Next generation sequencing in cardiovascular diseases

Faita, Francesca; Vecoli, Cecilia; Foffa, Ilenia; Andreassi, Maria Grazia

doi:10.4330/wjc.v4.i10.288

Cited by 33 publications

(22 citation statements)

References 55 publications

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“…Efforts seeking to improve the state of genome editing for investigating or treating cardiomyopathies and other genetic disorders are actively ongoing. Next-generation sequencing, bioinformatics analyses, clinical discoveries, and basic research are constantly identifying new genes involved in cardiomyopathies, providing novel therapeutic targets for genome editing [120,121]. This includes genes that give rise to non-coding RNA, e.g.…”

Section: Recent Advances In Crispr Genome Editing With Potential For mentioning

confidence: 99%

Genome Editing for the Understanding and Treatment of Cardiomyopathies

Nguyen¹,

Lim²,

Yokota³

2019

Preprint

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Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.Keywords: dilated cardiomyopathy (DCM); hypertrophic cardiomyopathy (HCM); restrictive cardiomyopathy (RCM); arrhythmogenic right ventricular cardiomyopathy (ARVC); left ventricular non-compaction cardiomyopathy (LVNC); Duchenne muscular dystrophy; dystrophin; genome editing; CRISPR/Cas9; Cpf1 (Cas12a) Cardiomyopathy is also a major manifestation in a subset of neuromuscular disorders [7,8]. Cardiomyopathy is most commonly associated with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), both X-linked recessive disorders caused by mutations in the dystrophin (DMD) gene [8]. DMD codes for dystrophin, a cytoskeletal protein that maintains the Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: structural integrity of muscle fibres during contraction-relaxation cycles. Loss-of-function mutations in the DMD gene result in an absence of dystrophin, leading to DMD [9][10][11]. Mutations maintaining the DMD reading frame produce truncated but partly functional dystrophin, and often result in a milder form of the disease known as BMD [12,13]. Cardiomyopathy is a leading cause of death in both DMD and BMD patients and is routinely described as being DCM [13,14]. Other neuromuscular disorders associated with cardiomyopathy include the limb girdle muscle dystrophies, myotonic dystrophy, and Friedreich ataxia [15].Advances in molecular genetics enable genome editing to be incorporated into various fields of biomedical research, including the cardiovascular sciences. Currently, the most commonly used tools are zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) [16]. Both ZFNs and TALENs are engineered restriction enzymes created by combining a DNA binding domain with a DNA cleavage domain adapted from the FokI restriction enzyme [17][18][19]. The DNA binding domain in Z...

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Section: Recent Advances In Crispr Genome Editing With Potential For mentioning

confidence: 99%

Genome Editing for the Understanding and Treatment of Cardiomyopathies

Nguyen¹,

Lim²,

Yokota³

2019

Preprint

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“…However, for complex diseases such as CVDs, candidate biomarkers based on a single omic data modality suffer from the reproducibility issue. 72 To address this issue, we need to research novel NGS bioinformatics methods that not only can integrate multiple omic data modalities (e.g., genetic variations, transcriptional regulation, and epigenetic modifications), but also can associate heterogeneous omic information with CVD phenotypes. Associations (e.g., correlation and causality) resulted from NGS bioinformatics present a great opportunity for researchers to obtain further insights on disease mechanisms and to improve risk predictions for complex CVDs.…”

Section: The Opportunities Of Ngs For Cvdmentioning

confidence: 99%

Cardiovascular Transcriptomics and Epigenomics Using Next-Generation Sequencing

Chandramohan

Phan

et al. 2014

Circ Cardiovasc Genet

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“…66 It is expected that NGS will become more important in the study of inherited and complex cardiovascular diseases (CVDs). 67 (For example, recent studies using NGS efficiently and successfully identified frameshift mutations in the SMAD3 gene as the cause of vascular disease in a family with arterial aneurysms and dissections inherited in an autosomal dominant pattern. 68 ) However, the NGS approach to the genetics of CVDs represents a territory, which has not been widely investigated.…”

Section: Genomics and Epigenomicsmentioning

confidence: 99%

Hierarchical approaches for systems modeling in cardiac development

Gould

Aboulmouna

Varner

et al. 2013

WIREs Mechanisms of Disease

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Ordered cardiac morphogenesis and function is essential for all vertebrate life. The heart begins as a simple contractile tube, but quickly grows and morphs into a multi-chambered pumping organ, complete with valves, while maintaining regulation of blood flow and nutrient distribution. Though not identical, cardiac morphogenesis shares many molecular and morphological processes across vertebrate species. Quantitative data across multiple time and length scales have been gathered through decades of reductionist single variable analyses. These range from detailed molecular signaling pathways at the cellular levels to cardiac function at the tissue/organ levels. However, none of these components act in true isolation from others, and each, in turn, exhibits short- and long-range effects in both time and space. With the absence of a gene, entire signaling cascades and genetic profiles may be shifted, resulting in complex feedback mechanisms. Also taking into account local microenvironmental changes throughout development, it is apparent that a systems level approach is an essential resource to accelerate information generation concerning the functional relationships across multiple length scales (molecular data vs. physiological function) and structural development. In this review, we discuss relevant in vivo and in vitro experimental approaches, compare different computational frameworks for systems modeling, and the latest information about systems modeling of cardiac development. Lastly, we conclude with some important future directions for cardiac systems modeling.

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Next generation sequencing in cardiovascular diseases

Cited by 33 publications

References 55 publications

Genome Editing for the Understanding and Treatment of Cardiomyopathies

Genome Editing for the Understanding and Treatment of Cardiomyopathies

Cardiovascular Transcriptomics and Epigenomics Using Next-Generation Sequencing

Hierarchical approaches for systems modeling in cardiac development

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