%0 Journal Article
%T In Silico profiling of deleterious amino acid substitutions of potential pathological importance in haemophlia A and haemophlia B
%A George Priya Doss C
%J Journal of Biomedical Science
%D 2012
%I BioMed Central
%R 10.1186/1423-0127-19-30
%X We performed an in silico analysis of deleterious mutations and their protein structure changes in order to analyze the correlation between mutation and disease. Deleterious nsSNPs were categorized based on empirical based and support vector machine based methods to predict the impact on protein functions. Furthermore, we modeled mutant proteins and compared them with the native protein for analysis of protein structure stability.Out of 510 nsSNPs in F8, 378 nsSNPs (74%) were predicted to be 'intolerant' by SIFT, 371 nsSNPs (73%) were predicted to be 'damaging' by PolyPhen and 445 nsSNPs (87%) as 'less stable' by I-Mutant2.0. In F9, 129 nsSNPs (78%) were predicted to be intolerant by SIFT, 131 nsSNPs (79%) were predicted to be damaging by PolyPhen and 150 nsSNPs (90%) as less stable by I-Mutant2.0. Overall, we found that I-Mutant which emphasizes support vector machine based method outperformed SIFT and PolyPhen in prediction of deleterious nsSNPs in both F8 and F9.The models built in this work would be appropriate for predicting the deleterious amino acid substitutions and their functions in gene regulation which would be useful for further genotype-phenotype researches as well as the pharmacogenetics studies. These in silico tools, despite being helpful in providing information about the nature of mutations, may also function as a first-pass filter to determine the substitutions worth pursuing for further experimental research in other coagulation disorder causing genes.Hereditary haemophilias are the most frequently encountered recessive inherited disease of coagulation disorders in blood. Haemophilia A and Haemophilia B are X-linked inherited bleeding disorder caused by a decreased activity or lack of coagulation factor VIII cofactor activity (haemophilia A) or coagulation factor IX enzyme activity (haemophilia B) due to heterogenous mutations in the F8 and F9 coding gene [1,2]. Factor VIII is a protein cofactor with no enzyme activity that, when activated, form
%K In silico
%K F8
%K F9
%K Haemophilia A
%K Haemophilia B
%U http://www.jbiomedsci.com/content/19/1/30