西非及柬埔寨西部地区恶性疟原虫基因组拷贝数变异研究  

Copy number variation of genome of Plasmodium falciparum isolates from West Africa and West Cambodia

作　　者：田一妮 叶润 潘卫庆 张冬梅 TIAN Yini;YE Run;PAN Weiqing;ZHANG Dongmei(Department of Tropical Diseases,the Navy Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学热带病学教研室,上海200433

出　　处：《中国热带医学》2018年第10期980-983,共4页China Tropical Medicine

基　　金：国家自然科学基金资助项目(No.81220108019)

摘　　要：目的对非洲地区(马里)及柬埔寨西部(菩萨和拜林)地区恶性疟原虫基因组的拷贝数变异情况进行初步研究。方法从疟原虫基因组数据库下载西非及柬埔寨西部地区20个恶性疟原虫样本的全基因组测序数据,预处理过滤后得到14个虫株样本测序数据纳入下一步研究(西非地区6个,柬埔寨西部地区8个)。用生物信息学软件检测拷贝数变异情况,并对发生拷贝数变异的基因进行功能注释和功能富集分析。结果西非地区在14条染色体上共检测到112个拷贝数变异区域,包含230个基因;柬埔寨西部地区在14条染色体上共检测到111个拷贝数变异区域,包含179个基因。GO富集分析显示,西非地区拷贝数变异基因主要与恶性疟原虫微管运动活性过程有关;柬埔寨西部地区主要与恶性疟原虫天冬氨酸肽链内切酶活性及细胞内小泡等相关。对于恶性疟原虫药物抗性相关基因,在西非地区检测到pfmrp-1及pfmrp-2发生了拷贝数增加,柬埔寨西部地区检测到pfmdr-1、pfmrp-1、plasmepsin-2、plasmepsin-3发生拷贝数增加。结论西非及柬埔寨西部地区恶性疟原虫基因组内存在较多拷贝数变异,且发生拷贝数变异的大部分基因与微管运动活性过程、天冬氨酸肽链内切酶活性及细胞内小泡相关。Objective To investigate the copy number variation of genome of Plasmodium falciparum isolates from WestAfrica and West Cambodia. Methods Fastq files of 20 P. falciparum isolates were downloaded from the Sequence ReadArchive（SRA） of the European Nucleotide Archive--10 from West Cambodia and 10 from West Africa. The isolates thatfailed to meet certain criteria were removed, and 14 isolates were remained for next analysis--8 from West Cambodia and 6 from West Africa. The copy number variants（CNVs） of the P. falciparum strains were detected and CNVs were annotated withRefseq annotation on SnpEff 4.3. Then the genes located in the CNV region were selected for GO analysis by bioinformatictools. Results Totally 112 high-confidence CNVs including 230 CNV genes were scored across the whole parasite genome ofWest Africa and 111 CNVs including 179 CNV genes were obtained from the whole genome of West Cambodia strains. TheCNV gene annotation and GO analysis indicated that the CNV genes of West Africa involved in microtubule motor activity andCNV genes of West Cambodia were related to aspartic-type endopeptidase activity and endocytic vesicle. Meanwhile, somegenes associated with drug resistance were detected. For example, duplications of pfmrp-1 and pfmrp-2 were discovered in thestrains from West Africa and duplications of pfmdr1, pfmrp 1, plasmepsin 2, plasmepsin 3 were found in the isolates from WestCambodia. Conclusions CNVs are widespread in P. falciparum genomes isolated from West Africa and West Cambodia,especially in the genes related to microtubule motor activity, aspartic-type endopeptidase activity and endocytic vesicle.

关 键 词：恶性疟原虫 西非 柬埔寨西部 全基因组测序 拷贝数变异 

分 类 号：R531.3[医药卫生—内科学]