Scientists have identified genetic mutations that appear to be a key culprit behind a suite of birth defects called ciliopathies, which affect an estimated 1 in 1,000 births. In a paper published online this week in Nature Genetics, a team of researchers led by The University of Texas at Austin's John Wallingford reveals that these mutations prevent certain proteins from working together to smooth the way for cells to communicate with one another.
Birth defects from genetic disorders of the cilia -- tentacle-like structures in cells that coordinate cell-to-cell communication in healthy people -- are varied, ranging from oral-facial-digital syndrome, which can cause extra toes, misshapen teeth, an abnormal tongue and other defects, to short rib polydactyly syndrome, a lethal birth defect that causes every organ in the body to be defective.
"For cells to talk to each other, functioning cilia are needed," says Wallingford, a professor in the Department of Molecular Biosciences. "We identified a group of proteins that form part of the base that cilia need in order to function. If that base is defective, it can cause serious birth defects that are frequently lethal."
The new research pinpoints how three proteins work together to form a base that allows cilia to carry critical cell-to-cell communications. Wallingford and his colleagues discovered that, much the way that cellphone towers provide a base for the antennas that assist with communication, these proteins together construct a base that anchors the cilia.
Disturbances in the little-known group of proteins, which the researchers called CPLANE, led to disturbed cell communication and observable ciliopathy in mouse models. The team also asked human geneticists to screen for the genes among their patients with similar birth defects and found that mutations in the same genes resulted in ciliopathies in humans.
Wallingford points out that the research is important, given that ciliopathies are more widespread than most people realize. Polycystic kidney disease, for example, which causes the abnormal growth of cysts on kidneys, is a disorder arising from defective cilia and afflicts about 600,000 people in the U.S.
"If you lump ciliopathies, the prevalence is high, and they will become one of the more common congenital diseases," says Wallingford. "Birth defects are an underappreciated problem, and we have little understanding of their genetic underpinnings despite their prevalence, not to mention their environmental underpinnings."
This research was funded by the National Institutes of Health and the Howard Hughes Medical Institute. Co-authors of the paper are from the University of California, Los Angeles; FHU TRANSLAD, Burgundy University, France; Stanford University School of Medicine; Boston Children's Hospital, Harvard Medical School; University Hospital Center, Liège, Belgium; Hospital Center, Luxembourg; Universitair Ziekenhuis Brussel, Belgium; Pediatric Centre PGIMER, Chandigarh, India; Federico II University of Naples, Italy; Telethon Institute of Genetics and Medicine, Naples, Italy; Dental Institute, King's College London, U.K.; Stony Brook University, New York; Mendelian Center, University of Washington; and Children Hospital, Dijon, France.
Kristin Elise Phillips | EurekAlert!
Research offers clues for improved influenza vaccine design
09.04.2018 | NIH/National Institute of Allergy and Infectious Diseases
Injecting gene cocktail into mouse pancreas leads to humanlike tumors
06.04.2018 | University of Texas Health Science Center at San Antonio
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
19.04.2018 | Materials Sciences
19.04.2018 | Physics and Astronomy
19.04.2018 | Physics and Astronomy