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River Blindness Parasite Genome Studies Provide Resources for Neglected Disease

NEW YORK (GenomeWeb) – Two independent research teams have used genomics to explore the genetic variability — and potential vulnerabilities — of Onchocerca volvulus, a parasitic roundworm transmitted by blackflies that can cause river blindness, also known as onchocerciasis. The chronic, neglected tropical disease affects tens of millions of people globally, leading to blindness or vision problems in a subset of sufferers.

For one of the two studies, both published in Nature Microbiology today, a team led by investigators at the Wellcome Trust Sanger Institute, New York University, and the New York Blood Center presented information gleaned from a newly generated draft genome assembly for O. volvulus.

Using a combination of paired-end and mate-pair Illumina sequencing, the researchers sequenced genomic DNA from an adult female O. volvulus representative and from an adult female O. ochengi, a related species that parasitizes cattle.

When they put together the resulting O. volvulus sequences, with the help of an optical map and manual assembly steps, the resulting nuclear genome assembly spanned 97 megabases and contained an estimated 12,143 protein-coding genes — an annotation helped along by RNA sequences generated across eight parasite stages.

The team also generated a mitochondrial genome sequence for the parasite and a genome for a Wolbachia bacterial endosymbiont associated with the nematode. The latter genome was about 956,000 bases in size and housed some 785 suspected protein-coding genes, offering a look at Wolbachia-encoded metabolic enzymes that may boost functions performed by O. volvulus.

From these sequences and data for resequenced male and female O. volvulus nematodes, the researchers also got a glimpse at the X and Y chromosomes, identifying sites of divergence between the sex chromosomes. More than 90 percent of the O. volvulus genes were orthologous to those found in other roundworms, while almost 1,200 genes appeared to be specific to the river blindness parasite. The genome is expected to offer insights into host-parasite interactions, along with potential drug targets, the researchers explained.

"Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability," the authors wrote. "In addition, we have generated a list of proteins that could be targeted by … approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development."

Meanwhile, researchers from Washington University's McDonnell Genome Institute and elsewhere compared genomic patterns in more than two dozen O. volvulus isolates collected in Ecuador, Uganda, forest regions of West Africa, and West African savanna sites more than two decades ago, prior to mass treatment efforts. In addition to identifying groups of parasites that clustered by locale, their data helped to narrow in on ancestry-informative loci.

Members of that team used Illumina technology to sequence the genomes of 27 O. volvulus samples, including six West African savanna isolates, nine isolates from forest regions in West Africa, two Ugandan isolates, and 10 isolates from Ecuador. The O. volvulus nuclear genomes were covered to an average depth of 66-fold, while mitochondrial genomes were covered to almost 4,600-fold, on average, and Wolbachia endosymbionts were sequenced to an average depth of 216-fold.

Based on the 1.3 million nuclear SNPs and other variants detected in the genomes, the investigators saw genetic clusters of parasites corresponding to the Ugandan, West African, and Ecuadorian sites — information they drew on to develop ancestry-informative markers that separated the parasites in different countries and in the forest and savanna sites.

"The catalogue of the nuclear, mitochondrial, and endosymbiont DNA variants generated in this study will support future basic and translational onchocerciasis research, with particular relevance for ongoing control programs, and boost efforts to characterize drug, vaccine, and diagnostic targets," senior author Makedonka Mitreva, an infectious disease researcher at Washington University, and her co-authors wrote.