基于高通量测序数据构建斑马鱼隐性遗传突变筛选系统  

Screening System of Germline Recessive Mutations in Zebrafish Constructed from High-throughput Sequencing Data

作　　者：张自冠[1,2] 施静艺[2] 陈漪[2] 孔杰[2] 陈赛娟[1,2] 黄金艳[2] 

机构地区：[1]上海交通大学系统生物医学研究院,上海200240 [2]上海交通大学医学院附属瑞金医院上海血液学研究所,医学基因组学国家重点实验室,上海200025

出　　处：《现代生物医学进展》2016年第9期1606-1609,1618,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金面上项目(81270624)

摘　　要：目的:针对斑马鱼高通量测序数据,通过一系列质量控制和突变过滤,构建一套有效隐性遗传突变筛选系统。方法:A)经过与斑马鱼参考基因组比对,利用GATK获得初始的VCF格式突变信息。B)使用perl语言编写本地脚本,对突变信息进行过滤,注释等。C)通过绘制纯合突变点分布图,找出突变富集区域。整合以上步骤,构建出一套针对斑马鱼高通量测序数据的遗传性突变筛选系统。结果:对获得的突变位点进行了一系列的质量控制,定位到具体染色体上的特定区域,并且对获得的突变进行了功能上的注释。结论:本过滤筛选系统能有效控制检测的假阳性率,对斑马鱼致病性的隐性突变位点筛查提供有力参考。Objective： An inherited recessive mutations screening system was established through a series of strict quality control and mutations filtration pipeline to investigate the high-throughput sequencing data of zebrafish. Methods： A） In this system, we mapped sequencing reads to the reference genome and called mutations of VCF format with GATK software. B） We wrote Perl scripts to filter mutations and make local annotation. C） With these scripts, we can plot the scatter distribution to focus on the homozygous mutations-rich area. Therefore, we developed an inherited recessive mutations screening system. Results： After a series of mutations quality control processing, we localized the mutation loci to a narrow specific DNA region of chromosome and annotated mutations. Conclusion：This screening system can easily reduce the false positive rate of verification mutations and facilitate the zebrafish inherited recessive mutations acquisition.

关 键 词：二代测序 Illumina测序平台 突变点富集 隐性遗传 

分 类 号：Q75[生物学—分子生物学] Q78