Nature Genetics
1, 99 - 103 (1992)
doi:10.1038/ng0592-99
The Huntington's disease candidate region exhibits many different haplotypesMarcy E. MacDonald1, Andrea Novelletto2, Carol Lin1, Dan Tagle3, Glenn Barnes1, Gillian Bates4, Sherry Taylor1, Bernice Allitto1, Michael Altherr5, Richard Myers6, Hans Lehrach4, Francis S. Collins3, John J. Wasmuth5, Marina Frontali7
& James F. Gusella1
1Neurogenetics Laboratory, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
2Dipartimento di Biologia, Universita' Tor Vergata, Roma, Italy
3Department of Internal Medicine and Human Genetics, and the Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
4Imperial Cancer Research Fund, Lincoln's Inn Fields, London, WC2A 3PX, UK
5Department of Biological Chemistry, University of California, Irvine California 92717, USA
6Department of Neurology, Boston University Medical School, 80 East Concord Street, Boston, Massachusetts 02118, USA
7Istituto di Medicina Sperimentale, CNR, Roma, Italy Analysis of 78 Huntington's disease (HD) chromosomes with multi−allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diverstiy. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and DAS180.
REFERENCES
- Martin, J.B. & Gusella, J.F. New Engl. J. Med. 315, 1267−1276 (1986). | PubMed | ISI | ChemPort |
- Gusella, J.F. Adv. hum. Genet. 20, 125−151 (1991). | PubMed | ChemPort |
- MacDonald, M.E. et al. Neuron 3, 183−190 (1989). | Article | PubMed | ISI | ChemPort |
- Snell, R.G. et al. J. med. Genet. 26, 673−675 (1989). | PubMed | ISI | ChemPort |
- Theilmann, J. et al. J. med. Genet. 26, 676−681 (1989). | PubMed | ISI | ChemPort |
- Novelletto, A. et al. Am. J. med. Genet. 40, 374−376 (1991). | PubMed | ISI | ChemPort |
- Adam, S. et al. Am. J. hum. Genet. 48, 595−603 (1991). | PubMed | ISI | ChemPort |
- MacDonald, M.E. et al. Am. J. hum. Genet. 49, 723−734 (1991). | PubMed | ISI | ChemPort |
- Kerem, B. et al. Science 245, 1073−1080 (1989). | PubMed | ISI | ChemPort |
- Lin, C.S. et al. Somat. Cell molec. Genet. 17, 481−488 (1991). | PubMed | ISI | ChemPort |
- Bates, G.P. et al. Am. J. hum. Genet. 49, 7−16 (1991). | PubMed | ISI | ChemPort |
- Taylor, S.A.M., Barnes, G.T., MacDonald, M.E. & Gusella, J.F. Nucleic Acids Res. (in the press).
- Allitto, B.A. et al. Nucleic Acids Res. 19, 4015 (1991). | PubMed | ISI | ChemPort |
- Wasmuth, J.J. et al. Nature 332, 734−736 (1988). | Article | PubMed | ISI | ChemPort |
- Stevens, D. & Parsonage, M. J. Neurol. Neurosurg. Psychiatry 32, 140−143 (1969). | PubMed | ISI | ChemPort |
- Shaw, M. & Caro, A.J. J. med. Genet. 19, 161−167 (1982). | PubMed | ISI | ChemPort |
- Seizinger, B.R., Martuza, R.L. & Gusella, J.F. Nature 322, 664−667 (1986). | PubMed |
- Anderson, M.A. & Gusella, J.F. In Vitro 11, 856−858 (1984).
- Gusella, J.F. et al. Proc. natn. Acad. Sci. U.S.A. 76, 5239−5243 (1979). | ChemPort |
- Gusella, J.F. et al. Nature 306, 234−238 (1983). | PubMed | ISI | ChemPort |
- Feinberg, A.P. & Vogelstein, B. Anal. Biochem. 137, 266−267 (1984). | PubMed | ISI | ChemPort |
- Whaley, W.L. et al. Somat. Cell molec. Genet. 17, 83−91 (1991). | PubMed | ISI | ChemPort |
|
