Whole Exome Sequencing To Explore Genes Related To Spleen And Kidney Yang Deficiency In Postmenopausal Osteoporosi

Purpose: We use whole exome sequencing(WES)to filter the mutation sites in the whole exome of postmenopausal osteoporosis(PMO)patients with spleen-kidney yang deficiency syndrome.Then use NCBI to review and confirm its possible pathogenic gene.Material and method: In this study,8 postmenopausal osteoporosis patients with spleen-kidney yang deficiency syndrome were selected as the PMO case group,8 cases of healthy postmenopausal women were used as a control group.DNA was extracted from peripheral venous blood of all subjects,and the quality of DNA samples was tested.After qualified,whole exon capture and high-throughput sequencing were performed.Quality assessment and variation analysis were performed on the sequencing results,and then the disease-related gene variations were obtained by comparison and screening between groups.Finally,bioinformatics analysis and NCBI literature review were carried out to further identify the possible pathogenic genes.Results:1.Using whole exome sequencing and mutation site analysis,a total of 550,933 SNP and 36,262 In Del mutations were detected in 16 samples.After rare mutation screening,harmful screening,intergroup contrast screening and ACMG classification,83 candidate genes were finally obtained.2.Enrichment analysis of candidate genes showed that they were involved in the biological processes such as positive regulation of transcription and DNA-templated,and involved in the regulation of protein digestion and absorption,purine metabolism,and ECM-receptor interaction.3.Candidate genes were sequenced for gene-disease association,and the top 20candidate genes included in the association were referred to relevant literatures in NCBI to further determine the possible pathogenic genes of the disease as CREB1,FOXO3 and WNT16.Conclusion:1.Through whole exome sequencing,it was found that there were a large number of gene mutation sites in postmenopausal osteoporosis patients with spleen-kidney Yang deficiency syndrome,and the mutation sites were significantly different from healthy postmenopausal women.2.Candidate genes of postmenopausal osteoporosis with spleen-kidney yang deficiency syndrome may be involved in the positive regulation of transcription,DNA template and other biological processes,and participate in the regulation of protein digestion and absorption,purine metabolism,ECM-receptor interaction and other pathways.3.CREB1,FOXO3 and WNT16 may be pathogenic genes in postmenopausal osteoporosis patients with spleen-kidney yang deficiency syndrome,but large sample experiments are still needed to verify them.