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. 1989 Sep;84(3):1013–1016. doi: 10.1172/JCI114222

Clustering of multiallele DNA markers near the Huntington's disease gene.

M E MacDonald 1, S V Cheng 1, M Zimmer 1, J L Haines 1, A Poustka 1, B Allitto 1, B Smith 1, W L Whaley 1, D M Romano 1, J Jagadeesh 1, et al.
PMCID: PMC329749  PMID: 2569477

Abstract

Five highly informative multiallele restriction fragment length polymorphisms (RFLPs) of value for preclinical diagnosis of Huntington's disease (HD) have been genetically characterized. One RFLP was uncovered by expansion of the D4S43 locus while three others are at D4S111 and D4S115, loci defined by NotI-linking clones. The final marker, D4S125, represents a recently discovered VNTR locus. All four loci map closer to the HD gene and to the telomere than D4S10, the original linked marker for HD. In combination with two multiallele RFLPs previously identified for D4S43 and another linked locus, D4S95, these five new multiallele markers will dramatically improve the speed and accuracy of predictive testing in HD, and increase its applicability by maximizing the chances of an informative test for anyone with appropriate family structure.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Botstein D., White R. L., Skolnick M., Davis R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PMC free article] [PubMed] [Google Scholar]
  2. Conneally P. M., Edwards J. H., Kidd K. K., Lalouel J. M., Morton N. E., Ott J., White R. Report of the Committee on Methods of Linkage Analysis and Reporting. Cytogenet Cell Genet. 1985;40(1-4):356–359. doi: 10.1159/000132186. [DOI] [PubMed] [Google Scholar]
  3. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  4. Gilliam T. C., Bucan M., MacDonald M. E., Zimmer M., Haines J. L., Cheng S. V., Pohl T. M., Meyers R. H., Whaley W. L., Allitto B. A. A DNA segment encoding two genes very tightly linked to Huntington's disease. Science. 1987 Nov 13;238(4829):950–952. doi: 10.1126/science.2890209. [DOI] [PubMed] [Google Scholar]
  5. Gilliam T. C., Healey S. T., MacDonald M. E., Stewart G. D., Wasmuth J. J., Tanzi R. E., Roy J. C., Gusella J. F. Isolation of polymorphic DNA fragments from human chromosome 4. Nucleic Acids Res. 1987 Feb 25;15(4):1445–1458. doi: 10.1093/nar/15.4.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gilliam T. C., Tanzi R. E., Haines J. L., Bonner T. I., Faryniarz A. G., Hobbs W. J., MacDonald M. E., Cheng S. V., Folstein S. E., Conneally P. M. Localization of the Huntington's disease gene to a small segment of chromosome 4 flanked by D4S10 and the telomere. Cell. 1987 Aug 14;50(4):565–571. doi: 10.1016/0092-8674(87)90029-8. [DOI] [PubMed] [Google Scholar]
  7. Gusella J. F., Tanzi R. E., Anderson M. A., Hobbs W., Gibbons K., Raschtchian R., Gilliam T. C., Wallace M. R., Wexler N. S., Conneally P. M. DNA markers for nervous system diseases. Science. 1984 Sep 21;225(4668):1320–1326. doi: 10.1126/science.6089346. [DOI] [PubMed] [Google Scholar]
  8. Gusella J. F., Wexler N. S., Conneally P. M., Naylor S. L., Anderson M. A., Tanzi R. E., Watkins P. C., Ottina K., Wallace M. R., Sakaguchi A. Y. A polymorphic DNA marker genetically linked to Huntington's disease. Nature. 1983 Nov 17;306(5940):234–238. doi: 10.1038/306234a0. [DOI] [PubMed] [Google Scholar]
