高通量测序筛查多巴反应性肌张力障碍家系突变基因  

Screening the Mutant Genes Involved in Dopa-Responsive Dystonia(DRD) Family by High-Throughput Sequencing

作　　者：柳明玉[1] 范维 徐博 杨俊 杜红丽[1] Liu Mingyu;Fan Wei;Xu Bo;Yang Jun;Du Hongli(School of Biology Science and Engineering, South China University of Technology, Guangzhou, 510006;China Affiliated Shunde Heping Surgical Hospital of GUCM, Dept. ofNeurosurgery, Shunde, 528308)

机构地区：[1]华南理工大学,生物科学与工程学院,广州510006 [2]广州中医药大学顺德和平外科医院神经外科,顺德528308

出　　处：《基因组学与应用生物学》2017年第11期4438-4444,共7页Genomics and Applied Biology

基　　金：华南理工大学创新基金(SW20130802);华南理工大学基金(2015ZZ125);广州市科技计划项目(201508020040)共同资助

摘　　要：快速发展的高通量测序技术使遗传病家系突变基因的筛查鉴定成为可能,本研究通过全外显子测序、生物信息分析和PCR-测序技术筛选一个多巴反应性肌张力障碍(DRD)家系中可能的致病突变位点,从1 005个低频位点中选出在3个疾病个体至少有一个杂合突变的9个候选SNP,再通过DRD家系12个个体PCR扩增测序验证,新发现突变基因SLC18A1可能是该DRD家系的致病基因。此外,PCR和Sanger测序发现高通量外显子测序和信息分析的SNP分型准确性可高达96.3%,是一种遗传病家系突变基因筛查鉴定高效、准确的方法。The advanced high-throughput sequencing technology makes it possible to screen the mutant genes in genetic disease family, and the study screened the potential mutant sites in a dopa-responsive dystonia （DRD） family by whole exome sequencing, PCR-sequencing and bioinformatics analysis, screened 9 candidate SNPs which repre- sented at least a heterozygous mutant in three DRD patients, then identified in all the 12 members in the DRD family by PCR amplification and sequencing, the results revealed that SLC18A 1 gene may be the potential pathogenic gene of the DRD family. Besides, PCR and Sanger sequencing verified that the accuracy of SNP genotype identified by whole exome sequencing and informatics analysis was up to 96.3%, which is an efficient and accurate methods for screening the mutant genes of genetic disease family.

关 键 词：多巴反应性肌张力障碍疾病 全外显子测序 SLC18A1基因 

分 类 号：R746[医药卫生—神经病学与精神病学]