Publications
79 results found
Pua CJ, Bhalshankar J, Miao K, et al., 2016, Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Journal of Cardiovascular Translational Research, Vol: 9, Pages: 3-11, ISSN: 1937-5395
Inherited cardiac conditions (ICCs) are characterisedby marked genetic and allelic heterogeneity and require extensivesequencing for genetic characterisation. We iterativelyoptimised a targeted gene capture panel for ICCs that includesdisease-causing, putatively pathogenic, research and phenocopygenes (n = 174 genes). We achieved high coverage ofthe target region on both MiSeq (>99.8 % at ≥20× read depth,n= 12) and NextSeq (>99.9 % at ≥20×, n= 48) platforms with100 % sensitivity and precision for single nucleotide variantsand indels across the protein-coding target on the MiSeq. In thefinal assay, 40 out of 43 established ICC genes informative inclinical practice achieved complete coverage (100 % at ≥20×).By comparison, whole exome sequencing (WES; ∼80×),deep WES (∼500×) and whole genome sequencing(WGS; ∼70×) had poorer performance (88.1, 99.2 and99.3 % respectively at ≥20×) across the ICC target. Theassay described here delivers highly accurate and affordablesequencing of ICC genes, complemented by accessiblecloud-based computation and informatics.
Mazzarotto F, Walsh R, Buchan RJ, et al., 2015, Comprehensive sequencing of dilated cardiomyopathy genes reveals additive effects of multiple genes on disease risk and severity, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 523-523, ISSN: 0195-668X
Tayal U, Mazzarotto F, Buchan R, et al., 2015, Comprehensive Assessment of Rare Genetic Variation in Dilated Cardiomyopathy Genes in Patients and Controls (vol 101, pg A41, 2015), HEART, Vol: 101, ISSN: 1355-6037
Francis C, de Marvao A, O'Regan DP, et al., 2015, AORTOPATHY-CAUSING MUTATIONS INCREASE AORTIC STIFFNESS IN HEALTHY INDIVIDUALS, British-Cardiac-Society (BCS) Annual Conference on Hearts and Genes, Publisher: BMJ PUBLISHING GROUP, Pages: A99-A99, ISSN: 1355-6037
Tayal U, Mazzarotto F, Buchan R, et al., 2015, COMPREHENSIVE ASSESSMENT OF RARE GENETIC VARIATION IN DILATED CARDIOMYOPATHY GENES IN PATIENTS AND CONTROLS, British-Cardiac-Society (BCS) Annual Conference on Hearts and Genes, Publisher: BMJ PUBLISHING GROUP, Pages: A41-A42, ISSN: 1355-6037
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- Citations: 1
Roberts AM, Ware J, Herman D, et al., 2015, INTEGRATED ALLELIC, TRANSCRIPTIONAL, AND PHENOTYPIC DISSECTION OF THE CARDIAC EFFECTS OF TITIN VARIATION IN HEALTH AND DISEASER, British-Cardiac-Society (BCS) Annual Conference on Hearts and Genes, Publisher: BMJ PUBLISHING GROUP, Pages: A126-A126, ISSN: 1355-6037
Rea G, Petyrka J, Vieira M, et al., 2015, THE GENETIC SIGNATURE IN ISCHAEMIC HEART DISEASE WITH MYOCARDIAL INFARCTION (MI) AND SIGNIFICANT LEFT VENTRICULAR (LV) DYSFUNCTION, British-Cardiac-Society (BCS) Annual Conference on Hearts and Genes, Publisher: BMJ PUBLISHING GROUP, Pages: A97-A97, ISSN: 1355-6037
Roberts A, Ware J, Herman D, et al., 2015, INTEGRATED ALLELIC, TRANSCRIPTIONAL, AND PHENOTYPIC DISSECTION OF THE CARDIAC EFFECTS OF TITIN VARIATION IN HEALTH AND DISEASE, British-Cardiac-Society (BCS) Annual Conference on Hearts and Genes, Publisher: BMJ PUBLISHING GROUP, Pages: A93-A93, ISSN: 1355-6037
Sanoudou D, Kolokathis F, Arvanitis D, et al., 2015, Genetic modifiers to the PLN L39X mutation in a patient with DCM and sustained ventricular tachycardia?, Global Cardiology Science and Practice, Vol: 2015, ISSN: 2305-7823
Roberts AM, Ware JS, Herman DS, et al., 2015, Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease, Science Translational Medicine, Vol: 7, Pages: 270ra6-270ra6, ISSN: 1946-6234
The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization of this opportunity has been hindered by the burden of TTN-truncating variants (TTNtv) in the general population and uncertainty about their consequences in health or disease. To elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac phenotyping in 5267 individuals across the spectrum of cardiac physiology and integrated these data with RNA and protein analyses of human heart tissues. We report diversity of TTN isoform expression in the heart, define the relative inclusion of TTN exons in different isoforms (using the TTN transcript annotations available at http://cardiodb.org/titin), and demonstrate that these data, coupled with the position of the TTNtv, provide a robust strategy to discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common genetic cause of DCM in ambulant patients in the community, identify clinically important manifestations of TTNtv-positive DCM, and define the penetrance and outcomes of TTNtv in the general population. By integrating genetic, transcriptome, and protein analyses, we provide evidence for a length-dependent mechanism of disease. These data inform diagnostic criteria and management strategies for TTNtv-positive DCM patients and for TTNtv that are identified as incidental findings.
Roberts AM, Ware JS, Herman DS, et al., 2015, What Happens When Titins Are Trimmed?, SCIENCE TRANSLATIONAL MEDICINE, Vol: 7, ISSN: 1946-6234
Francis C, Prapa S, Abdulkareem N, et al., 2014, IDENTIFICATION OF LIKELY PATHOGENIC VARIANTS IN PATIENTS WITH BICUSPID AORTIC VALVE: CORRELATION OF COMPLEX GENOTYPE WITH A MORE SEVERE AORTIC PHENOTYPE, Annual Conference of the British-Cardiovascular-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A55-A56, ISSN: 1355-6037
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- Citations: 4
Baksi AJ, Roberts AM, Ware JS, et al., 2014, Titin: a phenotype-genotype descriptive comparison of dilated cardiomyopathy, ISSN: 1097-6647
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- Citations: 2
Keenan NG, Varkey S, Buchan RJ, et al., 2014, Genotype positive hypertrophic cardiomyopathy is associated with myocardial perfusion abnormalities, Journal of Cardiovascular Magnetic Resonance, Vol: 16, Pages: P342-P342, ISSN: 1097-6647
Ware JS, John S, Roberts AM, et al., 2013, Next Generation Diagnostics in Inherited Arrhythmia Syndromes, JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH, Vol: 6, Pages: 94-103, ISSN: 1937-5387
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- Citations: 26
Sanchez-Cabo F, Torroja C, Benguria A, et al., 2012, Regulation of alternative splicing in the infarcted heart, 2nd Congress of the European-Society-of-Cardiology Council on Basic Cardiovascular Science - Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S10-S10, ISSN: 0008-6363
McDermott-Roe C, Ye J, Ahmed R, et al., 2011, Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function, Nature, Vol: 478, Pages: 114-118
Heinig M, Petretto E, Wallace C, et al., 2010, A <i>trans</i>-acting locus regulates an anti-viral expression network and type 1 diabetes risk, NATURE, Vol: 467, Pages: 460-464, ISSN: 0028-0836
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- Citations: 216
Lu H, Buchan RJ, Cook SA, 2010, MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism, CARDIOVASCULAR RESEARCH, Vol: 86, Pages: 410-420, ISSN: 0008-6363
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- Citations: 269
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