Charles M. Perou, Antoine L. Perchellet[1], Jerry Kaplan, and Monica J. Justice[2]
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132.
Mouse Chromosome 13 contains regions conserved on human chromosomes 1q41q43, 6p23-p21, 7p22-p13 and 5q11.2-q35. These regions contain numerous models for human disease, such as Chediak Higashi syndrome (mouse beige) [1], Greig cephalopolysyndactly syndrome (mouse extra-toes) [2], and cancer [3, 4, 5, 6]. The mouse provides a useful genetic model organism for understanding the mechanism of disease in humans, as well as for dissecting the biological function of other genes that are conserved between mouse and human.
As a first step in examining the function of genes in the proximal region of mouse chromosome 13, we are creating a fine structure genetic linkage map of the genomic region encompassing beige (bg) and satin (sa). An interspecific backcross involving SB/Le and Mus spretus mice was used to generate a molecular genetic linkage map of mouse chromosome 13 [7]. This map provides the gene order of the two phenotypic markers bg and sa relative to restriction fragment length variants and simple sequence length variants. Our initial study involves 132 backcross animals, and spans the entire chromosome. The results from these data will direct "interval mapping" of the bg-sa region on an additional 400 animals. In the bg-sa region of 6 cM, the marker density of our map exceeds 7 markers/cM.
In parallel to the genetic linkage mapping, we are creating a physical map of the region using Nidogen (Nid) as a molecular starting point for cloning a YAC contig. Multiple cDNAs have been isolated from these YACs, and the results show that linkage homology with human chromosome 1q41-43 is highly conserved in the mouse. The results also precisely localize a breakpoint in homology between human chromosomes 1q43 and 7p 13 in the region. The genetic and physical mapping results will provide valuable resources for further functional studies of the conserved genes in the region using induced mutations.
MJJ is supported by the U.S. Department of Energy, work proposal No. ERKP057, by the National Institutes of Health, 7R29CA63229-02, and by an award from the American Cancer Society, JFRA-553. J.K. is supported by the National Institutes of Health, HL26922, and C.M.P. is the recipient of an NIH Genetics Training Grant T32GM07464.
[1] Division of Biology, Kansas State University, Manhattan, KS 66506; [2] Biology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831
[1] Holcombe, R.F., Strauss, W., Owen, F.L., Boxer, L.A., Warren, R.W., Conley, M.E., Ferrara, J., Leavitt, R.Y., Fauci, A.S., Taylor, B.A., and Seidman, J.G. (1987) Genomics 1, 287-291
[2] Winter,R.M. (1988) J Med Genet 25, 480-487
[3] Rousseau-Merck, M., Bernheim, A., Chardin, P., Miglierina, R., Tavitian, A., and Berger, R. (1988) Hum Genet 79, 132-136
[4] Van Cong, N., Fichelson, S., Gross, M.S., Sola, B., Bordereaux, D., de Tand, M.F., Guilhot, S., Gisselbrecht, S., Frezal, J., and Tambourin, P. (1989) Hum Genet 81, 257263
[5] Vortkamp, A., Franz, T., Gessler, M., and Grzeschik, K. (1992) Mammalian Genome 3, 461-463
[6] Hsieh, C., Vogel, U.S., Dixon, R.A.F., and Francke, U. (1989) Somatic Cell Mol Genet 15, 579-590
[7] Justice, M.J., Silan, C.M., Ceci, J.D., Buchberg, A.M., Copeland, N.G., and Jenkins, N.A. (1990) Genomics 6, 341-351