Summary
The rare fragile site at 16q22 was experimentally induced in lymphocyte cultures with various AT-specific, non-intercalating DNA-ligands. The optimum conditions for the induction of fra (16)(q22) were determined. The best expression of fra (16)(q22) was found with the aromatic diamidine berenil which is recommended for further studies on this fragile site. The results indicate that fra (16)(q22) is a region with AT-rich, late replicating DNA. The simultaneous treatment of lymphocytes with berenil and aphidicolin (inhibitor of DNA polymerase α) induces both the rare fra (16) (q22) and the common fra (16) (q23) within the same chromosome. A population study on 350 unselected individuals showed that fra (16)(q22) is the most common of all rare autosomal fragile sites in man. The frequency of individuals heterozygous for fra (16)(q22) is 5.1% no homozygosity for fra (16) (q22) was detected. Statistical analysis indicates that the population is in Hardy-Weinberg equilibrium with respect to the fragile and non-fragile chromosomes 16.
Similar content being viewed by others
References
Behr W, Honikel, K, Hartmann G (1969) Interaction of the RNA polymerase inhibitor chromomycin with DNA. Eur J Biochem 9: 82–92
Berg JM, Faunch JA, Pendrey MJ, Penrose LS, Ridler, MAC, Shapiro A (1969) A homozygous chromosomal variant. Lancet I:531
Berger R Bloomfield CD, Sutherland GR (1985) Report of the committee on chromosome rearrangements in neoplasia and on fragile sites. (8th International Workshop on Human Gene, Mapping). Cytogenet Cell Genet 40:490–535
Burger A (1970) Medical chemistry, vol. 3. Wiley, New York
Caspersson T, Zech L, Johannsson C, Modest EJ (1970) Identification of human chromosomes by DNA-binding fluorescent agents. Chromosoma 30:215–227
Comings DE, Kovacs BW, Avelino E, Harris DC (1975) Mechanisms of chromosome banding. V. Quinacrine banding. Chromosoma 50:111–145
Couturier J, Dutrillaux B, Lejeume J (1973) Etude des fluorescences spécifique des bandes R et des bandes Q des chromosomes humains. CR Seances Acad Sci (III) 276:339–342
De Braekeleer, M, Smith B, Lin CC (1985) Fragile sites and structural rearrangements in cancer. Hum Genet 69:112–116
Dunner, JA, Martin AO, Traisman ES, Traisman HS, Elias S (1983) Enhancement of a fra (16) (q22) with distamycin A: a family acertained through an abnormal proposita. Am J Hum Genet 16:277–284
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
Haaf T, Weis H, Schindler D, Schmid M (1984) Specific silver staining of experimentally undercondensed chromosome regions. Chromosoma 90:149–155
Hahn FE (1975) Distamycin A and netropsin. In: Corcoran JW, Hahn FE (eds) Antibiotics, vol. III. Springer Berlin Heidelberg New York, pp 79–100
Hecht F, Sutherland GR (1984) Fragile sites and cancer breakpoints. Cancer Genet Cytogenet 12:179–181
Izakoviĉ V (1984) Homozygosity for fragile site at 17p12 in a 28-year-old healthy man. Hum Genet 68:340–341
Krey AK (1980) Non-intercalative binding to DNA. In: Hahn FE, Kersten W, Szybalski, W (eds) Progress in molecular and subcellular biology, vol 7. Springer, Berlin Heidelberg New York, pp 43–87
LeBeau MM, Rowley JD (1984) Heritable fragile sites in cancer. Nature 308:607–608
Manzini G, Barcellona ML, Avitabile M, Quadrifoglio F (1983) Interaction of diamidino-2-phenylindole (DAPI) with natural and synthetic nucleic acids. Nucleic Acids Res 11:8861–8876
Martindale W (1977) The extrapharmacopeia. Incorporating Squire's companion, 27th edn. Pharmaceutical Press, London, p 1572
