Computational Analysis of the Coding Single Nucleotide Polymorphisms of Disrupted in Schizophrenia 1 (DISC 1) Gene

Bipolar disorder is one of the major psychiatric disorders that are still left unexplored on the genetic level. One of the major genes that play an important role in the onset of this illness is DISC1 (disrupted in schizophrenia 1) located on chromosome 1.42q. The focus of the study was Single Nucleotide Polymorphisms (SNPs) to understand the biological basis of complex traits and diseases as the Genetics of human phenotype variation could be understood by knowing the functions of SNPs. We applied an evolutionary perspective to screen the SNPs using a sequence homology-based SIFT tool, which suggested that 9 nsSNPs (38%) were found to be deleterious of 24 coding SNPs. The structure based approach PolyPhen server suggested that 13 nsSNPs (55%) may disrupt protein function and structure along with software Panther stating 4 nsSNPs (17%) above the damage threshold. The PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Finally the mutational risk analysis of the deleterious SNPs was performed using FastSNP server. The further study can be done on the structural modeling of DISC1 and analyze the structural changes that these damaging mutations can probably cause.