基于重测序技术对瘢痕疙瘩形成相关基因结构变异的初步探讨  

The preliminary study of structure variation related to keloid based on the whole-gene resequencing technique

作　　者：刘畅[1] 滕国栋[1] 陈敏亮[1] 马奎[1] 颜彤彤 

机构地区：[1]解放军总医院第一附属医院,北京100048

出　　处：《中华整形外科杂志》2014年第4期279-282,共4页Chinese Journal of Plastic Surgery

基　　金：国家自然科学基金（81272103）

摘　　要：目的 利用全基因重测序技术初步探讨与瘢痕疙瘩形成相关基因的结构变异.方法 选取1个典型瘢痕疙瘩家系,共4代27例,利用全基因组重测序技术,对该家系中5例（4例瘢痕疙瘩患者,1例正常人）基因组DNA进行数据分析,并对所获信息进行数据库比对和变异注释.结果 通过生物信息学分析、数据库比对及变异注释后,发现了2个与瘢痕疙瘩相关的结构变异.利用靶基因功能分析软件DAVID对筛选出来的结构变异进行注释和信号通路分析,发现人四旋蛋白8（TSPAN8）在所有检测的瘢痕疙瘩患者中,均有一段168 bp的倒置,其包含了TSPAN8基因的第4个外显子.结论 TSPAN8表达的肿瘤细胞,可通过上调血管内皮生长因子及其受体的表达,促进相邻的成纤维细胞分泌基质金属蛋白酶及尿激酶.此家系中该基因4号外显子的倒置,可能会导致该蛋白在信号转导过程的调节紊乱,从而导致瘢痕疙瘩的形成.Objective To investigate the genome structure variation （SV） related with keloid using the whole-gene resequencing technology.Methods We studied a keloid pedigree containing 4 generation of 27 people.5 people （4 cases of keloid patients,and 1 case of normal） were selected to extract the genomic DNA.Then the whole-gene resequencing technique was used to check the variations.Results Through database comparison and variation annotation analysis,we obtained 2 SVs associated with keloid formation.We used DAVID software to do the gene ontology and pathway analysis.We found a 168 bp inversion in gene tetraspanin 8（TSPAN8） in all keloid patients,which contained the forth exon of TSPAN8.Conclusions There was no report about SVs related to keloid.In this study,we found 2 SVs associated with keloid,especially TSPAN8.The tumor cells express the TSPAN8 can up-regulate the vascular endothelial growth factor and its receptors,promote the adjacent fibroblasts secrete matrix metalloproteinases and uridylyl phosphate adenosine.So we hypothesis that the inversion of the forth exon in TSPAN8 may lead to the signal transduction disorder in the keloid patients.This study was a preliminary research.It needs a further study containing large sample to confirm.

关 键 词：瘢痕疙瘩 全基因组重测序 结构变异 人四旋蛋白8 

分 类 号：R622[医药卫生—整形外科]