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. 1981 Oct 10;9(19):5037–5047. doi: 10.1093/nar/9.19.5037

Duplication/deletion polymorphism 5' - to the human beta globin gene.

R A Spritz
PMCID: PMC327497  PMID: 7312624

Abstract

DNA sequence analysis of the human beta globin locus has identified an array of simple tandem repeated sequences upstream from the beta globin structural gene. Comparison of several cloned human beta globin alleles demonstrated a high frequency of sequence heteromorphism at this site apparently due to duplication or deletion of single units of the repeat array. At least two such duplication/deletion events are necessary to account for the observed variation. No other sequence variation was observed, suggesting that duplication/deletion events within the tandem repeat array may be at least 13 to 14 times more frequent than nucleotide substitutions in the surrounding DNA.

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Selected References

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  1. Arnheim N. Characterization of mouse ribosomal gene fragments purified by molecular cloning. Gene. 1979 Oct;7(2):83–96. doi: 10.1016/0378-1119(79)90025-8. [DOI] [PubMed] [Google Scholar]
  2. Arnheim N., Krystal M., Schmickel R., Wilson G., Ryder O., Zimmer E. Molecular evidence for genetic exchanges among ribosomal genes on nonhomologous chromosomes in man and apes. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7323–7327. doi: 10.1073/pnas.77.12.7323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arnheim N., Kuehn M. The genetic behaviour of a cloned mouse ribosomal DNA segment mimics mouse ribosomal gene evolution. J Mol Biol. 1979 Nov 15;134(4):743–763. doi: 10.1016/0022-2836(79)90483-2. [DOI] [PubMed] [Google Scholar]
  4. Arnheim N., Southern E. M. Heterogeneity of the ribosomal genes in mice and men. Cell. 1977 Jun;11(2):363–370. doi: 10.1016/0092-8674(77)90053-8. [DOI] [PubMed] [Google Scholar]
  5. Bedbrook J. R., Jones J., O'Dell M., Thompson R. D., Flavell R. B. A molecular description of telometic heterochromatin in secale species. Cell. 1980 Feb;19(2):545–560. doi: 10.1016/0092-8674(80)90529-2. [DOI] [PubMed] [Google Scholar]
  6. Biro P. A., Carr-Brown A., Southern E. M., Walker P. M. Partial sequence analysis of mouse satellite DNA evidence for short range periodicities. J Mol Biol. 1975 May 5;94(1):71–86. doi: 10.1016/0022-2836(75)90405-2. [DOI] [PubMed] [Google Scholar]
  7. Bond H. E., Flamm W. G., Burr H. E., Bond S. B. Mouse satellite DNA. Further studies on its biological and physical characteristics and its intracellular localization. J Mol Biol. 1967 Jul 28;27(2):289–302. doi: 10.1016/0022-2836(67)90021-6. [DOI] [PubMed] [Google Scholar]
  8. Botchan M. R. Bovine satellite I DNA consists of repetitive units 1,400 base pairs in length. Nature. 1974 Sep 27;251(5473):288–292. doi: 10.1038/251288a0. [DOI] [PubMed] [Google Scholar]
  9. Botchan P., Reeder R. H., Dawid I. B. Restriction analysis of the nontranscribed spacers of Xenopus laevis ribosomal DNA. Cell. 1977 Jul;11(3):599–607. doi: 10.1016/0092-8674(77)90077-0. [DOI] [PubMed] [Google Scholar]
  10. Brownlee G. G., Cartwright E. M., Brown D. D. Sequence studies of the 5 S DNA of Xenopus laevis. J Mol Biol. 1974 Nov 15;89(4):703–718. doi: 10.1016/0022-2836(74)90046-1. [DOI] [PubMed] [Google Scholar]
  11. Carroll D., Brown D. D. Repeating units of Xenopus laevis oocyte-type 5S DNA are heterogeneous in length. Cell. 1976 Apr;7(4):467–475. doi: 10.1016/0092-8674(76)90198-7. [DOI] [PubMed] [Google Scholar]
  12. Chambers C. A., Schell M. P., Skinner D. M. The primary sequence of a crustacean satellite DNA containing a family of repeats. Cell. 1978 Jan;13(1):97–110. doi: 10.1016/0092-8674(78)90141-1. [DOI] [PubMed] [Google Scholar]
