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. 1990 Oct;27(10):614–617. doi: 10.1136/jmg.27.10.614

Two step procedure for early diagnosis of polycystic kidney disease with polymorphic DNA markers on both sides of the gene.

M H Breuning 1, F G Snijdewint 1, J G Dauwerse 1, J J Saris 1, E Bakker 1, P L Pearson 1, G J vanOmmen 1
PMCID: PMC1017239  PMID: 1978861

Abstract

Polymorphic DNA markers can now be used for presymptomatic and prenatal diagnosis of the autosomal dominant form of polycystic kidney disease (PKD). A detailed map is known for the chromosomal region around the PKD1 gene on the short arm of chromosome 16. We present here a simple, two step procedure for diagnosis of PKD1 by family studies. Using this approach, at least 92% of random subjects are informative for polymorphic DNA markers bracketing the PKD1 gene. The recombination rate between these flanking markers is on average 10%. In non-recombinants (90% of family members), the accuracy of diagnosis using DNA markers is greater than 99%. We conclude that sufficient well defined DNA markers are now available for routine diagnosis of PKD1. We recommend, however, that prenatal diagnosis of PKD by chorionic villi sampling should be attempted only after the linkage phase of the DNA markers has been established by haplotyping the index family. Since autosomal dominant PKD has been found to be genetically heterogeneous, families should be of sufficient size to rule out the rare form of PKD not caused by a mutation on the short arm of chromosome 16.

