Approved Research

Identifying alternative splicing variants in heritable cardiac diseases.

Lay summary

In the last few decades, a strong connection between genetics and heart disease has been established. Certain genetic defects have been shown to profoundly impair the heart's structure and function. Patients living with these genetic defects are often asymptomatic and are unaware of their condition until a sudden cardiac arrest occurs. While much research has been directed towards understanding the genetic basis of heart disease, the topic remains unclear and is ever evolving. With heart disease being one of the leading causes of death in the world, gaining a better understanding of how genes drive heart disease is paramount to improving the quality and precision of treatment options.

In our study, we will focus on a genetic phenomenon called "Alternative Splicing". Each gene, which provides the blueprints for the building blocks of our body, can be likened to a song. Alternative splicing would be the process analogous to music editing. The lyrics or tunes of an original song can be cut out and rearranged to create variations, resulting in a slightly melody that has similar core elements. Similarly, each alternative splicing product from the same gene will have similar core elements, but with a slightly different structure and function. Studies have shown that defects in our body's alternative splicing mechanism have resulted in various diseases. By gaining access to the UK BioBank, we intend to investigate the genetic drivers and the role of alternative splicing in heart disease.

As such, upon access to the UK BioBank and over the next 36 months, our study will be split into three different aims. The first aim is to identify any frequently repeated genetic variations within the alternative splicing machinery. Once variations have been found, our second aim is to find the connection of these genetic alternative splicing variations to any form of heart disease. If a connection to heart disease is found, then our final aim is to see whether common clinical tests, such as ECG and MRI, will be able to detect and predict the effects of these genetic variations.

Identifying and understanding the contribution of alternative splicing in heart disease will be the first step towards personalizing more precise and efficacious treatment options for patients. The findings from our study can give insight to boost the detection and screening efforts of these genetic variants, allowing physicians to manage these conditions more proactively and proficiently.