Genetic dissection of complex genetic factor involved in NIDDM of OLETF rat.

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-10-15 DOI:10.1155/2012/582546
Takahisa Yamada, Hiroyuki Kose, Takeshi Ohta, Kozo Matsumoto
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引用次数: 10

Abstract

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, noninsulin-dependent diabetes mellitus (NIDDM) in humans. NIDDM in this rat model was shown to be regulated by multiple genes. We have identified 14 quantitative trait loci (QTLs) responsible for NIDDM (Nidd1-14/of) on chromosomes 1, 5, 7, 8, 9, 11, 12, 14, 16, and 17 by a whole genome search in 160 F2 progenies obtained by mating the OLETF and the F344 rats. Among these loci, two QTLs, Nidd1 and 2/of, were declared significant loci at a genome-wide level. Nidd3, 8, 9, and 13/of exhibited heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) between Nidd1/of and Nidd2/of, between Nidd1/of and Nidd10/of, between Nidd2/of and Nidd8/of, and between Nidd2/of and Nidd14/of. Furthermore, Nidd6 and 11/of showed linkage with body weight, and Nidd1, 2, 8, 9, 10, and 12/of had an interaction with body weight. These indicated that NIDDM in the OLETF would have a higher degree of genetic complexity. We suggest several interesting candidate genes located in rat genomic regions for Nidd1-14/of or the syntenic regions in human genome.

OLETF大鼠NIDDM复杂遗传因子的遗传解剖。
大冢Long-Evans德岛脂肪(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。NIDDM在该大鼠模型中被证明是由多个基因调控的。通过对OLETF和F344大鼠交配获得的160个F2后代进行全基因组搜索,我们在染色体1、5、7、8、9、11、12、14、16和17上发现了14个与NIDDM有关的数量性状位点(Nidd1-14/of)。在这些位点中,Nidd1和2/of两个qtl在全基因组水平上被宣布为显著位点。Nidd3、8、9和13/ 3表现出杂种优势:杂合子的血糖水平明显高于OLETF或F344纯合子。我们还发现了Nidd1/of与Nidd2/of、Nidd1/of与Nidd10/of、Nidd2/of与Nidd8/of、Nidd2/of与Nidd14/of之间相互作用(上位性)的证据。Nidd1、2、8、9、10和12/of与体重存在交互作用,Nidd1、11/of与体重存在交互作用。这表明OLETF中的NIDDM具有更高程度的遗传复杂性。我们提出了几个有趣的候选基因,这些基因位于大鼠基因组区域,用于人类基因组的Nidd1-14/ /或syntenic区域。
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来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
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3-8 weeks
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