Computational Analysis of Protein Structure Changes as a Result of Nondeletion Insertion Mutations in Human β-Globin Gene Suggests Possible Cause of β-Thalassemia
Beta-thalassemia is described as a group of hereditary blood disorders characterized by abnormalities in the synthesis of beta chains of hemoglobin. These anomalies result in different phenotypes ranging from moderate to severe clinical symptoms to no symptoms at all. Most of the defects in hemoglob...
Main Authors: | , |
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Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2019-01-01
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Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2019/9210841 |
Summary: | Beta-thalassemia is described as a group of hereditary blood disorders characterized by abnormalities in the synthesis of beta chains of hemoglobin. These anomalies result in different phenotypes ranging from moderate to severe clinical symptoms to no symptoms at all. Most of the defects in hemoglobin arise directly from the mutations in the structural β-globin gene (HBB). Recent advances in computational tools have allowed the study of the relationship between the genotype and phenotype in many diseases including β-thalassemia. Due to high prevalence of β-thalassemia, these analyses have helped to understand the molecular basis of the disease in a better way. In this direction, a relational database, named HbVar, was developed in 2001 by a collective academic effort to provide quality and up-to-date information on the genomic variations leading to hemoglobinopathies and thalassemia. The database recorded details about each variant including the altered sequence, hematological defects, its pathology, and its occurrence along with references. In the present study, an attempt was made to investigate nondeletion mutations in the HBB picked up from HbVar and their effects using the in silico approach. Our study investigated 12 nucleotides insertion mutations in six different altered sequences. These 12 extra nucleotides led to the formation of a loop in the protein structure and did not alter its function. It appears that these mutations act as ‘silent’ mutations. However, further in vitro studies are required to reach definitive conclusions. |
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ISSN: | 2314-6133 2314-6141 |