Abstract:
Endometriosis is the growth of ectopic endometrial tissue outside of the uterine cavity. Uterine
leiomyomas are non-cancerous tumors that grow from the walls of the uterus. The diseases effect
women worldwide and can cause extreme discomfort and severe pain. The involvement of the
ESR1 and WNT4 genes has been reported in both the diseases. Since SNPs are the most common
type of genetic variation among individuals, this study aims to identify the most damaging or the
most functionally significant non-synonymous SNPs of ESR1 and WNT4. The rs_IDs of ESR1
and WNT4 were retrieved from Ensembl and categorized as deleterious and non-deleterious
through different bioinformatics tools. The deleterious SNPs, which were 7 out of the total 22
SNPs retrieved for WNT4, and 2 of the 13 missense SNPs initially retrieved for ESR1 were then
further studied in terms of protein stability, their conservation analysis, the properties of the
mutant residue, and the predicted effect of the substitution on protein structure. HOPE found 4
SNPs, of WNT4 for which the mutant residue was of different properties than the wild-type,
however, as per the available data, no SNP of ESR1 differed greatly in properties from the wild type residue. Through conservation analysis, and the predicted effect of the substitution on
protein structure, 1 SNP of each gene was labelled as the most-damaging. These results need to
be further validated by wet-lab testing. This would lead to the development of better diagnostic
techniques and better treatment options by personalized medication.
