Development of a next generation sequencing panel and software for diagnosis of hypetrophic cardiomyopathy

To develop a genetic screening panel and its bioinformatic analysis software in order to detect mutations associated with hypertrophic cardiomyopathy. Required experimental methods and analysis pipeline will be developed.

Hypertrophic cardiomyopathy (HCM) is the most common form of heart muscle diseases and has been intensely subjected for more than 40 years. HCM is a disease in which heart muscle becomes thickened and patients are suffered due to difficulties on pumping capability of the heart. This genetic heart disease affects 1:500 in the general adult population and also most common cause of sudden cardiac death in people under 30 years of age. Diagnosis of HCM is challenging due to presence of many other diseases causing heart muscle thickening. In addition, HCM is uncommon in routine cardiologic practice and this limited exposure of cardiologists to HCM generates uncertainty that can prevent disease diagnosis and its management. HCM is a heterogeneous monogenic heart disease inherited mostly autosomal dominant manner. It affects people of both gender and of various ethnic origins with similar causal mutations due to its autosomal dominant inheritance. Findings of genetic studies show that HCM is caused by mutations in 11 or more genes encoding mainly sarcomere proteins. 70% of patients have mutations in two genes and other genes counts for approximately 5% or less of cases. In addition, most of mutations in those genes affecting people are unique to individual families. Due to family specific inheritance of this condition, more than 1400 mutations on those genes identified. It is absolutely not effective to perform mutation screening with conventional Sanger sequencing method in suspicious or diagnosed patients and their families due to technical difficulties. Recently, genomic technologies have rapidly developed and cost of gene sequencing is reduced by use of next generation sequencing technologies (NGS). These developments in sequencing technologies created the most accurate, fast and efficient way for screening many genes at the same time. There are also many gene panels targeting HCM-like complex and heterogeneous diseases are in development stage in the world based on NGS technologies. Our aim is to design and validate a targeted gene-sequencing panel in order to screen patients with diagnosis or suspicion of HCM. We plan to develop a kit that can enrich the target gene regions associated with HCM based on all kinds of NGS instruments. All substitution, small deletion, insertion and duplication mutations is aimed to be identified with product of this project. In addition to developing target enrichment strategy for HCM associated gene regions, we plan to generate an analysis pipeline for the analysis of NGS data. High throughput sequencing systems produce large amounts of data to be analyzed carefully. In order to clarify and determine suitable analysis pipeline, we will also generate analysis methods to be followed by laboratories in interpretation step. As a result, we are aiming to design and develop ready to use gene-screening kit targeting majority of HCM associated mutations. Any laboratory that has an NGS instrument can use final product in order to analyze genetic background of individuals to reveal the potential risk factors. These laboratories will be available to analyze HCM diagnosed patients and when mutation analysis reveals a causative mutation, it will be possible to analyze family members for their risk assessment. Aimed cost effective, easy to use and analytically powered HCM mutation screening kit will not only enlighten the way for cardiologists to diagnose HCM but also it will be available for researchers in order to investigate disease etiology and find novel causative mutations in target populations.
Project ID: 
8 818
Start date: 
Project Duration: 
Project costs: 
600 000.00€
Technological Area: 
Diagnostics, Diagnosis
Market Area: 
Diagnostic services

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