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Human
Genome News Archive Edition |
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Sponsored
by the U.S. Department of
Energy Human Genome Program
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In this issue... 1997 Santa Fe Highlights Human Genome Project Administration In the News Publications Software and the Internet Funding Meeting Calendars & Acronyms |
Functional GenomicsDeciphering the function of each human gene is a daunting prospect that will continue far past the projected 2005 deadline for completing the Human Genome Project. Researchers use model organisms such as the laboratory mouse to help guide these explorations. In Santa Fe, Eddy Rubin (Lawrence Berkeley National Laboratory) and Monica Justice (Oak Ridge National Laboratory) discussed the value of detailed comparative mouse and human linkage maps and the technologies available for manipulating the mouse genome. Rubin described an in vivo approach for tracking down gene function. His group has generated YAC and P1 transgenic mice panels that contain defined contiguous regions of the human genome. The mice are assessed for a phenotype attributed to a candidate genomic region such as the human chromosome 21 Down's -syndrome critical region, which has been linked to learning and behavior. Using three lines of transgenic mice containing up to 2 Mb of human DNA, the group identified a human gene that affects learning in mice. Supporting evidence points to the gene's expression in the developing mouse nervous system and also to a homologous fruit fly gene shown to impact learning in that insect as well. Other potential applications for in vivo libraries include mutation cloning and identifying genes rather than just map locations (quantitative trait loci) in the study of such common complex human disorders as asthma and schizophrenia. Justice spoke about the potential for studying human disease by using deletions of mouse genomic regions coupled with chemical mutagenesis using ethylnitrosourea (ENU), a supermutagen that primarily causes single base changes. She observed that a series of overlapping deletions generated by ENU can be useful for generating fine-structure physical maps, gene cloning, and further mutational analysis of the region. Her group's work focuses on the mouse chromosome 7 albino (c) region, which is homologous to human chromosome 11q13-q21. This region is linked to the mouse homologue of the human disorder oculocutaneous albinism. Justice showed dramatic photographs of a baby and mouse, both bearing the disorder's characteristic coloring. Using this paradigm, she observed that such mouse-human comparative analyses, with additional induced and targeted deletions and chemical mutagenesis, will provide essential data for large-scale expansions of the mouse functional map in parallel with human gene maps. The electronic form of the newsletter may be cited in the following
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