Researchers find clues to common birth defect in gene expression data

February 6, 2012, Jackson Laboratory

Researchers at MassGeneral Hospital for Children (MGHfC), The Jackson Laboratory and other institutes have uncovered 27 new candidate genes for congenital diaphragmatic hernia (CDH), a common and often deadly birth defect.

Their sophisticated data-filtering strategy, which uses during normal development as a starting point, offers a new, efficient and potentially game-changing approach to .

born with CDH—representing one in every 3,000 live births—have a hole in the diaphragm that separates the abdominal cavity from the chest cavity, and may die due to poor growth of the lung.

Patricia K. Donahoe, M.D., director of the Pediatric Surgical Research Laboratories at MGHfC, explained, "That hole can be fixed surgically if CDH has been diagnosed in time. But even surgery does not rescue the infants' impaired lung development, which often leads to fatal respiratory complications." Patients who survive into adulthood "tend to have a lot of ongoing health issues," she noted.

Donahoe and her colleagues Meaghan Russell, Ph.D., and Mauro Longoni, M.D., and Jackson Laboratory Professor Carol J. Bult, Ph.D., a computational biologist, led the research, published in the Proceedings of the National Academy of Sciences. The team had two goals: to identify the genes and gene networks that cause the hole in the diaphragm in order to develop new diagnostics and preventive treatments, and to learn more about how healthy lungs form to boost lung development in post-operative infant patients.

Bult and her Jackson colleague Julie Wells, Ph.D., generated gene expression profiles—snapshots of gene activity—for embryonic mouse diaphragms at multiple stages of development. Using algorithms designed by the JAX-MGH team, they used these data to then predict genes likely to contribute to diaphragm defects.

Bult said, "We asked which genes in our developmental data sets work together in common pathways, and which of these pathways contain previously known CDH genes from human studies and mouse models?"

To build gene networks, the researchers used the Mouse Genome Informatics (MGI) data base resource based at The Jackson Laboratory. MGI, freely available to the research community, maintains the most comprehensive collection of mouse genetic and genomic information.

The researchers' filtering strategy identified 27 new for CDH. When the investigators examined the diaphragms of knockout mice for one of these candidate genes—pre-B cell leukemia transcription factor 1 or Pbx1—they found previously unreported diaphragmatic defects, confirming the prediction.

The next step in the project is to screen patients for mutations in Pbx1 using the collection of CDH patient data and DNA that MGHfC and Children's Hospital Boston have been accumulating for years in collaboration with hospitals from around the world.

The research reported in the paper opens the door "not only to further research to explore the effects of the other 26 CDH candidate genes," Bult said, "but to a disease gene identification and prioritization strategy for CDH, an approach that can be extended to other diseases and developmental anomalies."

Explore further: In-utero procedure for birth defect of the diaphragm significantly improves infant survival

Related Stories

In-utero procedure for birth defect of the diaphragm significantly improves infant survival

December 14, 2011
A new study published in the journal Ultrasound in Obstetrics & Gynecology reveals that fetal tracheal occlusion (FETO) improves infant survival rate in severe cases of congenital diaphragmatic hernia (CDH).

'Imprinted' developmental genes gain new roles in adult stem cells

September 8, 2011
(PhysOrg.com) -- The repair of tissues damaged by injury or illness relies on the ability of adult stem cells to grow and self-renew. But this ability needs to be tightly controlled; if regulation is lost, the stem cells ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.