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[
Parasitol Today,
1999]
Four years ago, a WHO/United Nations Development Programme/World Bank-sponsored genome project to study the filarial lymphatic nematode parasite Brugia malayi was initiated. The project took as its aims gene discovery for drug target and vaccine candidate identification, genome mapping, dissemination of genomic data to the world community and training of endemic country partners in genomic research. In this article, the principal investigators in the laboratories behind the project describe the background to the project, the data now emerging and goals for the future. Open access to filarial genome data is emphasized.
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[
Parasitology,
1999]
The initiation of genome projects on helminths of medical importance promises to yield new drug targets and vaccine candidates in unprecedented numbers. In order to exploit this emerging data it is essential that the user community is aware of the scope and quality of data available, and that the genome projects provide analyses of the raw data to highlight potential genes of interest. Core bioinformatics support for the parasite genome projects has promoted these approaches. In the Brugia genome project, a combination of expressed sequence tag sequencing from multiple DNA libraries representing the complete filarial nematode lifecycle, and comparative analysis of the sequence dataset, particularly using the complete genome sequence of the model nematode C. elegans, has proved very effective in gene discovery.
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[
Parasitology,
1999]
Genome projects for the parasitic helminths Brugia malayi (a representative filarial nematode) and Schistosoma were initiated in 1995 by the World Health Organization with the ultimate objectives of identifying new vaccine candidates and drug targets and of developing low resolution genome maps. Because no genetic maps are available, and very few genes have been characterized from either parasite group, the first goal of both Initiatives has been to catalogue new genes for future placement on chromosome and physical maps. These genes have been identified by the expressed sequence tag (EST) approach, utilising cDNA libraries constructed from diverse life cycle stages. To date, the Initiatives have deposited over 16,000 Brugia ESTs and nearly 8000 Schistosoma ESTs in Genbank's dbEST database, corresponding to 6000 and over 3600 genes respectively (33% of Brugia's estimated gene compliment, 18-24% of that of Schistosoma). Large fragment, genomic libraries have been constructed in BAC and YAC vectors for studies of genomic organization and for physical and chromosome mapping, and public, hypertext genomic databases have been established to facilitate data access. We present a summary of progress within the helminth genome initiatives and give several examples of important gene discoveries and future applications of these data.
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[
Int J Parasitol,
2000]
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.
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Mike Quail, Mark Blaxter, Jenna Ware, Jeremy Foster, Jen Daub, Ibrahim Kamal, Barton Slatko, The Filarial Genome Project, Bart Barrell, Neil Hall, Mehul Ganatra, David Guiliano
[
International C. elegans Meeting,
2001]
The human-infective filarial nematode parasite Brugia malayi contains three genomes : the mitochondrial genome, the genome of the rickettsia-like Wolbachia endosymbiont and the nuclear genome. We have sequenced the mitochondrial genome of Brugia malayi and compared it to the other sequenced nematode mitochondria. The genome is, as expected, very similar to that of Onchocerca volvulus , and is remarkably different from C. elegans in gene order and sequence. Phylogenetic anlysis of nematode mitochondrial DNAs conflict with phylogenies derived from nuclear genes. Most filarial species harbour an bacterium that is believed to be in mutualistic symbiosis with the nematode. The bacteria are closely related to the Wolbachia endosymbionts of arthropods. The genome of the Wolbachia endosymbiont is being mapped and sequenced by a consortium headed by Barton Slatko at New England Biolabs. The nuclear genome of B. malayi is estimated to be 100 Mbp with an expected gene number comparable to C. elegans . To date, the Filarial Genome Project has produced 22,441 ESTs from 11 different cDNA libraries from various stages of the life cycle. These are estimated to represent ~8000 different genes. As a prelude to whole genome sequencing we are now in the process of constructing a physical map for the nuclear genome. A BAC library is being end sequenced, and BAC-derived end-probes hybridised to the gridded library to create contigs in a sampling-without replacement strategy. A number of EST clones have also been hybridised. In the course of this mapping program we have defined the distribution of sattelite repeats in the library, and have identified at least two families of retrotransposon-like elements.
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[
Parasitol Int,
2009]
Filarial nematode parasites, the causative agents of elephantiasis and river blindness, undermine the livelihoods of over one hundred million people in the developing world. Recently, the Filarial Genome Project reported the draft sequence of the ~95 Mb genome of the human filarial parasite Brugia malayi - the first parasitic nematode genome to be sequenced. Comparative genome analysis with the prevailing model nematode Caenorhabditis elegans revealed similarities and differences in genome structure and organization that will prove useful as additional nematode genomes are completed. The Brugia genome provides the first opportunity to comprehensively compare the full gene repertoire of a free-living nematode species and one that has evolved as a human pathogen. The Brugia genome also provides an opportunity to gain insight into genetic basis for mutualism, as Brugia, like a majority of filarial species, harbors an endosybiotic bacterium (Wolbachia). The goal of this review is to provide an overview of the results of genomic analysis and how these observations provide new insights into the biology of filarial species.
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[
Parasite Immunol
]
Filarial nematode parasites, the causative agents for a spectrum of acute and chronic diseases including lymphatic filariasis and river blindness, threaten the well-being and livelihood of hundreds of millions of people in the developing regions of the world. The 2007 publication on a draft assembly of the 95-Mb genome of the human filarial parasite Brugia malayi- representing the first helminth parasite genome to be sequenced - has been followed in rapid succession by projects that have resulted in the genome sequencing of six additional filarial species, seven nonfilarial nematode parasites of animals and nearly 30 plant parasitic and free-living species. Parallel to the genomic sequencing, transcriptomic and proteomic projects have facilitated genome annotation, expanded our understanding of stage-associated gene expression and provided a first look at the role of epigenetic regulation of filarial genomes through microRNAs. The expansion in filarial genomics will also provide a significant enrichment in our knowledge of the diversity and variability in the genomes of the endosymbiotic bacterium Wolbachia leading to a better understanding of the genetic principles that govern filarial-Wolbachia mutualism. The goal here is to provide an overview of the trends and advances in filarial and Wolbachia genomics.
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[
Trends Genet,
1998]
From their earliest experiments, researchers using Caenorhabditis elegans have been interested in the role of genes in the development and function of the nervous system. As the C. elegans Genome Project completes the genomic sequence, we review the accomplishments of these researchers and the impact that the Genome Project has bad on their research. We also speculate on future directions in this research that are enabled by the efforts of the Genome Project.
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[
Worm Breeder's Gazette,
1994]
The C. elegans genome sequencing project: A progress report. The C. elegans Genome Consortium, Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri, USA and Sanger Centre, Hinxton Hall, Cambridge, UK.
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[
Worm Breeder's Gazette,
1994]
The C. elegans genome sequencing project: A progress report. The C. elegans Genome Consortium, Genome Sequencing Center, Washington University School of Medicine, St. Louis, Missouri, USA and Sanger Centre, Hinxton Hall, Cambridge, UK.