Cystic fibrosis (CF) is a progressive recessive genetic disease that causes persistent pulmonary infections and, over time, limits breathing capacity. CF is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. People with a single working copy are carriers and otherwise mostly healthy. CFTR is involved in the production of sweat, digestive fluids, and mucus. When the CFTR is not functional, chloride – the component of salt – cannot be transfered to the surface of the cell. Without chloride to attract water to the cell surface, secretions in various organs which are usually thin become dense and sticky. In the lungs mucus clogs the airways and traps germs such as bacteria, leading to infections, inflammation, respiratory failure and other complications. In the pancreas, mucus accumulation prevents the release of digestive enzymes, which otherwise help the body absorb food and key nutrients, resulting in malnutrition and poor growth. In the liver, thick mucus can block the bile duct, causing liver disease. In men, CF can also affect their ability to have children. The first mutation for CF, ΔF508 was discovered in 1988, and more than 1,000 other mutations that cause CF were detected in subsequent studies. In European ancestry CF affects about one out of every 3,000 newborns, and about one in 25 people is a carrier. There is currently no cure for CF. Accurate genetic diagnostics, however, has greatly improved the medical management of the symptoms of the disease, which has led to an improvement in the quality of life and an increase in the life expectancy of patients up to forties or fifties, or longer.
Cystic fibrosis was the first genetic disease studied by genetic analysis in our laboratory and in Slovenia (1988 – 1994 – 2000).
Research projects:
- Interinstitutional national research program P1-0104 Functional Genomics and Biotechnology for Health; R. Komel, 1/1/1999―31/12/2003; WP1 – Molecular genetic analysis of monogenic diseases.
- J1―8762 Molecular biology and genetics in biomedical research; national basic research project, R. Komel, 1/1/1997―31/12/1999.
- INCO ECCACF European Community Action for Cystic Fibrosis [Commission of the European Communities, Joint European Project]. R. Komel: Slovenian Project Partner, 1996-1999.
- C1-0509 Molecular biology in biotechnology and medicine; national basic research project [URP (RF) Molecular Biology], R. Komel, 1986―1991―1992/93.
- Introduction of recombinant DNA methodology in diagnostic of selected diseases. Federal Project GIBIT (Genetic Engineering & Biotechnology) / SZNJ (Science Council of Yugoslavia)]. R. Komel: Project Leader; Kniewald (PBT, Zagreb): General Coordinator; 1988-1990.
Clinical partners:
- Gyneacological Clinic UKC (Prof. Srečko Rainer, M.D.; Nina Canki Klain, M.D.)
- Paediatric Clinic UKC (Prof. Milan Štrukelj, M.D.)
Support from abroad:
- Medical Faculty in Verona, Italy (Prof. Pier-Franco Pignatti, M.D.).
- INSERM, Paris, France (Prof. André Boué, M.D.)
Clinical translation:
In August 1990 we joined the worldwide Cystic Fibrosis Genetic Analysis Consortium and in the years to follow a systematic mutation analysis of Slovenian CF population was carried out, and the results were shared with other European and wider populations. In the period 1990 – 2000, being also a member and registered laboratory of INCO ECCACF (European Community Concerned Action for Cystic Fibrosis; 1996 – 1999), we performed routine direct and indirect CF DNA analysis for our clinical institutions, in particular for Gyneacological Clinic and Paediatric Clinic in Ljubljana, and finally molecular genetic analysis was introduced as a diagnostic procedure to Gyneacological Clinic of the University Clinical Centre in Ljubljana.
Researchers involved:
| Researcher | Position |
| Radovan Komel | Head of Department / Project leader |
| Metka Ravnik Glavač | PhD student |
| Borut Peterlin | PrePhD and PostDoc trainee from Gyn. Clinic |
| Damjan Glavač | Guest PostDoc researcher |
| Katja Vouk | PhD student |
| Lana Strmecki | PhD student |
Education:
| Student | Thesis | Title | Year | Supervisors |
| Katja Vouk | MSc | Improvment of the molecular genetic approach to cystic fibrosis diagnosis. | 1998 | Radovan Komel |
| Mirjana Liović | MSc | Determination of candidate genes by single stranded conformation polymorphism analysis. | 1996 | Radovan Komel |
| Katja Vouk | Dipl | Molecular analysis of diagnostic polymorphisms and CF mutations in the selected Slovene families at risk. | 1995 | Radovan Komel |
| Borut Peterlin |
PhD [trainee] |
Physical and genetic analysis at chromosomal region Xq28. [at MCMB: specialisation on gene technology and CF genetic analysis, 1986 – 1992 and 1993-1995; supervisor: R. Komel] |
1993 |
M.C. Hors-Cayla Srečko Rainer [Radovan Komel] |
| Metka Ravnik Glavač | PhD | Genetic analysis of cystic fibrosis with the methods of recombinant DNA technology. | 1992 | Radovan Komel |
| Miranda Mladinić | Dipl | Comparison of different recombinant DNA methods in cystic fibrosis diagnostics. | 1992 |
Radovan Komel Metka Ravnik G. |
Selected publications:
- Vouk K. et al. (2000): Mutational analysis of 30 Slovenian cystic fibrosis patients compared to known Slovenian and European CF mutation spectra. J. Physiol. – Pflügers Archiv 439(2 – Suppl.): R63-R65.
- Doerk T. et al. (2000): Characterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene : a cystic fibrosis mutation of Slavic origin common in Central and East Europe. Hum. Genet. 106(3): 259-268.
- Ravnik-Glavač M. et al. (1993): Single-stranded conformation polymorphism analysis of the CFTR gene in Slovenian cystic fibrosis patients: detection of mutations and sequence variations. Human Mutation 2: 286-292.
- Ravnik-Glavač M. et al. (1992): Cystic fibrosis gene mutations and linked RFLPs in the Slovenian population. Annales de Génétique 35(2): 85-88.
- Nunes V. et al. (1991): Analysis of 14 cystic fibrosis mutations in five South European populations. Genet. 87(6): 737-738.
- Worldwide survey of the deltaF508 mutation – report from the Cystic Fibrosis Genetic Analysis Consortium. J. Hum. Genet. (1990); 47(2): 354-359.
- Gasparini P. et al. (1990): Mutation analysis in cystic fibrosis : to the editor. New Engl J. Med. 323(1): 62-63.
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