Polymorphism studies on microRNA targetome of thalassemia.

Hamid Galehdari,Mohammad Shafiei,Mehdi Bijanzadeh,Seyedeh Zohreh Azarshin

doi:10.6026/97320630014252

Hamid Galehdari, Mohammad Shafiei + Show 2 more

Open Access

https://doi.org/10.6026/97320630014252

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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.

Highlights

Thalassemia is one of the most frequent inherited blood disorders with an autosomal recessive inheritance in the world. βthalassemia is the result of decreased or complete absence of βglobin chain expression, leading to the imbalances of α/β rate
In order to make sure that the candidate genes are expressed in the affected tissues in thalassemia, the expression profile of each gene was obtained from TIGER
Extraction of gene expression profile: The expression profile of candidate genes was retrieved from TiGER (Tissue-specific Gene Expression and Regulation)

Summary

Introduction

Thalassemia is one of the most frequent inherited blood disorders with an autosomal recessive inheritance in the world. βthalassemia is the result of decreased or complete absence of βglobin chain expression, leading to the imbalances of α/β rate. Prediction of clinical severity in β-thalassemia intermedia patients is difficult due to some genetic factors that have been identified as modifying factors [2]. These factors cause phenotypic diversity, such as severity of anemia, bone marrow hyperplasia, need to blood transfusion and splenectomy requirements [3]. The third modifiers are variations that occur outside the globin gene cluster. These variations can affect bone, iron and bilirubin metabolism [3]. The free-alpha globin chains and iron overload can produce elevated levels of reactive oxygen species (ROS), resulting in oxidative stress in β-thalassemia. The COLIA1 gene plays a major role in osteoporosis and has associated with low BMD in TM patients [8]

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