HIGH THROUGHPUT FISH MAPPING

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DESCRIPTION: (Applicant's Abstract): Project 1 (High Throughput FISH Mapping) will focus on the collection, cataloguing and chromosomal breakpoint mapping of individuals with apparently balanced rearrangements and congenital anomalies. Karyotypes, annotated breakpoints and clinical information will be deposited in the DGAP database (http://dgap.harvard.edu/). Human cell lines will be obtained or established from a national and international network of Clinical Geneticists and Clinical Cytogeneticists in addition to the NIGMS Human Genetic Mutant Cell Respository. Fluorescence in situ hybridization (FISH) using human BAC clones will be used to identify genomic segments that span chromosomal breakpoints. To accomplish high throughput FISH mapping, collaborations have been established with members of the "genome community" who are already providing us with human BACs representing a collection of FISH-mapped clones spaced at an approximately 1 Mb interval throughout the genome and correlated with radiation hybrid-based physical maps. About 100 new breakpoint cases are estimated to be accessioned per year including archived and prospective collections. A well-defined clinical prioritization scheme based on the identification of "two-hit" cases (i.e., patients with similar breakpoints and anomalies) and a biological resources prioritization plan will be employed with the aim of identifying 8 breakpoints per year to be passed to Project 2 (Rapid Gene Discovery). Gene identification and characterization studies from Projects 2 and 3 (Developmental Analysis of Genes in Model Organisms) will be posted on the DGAP database. In overview, Project 1 will serve as the entry point for a functional genomics project that will generate a public resource of genes critical in human development.