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. 2016 Jan 29;11(1):e0147702.
doi: 10.1371/journal.pone.0147702. eCollection 2016.

In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene

Sayed AbdulAzeez  1 , J Francis Borgio  1
Affiliations

In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene

Sayed AbdulAzeez et al. PLoS One. .

Abstract

Background: α-Thalassemia (α-thal) is a genetic disorder caused by the substitution of single amino acid or large deletions in the HBA1 and/or HBA2 genes.

Method: Using modern bioinformatics tools as a systematic in-silico approach to predict the deleterious SNPs in the HBA1 gene and its significant pathogenic impact on the functions and structure of HBA1 protein was predicted.

Results and discussion: A total of 389 SNPs in HBA1 were retrieved from dbSNP database, which includes: 201 non-coding synonymous (nsSNPs), 43 human active SNPs, 16 intronic SNPs, 11 mRNA 3' UTR SNPs, 9 coding synonymous SNPs, 9 5' UTR SNPs and other types. Structural homology-based method (PolyPhen) and sequence homology-based tool (SIFT), SNPs&Go, PROVEAN and PANTHER revealed that 2.4% of the nsSNPs are pathogenic.

Conclusions: A total of 5 nsSNPs (G60V, K17M, K17T, L92F and W15R) were predicted to be responsible for the structural and functional modifications of HBA1 protein. It is evident from the deep comprehensive in-silico analysis that, two nsSNPs such as G60V and W15R in HBA1 are highly deleterious. These "2 pathogenic nsSNPs" can be considered for wet-lab confirmatory analysis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Graphic illustration of bioinformatic tools used for the precise identification of the most deleterious nsSNPs of HBA1 gene.
Fig 2
Fig 2. Prediction matching to the highly pathogenic nsSNPs of HBA1 gene.
The 2 highly pathogenic nsSNPs are having the scores: Polyphen >0.9; Panther >0.55; SNPs&Go >0.8; SIFT = 0; PROVEAN < -8; mCSM < -0.1; SNAP2 >65.
Fig 3
Fig 3. A: Comparing the secondary structure of the mutated and native HBA1 protein. B: Ramachandran plot of constructed HBA1 protein. Most of the amino acid residues were in the most favored region. C: Protein binding regions in the secondary structure of HBA1 protein. D: States of the secondary structure. E: Eight class Secondary structure of HBA1 protein by RaptorX.
Fig 4
Fig 4. Super imposed 3D structures of the native and highly deleterious mutated HBA1 proteins.
See this image and copyright information in PMC

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