Polymorphism studies on microRNA targetome of thalassemia

Abstract

Thalassemia is one of the most prevalent hemoglobin disorders. It is caused by the decreased or absent synthesis of one globin chain that leads to moderate to severe hemolytic anemia in clinical complications. Some genetic factors cause these phenotypic variations by the alteration of gene expression. MicroRNAs (miRNAs) are post-transcriptional regulators in gene expression. Therefore, variations in 3'-untranslated region (3'-UTR) of target genes may affect gene expression. It is of interest to evaluate the impact of noncoding SNPs in thalassemia related genes on miRNA: mRNA interactions in the severity of thalassemia. Polymorphisms that alter miRNA: mRNA interactions were predicted using PolymiRTS and Mirsnpscore tools. Then, the effect of predicted target SNPs on thermodynamic stability, local RNA structure and regulatory elements was investigated using RNAhybrid, RNAsnp and RegulomeDB, respectively. The molecular functions and the Biological process of candidate genes were extracted and interaction network was created. Forty-six SNPs were predicted to affect 188 miRNA interactions. These results suggest that 3'-UTR SNP may affect gene expression and cause phenotypic variation in thalassemia patients.

Keywords: MicroRNA; polymorphism; thalassemia.

Figure 1

The workflow of bioinformatics procedure in this study

Figure 2

(A) The plot of ΔMFEhybrid for miRNA:mRNA (target SNPs) interactions. (B) The distribution plot of dmax p-value for target- SNPs by RNAsnp web tool. Each SNP with dmax P-value < 0.2 is significant.

Figure 3

Network of gene-gene interaction derived from GeneMANIA. Circles with diagonal line represent the queried genes and circles without diagonal line represent mediated genes for interactions. These candidate genes represent co-expression, co-localization, predicted and physical interaction networks with themselves. some important functions of genes are shown with the color triangles in the circle: red triangle response to xenobiotic stimulus, blue triangle antioxidant activity, yellow triangle response to reactive oxygen species, violet triangle response to oxidative stress and green triangle response to toxic substance.