Genomic and molecular cardiovascular medicine / edited by Dhavendra Kumar, Arthur A. M. Wilde, and Perry Mark Elliott.

Format:

Book

Contributor:

Kumar, Dhavendra, editor.

Wilde, A. A. M., editor.

Elliott, Perry Mark, editor.

Series:

Genomic and Precision Medicine in Clinical Practice Series

Language:

English

Subjects (All):

Cardiovascular system--Surgery.

Cardiovascular system.

Physical Description:

1 online resource (462 pages)

Edition:

First edition.

Place of Publication:

London, England : Academic Press, [2024]

Summary:

This comprehensive volume, 'Genomic and Molecular Medicine,' delves into the applications of genomic and precision medicine in clinical practice. Edited by Dhavendra Kumar and contributions from various experts, it covers foundational topics in genomic and molecular biology, exploring the human genome, genetic variations, and inheritance patterns. The book discusses advanced sequencing technologies, their role in diagnosing inherited conditions, and the genomic basis of heart and vascular diseases. It emphasizes the integration of genomics in understanding complex conditions like pulmonary arterial hypertension and myocarditis, and the role of metabolomics in cardiovascular health. This work is designed for medical professionals, researchers, and students in genomic medicine, aiming to enhance their understanding of the molecular mechanisms underlying various diseases and the emerging therapeutic strategies. Generated by AI.

Contents:

Front Cover

Genomic and Molecular Cardiovascular Medicine

Copyright

Contents

Contributors

Foreword

Preface

1 - Introduction to genomic and molecular biology

Introduction

Basic facts - Cell biology, nucleic acids, gene, genome

Human genome - Structure and functional organisation

The mitochondrial genome - Structure and function

The morbid genome

Genetic variation or genetic differences

Coding and non-coding genome

Epigenome

Traditional inheritance

Chromosomal

Mendelian

Autosomal recessive

Autosomal dominant

X-linked recessive

X-linked dominant

Mitochondrial

Polygenic/multi-factorial

Non-traditional inheritance

Epigenetics/genetic imprinting/uniparental disomy

Trinucleotide (triplet) repeats

Non-allelic homologous recombination

Digenic, oligogenic and multigenic inheritance

Mosaicism - Somatic and gonadal

Summary - Key learning points

References

Further reading

2 - Genetic and genomic technologies for inherited cardiovascular conditions

Introduction: What is 'next generation sequencing' and why we need it in inherited cardiovascular conditions

Next-generation sequencing technologies

General overview of the process

Sample preparations

DNA and RNA extraction

DNA/RNA fragmentation

Enrichment technologies

Direct amplification technologies

Sequencing process and equipment

Bioinformatics analysis

Base calling

Demultiplexing

Alignment

Identification and annotation of the variants present in the sample

Copy number variation analysis

Variants annotation

The interpretation of next-generation sequencing results

Quality of the results and validation

Pathogenicity of the identified variants

Epidemiological information.

Information related to molecular biology

Types of mutations

Functional consequences of the mutations in terms of gain or loss of function

Relevance of the regions and isoforms affected by the mutation

Bioinformatics studies

Functional studies and animal models

Transcriptomics and proteomics: From genes to functional defects

Clinical information

Pre-test and post-test probabilities

The yield of the tests

Relation between yield of the test and experiment design: Panel, exome or whole-genome sequencing?

Relation between yield of the test and clinical pre-test: Probability of finding a disease-causing mutation

From diagnosis to prognosis

3 - Cardiovascular embryology and foetal heart development

Genetics of cardiac development

Use of animal models in the exploration of genetics of CHD

Early embryological development

Heart looping and creation of atria

Valve development

Formation of septa

Outflow tract development

Development of the myocardium and coronary vasculature

Conclusions

4 - Genomic basis of heart rate and rhythm generation

The cardiac conduction system

The cardiac action potential

The sinoatrial node

Atrial cardiomyocyte impulse propagation

Atrioventricular nodal conduction

The His-Purkinje system

The ventricular myocardium

Ectopic rhythms

Clinical implications

Summary

5 - Molecular and immunological basis of pulmonary arterial hypertension and pulmonary veno-occlusive disease

Molecular basis for pulmonary arterial hypertension and pulmonary veno-occlusive disease

Histopathology in PAH and PVOD

Alteration of vascular tone in PAH/PVOD

PAH-specific drug therapy

Cellular and molecular consequences of BMPRII mutations.

