1st International and 10th National Iranian Conference on Bioinformatics

In-silico analysis of a missense SNP (rs1805323 C>T) in human PMS2 gene

Paper ID : 1096-ICB10

Authors:

Sahar Yaqubi *

Abstract:

Research has shown that the endometrial cancer is the most common type of uterine cancer, affecting most often women over 55. The incidence rate of endometrial cancer is increasing rapidly, so much so that the cancer is estimated to increase by more than 50% worldwide by 2040. About 5% of endometrial cancers are linked to hereditary factors. One of the genes playing a significant role in endometrial cancer is PMS2. PMS2 (PMS1 homolog 2), which is located on chromosome 7p. It encodes a protein that functions to correct DNA mismatches and deletions that can occur during DNA replication and homologous recombination. There is, however, little experimental research into the relationship between SNPs occurring within the PMS2 and endometrial cancer. To address this gap, missense SNP and its FASTA sequence were first retrieved from NCBI. It was subsequently evaluated through the following seven software: SIFT, POLYPHEN-2, PORVERN, PhD-SNP, SNPs&GO, I-Mutant, and HOPE. The purpose was to determine whether the retrieved SNP affects the stability and functions of the protein encoded from the PMS2 gene. According to I-Mutant report, a decrease in the stability of the encoded protein happens during the single-nuclotid polymerization. HOPE confirms I-Mutant’s prediction that the wild-type residue is more hydrophobic than the mutant residue. While the mutant residue charge is positive, the wild-type residue charge was neutral. As to the functions of the encoded protein, SIFT predicts that this SNP deleteriously affects the protein function. HOPE confirms SIFT prediction: the mutated residue is located in a domain that is important for the main activity of the protein. Hence, the mutation of the residue might disturb this function. According to the results of this study, with the decrease in the stability and disturbance in the function of the protein in the uterine cells, the probability of endometrial cancer increases.

Keywords:

endometrial cancer; PMS2; single-nucleotide polymorphism (SNP); mutation effect prediction

Status : Paper Accepted (Poster Presentation)