Abstract
We have characterised an unusual, highly polymorphic region of DNA located 8-kb downstream of the human alpha-globin gene complex. This hypervariable region (alpha-globin 3' HVR) is composed of an array of 17-bp tandem repeats, the number of which differs considerably (70-450) from one allele to another. The sequence of the 17-bp repeats is highly conserved within and between alleles. Furthermore, this sequence identifies a core oligonucleotide [5'-GNGGGG(N)ACAG-3'] that is common to three previously characterised hypervariable regions. At reduced stringency, a probe to the 3' HVR detects a new family of multiallelic loci that will be of value in the study of human genetics.
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- Bell G. I., Selby M. J., Rutter W. J. The highly polymorphic region near the human insulin gene is composed of simple tandemly repeating sequences. Nature. 1982 Jan 7;295(5844):31–35. doi: 10.1038/295031a0. [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]
- Capon D. J., Chen E. Y., Levinson A. D., Seeburg P. H., Goeddel D. V. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature. 1983 Mar 3;302(5903):33–37. doi: 10.1038/302033a0. [DOI] [PubMed] [Google Scholar]
- Casey T. A., Ruyechan W. T., Flora M. N., Reinhold W., Straus S. E., Hay J. Fine mapping and sequencing of a variable segment in the inverted repeat region of varicella-zoster virus DNA. J Virol. 1985 May;54(2):639–642. doi: 10.1128/jvi.54.2.639-642.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gill P., Jeffreys A. J., Werrett D. J. Forensic application of DNA 'fingerprints'. Nature. 1985 Dec 12;318(6046):577–579. doi: 10.1038/318577a0. [DOI] [PubMed] [Google Scholar]
- Goodbourn S. E., Higgs D. R., Clegg J. B., Weatherall D. J. Allelic variation and linkage properties of a highly polymorphic restriction fragment in humans. Mol Biol Med. 1984 Jun;2(3):223–238. [PubMed] [Google Scholar]
- 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]
- Higgs D. R., Goodbourn S. E., Wainscoat J. S., Clegg J. B., Weatherall D. J. Highly variable regions of DNA flank the human alpha globin genes. Nucleic Acids Res. 1981 Sep 11;9(17):4213–4224. doi: 10.1093/nar/9.17.4213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeffreys A. J., Brookfield J. F., Semeonoff R. Positive identification of an immigration test-case using human DNA fingerprints. 1985 Oct 31-Nov 6Nature. 317(6040):818–819. doi: 10.1038/317818a0. [DOI] [PubMed] [Google Scholar]
- Jeffreys A. J., Wilson V., Thein S. L. Hypervariable 'minisatellite' regions in human DNA. Nature. 1985 Mar 7;314(6006):67–73. doi: 10.1038/314067a0. [DOI] [PubMed] [Google Scholar]
- Jeffreys A. J., Wilson V., Thein S. L. Individual-specific 'fingerprints' of human DNA. Nature. 1985 Jul 4;316(6023):76–79. doi: 10.1038/316076a0. [DOI] [PubMed] [Google Scholar]
- Lauer J., Shen C. K., Maniatis T. The chromosomal arrangement of human alpha-like globin genes: sequence homology and alpha-globin gene deletions. Cell. 1980 May;20(1):119–130. doi: 10.1016/0092-8674(80)90240-8. [DOI] [PubMed] [Google Scholar]
- Liebermann D., Hoffman-Liebermann B., Weinthal J., Childs G., Maxson R., Mauron A., Cohen S. N., Kedes L. An unusual transposon with long terminal inverted repeats in the sea urchin Strongylocentrotus purpuratus. Nature. 1983 Nov 24;306(5941):342–347. doi: 10.1038/306342a0. [DOI] [PubMed] [Google Scholar]
- Lupton S., Levine A. J. Mapping genetic elements of Epstein-Barr virus that facilitate extrachromosomal persistence of Epstein-Barr virus-derived plasmids in human cells. Mol Cell Biol. 1985 Oct;5(10):2533–2542. doi: 10.1128/mcb.5.10.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nicholls R. D., Hill A. V., Clegg J. B., Higgs D. R. Direct cloning of specific genomic DNA sequences in plasmid libraries following fragment enrichment. Nucleic Acids Res. 1985 Nov 11;13(21):7569–7578. doi: 10.1093/nar/13.21.7569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Reeder R. H. Enhancers and ribosomal gene spacers. Cell. 1984 Sep;38(2):349–351. doi: 10.1016/0092-8674(84)90489-6. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Rosenthal N., Kress M., Gruss P., Khoury G. BK viral enhancer element and a human cellular homolog. Science. 1983 Nov 18;222(4625):749–755. doi: 10.1126/science.6314501. [DOI] [PubMed] [Google Scholar]
- Scott J. R. Regulation of plasmid replication. Microbiol Rev. 1984 Mar;48(1):1–23. doi: 10.1016/b978-0-12-048850-6.50006-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith G. P. Evolution of repeated DNA sequences by unequal crossover. Science. 1976 Feb 13;191(4227):528–535. doi: 10.1126/science.1251186. [DOI] [PubMed] [Google Scholar]
- 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]
- Southern E. M. Base sequence and evolution of guinea-pig alpha-satellite DNA. Nature. 1970 Aug 22;227(5260):794–798. doi: 10.1038/227794a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Southern E. M. Long range periodicities in mouse satellite DNA. J Mol Biol. 1975 May 5;94(1):51–69. doi: 10.1016/0022-2836(75)90404-0. [DOI] [PubMed] [Google Scholar]
- Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
- Truett M. A., Jones R. S., Potter S. S. Unusual structure of the FB family of transposable elements in Drosophila. Cell. 1981 Jun;24(3):753–763. doi: 10.1016/0092-8674(81)90101-x. [DOI] [PubMed] [Google Scholar]
- Ullrich A., Dull T. J., Gray A., Philips J. A., 3rd, Peter S. Variation in the sequence and modification state of the human insulin gene flanking regions. Nucleic Acids Res. 1982 Apr 10;10(7):2225–2240. doi: 10.1093/nar/10.7.2225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winichagoon P., Higgs D. R., Goodbourn S. E., Clegg J. B., Weatherall D. J., Wasi P. The molecular basis of alpha-thalassaemia in Thailand. EMBO J. 1984 Aug;3(8):1813–1818. doi: 10.1002/j.1460-2075.1984.tb02051.x. [DOI] [PMC free article] [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]
- Wyman A. R., Wolfe L. B., Botstein D. Propagation of some human DNA sequences in bacteriophage lambda vectors requires mutant Escherichia coli hosts. Proc Natl Acad Sci U S A. 1985 May;82(9):2880–2884. doi: 10.1073/pnas.82.9.2880. [DOI] [PMC free article] [PubMed] [Google Scholar]