Inherited Diseases I – Genetic Research
RNDr. Lenka Fajkusová , CSc.
THEMATIC RESEARCH FOCUS
- Molecular diagnostics of inherited neuromuscular, neurodegenerative, metabolic, and skin diseases (molecular diagnostics of 37 inherited diseases is performed at present)
- Molecular modelling of mutations by methods of molecular dynamics
- Introduction of high-throughput analyses into medical research and molecular diagnostics Transcriptional Regulation
- Detection of mutation/mutations associated with a disease, analysis of correlation between patient‘s genotype and phenotype, molecular modelling and functional analysis of detected mutations.
- Introduction of high-throughput analyses (sequence capture and targeted resequencing, whole genome sequencing, transcriptome profiling) of human genomes. Utilisation of these technologies in diagnostics and development of diagnostic tests.
CONTENT OF RESEARCH
Genetics of inherited disorders
This work-package is focused on the following topics:
- molecular genetic diagnostics of inherited neuromuscular, neurodegenerative, metabolic, and skin diseases;
- introduction of new methodical approaches in the field of DNA diagnostics (sequence capture and targeted resequencing, whole genome sequencing).
Determination of mutation/mutations on DNA level is the principal step of molecular genetic diagnostics of inherited diseases. This step is essential for definitive confirmation of diagnosis, which was preliminary established on the basis of clinical symptoms and biochemical, histological, histochemical, and imunohistochemical findings. In neuromuscular and neurodegenerative disorders, tens of genes can be associated with one specific phenotype. In these cases, we will perform high-throughput DNA sequencing to detect genetic defects associated with the disease. Detected mutations will be evaluated using literature data and mutation databases. In cases of newly found mutations, prediction programmes, molecular modelling, and functional analyses will be used for analysis of the impact of a mutation on the protein structure and function.
Technologies used: sequence capture and targeted resequencing, whole genome sequencing, classic DNA sequencing, molecular modelling
KEY RESEARCH EQUIPMENT
PLANNED RESEARCH INFRASTRUCTURE
The research group will be one of the principal users of the equipment available within CEITEC Genomics Core Facility.
CURRENT RESEARCH INFRASTRUCTURE
Laboratories equipped with technologies used in molecular biological analysis of inherited disorders (mainly for mutational analysis): Automatic sequencers ABI PRISM 310, 3130xl Genetic Analyser, and Beckman Coulter CEQ 8000, DHPLC Helix ProStar, DNA chip scanner Genorama Quattrolmager model 2, Puls-field electrophoresis CHEF Mapper® XA, RealTime PCR cyclers Corbett research RG 6000, PCR cyclers Biometra T3000, Biorad C1000 and Bioer TC-XP.
- Introduction of complex diagnostics of epidermolysis bullosa congenita in the Czech Republic (NR9346), Ministry of Health, 2007-2009, Lenka Fajkusová, University Hospital Brno, Karel Veselý, St. Anne´s University Hospital Brno.
- Development of diagnostics and treatment of serious heart and vascular diseases using genomic and proteomic approaches (2B08060), Ministry of Education, Youth and Sports, 2008-2011, Lenka Fajkusová, University Hospital Brno, Tomáš Freiberger, Centre of Cardiovascular and Transplant Surgery, Zbynek Zdráhal, Masaryk University.
- Integrated bioanalytical technologies for microanalyses and diagnostics with laser induced fluorescence and mass spectrometry coupling (LC06023), Ministry of Education, Youth and Sports, 2006-2011, Zdenek Glatz, Masaryk University, Lenka Fajkusová, University Hospital Brno, František Foret, Institute of Analytical Chemistry AS CR.
- DUSKOVA, L., KOPECKOVA, L., JANSOVA, E., TICHY, L., FREIBERGER, T., ZAPLETALOVA, P., SOSKA, V., RAVCUKOVA, B., FAJKUSOVA, L. An APEX-based genotyping microarray for the screening of 168 mutations associated with familial hypercholesterolemia. Atherosclerosis. 2011, 216(1), p. 139-145.
- JERABKOVA, B., MAREK, J., BUCKOVA, H., KOPECKOVA, L., VESELY, K., VALICKOVA, J., FAJKUS, J., FAJKUSOVA, L. Analysis of the COL7A1 gene in Czech patients with dystrophic epidermolysis bullosa reveals novel and recurrent mutations. J Dermatol Sci. 2010, 59(2), p. 136-140.
- GOLDMANN, R., TICHY, L., FREIBERGER, T., ZAPLETALOVA, P., LETOCHA, O., SOSKA, V., FAJKUS, J., FAJKUSOVA, L. Genomic characterization of large rearrangements of the LDLR gene in Czech patients with familial hypercholesterolemia. BMC Med Genet. 2010, 11, p. 115-125.
- JERABKOVA, B., MAREK, J., BUCKOVA, H., KOPECKOVA, L., VESELY, K., VALICKOVA, J., FAJKUS, J., FAJKUSOVA, L. Keratin mutations in epidermolysis bullosa simplex patients: correlations between phenotype severity and disturbance of intermediate filament molecular structure. Br J Dermatol. 2010, 162(5), p. 1004-1013.
- SEDLACKOVA, J., VONDRACEK, P., HERMANOVA, M., ZAMECNIK, J., HRUBA, Z., HABERLOVA, J., KRAUS, J., MARIKOVA, T., HEDVICAKOVA, P., VOHANKA, S., FAJKUSOVA, L. Point mutations in Czech DMD/BMD patients and their phenotypic outcome. Neuromuscul Disord. 2009, 19(11), p. 749-753.