Analysis of molecular mechanisms of cardiac arrhythmia.

• Main Author: Wong, Samantha Zhu Er.
• Other Authors: Surajit Bhattacharyya
• Format: Final Year Project
• Language: English
• Published: 2012
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/50652
• Institution: Nanyang Technological University

Long QT Syndrome (LQTS) is a cardiac disorder that results in lethal arrhythmia in individuals. KCNH2 has been identified as one of the affected genes for the disease. In this study, we analyze molecular mechanisms that would complement diagnostic tools to diagnose LQTS. Zebrafish has been chosen as the model system for this study. Morpholino antisense oligonucleotides was used to knockdown kcnh6 (the functional homolog of KCNH2 in zebrafish) gene, and the same phenotype as with mutants were observed. Zebrafish wild-type, mutant and morphant hearts were acquired for transcriptome analysis and for the construction of a cDNA library which would be used to compare genetic differences between the three groups. Polymorphic variants of KCNH2 were also generated via site-directed mutagenesis to raise stable zebrafish transgenic lines. 25% of the progeny of these heterozygotic lines would express KCNH2-variant mutated hearts and these embryos would be used to analyze zebrafish cardiac electrical profile.