title: In-Silico Computing of the Most Deleterious nsSNPs in HBA1 Gene.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Research and Medical Consultation (IRMC), University of Dammam, Dammam, Saudi Arabia.
authors.forename: Sayed
authors.initials: S
authors.lastname: AbdulAzeez
authors.affiliation: Institute for Research and Medical Consultation (IRMC), University of Dammam, Dammam, Saudi Arabia.
authors.forename: J Francis
authors.initials: JF
authors.lastname: Borgio
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D030541:Databases, Genetic; D006442:Glycated Hemoglobin / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007438:Introns; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D006442:Glycated Hemoglobin
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