Molecular approaches to gene identification in congenital heart disease

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DESCRIPTION (provided by applicant): Congenital heart disease (CHD) is the most common birth defect with an incidence of 1% of all live births. Many cytogenetic abnormalities have been associated with CHD, and evidence is accumulating that many developmental defects can result from small genomic alternations invisible at the cytogenetic level, resulting in changes in copy number of contiguous genes. We propose to identify genetic contributions to CHD by screening for changes in gene copy number, using genome-wide high resolution oligonucleotide microarrays. We will also screen for genetic mutations in candidate genes in intervals of segmental aneuploidies and in candidate genes identified molecular cardiac development pathways and through model organism screens in the Cardiac Genetics Consortium using high throughput sequencing and analysis of intragenic deletions/duplications using customized oligonucleotide microarrays. Our long-term goals are to define a set of novel genetic and genomic aberrations important in the etiology of CHD, to characterize new syndromes associated with CHD, and to develop improved methods of clinical genetic diagnostics for CHD. We believe this information will provide more accurate clinical prognostic information that can improve genetic counseling and assist families in accurately determining risk of recurrence and prognosis associated with CHD RELEVANCE (See instructions): As CHD is increasingly diagnosed within the second trimester prenatally and as adults with CHD are living to reproductive age, some of the most critical clinical questions for prospective parents are whether or not the CHD in their family has an underlying genetic basis, quantifying the risk of recurrence, and determining prognosis including predictions of neurological function and systemic disease.