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

Backgroundα-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.MethodUsing 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 DiscussionA 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.ConclusionsA 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 G60Vand W15R in HBA1 are highly deleterious. These “2 pathogenic nsSNPs” can be considered for wet-lab confirmatory analysis.