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丝虫基因组计划:马来布鲁线虫核基因组、线粒体基因组及内共生菌基因组分析

The filarial genome project: analysis of the nuclear, mitochondrial and endosymbiont genomes of Brugia malayi.

作者信息

Williams S A, Lizotte-Waniewski M R, Foster J, Guiliano D, Daub J, Scott A L, Slatko B, Blaxter M L

机构信息

Filarial Genome Project Resource Center, Department of Biological Sciences, Smith College, Northampton, MA 01063, USA.

出版信息

Int J Parasitol. 2000 Apr 10;30(4):411-9. doi: 10.1016/s0020-7519(00)00014-x.

DOI:10.1016/s0020-7519(00)00014-x
PMID:10731564
Abstract

The Filarial Genome Project (FGP) was initiated in 1994 under the auspices of the World Health Organisation. Brugia malayi was chosen as the model organism due to the availability of all life cycle stages for the construction of cDNA libraries. To date, over 20000 cDNA clones have been partially sequenced and submitted to the EST database (dbEST). These ESTs define approximately 7000 new Brugia genes. Analysis of the EST dataset provides useful information on the expression pattern of the most abundantly expressed Brugia genes. Some highly expressed genes have been identified that are expressed in all stages of the parasite's life cycle, while other highly expressed genes appear to be stage-specific. To elucidate the structure of the Brugia genome and to provide a basis for comparison to the Caenorhabditis elegans genome, the FGP is also constructing a physical map of the Brugia chromosomes and is sequencing genomic BAC clones. In addition to the nuclear genome, B. malayi possesses two other genomes: the mitochondrial genome and the genome of a bacterial endosymbiont. Eighty percent of the mitochondrial genome of B. malayi has been sequenced and is being compared to mitochondrial sequences of other nematodes. The bacterial endosymbiont genome found in B. malayi is closely related to the Wolbachia group of rickettsia-like bacteria that infects many insect species. A set of overlapping BAC clones is being assembled to cover the entire bacterial genome. Currently, half of the bacterial genome has been assembled into four contigs. A consortium has been established to sequence the entire genome of the Brugia endosymbiont. The sequence and mapping data provided by the FGP is being utilised by the nematode research community to develop a better understanding of the biology of filarial parasites and to identify new vaccine candidates and drug targets to aid the elimination of human filariasis.

摘要

丝虫基因组计划(FGP)于1994年在世界卫生组织的支持下启动。马来布鲁线虫被选为模式生物,因为其所有生命周期阶段都可用于构建cDNA文库。迄今为止,已对20000多个cDNA克隆进行了部分测序,并提交到了EST数据库(dbEST)。这些EST定义了大约7000个新的布鲁线虫基因。对EST数据集的分析提供了有关布鲁线虫中表达最丰富的基因的表达模式的有用信息。已鉴定出一些在寄生虫生命周期的所有阶段都表达的高表达基因,而其他高表达基因似乎是阶段特异性的。为了阐明布鲁线虫基因组的结构,并为与秀丽隐杆线虫基因组进行比较提供基础,FGP还在构建布鲁线虫染色体的物理图谱,并对基因组BAC克隆进行测序。除了核基因组外,马来布鲁线虫还拥有另外两个基因组:线粒体基因组和细菌内共生体的基因组。马来布鲁线虫线粒体基因组的80%已被测序,并正在与其他线虫的线粒体序列进行比较。在马来布鲁线虫中发现的细菌内共生体基因组与感染许多昆虫物种的立克次氏体样细菌的沃尔巴克氏体属密切相关。一组重叠的BAC克隆正在组装,以覆盖整个细菌基因组。目前,细菌基因组的一半已组装成四个重叠群。已经成立了一个财团来对布鲁线虫内共生体的整个基因组进行测序。线虫研究界正在利用FGP提供的序列和图谱数据,以更好地了解丝虫寄生虫的生物学特性,并确定新的疫苗候选物和药物靶点,以帮助消除人类丝虫病。

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