Researchers from the Department of Biology at the University of Copenhagen have now contributed to solving this problem for a specific gene called GCK. The study has just been published in genome biology.
Figure: GCK gene
Rasmus Hartmann-Petersen, a professor in the Department of Biology, explains:
– “He GCK gene, encoding the enzyme glucokinase, regulates insulin secretion from the pancreas. GCK Therefore, genetic variants can cause a hereditary form of diabetes. Although the connection between GCKand diabetes has been known for several years, so far we only know the effect of a small percentage of the possible variants of this gene.”
Together with colleagues from the PRISM center, UCPH, who are currently studying the effects of genetic variations, the researchers measured the effect of all possible variants of GCK.
PhD student Sarah Gersing, who is the first author of the paper, explains:
– “We use yeast cells to measure the activity of more than 9000 different GCK variants. In this way, we were able to generate a list of effects, both for variants already known as well as variants that patients may have but have not yet been discovered. This provides us with a reference for future GCK diagnoses”.
Prof. Kresten Lindorff-Larsen, who runs the PRISM center, continues:
– “Our results are quite unique; not only have we measured the effect of several thousand variants, but for many of the variants, we can now explain what they do to protein glucokinase. At our center, we have brought together researchers working in a variety of research fields, from data analysis and biophysics to cell biology and medicine, and it is now clear how this broad approach pays off in explaining how the diseases”.
genetic variants of GCK It can, among other things, cause a form of hereditary diabetes called “GCK maturity-onset diabetes of the young” (GCK-MODY).
Professor of genetics, dr. medicine Torben Hansen, who is also a member of the PRISM center, says: “Although patients with GCK-MODY show elevated blood glucose levels, this is often not associated with complications. Therefore, unlike other forms of diabetes , most GCK-MODY patients can therefore do not need to be treated with drugs.However, due to missing or inaccurate genetic data, more than half of GCK-MODY patients are classified as having type 1 diabetes. or type 2 and are therefore receiving medication unnecessarily We estimate that approximately 1% of those newly diagnosed with type 2 diabetes in Denmark have a variant in type 2 GCK gene, which means they don’t need treatment, or they need to be treated differently. Our new map of GCK It is hoped that the variants can help give these patients a more correct diagnosis.”
PRISM’s next step is to transfer these methods to other genes and diseases.
– “We are already quite advanced with the genes involved in, for example, neurodegenerative diseases, and we are trying to develop precise methods that can give us information about the mechanisms of the disease,” says Rasmus Hartmann-Petersen.
Kresten Lindorff-Larsen continues:
– “Our data give us the opportunity to test and develop computational models for variant effects, which will then be transferable to other genes and diseases.”
– “Now, we have measured the effects of almost all variants of GCK, giving us insight into which variants work and which don’t. The next step is to understand why and how the same underlying molecular mechanisms can give rise to a wide range of different diseases,” concludes Sarah Gersing.
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