Genome-Wide Analysis of MicroRNA-related Single Nucleotide Polymorphisms (SNPs) in Mouse Genome

Gideon Omariba,Maochun Wang,Yuxun Zhou,Kai Li,Junhua Xiao,Fuyi Xu

doi:10.1038/s41598-020-62588-6

Abstract

MicroRNAs are widely referred to as gene expression regulators for different diseases. The integration between single nucleotide polymorphisms (SNPs) and miRNAs has been associated with both human and animal diseases. In order to gain new insights on the effects of SNPs on miRNA and their related sequences, we steadily characterized a whole mouse genome miRNA related SNPs, analyzed their effects on the miRNA structural stability and target alteration. In this study, we collected 73643859 SNPs across the mouse genome, analyzed 1187 pre-miRNAs and 2027 mature miRNAs. Upon mapping the SNPs, 1700 of them were identified in 702 pre-miRNAs and 609 SNPs in mature miRNAs. We also discovered that SNP densities of the pre-miRNA and mature miRNAs are lower than the adjacent flanking regions. Also the flanking regions far away from miRNAs appeared to have higher SNP density. In addition, we also found that transitions were more frequent than transversions in miRNAs. Notably, 841 SNPs could change their corresponding miRNA’s secondary structure from stable to unstable. We also performed target gain and loss analysis of 163 miRNAs and our results showed that few miRNAs remained unchanged and many miRNAs from wild mice gained target site. These results outline the first case of SNP variations in the mouse whole genome scale. Those miRNAs with changes in structure or target could be of interest for further studies.

Highlights

Single nucleotide polymorphism (SNP) is one of the most common genetic variations in a genome[12]
We discovered that SNP densities of the pre-miRNA and mature miRNAs are lower than the adjacent flanking regions
The results depict a significant change in miRNA target interaction in the miRNA seed region. These results outline the first case of SNP variations in the whole mice genome, which creates a better platform for further analysis and applications on human disease

Summary

Introduction

Single nucleotide polymorphism (SNP) is one of the most common genetic variations in a genome[12]. These SNPs can effectually cause target alterations and gene expression interference[17] To date, it has been reported by a number studies that SNPs in miRNAs genes or in the target site are involved in complex traits and diseases[18,19,20,21,22,23,24,25]. A number of lines of inbred mice with several isolated mutations have been established This has enriched genetic diversity and alterations giving light to mammalian biology and human disease at large[26,27]. The results depict a significant change in miRNA target interaction in the miRNA seed region These results outline the first case of SNP variations in the whole mice genome, which creates a better platform for further analysis and applications on human disease. We discovered that out of the 1700 SNPs, 609 of them are located in 4624 mature miRNAs while 173 of them are located in 163 seed regions of the miRNA (Table 1)

Methods

Findings

Conclusion