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人类和小鼠模型中与饮酒表型相关的部分数量性状位点的比较。

A comparison of selected quantitative trait loci associated with alcohol use phenotypes in humans and mouse models.

机构信息

Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA 92037, USA.

出版信息

Addict Biol. 2010 Apr;15(2):185-99. doi: 10.1111/j.1369-1600.2009.00195.x.

Abstract

Evidence for genetic linkage to alcohol and other substance dependence phenotypes in areas of the human and mouse genome have now been reported with some consistency across studies. However, the question remains as to whether the genes that underlie the alcohol-related behaviors seen in mice are the same as those that underlie the behaviors observed in human alcoholics. The aims of the current set of analyses were to identify a small set of alcohol-related phenotypes in human and in mouse by which to compare quantitative trait locus (QTL) data between the species using syntenic mapping. These analyses identified that QTLs for alcohol consumption and acute and chronic alcohol withdrawal on distal mouse chromosome 1 are syntenic to a region on human chromosome 1q where a number of studies have identified QTLs for alcohol-related phenotypes. Additionally, a QTL on human chromosome 15 for alcohol dependence severity/withdrawal identified in two human studies was found to be largely syntenic with a region on mouse chromosome 9, where two groups have found QTLs for alcohol preference. In both of these cases, while the QTLs were found to be syntenic, the exact phenotypes between humans and mice did not necessarily overlap. These studies demonstrate how this technique might be useful in the search for genes underlying alcohol-related phenotypes in multiple species. However, these findings also suggest that trying to match exact phenotypes in humans and mice may not be necessary or even optimal for determining whether similar genes influence a range of alcohol-related behaviors between the two species.

摘要

在人类和小鼠基因组的某些区域,已经有一些研究一致地报告了与酒精和其他物质依赖表型相关的遗传连锁证据。然而,问题仍然是,在小鼠中观察到的与酒精相关的行为所涉及的基因是否与在人类酗酒者中观察到的行为所涉及的基因相同。目前这组分析的目的是通过同线性映射,在人类和小鼠中确定一小部分与酒精相关的表型,以便比较物种之间的数量性状基因座(QTL)数据。这些分析确定了小鼠远端 1 号染色体上的酒精消耗和急性及慢性酒精戒断的 QTL 与人类 1 号染色体 1q 上的一个区域同线性,许多研究已经确定了与酒精相关表型的 QTL。此外,在两项人类研究中发现的人类染色体 15 上与酒精依赖严重程度/戒断相关的 QTL 与小鼠染色体 9 上的一个区域同线性,两个研究小组已经在该区域发现了与酒精偏好相关的 QTL。在这两种情况下,虽然 QTL 被发现是同线性的,但人类和小鼠之间的表型并不一定完全重叠。这些研究表明,这种技术如何在多种物种中寻找与酒精相关表型相关的基因方面是有用的。然而,这些发现也表明,试图在人类和小鼠中匹配确切的表型可能不是必需的,甚至不是确定相似的基因是否影响两种物种之间一系列与酒精相关行为的最佳方法。

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