Prediction of deleterious single nucleotide polymorphisms and their effect on the sequence and structure of the human gene.

OBJECTIVE

The gene expresses a protein, G1/S-specific cyclin, that regulates the G1/S transition in the cell cycle and also inhibits retinoblastoma (RB) proteins. Overexpression or rearrangements of this gene can result in various tumours. This study aimed to identify possible deleterious non-synonymous single nucleotide polymorphisms (SNP's) of using computational methods.

METHODS

SNPs in the human gene were retrieved from dbSNP. These SNPs were screened by the Sorting Intolerant From Tolerant (SIFT) algorithm and the PredictSNP classification. Mutants with deleterious SNPs were built using Discovery Studio 3.5, and dynamics studies were performed on native and mutant varieties.

RESULTS

In , 1194 SNPs were found, of which 94 were missense and 2 were nonsense SNPs. Three SNPs were found to be deleterious. Molecular dynamics and trajectory analysis showed that there was a significant deviation of the root mean square deviation (RMSD) values in the N216K mutant from the values of the native protein.

CONCLUSION

Based on this study, we propose that the SNP with SNP ID rs112525097 (NM_053056.2:c.648C>G) might cause aberrations in , which might lead to a change in the function of the G1/S-specific cyclin protein. This, in turn, may lead to the development of acute myeloid leukaemia (AML).