Skip to main content
Log in

Evolutionary conservation of fragile sites induced by 5-azacytidine and 5-azadeoxycytidine in man, gorilla, and chimpanzee

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

Lymphocyte cultures from man, gorilla, and chimpanzee were treated with 5-azacytidine and 5-azadeoxycytidine. These cytidine analogues induce common fragile sites in the chromosome bands 1q42 and 19q13 of man. A rare fragile site is induced by 5-azadeoxycytidine in the band 1q24. The optimum conditions required for inducing these new fragile sites were determined by a series of experiments. The common fragile site in human chromosome 1q42 also exists in the gorilla and chimpanzee in the homologous band 1q32. The fragile site in human chromosome 19q13 was demonstrated in the gorilla in the homologous chromosome band 20q13. These are the first examples found of evolutionary highly conserved fragile sites in homologous chromosome bands in related primate species. The interaction between 5-azacytidine, 5-azadeoxycytidine, and chromosomal DNA; the evolutionary conservation of genes located within or closely adjacent to the fragile sites in the chromosome 1 of Hominoidea; and the phylogenetic origin of the two new common fragile sites are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Caspersson T, Zech L, Johannsson C, Modest EJ (1970) Identification of human chromosomes by DNA-binding fluorescent agents. Chromosoma 30:215–227

    Article  PubMed  Google Scholar 

  • Cihak A (1974) Biological effects of 5-azacytidine in eukaryotes. Oncology 30:405–422

    PubMed  Google Scholar 

  • Clough DW, Kunkel LM, Davidson RL (1982) 5-Azacytidine-induced reactivation of a herpes simplex thymidine kinase gene. Science 216:70–73

    PubMed  Google Scholar 

  • Compere SJ, Palmiter RD (1981) DNA methylation controls the inducibility of the mouse metallothionein-1 gene in lymphoid cells. Cell 25:233–240

    Article  PubMed  Google Scholar 

  • Creuso F, Acs G, Christman JK (1982) Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidine and 5-aza-2-deoxycytidine. J Biol Chem 257:2041–2048

    PubMed  Google Scholar 

  • De Braekeleer M, Smith B, Lin CC (1985) Fragile sites and structural rearrangements in cancer. Hum Genet 69:112–116

    Article  PubMed  Google Scholar 

  • Glover TW (1981) FUdR induction of the X chromosome fragile site: evidence for the mechanism of folic acid and thymidine inhibition. Am J Hum Genet 33:234–242

    PubMed  Google Scholar 

  • Glover TW, Berger C, Coyle J, Echo B (1984) DNA polymerase α inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes. Hum Genet 67:136–142

    Article  PubMed  Google Scholar 

  • Groudine M, Eisenman R, Weintraub H (1981) Chromatin structure of endogenous retroviral genes and activation by an inhibitor of DNA methylation. Nature 292:311–317

    PubMed  Google Scholar 

  • Hecht F, Sutherland GR (1984) Fragile sites and cancer breakpoints. Cancer Genet Cytogenet 12:179–181

    Article  PubMed  Google Scholar 

  • Henderson AS, Atwood KC, Yu MT, Warburton D (1967) The site of 5S RNA genes in primates. I. The great apes. Chromosoma 56: 29–32

    Article  Google Scholar 

  • Jones PA, Taylor SM (1980) Cellular differentiation, cytidine analogs and DNA methylation. Cell 20:85–93

    Article  PubMed  Google Scholar 

  • Jones PA, Taylor SM (1981) Hemimethylated duplex DNAs prepared from 5-azacytidine-treated cells. Nucleic Acids Res 9:2933–2947

    PubMed  Google Scholar 

  • Jones PA, Taylor SM, Mohandas T, Shapiro LJ (1982) Cell cyclespecific reactivation of an inactive X-chromosome locus by 5-azadeoxycytidine. Proc Natl Acad Sci USA 79:1215–1219

    PubMed  Google Scholar 

  • Kotala GB (1977) Human evolution: hominoids of the miocene. Science 197:244–245

    Google Scholar 

  • Mattei MG, Mattei JF, Vidal I, Giraud F (1981) Expression in lymphocyte and fibroblast culture of the fragile X chromosome: a new technical approach. Hum Genet 59:166–169

    PubMed  Google Scholar 

  • Mohandas T, Shapiro LJ (1983) Factors involved in X-chromosome inactivation. In: Sandberg AA (ed) Progress and topics in cytogenetics, part A: Basic mechanisms of X chromosome behavior. Liss, New York, pp 271–297

    Google Scholar 

  • Paris Conference (1971), Supplement (1975) Standardization in human cytogenetics. Cytogenet Cell Genet 15:201–238

