Parasitology Today,vol. IO, no. I I, I994 The Filarial Genome Project Beverly, USA February - March 1994 Recently, the Strategic Research Branch of the Special Programme for Research and Training in Tropical Diseases (TDR) of the World Health Organization (WHO) has identified the study of the genomic structure of parasites as a research goal. In keeping with this goal, TDR sponsored a meeting to discuss the study of the genome of the filarial parasites of humans. The purpose of the meeting was to develop a frame- work for the study of the genome of filarial parasites. It was expected that the participants would identify a single species to be examined, and that they would develop a specific approach to the study of the parasite’s genome. It was also necessary to develop a plan for collating and disserninating data and reagents produced by individuals involved in the project, and to ensure that investigators in endemic countries would be involved in the piroject. Aims and Approauhes The program of the rneeting was designed to assist the participants in developing a framework for the filarial genome project. Initially, the strategies that may be used in a genome mapping initiative were summarized by B. Slatko (New England Biolabs, Beverly, USA). In the ‘top down’ approach, a coarse genetic or physical map of the genome is first generated. Individual DNA se- quences are then mapped with respect to one another, and to th’e previously detetmined map. In the ‘bottom up’ approach, individual clones are isolated and characterized. Attempts are then made to derive a linkage map by ident- ifying clones that share overlapping sequences. These strategies: have often been combined, as has been the case with the Caenorhabditis eleguns genome-sequencing initiative. A second series of presentations deatt with the advantages and limitations of undertaking a genome project on each of the filarial, parasites of humans, ie. Onchocerca vo/v~~l~~s, Wuchereria bancrofii and Brugia malayi. Factors considered 0 1994. Else&r Science Ltd T.R. Unnasch included the current state of knowledge about each parasite’s genome, the avail- ability of material from each organism, and the relative public health importance of each of the parasites. It was noted that molecular phylogenetic studies have shown that divergence in the nematode lineage is an ancient phenomenon. Thus, any attempt to extrapolate findings from free-living nematodes, such as C elegans, to filarial parasites should be done with the understanding that the organisms may not be closely related evolutionatily. Despite this caveat, it is clear that para- sitic nematodes share many common features with C. elegans. Thus, a filarial parasite genome project should attempt to utilize the C eleguns resource to the greatest extent possible. A third series of presentations pro- vided an update on Plasmodium fakci- parum and Schistosomo mansoni genome projects, which are already underway. The malaria project was summarized by A. Craig (John Radcliffe Hospital, Oxford, UK). The P. falciparum genome is being mapped, utilizing a library of yeast artificial chromosomes (YACs). The YACs are being connected by satu- ration mapping and hybridization, using sequence tags developed from pre- viously characterized YACs. The data developed from this project are cen- tralized and are being made available to all interested investigators. The S. man- soni project was summarized by M. Adams (Institute for Genomic Research, Gaithenburg, USA). In contrast to the malaria project, the 5. mansoni genome project is taking a strictly ‘bottom up’ approach of developing a survey of expressed sequence tags (ESTs). To accomplish this, randomly selected cDNA clones present in a cDNA library prepared from adult mixed-sex mRNA are being sequenced. This approach has the advantage of pro- viding a rapid payoff in the production of new data, but the level of redun- dancy in the sequencing will rise as the project progresses. Caenorhobditis elegans Database A major concern of any genome project involves the manner in which the information collected will be otgan- ized and disseminated to interested investigators. To this end, A. Coulson (Sanger Centre, Cambridge, UK) presented a hands-on demonstration of a C. elegans database (ACeDB), the database that is central to the C. elegans genome project. He empha- sized that ACeDB has been developed with an open architecture. This makes it possible to incorporate data produced by other genome projects into ACeDB, or into a separate but related database. Recommendations Based upon the presentations given at the meeting, the participants agreed that B. malayi should be the organism of choice for a filarial genome project. Brugia m a lo y i has several advantages over W. bancrofi and 0. ~o/vu/us, the most important being that parasite material from all life cycle stages is more readily available from B. m a la y i than the other human filaria, and that cDNA libraries from most stages of the pamsite life cycle have been produced. Because of the difficulty in generating a genetic or physical map for the filarial parasites, it was the consensus that a ‘bottom up’ approach would be the most practical. It was thought that the best strategy would be to follow the example of the 5. mansoni project and embark on a study of ESTs in 8. malayi. This approach should produce a high initial payoff in terms of data pro- duction. Furthermore, by including cDNAs derived from all the life cycle stages, information about develop mental expression of various genes would also be obtained. Much of the DNA sequencing necessary for the project might be undertaken by laboratories located in endemic countries. The sequencing effort could be spread over a number of laboratories worldwide, by preparing grids from each cDNA library, and by providing different sets of grids to each laboratory. It was recommended that a high priority be placed on the establish- ment of a central facility, which would be responsible for preparing and maintaining the grids, and for collating