| First Author | Dixkens C | Year | 1997 |
| Journal | Mouse Genome | Volume | 95 |
| Issue | 4 | Pages | 886-88 |
| Mgi Jnum | J:45472 | Mgi Id | MGI:1195493 |
| Citation | Dixkens C, et al. (1997) Refinement of Genetic Mapping of the coat colour mutant belted, bt, on distal mouse Chromosome 15. Mouse Genome 95(4):886-88 |
| abstractText | Full text of Mouse Genome contribution: REFINEMENT OF GENETIC MAPPING OF THE COAT COLOUR MUTANT BELTED, bt, ON DISTAL MOUSE CHROMOSOME 15. Ch. Dixkens, H. Hameister; Department of Medical Genetics, University Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany; Tel: 731-5023436; Fax: 731-5023438; e-mail: horst.hameister@medizin.uni-ulm.de Introduction: bt/bt mice are characterized by a white patch of hair located across the back posterior to the midline. This patch varies in size and may fuse with a ventral patch to a belt. The ventral patch is usually smaller in size and may not be present at all. bt arose as a spontaneous mutation in the DBA stock (1). Tight linkage was reported with Ca and N. Thus, bt was mapped to the sixth linkage group (1). Later, the sixth linkage group was assigned to chromosome 15. In the consensus maps Ca maps at 67.4 cM near the distal end of chromosome 15 in the vicinity of other structural hair defect mutants as: naked, N, and crimpy, cpy. bt maps at 44.4 cM (2, 3). Here we report our mapping results of a bt backcross. Materials and methods: A total of 158 progeny from the intersubspecific backcross [(C57BL/6J-uw bt2J x CAST/Ei)Fl x C57BL/6J-uw bt2J] were analyzed. Microsatellite markers were purchased from Research Genetics, Huntsville. The PCR products were run in 4% NuSieve agarose gels. The fragment sizes of the strain specific alleles are available under http://www.resgen.com. Results and discussion 64 backcross animals were of the belted, bt, phenotype. There was a wide variation in size of the white patch which ranged from a whole belt to only some white hairs on the back. When testing the BC1 animals it was apparent that there are animals which according to genotype are unequivocally bt/bt but did not show the bt phenotype. In Fig. 1, column 2, there are listed 73 BC1 animals with a non-recombinant bt haplotype on their maternal chromosome. According to genotype these animals should show the belted phenotype, but only 56 animals did so. On the contrary from the 71 heterozygote animals listed in column 1 (Fig. 1) two animals were noted with the belted phenotype. Variability of the belted phenotype and the occasional appearance of bt even in heterozygotes is known (l, 4). But reduced penetrance as observed in our intersubspecific backcross with M. castaneus has never been reported. In the cross analyzed during this study the 95% confidence interval for penetrance difference is 0.764 +/- 0.197 (t-test) for bt. In the 14 BC1 animals with recombinant haplotypes linkage is evident with the marker D15Mit108 (Fig. 1). In these animals no deviation from the expected phenotype/genotype correlation was observed. In Fig. 2a are summarized the order of the loci and the inter-marker distances as determined in our bt backcross. D15Mit34 is listed as the most proximal marker. The map position for D15Mit34 is taken from the EUCIB database (5) to position our map to the rest of chromosome 15. According to these data D15Mit108/bt maps between 55.2 - 57.58 cM. In an attempt to integrate more structural gene loci into the genetic map markers specific for the loci Krt2 (6) and Wntl (7) were tested in the bt intersubspecific backcross. These data are listed too in Fig. 2a. Both genes show a map position different from bt. The resolution obtained with our bt backcross is limited. Wnt1 and Krt2 were therefore tested too on informative animals of the EUCIB backcross. The genetic map for distal mouse chromosome 15 is well developed in the EUCIB data base (e.g. 8). The mapping data integrated into the EUCIB map are shown in Fig. 2b. According to this high resolution map D15Mit108 maps to 55.80 cM, Wnt1 to 59.58 cM, and Krt2 to 59.82 cM. One should keep in mind that in our backcross and in the EUCIB backcross the genetic map is based only on female meiosis. Distal mouse chromosome 15 is a region where the male recombination rate exceeds the female rate by a factor of 4 (1; 9). At the present it is difficult to decide where the homolog of bt may reside in the human genome. In a similar mapping study of distal mouse chromosome 15 Jones et al., 1996, (10) have mapped the cell surface protein contactin, Cntnl, 2.2 cM distal from D15Mit34. This coincides very well with the above reported mapping for bt. In human CNTN1 maps to 12cen-q13 (11) as do all other mouse chromosome 15 genes distal from bt. References (1) Murray, J.M., Snell, G.D. (1945). J. Hered. 36, 266-268. (2) Huppi, K., Siwarski, D., Eppig, J.T., Mock, B.A. (1996). Mammalian Genome 6, S256-S270. (3) Mouse Genome Database (MGD) 3.1 (1996) Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web (URL: http//www.informatics.jax.org/) (4) Silvers, W.K. (1979). The coat colours of mice. Springer Verlag, New York. (5) Breen, M., Deakin, L., MacDonald, B., Miller, S., Sibson, R., Tartelin, E., Avner, P., et al. (1994). Hum. Mol. Genet. 3, 621-627. (6) Fowlis, G.A., Adelman, S., Knight, A.M., Simpson, E. (1992). Mammalian Genome 3, 192-196. (7) Santos, J., Perez de Castro, I., Herranz, M., Fernandez-Piqueras, J. (1995). Cytogenet, Cell Genet. 71, 223-224. (8) Puliti, A., Prehu, M.O., Simon-Chazottes, D., Ferkdadji, L., Peuchmaur, M., Goosens, M., Guenet, J.L. (1995). Mammalian Genome 6, 763-768. (9) Wallace, M.E., Mallyon, S.A. (1972). Genet. Res. 20, 257-262. (10) Jones, J.M., Ranscht, B., Berglund, E.O., Gruenheid, S., Gros, P., Meisler, M.H. (1996). Mammalian Genome 7, 696-697. (11) Berglund, E.O., Ranscht, B. (1994). Genomics 21, 571-582. (12) Dietrich, W.F., Miller, J.C., Steen, R.G., Merchant, M., Damron, D., Nahf, R., Gross, A., Joyce, D.C., Wessel, M., Dredge, R.D., Marquis, A., Stein, L.D., Goodman, N., Page, D.C., Lander, E.S. (1994). Nature Genet. 7, 220-245. Fig. 1: (Legend). Haplotypes of 158 (bt/+ x bt/bt) animals. Each column represents a specific haplotype. Filled boxes are CAST/Ei alleles, open boxes C57BL6J-bt alleles. The number of animals with the specific haplotype is given below. In brackets are listed the animals with deviant bt phenotype (see text). The microsatellite primers were chosen from (12), for Krt2 the primer M22832 (6) and for Wntl the primer MUSINTIA (7) were used. Fig. 2: (Legend). (a) Genetic map of distal mouse chromosome 15 derived from the bt backcross. Genomic DNA from 158 backcross animals was typed for the indicated loci. The map is positioned according to the map position of D15Mit34 in the EUCIB map. (b) The same map, but derived from the high resolution EUCIB backcross. The loci integrated into this map during this study are shown in bold. |
