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. 1989 Aug;45(2):304–309.

Linkage analysis of families with fragile-X mental retardation, using a novel RFLP marker (DXS 304).

N Dahl 1, P Goonewardena 1, H Malmgren 1, K H Gustavson 1, G Holmgren 1, E Seemanova 1, G Annerén 1, A Flood 1, U Pettersson 1
PMCID: PMC1683358  PMID: 2569270

Abstract

A new polymorphic DNA marker U6.2, defining the locus DXS304, was recently isolated and mapped to the Xq27 region of the X chromosome. In the previous communication we describe a linkage study encompassing 16 fragile-X families and using U6.2 and five previously described polymorphic markers at Xq26-q28. One recombination event was observed between DXS304 and the fragile-X locus in 36 informative meioses. Combined with information from other reports, our results suggest the following order of the examined loci on Xq: cen-F9-DXS105-DXS98-FRAXA-DXS304-(DXS52-F8 -DXS15). The locus DXS304 is closely linked to FRAXA, giving a peak lod score of 5.86 at a corresponding recombination fraction of .00. On the basis of the present results, it is apparent that U6.2 is a useful probe for carrier and prenatal diagnosis in fragile-X families.

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Selected References

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

  1. Antonarakis S. E., Youssoufian H., Kazazian H. H., Jr Molecular genetics of hemophilia A in man (factor VIII deficiency). Mol Biol Med. 1987 Apr;4(2):81–94. [PubMed] [Google Scholar]
  2. Arveiler B., Oberlé I., Vincent A., Hofker M. H., Pearson P. L., Mandel J. L. Genetic mapping of the Xq27-q28 region: new RFLP markers useful for diagnostic applications in fragile-X and hemophilia-B families. Am J Hum Genet. 1988 Feb;42(2):380–389. [PMC free article] [PubMed] [Google Scholar]
  3. Boggs B. A., Nussbaum R. L. Two anonymous X-specific human sequences detecting restriction fragment length polymorphisms in region Xq26----qter. Somat Cell Mol Genet. 1984 Nov;10(6):607–613. doi: 10.1007/BF01535226. [DOI] [PubMed] [Google Scholar]
  4. Brown W. T., Gross A., Chan C., Jenkins E. C., Mandel J. L., Oberlé I., Arveiler B., Novelli G., Thibodeau S., Hagerman R. Multilocus analysis of the fragile X syndrome. Hum Genet. 1988 Mar;78(3):201–205. doi: 10.1007/BF00291662. [DOI] [PubMed] [Google Scholar]
  5. Brown W. T., Wu Y., Gross A. C., Chan C. B., Dobkin C. S., Jenkins E. C. RFLP for linkage analysis of fragile X syndrome. Lancet. 1987 Jan 31;1(8527):280–280. doi: 10.1016/s0140-6736(87)90103-6. [DOI] [PubMed] [Google Scholar]
  6. Camerino G., Mattei M. G., Mattei J. F., Jaye M., Mandel J. L. Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male. Nature. 1983 Dec 15;306(5944):701–704. doi: 10.1038/306701a0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Davies K. E., Mattei M. G., Mattei J. F., Veenema H., McGlade S., Harper K., Tommerup N., Nielsen K. B., Mikkelsen M., Beighton P. Linkage studies of X-linked mental retardation: high frequency of recombination in the telomeric region of the human X chromosome (fragile site/linkage/recombination/X chromosome). Hum Genet. 1985;70(3):249–255. doi: 10.1007/BF00273451. [DOI] [PubMed] [Google Scholar]
  9. Gitschier J., Drayna D., Tuddenham E. G., White R. L., Lawn R. M. Genetic mapping and diagnosis of haemophilia A achieved through a BclI polymorphism in the factor VIII gene. 1985 Apr 25-May 1Nature. 314(6013):738–740. doi: 10.1038/314738a0. [DOI] [PubMed] [Google Scholar]
  10. Gustavson K. H., Blomquist H. K., Holmgren G. Prevalence of the fragile-X syndrome in mentally retarded boys in a Swedish county. Am J Med Genet. 1986 Jan-Feb;23(1-2):581–587. doi: 10.1002/ajmg.1320230152. [DOI] [PubMed] [Google Scholar]
