In silico characterization of structural and functional impact of the deleterious SNPs on FSHR gene

492-499FSHR is an important gene which plays a major role in the development of secondary sex characteristics and influences the female reproductive cycle by regulating the Follicle Stimulating Hormone. Though this gene and its protein are extensively studied, no attempts have been made yet to methodically analyze the variants in this gene. One of the chief objectives during the analysis of human genetic variation is to distinguish between the Single Nucleotide Polymorphisms (SNPs) that are functionally neutral from those that contribute to the disorder. To predict the possible impact of SNPs on the FSHR structure and function, data were obtained from NCBI (dbSNP and dbVar) and validated manually. Various bioinformatics tools were used to predict the alterations at transcriptional, post transcriptional stages and protein interaction. Around 38 variants reported by NCBI Variation Viewer were sorted by SIFT and 14 of them were reported damaging, 13 were reported to be either benign or damaging by PROVEAN and Panther. From these 13 SNPs, the most damaging (11 SNPs) were modeled using Pymol and the energy difference between the native and mutated structure was calculated by Swiss PDB – Viewer. Based on our analysis, we have reported potential candidate SNPs for the FSHR gene involved in the regulation of ovarian pathophysiology

In silico characterization of structural and functional impact of the deleterious SNPs on FSHR gene

FSHR is an important gene which plays a major role in the development of secondary sex characteristics and influences the female reproductive cycle by regulating the Follicle Stimulating Hormone. Though this gene and its protein are extensively studied, no attempts have been made yet to methodically analyze the variants in this gene. One of the chief objectives during the analysis of human genetic variation is to distinguish between the Single Nucleotide Polymorphisms (SNPs) that are functionally neutral from those that contribute to the disorder. To predict the possible impact of SNPs on the FSHR structure and function, data were obtained from NCBI (dbSNP and dbVar) and validated manually. Various bioinformatics tools were used to predict the alterations at transcriptional, post transcriptional stages and protein interaction. Around 38 variants reported by NCBI Variation Viewer were sorted by SIFT and 14 of them were reported damaging, 13 were reported to be either benign or damaging by PROVEAN and Panther. From these 13 SNPs, the most damaging (11 SNPs) were modeled using Pymol and the energy difference between the native and mutated structure was calculated by Swiss PDB – Viewer. Based on our analysis, we have reported potential candidate SNPs for the FSHR gene involved in the regulation of ovarian pathophysiology

In silico analysis of functional non-synonymous and intronic variants found in a polycystic ovarian syndrome (PCOS) candidate gene: DENND1A

584-593The major thrust of our study confers to the identification of non-synonymous and intronic variants of the DENND1A gene via in silico methods and determination of its effect on the structural integrity of the protein. The outcome identifies potential disease -causing SNPs. The pathogenic variants of DENND1A were deduced via in silico analysis using various tools that include SIFT, PolyPhen-2, PROVEAN, SNP & GO, and PANTHER. The intronic variants were analysed using RegulomeDB. The 3D protein structure was obtained using the SWISS PDB modeler and validated by Ramachandran plots and QMEAN server. The effect on the stability of the protein structure caused by the SNPs was evaluated on the PYMOL and SWISS model platform. The functional changes caused by the SNPs were analysed in silico with I Mutant and Mutation Taster. The post-translational modifications were also predicted. STRING database was used for screening the protein interaction network. The SNPs rs2479106 and rs10986105 on the splice sites were found to be pathogenic for PCOS. The amino acid changes V179G and P331L were found to be disease-causing but the disease association with PCOS is yet to be validated

In silico analysis of functional non-synonymous and intronic variants found in a polycystic ovarian syndrome (PCOS) candidate gene: DENND1A

