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. 1985 Jul;37(4):635–649.

A systematic approach for detecting high-frequency restriction fragment length polymorphisms using large genomic probes.

J Feder 1, L Yen 1, E Wijsman 1, L Wang 1, L Wilkins 1, J Schroder 1, N Spurr 1, H Cann 1, M Blumenberg 1, L L Cavalli-Sforza 1
PMCID: PMC1684621  PMID: 9556655

Abstract

Thirteen phage clones containing low-copy sequences were isolated from a human DNA library and tested for their ability to detect restriction fragment length polymorphisms (RFLPs). Reported are the RFLPs revealed with each clone, all found in frequencies useful for linkage studies. Cytological data are available for five of the 13 clones, with regional assignments made for three of the markers by in situ hybridization. It is concluded that phage clones containing large unique DNA inserts detect multiple RFLPs with high efficiency. An analysis of the relative efficiency of 20 restriction enzymes for detecting single nucleotide changes is discussed by comparing the observed data to those expected on the basis of recognition and potential site frequencies, as computed from the dinucleotide distribution. Finally, in an effort to facilitate linkage studies using polymorphic DNA sequences, experiments were made with pools of probes from various sources.

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Selected References

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

  1. Aldridge J., Kunkel L., Bruns G., Tantravahi U., Lalande M., Brewster T., Moreau E., Wilson M., Bromley W., Roderick T. A strategy to reveal high-frequency RFLPs along the human X chromosome. Am J Hum Genet. 1984 May;36(3):546–564. [PMC free article] [PubMed] [Google Scholar]
  2. Antonarakis S. E., Phillips J. A., 3rd, Mallonee R. L., Kazazian H. H., Jr, Fearon E. R., Waber P. G., Kronenberg H. M., Ullrich A., Meyers D. A. Beta-globin locus is linked to the parathyroid hormone (PTH) locus and lies between the insulin and PTH loci in man. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6615–6619. doi: 10.1073/pnas.80.21.6615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barker D., Schafer M., White R. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell. 1984 Jan;36(1):131–138. doi: 10.1016/0092-8674(84)90081-3. [DOI] [PubMed] [Google Scholar]
  4. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Cavenee W. K., Dryja T. P., Phillips R. A., Benedict W. F., Godbout R., Gallie B. L., Murphree A. L., Strong L. C., White R. L. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. 1983 Oct 27-Nov 2Nature. 305(5937):779–784. doi: 10.1038/305779a0. [DOI] [PubMed] [Google Scholar]
  8. Cavenee W., Leach R., Mohandas T., Pearson P., White R. Isolation and regional localization of DNA segments revealing polymorphic loci from human chromosome 13. Am J Hum Genet. 1984 Jan;36(1):10–24. [PMC free article] [PubMed] [Google Scholar]
  9. Cooper D. N., Schmidtke J. DNA restriction fragment length polymorphisms and heterozygosity in the human genome. Hum Genet. 1984;66(1):1–16. doi: 10.1007/BF00275182. [DOI] [PubMed] [Google Scholar]
  10. Denhardt D. T. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. doi: 10.1016/0006-291x(66)90447-5. [DOI] [PubMed] [Google Scholar]
  11. Drayna D., Davies K., Hartley D., Mandel J. L., Camerino G., Williamson R., White R. Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms. Proc Natl Acad Sci U S A. 1984 May;81(9):2836–2839. doi: 10.1073/pnas.81.9.2836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dryja T. P., Rapaport J. M., Weichselbaum R., Bruns G. A. Chromosome 13 restriction fragment length polymorphisms. Hum Genet. 1984;65(4):320–324. doi: 10.1007/BF00291555. [DOI] [PubMed] [Google Scholar]
  13. Fearon E. R., Vogelstein B., Feinberg A. P. Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours. Nature. 1984 May 10;309(5964):176–178. doi: 10.1038/309176a0. [DOI] [PubMed] [Google Scholar]
  14. Francke U., Oliver N. Quantitative analysis of high-resolution trypsin-giemsa bands on human prometaphase chromosomes. Hum Genet. 1978 Dec 18;45(2):137–165. doi: 10.1007/BF00286957. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Harper M. E., Saunders G. F. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981;83(3):431–439. doi: 10.1007/BF00327364. [DOI] [PubMed] [Google Scholar]
  17. Helentjaris T., Gesteland R. Evaluation of random cDNA clones as probes for human restriction fragment polymorphisms. J Mol Appl Genet. 1983;2(3):237–247. [PubMed] [Google Scholar]
  18. Kao F. T., Hartz J. A., Law M. L., Davidson J. N. Isolation and chromosomal localization of unique DNA sequences from a human genomic library. Proc Natl Acad Sci U S A. 1982 Feb;79(3):865–869. doi: 10.1073/pnas.79.3.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koufos A., Hansen M. F., Lampkin B. C., Workman M. L., Copeland N. G., Jenkins N. A., Cavenee W. K. Loss of alleles at loci on human chromosome 11 during genesis of Wilms' tumour. Nature. 1984 May 10;309(5964):170–172. doi: 10.1038/309170a0. [DOI] [PubMed] [Google Scholar]
  20. Orkin S. H., Goldman D. S., Sallan S. E. Development of homozygosity for chromosome 11p markers in Wilms' tumour. Nature. 1984 May 10;309(5964):172–174. doi: 10.1038/309172a0. [DOI] [PubMed] [Google Scholar]
  21. Reeve A. E., Housiaux P. J., Gardner R. J., Chewings W. E., Grindley R. M., Millow L. J. Loss of a Harvey ras allele in sporadic Wilms' tumour. Nature. 1984 May 10;309(5964):174–176. doi: 10.1038/309174a0. [DOI] [PubMed] [Google Scholar]
  22. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  23. Skolnick M. H., White R. Strategies for detecting and characterizing restriction fragment length polymorphisms (RFLP's). Cytogenet Cell Genet. 1982;32(1-4):58–67. doi: 10.1159/000131687. [DOI] [PubMed] [Google Scholar]
  24. Skolnick M. H., Willard H. F., Menlove L. A. Report of the Committee on Human Gene Mapping by Recombinant DNA Techniques. Cytogenet Cell Genet. 1984;37(1-4):210–273. doi: 10.1159/000132011. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Wijsman E. M. Optimizing selection of restriction enzymes in the search for DNA variants. Nucleic Acids Res. 1984 Dec 11;12(23):9209–9226. doi: 10.1093/nar/12.23.9209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wyman A. R., White R. A highly polymorphic locus in human DNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6754–6758. doi: 10.1073/pnas.77.11.6754. [DOI] [PMC free article] [PubMed] [Google Scholar]

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