摘要
目的在染色体水平对脂肪瘤型脊髓栓系综合征的病因进行研究，分析脂肪瘤型脊髓栓系综合征患者的基因组中可能存在的致病性拷贝数变异（CNV），为进一步研究致病基因提供理论基础。方法采集2015年3至5月期间解放军总医院神经外科收治的11例脂肪瘤型脊髓栓系患者及其父母的静脉血样本，提取DNA，利用Agilent比较基因组杂交芯片筛查全基因组CNV，将所得CNV在基因数据库中进行比对，去除多态性，对所得基因同时进行基因功能、相关疾病和基因通路分析，以验证CNV与脂肪瘤型脊髓栓系之间的关系并对研究方法进行评价。结果在11例患者中共发现17个异常的CNV，其中Chr8：39258894—39386158和Chr15：20481702—22509254两个片段的出现频率为5／11，在DECIPHER数据库中查询到2个与其相关的有神经系统症状的疾病：Angelman综合征和Prader—Wolli综合征，对基因富集分析结果显示，所得CNV所包含的ADAM5P和ADAM3A基因与先天性唇腭裂的形成明显相关。结论Chr8：39258894．39386158和Chr15：20481702—22509254两个片段在脂肪瘤型脊髓栓系患者基因组中存在CNV的概率远高于普通人群，与脂肪瘤型脊髓栓系的发生可能存在相关性。在神经管畸形（NTD）相关基因的研究中，将某种特定类型的NTD孤立出来，进行分别研究可以在一定程度上提高研究效率，得到更为精确的研究结果。
Objective To explore the abnormality of chromosomes of patients with lipoma tethered cord syndrome and the probable association between Copy Number Variations （CNV） and lipoma tethered cord syndrome. Methods By using the Agilent SurePrint G3 Human CGH 8×60K Microarray Kit, we performed genome-wide screening for CNV on 11 patients with lipoma tethered cord syndrome adopted by the Neurosurgery Department of Chinese PLA General Hospital and their healthy parents from March 2015 to May 2015. We analyze CNVs got by the kit against the gene databases. Unrelated confirmed polymorphisms contained in Database of Genomic Variants （DGV） were discarded. Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources （DECIPHER） helps us with similarity inquiry, and UCSC Genome Browser helps in identification of non-polymorphie CNV. Biological process, cellular component and molecular function enrichment of these genes were conducted to confirm the association between the CNV and lipoma tethered cord syndrome. Results 17 CNV were discovered by aCGH in ll patients. Chr8：39258894-39386158 and Chr15：20481702-22509254 showed a high frequency of 5/11. Angelman syndrome and Prader-Wolli syndrome were found to be associated with the CNV of Chr15. Gene function enrichment analysis revealed that ADAMSP and ADAM3A contained in CNV obtained from patients with lipoma tethered cord syndrome was also associated with orofacial clefts. Conclusions CNV in Chr8 and Chr15 of patients with lipoma tethered cord syndrome had a higher frequency than that of common human. It revealed that there is probable association between these two pieces of CNV and lipoma tethered cord syndrome. To explorer relaled genes or CNV, focusing on certain type of NTDs may increase the research efficiency and gel more at.curate resuhs.
作者
陶本章
余新光
程诚
宗睿
赵振宇
王乐凯
尚爱加
Tao Benzhang;Yu Xinguang;Cheng Cheng;Zong Rui;Zhao Zhenyu;Wang Lekai;Shang Aijica(Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China;不详)
出处
《中华医学杂志》
CAS
CSCD
北大核心
2017年第1期12-16,共5页
National Medical Journal of China
基金
全军医药卫生科研基金（IOBJZ04）
解放军总医院临床科研扶持基金（2016FC-CXYY-1006）
志谢 北京博奥晶典生物技术有限公司对本研究提供了技术支持
关键词
神经管缺损
比较基因组杂交技术
基因拷贝数变异
Neural tube defects
Array comparative genomic hyllridizaliou
Copy number variants
