title: A Large-Scale Analysis of the Relationship of Synonymous SNPs Changing MicroRNA Regulation with Functionality and Disease.
abstract: Historically, owing to not changing amino acid composition of protein sequences, synonymous mutations are commonly assumed to be neutral during evolution and therefore have no effect on the phenotype and disease. Here, based on observations from large-scale analysis of genomic data, we predicted the putative synonymous SNPs that could result in functional consequences and disease risk through changing the microRNA-mediated gene regulation. We found that nearly half of the synonymous SNPs could affect protein expression by changing microRNA regulation in human genome and these SNPs significantly prefer to be associated with human diseases and traits. The synonymous SNPs changing microRNA-mediated gene regulation tend to be more under recent positive selection, prefer to affect gene expression, and implicate in human disease. We conclude that the miRNA-mediated regulation changes could be a potential mechanism for the contributions of synonymous SNPs to protein functions and disease risks.
authors.affiliation: Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing 100191, China. wangyuchen@bjmu.edu.cn.|Center for Noncoding RNA Medicine, Peking University Health Science Center, Beijing 100191, China. wangyuchen@bjmu.edu.cn.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing 100191, China. qiuchengxiang@bjmu.edu.cn.|Center for Noncoding RNA Medicine, Peking University Health Science Center, Beijing 100191, China. qiuchengxiang@bjmu.edu.cn.
authors.forename: Chengxiang
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing 100191, China. cuiqinghua@bjmu.edu.cn.|Center for Noncoding RNA Medicine, Peking University Health Science Center, Beijing 100191, China. cuiqinghua@bjmu.edu.cn.|MOE Key Lab of Molecular Cardiovascular Science, Peking University, Beijing 100191, China. cuiqinghua@bjmu.edu.cn.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Cui
mesh_terms: D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D035683:MicroRNAs
keywords: functionality; microRNA; synonymous SNP