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New Mosquito Genome Expected to Serve as Infectious Disease Resource

NEW YORK (GenomeWeb) – An international research team has published a high-quality and re-annotated version of the Aedes aegypti mosquito genome that is intended to aid in future infectious disease research and control efforts.

"The resulting annotated genome is really impressively complete and has already had a huge impact on the field, allowing scientists around to world to carry out a number of experiments that were previously impossible," senior author Leslie Vosshall, a neurogenetics and behavior researcher at Rockefeller University, said in a statement.

As part of a crowd-sourced research effort, members of the Aedes Genome Working Group put together a roughly 1.3-billion-base genome assembly for Ae. aegypti — a vector for many important infectious disease agents, including the Zika virus — using a combination of Pacific Biosciences single-molecule, real-time, long-read sequence data, Bionano Genomics optical mapping, Hi-C profiling, 10x Genomics Chromium linked-read sequencing, Illumina short-read sequencing, and RNA sequencing.

The genome, described in more detail today in a paper online in Nature, is expected to serve as a resource for scientists pursuing mosquito genome editing  and other approaches aimed at curbing infectious disease transmission by mosquitoes.

"To effectively edit the genome of the mosquito, you need to know more than just the sequence of the genes involved. You also need to know the sequence of the surrounding DNA regions, so that you know where to insert the desired genes. And that's why it's so important that this new genome is correct and complete," co-first author Benjamin Matthews, a researcher in Vosshall's lab, said in a statement, noting that "[d]ozens, if not hundreds, of labs" have already accessed the new genome assembly.

The team's effort was spurred by gaps and incomplete information in a draft version of the repeat-rich Ae. aegypti genome that was published in Science more than a decade ago, despite improvements in the Ae. aegypti genome achieved by a Baylor College of Medicine-, Rice University-, and Broad University-led team that incorporated Hi-C data for another Science paper published last year.

"The genome was in so many pieces that we weren't sure how they fit together, and we also weren't sure that it was complete. And if you can't trust that the DNA sequence was correctly assembled, you're not going to get very far," Matthews said.

Compared to previous versions of the Ae. aegypti genome, for example, the new assembly had dramatically increased contiguity, the researchers reported, revealing dozens of previously unappreciated genes, structural variants not described in the past, and other more refined views of Ae. aegypti genome features such as sex determination.

And in proof-of-principle analyses, the team demonstrated that restriction site-associated DNA marker mapping with the new "AaegL5" genome assembly could help in identifying quantitative trait loci that mediate the mosquito's ability to serve as a vector for the dengue virus, while genome-wide screening based on the chromosome-scale assembly led to candidate sites for insecticide resistance.

Based on these and other findings, the authors suggested that AaegL5 "will catalyze new biological insights and intervention strategies to fight this deadly disease vector."

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