Morphomechanic phenotypic variability of sarcomeric cardiomyopathies: A multifactorial polygenic perspective
Autor: | Ares Pasipoularides |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Sarcomeres Multifactorial Inheritance Systems biology Population Genomics Computational biology 030204 cardiovascular system & hematology Biology Article Translational Research Biomedical 03 medical and health sciences symbols.namesake 0302 clinical medicine Pleiotropy Humans education Molecular Biology Genetic association education.field_of_study business.industry Penetrance Biomechanical Phenomena 030104 developmental biology Biological Variation Population Mendelian inheritance symbols Personalized medicine Cardiology and Cardiovascular Medicine business Cardiomyopathies |
Zdroj: | Journal of molecular and cellular cardiology. 126 |
ISSN: | 1095-8584 |
Popis: | Morphology underlies subdivision of the primary/heritable sarcomeric cardiomyopathies (CMs) into hypertrophic (HCM) and dilated (DCM). Next-generation DNA-sequencing (NGS) has identified important disease-variants, improving CM diagnosis, management, genetic screening, and prognosis. Although monogenic (Mendelian) analyses directly point at downstream studies, they disregard coexisting genomic variations and gene-by-gene interactions molding detailed CM-phenotypes. In-place of polygenic models, in accounting for observed defective genotype-phenotype correlations, fuzzy concepts having gradations of significance and unsharp domain-boundaries are invoked, including pleiotropy, genetic-heterogeneity, incomplete penetrance, and variable expressivity. HCM and DCM undoubtedly entail cooperativity of unidentified/elusive causative genomic-variants. Modern genomics can exploit comprehensive electronic/digital health records, facilitating consideration of multifactorial variant-models. Genome-wide association studies entailing high-fidelity solid-state catheterization, multimodal-imaging, molecular cardiology, systems biology and bioinformatics, will decipher accurate genotype-phenotype correlations and identify novel therapeutic-targets, fostering personalized medicine/cardiology. This review surveys successes and challenges of genetic/genomic approaches to CMs, and their impact on current and future clinical care. |
Databáze: | OpenAIRE |
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