Abstract
We have identified and characterized 40 DNA probes detecting restriction fragment length polymorphism (RFLP) on human chromosome 4. Single copy human clones were isolated from a bacteriophage library enriched for chromosome 4 sequences. Each clone was hybridized to somatic cell hybrid DNAs for verification of its species and chromosomal origin and for regional localization. Sequences specific for chromosome 4 were tested for their ability to detect RFLPs in human DNA and their potential utility as genetic markers was assessed. Approximately 263,000 base pairs or 0.13% of the chromosome was screened for sequence variation. The estimate of heterozygosity calculated from this large body of data, H = 0.0021, indicates that the degree of sequence variation on chromosome 4 is comparable to other autosomes. The characterization of these 40 markers has tripled the number of polymorphic loci available for linkage studies on chromosome 4, making it feasible to begin construction of a detailed linkage map that will span the entire chromosome.
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- 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]
- Barker D., McCoy M., Weinberg R., Goldfarb M., Wigler M., Burt R., Gardner E., White R. A test of the role of two oncogenes in inherited predisposition to colon cancer. Mol Biol Med. 1983 Sep;1(2):199–206. [PubMed] [Google Scholar]
- 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]
- 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]
- Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Carle G. F., Frank M., Olson M. V. Electrophoretic separations of large DNA molecules by periodic inversion of the electric field. Science. 1986 Apr 4;232(4746):65–68. doi: 10.1126/science.3952500. [DOI] [PubMed] [Google Scholar]
- 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]
- Cooper D. N., Smith B. A., Cooke H. J., Niemann S., Schmidtke J. An estimate of unique DNA sequence heterozygosity in the human genome. Hum Genet. 1985;69(3):201–205. doi: 10.1007/BF00293024. [DOI] [PubMed] [Google Scholar]
- 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]
- Gilliam T. C., Scambler P., Robbins T., Ingle C., Williamson R., Davies K. E. The positions of three restriction fragment length polymorphisms on chromosome 4 relative to known genetic markers. Hum Genet. 1984;68(2):154–158. doi: 10.1007/BF00279306. [DOI] [PubMed] [Google Scholar]
- Gusella J. A., Gilliam T. C., MacDonald M. E., Cheng S. V., Tanzi R. E. Molecular genetics of human chromosome 4. J Med Genet. 1986 Jun;23(3):193–199. doi: 10.1136/jmg.23.3.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gusella J. F. DNA polymorphism and human disease. Annu Rev Biochem. 1986;55:831–854. doi: 10.1146/annurev.bi.55.070186.004151. [DOI] [PubMed] [Google Scholar]
- Gusella J. F., Keys C., VarsanyiBreiner A., Kao F. T., Jones C., Puck T. T., Housman D. Isolation and localization of DNA segments from specific human chromosomes. Proc Natl Acad Sci U S A. 1980 May;77(5):2829–2833. doi: 10.1073/pnas.77.5.2829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gusella J. F., Tanzi R. E., Anderson M. A., Hobbs W., Gibbons K., Raschtchian R., Gilliam T. C., Wallace M. R., Wexler N. S., Conneally P. M. DNA markers for nervous system diseases. Science. 1984 Sep 21;225(4668):1320–1326. doi: 10.1126/science.6089346. [DOI] [PubMed] [Google Scholar]
- Gusella J. F., Tanzi R. E., Bader P. I., Phelan M. C., Stevenson R., Hayden M. R., Hofman K. J., Faryniarz A. G., Gibbons K. Deletion of Huntington's disease-linked G8 (D4S10) locus in Wolf-Hirschhorn syndrome. Nature. 1985 Nov 7;318(6041):75–78. doi: 10.1038/318075a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Gusella J., Varsanyi-Breiner A., Kao F. T., Jones C., Puck T. T., Keys C., Orkin S., Housman D. Precise localization of human beta-globin gene complex on chromosome 11. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5239–5242. doi: 10.1073/pnas.76.10.5239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeffreys A. J. DNA sequence variants in the G gamma-, A gamma-, delta- and beta-globin genes of man. Cell. 1979 Sep;18(1):1–10. doi: 10.1016/0092-8674(79)90348-9. [DOI] [PubMed] [Google Scholar]
- Kidd K. K., Gusella J. Report of the Committee on the Genetic Constitution of Chromosomes 3 and 4. Cytogenet Cell Genet. 1985;40(1-4):107–127. doi: 10.1159/000132171. [DOI] [PubMed] [Google Scholar]
- Magenis R. E., Gusella J., Weliky K., Olson S., Haight G., Toth-Fejel S., Sheehy R. Huntington disease-linked restriction fragment length polymorphism localized within band p16.1 of chromosome 4 by in situ hybridization. Am J Hum Genet. 1986 Sep;39(3):383–391. [PMC free article] [PubMed] [Google Scholar]
- Murray J. C., Mills K. A., Demopulos C. M., Hornung S., Motulsky A. G. Linkage disequilibrium and evolutionary relationships of DNA variants (restriction enzyme fragment length polymorphisms) at the serum albumin locus. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3486–3490. doi: 10.1073/pnas.81.11.3486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Saxon P. J., Srivatsan E. S., Leipzig G. V., Sameshima J. H., Stanbridge E. J. Selective transfer of individual human chromosomes to recipient cells. Mol Cell Biol. 1985 Jan;5(1):140–146. doi: 10.1128/mcb.5.1.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsui L. C., Buchwald M., Barker D., Braman J. C., Knowlton R., Schumm J. W., Eiberg H., Mohr J., Kennedy D., Plavsic N. Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science. 1985 Nov 29;230(4729):1054–1057. doi: 10.1126/science.2997931. [DOI] [PubMed] [Google Scholar]
- Wainwright B. J., Scambler P. J., Schmidtke J., Watson E. A., Law H. Y., Farrall M., Cooke H. J., Eiberg H., Williamson R. Localization of cystic fibrosis locus to human chromosome 7cen-q22. 1985 Nov 28-Dec 4Nature. 318(6044):384–385. doi: 10.1038/318384a0. [DOI] [PubMed] [Google Scholar]
- Wasmuth J. J., Carlock L. R., Smith B., Immken L. L. A cell hybrid and recombinant DNA library that facilitate identification of polymorphic loci in the vicinity of the Huntington disease gene. Am J Hum Genet. 1986 Sep;39(3):397–403. [PMC free article] [PubMed] [Google Scholar]
- White R., Woodward S., Leppert M., O'Connell P., Hoff M., Herbst J., Lalouel J. M., Dean M., Vande Woude G. A closely linked genetic marker for cystic fibrosis. 1985 Nov 28-Dec 4Nature. 318(6044):382–384. doi: 10.1038/318382a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Zabel B. U., Naylor S. L., Sakaguchi A. Y., Gusella J. F. Mapping of the DNA locus D4S10 and the linked Huntington's disease gene to 4p16----p15. Cytogenet Cell Genet. 1986;42(4):187–190. doi: 10.1159/000132276. [DOI] [PubMed] [Google Scholar]