期刊
GENES BRAIN AND BEHAVIOR
卷 7, 期 6, 页码 690-697出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1601-183X.2008.00407.x
关键词
expression; polymorphism; primate; serotonin; variation
资金
- NCRR NIH HHS [RR00168] Funding Source: Medline
- NIAAA NIH HHS [AA016194] Funding Source: Medline
- NIDA NIH HHS [DA021180, DA06303, DA016606] Funding Source: Medline
- NIMH NIH HHS [MH082507] Funding Source: Medline
The serotonin system underlies a wide variety of behavioral traits and its dysregulation is the cause of numerous neuropsychiatric disorders. Among genes involved in the system, the serotonin transporter (SERT) is integral and has been repeatedly shown to be associated with disease as well as being a primary drug target. In addition to promoter region variation, we identify here variation in a regulatory region in the 3' untranslated region (UTR) of the SERT gene in both humans and rhesus macaques. We comprehensively survey the 3' UTR of SLC6A4 in Indian-origin rhesus macaques to identify three single nucleotide polymorphisms (SNPs) creating two haplotypes, both derived from an ancestral sequence, that represent the vast majority of the alleles in the population. Through the use of a luciferase reporter gene assay, we are able to show that not only do these alleles have differential effects on gene expression, modulated through changes in messenger RNA stability, but that different commonly occurring SNPs in the human 3' UTR also have similar effects. This finding not only offers additional insight into the regulation, and thus dysregulation, of SERT expression, but also suggests the role of natural selection in maintaining both high and low SERT expression levels broadly across populations of multiple primate species.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据