Next generation sequencing in cardiovascular diseases

Abstract

In the last few years, the advent of next generation sequencing (NGS) has revolutionized the approach to genetic studies, making whole-genome sequencing a possible way of obtaining global genomic information. NGS has very recently been shown to be successful in identifying novel causative mutations of rare or common Mendelian disorders. At the present time, it is expected that NGS will be increasingly important in the study of inherited and complex cardiovascular diseases (CVDs). However, the NGS approach to the genetics of CVDs represents a territory which has not been widely investigated. The identification of rare and frequent genetic variants can be very important in clinical practice to detect pathogenic mutations or to establish a profile of risk for the development of pathology. The purpose of this paper is to discuss the recent application of NGS in the study of several CVDs such as inherited cardiomyopathies, channelopathies, coronary artery disease and aortic aneurysm. We also discuss the future utility and challenges related to NGS in studying the genetic basis of CVDs in order to improve diagnosis, prevention, and treatment.

Keywords: Cardiomyopathies; Complex disease; Coronary artery disease; Genetics of cardiovascular diseases; Next generation sequencing.

Figure 1

Basic principles of next generation sequencing. A whole genome or a targeted region of the genome are randomly digested into small fragments and then sequenced. The sequence obtained is subsequently aligned to a reference genome or de novo assembled.

Figure 2

Genetic contribution to monogenic and multigenic cardiovascular diseases and their study approach. The monogenic diseases are caused by a rare mutation in a specific gene and are very rare (< 10 individuals). In the complex diseases, many common genetic variants occur and have a major frequency in the population (> 100 000). The study approach for monogenic diseases is a genome wide linkage study in which one single mutation is identified. Conversely, for complex diseases the genome wide association study is very important to identify a series of common variants contributing to the etiology of the disease. Target re-sequencing by next generation sequencing is an approach which permits the study of both monogenic and complex diseases.