目标基因测序技术检测与下颌前突相关的BMP-Smad信号通路基因突变

doi:10.3969/j.issn.1005-4979.2016.06.004

《口腔颌面外科杂志》 ›› 2016, Vol. 26 ›› Issue (6): 399-. doi: 10.3969/j.issn.1005-4979.2016.06.004

目标基因测序技术检测与下颌前突相关的BMP-Smad信号通路基因突变

李偲，陈凤山

同济大学口腔医学院，同济大学附属口腔医院口腔正畸科

收稿日期:2016-03-30 修回日期:2016-05-17 出版日期:2016-12-28 发布日期:2017-06-30
通讯作者: 陈凤山,教授. E-mail: orthodboy@126.com E-mail:orthodboy@126.com
作者简介:李偲（1991—）,女,浙江人,硕士研究生.E-mail: lc522759746@126.com
基金资助:
国家自然科学基金面上项目（81371129）

Targeted Sequencing in Genes of BMP-smad Signaling Pathway for Mandibular Prognathism

LI Cai, CHEN Feng-shan

Department of Orthodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration

Received:2016-03-30 Revised:2016-05-17 Online:2016-12-28 Published:2017-06-30

摘要/Abstract

摘要： 目的：采用目标基因捕获联合二代测序技术探索BMP-Smad信号通路基因与下颌前突（mandibular prognathism）相关的变异。方法：从同济大学附属口腔医院收集176例下颌前突患者及155例正常对照，分别采集5 mL静脉血并提取基因组DNA。采用NimbleGen捕获富集系统对病例对照组的23个目标基因的编码区和侧翼区进行捕获富集，通过Illumina Hiseq 2000测序平台进行测序。通过比较变异位点基因型及等位基因分布频率的差异，探索与下颌前突相关的突变位点。结果：共发现7个与下颌前突相关的常见变异，分别位于5个基因上：chr4:81975103（BMP3）、rs7078571（BMPR1A）、chr2:148686946（ACVR2A）、rs1128919（ACVR2A）、rs2070489（ACVR2B）、chr18:48610378（SMAD4）、chr18:48610376（SMAD4）。未发现罕见变异的分布差异有显著性。结论：通过目标基因测序的方法检测到了病例对照组中的常见变异和罕见变异，并发现了与下颌前突相关的可能致病基因BMP3、BMPR1A、ACVR2A、ACVR2B、Smad4。未检测到下颌前突的罕见致病位点。

关键词: 下颌前突, 目标基因捕获, 新一代测序, BMP-Smad信号通路, 突变

Abstract: Objective: To identify variants of the genes in BMP-Smad signaling pathway that predisposing to mandibular prognathism in Chinese population. Methods: 176 mandibular prognathism individuals and 155 controls were recruited and provided informed consent from affiliated stomatology hospital of Tongji University, 5 mL peripheral blood were obtained from each individual and genomic DNA was extracted. The coding and flanking regions of 23 candidate genes in the BMP-smad signaling pathway were captured by using NimbleGen Targeted Enrichment System and then sequenced on the Illumina Hiseq2000 platform. Comparing the allelic and genotypic distribution in the cases and controls, the variants related to mandibular prognathism were identified. Results: 7 common variants in 5 genes were identified, which associated with mandibular prognathism in the following loci: chr4:81975103 in BMP3, rs7078571 in BMPR1A, chr2:148686946 and rs1128919 in ACVR2A, rs2070489 in ACVR2B chr18:48610378, chr18:48610376 in SMAD4. No significant difference in rare variants between case and control were found. Conclusions: Via targeted sequencing analysis, new genes that associated with mandibular prognathism were identified, which were BMP3, BMPR1A, ACVR2A, ACVR2B, Smad4. We do not identify any rare variants related to this disease, which might affect this disease.

Key words: mandibular prognathism, targeted gene capture, next-generation sequencing, BMP-smad signaling pathway, variant

中图分类号:

R782

李偲，陈凤山. 目标基因测序技术检测与下颌前突相关的BMP-Smad信号通路基因突变[J]. 《口腔颌面外科杂志》, 2016, 26(6): 399-.

LI Cai, CHEN Feng-shan. Targeted Sequencing in Genes of BMP-smad Signaling Pathway for Mandibular Prognathism[J]. 《Journal of Oral and Maxillofacial Surgery》, 2016, 26(6): 399-.

https://journal06.magtech.org.cn/Jweb_joms/CN/Y2016/V26/I6/399

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