Human homolog of a mouse sequence from the dystonia musculorum locus is on Chromosome 6p12
- 22 Downloads
Dystonia musculorum is a hereditary neurodegenerative disease in mice that affects sensory neurons. In an effort to clone the gene responsible for this disorder, we have assembled a genomic contig spanning 75 kb of the dystonia musculorum (dt) locus. Within this genomic contig, we have identified a small restriction fragment that shows evolutionary conservation to rat, hamster, rabbit, and human genomic DNA. Using this mouse sequence, we have cloned the conserved human genomic fragment. Sequence analysis of the mouse and human genomic fragments revealed that they share a sequence similarity of 82% over 175 bp. A panel of human/rodent somatic cell hybrids was used to map the human genomic sequence to Chromosome (chr) 6, and high-resolution in situ hybridization (FISH) allowed it to be sublocalized to 6p12. The human homolog of the mouse Bpag1 gene, a gene tightly linked to the mouse dt gene, also maps to Chr 6. Thus this comparative mapping reveals a new region of conserved synteny between the chromosomes of mouse and human. Mapping the human homolog of the mouse dt gene enables us to initiate linkage studies to identify neurodegenerative disorders that may be caused by mutations in this gene.
Unable to display preview. Download preview PDF.
- Brown, A., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Rossant, J., Kothary, R. (1994). The genomic structure of an insertional mutation in the dystonia musculorum locus. Genomics, in press.Google Scholar
- Copeland, N.G., Gilbert, D.J., Li, K., Sawamura, D., Giudice, G.J., Chu, M.-L., Jenkins, N.G., Uitto, J. (1993). Chromosomal localization of mouse bullous pemphigoid antigens, BPAG1 and BPAG2: identification of a new region of homology between mouse and human chromosomes. Genomics 15, 180–181.Google Scholar
- Drouin, R., Lemieux, N., Richer, C.L. (1988). High resolution R-banding at the 1250 band level. I. Technical considerations on cell synchronization and R-banding (RHG and RBG). Cytobios 56, 107–125Google Scholar
- Drwinga, H.L., Toji, L.H., Kim, C.H., Greene, A.E., Mulivor, R.A. (1993). NIGMS human/rodent somatic cell hybrid mapping panels 1 and 2. Genomics 16, 311–314.Google Scholar
- Dubois, B.L., Naylor, S.L. (1993). Characterization of NIGMS human/rodent somatic cell hybrid mapping panel 2 by PCR. Genomics 16, 315–319.Google Scholar
- Feinberg, A.P., Vogelstein, B. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13.Google Scholar
- Kothary, R., Clapoff, S., Brown, A., Campbeli, R., Peterson, A., Rosant, J. (1988) A transgene containing lacZ inserted into the dystonia locus is expressed in neural tube. Nature 335, 435–437.Google Scholar
- Lemieux, N., Dutrillaux, B., Viegas-Péquignot, E., (1992) Simultaneous R- or G-banding and fluorescence in situ hybridization of small single-copy genes: a very simple method. Cytogenet. Cell Genet. 59, 311–312.Google Scholar
- O'Brien, S.J., Womack, J.E., Lyons, L.A., Moore, K.J., Jenkins, N.A., Copeland, N.G. (1993). Anchored reference loci for comparative genome mapping in mammals. Nature Genet. 3, 103–112.Google Scholar
- Sambrook, J., Fritsch, E.F., Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual. (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press).Google Scholar
- Sawamura, D., Nomura, K., Sugita, Y., Mattei, M.-G., Chu, M.-L., Knowlton, R., Uitto, J. (1990). Bullous Pemphigoid Antigen (BPAG1): cDNA cloning and mapping of the gene to the short arm of human chromosome 6. Genomics 8, 722–726.Google Scholar