Yu-Huan Shih1, Yuji Zhang1, Yonghe Ding1, Christian A Ross1, Hu Li1, Timothy M Olson1, Xiaolei Xu2. 1. From the Department of Biochemistry and Molecular Biology (Y.-H.S., Y.D., X.X.), Information Technology (C.A.R.), Department of Molecular Pharmacology and Experimental Therapeutics (H.L.), Department of Pediatric and Adolescent Medicine (T.M.O.), and Division of Cardiovascular Diseases (T.M.O., X.X.), Mayo Clinic, Rochester, MN; Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, Baltimore (Y.Z.); and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Y.Z.). 2. From the Department of Biochemistry and Molecular Biology (Y.-H.S., Y.D., X.X.), Information Technology (C.A.R.), Department of Molecular Pharmacology and Experimental Therapeutics (H.L.), Department of Pediatric and Adolescent Medicine (T.M.O.), and Division of Cardiovascular Diseases (T.M.O., X.X.), Mayo Clinic, Rochester, MN; Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, Baltimore (Y.Z.); and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore (Y.Z.). xu.xiaolei@mayo.edu.
Abstract
BACKGROUND: Genetic studies of cardiomyopathy and heart failure have limited throughput in mammalian models. Adult zebrafish have been recently pursued as a vertebrate model with higher throughput, but genetic conservation must be tested. METHODS AND RESULTS: We conducted transcriptome analysis of zebrafish heart and searched for fish homologues of 51 known human dilated cardiomyopathy-associated genes. We also identified genes with high cardiac expression and genes with differential expression between embryonic and adult stages. Among tested genes, 30 had a single zebrafish orthologue, 14 had 2 homologues, and 5 had ≥3 homologues. By analyzing the expression data on the basis of cardiac abundance and enrichment hypotheses, we identified a single zebrafish gene for 14 of 19 multiple-homologue genes and 2 zebrafish homologues of high priority for ACTC1. Of note, our data suggested vmhc and vmhcl as functional zebrafish orthologues for human genes MYH6 and MYH7, respectively, which are established molecular markers for cardiac remodeling. CONCLUSIONS: Most known genes for human dilated cardiomyopathy have a corresponding zebrafish orthologue, which supports the use of zebrafish as a conserved vertebrate model. Definition of the cardiac transcriptome and fetal gene program will facilitate systems biology studies of dilated cardiomyopathy in zebrafish.
BACKGROUND: Genetic studies of cardiomyopathy and heart failure have limited throughput in mammalian models. Adult zebrafish have been recently pursued as a vertebrate model with higher throughput, but genetic conservation must be tested. METHODS AND RESULTS: We conducted transcriptome analysis of zebrafish heart and searched for fish homologues of 51 known humandilated cardiomyopathy-associated genes. We also identified genes with high cardiac expression and genes with differential expression between embryonic and adult stages. Among tested genes, 30 had a single zebrafish orthologue, 14 had 2 homologues, and 5 had ≥3 homologues. By analyzing the expression data on the basis of cardiac abundance and enrichment hypotheses, we identified a single zebrafish gene for 14 of 19 multiple-homologue genes and 2 zebrafish homologues of high priority for ACTC1. Of note, our data suggested vmhc and vmhcl as functional zebrafish orthologues for human genes MYH6 and MYH7, respectively, which are established molecular markers for cardiac remodeling. CONCLUSIONS: Most known genes for humandilated cardiomyopathy have a corresponding zebrafish orthologue, which supports the use of zebrafish as a conserved vertebrate model. Definition of the cardiac transcriptome and fetal gene program will facilitate systems biology studies of dilated cardiomyopathy in zebrafish.
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