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Selected References

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

  1. Bakker E., Bonten E. J., De Lange L. F., Veenema H., Majoor-Krakauer D., Hofker M. H., Van Ommen G. J., Pearson P. L. DNA probe analysis for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy: a standard diagnostic procedure. J Med Genet. 1986 Dec;23(6):573–580. doi: 10.1136/jmg.23.6.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bear J. C., McManamon P., Morgan J., Payne R. H., Lewis H., Gault M. H., Churchill D. N. Age at clinical onset and at ultrasonographic detection of adult polycystic kidney disease: data for genetic counselling. Am J Med Genet. 1984 May;18(1):45–53. doi: 10.1002/ajmg.1320180108. [DOI] [PubMed] [Google Scholar]
  3. Breuning M. H., Snijdewint F. G., Brunner H., Verwest A., Ijdo J. W., Saris J. J., Dauwerse J. G., Blonden L., Keith T., Callen D. F. Map of 16 polymorphic loci on the short arm of chromosome 16 close to the polycystic kidney disease gene (PKD1). J Med Genet. 1990 Oct;27(10):603–613. doi: 10.1136/jmg.27.10.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cotton R. G., Rodrigues N. R., Campbell R. D. Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4397–4401. doi: 10.1073/pnas.85.12.4397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Darras B. T., Harper J. F., Francke U. Prenatal diagnosis and detection of carriers with DNA probes in Duchenne's muscular dystrophy. N Engl J Med. 1987 Apr 16;316(16):985–992. doi: 10.1056/NEJM198704163161604. [DOI] [PubMed] [Google Scholar]
  6. Den Dunnen J. T., Grootscholten P. M., Bakker E., Blonden L. A., Ginjaar H. B., Wapenaar M. C., van Paassen H. M., van Broeckhoven C., Pearson P. L., van Ommen G. J. Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. Am J Hum Genet. 1989 Dec;45(6):835–847. [PMC free article] [PubMed] [Google Scholar]
  7. Fowler S. J., Gill P., Werrett D. J., Higgs D. R. Individual specific DNA fingerprints from a hypervariable region probe: alpha-globin 3'HVR. Hum Genet. 1988 Jun;79(2):142–146. doi: 10.1007/BF00280553. [DOI] [PubMed] [Google Scholar]
  8. Germino G. G., Barton N. J., Lamb J., Higgs D. R., Harris P., Xiao G. H., Scherer G., Nakamura Y., Reeders S. T. Identification of a locus which shows no genetic recombination with the autosomal dominant polycystic kidney disease gene on chromosome 16. Am J Hum Genet. 1990 May;46(5):925–933. [PMC free article] [PubMed] [Google Scholar]
  9. Gibbs R. A., Nguyen P. N., Caskey C. T. Detection of single DNA base differences by competitive oligonucleotide priming. Nucleic Acids Res. 1989 Apr 11;17(7):2437–2448. doi: 10.1093/nar/17.7.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grimm T., Müller B., Dreier M., Kind E., Bettecken T., Meng G., Müller C. R. Hot spot of recombination within DXS164 in the Duchenne muscular dystrophy gene. Am J Hum Genet. 1989 Sep;45(3):368–372. [PMC free article] [PubMed] [Google Scholar]
  11. Hogewind B. L., Veltkamp J. J., Koch C. W., de Graeff J. Genetic counselling for adult polycystic kidney disease. Ultrasound a useful tool in pre-symptomatic diagnosis? Clin Genet. 1980 Sep;18(3):168–172. doi: 10.1111/j.1399-0004.1980.tb00865.x. [DOI] [PubMed] [Google Scholar]
  12. Jarman A. P., Higgs D. R. A new hypervariable marker for the human alpha-globin gene cluster. Am J Hum Genet. 1988 Sep;43(3):249–256. [PMC free article] [PubMed] [Google Scholar]
  13. Jarman A. P., Nicholls R. D., Weatherall D. J., Clegg J. B., Higgs D. R. Molecular characterisation of a hypervariable region downstream of the human alpha-globin gene cluster. EMBO J. 1986 Aug;5(8):1857–1863. doi: 10.1002/j.1460-2075.1986.tb04437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kidd K. K., Bowcock A. M., Schmidtke J., Track R. K., Ricciuti F., Hutchings G., Bale A., Pearson P., Willard H. F., Gelernter J. Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms. Cytogenet Cell Genet. 1989;51(1-4):622–947. doi: 10.1159/000132810. [DOI] [PubMed] [Google Scholar]
  15. Kimberling W. J., Fain P. R., Kenyon J. B., Goldgar D., Sujansky E., Gabow P. A. Linkage heterogeneity of autosomal dominant polycystic kidney disease. N Engl J Med. 1988 Oct 6;319(14):913–918. doi: 10.1056/NEJM198810063191405. [DOI] [PubMed] [Google Scholar]
  16. Myers R. M., Maniatis T., Lerman L. S. Detection and localization of single base changes by denaturing gradient gel electrophoresis. Methods Enzymol. 1987;155:501–527. doi: 10.1016/0076-6879(87)55033-9. [DOI] [PubMed] [Google Scholar]
  17. Nakamura Y., Martin C., Krapcho K., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pCMM65) on chromosome 16 [D16S84]. Nucleic Acids Res. 1988 Apr 11;16(7):3122–3122. doi: 10.1093/nar/16.7.3122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Newton C. R., Graham A., Heptinstall L. E., Powell S. J., Summers C., Kalsheker N., Smith J. C., Markham A. F. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res. 1989 Apr 11;17(7):2503–2516. doi: 10.1093/nar/17.7.2503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  20. Reeders S. T., Breuning M. H., Corney G., Jeremiah S. J., Meera Khan P., Davies K. E., Hopkinson D. A., Pearson P. L., Weatherall D. J. Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16. Br Med J (Clin Res Ed) 1986 Mar 29;292(6524):851–853. doi: 10.1136/bmj.292.6524.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Reeders S. T., Breuning M. H., Davies K. E., Nicholls R. D., Jarman A. P., Higgs D. R., Pearson P. L., Weatherall D. J. A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature. 1985 Oct 10;317(6037):542–544. doi: 10.1038/317542a0. [DOI] [PubMed] [Google Scholar]
  22. Reeders S. T., Breuning M. H., Ryynanen M. A., Wright A. F., Davies K. E., King A. W., Watson M. L., Weatherall D. J. A study of genetic linkage heterogeneity in adult polycystic kidney disease. Hum Genet. 1987 Aug;76(4):348–351. doi: 10.1007/BF00272443. [DOI] [PubMed] [Google Scholar]
  23. Reeders S. T., Hildebrand C. E. Report of the committee on the genetic constitution of chromosome 16. Cytogenet Cell Genet. 1989;51(1-4):299–318. doi: 10.1159/000132796. [DOI] [PubMed] [Google Scholar]
  24. Romeo G., Devoto M., Costa G., Roncuzzi L., Catizone L., Zucchelli P., Germino G. G., Keith T., Weatherall D. J., Reeders S. T. A second genetic locus for autosomal dominant polycystic kidney disease. Lancet. 1988 Jul 2;2(8601):8–11. doi: 10.1016/s0140-6736(88)92943-1. [DOI] [PubMed] [Google Scholar]
  25. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  26. Saiki R. K., Walsh P. S., Levenson C. H., Erlich H. A. Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6230–6234. doi: 10.1073/pnas.86.16.6230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saris J. J., Breuning M. H., Dauwerse H. G., Snijdewint F. G., Top B., Fodde R., van Ommen G. J. Rapid detection of polymorphism near gene for adult polycystic kidney disease. Lancet. 1990 May 5;335(8697):1102–1103. doi: 10.1016/0140-6736(90)92680-g. [DOI] [PubMed] [Google Scholar]
  28. Smeets H. J., Brunner H. G., Ropers H. H., Wieringa B. Use of variable simple sequence motifs as genetic markers: application to study of myotonic dystrophy. Hum Genet. 1989 Oct;83(3):245–251. doi: 10.1007/BF00285165. [DOI] [PubMed] [Google Scholar]
  29. Tautz D. Hypervariability of simple sequences as a general source for polymorphic DNA markers. Nucleic Acids Res. 1989 Aug 25;17(16):6463–6471. doi: 10.1093/nar/17.16.6463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zerres K., Völpel M. C., Weiss H. Cystic kidneys. Genetics, pathologic anatomy, clinical picture, and prenatal diagnosis. Hum Genet. 1984;68(2):104–135. doi: 10.1007/BF00279301. [DOI] [PubMed] [Google Scholar]

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