P-85: How a Frame Shift Caused by a Single Base Deletion In SEPT12 Gene Shed Lights As a Polymorphism

Background: Septins are members of highly conserved polymerizing GTP binding proteins well described in the animal kingdom. 14 Septin proteins have been characterized in humans (SEPT1-SEPT14), some of which are tissue-specific. All of 14 genome-mapped human septins contain a highly conserved central GTP-binding domain which is very critical in GTPase signaling properties as well as oligomerization between septins and other filamentous proteins. Among all Septins, SEPT12 is characteristically expressed in testis tissue of adults, and the coding gene of this protein is recently reported as a critical gene for spermatogenesis. There are three major functional areas in SEPT12, named coding regions G1, G3 and G4, which form the active site of the protein for binding to GTP. Materials and Methods: Computational study of the polymorphisms of SEPT12 showing that an SNP in the position [001154458.1:c.521.522insG] theoretically causes a frame shift in the coding region of the gene, creating a stop codon after the active region G4. In an ongoing effort to analyze the biochemical consequence of this alteration in the protein structure of SEPT12, we compared the 3-D structures of the normal and the truncated proteins using Swiss-Pdb Viewer software. Results: Our data shows that this alteration in the primary amino acid sequence of SEPT12 is in the way that the 3-D structure of the truncated protein mimics the active structure in the normal SEPT12 molecule. Conclusion: This computational analysis shows that how a frame-shift genetic alteration can be considered as a polymorphism in the nature.