Filarial worms genome project
Filarial worms and their larvae are parasitic thread-like round nematodes that cause a group of tropical infectious disease called Filariasis (Philariasis). The larvae are transmitted to humans through a mosquito bite. Filariasis is characterized by fever, chills, headache, and skin lesions in the early stages and, if untreated, can progress to include gross enlargement of the limbs and genitalia in a condition called elephantiasis. The worms dwell within the lymphatic and subcutaneous tissues. Up to 170 million people worldwide in the tropical and subtropical areas of Southeast Asia, South America, Africa, and the islands of the Pacific are affected by this debilitating parasitic disease. While filariasis is rarely fatal, it is the second leading cause of permanent and long-term disability in the world.
The Filarial worm sequencing project had two main goals:
Generate a high quality draft genome assembly and automated annotation for the filarial worm Loa loa.
Test ability of using single worm whole genome amplified DNA to generate low coverage assemblies and automated annotation of two additional worms, Wuchereria bancrofti and Onchocerca volvulus.
Filarial worms are parasitic nematodes that dwell within the lymphatics and the subcutaneous tissues of up to 170 million people worldwide. Among the eight filarial infections of humans, those that cause loiasis, onchocerciasis, and lymphatic filariasis are important causes of morbidity. These include the causative agents of lymphatic filariasis Wuchereria bancrofti, Brugia malayi, and Brugia timori--and the subcutaneous filariid Onchocerca volvulus, the causative agent of river blindness, or onchocerciasis. The other filarial parasites of humans (Loa loa, Mansonella perstans, Mansonella streptocerca, and Mansonella ozzardi) show greatly reduced pathogenicity. The study of these parasites and the diseases they cause has been greatly hampered by the fact that for most of these organisms, humans are the only definitive host and parasite material must be purified from human blood or tissues. In fact, B. malayi, was selected to be the first parasitic nematode to be fully sequenced despite its relatively minor current importance as a human pathogen because it is the only major filarial parasite of humans that can be maintained in small laboratory animals.
The three filarial worms being sequenced here infect an estimated 153 million people. W. bancrofti (~120 million people), O. volvulus (~20 million people), and Loa loa (~13 million people). The genome sequences generated here will enable us to study crucial phenotypic differences, including drug resistance, between these closely related filarial species. In addition, these data will allow us to start to define the extent of synteny, to characterize heterozygosity and produce microsatellite makers, which will help us plan the more comprehensive studies of population genetics that are needed. Finally, from a practical point of view, there is an extreme need to generate proteomic information from these parasites that requires this genomic data to interpret them.
We targeted Loa loa for this initial work for two important reasons. First, among the four pathogenic filarial parasites described above, Loa loa is the least well studied. However, Loa loa, is gaining clinical prominence because of serious adverse events following treatment, including death. As a result, the parasitological community has called for a better understanding of this organism to promote better methods of diagnosis, treatment and prevention. A second justification for prioritizing Loa loa is the fact that unlike any of the other filarial parasites of humans, Loa loa does not contain the alpha-proteobacterial endosymbiont, Wolbachia. This suggests that either there has been lateral transfer of important bacterially-encoded genes or that the obligate relationship between the endosymbiont and its filarial host is dispensable. Initial analysis of the B. malayi genome revealed adaptations that appear to have evolved in response to the pressures of parasitism and to the presence of the parasite's Wolbachia endosymbiont, wBm. Testing this and understanding the comparable adaptations of Loa loa will be extremely important to understand the potential impact of the endosymbiont on pathogenicity. Because Loa loa is more distantly related to the previously sequenced Brugia malayi (the only parasitic nematode to be fully sequenced) than is W. bancrofti or O. volvulus, the Loa loa sequence will help inform more generally about the genomic structure and biological diversity of these organisms.
We produced 3 whole genome shotgun assemblies using data generated from fragment and 3kb paired-end libraries sequenced using Roche/454 sequencing technologies. Only fragment reads were used for whole genome amplified worm samples (Wuchereria bancrofti and Onchocerca volvulus). The resulting assemblies and annotations were made public in May of 2010. Questions about the project should be directed to firstname.lastname@example.org.
Bruce Birren - Broad Institute
Doran Fink - NIH/NIAID
Thomas Nutman - NIH/NIAID
Image captions and credits
The images on the home page are, from left to right:
Micrograph of the anterior end of a Wuchereria bancrofti microfilaria in a blood smear using Giemsa stain. Content Provider: CDC/Dr. Mae Melvin
Micrograph of the posterior end of a Brugia malayi microfilaria in a thick blood smear using Giemsa stain. Content Providers: CDC/Dr. Mae Melvin
Loa loa, agent of filariasis. Anterior end. Content Providers: CDC/ Dr. Lee Moore
Loa loa, posterior end. Agent of filariasis. Content Providers: CDC/ Dr. Lee Moore
Elephantiasis of leg due to filariasis. Luzon, Philippines. Content Providers: CDC
This sequencing project was supported by the National Institute of Allergy and Infectious Disease, National Institutes of Health funded Genome Sequencing Center for Infectious Diseases at the Broad Institute.