By working with Canadians of French ancestry who suffer a rare genetic disease, researchers have discovered how three genes contribute to abnormal growth, making a breakthrough that will improve our understanding of many disorders such as foetal and childhood growth retardation, abnormal development of body parts and cancer.
"As a result of the Human Genome Project, we know the basic identity of essentially all the genes in the human body, but we don't automatically know what they do in detail," explained lead researcher Dr. Mark Samuels of the University of Montreal's Department of Medicine and the Sainte-Justine University Hospital Research Centre. "It's like opening your car and seeing the parts, but not knowing what each one does. When a part breaks however, you learn how it fits with the rest of the machine. Working with people who have specific health or development problems linked to specific genes enables us to see how those genes contribute to our bodies' development and functioning."
In this case, the team of researchers characterized the molecular basis in patients who suffer from Meier-Gorlin Syndrome (MGS), a rare disorder that is characterized by short stature, small ears, and absent or underdeveloped knee-caps. The patients were mostly francophonic, coming from the Maritimes, Quebec, British Columbia as well as the Louisiana Cajun community. MGS is a classic "single gene disorder," meaning it is related to mutations in individual genes, although in the case of MGS different patients surprisingly seem to carry mutations in any of three different genes.
The genes are called ORC1L, ORC4L and CDT1, and are known to play a critical role in correct copying of DNA. Cells reproduce by dividing in two. All the chromosomes must also be duplicated. This process is tightly controlled to prevent having too many or two few copies of large segments of the genome. "This seems to be the first example of any naturally occurring, inherited mutations identified in this set of important regulatory genes in any mammal. Finding the genes is a great example of the value of this type of research," Samuels said. "We learn the cause of the disease, and discover new things about our cellular function. However we still have a lot to learn about why mutations in these genes lead to the specific consequences in Meier-Gorlin patients."
There are 20-25,000 genes in the human genetic sequence, and it's important to note that they don't necessarily each correspond to a specific function or group of functions, or indeed to a single disease. The same gene can have subtle effects on a number of bodily functions. Moreover, in complex genetic diseases – diabetes, for example – environment and lifestyle have as much or more of an impact on health than a person's genetic background.
"Understanding rare genetic conditions like MGS is important to the general public for two reasons," Samuels stressed. "Firstly, they provide insight into how our genes, and therefore our bodies, work. Secondly, although there are few people concerned for each particular disorder, in sum all patients with genetic conditions consume substantial amounts of health resources, and by diagnosing them more quickly, we can improve patient management and reduce the strain on the health care system." Research suggests that up to 70% of admissions to paediatric hospitals may be related to some kind of genetic disorder. "It's also important to note that behind the science and the statistics, there are real people suffering. It's an immense relief for patients and their families to finally have a clear diagnosis," Samuels added.
In an unusual coincidence, a competing team of researchers obtained similar findings on Meier-Gorlin Syndrome in a different set of patients. These findings were published in the same issue of Nature Genetics. Samuels notes, "Neither team can claim absolute priority in the discovery. However this is the way science works best: when important results are quickly verified by multiple teams independently."
The Canadian work was carried out as part of a long term commitment to rare genetic disease research by the Atlantic Medical Genetic and Genomic Initiative (AMGGI). The findings were published in Nature Genetics and involved researchers from Dalhousie University, the University of Montreal-CHU Ste-Justine, the University of Louisiana and the University of British Columbia. The AMGGI project is funded by Industry Canada via Genome Canada and Genome Atlantic, as well as a large number of organizations, including the Atlantic Canada Opportunities Agency – Atlantic Innovation Fund, Dalhousie University, Capital Health and the IWK Foundation. The full list can be found at Genome Atlantic's website.
William Raillant-Clark | EurekAlert!
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
18.07.2018 | Life Sciences
18.07.2018 | Materials Sciences
18.07.2018 | Health and Medicine