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J Neuropathol Exp Neurol,
2000]
Invertebrate models of several human neurodegenerative diseases have recently been described. These models faithfully replicate key neuropathological features of the human disorders. Because the basic cell biology of the nervous system is very similar in vertebrates and invertebrates, the sophisticated and rapid genetic analysis feasible in Drosophila and C. elegans promises significant insight into human neurodegenerative syndromes. In addition, the short lifespan, small size, and ease of culturing make worms and flies ideal for drug testing.
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Prog Neurobiol,
2010]
Parkinson's disease (PD) was one of the first neurological disorders to have aspects of the disease modeled faithfully in non-human animal species. A key feature of the disease is a diminished control over voluntary movement and progressive depletion of brain dopamine (DA) levels that stems from the large-scale loss of DA-producing neurons. Despite their inherent limitations, rodent and non-human primate models of PD have helped unravel several aspects of PD pathogenesis. Thus, we now have neurotransmitter replacement therapy for PD, and a number of neuroprotective compounds that can be assessed in clinical trials. However, no treatment is currently available that can halt or retard the progressive loss of DA neurons, which underlies PD pathology. Moreover, no therapies can permanently alleviate the clinical features of the disease. The lack of a cure or long-term effective treatment is paralled by our incomplete understanding of the underlying pathomechanisms of the disease. A range of robust, flexible, and complementary animal models will be an invaluable tool with which to unravel the pathogenesis of PD. Here we review the most important contributions made by non-mammalian model organisms. These include zebrafish (Danio rerio), flies (Drosophila melanogaster), anurans (frogs and toads) and nematodes (Caenorhabditis elegans). While it is not anticipated that they will replace rodent and primate-based ones, they offer convenient systems with which to explore the relative contribution made by genetic and environmental factors to PD pathology. In addition, they offer an economic and rapid alternative for testing compounds that target PD. Most importantly, the combined use of these models allow for ongoing research to uncover the basic mechanisms underlying PD pathogenesis.
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Curr Opin Genet Dev,
1995]
A number of prokaryotic and eukaryotic genomes are currently being sequenced. Already, the nucleotide sequences of four yeast chromosomes and of 2.2 Mb from Caenorhabditis elegans have been reported. Human genomic sequences have also been used in comparative studies with both mouse and Fugu rubripes.
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Curr Opin Genet Dev,
1996]
The sequencing of the 100 Mb Caenorhabditis elegans genome-containing approximately 14,000 genes-is approximately 50% complete. One of its most interesting features is its compactness; introns and intergenic distances are unusually small and, surprisingly, approximately 25% of genes are contained in polycistronic transcription units (operons) with only approximately 100 bp between genes.
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Genome Res,
1995]
Caenorhabditis elegans, a free-living nematode worm, has proved a particularly useful model organism for studying the anatomy, behavior, genetics, and development of a metazoan. It also has one of the smallest genomes of the higher eukaryotes (100 Mb distributed over six chromosomes), making it an ideal candidate for detailed molecular analysis. The C. elegans genome project began over 10 years ago and is a collaberative effort between two laboratories (St. Louis, MO, USA and Cambridge, UK), with the ultimate aim of mapping and sequencing the whole of the 100-Mb genome. The consortium has now completed the sequence of approximately one-fifth of the genome and plans to have sequenced more than half the genome before the end
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J Inherit Metab Dis,
2001]
The 100 Mb Caenorhabditis elegans genome sequence is the first animal genome to be sequenced in its entirety. Many reverse-genetics tools have been developed to mine the genome sequence and to facilitate the jump between the identification of a gene sequence and the understanding of its function. Here we discuss how C. elegans can contribute to understanding of the function of genes involved in human development and disease.
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Methods Cell Biol,
1995]
The clone-based physical map of the 100-Mb Caenorhabditis elegans genome has evolved over a number of years. Although the detection of clone overlaps and construction of the map have of necessity been carried out centrally, it has been essentially a community project. Without the provision of cloned markers and relevant map information by the C. elegans community as a whole, the map would lack the genetic anchor points and coherent structure that make it a viable entity. Currently, the map consists of 13 mapped contigs totaling in excess of 95 Mb and 2 significant unmapped contigs totaling 1.3 Mb. Telomeric clones are not yet in place. The map carries 600 physically mapped loci, of which 262 have genetic map data. With one exception, the physical extents of the remaining gaps are not known. The exception is the remaining gap on linkage group (LG) II. This has been shown to be bridged by a 225-kb Sse83871 fragment. Because the clones constituting the map are a central resource, there is essentially no necessity for individuals to construct cosmid and yeast artificial chromosome (YAC) libraries. Consequently, such protocols are not included here. Similarly, protocols for clone fingerprinting, which forms the basis of the determination of cosmid overlaps and the mapping of clones received from outside sources and has to be a centralized operation, and YAC linkage are not give here. What follows is essentially a "user's guide" to the physical map. Details of map construction are given where required for interpretation of the map as distributed. The physical mapping has been a collaboration between the MRC Laboratory of Molecular Biology, Cambridge, United Kingdom (now at The Sanger Centre, Cambridge, UK) and Washington University School of Medicine, St. Louis, Missouri. Inquiries regarding map interpretation, information, and materials should be addressed to alan@sanger.ac.uk or rw@nematode.wustl.edu.
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Trends Genet,
1997]
The 100 Mb sequence of the nematode Caenorhabditis elegans genome will be completed in 1998. More than 10,000 predicted genes have been identified to date, so it should come as no surprise to find a C. elegans homologue of your favourite gene in current databases. For some investigators, the discovery of a C. elegans homologue represents a unique opportunity to adopt a genetic approach and to take advantage of the extensive repertoire of C. elegans gene characterization and manipulation tools. RNA injection provides a quick and efficient method for obtaining clues about wild-type gene function. Reverse genetic approaches also make it feasible to screen de novo for mutations in specific gene sequences. This review highlights the resources available for analysing a C. elegans homologue, starting from the gene sequence and proceeding to the biological function.
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Methods Mol Biol,
1999]
The nematode Caenorhabditis elegans has gained widespread popularity for use in addressing many biological problems, particularly those relating to development (for brief topical reviews, see 1-5; for comprehensive treatises, see 6-10). This can be attributed to both inherent properties of the organism as well as the collegiality extant within the "worm community". With respect to the former, C. elegans is extremely east to grow in the laboratory (animals are typically propagated on agar-filled Petri dishes seeded with the bacterium Escherichia coli) and possesses a short generation time (3 d at 20C). The system is genetically robust, with the availability of thousands of mutants as well as the existence of a physical map whose sequencing (over 82 Mb finished at present) is scheduled for completion in 1999. Developmental studies have been advantaged by the animal's transparent nature, facilitating complete elucidation of C. elegans' largely invariant cell
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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.