Genomic features of the human dopamine transporter gene and its potential epigenetic States: implications for phenotypic diversity.
Genomic features of the human dopamine transporter gene and its potential epigenetic States: implications for phenotypic diversity.
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DOI：
10.1371/journal.pone.0011067
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发表时间：
2010-06-10
期刊：
影响因子：
3.7
通讯作者：
Volkow ND
中科院分区：
文献类型：
--
作者：
Shumay E;Fowler JS;Volkow ND
人类多巴胺转运蛋白基因（DAT 1或SLC 6A 3）与各种脑相关疾病和行为特征相关，因此，在实验和临床环境中进行了深入研究。然而，大量的研究数据并没有阐明DAT调控的生物学机制;同样，DAT基因型-表型关联的研究也产生了不一致的结果。因此，我们对DAT蛋白产物的控制的理解是不完整的;拥有这些知识是至关重要的，因为DAT在大脑的多巴胺能回路中起着主要作用。因此，我们重新评估了SLC 6A 3基因的基因组属性，可能赋予调节的敏感性，假设其独特的基因组特征可能有助于高度动态，区域特异性DAT表达，从而实现多种调控模式。我们全面的生物信息学分析揭示了SLC 6A 3非常独特的基因组特征，包括其序列的高度个体间变异性（897个SNP，约90个重复序列和几个CNV在摘要中拼出了所有缩写），并对表观遗传机制的调节具有明显的敏感性，如GC偏好组成所示。（0.55）的SLC 6A 3，和许多基因内CpG岛（27 CGIs）。我们建议，这种独特的组合的基因组特征和监管属性，使差异表达的DAT 1基因，并满足看似矛盾的要求，其监管，即，鲁棒性的区域特异性表达和功能动力学。
Human dopamine transporter gene (DAT1 or SLC6A3) has been associated with various brain-related diseases and behavioral traits and, as such, has been investigated intensely in experimental- and clinical-settings. However, the abundance of research data has not clarified the biological mechanism of DAT regulation; similarly, studies of DAT genotype-phenotype associations yielded inconsistent results. Hence, our understanding of the control of the DAT protein product is incomplete; having this knowledge is critical, since DAT plays the major role in the brain's dopaminergic circuitry. Accordingly, we reevaluated the genomic attributes of the SLC6A3 gene that might confer sensitivity to regulation, hypothesizing that its unique genomic characteristics might facilitate highly dynamic, region-specific DAT expression, so enabling multiple regulatory modes. Our comprehensive bioinformatic analyzes revealed very distinctive genomic characteristics of the SLC6A3, including high inter-individual variability of its sequence (897 SNPs, about 90 repeats and several CNVs spell out all abbreviations in abstract) and pronounced sensitivity to regulation by epigenetic mechanisms, as evident from the GC-bias composition (0.55) of the SLC6A3, and numerous intragenic CpG islands (27 CGIs). We propose that this unique combination of the genomic features and the regulatory attributes enables the differential expression of the DAT1 gene and fulfills seemingly contradictory demands to its regulation; that is, robustness of region-specific expression and functional dynamics.
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影响因子：
4.2
作者：
Cruz-Muros, Ignacio;Afonso-Oramas, Domingo;Gonzalez-Hernandez, Tomas
通讯作者：
Gonzalez-Hernandez, Tomas
影响因子：
2.9
作者：
Burt, S. Alexandra;Mikolaiewski, Amy J.
通讯作者：
Mikolaiewski, Amy J.
影响因子：
30.8
作者：
Cooper, Gregory M.;Zerr, Troy;Kidd, Jeffrey M.;Eichler, Evan E.;Nickerson, Deborah A.
通讯作者：
Nickerson, Deborah A.
DOI：
10.1073/pnas.0902833106
发表时间：
2009-09-22
影响因子：
11.1
作者：
Chiaruttini, C.;Vicario, A.;Tongiorgi, E.
通讯作者：
Tongiorgi, E.
影响因子：
64.8
作者：
Cheng, Z;Ventura, M;Eichler, EE
通讯作者：
Eichler, EE