Michael Doubek

The ability to diagnose rare inherited blood disorders has improved due to massive parallel sequencing (MPS). MPS generates such a big volume of genetic information, that new challenges are created for accurate assessment and reporting of identified variants. Thus, our ability to acquire genetic information has vastly outpaced our ability to understand the relationship between genetic variation and disease. This gap in understanding has led to an explosion in the number of variants of uncertain significance (VUS) in variant aggregation databases. To fill this gap, information on genetic variants along with patient’s phenotype will need to be shared through international initiatives. Integration of these results into routine clinical practice for patients and optimizing the management and surveillance of patients and carriers who have not developed malignancy is a part of precision medicine.

Research objectives

1. Analyzing the frequency of occurrence of suspected pathogenic variants in the healthy population (individuals from 1000 Czech genomes project; A-C-G-T) and the occurrence in patients (according to specific diagnosis; patients with newly diagnosed disease as well as patients from our databases: patients with myeloid and lymphoid malignancies, cytopenia and bone marrow failure syndromes).
2. Functional analysis of selected variants (including use of CRISPR/Cas9 method).
3. Assessment of the impact of variants on phenotype – blood cell number, morphology and function, cell phenotype, clinical signs of disease, other laboratory findings.
4. Analysis of changes in the genome during the development of a blood disorder.