Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease.
Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease.
复制标题
外显子组测序将 FGF12 鉴定为大骨节病的新候选基因。
DOI：
10.1007/s10142-015-0462-z
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Guo Xiong
中科院分区：
文献类型：
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作者：
Zhang Feng;Dai Lanlan;Lin Weimin;Wang Wenyu;Liu Xuanzhu;Zhang Jianguo;Yang Tielin;Liu Xiaogang;Shen Hui;Chen Xiangding;Tan Lijun;Tian Qing;Deng Hong-Wen;Xu Xun;Guo Xiong
本研究的目的是确定参与大骨节病（KBD）发病机制的新致病基因。使用Illumina Hiseq2000平台对具有代表性的严重骨骼生长发育失败的III级KBD sib对进行外显子组测序。然后将检测到的基因突变与1000基因组计划、dbSNP数据库和华大基因内部数据库的数据进行筛选，并通过大骨节病全基因组关联研究（GWAS）进行复制。GWAS纳入了90例极端大肠癌表型的II级或III级大肠癌患者和1627名健康对照。应用Affymetrix Genome-Wide Human SNP Array 6.0进行基因分型。采用PLINK软件进行关联分析。我们在FGF12基因的3'UTR处发现了一个新的106T>C，目前尚未报道。序列比对发现，突变的3'UTR +106T>C位点在不同脊椎动物中具有较高的对话率。在大骨病的GWAS中，我们检测到FGF12基因的9个snp与大骨病有关联（p值< 0.05）。在rs1847340位点观察到最显著的关联信号（p值= 1.90 × 10−5）。本研究提示FGF12是大骨节病的易感基因。我们的研究结果为揭示大骨病的发病机制和FGF12的生物学功能提供了新的线索。
The objective of this study was to identify novel causal genes involved in the pathogenesis of Kashin-Beck disease (KBD). A representative grade III KBD sib pair with serious skeletal growth and development failure was subjected to exome sequencing using the Illumina Hiseq2000 platform. The detected gene mutations were then filtered against the data of 1000 Genome Project, dbSNP database, and BGI inhouse database, and replicated by a genome-wide association study (GWAS) of KBD. Ninety grade II or III KBD patients with extreme KBD phenotypes and 1627 healthy controls were enrolled in the GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was applied for genotyping. PLINK software was used for association analysis. We identified a novel 106T>C at the 3′UTR of the FGF12 gene, which has not been reported by now. Sequence alignment observed high conversation at the mutated 3′UTR+106T>C locus across various vertebrates. In the GWAS of KBD, we detected nine SNPs of the FGF12 gene showing association evidence (Pvalue < 0.05) with KBD. The most significant association signal was observed at rs1847340 (Pvalue = 1.90 × 10−5). This study suggests that FGF12 was a susceptibility gene of KBD. Our results provide novel clues for revealing the pathogenesis of KBD and the biological function of FGF12.