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. 1986 Jun;38(6):793–804.

Regional localization of DNA sequences on chromosome 21 using somatic cell hybrids.

M L Van Keuren, P C Watkins, H A Drabkin, E W Jabs, J F Gusella, D Patterson
PMCID: PMC1684850  PMID: 3014865

Abstract

We have used a panel of Chinese hamster X human somatic cell hybrids, each containing various portions of chromosome 21 as the only detectable human chromosome component, for regional mapping of cloned, chromosome 21-derived DNA sequences. Thirty unique and very low-repeat sequences were mapped to the short arm and three sections of the long arm. Three unique sequences map to the proximal part of the terminal band 21q22.3, and five to the distal part of this band. Some of these may represent parts of gene sequences that may be relevant to the pathogenesis of Down syndrome, as 21q22 is the area required to be present in triplicate for the full clinical picture.

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Selected References

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  1. Adams M. M., Erickson J. D., Layde P. M., Oakley G. P. Down's syndrome. Recent trends in the United States. JAMA. 1981 Aug 14;246(7):758–760. doi: 10.1001/jama.246.7.758. [DOI] [PubMed] [Google Scholar]
  2. Alhadeff B., Velivasakis M., Siniscalco M. Simultaneous identification of chromatid replication and of human chromosomes in metaphases of man-mouse somatic cell hybrids. (With 1 color plate). Cytogenet Cell Genet. 1977;19(4):236–239. doi: 10.1159/000130814. [DOI] [PubMed] [Google Scholar]
  3. Bartley J. A., Epstein C. J. Gene dosage effect for glycinamide ribonucleotide synthetase in human fibroblasts trisomic for chromosome 21. Biochem Biophys Res Commun. 1980 Apr 29;93(4):1286–1289. doi: 10.1016/0006-291x(80)90629-4. [DOI] [PubMed] [Google Scholar]
  4. Cervenka J., Gorlin R. J., Djavadi G. R. Down syndrome due to partial trisomy 21q. Clin Genet. 1977 Feb;11(2):119–121. doi: 10.1111/j.1399-0004.1977.tb01288.x. [DOI] [PubMed] [Google Scholar]
  5. Chadefaux B., Allard D., Rethoré M. O., Raoul O., Poissonnier M., Gilgenkrantz S., Cheruy C., Jérôme H. Assignment of human phosphoribosylglycinamide synthetase locus to region 21q221. Hum Genet. 1984;66(2-3):190–192. doi: 10.1007/BF00286599. [DOI] [PubMed] [Google Scholar]
  6. Chadefaux B., Rethoré M. O., Raoul O., Ceballos I., Poissonnier M., Gilgenkranz S., Allard D. Cystathionine beta synthase: gene dosage effect in trisomy 21. Biochem Biophys Res Commun. 1985 Apr 16;128(1):40–44. doi: 10.1016/0006-291x(85)91641-9. [DOI] [PubMed] [Google Scholar]
  7. Davies K. E., Harper K., Bonthron D., Krumlauf R., Polkey A., Pembrey M. E., Williamson R. Use of a chromosome 21 cloned DNA probe for the analysis of non-disjunction in Down syndrome. Hum Genet. 1984;66(1):54–56. doi: 10.1007/BF00275186. [DOI] [PubMed] [Google Scholar]
  8. Devine E. A., Nolin S. L., Houck G. E., Jr, Jenkins E. C., Brown W. T. Chromosomal localization of several families of repetitive sequences by in situ hybridization. Am J Hum Genet. 1985 Jan;37(1):114–123. [PMC free article] [PubMed] [Google Scholar]
  9. Devine E. A., Nolin S. L., Houck G. E., Jr, Jenkins E. C., Miller D. L., Brown W. T. Isolation and regional localization by in situ hybridization of a unique gene segment to chromosome 21. Biochem Biophys Res Commun. 1984 May 31;121(1):380–385. doi: 10.1016/0006-291x(84)90733-2. [DOI] [PubMed] [Google Scholar]
  10. Drabkin H. A., Diaz M., Bradley C. M., Le Beau M. M., Rowley J. D., Patterson D. Isolation and analysis of the 21q+ chromosome in the acute myelogenous leukemia 8;21 translocation: evidence that c-mos is not translocated. Proc Natl Acad Sci U S A. 1985 Jan;82(2):464–468. doi: 10.1073/pnas.82.2.464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ellis W. G., McCulloch J. R., Corley C. L. Presenile dementia in Down's syndrome. Ultrastructural identity with Alzheimer's disease. Neurology. 1974 Feb;24(2):101–106. doi: 10.1212/wnl.24.2.101. [DOI] [PubMed] [Google Scholar]
