Skip to main content
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1984 Nov;36(6):1159–1171.

A locus on chromosome 11p with multiple restriction site polymorphisms.

D Barker, T Holm, R White
PMCID: PMC1684654  PMID: 6097109

Abstract

We have discovered and characterized a new polymorphic locus on chromosome 11p, D11S12, defined by an arbitrary genomic DNA segment cloned in the plasmid pADJ762. Four different polymorphic restriction sites with minor allele frequencies greater than 5% are revealed by Southern hybridization of this probe and its derivatives to digests of human DNAs. These include two MspI sites, a TaqI site, and a BclI site. The frequencies of the common haplotypes at this locus have been determined in a Utah population. Significant linkage disequilibrium has been demonstrated to exist between some pairs of polymorphic sites. A molecular map of this region has been determined, and the polymorphic sites have been localized. Comparison of physical separation with degree of linkage disequilibrium reveals an interesting case where an MspI site and a TaqI site that are separated by 6.8 kilobases (kb) show a greater degree of disequilibrium with each other than they do with two polymorphic sites located between them. One of the two interior sites is a BclI site that is approximately 0.2 kb away from the TaqI site but shows the same degree of disequilibrium with the TaqI site as with the MspI site 6.7 kb away. Although there is significant linkage disequilibrium at this locus, there are four major haplotypes with frequencies of 5% or greater, and the polymorphic information content (PIC) of this locus is .64.

Full text

PDF
1159

Images in this article

Selected References

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

  1. Adams J. W., Kaufman R. E., Kretschmer P. J., Harrison M., Nienhuis A. W. A family of long reiterated DNA sequences, one copy of which is next to the human beta globin gene. Nucleic Acids Res. 1980 Dec 20;8(24):6113–6128. doi: 10.1093/nar/8.24.6113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alwine J. C., Kemp D. J., Parker B. A., Reiser J., Renart J., Stark G. R., Wahl G. M. Detection of specific RNAs or specific fragments of DNA by fractionation in gels and transfer to diazobenzyloxymethyl paper. Methods Enzymol. 1979;68:220–242. doi: 10.1016/0076-6879(79)68017-5. [DOI] [PubMed] [Google Scholar]
  3. Antonarakis S. E., Boehm C. D., Giardina P. J., Kazazian H. H., Jr Nonrandom association of polymorphic restriction sites in the beta-globin gene cluster. Proc Natl Acad Sci U S A. 1982 Jan;79(1):137–141. doi: 10.1073/pnas.79.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Antonarakis S. E., Orkin S. H., Kazazian H. H., Jr, Goff S. C., Boehm C. D., Waber P. G., Sexton J. P., Ostrer H., Fairbanks V. F., Chakravarti A. Evidence for multiple origins of the beta E-globin gene in Southeast Asia. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6608–6611. doi: 10.1073/pnas.79.21.6608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barker D., Hoff M., Oliphant A., White R. A second type II restriction endonuclease from Thermus aquaticus with an unusual sequence specificity. Nucleic Acids Res. 1984 Jul 25;12(14):5567–5581. doi: 10.1093/nar/12.14.5567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Bolivar F. Construction and characterization of new cloning vehicles. III. Derivatives of plasmid pBR322 carrying unique Eco RI sites for selection of Eco RI generated recombinant DNA molecules. Gene. 1978 Oct;4(2):121–136. doi: 10.1016/0378-1119(78)90025-2. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Goldfarb M., Shimizu K., Perucho M., Wigler M. Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells. Nature. 1982 Apr 1;296(5856):404–409. doi: 10.1038/296404a0. [DOI] [PubMed] [Google Scholar]
  11. Goodbourn S. E., Higgs D. R., Clegg J. B., Weatherall D. J. Molecular basis of length polymorphism in the human zeta-globin gene complex. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5022–5026. doi: 10.1073/pnas.80.16.5022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lange K., Boehnke M. Some combinatorial problems of DNA restriction fragment length polymorphisms. Am J Hum Genet. 1983 Mar;35(2):177–192. [PMC free article] [PubMed] [Google Scholar]
  13. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  14. Migone N., Feder J., Cann H., van West B., Hwang J., Takahashi N., Honjo T., Piazza A., Cavalli-Sforza L. L. Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man. Proc Natl Acad Sci U S A. 1983 Jan;80(2):467–471. doi: 10.1073/pnas.80.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Naylor S. L., Sakaguchi A. Y., Barker D., White R., Shows T. B. DNA polymorphic loci mapped to human chromosomes 3, 5, 9, 11, 17, 18, and 22. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2447–2451. doi: 10.1073/pnas.81.8.2447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Orkin S. H., Kazazian H. H., Jr, Antonarakis S. E., Goff S. C., Boehm C. D., Sexton J. P., Waber P. G., Giardina P. J. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature. 1982 Apr 15;296(5858):627–631. doi: 10.1038/296627a0. [DOI] [PubMed] [Google Scholar]
  17. Proudfoot N. J., Gil A., Maniatis T. The structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene. Cell. 1982 Dec;31(3 Pt 2):553–563. doi: 10.1016/0092-8674(82)90311-7. [DOI] [PubMed] [Google Scholar]
  18. Shafit-Zagardo B., Brown F. L., Maio J. J., Adams J. W. KpnI families of long, interspersed repetitive DNAs associated with the human beta-globin gene cluster. Gene. 1982 Dec;20(3):397–407. doi: 10.1016/0378-1119(82)90208-6. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Smith H. O., Birnstiel M. L. A simple method for DNA restriction site mapping. Nucleic Acids Res. 1976 Sep;3(9):2387–2398. doi: 10.1093/nar/3.9.2387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Taparowsky E., Suard Y., Fasano O., Shimizu K., Goldfarb M., Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982 Dec 23;300(5894):762–765. doi: 10.1038/300762a0. [DOI] [PubMed] [Google Scholar]
  23. Taub R. A., Hollis G. F., Hieter P. A., Korsmeyer S., Waldmann T. A., Leder P. Variable amplification of immunoglobulin lambda light-chain genes in human populations. Nature. 1983 Jul 14;304(5922):172–174. doi: 10.1038/304172a0. [DOI] [PubMed] [Google Scholar]
  24. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. de Wet J. R., Daniels D. L., Schroeder J. L., Williams B. G., Denniston-Thompson K., Moore D. D., Blattner F. R. Restriction maps for twenty-one Charon vector phages. J Virol. 1980 Jan;33(1):401–410. doi: 10.1128/jvi.33.1.401-410.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES