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. 1987 Sep;41(3):374–390.

Characterization of human centromeric regions of specific chromosomes by means of alphoid DNA sequences.

E W Jabs, M G Persico
PMCID: PMC1684186  PMID: 3631075

Abstract

The alphoid DNA family is composed of tandemly repeated sequences whose organization is chromosome specific. Under stringent conditions of hybridization, subsets of these sequences localize specifically to the centromeric region of a given chromosome. The alphoid clone, 308 (D6Z1), is a 3-kb BamHI DNA fragment that is repeated at the centromere of chromosome 6. Sequences homologous to 308 are organized as 2-kb BamHI repeats on X. We used 308 to screen a 2-kb BamHI genomic library and obtained the cloned homologue, XC, which hybridizes, in situ, to the centromere of X. These probes provide a means of analyzing the centromeric region on two different human chromosomes. The complete nucleotide sequence of 308 shows that it is composed of 20 variant 173-bp repeats. The organization of the 173-bp monomers is not a repetitious but a symmetric pattern, and an inversion is present. The chromosome specificity of 308 to chromosome 6 is determined by the entire 3-kb sequence and not by an amplified 173-bp monomer, because the divergence among the 173-bp units on chromosome 6 is as great as that between monomers on chromosomes 6 and X. Therefore, the organization of monomers is specific for a chromosome, and the monomers themselves are not specific. Analysis of the sequence data from these two alphoid sequences and other published sequences shows that some chromosomes have sequences that are more homologous than others. These subsets of alphoid sequences reflect the latters' chromosomal distribution and evolution. By using probes 308 and XC, we found that alphoid repeats from specific chromosomes are similar in that there is no evidence for their transcription in lymphoblasts and fibroblasts, and we demonstrated the possibility that all of these sequences are late replicating.

