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Effects of genetic variations on microRNA: target interactions.

Liu C, Rennie WA, Carmack CS, Kanoria S, Cheng J, Lu J, Ding Y - Nucleic Acids Res. (2014)

Bottom Line: We perform a transcriptome-scale analysis of genetic variants and miRNA:target interactions identified by CLASH.Furthermore, an overwhelming majority of genetic variants within or near miRNA binding sites can alter not only the potential of miRNA:target hybridization but also the structural accessibility of the binding sites and flanking regions.Our data will be valuable for discovering new associations among miRNAs, genetic variations and human diseases.

View Article: PubMed Central - PubMed

Affiliation: Wadsworth Center, New York State Department of Health, Center for Medical Science, 150 New Scotland Avenue, Albany, NY 12208, USA.

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The histograms of effect measures for common (MAF ≥1%) and rare (MAF <1%) SNPs in 25-nt blocks upstream or downstream of miRNA binding sites. (A) ΔΔGtotal for SNPs upstream of sites; (B) ΔΔGtotal for SNPs downstream of sites; (C) Δsite_access for SNPs upstream of sites; (D) Δsite_access for SNPs downstream of sites; (E) Δupstream_access for SNPs upstream of sites; (F) Δupstream_access for SNPs downstream of sites; (G) Δdownstream_access for SNPs upstream of sites; (H) Δdownstream_access for SNPs downstream of sites.
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Figure 3: The histograms of effect measures for common (MAF ≥1%) and rare (MAF <1%) SNPs in 25-nt blocks upstream or downstream of miRNA binding sites. (A) ΔΔGtotal for SNPs upstream of sites; (B) ΔΔGtotal for SNPs downstream of sites; (C) Δsite_access for SNPs upstream of sites; (D) Δsite_access for SNPs downstream of sites; (E) Δupstream_access for SNPs upstream of sites; (F) Δupstream_access for SNPs downstream of sites; (G) Δdownstream_access for SNPs upstream of sites; (H) Δdownstream_access for SNPs downstream of sites.

Mentions: The histograms of ΔΔGtotal for common and rare SNPs in upstream regions are shown in Figure 3A. Among common SNPs, 24.2% decrease and 21.5% increase the hybridization potential by at least 1 kcal/mol. A similar histogram is also shown for the rare SNPs. The results are similar for the downstream regions (Figure 3B). By varying the change in the total hybridization energy, we also present cumulative distributions of absolute value of ΔΔGtotal for common and rare variants in the flanking regions of miRNA binding sites (Supplementary Figure S3A and B). Overall, about half of the SNPs in the flanking regions of miRNA binding sites can alter the potential of the miRNA:target hybridization by at least 1 kcal/mol, and by over 10 kcal/mol in some cases. The nearly symmetric distributions indicate that these SNPs are nearly equally likely to decrease or increase miRNA:target hybridization potential. Furthermore, the histograms have heavier weights in the center than those in Figure 2B, indicating that the effects of variants outside miRNA binding sites are more moderate than those within the binding sites.


Effects of genetic variations on microRNA: target interactions.

Liu C, Rennie WA, Carmack CS, Kanoria S, Cheng J, Lu J, Ding Y - Nucleic Acids Res. (2014)

The histograms of effect measures for common (MAF ≥1%) and rare (MAF <1%) SNPs in 25-nt blocks upstream or downstream of miRNA binding sites. (A) ΔΔGtotal for SNPs upstream of sites; (B) ΔΔGtotal for SNPs downstream of sites; (C) Δsite_access for SNPs upstream of sites; (D) Δsite_access for SNPs downstream of sites; (E) Δupstream_access for SNPs upstream of sites; (F) Δupstream_access for SNPs downstream of sites; (G) Δdownstream_access for SNPs upstream of sites; (H) Δdownstream_access for SNPs downstream of sites.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150780&req=5

Figure 3: The histograms of effect measures for common (MAF ≥1%) and rare (MAF <1%) SNPs in 25-nt blocks upstream or downstream of miRNA binding sites. (A) ΔΔGtotal for SNPs upstream of sites; (B) ΔΔGtotal for SNPs downstream of sites; (C) Δsite_access for SNPs upstream of sites; (D) Δsite_access for SNPs downstream of sites; (E) Δupstream_access for SNPs upstream of sites; (F) Δupstream_access for SNPs downstream of sites; (G) Δdownstream_access for SNPs upstream of sites; (H) Δdownstream_access for SNPs downstream of sites.
Mentions: The histograms of ΔΔGtotal for common and rare SNPs in upstream regions are shown in Figure 3A. Among common SNPs, 24.2% decrease and 21.5% increase the hybridization potential by at least 1 kcal/mol. A similar histogram is also shown for the rare SNPs. The results are similar for the downstream regions (Figure 3B). By varying the change in the total hybridization energy, we also present cumulative distributions of absolute value of ΔΔGtotal for common and rare variants in the flanking regions of miRNA binding sites (Supplementary Figure S3A and B). Overall, about half of the SNPs in the flanking regions of miRNA binding sites can alter the potential of the miRNA:target hybridization by at least 1 kcal/mol, and by over 10 kcal/mol in some cases. The nearly symmetric distributions indicate that these SNPs are nearly equally likely to decrease or increase miRNA:target hybridization potential. Furthermore, the histograms have heavier weights in the center than those in Figure 2B, indicating that the effects of variants outside miRNA binding sites are more moderate than those within the binding sites.

Bottom Line: We perform a transcriptome-scale analysis of genetic variants and miRNA:target interactions identified by CLASH.Furthermore, an overwhelming majority of genetic variants within or near miRNA binding sites can alter not only the potential of miRNA:target hybridization but also the structural accessibility of the binding sites and flanking regions.Our data will be valuable for discovering new associations among miRNAs, genetic variations and human diseases.

View Article: PubMed Central - PubMed

Affiliation: Wadsworth Center, New York State Department of Health, Center for Medical Science, 150 New Scotland Avenue, Albany, NY 12208, USA.

Show MeSH