Molecular similarities between cancer and pulmonary arterial hypertension

Immunological and cellular basis for pulmonary arterial and venous pulmonary hypertension

Dysregulated immune responses in PAH and PVOD

Innate immunity

Macrophages

Neutrophils

Mast cells

Natural killer cells

Linking innate and adaptive immunity

Dendritic cells

Adaptive immunity

T cells

B cells and humoral immune responses

Immunomodulatory therapy in PAH and PVOD

Summary and conclusions

6 - Genetic and immunogenetic basis of myocarditis

Definitions of myocarditis and of inflammatory cardiomyopathy

Aetiopathogenesis of myocarditis

Clinical presentation and diagnosis of myocarditis

Myocarditis and genetics

Infectious or post-infectious myocarditis and genetics

Coxsackievirus B3- myocarditis and genetics

Parvovirus B19 (B19V) myocarditis and genetics

Human herpes virus 6 myocarditis and genetics

Chagas disease (CD) and genetics

Rheumatic fever (RF)/Rheumatic heart disease (RHD) and genetics

Non-infectious myocarditis in systemic immune-mediated diseases and genetics

Sarcoidosis and genetics

Giant cell myocarditis and genetics

Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) and genetics

Single gene defects and myocarditis

Immunity genes and infectious myocarditis

Non-immunity genes associated with hereditary cardiomyopathies and myocarditis

Autoimmunity as the missing link between genetic cardiomyopathies and myocarditis

7 - Cardiovascular metabolomics

Metabolomics

Targeted and non-targeted

Technology

Samples

Metabolite identification

Data and analytic considerations

Sources of metabolites relevant to cardiovascular system

Gut microbiome.

Cardiovascular disorders and metabolomics

Hypertension

Cardiac hypertrophy

Coronary artery disease

Heart failure

Cardiometabolic diseases

Diabetes

Insulin resistance/glucose homoeostasis

Obesity

Applications of cardiovascular metabolomics: Dietary modulation of the gut microbiome

Fibre-rich diet

Omega-3-rich diets

Dairy products fermented or supplemented with beneficial bacteria

8 - Developmental disorders of the heart

Genetic testing in CHD

Aneuploidy and karyotyping

Fluorescent in-situ hybridisation

Array comparative genomic hybridisation

Single nucleotide polymorphism array testing (SNP array)

DNA point mutations

Genomic sequencing

Epigenetics and congenital heart disease

Clinical approach to genetic assessment of CHD

Foetal life

Neonate and infant

Older child/young person

Adult

9 - Application of molecular genetics to congenital vascular anomalies

Clinical characteristics of vascular anomalies: example lymphatic malformations

Lymphatic malformation related to syndromes

Unexplained features of head and neck lymphatic malformations

Genetic aetiology of head and neck lymphatic malformation

Therapy for head and neck lymphatic malformations based on malformation genotype

Funding

10 - Aortic and arterial diseases (Aortopathies)

The aorta

Aortic aneurysm

Syndromic thoracic aortic disorders

Marfan syndrome

Loeys-Dietz syndrome

Meester-Loeys syndrome

IPO8-mediated syndromic TAA

Shprintzen-Goldberg syndrome

Ehlers-Danlos syndrome

Osteogenesis imperfecta

Arterial tortuosity syndrome

Lysyl oxidase - LOX-mediated aortic aneurysm

EFEMP2 (FBLN4) autosomal recessive cutis laxa type 1B.

Other syndromic TAA causes: ABL1, ARIH1, EP300, FLNA, SMAD4 and EMILIN1

BAV-related TAA

Non-syndromic TAA

Aortic aneurysmal disease-related mechanisms

Extracellular matrix homeostasis

VSMC contractile unit function

TGFβ signaling pathway

NO-sGC-PRKG signaling in TAAD

VSMC mitochondrial dysfunction in TAAD

Inflammation in TAAD

Molecular diagnostics

Conclusion and future perspectives

11 - Collagenopathies - The Ehlers-Danlos syndromes

The Ehlers-Danlos syndromes, a general introduction

Clinical hallmarks of the Ehlers-Danlos syndromes

Vascular Ehlers-Danlos syndrome

The 'typical' presentation of vascular EDS

Defects in type III collagen that result in 'atypical' vEDS phenotypes

Classical EDS

Classical EDS due to type V collagen defects

Classical-like EDS variants due to atypical variants in type I procollagen

Classical-like EDS due to proα1(I) p.Arg312Cys substitution

Collagen I-related overlap disorder (C1ROD), arthrochalasia and dermatosparaxis type of EDS

Cardiac-valvular type of EDS

Kyphoscolitic EDS

Kyphoscoliotic EDS due to LH1 deficiency

Kyphoscoliotic EDS due to FKBP22 defects

EDS types caused by defects in non-collagenous ECM molecules

Diagnostic approach

Funding Information

12 - Collagenopathies: Osteogenesis imperfecta and related disorders

Aetiology of OI

Classification of OI

Genetics of OI

Clinical manifestations in OI

Main clinical features in OI

Extra-skeletal features

Diagnosis in OI

Management in OI

13 - Cardiomyopathies - Inherited subtypes and phenocopies

Hypertrophic cardiomyopathy

Definition and epidemiology

Genetic background

Functional anatomy

The role of the sarcomere in pathophysiology.

Genetic architecture of the sarcomere.

Notes:

Includes bibliographical references and index.

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Part of the metadata in this record was created by AI, based on the text of the resource.

Description based on print version record.

ISBN:

9780128229200

0128229209

OCLC:

1443083918