Ferret genome hold clues to respiratory diseases

The National Institute of Health funded a project coordinated by Michael Katze and Xinxia Peng at the University of Washington in Seattle and Federica Di Palma and Jessica Alfoldi at the Broad Institute of MIT and Harvard. This study takes a look at the ferret genome in hopes that it can provide important information on human diseases such as cystic fibrosis and influenza.

An internationalized research effort has a draft sequence of the ferret genome, this sequence was used to analyze how flu and cystic fibrosis affect the respiratory track at the cellular level. The ferret was used because they are a good model for the study of human diseases especially influenza because they can be infected by the same strains as humans.

The scientist at Broad Institute of MIT and Harvard sequenced and annotated the genome of a domestic sable ferret. They then collaborated with Katze group on the analysis. They used transcriptome analysis which identifies all the RNA that is being produced, or transcribed, from areas of the genome that is begin activated at a specific time. This analysis helps scientist determine how ferrets cells are responding when challenged by influenza and in cystic fibrosis.

The part of the study that deals with influenza was conducted at the University of Wisconsin-Madison by Yoshihio Kawaoka's group. They exposed the ferrets to reconstructed version of the virus that caused the flu of 1918, 2009 swine flu, and Spanish flu. They then collected trachea and lung samples on the first, third, and eighth days of infection. The samples were then used for transcriptome analysis. 

Katze team found that there were two viruses that affected the trachea and lungs differently. The 1918 virus triggered marked transcriptional responses on the first day of infection and this response sustained through day eight. The 2009 swine flu strain triggered a response that started slow and grew with it peaking at day eight. In the lungs the gene transcription triggered was about the same for both viruses.

John Engelhard's group at Iowa wanted to better understand cystic fibrosis. To do this they genetically engineered a ferret lacking the gene for the membrane protein called cystic fibrosis trans membrane conductive regulator, this detective gene is responsible for the disease. 

The analysis of the transcriptome of the gene knock-out ferrets reveled that the changes in the expression of the gene can be seen on the first day of life and increase for 15 days. These changes were similar to those found in humans for both diseases. The findings suggest that the disease processes responsible for lung damage occur early in life.

This study is very important to future research in influenza, cystic fibrosis and possible other diseases. The ferrets have proved to be a good model to use for research into these diseases because they respond similarly to humans. Hopefully discoveries are made by learning more about these diseases that can help those who are affected by them.

Article: http://www.sciencedaily.com/releases/2014/11/141117130222.htm
Related article:http://www.genome.gov/pages/research/sequencing/seqproposals/ferretseq.pdf