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. 2009 Sep-Oct;6(4):412-25.
doi: 10.4161/rna.6.4.8830. Epub 2009 Sep 23.

Comprehensive analysis of the impact of SNPs and CNVs on human microRNAs and their regulatory genes

Shiwei Duan  1 , Shuangli Mi, Wei Zhang, M Eileen Dolan
Affiliations

Comprehensive analysis of the impact of SNPs and CNVs on human microRNAs and their regulatory genes

Shiwei Duan et al. RNA Biol. 2009 Sep-Oct.

Abstract

Human microRNAs (miRNAs) are potent regulators of gene expression and thus involved in a broad range of biological processes. The objective of this study was to update the properties of human miRNAs and to search for SNPs and CNVs with potential effects on them. Based on the miRBase 13.0 database, we identified 380 (53.9%) precursor miRNAs (pre-miRNAs) embedded in gene loci that are enriched in biological processes such as "neuronal activities", "cell cycle" and "protein phosphorylation" (Bonferroni p < 0.05). Gene lengths of the pre-miRNA host genes are significantly larger than other genes in the genome (p < 2.2E-16). Using data mining public resources, we performed a genome-scale search for the regulatory polymorphisms in the loci of pre-miRNAs and their related genes. Altogether, we found 187 SNPs in the pre-miRNAs, 497 consensus SNPs in the seed-matching untranslated regions of target genes, 385 CNVs harboring pre-miRNA precursors and 9 CNVs covering important miRNA processing genes. We also noticed that minimum free energy changed by pre-miRNA-residing SNPs could be ranked by the order from low to high as the SNPs in the loop domain, the SNPs in the adjacent stem and basal stem domains, and the SNPs in mature miRNA and its complementary sequence domains (p = 0.0065). With a full list of miRNA-related polymorphisms, this study will facilitate future association studies between the genetic polymorphisms in miRNA targets or pre-miRNAs and the disease susceptibility or therapeutic outcome.

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Figures

Figure 1
Figure 1
Genomic distribution of the pre-miRNAs in humans. The ticks in the right of ideogram are the locations of pre-miRNAs. The darker bands in the ideogram are AT-rich, while the lighter bands are GC-rich.
Figure 2
Figure 2
Gene length comparison between all PCGs and miRNA host PCGs.
Figure 3
Figure 3
(A) SNP densities in the human pre-miRNA loci. (B) MFE changes in miRNA domains.
Figure 4
Figure 4
miRNA process pathway. The figure is recreated according to refs.,,–,
See this image and copyright information in PMC

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