The Primary Study On The Mechanism Of Scar Hyperplasia By The Whole Gene Resequencing

Objective: Inorder to find the related genes and/or the interaction between the genesassociated with scar hypertroplasia, the whole gene resequencing technology was used.Method：1、object：1）collected keloid pedigrees through epidemiological investigation;2）collected patients with keloid and hypertrophic scar and normal population.2、The whole gene resequencing technology:1)5people (4cases of keloid patients, and1case of normal) were selected toextract the genomic DNA.2) By comparing, we picked out the mutations which the4patients got but thenormal did not have.3) Through GO annotation and pathway analysis, to determine the possible genesmutation association with scar hyperplasia.3、Sequenome SNP detection technology was used in the crowd and pedigrees peoplewith keloid to validate the selected gene mutations.Results:1、 Through the whole gene resequecing technology, we selected25SNPs,19INDELs,2SV and15CNV;2、 After GO annotation and pathway analysis, we picked out19genes associationwith cell apoptosis, cell cycle, cell formation and differentiation, cell exocrine and cell adhesion.1)5CNVs were located at GRB7, MAP3K15, MAP4K4, KLF7andNKX2-2;2)2SV were ZAN and a168bp long gene inversion at TSPAN8;3、 The validation results in sporadic KDs:1) comparing with N, the mutation of ZANand ITGB5in the HS and KD had statistical significance;2) comparing with HS, themutation of HUS1B,MYH8, SIRT3and GPR126in the KD had statisticalsignificance.4、 The validation results in KD pedigrees:1) all the KD in the pedigrees took themutation both in COL17A1and SH3RF1;2) all the HS in the pedigrees took themutation in COL17A1;3) a five years old child took both the mutation of COL17A1and SH3RF1did not show the KDConclutions:1、 the whole gene resequecing technology was an useful for detecting the genesequencing differences related to the important disease in the whole genome level. Itis an effective way to analysis the genetic evolution and predicting the importantcandidate genes.2、 According to the results, we took following speculations:1) The copy number variation of MAP3K15and MAP4K4and a168bp longgene inversion in TSPAN8were closely related to the scar hyperplasia;2) In the sporadic KDs, the gene mutations of ITGB5and ZAN were associatedwith scar hyperplasia, the mutations of HUS1B, MYH8and GPR126wererelated to the KD formation;3) In the KD pedigrees, the people who took both COL17A1and SH3RF1mutations will probably got KD; if only got the mutation in COL17A1, HSmight happen.