  13. Davis M. M., Kim S. K., Hood L. E. DNA sequences mediating class switching in alpha-immunoglobulins. Science. 1980 Sep 19;209(4463):1360–1365. doi: 10.1126/science.6774415. [DOI] [PubMed] [Google Scholar]
  14. Donehower L., Furlong C., Gillespie D., Kurnit D. DNA sequence of baboon highly repeated DNA: evidence for evolution by nonrandom unequal crossovers. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2129–2133. doi: 10.1073/pnas.77.4.2129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Donehower L., Gillespie D. Restriction site periodicities in highly repetitive DNA of primates. J Mol Biol. 1979 Nov 15;134(4):805–834. doi: 10.1016/0022-2836(79)90487-x. [DOI] [PubMed] [Google Scholar]
  16. Dunnick W., Rabbitts T. H., Milstein C. An immunoglobulin deletion mutant with implications for the heavy-chain switch and RNA splicing. Nature. 1980 Aug 14;286(5774):669–675. doi: 10.1038/286669a0. [DOI] [PubMed] [Google Scholar]
  17. Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
  18. Farabaugh P. J., Schmeissner U., Hofer M., Miller J. H. Genetic studies of the lac repressor. VII. On the molecular nature of spontaneous hotspots in the lacI gene of Escherichia coli. J Mol Biol. 1978 Dec 25;126(4):847–857. doi: 10.1016/0022-2836(78)90023-2. [DOI] [PubMed] [Google Scholar]
  19. Fedoroff N. V., Brown D. D. The nucleotide sequence of oocyte 5S DNA in Xenopus laevis. I. The AT-rich spacer. Cell. 1978 Apr;13(4):701–716. doi: 10.1016/0092-8674(78)90220-9. [DOI] [PubMed] [Google Scholar]
  20. Fritsch E. F., Lawn R. M., Maniatis T. Molecular cloning and characterization of the human beta-like globin gene cluster. Cell. 1980 Apr;19(4):959–972. doi: 10.1016/0092-8674(80)90087-2. [DOI] [PubMed] [Google Scholar]
  21. Fry K., Salser W. Nucleotide sequences of HS-alpha satellite DNA from kangaroo rat Dipodomys ordii and characterization of similar sequences in other rodents. Cell. 1977 Dec;12(4):1069–1084. doi: 10.1016/0092-8674(77)90170-2. [DOI] [PubMed] [Google Scholar]
  22. Gall J. G., Atherton D. D. Satellite DNA sequences in Drosophila virilis. J Mol Biol. 1974 Jan 5;85(4):633–664. doi: 10.1016/0022-2836(74)90321-0. [DOI] [PubMed] [Google Scholar]
  23. Goossens M., Dozy A. M., Embury S. H., Zachariades Z., Hadjiminas M. G., Stamatoyannopoulos G., Kan Y. W. Triplicated alpha-globin loci in humans. Proc Natl Acad Sci U S A. 1980 Jan;77(1):518–521. doi: 10.1073/pnas.77.1.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Higgs D. R., Old J. M., Pressley L., Clegg J. B., Weatherall D. J. A novel alpha-globin gene arrangement in man. Nature. 1980 Apr 17;284(5757):632–635. doi: 10.1038/284632a0. [DOI] [PubMed] [Google Scholar]
  25. KIMURA M., CROW J. F. THE NUMBER OF ALLELES THAT CAN BE MAINTAINED IN A FINITE POPULATION. Genetics. 1964 Apr;49:725–738. doi: 10.1093/genetics/49.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. KORNBERG A., BERTSCH L. L., JACKSON J. F., KHORANA H. G. ENZYMATIC SYNTHESIS OF DEOXYRIBONUCLEIC ACID, XVI. OLIGONUCLEOTIDES AS TEMPLATES AND THE MECHANISM OF THEIR REPLICATION. Proc Natl Acad Sci U S A. 1964 Feb;51:315–323. doi: 10.1073/pnas.51.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kan Y. W., Dozy A. M., Varmus H. E., Taylor J. M., Holland J. P., Lie-Injo L. E., Ganesan J., Todd D. Deletion of alpha-globin genes in haemoglobin-H disease demonstrates multiple alpha-globin structural loci. Nature. 1975 May 15;255(5505):255–256. doi: 10.1038/255255a0. [DOI] [PubMed] [Google Scholar]
  28. Kataoka T., Miyata T., Honjo T. Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes. Cell. 1981 Feb;23(2):357–368. doi: 10.1016/0092-8674(81)90131-8. [DOI] [PubMed] [Google Scholar]
