CASyM winter school of Systems Medicine took place between March 29th and April 1st 2017 in Ljubljana, Slovenia and is entitled »The 3rd SysBioMed hands-on tutorial: Systems Medicine Approaches in Personalized Medicine«
1Medical Center for Molecular Biology, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia,2Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia,3Master study programme in Biotechnology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
Introduction Erythrocytosis is a heterogeneous group of disorders defined by increased red blood cell (RBC) number, haemoglobin (Hb) and haematocrit (Ht). Primary and secondary type of rare congenital disorder familial erythrocytosis (FE) is caused by variants in various genes. Causes for secondary FE are typically associated with variants in erythropoietin (EPO) gene and other genes involved in oxygen-sensing pathway, such as Von Hippel-Lindau tumor suppressor (VHL) and endothelial PAS domain (EPAS1). Hormone EPO is the main regulator of red blood cell production in bone marrow and its transcription is activated by EPAS1 gene in low-oxygen conditions. In normoxic conditions, EPAS1 is rapidly degraded by VHL protein . Recently, variants in EPO associated with FE were confirmed and are in the process of integration into diagnostic procedures for FE in Slovenia . The aim of the present study was to screen genomic browsers and literature for sequence variants and regulatory regions with potential effect on erythrocytosis with a view to establish the mutation analysis for VHL and EPAS1 genes as the basis for novel molecular-genetic test in JAK2 negative erythrocytosis. Results Ensembl browser and literature search identified several VHL and EPAS1 variants associated with FE; 743 within transcript EPAS1-001 and 1927 in transcript VHL-001. Accordingly 12 and 20 missense substitutions have been reported to be associated with FE. In both genes, variants associated with FE are often located close to important protein-protein interacting sites or post-translational-modification sites, with effect on proteins stability and activity. Conclusions We have assembled and located VHL and EPAS1 variants associated with FE, reported in Ensembl database and literature. Confirmation sequence analysis on patients with FE in Slovenia is currently undergoing. References: 1. Lee FS and Percy MJ (2010) Annu Rev Pathol 6, pp.165-92. 2. Vočanec D., Prijatelj T., Debeljak N., Kunej T. (2017) in preparation.
2006 - University of Ljubljana, Faculty of Medicine, Center for Functional Genomics and Bio-chips.