Bioinformatics Analysis and the Revelation of Thirteen Novel Mutations in Human LH-B Gene Related to PCOS

摘要

Luteinizing hormone beta subunit (LH-B) (protein ID P01229) is gonadotropin hormone secreted from the anterior pituitary belongs to the glycoprotein family, mapped on chr19p13.3 and consists of three exons, three transcript variants with two phenotypes encoded for one protein known as Lutropin subunit beta (P01229) It has a central role in promoting spermatogenesis and ovulation by stimulating the testes and ovaries for steroidogenesis. PCOS is a common endocrinopathy affecting of women within the reproductive age, abnormal ovulation associated with a high level of LH as a result of gene polymorphisms lead to infertility problems. In this study, we used various computational approaches to identify nsSNPs which probably be deleterious to the structure and/or function of LH-B protein that might be associated with polycystic ovary syndrome. The data on human LH-B gene was retrieved from dbSNP/NCBI. Eleven different bioinformatics prediction algorithms; SIFT, Polyphen, PROVEAN, SNAP2, Pmut, PhD-SNP, I-Mutant and Project Hope were used to analyze the effect of nsSNPs on functions and structure of the LH-B protein, and RaptorX for protein modeling and Chimera for visualization of the model, in addition, we used PolymiRTS to detect SNPs on miRNA binding sites. After retrieval of SNPs from the NCBI database, 140SNPs were classified as missense SNPs. From functional analysis software, 39 SNP were predicted to be deleterious then they analyzed by disease-related software 13 SNPs, when checked for protein stability, 12 of them decreased protein stability and one SNP increased its stability. Hence, application of these 13 novel mutations through genetic studies will contribute towards our understanding of the pathophysiology of PCOS.