Gene investigation and analysis in cardiac development

Congenital heart disease (CHD) is a leading non-infectious cause of death in children. Dysregulation of heart development is at the root of the disease, which is determined to some extent by genetic factors. TBX5 and MEF2A are two of the transcription factors implicated in the process of heart development. Mutations of TBX5 cause Holt-Oram syndrome with cardiac abnormalities, and mutations of MEF2A were found in coronary heart disease patients. To widen the knowledge of CHD and to investigate more genes involved in cardiac development, we performed micro array analysis on RNA from heart tissues following knockdown of TBX5 and MEF2A in chick embryos. Out of 32,773 transcripts screened, 16 novel chick genes were selected for further analysis. One of them, designated LOC418543, shows specific expression in the inflow and outflow tracts during the early stages of chick embryonic heart development. The expression of this gene remains obvious in the outflow tract during heart tube looping, suggesting a potential involvement in heart morphogenesis. In humans, a predicted gene, hmm296404, has been identified as the potential homolog of LOC418543, and hmm296404 is expressed in human fetal heart RNA samples. During the study, the extracelluar matrix coding genefibulin 2 has attracted our attention as it shares similarity with LOC418543 at the protein level, and its high expression pattern in the outflow tract of the heart. Mutational scanning was performed for the whole coding region of the gene in 174 CHD patients having outflow tract defects. Eight putative non-synonymous mutations were found, and five of them are unique to the CHD patients in my study.EThOS - Electronic Theses Online ServiceGBUnited Kingdo