Steffan Noe Niikanoff Christiansen - Postdoctoral Fellowship 2024
Project summary:
The Deadly, the Deleterious, and the Dangerous – Decoding the Differential Pathogenicity among CALM1, CALM2, and CALM3
Mutations in any of the three genes encoding the calmodulin protein, CALM1, CALM2, and CALM3, may cause ventricular arrhythmias and sudden cardiac death. The three genes are evolutionary conserved. Therefore, it is currently assumed that alterations in any of the genes are equally harmful. I want to test the hypothesis that the disease severity is dependent on which of the calmodulin genes that is mutated.
Project Title
The Deadly, the Deleterious, and the Dangerous – Decoding the Differential Pathogenicity among CALM1, CALM2, and CALM3
Background
Early and accurate diagnosis is crucial for individuals affected by mutations in CALM1, CALM2, and CALM3, given that 50% experience a major arrhythmic event by the age of ten. The ability to predict the disease severity from the DNA is the key to early and accurate diagnosis. This can only be achieved with a deep understanding of the role of each of these genes.
Aim
The aim of this project is to decode the differential pathogenicity among mutations in CALM1, CALM2, and CALM3 to improve the diagnosis of calmodulinopathy.
Methods
In this project, I will compare DNA alterations among human populations and > 230 primate species to identify which mutations are harmless and which are harmful. I will use RNA data from human hearts to study the role of the CALM1, CALM2, and CALM3 genes. Based on these analyses, I want to characterize the traits of individuals with DNA alterations in either CALM1, CALM2, or CALM3 in the UK Biobank that contains data of more than 500,000 individuals.
Steffan Noe Niikanoff Christiansen
- MSc and PhD
- Department of Health Science and Technology, Aalborg University
Mentors:
Mette Nyegaard, Professor, Department of Health Science and Technology, Aalborg University and Department for Congenital Disorders, Statens Serum Institut
Jacob Tfelt-Hansen, Professor, and consultant cardiologist, Department of Forensic Medicine, University of Copenhagen and Department of Cardiology, Copenhagen University Hospital
Collaborators:
Mikkel Heide Schierup, Professor, Bioinformatics Research Centre, Aarhus University
Michael Toft Overgaard, Professor, Department of Chemistry and Bioscience, Aalborg University
Peter J. Schwartz, Professor and Director of Center for Cardiac Arrhythmias of Genetic Origin, Istituto Auxologico Italiano