中文摘要：

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 m L静脉血并提取基因组DNA。采用Nimble Gen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。

英文摘要：

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 allelie 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 Ioci： chr4：81975103 in BMP3, rs7078571 in BMPRIA, chr2：148686946 and rsl128919 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, BMPRIA, ACVR2A, ACVR2B, Smad4. We do not identify any rare variants related to this disease, which might affect this disease.