The major thrust of our study confers to the identification of non-synonymous and intronic variants of the DENND1A gene via in silico methods and determination of its effect on the structural integrity of the protein. The outcome identifies potential disease -causing SNPs. The pathogenic variants of DENND1A were deduced via in silico analysis using various tools that include SIFT, PolyPhen-2, PROVEAN, SNP & GO, and PANTHER. The intronic variants were analysed using RegulomeDB. The 3D protein structure was obtained using the SWISS PDB modeler and validated by Ramachandran plots and QMEAN server. The effect on the stability of the protein structure caused by the SNPs was evaluated on the PYMOL and SWISS model platform. The functional changes caused by the SNPs were analysed in silico with I Mutant and Mutation Taster. The post-translational modifications were also predicted. STRING database was used for screening the protein interaction network. The SNPs rs2479106 and rs10986105 on the splice sites were found to be pathogenic for PCOS. The amino acid changes V179G and P331L were found to be disease-causing but the disease association with PCOS is yet to be validated

Clinical and MRI profile of patients with knee injuries and correlation of MRI with arthroscopic findings

Background: MRI is radiation free modality and has ability to understand the soft tissue, anatomy and musculoskeletal system pathologies. MRI has the advantage of demonstrating the cartilages, bones, soft tissue in detail. Objectives of current study were evaluation of ligaments and meniscal injuries using magnetic resonance imaging, to study the pattern and spectrum of knee injuries in relation to mechanism of injury and to correlate MRI findings with that of arthroscopic findings. Methods: All the MRI studies were done using a 1.5T MRI scanner (Siemens Magnetom) in our department, department of radiodiagnosis, ACS medical college, Chennai. Patient taken up for arthroscopy and the arthroscopic findings were collected. The data of MRI collected was compared with arthroscopy findings. Results: On correlation of the overall findings the sensitivity of MRI versus arthroscopy was 90.62% Specificity was 84.55% positive predictive value was 92.06%, negative predictive value was 80.00% Between them with a kappa 0.059 Conclusions: MRI of knee is considered efficacious especially in the setting of indeterminate clinical finding and can stratify patients, thereby increasing the diagnostic confidence of the clinicians leading to appropriate surgical planning and management

Oocyte quality and ABO blood group system: are they connected?

Background: Blood groups of women have been associated with infertility and other related conditions like diminished ovarian reserve. We have tried to find, if there is any association between blood group of women and the quality of their oocytes.Methods: Present study is a retrospective analysis from the available data of IVF patients on standard ICSI protocols in our tertiary care clinic over 32 months. Oocytes were grouped into GOOD & POOR quality oocytes. Good quality oocytes were further graded into Grade 1, 2, 3. SPSS 15.0 was used for statistical analysis.Results: Good quality oocytes were almost similarly distributed among the blood groups. Among the good quality oocytes, Grade ‘1’ Oocytes were found higher in ‘O’ blood group women.  Conclusions: Blood group alone was found to play no major role in determining the oocyte quality of women

An epidemiological survey: Effect of predisposing factors for PCOS in Indian urban and rural population

Study objective: Polycystic ovarian syndrome (PCOS) is a common multifaceted disorder found among females of the reproductive age presenting major clinical conditions of hirsutism, oligomenorrhea and infertility. Socioeconomic studies from India have observed PCOS as a lifestyle disorder highly prevalent among middle and high income urban population as compared to rural population. A large ethnographic study that identifies the prevalence of PCOS among different socioeconomic groups would be greatly helpful to reiterate women about lifestyle modifications. Design: Cross – sectional survey study. Setting: Random from the general population. Materials and methods: A survey was taken up by 502 young women (between 18 and 24 years) from Chennai and collectively 566 girls from Thiruvallur and Dindugal districts to represent urban and rural population respectively. The responses were entered into an excel workbook and were analyzed statistically for correlation of influencing parameters and manifestation of the disorder. Main outcome measures: From our survey, we have identified a PCOS prevalence rate of 6% in south India, according to the Rotterdam criteria. We have observed that the odds of urban women prone to acquiring PCOS are 0.1 times higher than women in rural India. Major conclusions: Family history was found to have a strong association in incidence and manifestation of the disorder. Stress was found to set off the symptoms pertaining to PCOS. We also noticed that the awareness, among the rural population especially, was very minimum and thus they were not oblivious of diagnosis