Study On The Use Of Whole Exome Sequencing Technology To Screen Different Family Pathogenic Genes And Physical Characteristics Of Traditional Chinese Medicine For Vestibular Migraine

Objective: The whole exome sequencing of different families of vestibular migraine(VM)was performed by high-throughput sequencing platform to screen the causative genes,to explore the pathogenesis of VM at the genetic level,to further understand its molecular genetic mechanism,and to understand the TCM physical characteristics of VM patients in different families,to clarify the pathogenesis pattern and TCM physical characteristics of VM in different families,and to enrich its etiogenetic study.Methods: Four patients with confirmed VM(prior witnesses)attending the vertigo treatment center of the First Clinical Hospital of Jilin Academy of Chinese Medicine and two to three VM patients from each of their families were selected as subjects to collect basic information,kinship,clinical characteristics,and to identify TCM physical typing.At the same time,blood was collected from the subjects,blood DNA samples were extracted,and Agilent’s liquid-phase microarray capture system was used for efficient enrichment of human DNA in the whole exonic region,followed by high-throughput and high-deep sequencing on the Illumina platform to obtain raw sequence data,and the sequencing data were quality controlled to remove high-frequency mutations and synonymous mutations,which were then analyzed by the Thousand Genome Project database,the The data were compared with several biological databases,such as the Human Mendelian Genetic Diseases Database and the Human Gene Mutation Database,to screen and analyze the non-synonymous mutations in family and inter-family samples,and to obtain disease-related mutation loci,and finally to obtain candidate disease-causing genes.Meanwhile,based on the results of deleteriousness classification screening,the genetic loci classified as pathogenic and potentially pathogenic were statistically analyzed according to individuals of different VM fitness samples to clarify the TCM fitness characteristics of different VM families.Results:1.A total of 11 patients with VM in 4 family lines,11 females and 4 males,aged between 8 and 77 years,were included in this study.2.Data from a total of 15 samples from the four family lines were screened,and the MYO7 A gene on chromosome 11q13.5 was identified as a possible pathogenic gene for VM based on disease phenotype-gene association analysis;after screening for genes common to single or multiple family lines and pathogenicity genes,ASB13,IGDCC3,ITGB6,RANBP6,KCNJ12/KCNJ18 A total of 25 genes,including ASB13,IGDCC3,ITGB6,RANBP6,KCNJ12/KCNJ18,INPP5 E,ADSL1,CPD,ENO3,HS3ST3A1,KLHDC8 A,MAPK8IP1,PLOD3,QRFPR,RASD1,SHPK,TRPC4,XRCC3,ASCL3,GRM7,PRKAR1 B,TCF25,and BAGE gene family,were identified as possible VM susceptibility genes.The above results still need to be verified by follow-up studies.3.The TCM constitution of the 15 patients in the four families was mainly qi-yu constitution,with 8 cases,and the rest were ping-he constitution in 3 cases,blood stasis constitution,phlegm-damp constitution,damp-heat constitution,and yang-vacant constitution in 1 case each.4.Among the nine TCM constitutions,the most pathogenic mutation loci of genes are contained under the qi-yu constitution,and the difference was statistically significant(P <0.05)compared with the rest of the constitutions.49 cases(38%)were found,and the rest of the constitutions were Blood stasis 23 cases(18%),Phlegm-damp 23 cases(18%),Damp-heat 21 cases(16%),and Yang deficiency 13 cases(10%).5.The extant gastric stroma-associated gene PLXNA2,identified by known predecessors,was also found in samples B＿2,B＿3 and B＿4 in the B family.Conclusion:1.The MYO7 A gene is a possible pathogenic gene of VM,which is located on chromosome 11q13.5 and to some extent confirms the conclusion of previous studies that it may be involved in the disease process of VM by affecting the binding of calmodulin in vestibular organ tissues and vestibular-related signaling pathways.2.A total of 25 genes,including ASB13,IGDCC3 and BAGE,are possible susceptibility genes for VM and may be directly or indirectly involved in the disease process.3.Among the nine TCM constitutions,the number of deleterious gene mutations in qi-yu constitution is higher compared to other constitutions,probably because qi-yu constitution is more susceptible to VM-related pathogenic mutations.4.The presence of PLXNA2,a currently known pneumoconiosis-associated mutation gene in VM families,and the familial aggregation of VM are closely related to the inheritance of pneumoconiosis in family lines,and pneumoconiosis may induce the development of VM by affecting mood.