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Selected References

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

  1. Brutlag D. L. Molecular arrangement and evolution of heterochromatic DNA. Annu Rev Genet. 1980;14:121–144. doi: 10.1146/annurev.ge.14.120180.001005. [DOI] [PubMed] [Google Scholar]
  2. Camargo M., Cervenka J. Patterns of DNA replication of human chromosomes. II. Replication map and replication model. Am J Hum Genet. 1982 Sep;34(5):757–780. [PMC free article] [PubMed] [Google Scholar]
  3. Carbon J. Yeast centromeres: structure and function. Cell. 1984 Jun;37(2):351–353. doi: 10.1016/0092-8674(84)90363-5. [DOI] [PubMed] [Google Scholar]
  4. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  5. Clarke L., Amstutz H., Fishel B., Carbon J. Analysis of centromeric DNA in the fission yeast Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8253–8257. doi: 10.1073/pnas.83.21.8253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Comings D. E. Mechanisms of chromosome banding and implications for chromosome structure. Annu Rev Genet. 1978;12:25–46. doi: 10.1146/annurev.ge.12.120178.000325. [DOI] [PubMed] [Google Scholar]
  7. Devilee P., Slagboom P., Cornelisse C. J., Pearson P. L. Sequence heterogeneity within the human alphoid repetitive DNA family. Nucleic Acids Res. 1986 Mar 11;14(5):2059–2073. doi: 10.1093/nar/14.5.2059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dutrillaux B., Couturier J., Richer C. L., Viegas-Péquignot E. Sequence of DNA replication in 277 R- and Q-bands of human chromosomes using a BrdU treatment. Chromosoma. 1976 Oct 12;58(1):51–61. doi: 10.1007/BF00293440. [DOI] [PubMed] [Google Scholar]
  9. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Goldman M. A., Holmquist G. P., Gray M. C., Caston L. A., Nag A. Replication timing of genes and middle repetitive sequences. Science. 1984 May 18;224(4650):686–692. doi: 10.1126/science.6719109. [DOI] [PubMed] [Google Scholar]
  12. Hieter P., Pridmore D., Hegemann J. H., Thomas M., Davis R. W., Philippsen P. Functional selection and analysis of yeast centromeric DNA. Cell. 1985 Oct;42(3):913–921. doi: 10.1016/0092-8674(85)90287-9. [DOI] [PubMed] [Google Scholar]
  13. Holmquist G., Gray M., Porter T., Jordan J. Characterization of Giemsa dark- and light-band DNA. Cell. 1982 Nov;31(1):121–129. doi: 10.1016/0092-8674(82)90411-1. [DOI] [PubMed] [Google Scholar]
  14. Jabs E. W., Meyers D. A., Bias W. B. Linkage studies of polymorphic, repeated DNA sequences in centromeric regions of human chromosomes. Am J Hum Genet. 1986 Mar;38(3):297–308. [PMC free article] [PubMed] [Google Scholar]
  15. Jabs E. W., Wolf S. F., Migeon B. R. Characterization of reiterated human DNA with respect to mammalian X chromosome homology. Somat Cell Mol Genet. 1984 Jan;10(1):93–103. doi: 10.1007/BF01534476. [DOI] [PubMed] [Google Scholar]
  16. Jørgensen A. L., Bostock C. J., Bak A. L. Chromosome-specific subfamilies within human alphoid repetitive DNA. J Mol Biol. 1986 Jan 20;187(2):185–196. doi: 10.1016/0022-2836(86)90227-5. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. McDermid H. E., Duncan A. M., Higgins M. J., Hamerton J. L., Rector E., Brasch K. R., White B. N. Isolation and characterization of an alpha-satellite repeated sequence from human chromosome 22. Chromosoma. 1986;94(3):228–234. doi: 10.1007/BF00288497. [DOI] [PubMed] [Google Scholar]
  19. Meneveri R., Agresti A., Breviario D., Ginelli E. Replication pattern of human repeated DNA sequences. Biochim Biophys Acta. 1984 Oct 5;783(1):53–59. doi: 10.1016/0167-4781(84)90077-0. [DOI] [PubMed] [Google Scholar]
  20. Mitchell A. R., Gosden J. R., Miller D. A. A cloned sequence, p82H, of the alphoid repeated DNA family found at the centromeres of all human chromosomes. Chromosoma. 1985;92(5):369–377. doi: 10.1007/BF00327469. [DOI] [PubMed] [Google Scholar]
  21. Nakaseko Y., Adachi Y., Funahashi S., Niwa O., Yanagida M. Chromosome walking shows a highly homologous repetitive sequence present in all the centromere regions of fission yeast. EMBO J. 1986 May;5(5):1011–1021. doi: 10.1002/j.1460-2075.1986.tb04316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Queen C., Korn L. J. A comprehensive sequence analysis program for the IBM personal computer. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):581–599. doi: 10.1093/nar/12.1part2.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rao P. N. Mitotic synchrony in mammalian cells treated with nitrous oxide at high pressure. Science. 1968 May 17;160(3829):774–776. doi: 10.1126/science.160.3829.774. [DOI] [PubMed] [Google Scholar]
  24. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schmeckpeper B. J., Scott A. F., Smith K. D. Transcripts homologous to a long repeated DNA element in the human genome. J Biol Chem. 1984 Jan 25;259(2):1218–1225. [PubMed] [Google Scholar]
  26. Shmookler Reis R. J., Srivastava A., Beranek D. T., Goldstein S. Human alphoid family of tandemly repeated DNA. Sequence of cloned tetrameric fragments and analysis of familial divergence. J Mol Biol. 1985 Nov 5;186(1):31–41. doi: 10.1016/0022-2836(85)90254-2. [DOI] [PubMed] [Google Scholar]
  27. Singer M. F. Highly repeated sequences in mammalian genomes. Int Rev Cytol. 1982;76:67–112. doi: 10.1016/s0074-7696(08)61789-1. [DOI] [PubMed] [Google Scholar]
  28. Solomon M. J., Strauss F., Varshavsky A. A mammalian high mobility group protein recognizes any stretch of six A.T base pairs in duplex DNA. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1276–1280. doi: 10.1073/pnas.83.5.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Strauss F., Varshavsky A. A protein binds to a satellite DNA repeat at three specific sites that would be brought into mutual proximity by DNA folding in the nucleosome. Cell. 1984 Jul;37(3):889–901. doi: 10.1016/0092-8674(84)90424-0. [DOI] [PubMed] [Google Scholar]
  30. Waye J. S., Willard H. F. Chromosome-specific alpha satellite DNA: nucleotide sequence analysis of the 2.0 kilobasepair repeat from the human X chromosome. Nucleic Acids Res. 1985 Apr 25;13(8):2731–2743. doi: 10.1093/nar/13.8.2731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Willard H. F. Chromosome-specific organization of human alpha satellite DNA. Am J Hum Genet. 1985 May;37(3):524–532. [PMC free article] [PubMed] [Google Scholar]
  32. Willard H. F., Smith K. D., Sutherland J. Isolation and characterization of a major tandem repeat family from the human X chromosome. Nucleic Acids Res. 1983 Apr 11;11(7):2017–2033. doi: 10.1093/nar/11.7.2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wolfe J., Darling S. M., Erickson R. P., Craig I. W., Buckle V. J., Rigby P. W., Willard H. F., Goodfellow P. N. Isolation and characterization of an alphoid centromeric repeat family from the human Y chromosome. J Mol Biol. 1985 Apr 20;182(4):477–485. doi: 10.1016/0022-2836(85)90234-7. [DOI] [PubMed] [Google Scholar]
  34. Wu J. C., Manuelidis L. Sequence definition and organization of a human repeated DNA. J Mol Biol. 1980 Sep 25;142(3):363–386. doi: 10.1016/0022-2836(80)90277-6. [DOI] [PubMed] [Google Scholar]
  35. Yang T. P., Hansen S. K., Oishi K. K., Ryder O. A., Hamkalo B. A. Characterization of a cloned repetitive DNA sequence concentrated on the human X chromosome. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6593–6597. doi: 10.1073/pnas.79.21.6593. [DOI] [PMC free article] [PubMed] [Google Scholar]

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