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Additional info for Congenital Heart Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References
These specific aims have been developed based upon the rationale and feasibility demonstrated in preliminary data. The availability of multiple kindreds at different stages of genetic evaluation is key to ensuring successful completion of the proposed studies. Based on preliminary studies, at least three genes can cause ASD. To date there have been no report of a gene whose mutation causes a simple, common heart defect such as ASD. Identification of such genes would provide an important perspective of both normal and abnormal cardiac development.
Systematic studies of the cis-acting sequences that control cardiac-restricted genes, the trans-acting factors binding these regions, circuits governing the factors' expression or function, and other circuits affecting morphogenesis itself have, in these five years, culminated in gratifying new insights and opportunities within the field, in large part through the efforts of these PPG investigators. 5 gene regulation via BAC transgenics and interacting proteins, focused on SRF, CRP 1/2/3 lim only factors, GATA-4 and dHAND and their knockouts, including an emphasis on combinatorial transcription factor complexes with SRF (Schwartz) Genes That Regulate Heart Development: Myocardin, interacting proteins, Myocardin relatives and knockouts, with an emphasis on the association with SRF and other Myocardin accessory factors (Olson) Adult Cardiac Myogenesis by Heart-derived Progenitor Cells.
The possibility that one of the candidate genes, which encodes a novel cell adhesion molecule, called DS-CAM, is a transcriptional target for MEF2 will also be addressed. Each of these projects is interrelated through the creation of novel strains of mouse mutants in which key cardiogenic regulatory genes can be inactivated in a temporaland compartment-specific manner within the developing heart. These studies will provide an in-depth understanding of the basic molecular pathways that regulate heart development and the ways in which these pathways can be disrupted in congenital heart diseases.