Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study finds genetic variant plays role in cleft lip

07.10.2008
First time a genetic variant has been associated with cleft lip alone
University of Iowa researchers and collaborators have found, in a previously identified gene, a variation that likely contributes to one in five cases of isolated cleft lip. It is the first time a genetic variant has been associated with cleft lip alone, rather than both cleft lip and palate.

The study provides insight on a previously unknown genetic mechanism and could eventually help with diagnosis, prevention and treatment of cleft lip, which affects more than five million people worldwide. The findings appeared Oct. 5 in the journal Nature Genetics.

In 2004, a worldwide team involving the University of Iowa identified the gene IRF6 as a contributor to about 12 percent of cases of the common form of cleft lip and palate. The new finding pinpoints a regulatory part of the IRF6 gene that binds to a protein called AP2. This regulatory part controls how much and when the critical IRF6 protein is made.

The finding involved the lab of University of Iowa Carver College of Medicine faculty member Jeff Murray in collaboration with the University of Iowa lab of Frederick Domann, Ph.D., and adjunct faculty member Brian Schutte, Ph.D. Other investigators in Denmark, Norway, Scotland, Italy, the Philippines, California, and at the National Institutes of Health and the University of Pittsburgh were also critical to the investigation.

"We knew from the earlier study that IRF6 increases the risk of clefting. There are millions of common variants in the humane genome, but only a fraction have beneficial or harmful functions," said Fedik Rahimov, Ph.D., the lead author of the study and a graduate of the University of Iowa Interdisciplinary Program in Genetics, who worked in Murray's lab.

"We found that a common variant in the IRF6 gene severely disrupts the ability of AP2 to bind to it. This in turn disrupts proper expression of the IRF6 gene," said Rahimov, who is now a postdoctoral research fellow at Harvard Medical School.

The team used computational and biological approaches to conduct the study. First, with assistance from the NIH Intramural Sequencing Center at the National Human Genome Research Institute and based on previous University of Iowa research, the investigators used nonhuman DNA to predict potential regulatory sections around the gene in question.

Regulatory sections are separate from, but affect, the protein coding sections of genes. Regulatory sections are generally highly "conserved," meaning they have not changed much over evolution. However, one of the regulatory sections around IRF6 revealed a single nucleotide variant, so the team focused on the corresponding area in human DNA already identified by a previous UI graduate student.

Next, through a connection with the Lawrence Berkeley National Laboratory at the University of California, the variant was shown to reside in a regulatory element that controls IRF6 expression. The team then studied large DNA collections on cleft lip and palate and found that among nearly 3,000 families those with cleft lip only were far more likely to have the genetic variant.

"It was most striking that this variant was associated with clefts of the lip only," Rahimov said. "We always thought that cleft lip alone and cleft lip with cleft palate were the same disease. Now we see a difference and will analyze patients with cleft lip separately from those who have both cleft lip and palate."

The investigative work on AP2 involved collaboration between Rahimov and Michael Hitchler, Ph.D., currently a post-doctoral fellow at the University of Southern California and a recent graduate of the University of Iowa Graduate Program in Free Radical and Radiation Biology, who worked in Domann's lab. That lab was studying the role of AP2 in cancer, and so, already had developed research technology to study AP2 binding. Using this technology, the lab was able to rapidly provide evidence that AP2 was bound to the IRF6 regulatory region.

"Mike Hitchler was able to help Fedik show that the IRF6 gene had a bona fide binding site for the AP2 transcription factor, and that this binding site was disrupted by the genetic variant," said Domann, University of Iowa professor of radiation oncology. "This was very solid evidence for understanding this newly discovered mechanism behind cleft lip.

"It's a great example of what can be achieved when investigators from seemingly disparate fields collaborate and cooperate," Domann added.

Becky Soglin | EurekAlert!
Further information:
http://www.uiowa.edu

Further reports about: AP2 DNA Genetics IRF6 Rahimov bind cleft lip genetic mechanism genetic variant humane genome lip palate regulatory variant

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>