Researchers at the Baylor College of Medicine, Massachusetts Institute of Technology and Harvard University have devised a new method of genome sequencing, which they have used to decipher the genetic code of the mosquito that carries the Zika virus; Aedes aegypti as well as that of Culex quinquefasciatus, a mosquito that transmits West Nile virus.

Genome sequencing is not cheap and nor is it easy, given that a chromosome can have hundreds of millions of genetic base pairs. In 2003, the Human Genome Project announced the completion of the human genome after 13 years which cost USD2.7 billion in total.

The new method, called “3D assembly”, proves to be a lot less laborious and is said to be able to sequence and build genomes in a couple of weeks for less than USD10,000.

New method analyses chromosome folds

Genome sequencing has advanced since the first human genome was completed, but current sequencing technologies require DNA to be cut into short snippets to piece them back together, forming continuous strings of letters.

This makes it difficult to ascertain where smaller DNA sections connect, in part because DNA is folded like molecular origami to squeeze six and a half feet of genetic material into each cell’s nucleus.

“It’s like a puzzle that’s missing a few pieces from the box,” said Daniel Neafsey, a geneticist at the Broad Institute Massachusetts and co-author of the paper.

In the new method, researchers take advantage of the technique of folding maps to quickly build a sequence. By looking at how chromosomes fold, researchers use a method called ‘Hi-C’ to create a guide to identify the proximity of the genome fragments. This method uses shorter reads of DNA which lowers the cost.

To prove that this method works, researchers sequenced the entire genome of an Aedes mosquito, which carries the Zika virus.

Mosquito’s ghost genes revealed

Although previous work was carried out in 2007, there was no complete genetic picture of the mosquito as scientists could not figure out how all of the DNA pieces fit together. With the 3D-assembly method, they were able to complete the missing pieces of the Aedes genome.

David Severson, a mosquito researcher at the University of Notre Dame, Indiana, who coordinated the initial Aedes genome project, lauded the team’s effort.

“I’ve been waiting to work with something like this for probably twenty years,” he said. The completed genome will help scientists formulate new questions about how genes combine to influence traits.

These genes were “like a ghost”, said Neafsey. “Even if you know functionally the gene should be there, you don’t have the means to study it.”

However, this improved genome is still not perfect: it omits millions of DNA bases, and some sequences are likely in the wrong orientation. The Aedes Genome Working Group, which formed last year after the Zika outbreak, is in progress of constructing an even more complete and accurate genome.

One step closer to personalised healthcare

Although more complex organisms would require more work, scientists hope the dramatically lower cost provides the approach widespread use, both in biology and medicine. For example, it could be used to review the current Zika virus and aid in the combat against the spread of mosquito-borne diseases.

Alternatively, physicians and researchers would be able to access genetic information of patients more easily, thereby helping create patient-specific medication and treatment. It could also aid researchers who are working on building a common genetic database for more efficient healthcare.

"To figure out what's going on, we need technologies that can report a patient's entire genome. But, we also can't afford to spend millions of dollars on every patient's genome." said Dr Aviva Presser Aiden, a physician scientist at Texas Children's Hospital, and co-author of the new study.

"Sequencing a patient's genome from scratch using 3D assembly is so inexpensive that it's comparable in cost to an MRI," said Olga Dudchenko, a postdoctoral associate at Baylor College of Medicine.

"Generating a de novo genome for a sick patient has become realistic." MIMS

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