Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1990 May;46(5):943–949.

Diagnosis of neurofibromatosis I by using tightly linked, flanking DNA markers.

K Ward 1, P O'Connell 1, J C Carey 1, M Leppert 1, S Jolley 1, R Plaetke 1, B Ogden 1, R White 1
PMCID: PMC1683585  PMID: 1971145

Abstract

We tested 132 individuals from 21 families segregating an allele for neurofibromatosis type 1 (NF-1), by using nine RFLPs tightly linked to the NF-1 locus. Family members had requested DNA testing either to determine whether "at risk" children were carrying the NF-1 allele or to determine whether their respective families would be informative for prenatal testing. Predictions about whether a child carries the NF-1 mutation were possible for all 32 at-risk offspring (greater than 98% accuracy based on the recombination estimates currently available for these DNA markers). At least one informative probe was available for all 23 matings in these 21 families; flanking markers were informative for 10 matings. Pairwise analysis showed that several of the polymorphisms were in tight linkage disequilibrium; few recombination events were observed with these markers in the families under study. We conclude that the DNA probes used in this study perform well for diagnostic testing of NF-1 in familial cases. A subset of five probe-enzyme systems (pHHH202/RsaI, p11-3C4.2/MspI, pTH17.19/Bg/II, p11-2C11.7/BamHI, and p11-2F9.8/TaqI) provide reliable linkage information for both clinical testing and prenatal diagnosis.

Full text

PDF
943

Selected References

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

  1. Barker D., Wright E., Nguyen K., Cannon L., Fain P., Goldgar D., Bishop D. T., Carey J., Baty B., Kivlin J. Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science. 1987 May 29;236(4805):1100–1102. doi: 10.1126/science.3107130. [DOI] [PubMed] [Google Scholar]
  2. Carey J. C., Baty B. J., Johnson J. P., Morrison T., Skolnick M., Kivlin J. The genetic aspects of neurofibromatosis. Ann N Y Acad Sci. 1986;486:45–56. doi: 10.1111/j.1749-6632.1986.tb48061.x. [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. Goldgar D. E., Green P., Parry D. M., Mulvihill J. J. Multipoint linkage analysis in neurofibromatosis type I: an international collaboration. Am J Hum Genet. 1989 Jan;44(1):6–12. [PMC free article] [PubMed] [Google Scholar]
  5. Hill W. G. Estimation of linkage disequilibrium in randomly mating populations. Heredity (Edinb) 1974 Oct;33(2):229–239. doi: 10.1038/hdy.1974.89. [DOI] [PubMed] [Google Scholar]
  6. Kobrin J. L., Blodi F. C., Weingeist T. A. Ocular and orbital manifestations of neurofibromatosis. Surv Ophthalmol. 1979 Jul-Aug;24(1):45–51. doi: 10.1016/0039-6257(79)90147-4. [DOI] [PubMed] [Google Scholar]
  7. Kopf A. W., Levine L. J., Rigel D. S., Friedman R. J., Levenstein M. Prevalence of congenital-nevus-like nevi, nevi spili, and café au lait spots. Arch Dermatol. 1985 Jun;121(6):766–769. [PubMed] [Google Scholar]
  8. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am J Hum Genet. 1985 May;37(3):482–498. [PMC free article] [PubMed] [Google Scholar]
  9. Lewontin R C. The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. Genetics. 1964 Jan;49(1):49–67. doi: 10.1093/genetics/49.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Moodie P., Liddell M. B., Peake I. R., Bloom A. L. Carrier detection in 50 haemophilia A kindred by means of three intragenic and two extragenic restriction fragment length polymorphisms. Br J Haematol. 1988 Sep;70(1):77–84. doi: 10.1111/j.1365-2141.1988.tb02437.x. [DOI] [PubMed] [Google Scholar]
  11. O'Connell P., Leach R. J., Ledbetter D. H., Cawthon R. M., Culver M., Eldridge J. R., Frej A. K., Holm T. R., Wolff E., Thayer M. J. Fine structure DNA mapping studies of the chromosomal region harboring the genetic defect in neurofibromatosis type I. Am J Hum Genet. 1989 Jan;44(1):51–57. [PMC free article] [PubMed] [Google Scholar]
  12. Reed K. C., Mann D. A. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. doi: 10.1093/nar/13.20.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Riccardi V. M., Lewis R. A. Penetrance of von Recklinghausen neurofibromatosis: a distinction between predecessors and descendants. Am J Hum Genet. 1988 Feb;42(2):284–289. [PMC free article] [PubMed] [Google Scholar]
  14. Seizinger B. R., Rouleau G. A., Ozelius L. J., Lane A. H., Faryniarz A. G., Chao M. V., Huson S., Korf B. R., Parry D. M., Pericak-Vance M. A. Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene. Cell. 1987 Jun 5;49(5):589–594. doi: 10.1016/0092-8674(87)90534-4. [DOI] [PubMed] [Google Scholar]
  15. Weir B. S. Inferences about linkage disequilibrium. Biometrics. 1979 Mar;35(1):235–254. [PubMed] [Google Scholar]
  16. White P. C., New M. I., Dupont B. Congenital adrenal hyperplasia (2). N Engl J Med. 1987 Jun 18;316(25):1580–1586. doi: 10.1056/NEJM198706183162506. [DOI] [PubMed] [Google Scholar]
  17. White R., Leppert M., Bishop D. T., Barker D., Berkowitz J., Brown C., Callahan P., Holm T., Jerominski L. Construction of linkage maps with DNA markers for human chromosomes. Nature. 1985 Jan 10;313(5998):101–105. doi: 10.1038/313101a0. [DOI] [PubMed] [Google Scholar]
  18. White R., Nakamura Y., O'Connell P., Leppert M., Lalouel J. M., Barker D., Goldgar D., Skolnick M., Carey J., Wallis C. E. Tightly linked markers for the neurofibromatosis type 1 gene. Genomics. 1987 Dec;1(4):364–367. doi: 10.1016/0888-7543(87)90040-1. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES