (Nidd14/of), in addition to Nidd1–11/of loci. The three QTLs, together with the Nidd1–11/of, account for a total of ∼70% and ∼85% of the genetic variance of the fasting and postprandial glucose levels, respectively, in the F2. While the OLETF allele corresponds with increased glucose levels as expected for Nidd12 and 14/of, the Nidd13/of exhibits heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. There is epistatic interaction between Nidd2 and 14/of. Additionally, our results indicated that the novel QTLs could show no linkage with body weight, but Nidd12/of has an interaction with body weight.
影响因子：
4.4
作者：
LINCOLN, SE;LANDER, ES
通讯作者：
LANDER, ES