Introduction to the Workshop
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The electronic form of this document may be cited in the following style:
Human Genome Program, U.S. Department of Energy, DOE Human Genome Program Contractor-Grantee Workshop IV, 1994.
Abstracts scanned from text submitted for November 1994 DOE Human Genome Program Contractor-Grantee Workshop. Inaccuracies have not been corrected.
Mouse Genome Studies Aimed at Deciphering Gene Function
Woychik, R.P., Stubbs, L., Mucenski, M.L., Moyer, J., Kwon, H., Richards, W.G., Yoder, B. and Wilkinson, J.E.
Biology Division, Oak Ridge National Laboratory, P.O. Box 2009, Oak Ridge, TN 37831-807,
We have initiated a comprehensive program aimed at man-mouse comparative genome studies in the Biology Division at the Oak Ridge National Laboratory. As one component of this effort, transgenic and targeted mutagenesis strategies are being developed in mice to begin to explore the function of individual genes derived from the human and mouse physical mapping initiatives. To illustrate the nature of this research, we have developed a mutation in the mouse which corresponds to a gene in humans mapping to Chromosome 13 at position 13q12.1. This gene is over 100-kb in length and is comprised of 25 individual exons, most of which are less than 100 bp in length. The gene gives rise to a 2.8 kb mRNA in humans and is expressed with a broad tissue distribution. In the mouse, the gene produces a 3.2 kb mRNA which is also expressed with a wide tissue distribution. The difference in size between the mouse and human mRNA's is due to a deletion within the 3' untranslated region of the human transcript. Computer analysis revealed that the putative coding region has the potential to produce an 825 amino acid protein in humans that contains a repeated motif called the tetratrico repeat (TPR). Inactivation of this gene in the mouse was most revealing in that the animals developed polycystic kidney disease and a specific liver lesion among other defects. The disease in the mouse closely resembles human autosomal recessive polycystic kidney disease (ARPKD). This approach is allowing us to correlate specific genes with functions and disease conditions in humans.
The submitted manuscript has been authored by a contractor of the U.S. Government under contract No. DE-AC05-840R21400. Accordingly, the U.S. Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purposes.