Bioinformatics Analyses of Single Nucleotide Polymorphism rs۲۲۹۳۰۲۴ in TDGF۱ growth factor gene in Congenital Heart Disease

Background and Aim: Congenital heart disease (CHD) is the most common birth defect and is the most prevalent non-infectious cause of infant death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart. Congenital heart defects can be attributed to a variety of large chromosomal structures or single gene mutations that cause monogenic syndromes. The target gene in this study is TDGF۱. It encodes an epidermal growth factor-dependent protein that encodes the Cripto, FRL-۱, and Cryptic domain. The encoded protein is an extracellular and membrane signaling protein and plays an important role in fetal and tumor growth. Mutations in this gene are associated with brain defects. TDGF۱ growth factor is located in ۳p۲۱.۳۱. This gene has ۷ exons and ۲ isoforms. Alternative splicing proses results in multiple transcript variants. ۲۶۹۶ SNPs are reported for TDGF۱ gene until now. Rs۲۲۹۳۰۲۴ of the TDGF۱ gene is located in coding region and is a missense mutation (G>A,C). In this study, we analyzed pathogenicity effects of this SNP in TDGF۱ gene.Methods: In this study, we analyzed pathogenicity effects of this SNP in TDGF۱ gene by SIFT (is a server that predicts the replacement of the amino acids that affects on protein function) Polyphen۲ (is a tool for annotating coding non-synonymous SNPs), I-mutant۲.۰ (is a tool for prediction of protein stability changes upon single point mutation) and MUpro (is a tool for predicting energy changes that will ultimately reduce or increase protein stability) prediction databases.Results: SIFT database predicted that rs۲۲۹۳۰۲۴ effects on the protein function. Polyphen۲ database is predicted this SNP probably damaging with a score of ۰.۹۵۸. I-mutant۲.۰ database is predicted this SNP decrease stability and MUpro is predicted that rs۲۲۹۳۰۲۴ decrease the stability of protein structure.Conclusion: In conclusion rs۲۲۹۳۰۲۴ of TDGF۱ gene reduces protein stability and probably associated with disease in humans.

Keywords:

Congenital Heart Defects , SNP , mutation , TDGF۱ , bioinformatics