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Winter 2015

Ferret genome study provides respiratory system clues

Copyright: Craig M. Groshek
News from: The Genome Analysis Centre

The study was coordinated by Michael Katze and Xinxia Peng at the University of Washington (UW) and Federica Di Palma at The Genome Analysis Centre (TGAC), and Jessica Alfoldi at the Broad Institute of MIT and Harvard.

"By creating a high quality genome and transcriptome resource for the ferret, we have demonstrated how studies in non-conventional model organisms can facilitate essential bioscience research underpinning health," said Federica Di Palma, Director of Science at TGAC.

Ferrets have long been considered the best animal model for studying a number of human diseases, particularly influenza, because the strains that infect humans also infect ferrets and spread in a similar way.

The researchers first sequenced and annotated the genome of a domestic sable ferret, Mustela putorius furo, and then a technique called transcriptome analysis was used to reveal which genes were being turned on, or "expressed," in ferret tissues when challenged by influenza and in a "knock out" model of cystic fibrosis.

"This is a big deal," said Michael Katze, UW professor of Microbiology. "Every time you sequence a genome, it allows you to answer a wide range of questions you couldn't before. Having the genome changes a field forever."

Ferrets were exposed to a reconstructed version of the "Spanish flu" virus that caused pandemic flu in 1918 and the "swine-flu" virus of 2009-2010. Researchers then collected samples from the animals' tracheas and lungs on the first, third and eighth day of the infection for analysis.

The two viruses affected the ferret trachea and the lungs differently, says Xinxia Peng, a research assistant professor in the Katze lab: "The 1918 flu elicited a huge response on day one and that response was sustained. The 2009 pandemic flu triggered a response that gradually grew over several days. They had very different trajectories."

In the lung, gene transcription triggered by both viruses was roughly the same, but this was different from that seen in the trachea. "This side by side comparison reveals that the host response to these two viruses differs primarily in the trachea and may explain the course of infection," Peng said.

In a cystic fibrosis model, changes in the expression of genes can be seen on the first day of life and increase significantly over the next 15 days.

"We found that there are transcriptional changes from day one, right out-of-the-gate, and many of the changes are very similar to those seen in humans," says Peng. "The findings suggest that some of the disease processes responsible for the lung damage seen in cystic fibrosis begin very early in life."

Katze said transcriptome responses seen in both the influenza studies and the cystic fibrosis studies closely resemble those seen in humans, suggesting that ferret models will not only help scientists understand these two diseases but a broader set of diseases including heart disease and diabetes.

TGAC is strategically funded by BBSRC and operates a National Capability to promote the application of genomics and bioinformatics to advance bioscience research and innovation.

Notes to editors

The paper: The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease. Nature Biotechnology. DOI: doi:10.1038/nbt.3079.