  29. Kedes L. H. Histone genes and histone messengers. Annu Rev Biochem. 1979;48:837–870. doi: 10.1146/annurev.bi.48.070179.004201. [DOI] [PubMed] [Google Scholar]
  30. Kimura M., Ohta T. Distribution of allelic frequencies in a finite population under stepwise production of neutral alleles. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2761–2764. doi: 10.1073/pnas.72.7.2761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Korn L. J., Brown D. D. Nucleotide sequence of Xenopus borealis oocyte 5S DNA: comparison of sequences that flank several related eucaryotic genes. Cell. 1978 Dec;15(4):1145–1156. doi: 10.1016/0092-8674(78)90042-9. [DOI] [PubMed] [Google Scholar]
  32. Kurnit D. M. Satellite DNA and heterochromatin variants: the case for unequal mitotic crossing over. Hum Genet. 1979 Mar 12;47(2):169–186. doi: 10.1007/BF00273199. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Lawn R. M., Fritsch E. F., Parker R. C., Blake G., Maniatis T. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA. Cell. 1978 Dec;15(4):1157–1174. doi: 10.1016/0092-8674(78)90043-0. [DOI] [PubMed] [Google Scholar]
  35. Maio J. J., Brown F. L., Musich P. R. Subunit structure of chromatin and the organization of eukaryotic highly repetitive DNA: recurrent periodicities and models for the evolutionary origins of repetitive DNA. J Mol Biol. 1977 Dec 15;117(3):637–655. doi: 10.1016/0022-2836(77)90062-6. [DOI] [PubMed] [Google Scholar]
  36. Manuelidis L. Complex and simple sequences in human repeated DNAs. Chromosoma. 1978 Mar 22;66(1):1–21. doi: 10.1007/BF00285812. [DOI] [PubMed] [Google Scholar]
  37. Manuelidis L., Wu J. C. Homology between human and simian repeated DNA. Nature. 1978 Nov 2;276(5683):92–94. doi: 10.1038/276092a0. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Moss B., Winters E., Cooper N. Instability and reiteration of DNA sequences within the vaccinia virus genome. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1614–1618. doi: 10.1073/pnas.78.3.1614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Musich P. R., Maio J. J., Brown F. L. Subunit structure of chromatin and the organization of eukaryotic highly repetitive DNA: indications of a phase relation between restriction sites and chromatin subunits in African green monkey and calf nuclei. J Mol Biol. 1977 Dec 15;117(3):657–677. doi: 10.1016/0022-2836(77)90063-8. [DOI] [PubMed] [Google Scholar]
  41. Nishioka Y., Leder P. Organization and complete sequence of identical embryonic and plasmacytoma kappa V-region genes. J Biol Chem. 1980 Apr 25;255(8):3691–3694. [PubMed] [Google Scholar]
  42. Nishioka Y., Leder P. The complete sequence of a chromosomal mouse alpha--globin gene reveals elements conserved throughout vertebrate evolution. Cell. 1979 Nov;18(3):875–882. doi: 10.1016/0092-8674(79)90139-9. [DOI] [PubMed] [Google Scholar]
  43. Overton G. C., Weinberg E. S. Length and sequence heterogeneity of the histone gene repeat unit of the sea urchin, S. purpuratus. Cell. 1978 Jun;14(2):247–257. doi: 10.1016/0092-8674(78)90111-3. [DOI] [PubMed] [Google Scholar]
  44. Perelson A. S., Bell G. I. Mathematical models for the evolution of multigene families by unequal crossing over. Nature. 1977 Jan 27;265(5592):304–310. doi: 10.1038/265304a0. [DOI] [PubMed] [Google Scholar]
  45. Reeder R. H., Brown D. D., Wellauer P. K., Dawid I. B. Patterns of ribosomal DNA spacer lengths are inherited. J Mol Biol. 1976 Aug 25;105(4):507–516. doi: 10.1016/0022-2836(76)90231-x. [DOI] [PubMed] [Google Scholar]
