Investigators' Abstract): The goals of the Human Genome Initiative include high resolution genetic and physical mapping of several species in addition to man. Genetic analysis of the mouse is especially important because the mouse can provide a model system for studies of many human genetic diseases. The availability in inbred mouse strains enhances the utility of the mouse for genetic studies and permits rapid construction of recombinational maps that predict gene order with a much higher degree of certainty than do maps of outbred species. A number of human genes including some involved in major human genetic diseases have been identified and localized based on their positions in the mouse genome. The specific goals of this project are to prepare high resolution recombinational and physical maps of mouse chromosome 16 and additional mouse chromosomes with homology to human chromosome 21. The recombinational maps will be constructed using an """"""""interval mapping"""""""" procedure, which requires 99% less effort than conventional mapping. The tools for this application include over 1,000 backcross DNAs from six previously constructed crosses between different subspecies of Mus. These crosses display a high level of polymorphism at the DNA level to simplify the search for polymorphism. Recombinational maps will provide the basis for physical maps of the chromosome made with """"""""radiation hybrids,"""""""" pulsed-field gel electrophoresis, and yeast artificial chromosomes. A maximal number of human probes will be utilized to emphasize the comparative value of the map. Recently developed methods which permit identification of genes on very large DNA segments cloned as YACs will be utilized to provide a profile of the distribution of transcribed segments on the chromosome. The comparative maps of mouse chromosome 16 and human chromosome 21 may provide insights into genes which play a critical role in the developmental anomalies that occur in Down syndrome.
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