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Novel In Vivo Genetic and Single-Cell Genomic Analyses for Understanding Congenital Heart Disease
This research project addresses the FY19 PRMRP Topic Area Congenital Heart Disease. Congenital heart disease (CHD) is a birth defect that is characterizedby improper cardiac development, resulting in the abnormal structure and function of the heart. It is the most common birth defect, affecting approximately 1percent of the population at varying severities. Understanding the causes of CHD is critical for military personnel and their families because undiagnosedcongenital heart defects can impact health and combat effectiveness. It is estimated that previous studies have thus far accounted for only about 10-20 percentof the genetic contribution to CHDs. Thus, many more human CHD genes, likely about 400 genes, await discovery. A major hurdle that remains forunderstanding the causes of CHD is the identification and validation of the many human CHD genes that are as yet unknown. If a better understanding of thegenetic and molecular bases of CHD could be obtained, then advances in genomic technologies now make it feasible to use genomic screening of militarypersonnel and recruits to identify at-risk individuals. The goal of this research project is to provide increased understanding of the genetic and molecularcauses of CHD, leading to more accurate diagnoses of CHD. The hypothesis of this proposal is that we can demonstrate functions for a novel set of CHDcandidate genes in heart development, using in vivo functional and genomic assays in the zebrafish animal model.
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