Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Mamm Genome. 2010 Apr;21(3-4):115-29. doi: 10.1007/s00335-010-9247-9. Epub 2010 Feb 3.
Discovery of genes that confer resistance to diseases such as diet-induced obesity could have tremendous therapeutic impact. We previously demonstrated that the C57BL/6J-Chr(A/J)/NaJ panel of chromosome substitution strains (CSSs) is a unique model for studying resistance to diet-induced obesity. In the present study, three replicate CSS surveys showed remarkable consistency, with 13 A/J-derived chromosomes reproducibly conferring resistance to high-fat-diet-induced obesity. Twenty CSS intercrosses, one derived from each of the 19 autosomes and chromosome X, were used to determine the number and location of quantitative trait loci (QTLs) on individual chromosomes and localized six QTLs. However, analyses of mean body weight in intercross progeny versus C57BL/6J provided strong evidence that many QTLs discovered in the CSS surveys eluded detection in these CSS intercrosses. Studies of the temporal effects of these QTLs suggest that obesity resistance was dynamic, with QTLs acting at different ages or after different durations of diet exposure. Thus, these studies provide insight into the genetic architecture of complex traits such as resistance to diet-induced obesity in the C57BL/6J-Chr(A/J)/NaJ CSSs. Because some of the QTLs detected in the CSS intercrosses were not detected using a traditional C57BL/6J x A/J intercross, our results demonstrate that surveys of CSSs and congenic strains derived from them are useful complementary tools for analyzing complex traits.
发现能抵抗疾病（如饮食诱导肥胖）的基因可能具有巨大的治疗效果。我们之前曾证明，C57BL/6J-Chr(A/J)/NaJ 染色体替换品系（CSS）面板是研究抵抗饮食诱导肥胖的独特模型。在本研究中，三次重复的 CSS 调查显示出显著的一致性，13 条 A/J 衍生染色体可重复地抵抗高脂肪饮食诱导的肥胖。使用 20 个 CSS 杂交，每个杂交都来自 19 条常染色体和 X 染色体，以确定单个染色体上的数量和位置和定位六个数量性状位点（QTL）。然而，对杂交后代与 C57BL/6J 的平均体重进行分析，提供了强有力的证据表明，在 CSS 调查中发现的许多 QTL 在这些 CSS 杂交中无法检测到。这些 QTL 的时间效应分析表明，肥胖抵抗是动态的，QTL 在不同年龄或不同饮食暴露时间后起作用。因此，这些研究为研究 C57BL/6J-Chr(A/J)/NaJ CSS 中复杂性状（如抵抗饮食诱导肥胖）的遗传结构提供了深入的了解。由于在 CSS 杂交中检测到的一些 QTL 在传统的 C57BL/6J x A/J 杂交中没有检测到，我们的结果表明，CSS 调查和源自它们的同系物的调查是分析复杂性状的有用互补工具。
