Conceptualization of functional single nucleotide polymorphisms of polycystic ovarian syndrome genes: an in silico approach

Prabhu, BN and Kanchamreddy, SH and Sharma, AR and Bhat, SK and Bhat, Parvati V and Kabekkodu, Shama Prasada and Satyamoorthy, K and Rai, Padmalatha S (2021) Conceptualization of functional single nucleotide polymorphisms of polycystic ovarian syndrome genes: an in silico approach. Journal of Endocrinological Investigation, 44. pp. 1783-1793. ISSN 0391-4097

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Abstract

Purpose Polycystic ovarian syndrome (PCOS) is a multi-faceted endocrinopathy frequently observed in reproductive-aged females, causing infertility. Cumulative evidence revealed that genetic and epigenetic variations, along with environmental factors, were linked with PCOS. Deciphering the molecular pathways of PCOS is quite complicated due to the availability of limited molecular information. Hence, to explore the infuence of genetic variations in PCOS, we mapped the GWAS genes and performed a computational analysis to identify the SNPs and their impact on the coding and non-coding sequences.Methods The causative genes of PCOS were searched using the GWAS catalog, and pathway analysis was performed using ClueGO. SNPs were extracted using an Ensembl genome browser, and missense variants were shortlisted. Further, the native and mutant forms of the deleterious SNPs were modeled using I-TASSER, Swiss- dbViewer, and PyMOL. MirSNP,PolymiRTS, miRNASNP3, and SNP2TFBS, SNPInspector databases were used to fnd SNPs in the miRNA binding site and transcription factor binding site (TFBS), respectively. EnhancerDB and HaploReg were used to characterize enhancer SNPs. Linkage Disequilibrium (LD) analysis was performed using LDlink.Results 25 PCOS genes showed interaction with 18 pathways. 7 SNPs were predicted to be deleterious using diferent pathogenicity predictions. 4 SNPs were found in the miRNA target site, TFBS, and enhancer sites and were in LD with reported PCOS GWAS SNPs.Conclusion Computational analysis of SNPs residing in PCOS genes may provide insight into complex molecular interactions among genes involved in PCOS pathophysiology. It may also aid in determining the causal variants and consequently contributing to predicting disease strategies

Item Type: Article
Uncontrolled Keywords: Polycystic ovarian syndrome; Single nucleotide polymorphisms; miRNAs; Transcription factors; Enhancers
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 13 Oct 2021 06:40
Last Modified: 13 Oct 2021 06:40
URI: http://eprints.manipal.edu/id/eprint/157541

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