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。