  12. Epstein C. J., McManus N. H., Epstein L. B., Branca A. A., D'Alessandro S. B., Baglioni C. Direct evidence that the gene product of the human chromosome 21 locus, IFRC, is the interferon-alpha receptor. Biochem Biophys Res Commun. 1982 Aug;107(3):1060–1066. doi: 10.1016/0006-291x(82)90629-5. [DOI] [PubMed] [Google Scholar]
  13. Erickson J. M., Rushford C. L., Dorney D. J., Wilson G. N., Schmickel R. D. Structure and variation of human ribosomal DNA: molecular analysis of cloned fragments. Gene. 1981 Dec;16(1-3):1–9. doi: 10.1016/0378-1119(81)90055-x. [DOI] [PubMed] [Google Scholar]
  14. Feaster W. W., Kwok L. W., Epstein C. J. Dosage effects for superoxide dismutase-1 in nucleated cells aneuploid for chromosome 21. Am J Hum Genet. 1977 Nov;29(6):563–570. [PMC free article] [PubMed] [Google Scholar]
  15. Friend K. K., Chen S., Ruddle F. H. Differential staining of interspecific chromosomes in somatic cell hybrids by alkaline Giemsa stain. Somatic Cell Genet. 1976 Mar;2(2):183–188. doi: 10.1007/BF01542631. [DOI] [PubMed] [Google Scholar]
  16. Graham G. J., Hall T. J., Cummings M. R. Isolation of repetitive DNA sequences from human chromosome 21. Am J Hum Genet. 1984 Jan;36(1):25–35. [PMC free article] [PubMed] [Google Scholar]
  17. Gusella J., Varsanyi-Breiner A., Kao F. T., Jones C., Puck T. T., Keys C., Orkin S., Housman D. Precise localization of human beta-globin gene complex on chromosome 11. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5239–5242. doi: 10.1073/pnas.76.10.5239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Habedank M., Rodewald A. Moderate Down's syndrome in three siblings having partial trisomy 21q22.2 to qter and therefore no SOD-1 excess. Hum Genet. 1982;60(1):74–77. doi: 10.1007/BF00281269. [DOI] [PubMed] [Google Scholar]
  19. Hagemeijer A., Smit E. M. Partial trisomy 21. Further evidence that trisomy of band 21q22 is essential for Down's phenotype. Hum Genet. 1977 Aug 31;38(1):15–23. doi: 10.1007/BF00295803. [DOI] [PubMed] [Google Scholar]
  20. Jabs E. W., Wolf S. F., Migeon B. R. Characterization of a cloned DNA sequence that is present at centromeres of all human autosomes and the X chromosome and shows polymorphic variation. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4884–4888. doi: 10.1073/pnas.81.15.4884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kao F. T., Puck T. T. Induction and isolation of auxotrophic mutants in mammalian cells. Methods Cell Biol. 1974;8(0):23–39. doi: 10.1016/s0091-679x(08)60441-0. [DOI] [PubMed] [Google Scholar]
  22. Kazazian H. H., Jr, Antonarakis S. E., Wong C., Trusko S. P., Stetten G., Oliver M., Potter M. J., Gusella J. F., Watkins P. C. Ring chromosome 21: characterization of DNA sequences at sites of breakage and reunion. Ann N Y Acad Sci. 1985;450:33–42. doi: 10.1111/j.1749-6632.1985.tb21481.x. [DOI] [PubMed] [Google Scholar]
  23. Kitsiou-Tzeli S., Hallett J. J., Atkins L., Latt S. A., Holmes L. B. Familial t (4;21)(q2.4;q2.2) leading to unbalanced offspring with partial duplication of 4q and of 21q without manifestations of the Down syndrome. Am J Med Genet. 1984 Aug;18(4):725–729. doi: 10.1002/ajmg.1320180419. [DOI] [PubMed] [Google Scholar]
  24. Kozak C. A., Lawrence J. B., Ruddle F. H. A sequential staining technique for the chromosomal analysis of the interspecific mouse/hamster and mouse/human somatic cell hybrids. Exp Cell Res. 1977 Mar 1;105(1):109–117. doi: 10.1016/0014-4827(77)90156-2. [DOI] [PubMed] [Google Scholar]
  25. Krumlauf R., Jeanpierre M., Young B. D. Construction and characterization of genomic libraries from specific human chromosomes. Proc Natl Acad Sci U S A. 1982 May;79(9):2971–2975. doi: 10.1073/pnas.79.9.2971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lieman-Hurwitz J., Dafni N., Lavie V., Groner Y. Human cytoplasmic superoxide dismutase cDNA clone: a probe for studying the molecular biology of Down syndrome. Proc Natl Acad Sci U S A. 1982 May;79(9):2808–2811. doi: 10.1073/pnas.79.9.2808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mattei J. F., Mattei M. G., Baeteman M. A., Giraud F. Trisomy 21 for the region 21q223: identification by high-resolution R-banding patterns. Hum Genet. 1981;56(3):409–411. doi: 10.1007/BF00274703. [DOI] [PubMed] [Google Scholar]
