Gene mutation responsible for lung and diaphragm defects

To breathe normally, people need more than just healthy lungs. A diaphragm - the large muscle that creates a vacuum to draw air into their lungs - is also crucial. Birth defects in the diaphragm, such as congenital diaphragmatic hernia (which are about as common as cystic fibrosis), are often fatal. "A lot of people haven't heard of this [disorder] because so many of the kids die early," said Kate Ackerman, Harvard Medical School researcher and lead author of the study in PLoS Genetics.

To explore the genetic roots of these birth defects - hitherto a mystery - Ackerman and her colleagues screened mice with induced genetic mutations. The researchers discovered that a mutation in the mouse Fog2 gene can cause small lungs and abnormal diaphragm development. Could the same gene be involved in human diaphragmatic defects? After studying children with similar problems, the authors did indeed identify a child with a serious Fog2 gene mutation who died on the first day of life with severe breathing difficulties, small lungs, and an abnormal diaphragm.

"This is the first identified cause of [this type of] diaphragmatic defect," Ackerman said. "And now we have a mouse model to try to learn more." This discovery means that researchers now have an important genetic starting point to generate further insight into a poorly understood range of human disorders.

Citation: Ackerman KG, Herron BJ, Vargas SO, Huang H, Tevosian SG, et al. (2005) Fog2 is required for normal diaphragm and lung development in mice and humans. PLoS Genet 1(1): e10.

CONTACT:
Kate G. Ackerman
Brigham and Women's Hospital
Harvard Medical School
Medicine
New Research Building 458
77 Avenue Louis Pasteur
Boston, MA USA 02115
1-617-525-4761
1-617-525-4751 (fax)
kackerman@rics.bwh.harvard.edu

PLoS Genetics (www.plosgenetics.org), a new open-access, peer-reviewed journal published by the Public Library of Science (PLoS), will premier on July 25, 2005. The journal is lead by the Editor-in-Chief, Dr. Wayne N. Frankel, a Senior Staff Scientist at The Jackson Laboratory in Bar Harbor, Maine.

PLoS Genetics will capture the breadth and scope of quality genetics research from around the world. We invite you to judge PLoS Genetics for yourself by reading the two papers we are previewing from the first issue.

Open access - free availability and unrestricted use­ to all articles published in the journal - is central to the mission of PLoS Genetics. "Genetics and genomics research have lead the way for timely, open access policies to all types of biological data - it is high time that we applied the same principle to our papers and unleash our creativity to develop new ways to use the scientific literature," the editorial team says.

The two papers released now report a gene involved in diaphragm defects in humans, and a community effort to annotate the genome of the yeast that causes thrush and other conditions. This sneak peek of the first issue will be available online at www.plosgenetics.org on June 17. The articles are free to download and to use by anyone with an internet connection.

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