Functional assessment of novel genetic mutations causing dilated cardiomyopathy using iPSC derived cardiomyocyte modeling in patients of Kazakhstan
Project goal: The main goals of this project are to define novel mutations in genes associated with dilated cardiomyopathy (DCM) in patients of Kazakhstan by performing a whole genome sequencing and bioinformatic analysis (Aim 1), to study the underlying mechanisms of how these novel mutations alter cardiomyocyte physiology and contribute to a DCM disease development by providing functional studies using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) models (Aim 2).
Project description: Functional characterization and validation of hiPSC-CM model using innovative imaging and electrophysiology methods will allow us to assess the effect of the mutation at the cellular level, proving its contribution to the etiology of the disease. Furthermore, after validating this model, we will apply this strategy to functionally assess the pathogenicity of genetic variants with unclear significance (VUS) detected in Kazakh patients with DCM using the created model.
The project is an interdisciplinary network of research groups with a research focus on cardiology, genomics, bioinformatics, functional genomics, biochemistry, electrophysiology, biotechnology.
Project facilitators: PI: Ainur Akilzhanova, Madina Zhalbinova, Ayaulym Chamoieva, Zhanel Mirmanova, Tomiris Shakhmarova
Realisation period:2024-2026
Expected results: The project results will include: Blood samples will be recruited from patients with DCM.
DNA will be extracted and replenish Biobank. Library preparation. Sequencing.
Bioinformatics analysis, will be performed. Genotype-phenotype relations between genetic variants, SNVs and subtypes of cardiomyopathy will be analyzed.
Protocols for the creation of iPSC-derived cardiomyocytes will be optimized.
iPSC cell lines will be established.
Cardiac differentiation of the established iPSC cell lines will be performed.
Methodology: Recruit and examine study participants, collect information data and obtain blood samples. Create Biobank. DNA extraction. Library preparation. Sequencing.
Perform bioinformatics analysis, examine genotype-phenotype relations between genetic variants, SNVs and subtypes of cardiomyopathy.
Creation of cardiomyocyte cell lines carrying the identified novel mutations by performing iPSC technology. Protocols optimization
Contacts: akilzhanova@nu.edu.kz
Project description: Functional characterization and validation of hiPSC-CM model using innovative imaging and electrophysiology methods will allow us to assess the effect of the mutation at the cellular level, proving its contribution to the etiology of the disease. Furthermore, after validating this model, we will apply this strategy to functionally assess the pathogenicity of genetic variants with unclear significance (VUS) detected in Kazakh patients with DCM using the created model.
The project is an interdisciplinary network of research groups with a research focus on cardiology, genomics, bioinformatics, functional genomics, biochemistry, electrophysiology, biotechnology.
Project facilitators: PI: Ainur Akilzhanova, Madina Zhalbinova, Ayaulym Chamoieva, Zhanel Mirmanova, Tomiris Shakhmarova
Realisation period:2024-2026
Expected results: The project results will include: Blood samples will be recruited from patients with DCM.
DNA will be extracted and replenish Biobank. Library preparation. Sequencing.
Bioinformatics analysis, will be performed. Genotype-phenotype relations between genetic variants, SNVs and subtypes of cardiomyopathy will be analyzed.
Protocols for the creation of iPSC-derived cardiomyocytes will be optimized.
iPSC cell lines will be established.
Cardiac differentiation of the established iPSC cell lines will be performed.
Methodology: Recruit and examine study participants, collect information data and obtain blood samples. Create Biobank. DNA extraction. Library preparation. Sequencing.
Perform bioinformatics analysis, examine genotype-phenotype relations between genetic variants, SNVs and subtypes of cardiomyopathy.
Creation of cardiomyocyte cell lines carrying the identified novel mutations by performing iPSC technology. Protocols optimization
Contacts: akilzhanova@nu.edu.kz