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用于识别酒精依赖易感性基因和治疗靶点的功能基因组学策略

Functional genomics strategies to identify susceptibility genes and treatment targets in alcohol dependence.

作者信息

Heilig Markus, Sommer Wolfgang

机构信息

Division of Psychiatry, NEUROTEC Department, Karolinska Institutet, M57 Huddinge University Hospital, S-141 86 Stockholm, Sweden.

出版信息

Neurotox Res. 2004;6(5):363-72. doi: 10.1007/BF03033310.

DOI:10.1007/BF03033310
PMID:15545019
Abstract

Genetic factors contribute to alcohol dependence through two main categories of mechanisms. The 50-60% heritability observed in this disorder is presumably conferred by polymorphic variants, encoding functionally altered proteins, or leading to differential transcriptional activity. Secondly, long term changes during the process of developing dependence are likely encoded by persistent changes in gene expression. Thus, genetic and environmental factors interact at the level of the transcriptome, making this an attractive level of analysis. For this purpose, we have applied differential display and more recently Affymetrix oligonucleotide gene arrays to models of genetic susceptibility and alcohol-induced neuroadaptation.

摘要

遗传因素通过两类主要机制导致酒精依赖。在这种疾病中观察到的50%-60%的遗传力可能由多态性变体赋予,这些变体编码功能改变的蛋白质,或导致转录活性差异。其次,在依赖形成过程中的长期变化可能由基因表达的持续变化编码。因此,遗传和环境因素在转录组水平上相互作用,使其成为一个有吸引力的分析层面。为此,我们已将差异显示技术以及最近的Affymetrix寡核苷酸基因芯片应用于遗传易感性和酒精诱导的神经适应模型。

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本文引用的文献

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Exploration, normalization, and summaries of high density oligonucleotide array probe level data.高密度寡核苷酸阵列探针水平数据的探索、标准化及汇总
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A temporal threshold for induction of persistent alcohol preference: behavioral evidence in a rat model of intermittent intoxication.诱导持续性酒精偏好的时间阈值:间歇性中毒大鼠模型的行为学证据
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Selective breeding, quantitative trait locus analysis, and gene arrays identify candidate genes for complex drug-related behaviors.
酒精成瘾及其他物质滥用障碍中的基因-环境相互作用:遗传力表现及影响易感性的因素
Neurotox Res. 2004;6(5):343-61. doi: 10.1007/BF03033309.
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alpha-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats.α-突触核蛋白定位于酒精偏好的数量性状基因座,并且在偏好酒精和不偏好酒精的大鼠中差异表达。
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A functional neuropeptide Y Leu7Pro polymorphism associated with alcohol dependence in a large population sample from the United States.一种与美国大量人群样本中的酒精依赖相关的功能性神经肽Y亮氨酸7脯氨酸多态性。
Arch Gen Psychiatry. 2002 Sep;59(9):825-31. doi: 10.1001/archpsyc.59.9.825.
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Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics.人类酗酒者额叶和运动皮层中的基因表达模式会发生改变。
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