title: Computational refinement of functional single nucleotide polymorphisms associated with ATM gene.
abstract: BACKGROUND
  Understanding and predicting molecular basis of disease is one of the major challenges in modern biology and medicine. SNPs associated with complex disorders can create, destroy, or modify protein coding sites. Single amino acid substitutions in the ATM gene are the most common forms of genetic variations that account for various forms of cancer. However, the extent to which SNPs interferes with the gene regulation and affects cancer susceptibility remains largely unknown.
  
  
  RESULTS
  We analyzed the deleterious nsSNPs associated with ATM gene based on different computational methods. An integrative scoring system and sequence conservation of amino acid residues was adapted for a priori nsSNP analysis of variants associated with cancer. We further extended our approach on SNPs that could potentially influence protein Post Translational Modifications in ATM gene.
  
  
  CONCLUSIONS
  In the lack of adequate prior reports on the possible deleterious effects of nsSNPs, we have systematically analyzed and characterized the functional variants in both coding and non coding region that can alter the expression and function of ATM gene. In silico characterization of nsSNPs affecting ATM gene function can aid in better understanding of genetic differences in disease susceptibility.
authors.affiliation: Centre for Nanobiotechnology, Medical Biotechnology Division, School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India. georgepriyadoss@vit.ac.in
authors.forename: C
authors.initials: C
authors.lastname: George Priya Doss
authors.forename: B
authors.initials: B
authors.lastname: Rajith
mesh_terms: D000595:Amino Acid Sequence; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases