Chromosome rearrangements frequently occur in human hereditary diseases and cancers. Cytogenetic analysis of nonrandom chromosome abnormalities in malignant cells has become an integral part of the clinical diagnostic and prognostic work-up of many human cancers, and their molecular analysis has facilitated the identification of genes related to the pathogenesis of both hereditary diseases and cancer. One significant technical limitation of conventional cytogenetic techniques is their inability to characterize unequivocally all cytogenetically visible chromosome rearrangements (e.g. unknown marker chromosomes and unidentifiable de novo unbalanced translocations). A recently developed techniques, Fluorescence in situ hybridization (FISH) with whole chromosome painting probes (WCPs), has been used to detect complex chromosome rearrangements. However, WCP probes cannot identify individually chromosome arms involved in rearrangements. The goal of this proposal is to generate libraries of whole chromosome- arm-painting probes (CAPs) of E and F group of human chromosomes (including short and long arms of chromosome 16, 17, 18, 19 and 20), by a recently developed technique termed chromosome microdissection. The development and application of CAP probes may greatly facilitate the cytogenetic study of human hereditary diseases and cancers because they can detect not only which chromosomes but also which arms are involved in complex chromosome rearrangements. These chromosome-arm-painting probes will be useful for the studies of human hereditary diseases, certain types of cancers and human genome research. In Phase II, DNA libraries for all human chromosome-arm-painting probes will be constructed from microdissected DNA.Proposed commercial application:Two important techniques changes the laboratory medicine. The discovery of PCR and FISH opens new doors for therapeutic research for the clinical scientists. The targets for treatment are no longer based on morphology, but rather depend on cytogenetics and molecular genetic techniques. The CAPs will be indispensable tools for the researchers trying to identify the genes that are responsible for certain diseases. In the future, CAPs will be used by regular lab technicians as well. They will be marketed worldwide.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
