Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR:: Evidence from brain and lymphocytes using quantitative RT-PCR
Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR:: Evidence from brain and lymphocytes using quantitative RT-PCR
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DOI：
10.1002/ajmg.b.10948
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发表时间：
2002-12-08
期刊：
影响因子：
--
通讯作者：
Craig, I
中科院分区：
文献类型：
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作者：
Mill, J;Asherson, P;Craig, I
遗传关联研究提供了相当多的证据表明，多巴胺转运蛋白基因（DAT 1）的3 '-非翻译区（3'-UTR）中的可变数目串联重复序列（VNTR）的10-重复等位基因与一系列精神病表型相关，最显著的是注意缺陷多动障碍。这种关联的机制尚不清楚，尽管有几条证据表明基因表达存在变异。在这项研究中，我们测量DAT 1信使RNA水平在小脑，颞叶，淋巴细胞使用定量实时逆转录聚合酶链反应。相对于一组四个控制管家基因（β-肌动蛋白，GAPD，核糖体18 S和β 2-微球蛋白），我们观察到DAT 1表达水平的增加与10个重复等位基因的数量相关。这些数据提供了直接的证据表明，VNTR，或与VNTR连锁不平衡的另一种多态性，参与调节该基因的表达。(C)2002 Wiley-Liss，Inc.
Genetic association studies provide considerable evidence that the 10-repeat allele of a variable number tandem repeat (VNTR) in the 3'-untranslated region (3'-UTR) of the dopamine transporter gene (DAT1) is associated with a range of psychiatric phenotypes, most notably, attention deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study, we measured DAT1 messenger RNA levels in cerebellum, temporal lobe, and lymphocytes using quantitative real-time reverse-transcription polymerase chain reaction. Relative to a set of four control housekeeping genes (beta-actin, GAPD, ribosomal 18S, and beta2-microglobulin) we observed that increased levels of DAT1 expression were associated with the number of 10-repeat alleles. These data provide direct evidence that the VNTR, or another polymorphism in linkage disequilibrium with the VNTR, is involved in regulating expression of this gene. (C) 2002 Wiley-Liss, Inc.