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Schistosomiasis: Sequencing the Parasites’ Genes
  
By Kate Ruder

Female S. mansoni worm ready to lay eggs in canal of male worm.

Scientists have sequenced the genes of two of the parasitic worms that cause schistosomiasis, a disease that causes malnutrition, kidney failure, bladder cancer, and other symptoms in millions of people throughout the world.

The new research also identifies proteins in the parasite that eventually could be disabled by vaccines or drugs. This news is especially welcome because there is no vaccine against schistosomiasis and resistance appears to be growing against the one drug used to treat the disease.

The two parasites sequenced are Schistosoma japonicum, which causes intestinal schistosomiasis in humans and farm animals in China and other Asian countries, and Schistosoma mansoni, which causes a more prevalent but less severe form of the disease throughout the tropics and sub-tropics and is found mostly in humans.

The Chinese National Human Genome Center in Shanghai, led the S. japonicum project. The State of São Paulo Research Foundation, a state-funded scientific institute in Brazil, led the sequencing of S. mansoni.

The parasite that causes the disease—a worm that lives in freshwater lakes and rivers—is a wily and terrifying predator.

Pair of S. mansoni worms.

The worms burrow through the unbroken skin of unsuspecting swimmers, bathers, and farmers. They travel through the victim's blood vessels and mature, meanwhile masking themselves with a protective membrane and shedding their tails.

Female worms produce up to 2,000 of the highly toxic eggs a day. The worms can live up to ten years inside the human body.

The worms' complex life cycle has proved resoundingly robust: Schistosomiasis has plagued humans for thousands of years. Worm eggs have even been found in Egyptian mummies.

Doctors desperately need more options to treat, prevent, and diagnose schistosomiasis. The drug Praziquantel has been used for years to treat the disease but resistance to the drug is developing in certain areas of the world such as Egypt.

The newly reported research published in two separate studies does not include whole-genome sequences but rather sequences and analyses of most of the 15,000 genes of both of these parasites.

The Chinese National Human Genome Center is now sequencing the complete genome of S. japonicum. The Institute for Genomic Research in Rockville, Maryland , along with the Wellcome Trust Sanger Institute in the United Kingdom, has begun to sequence S. mansoni and expects to complete the project this year.

Related Sites
Schistosoma mansoni EST Genome Project
TIGR S. mansoni Genome Project
Schistosoma japonicum cDNA Project

Potential treatments for schistosomiasis are probably a long way down the road, but the gene sequences have given scientists a fresh group of vaccine targets to test in the laboratory.

“There are a whole slew of potential proteins [in the parasite] that can now be examined,” says Paul J. Brindley of Tulane University Health Sciences Center in New Orleans, Louisiana, who worked on the S. japonicum project.

Researchers now have two online databases of sequences to probe for proteins in the parasite that could be disabled by drugs or vaccines. And scientists at the University of São Paulo are building DNA microarrays to study the effects of drugs on the worms and to study how genes are expressed at different stages of the parasite's lifecycle.

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Verjovski-Almeida, S. et al . Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni . Nature Genetics 35 , 148-157 (October 2003).

 

Hu, W. et al. Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource. Nature Genetics 35 , 139-147 (October 2003).

 

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