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Open AccessArticle

Single-Nucleotide Variations in Cardiac Arrhythmias: Prospects for Genomics and Proteomics Based Biomarker Discovery and Diagnostics

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Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC 20037, USA
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Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA
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McCormick Genomic and Proteomic Center, George Washington University, Washington, DC 20037, USA
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Author to whom correspondence should be addressed.
Genes 2014, 5(2), 254-269; https://doi.org/10.3390/genes5020254
Received: 21 November 2013 / Revised: 19 February 2014 / Accepted: 19 February 2014 / Published: 27 March 2014
(This article belongs to the Section Human Genomics and Genetic Diseases)
Cardiovascular diseases are a large contributor to causes of early death in developed countries. Some of these conditions, such as sudden cardiac death and atrial fibrillation, stem from arrhythmias—a spectrum of conditions with abnormal electrical activity in the heart. Genome-wide association studies can identify single nucleotide variations (SNVs) that may predispose individuals to developing acquired forms of arrhythmias. Through manual curation of published genome-wide association studies, we have collected a comprehensive list of 75 SNVs associated with cardiac arrhythmias. Ten of the SNVs result in amino acid changes and can be used in proteomic-based detection methods. In an effort to identify additional non-synonymous mutations that affect the proteome, we analyzed the post-translational modification S-nitrosylation, which is known to affect cardiac arrhythmias. We identified loss of seven known S-nitrosylation sites due to non-synonymous single nucleotide variations (nsSNVs). For predicted nitrosylation sites we found 1429 proteins where the sites are modified due to nsSNV. Analysis of the predicted S-nitrosylation dataset for over- or under-representation (compared to the complete human proteome) of pathways and functional elements shows significant statistical over-representation of the blood coagulation pathway. Gene Ontology (GO) analysis displays statistically over-represented terms related to muscle contraction, receptor activity, motor activity, cystoskeleton components, and microtubule activity. Through the genomic and proteomic context of SNVs and S-nitrosylation sites presented in this study, researchers can look for variation that can predispose individuals to cardiac arrhythmias. Such attempts to elucidate mechanisms of arrhythmia thereby add yet another useful parameter in predicting susceptibility for cardiac diseases. View Full-Text
Keywords: cardiac arrhythmia; SNP; genome-wide association; proteomics; next-generation sequencing; S-nitrosylation; cysteine; nsSNV; biocuration cardiac arrhythmia; SNP; genome-wide association; proteomics; next-generation sequencing; S-nitrosylation; cysteine; nsSNV; biocuration
MDPI and ACS Style

Abunimer, A.; Smith, K.; Wu, T.-J.; Lam, P.; Simonyan, V.; Mazumder, R. Single-Nucleotide Variations in Cardiac Arrhythmias: Prospects for Genomics and Proteomics Based Biomarker Discovery and Diagnostics. Genes 2014, 5, 254-269.

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