Abstract
Chronic kidney disease (CKD) is complex, clinically heterogeneous disease affecting ~10% population. Origin and course of CKD is determined by genetic and environmental factors.
Genetic factors account for 40-75%. Genetic component, genes and their variants, have been increasingly identified, either in families with monogenic forms of CKD or in genome-wide association studies in CKD cohorts.
Subsequently, the contribution of rare and common genetic variants in these genes to kidney disease is studied in patients with monogenic CKD and in the general population. At present, ~650 monogenic forms of CKD are known.
They are responsible for ~70% of paediatric and ~20% of adult cases. With exception of mutations in PKD1, PKD2, COL4A3-5, UMOD and MUC1 genes, their representation in patient populations is heterogeneous and individually rare.
Successful diagnostics and research depends on the motivation, active approach and cooperation of physicians, patients and specialized laboratories. Exome sequencing is basic tool for CKD diagnostics.
Depending on the clinical selection it may identify the genetic cause in TILDE ~30% of the cases. In unsolved cases we focus on better genetic and functional characterization of identified variants.
We perform whole-genome sequencing and analyse non-coding mutations. A special task presents the analysis of repetitive and homologous regions of the human genome and interpretation of their variability.
To determine the causality of most of these variants, we must perform a targeted analysis of body fluids and tissues of patients, or suitable cell and animal models prepared by methods of cell reprogramming or targeted changes in the genome.