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UK Team Develops Genetic Map for Plant Used In Malaria Treatment

NEW YORK (GenomeWeb News) – Researchers from the University of York reported in Science online today that they have created the first genetic map for the medicinal herb Artemisia annua, which contains an extract called artemisinin that's used to help treat some forms of malaria.

Through deep sequencing of a hybrid plant's transcriptome and pedigree experiments, the team found genetic variants that they used to develop an A. annua genetic map. By combining these newly developed genetic resources with field trials, the researchers have also started finding genetic markers expected to speed up selective breeding efforts aimed at improving artemisinin production.

"With our new understanding of Artemisia genetics, we can produce improved, non-[genetically modified] varieties of Artemisia much faster than would otherwise be possible," lead author Ian Graham, a biologist at the University of York's Centre for Novel Agricultural Products, said in a statement.

Artemisinin is typically used to treat forms of malaria caused by the parasite Plasmodium falciparum — particularly uncomplicated cases. Because artemisinin resistance is a growing problem, the compound is usually given in combination with other drugs as part of so-called Artemisinin Combination Therapies, or ACT, rather than on its own.

Nevertheless, artemisinin is quite difficult to produce. Despite efforts underway to synthesize artemisinin precursor compounds in microbes, most artemisinin is still extracted from A. annua, a crop plant containing variable levels of the compound.

Graham and his co-workers explained that new genetic tools could help in improving A. annua varieties, making them more reliable and economically viable for producers and subsequently increasing the amount of artemisinin available for treating malaria.

"Improved varieties of A. annua for developing world farmers would bring immediate benefits to the existing artemisinin supply chain by reducing production costs, stabilizing supplies, and improving grower confidence in the crop," they wrote.

For the current study, the researchers used Roche 454 sequencing to create expressed sequence tag databases representing several tissues from Artemis, a relatively high artemisinin-producing hybrid A. annua variety developed by the Swiss company Mediplant.

The team then sifted through the EST data to find clues about everything from the plant's metabolism to its phenotypic traits, looking for genetic insights into traits affecting artemisinin production.

In the process, they also identified more than 34,400 SNPs in the hybrid plant as well as 49 short sequence repeat markers. Of the 675 Artemis SNPs selected for further study, the researchers validated 398. A similar approach turned up more than 50,100 SNPs (of which 177 were validated) and 48,900 SNPs (191 validated) in A. annua populations grown in Uganda and Madagascar, respectively.

Using an Illumina GoldenGate platform and 1,536 SNPs picked from the three plant populations to genotype the Artemis pedigree, the team detected a great deal of heterozygosity in various Artemis populations and parental strains — consistent with the variable phenotypes and artimisinin concentrations observed in the plants.

Exploiting this heterozygosity, the researchers used data from 242 Artemis plants to come up with genetic linkage maps representing Artemis parental strains — an approach that revealed nine linkage groups. In addition, field trials and Artemis hybrid self-pollination experiments uncovered several quantitative trait loci associated with artemisinin yield.

Senior author Dianna Bowles, a University of York Centre for Novel Agricultural Products biologist, said in a statement today that she and her colleagues expect the genetic map to facilitate the development of new high-yielding A. annua strains within the next two or three years.

"Our study has established the molecular basis for marker-assisted breeding of this medicinal plant species and highlights the reduced timelines that are now feasible for developing this platform of knowledge and tools," the researchers concluded. "Development of new high-yielding varieties optimized for production in different geographic regions is now a realistic target."

In an accompanying article set to appear in the same issue of Science, University of South Florida researcher Wilbur Milhous and Walter Reed Army Institute of Research researcher Peter Weina agreed that Graham, Bowles, and colleagues "have paved the way to fast-track breeding varieties in A. annua plants with highly desirable genetic traits."

But while they praised the team's approach and findings, they also noted that additional research will likely be needed to tackle issues related to artemisinin resistance.

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