Newton BA (1975) Berenil: a trypanocide with selective activity against extra nuclear DNA. In: Corcoran JW, Hahn FE (eds) Antibiotics, vol III. Springer, Berlin Heidelberg New York, pp 34–47
Sanfilippo S, Neri G, Tedeschi B, Carlo-Stella N, Triolo O, Serra A (1983) Chromosomal fragile sites: preliminary data of a population survey. Clin Genet 24:295
Scheres JMJC, Hustinx TWJ (1980) Heritable fragile sites and lymphocyte culture medium containing BrdU. Am J Hum Genet 32: 628–629
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
Schmid M, Hungerford DA, Poppen A, Engel W (1984) The use of distamycin A in human lymphocyte cultures. Hum Genet 65:377–384
Schmid M, Ott G, Haaf T, Scheres JMJC (1985) Evolutionary conservation of fragile sites induced by 5-azacytidine and 5-azadeoxycytidine in man, gorilla, and chimpanzee. Hum Genet 71:342–350
Schwanitz G (1976) Die Normvarianten menschlicher Chromosomen. Perimed, Erlangen
Shabtai F, Bichacho S, Halbrecht I (1980) The fragile site on chromosome 16 (q21q22). Data on four new families Hum Genet 55:19–22
Shabtai F, Klar D, Bichacho S, Hart S, Halbrecht I (1983), Familial fragility on chromosome 16 (fra16q22) enhanced by both interferon and distamycin A. Hum Genet 63:341–344
Sherman SL, Morton NE, Jacobs PA, Turner G (1984) The marker (X) syndrome: a cytogenetic and genetic analysis. Ann Hum Genet 48:21–37
Sørensen K, Nielson J, Holm V, Haahr J (1979) Fragile site long arm chromosome 16. Hum Genet 48:131–139
Sutherland GR (1979) Heritable fragile sites on human chromosomes. II. Distribution, phenotypic effects, and cytogenetics. Am J Hum Genet 31:136–148
Sutherland GR (1981) Heritable fragile sites on human chromosomes. VII. Children homozygous for the BrdU-requiring fra(10)(q25) are phenotypically normal. Am J Hum Genet 33:946–949
Sutherland GR (1982a) 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
Sutherland GR (1982b) Heritable fragile sites on human chromosomes. IX. Population cytogenetics and segregation analysis of the BrdU-requiring fragile site at 10q25. Am J Hum Genet 34: 753–756
Sutherland GR (1983) The fragile X chromosome. Int Rev Cytol 81: 107–143
Sutherland GR (1985) Heritable fragile sites on human chromosomes. XII. Population cytogenetics. Ann Hum Genet 49:153–161
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
Thestrup-Pedersen K, Esmann V, Jensen JR, Hastrup J, Thorling K, Saemundsen AK, Bisballe S, Pallesen G, Madsen M, Masucci MG, Ernberg I (1980) Epstein-Barr-virus induced lymphoproliferative disorder converting to fatal Burkitt-like lymphoma in a boy with interferon inducible chromosomal defect. Lancet II: 997–1002
Thestrup-Pedersen K, Bisballe S, Jensen JR, Esmann V, Heron I (1981) Epstein-Barr-virus and chromosomal defect: a family study. Lancet II:636–637
Ward DC, Reich E, Goldberg IH (1965) Base specificity in the interaction of polynucleotides with antibiotic drugs. Science 149: 1259–1263
Waring M (1970a) Drugs and DNA: uncoiling of the DNA double helix as evidence of intercalation. Hum Genet 9:234–236
Waring M (1970b) Variation of the supercoils in closed circular DNA by binding of antibiotics and drugs evidence for molecular models involving intercalation. J Mol Biol 54:247–279
Yunis JJ (1983) The chromosomal, basis of human neoplasia. Science 221:227–236
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schmid, M., Feichtinger, W., Jeßberger, A. et al. The fragile site (16) (q22). Hum Genet 74, 67–73 (1986). https://doi.org/10.1007/BF00278788
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00278788