Genetic dissection of quantitative trait locus for ethanol sensitivity in long- and short-sleep mice
Genetic dissection of quantitative trait locus for ethanol sensitivity in long- and short-sleep mice
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DOI：
10.1111/j.1601-183x.2008.00403.x
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发表时间：
2008-08-01
影响因子：
2.5
通讯作者：
Johnson, T. E.
中科院分区：
文献类型：
--
作者：
Bennett, B.;Carosone-Link, P.;Johnson, T. E.
间隔特异性同源株系（ISCS）允许精细定位数量性状位点（QTL），将其置信区间缩小一个数量级或更多。在早期的工作中，我们绘制了四个QTL指定的差异乙醇敏感性，由于乙醇（LORE），在近交系长睡眠（ILS）和近交系短睡眠（ISS）株翻正反射的损失进行评估，约占50%的遗传变异，这个性状。随后，我们产生了相互同源株系，其中来自ILS的每个完整QTL区间被培育到ISS背景上，反之亦然。早期的论文报道了国际空间站背景上的ISCS的建设和结果，在这里，我们描述了这个过程，并报告ILS背景上的结果。我们为每个Lore QTL开发了多个ISCS，其中QTL区间被分成许多较小的区间。对于四个QTL区域（染色体1、2、11和15）中的每一个，我们成功地显著减小了间隔。将多个阳性菌株重叠，以生成单个缩短的间隔。随后，该减少的区域覆盖在先前从ISS背景同源物减少的区域上，导致所有QTL区域从初始作图研究大幅减少约75%。基因序列或表达多态性在减少的时间间隔是潜在的候选人，这些证据。遗传背景效应在单个QTL的检测中可能是重要的;如本文所述，将这些信息与两种背景上的同源基因的产生相结合，是精细定位QTL的有力方法。
Interval-specific congenic strains (ISCS) allow fine mapping of a quantitative trait locus (QTL), narrowing its confidence interval by an order of magnitude or more. In earlier work, we mapped four QTL specifying differential ethanol sensitivity, assessed by loss of righting reflex because of ethanol (LORE), in the inbred long-sleep (ILS) and inbred short-sleep (ISS) strains, accounting for approximately 50% of the genetic variance for this trait. Subsequently, we generated reciprocal congenic strains in which each full QTL interval from ILS was bred onto the ISS background and vice versa. An earlier paper reported construction and results of the ISCS on the ISS background; here, we describe this process and report results on the ILS background. We developed multiple ISCS for each Lore QTL in which the QTL interval was broken into a number of smaller intervals. For each of the four QTL regions (chromosomes 1, 2, 11 and 15), we were successful in reducing the intervals significantly. Multiple, positive strains were overlapped to generate a single, reduced interval. Subsequently, this reduced region was overlaid on previous reductions from the ISS background congenics, resulting in substantial reductions in all QTL regions by approximately 75% from the initial mapping study. Genes with sequence or expression polymorphisms in the reduced intervals are potential candidates; evidence for these is presented. Genetic background effects can be important in detection of single QTL; combining this information with the generation of congenics on both backgrounds, as described here, is a powerful approach for fine mapping QTL.