上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

外显子组测序筛查遗传性牙龈纤维瘤的致病基因

高炜炜，杨 静*，朱于非，伊现富，王 孟，胡兰靛   

  1. 中科院上海生命科学研究院/上海交通大学医学院 健康科学研究所， 上海 200025
  • 出版日期:2014-12-28 发布日期:2014-12-30
  • 通讯作者: 胡兰靛, 电子信箱: ldhu@sibs.ac.cn。
  • 作者简介:高炜炜（1986—）， 男， 硕士生; 电子信箱: gaowei05diyi@163.com；电子信箱： 杨 静（1986—）， 女， 博士生; 电子信箱: mercuryyangjing@sina.com。*为共同第一作者。
  • 基金资助:

    国家自然科学基金青年科学基金面上项目（30700463）

Screening pathogenic genes of hereditary gingival fibromatosis by exome sequencing

GAO Wei-wei, YANG Jing*, ZHU Yu-fei, YI Xian-fu, WANG Meng, HU Lan-dian   

  1. Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences,  Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2014-12-28 Published:2014-12-30
  • Supported by:

    General Program of Youth Science Foundation of National Natural Science Foundation of China, 30700463

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摘要：

目的 绘制并分析遗传性牙龈纤维瘤（HGF）突变遗传图谱，预测与其发病有关的特异性突变和基因。方法 利用第二代Sloxa测序技术对所收集到的一个具有明显母系遗传特征的家系样本进行全外显子组测序，结合生物信息学手段和实验验证，筛选可能与HGF发病有关的单核苷酸多态性（SNP）和基因，并在正常人群中进行验证。结果 筛选到17个可能与该病发生相关的SNP，在约200个正常人验证中出现了少量相同变异；在与表达谱芯片结果联合分析中，在5个母系印记基因中筛选出5个新的变异并加以验证。结论 成功绘制出HGF外显子组突变图谱，部分SNP在正常人群中有低频发生，并在5个母系印记基因中发现未报道的突变。通过引入全外显子组测序技术对该病进行开拓性的研究，为进一步研究该病有着借鉴意义。

关键词: 遗传性牙龈纤维瘤, 外显子测序技术, 单核苷酸多态性, 印记基因, 表观遗传

Abstract:

Objective To construct and analyze the mutant genetic profile of hereditary gingival fibromatosis (HGF) and to predict specific mutations and genes relevant to pathogenesis. Methods Samples from a family with obvious maternal inheritance were collected and whole exome sequencing was performed by Agilent SureSelect exome capture and Illumina Solxa sequencing platform. Single nucleotide polymorphisms (SNP) and genes relevant to the onset of HGF were screened by bioinformatic methods and experimental verification and verified against normal people. Results A total of 17 SNPs relevant to the onset of HGF were screened. Verification against about 200 normal people only found a small number of same mutations. Five novel mutations were screened from 5 maternal imprint genes by analyzing the results of expression profile chip. Conclusion The mutation profile of exome of HGF was successfully constructed. Some SNPs were found in normal people with low frequency. Novel mutations were found in 5 maternal imprint genes. Pioneering study has been conducted by introducing the whole exome sequencing technique and can provide reference for the further study.

Key words: hereditary gingival fibromatosis, single nucleotide polymorphism, exome sequencing technique, imprint genes, epigenetics