Genomic arrays, commonly referred to as chips, have been recently developed that can detect changes in the copy number of specific parts of the genome. The ability to reproducibly demonstrate aberrations in the number of copies of a given gene present in an individual provides a unique opportunity to assess this process as a disease mechanism for congenital birth defects. In this Core we will leverage our access to large samples of DNA from structural birth defect registries, the technical and informatics capabilities of the Human Genome Center and the Center for Genome Science and the genetics expertise of the Division of Genetics & Genomic Medicine to examine individual variation in copy number as causative for specific congenital heart defects and musculoskeletal disorders.

Over the past year, this Children’s Discovery Institute initiative has supported the work of many investigators who are actively pursuing a range of exciting projects. Christina Gurnett, MD, PhD is finding the underlying cause of limb deformity defects like club foot. Thomas Ferkol, MD is investigating the molecular mechanisms of primary ciliary dyskinesia, a problem that causes chronic lung disease. Justin Fay, PhD focused on identifying genetic causes of preterm birth, and Joshua Rubin, MD is developing new strategies to prevent and treat brain tumors. These diverse fields of investigation are united by the fact that all of these important types of pediatric disease have a genetic basis. Work over the past few years has demonstrated that copy number variants, small deletions and insertions in chromosomes, are a common and important cause of human disease and genetic variation. By using human DNA samples and an Affymetrix GeneChip Genome-Wide Human SNP Array 6.0 platform these investigators have been able to find new genetic problems that may underlie these diverse human diseases. Work is progressing well for each of these investigators as they pursue the new hypotheses based on their arrays. These ongoing studies provide new hope for preventing and treating these serious pediatric medical problems.