Genome-Wide Identification of SNPs in MicroRNA Genes and the SNP Effects on MicroRNA Target Binding and Biogenesis

被引:309
作者
Gong, Jing [1 ,2 ]
Tong, Yin [1 ]
Zhang, Hong-Mei [1 ]
Wang, Kai [3 ]
Hu, Tao [1 ]
Shan, Ge [4 ]
Sun, Jun [2 ]
Guo, An-Yuan [1 ]
机构
[1] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Dept Syst Biol, Hubei Bioinformat & Mol Imaging Key Lab, Wuhan 430074, Peoples R China
[2] Huazhong Univ Sci & Technol, Dept Biochem & Mol Biol, Tongji Med Coll, Wuhan 430074, Peoples R China
[3] Shanghai Bioladder Co Ltd, Shanghai, Peoples R China
[4] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China
基金
中国国家自然科学基金;
关键词
miRNASNP; database; target loss and gain; frequency; SINGLE NUCLEOTIDE POLYMORPHISM; COMPREHENSIVE DATABASE; UNTRANSLATED REGION; PREDICTION; SITE; ASSOCIATION; RESOURCE; COMPLEMENTARY; EXPRESSION; MECHANISM;
D O I
10.1002/humu.21641
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
MicroRNAs (miRNAs) are studied as key regulators of gene expression involved in different diseases. Several single nucleotide polymorphisms (SNPs) in miRNA genes or target sites (miRNA-related SNPs) have been proved to be associated with human diseases by affecting the miRNA-mediated regulatory function. To systematically analyze miRNA-related SNPs and their effects, we performed a genome-wide scan for SNPs in human pre-miRNAs, miRNA flanking regions, target sites, and designed a pipeline to predict the effects of them on miRNA-target interaction. As a result, we identified 48 SNPs in human miRNA seed regions and thousands of SNPs in 3' untranslated regions with the potential to either disturb or create miRNA-target interactions. Furthermore, we experimentally confirmed seven loss-of-function SNPs and one gain-of-function SNP by luciferase assay. This is the first case of experimental validation of an SNP in an miRNA creating a novel miRNA target binding. All useful data were complied into miRNASNP, a user-friendly free online database (http://www.bioguo.org/miRNASNP/). These data will be a useful resource for studying miRNA function, identifying disease-associated miRNAs, and further personalized medicine. Hum Mutat 33: 254-263, 2012. (C) 2011 Wiley Periodicals, Inc.
引用
收藏
页码:254 / 263
页数:10
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