  46. Rosenberg H., Singer M., Rosenberg M. Highly reiterated sequences of SIMIANSIMIANSIMIANSIMIANSIMIAN. Science. 1978 Apr 28;200(4340):394–402. doi: 10.1126/science.205944. [DOI] [PubMed] [Google Scholar]
  47. Russell R. L., Abelson J. N., Landy A., Gefter M. L., Brenner S., Smith J. D. Duplicate genes for tyrosine transfer RNA in Escherichia coli. J Mol Biol. 1970 Jan 14;47(1):1–13. doi: 10.1016/0022-2836(70)90397-9. [DOI] [PubMed] [Google Scholar]
  48. Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. doi: 10.1038/286676a0. [DOI] [PubMed] [Google Scholar]
  49. Salser W., Bowen S., Browne D., el-Adli F., Fedoroff N., Fry K., Heindell H., Paddock G., Poon R., Wallace B. Investigation of the organization of mammalian chromosomes at the DNA sequence level. Fed Proc. 1976 Jan;35(1):23–35. [PubMed] [Google Scholar]
  50. Schaffner W., Kunz G., Daetwyler H., Telford J., Smith H. O., Birnstiel M. L. Genes and spacers of cloned sea urchin histone DNA analyzed by sequencing. Cell. 1978 Jul;14(3):655–671. doi: 10.1016/0092-8674(78)90249-0. [DOI] [PubMed] [Google Scholar]
  51. Singer D., Donehower L. Highly repeated DNA of the baboon: organization of sequences homologous to highly repeated DNA of the African green monkey. J Mol Biol. 1979 Nov 15;134(4):835–842. doi: 10.1016/0022-2836(79)90488-1. [DOI] [PubMed] [Google Scholar]
  52. Skinner D. M., Beattie W. G., Blattner F. R., Stark B. P., Dahlberg J. E. The repeat sequence of a hermit crab satellite deoxyribonucleic acid is (-T-A-G-G-)n-(-A-T-C-C-)n. Biochemistry. 1974 Sep 10;13(19):3930–3937. doi: 10.1021/bi00716a018. [DOI] [PubMed] [Google Scholar]
  53. Slightom J. L., Blechl A. E., Smithies O. Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell. 1980 Oct;21(3):627–638. doi: 10.1016/0092-8674(80)90426-2. [DOI] [PubMed] [Google Scholar]
  54. 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]
  55. Spritz R. A., Jagadeeswaran P., Choudary P. V., Biro P. A., Elder J. T., deRiel J. K., Manley J. L., Gefter M. L., Forget B. G., Weissman S. M. Base substitution in an intervening sequence of a beta+-thalassemic human globin gene. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2455–2459. doi: 10.1073/pnas.78.4.2455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Streisinger G., Okada Y., Emrich J., Newton J., Tsugita A., Terzaghi E., Inouye M. Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday. Cold Spring Harb Symp Quant Biol. 1966;31:77–84. doi: 10.1101/sqb.1966.031.01.014. [DOI] [PubMed] [Google Scholar]
  57. Sures I., Lowry J., Kedes L. H. The DNA sequence of sea urchin (S. purpuratus) H2A, H2B and H3 histone coding and spacer regions. Cell. 1978 Nov;15(3):1033–1044. doi: 10.1016/0092-8674(78)90287-8. [DOI] [PubMed] [Google Scholar]
  58. Wellauer P. K., Dawid I. B., Brown D. D., Reeder R. H. The molecular basis for length heterogeneity in ribosomal DNA from Xenopus laevis. J Mol Biol. 1976 Aug 25;105(4):461–486. doi: 10.1016/0022-2836(76)90229-1. [DOI] [PubMed] [Google Scholar]
  59. Wellauer P. K., Dawid I. B. Ribosomal DNA in Drosophila melanogaster. II. Heteroduplex mapping of cloned and uncloned rDNA. J Mol Biol. 1978 Dec 25;126(4):769–782. doi: 10.1016/0022-2836(78)90019-0. [DOI] [PubMed] [Google Scholar]
  60. Wellauer P. K., Dawid I. B. The structural organization of ribosomal DNA in Drosophila melanogaster. Cell. 1977 Feb;10(2):193–212. doi: 10.1016/0092-8674(77)90214-8. [DOI] [PubMed] [Google Scholar]
  61. Wellauer P. K., Reeder R. H., Dawid I. B., Brown D. D. Arrangement of length heterogeneity in repeating units of amplified and chromosomal ribosomal DNA from Xenopus laevis. J Mol Biol. 1976 Aug 25;105(4):487–505. doi: 10.1016/0022-2836(76)90230-8. [DOI] [PubMed] [Google Scholar]

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