In Silico Analysis on the Structural and Functional Impact of one deleterious SNP in nkx۲.۵ gene Associated with Congenital Heart Disease (CHD)

Publish Year: 1399
نوع سند: مقاله کنفرانسی
زبان: English
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CIGS16_122

تاریخ نمایه سازی: 14 اردیبهشت 1400

Abstract:

Background and Aim: The heart is the first organ that formed in the vertebrate embryo. Its function is to collect blood from the body and send it to the lungs and receive blood from the lungs and send it to the rest organs of the body. Congenital heart disease (CHD), a type of cardiovascular disease, is the most common birth defect and refers to a defect in heart structure or function from birth. The most common CHD is a ventricle septal defect (VSD). Various environmental and genetic factors are involved in this disease. About ۱,۷۰۰ genes involved in cardiac development have been reported. Genes with mutations in congenital heart disease include NKX۲.۵, GATA۴, and TBX۵, all of which interact with each other. NKX۲.۵ transcription factor, located in ۵q۳۵.۱, is crucial in guiding the mesoderm to become heart tissue and activates the synthesis of other transcription factors such as members of the GATA۴ and MEF۲ family. This gene is a member of the homeobox NK gene family that has been conserved throughout evolution. Mutations in this gene have been reported in different types of CHDs. NKX۲.۵ protein acts as a key regulator in cardiac morphogenesis. Nkx۲.۵ gene has ۱۸۲۲ SNPs until now which among them ۴۴ SNPs are pathogenic. Rs۷۲۵۵۴۰۲۸ of the nkx۲.۵ gene is located in ۳' UTR region and is a missense mutation.Methods: In this study, we analyzed pathogenicity effects of this SNP in nkx۲.۵ gene by SIFT (sorting intolerant from tolerant, is a tool for prediction of SNP effect 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 SWISS-MODEL (is a tool for examining the ۳D structure of proteins) prediction databases.Results: . SIFT database predicted that rs۱۰۴۸۹۴۰۷۳ effects on the protein function. Polyphen۲ database is predicted this SNP probably damaging. I-mutant۲.۰ database is predicted this SNP decrease stability and SWISS-MODEL is predicted that the three-dimensional structure of the mutant protein was significantly different from the normal protein.Conclusion: . In conclusion rs۷۲۵۵۴۰۲۸ of nkx۲.۵ gene reduces protein stability and probably associated with disease in humans.

Authors

Sajedeh Ghorbani

Department of Biology, Faculty of science, Yazd University, Yazd, Iran.

Mehri Khatami

Department of Biology, Faculty of science, Yazd University, Yazd, Iran.

Mohammad Mehdi Heidari

Department of Biology, Faculty of science, Yazd University, Yazd, Iran.