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首页> 外文期刊>Journal of genetics >Population genetic variation of SLC6A4 gene, associated with neurophysiological development
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Population genetic variation of SLC6A4 gene, associated with neurophysiological development

机译：与神经生理学发育相关的SLC6A4基因的群体遗传变异

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The serotonin transporter 5-HTT is encoded by a single gene SLC6A4 . Polymorphisms in SLC6A4 has been associated with awide variety of neurological and psychiatric disorders including increased risk of posttraumatic stress disorder, higher likelihood fordepression, obsessive–compulsive disorder (OCD), increased hostility and criminal behaviour. Genes associated with complex diseasesoften exhibit strong signatures of purifying selection compared to others. Further, discernible population specific variation in the signatureof natural selection have been observed for several complex disease-related genes. In this project we aimed to investigate the populationgenetic variation of the serotonin transporter gene ( SLC6A4 ), focussing on the single nucleotide polymorphisms (SNPs). To this end, weemployed 2504 individuals around the globe available in 1000 Genome project Phase III data and classified them into five ethnic groups:Americans (AMR), Europeans (EUR), Africans (AFR), East Asians (EAS) and South Asians (SAS). Principal component analysis (PCA)performed on all annotated SNPs of SLC6A4 depicted clear clustering between Africans and the rest of the world along PC1, and EastAsians and other non-African populations along PC2. Further, these SNPs were found to be under strong selection pressure especiallyamong East Asian populations with significantly high positive cross-population extended haplotype homozygosity scores compared toAfricans, indicating that SLC6A4 has likely undergone a strong selective sweep among the East Asians in the recent past. Our study canpotentially explain the association between polymorphisms in SLC6A4 , and major depression and suicidal tendencies among people of EastAsian ancestry and the absence of such associations among people of European ancestry.
机译：血清素转运蛋白5-HTT由单个基因SLC6A4编码。 SLC6A4中的多态性已与神经系统和精神病疾病的似的多态性有关，包括增加创宫应激障碍的风险，较高的可能性毒性，强迫性疾病（OCD），敌对和犯罪行为增加。与复杂的疾病相关的基因表现出与他人相比纯化选择的强烈签名。此外，对于几种复杂的疾病相关基因，已经观察到自然选择特征的群体特异性变异。在该项目中，我们旨在探讨血清素转运蛋白基因（SLC6A4）的人口变异，侧重于单核苷酸多态性（SNP）。为此，在全球各地的2504个个人提供了1000个基因组项目III数据，并将其分为五个民族：美国人（AMR），欧洲人（EUR），非洲人（AFR），东亚人（EAS）和南亚人（ SAS）。在所有注释的SLC6A4中执行的主成分分析（PCA）描述了非洲人与PC1和沿PC2的驻地其他非洲群体之间的清晰聚类。此外，发现这些SNP受到强烈的选择压力，占多态度跨人群延长单倍型纯合理分数的大众东亚群体，表明SLC6A4可能在最近的过去的东亚人群中受到强烈的选择性扫描。我们的研究可以解释SLC6A4多态性之间的关联，以及驻地祖先人群中的主要抑郁和自杀趋势以及欧洲血统人群中的缺失。

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