Ensuring a Better Diagnosis of Hereditary Diseases

Researchers at the Department of Biology, University of Copenhagen, have now contributed to solving this problem for a specific gene called GCK.

Rasmus Hartmann-Petersen, Professor at the Department of Biology, explains:
– “The GCK gene, which codes for the enzyme glucokinase, regulates the secretion of insulin in the pancreas. GCK gene variants can therefore cause a form of hereditary diabetes. Although the connection between GCKand diabetes has been known for several years, we have, until now, only known the effect of a few percent of the possible variants of this gene”.

Together with colleagues, the researchers measured the effect of all of the possible variants of GCK.

PhD student Sarah Gersing, who is the first author of the article, explains:
– “We used yeast cells to measure the activity of over 9000 different GCK variants. In this way, we were able to generate a list of the effects — both of already known variants, but also of variants that patients might carry, but that have not yet been discovered. This provides us with a reference for future GCK diagnostics”. 

Prof. Kresten Lindorff-Larsen, who heads the PRISM centre, continues:
– “ 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 the glucokinase protein.”.

Gene variants of GCK can, among other things, cause a form of hereditary diabetes called “GCK maturity onset diabetes of the young” (GCK-MODY).

Professor of genetics, dr. med. Torben Hansen, says: – “Although GCK-MODY patients exhibit elevated blood glucose levels, this is often not associated with complications. Hence, unlike other forms of diabetes, most GCK-MODY patients might therefore not need to be treated with medication. However, due to missing or inaccurate genetic data, more than half of the GCK-MODY patients are classified with having either type 1 or type 2 diabetes – and are therefore unnecessarily medicated. We estimate that approx. 1% of those who have recently been diagnosed with type 2 diabetes in Denmark have a variant in the GCK gene, meaning that they don’t need treatment, or need to be treated differently. Our new map of GCK variants can hopefully help give these patients a more correct diagnosis.”

Kresten Lindorff-Larsen says:
– “Our data gives us the opportunity to test and develop computational models for variant effects, which will then be transferable to other genes and diseases.”


University of Copenhagen – Faculty of Science. “High-throughput experiments might ensure a better diagnosis of hereditary diseases.” ScienceDaily. ScienceDaily, 3 May 2023. <www.sciencedaily.com/releases/2023/05/230503105817.htm>.

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