  11. Mulley J., Turner G., Bain S., Sutherland G. R. Linkage between the fragile X and F9, DXS52 (St14), DXS98 (4D-8) and DXS105 (cX55.7). Am J Med Genet. 1988 May-Jun;30(1-2):567–580. doi: 10.1002/ajmg.1320300158. [DOI] [PubMed] [Google Scholar]
  12. Mulligan L. M., Grover H. J., Blanchette V. S., Giles A. R., Lillicrap D. P., Phillips A., Holden J. J., White B. N. Recombination between the factor VIII gene and the DXS52 locus gives the most probable genetic order as centromere-fra(X)-DXS15-DXS52-F8C-telomere. Am J Med Genet. 1987 Mar;26(3):751–760. doi: 10.1002/ajmg.1320260334. [DOI] [PubMed] [Google Scholar]
  13. Oberlé I., Camerino G., Wrogemann K., Arveiler B., Hanauer A., Raimondi E., Mandel J. L. Multipoint genetic mapping of the Xq26-q28 region in families with fragile X mental retardation and in normal families reveals tight linkage of markers in q26-q27. Hum Genet. 1987 Sep;77(1):60–65. doi: 10.1007/BF00284716. [DOI] [PubMed] [Google Scholar]
  14. Oberlé I., Heilig R., Moisan J. P., Kloepfer C., Mattéi G. M., Mattéi J. F., Boué J., Froster-Iskenius U., Jacobs P. A., Lathrop G. M. Genetic analysis of the fragile-X mental retardation syndrome with two flanking polymorphic DNA markers. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1016–1020. doi: 10.1073/pnas.83.4.1016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]
  16. Patterson M., Bell M., Kress W., Davies K. E., Froster-Iskenius U. Linkage studies in a large fragile X family. Am J Hum Genet. 1988 Nov;43(5):684–688. [PMC free article] [PubMed] [Google Scholar]
  17. Prouty L. A., Rogers R. C., Stevenson R. E., Dean J. H., Palmer K. K., Simensen R. J., Coston G. N., Schwartz C. E. Fragile X syndrome: growth, development, and intellectual function. Am J Med Genet. 1988 May-Jun;30(1-2):123–142. doi: 10.1002/ajmg.1320300111. [DOI] [PubMed] [Google Scholar]
  18. Sherman S. L., Jacobs P. A., Morton N. E., Froster-Iskenius U., Howard-Peebles P. N., Nielsen K. B., Partington M. W., Sutherland G. R., Turner G., Watson M. Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum Genet. 1985;69(4):289–299. doi: 10.1007/BF00291644. [DOI] [PubMed] [Google Scholar]
  19. Sherman S. L., Morton N. E., Jacobs P. A., Turner G. The marker (X) syndrome: a cytogenetic and genetic analysis. Ann Hum Genet. 1984 Jan;48(Pt 1):21–37. doi: 10.1111/j.1469-1809.1984.tb00830.x. [DOI] [PubMed] [Google Scholar]
  20. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  21. Tantravahi U., Murty V. V., Jhanwar S. C., Toole J. J., Woozney J. M., Chaganti R. S., Latt S. A. Physical mapping of the factor VIII gene proximal to two polymorphic DNA probes in human chromosome band Xq28: implications for factor VIII gene segregation analysis. Cytogenet Cell Genet. 1986;42(1-2):75–79. doi: 10.1159/000132255. [DOI] [PubMed] [Google Scholar]
  22. Thibodeau S. N., Dorkins H. R., Faulk K. R., Berry R., Smith A. C., Hagerman R., King A., Davies K. E. Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome. Hum Genet. 1988 Jul;79(3):219–227. doi: 10.1007/BF00366240. [DOI] [PubMed] [Google Scholar]
  23. Turner G., Robinson H., Laing S., Purvis-Smith S. Preventive screening for the fragile X syndrome. N Engl J Med. 1986 Sep 4;315(10):607–609. doi: 10.1056/NEJM198609043151002. [DOI] [PubMed] [Google Scholar]
  24. Veenema H., Carpenter N. J., Bakker E., Hofker M. H., Ward A. M., Pearson P. L. The fragile X syndrome in a large family. III. Investigations on linkage of flanking DNA markers with the fragile site Xq27. J Med Genet. 1987 Jul;24(7):413–421. doi: 10.1136/jmg.24.7.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Webb T. P., Bundey S. E., Thake A. I., Todd J. Population incidence and segregation ratios in the Martin-Bell syndrome. Am J Med Genet. 1986 Jan-Feb;23(1-2):573–580. doi: 10.1002/ajmg.1320230151. [DOI] [PubMed] [Google Scholar]

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