Simultaneous genotyping of multiple polymorphisms in human serotonin transporter gene and detection of novel allelic variants.
Simultaneous genotyping of multiple polymorphisms in human serotonin transporter gene and detection of novel allelic variants.
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DOI：
10.1038/tp.2011.34
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发表时间：
2011-08-16
影响因子：
6.8
通讯作者：
O'Kane DJ
中科院分区：
文献类型：
--
作者：
Avula R;Rand A;Black JL;O'Kane DJ
5-羟色胺转运蛋白，称为SLC 6A 4，SERT或5-HTT，通过从突触能神经元的突触中去除5-羟色胺来调节神经传递，促进5-羟色胺再摄取到突触前末梢。选择性5-羟色胺再摄取抑制剂阻断5-羟色胺转运体的作用，用于治疗抑郁症和其他神经精神疾病。5-HTT基因的三种多态性与治疗反应和神经精神疾病有关。一个44-bp的启动子插入/缺失多态性（5-HTTLPR）主要产生长和/或短等位基因，这是由于14（短）或16（长）重复的保守的20-23 bp单位。还暗示，内含子2中发现的17-18 bp可变数目串联重复（StIn 2）表示为具有9、10或12个重复的三等位基因含量（StIn2.9、StIn2.10或StIn2.12）。最后，位于启动子多态性连锁区域内的单核苷酸多态性rs 25531改变了长启动子等位基因的功能。我们开发了一种基于PCR的片段分析方法，该方法在ABI测序仪上进行分析，因此我们能够同时检测所有三种基因型。使用该技术，我们鉴定了新的序列，其显示启动子重复区域包含（1）具有rs 25531 A/G多态性的17个重复，（2）两个具有18个重复单元，（3）一个具有20个重复单元和（4）24个重复序列。通过凝胶纯化的扩增子的直接测序证实了新的重复序列。
The serotonin transporter, called SLC6A4, SERT or 5-HTT, modulates neurotransmission by removal of serotonin from the synapse of serotonergic neurons, facilitating serotonin reuptake into the presynaptic terminus. Selective serotonin reuptake inhibitors block the action of the serotonin transporter and are used to treat depression and other neuropsychiatric disorders. Three polymorphisms in the 5-HTT gene have been implicated in treatment response and neuropsychiatric disorders. A 44-bp promoter ins/del polymorphism (5-HTTLPR) produces primarily long and/or short alleles due to either 14 (short) or 16 (long) repeats of variably conserved 20–23 bp units. Also implicated, a 17–18 bp variable number tandem repeat found in intron2 (StIn2) is expressed as triallelic content with 9, 10, or 12 repeats (StIn2.9, StIn2.10 or StIn2.12). Finally, a single nucleotide polymorphism rs25531 located within the promoter polymorphic-linked region alters the function of the long promoter allele. We developed a PCR-based fragment analysis assay, which is analyzed on an ABI sequencer, whereby we are able to detect all three genotypes simultaneously. Using this technique, we identified novel sequences, which demonstrate promoter repeat regions containing (1) a 17 repeat with rs25531 A/G polymorphism, (2) two with 18-repeat units, (3) one with 20-repeat units and (4) a 24-repeat sequence. The novel repeats were confirmed by direct sequencing of gel-purified amplicons.
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