  9. Gusella J., Varsanyi-Breiner A., Kao F. T., Jones C., Puck T. T., Keys C., Orkin S., Housman D. Precise localization of human beta-globin gene complex on chromosome 11. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5239–5242. doi: 10.1073/pnas.76.10.5239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MacDonald M. E., Anderson M. A., Gilliam T. C., Tranejaerg L., Carpenter N. J., Magenis E., Hayden M. R., Healey S. T., Bonner T. I., Gusella J. F. A somatic cell hybrid panel for localizing DNA segments near the Huntington's disease gene. Genomics. 1987 Sep;1(1):29–34. doi: 10.1016/0888-7543(87)90101-7. [DOI] [PubMed] [Google Scholar]
  12. Martin J. B., Gusella J. F. Huntington's disease. Pathogenesis and management. N Engl J Med. 1986 Nov 13;315(20):1267–1276. doi: 10.1056/NEJM198611133152006. [DOI] [PubMed] [Google Scholar]
  13. Meissen G. J., Myers R. H., Mastromauro C. A., Koroshetz W. J., Klinger K. W., Farrer L. A., Watkins P. A., Gusella J. F., Bird E. D., Martin J. B. Predictive testing for Huntington's disease with use of a linked DNA marker. N Engl J Med. 1988 Mar 3;318(9):535–542. doi: 10.1056/NEJM198803033180903. [DOI] [PubMed] [Google Scholar]
  14. Nakamura Y., Culver M., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pYNZ32) on chromosome 4p [D4S125]. Nucleic Acids Res. 1988 May 11;16(9):4186–4186. doi: 10.1093/nar/16.9.4186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nakamura Y., Leppert M., O'Connell P., Wolff R., Holm T., Culver M., Martin C., Fujimoto E., Hoff M., Kumlin E. Variable number of tandem repeat (VNTR) markers for human gene mapping. Science. 1987 Mar 27;235(4796):1616–1622. doi: 10.1126/science.3029872. [DOI] [PubMed] [Google Scholar]
  16. Pohl T. M., Zimmer M., MacDonald M. E., Smith B., Bucan M., Poustka A., Volinia S., Searle S., Zehetner G., Wasmuth J. J. Construction of a NotI linking library and isolation of new markers close to the Huntington's disease gene. Nucleic Acids Res. 1988 Oct 11;16(19):9185–9198. doi: 10.1093/nar/16.19.9185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smith B., Skarecky D., Bengtsson U., Magenis R. E., Carpenter N., Wasmuth J. J. Isolation of DNA markers in the direction of the Huntington disease gene from the G8 locus. Am J Hum Genet. 1988 Feb;42(2):335–344. [PMC free article] [PubMed] [Google Scholar]
  18. Tanzi R. E., Haines J. L., Watkins P. C., Stewart G. D., Wallace M. R., Hallewell R., Wong C., Wexler N. S., Conneally P. M., Gusella J. F. Genetic linkage map of human chromosome 21. Genomics. 1988 Aug;3(2):129–136. doi: 10.1016/0888-7543(88)90143-7. [DOI] [PubMed] [Google Scholar]
  19. Wasmuth J. J., Hewitt J., Smith B., Allard D., Haines J. L., Skarecky D., Partlow E., Hayden M. R. A highly polymorphic locus very tightly linked to the Huntington's disease gene. Nature. 1988 Apr 21;332(6166):734–736. doi: 10.1038/332734a0. [DOI] [PubMed] [Google Scholar]
  20. Wexler N. S., Conneally P. M., Housman D., Gusella J. F. A DNA polymorphism for Huntington's disease marks the future. Arch Neurol. 1985 Jan;42(1):20–24. doi: 10.1001/archneur.1985.04060010026009. [DOI] [PubMed] [Google Scholar]
  21. Whaley W. L., Michiels F., MacDonald M. E., Romano D., Zimmer M., Smith B., Leavitt J., Bucan M., Haines J. L., Gilliam T. C. Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4. Nucleic Acids Res. 1988 Dec 23;16(24):11769–11780. doi: 10.1093/nar/16.24.11769. [DOI] [PMC free article] [PubMed] [Google Scholar]

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