University of Colorado Denver, School of Medicine, Department of Pharmacology, Aurora, CO 80045, USA.
Addict Biol. 2011 Jul;16(3):393-404. doi: 10.1111/j.1369-1600.2010.00254.x. Epub 2010 Nov 4.
The identification of genes that contribute to polygenic (complex) behavioral phenotypes is a key goal of current genetic research. One approach to this goal is to combine gene expression information with genetic information, i.e. to map chromosomal regions that regulate gene expression levels. This approach has been termed 'genetical genomics', and, when used in conjunction with the identification of genomic regions (QTLs) that regulate the complex physiological trait under investigation, provides a strong basis for candidate gene discovery. In this paper, we describe the implementation of the genetical genomic/phenotypic approach to identify candidate genes for sensitivity to the analgesic effect of morphine in BXD recombinant inbred mice. Our analysis was performed 'in silico', using an online interactive resource called PhenoGen (http://phenogen.ucdenver.edu). We describe in detail the use of this resource, which identified a set of candidate genes, some of whose products regulate the cellular localization and activity of the mu opiate receptor. The results demonstrate how PhenoGen can be used to identify a novel set of genes that can be further investigated for their potential role in pain, morphine analgesia and/or morphine tolerance.
鉴定与多基因（复杂）行为表型相关的基因是当前遗传研究的一个主要目标。实现这一目标的一种方法是将基因表达信息与遗传信息相结合，即绘制调节基因表达水平的染色体区域图谱。这种方法被称为“遗传基因组学”，当与鉴定调节所研究复杂生理性状的基因组区域（QTL）结合使用时，为候选基因的发现提供了强有力的基础。在本文中，我们描述了在 BXD 重组近交系小鼠中鉴定对吗啡镇痛作用敏感的候选基因的遗传基因组学/表型方法的实施。我们的分析是通过使用名为 PhenoGen（http://phenogen.ucdenver.edu）的在线交互式资源进行“计算机模拟”来完成的。我们详细描述了该资源的使用方法，该方法确定了一组候选基因，其中一些产物调节μ阿片受体的细胞定位和活性。研究结果表明，PhenoGen 如何用于鉴定一组新的候选基因，这些基因可以进一步研究其在疼痛、吗啡镇痛和/或吗啡耐受中的潜在作用。