    Google Scholar 

  • Pfeiffer RA (1974) Cell cultures from blood and bone marrow. In: Schwarzacher HG, Wolf U (eds) Methods in human cytogenetics. Springer, Berlin Heidelberg New York, pp 1–37

    Google Scholar 

  • Scheres JMJC, Hustinx TWJ (1980) Heritable fragile sites and lymphocyte culture medium containing BrdU. Am J Hum Genet 32: 628–629

    PubMed  Google Scholar 

  • Schmid M, Haaf T (1984) Distamycin A/DAPI bands and the effects of 5-azacytidine on the chromosomes of the chimpanzee, Pan troglodytes. Cytogenet Cell Genet 38:192–199

    PubMed  Google Scholar 

  • Schmid M, Klett C, Niederhofer A (1980) Demonstration of a heritable fragile site in human chromosome 16 with distamycin A. Cytogenet Cell Genet 28:87–94

    PubMed  Google Scholar 

  • Schmid M, Grunert D, Haaf T, Engel W (1983) A direct demonstration of somatically paired heterochromatin of human chromosomes. Cytogenet Cell Genet 36:554–561

    PubMed  Google Scholar 

  • Schmid M, Haaf T, Grunert D (1984) 5-Azacytidine-induced under-condensations in human chromosomes. Hum Genet 67:257–263

    Article  PubMed  Google Scholar 

  • Schnedl W, Dey VG, Tantravahi R, Miller DA, Erlanger BF, Miller OJ (1975) 5-Methylcytosine in heterochromatic regions of chromosomes: chimpanzee and gorilla compared to the human. Chromosoma 52:59–66

    Article  PubMed  Google Scholar 

  • Schweizer D (1980) Simultaneous fluorescent staining of R-bands and specific heterochromatic regions (DA-DAPI bands) in human chromosomes. Cytogenet Cell Genet 27:190–193

    PubMed  Google Scholar 

  • Sehested J (1974) A simple method for R banding of human chromosomes, showing a pH-dependent connection between R and G bands. Hum Genet 21:55–58

    Article  Google Scholar 

  • Steffensen DM (1977) Human gene localization by RNA: DNA hybridization in situ. In: Yunis JJ (ed) Molecular structure of human chromosomes. Academic Press, New York San Francisco London, pp 59–88

    Google Scholar 

  • Sumner AT (1972) A simple technique for demonstrating centromeric heterochromatin. Exp Cell Res 75:304–306

    PubMed  Google Scholar 

  • Sutherland GR (1979) Heritable fragile sites on human chromosomes. I. Factors affecting expression in lymphocyte culture. Am J Hum Genet 31:125–135

    PubMed  Google Scholar 

  • Sutherland GR (1982) Heritable fragile sites on human chromosomes. VIII. Preliminary population cytogenetic data on the folic acid-sensitive fragile sites. Am J Hum Genet 34:452–458

    PubMed  Google Scholar 

  • Sutherland GR (1983) The fragile X chromosome. Int Rev Cytol 81: 107–143

    PubMed  Google Scholar 

  • Sutherland GR, Baker E, Seshardi RS (1980) Heritable fragile sites on human chromosomes. V. A new class of fragile sites requiring BrdU for expression. Am J Hum Genet 32:542–548

    PubMed  Google Scholar 

  • Sutherland GR, Jacky PB, Baker EG (1984) Heritable fragile sites on human chromosomes. XI. Factors affecting expression of fragile sites at 10q25, 16q22, and 17q12. Am J Hum Genet 36:110–122

    PubMed  Google Scholar 

  • Taylor SM, Jones PA (1979) Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell 17:771–779

    Article  PubMed  Google Scholar 

  • Tommerup N, Poulsen H, Brøndum-Nielsen K (1981) 5-Fluoro-2′-deoxyuridine induction of the fragile site on Xq28 associated with X-linked mental retardation. J Med Genet 18:374–376

    PubMed  Google Scholar 

  • Viegas-Péquignot E, Dutrillaux B (1976) Segmentation of human chromosomes induced by 5-ACR (5-azacytidine). Hum Genet 34: 247–254

    PubMed  Google Scholar 

  • Warburton D, Yu MT, Atwood KC, Henderson AS (1976) The location of RN5S genes on the chromosomes of primates. Cytogenet Cell Genet 16:440–442

    PubMed  Google Scholar 

  • Yunis JJ (1983) The chromosomal basis of human neoplasia. Science 221:227–236

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmid, M., Ott, G., Haaf, T. et al. Evolutionary conservation of fragile sites induced by 5-azacytidine and 5-azadeoxycytidine in man, gorilla, and chimpanzee. Hum Genet 71, 342–350 (1985). https://doi.org/10.1007/BF00388461

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00388461

Keywords

Navigation