  28. Moore E. E., Jones C., Kao F. T., Oates D. C. Synteny between glycinamide ribonucleotide synthetase and superoxide dismutase (soluble). Am J Hum Genet. 1977 Jul;29(4):389–396. [PMC free article] [PubMed] [Google Scholar]
  29. Niebuhr E. Down's syndrome. The possibility of a pathogenetic segment on chromosome no. 21. Humangenetik. 1974 Jan 22;21(1):99–101. doi: 10.1007/BF00278575. [DOI] [PubMed] [Google Scholar]
  30. Oates D. C., Patterson D. Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism: characterization of Chinese hamster cell mutants defective in phosphoribosylpyrophosphate amidotransferase and phosphoribosylglycinamide synthetase and an examination of alternatives to the first step of purine biosynthesis. Somatic Cell Genet. 1977 Nov;3(6):561–577. doi: 10.1007/BF01539066. [DOI] [PubMed] [Google Scholar]
  31. Olson M. I., Shaw C. M. Presenile dementia and Alzheimer's disease in mongolism. Brain. 1969 Mar;92(1):147–156. doi: 10.1093/brain/92.1.147. [DOI] [PubMed] [Google Scholar]
  32. Patterson D., Graw S., Jones C. Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21. Proc Natl Acad Sci U S A. 1981 Jan;78(1):405–409. doi: 10.1073/pnas.78.1.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Patterson D., Jones C., Morse H., Rumsby P., Miller Y., Davis R. Structural gene coding for multifunctional protein carrying orotate phosphoribosyltransferase and OMP decarboxylase activity is located on long arm of human chromosome 3. Somatic Cell Genet. 1983 May;9(3):359–374. doi: 10.1007/BF01539144. [DOI] [PubMed] [Google Scholar]
  34. Pfeiffer R. A., Kessel E. K., Soer K. H. Partial trisomies of chromosome 21 in man. Two new observations due to translocations 19;21 and 4;21. Clin Genet. 1977 Mar;11(3):207–213. doi: 10.1111/j.1399-0004.1977.tb01301.x. [DOI] [PubMed] [Google Scholar]
  35. Poissonnier M., Saint-Paul B., Dutrillaux B., Chassaigne M., Gruyer P., de Blignières-Strouk G. Trisomie 21 partielle (21q21 leads to 21q22.2) Ann Genet. 1976 Mar;19(1):69–73. [PubMed] [Google Scholar]
  36. Quax-Jeuken Y., Quax W., van Rens G., Khan P. M., Bloemendal H. Complete structure of the alpha B-crystallin gene: conservation of the exon-intron distribution in the two nonlinked alpha-crystallin genes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5819–5823. doi: 10.1073/pnas.82.17.5819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. ROWE R. D., UCHIDA I. A. Cardiac malformation in mongolism: a prospective study of 184 mongoloid children. Am J Med. 1961 Nov;31:726–735. doi: 10.1016/0002-9343(61)90157-7. [DOI] [PubMed] [Google Scholar]
  38. Raziuddin A., Sarkar F. H., Dutkowski R., Shulman L., Ruddle F. H., Gupta S. L. Receptors for human alpha and beta interferon but not for gamma interferon are specified by human chromosome 21. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5504–5508. doi: 10.1073/pnas.81.17.5504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  40. Rowley J. D. Down Syndrome and acute leukaemia: increased risk may be due to trisomy 21. Lancet. 1981 Nov 7;2(8254):1020–1022. doi: 10.1016/s0140-6736(81)91218-6. [DOI] [PubMed] [Google Scholar]
  41. Schmickel R. D., Knoller M. Characterization and localization of the human genes for ribosomal ribonucleic acid. Pediatr Res. 1977 Aug;11(8):929–935. doi: 10.1203/00006450-197708000-00015. [DOI] [PubMed] [Google Scholar]
  42. Scholl T., Stein Z., Hansen H. Leukemia and other cancers, anomalies and infections as causes of death in Down's syndrome in the United States during 1976. Dev Med Child Neurol. 1982 Dec;24(6):817–829. doi: 10.1111/j.1469-8749.1982.tb13702.x. [DOI] [PubMed] [Google Scholar]
  43. Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. doi: 10.1016/s0140-6736(71)90287-x. [DOI] [PubMed] [Google Scholar]
  44. Sichitiu S., Sinet P. M., Lejeune J., Frézal J. Surdosage de la forme dimérique de l'indophénoloxydase dans la trisomie 21, secondaire au surdosage génique. Humangenetik. 1974 Jun 26;23(1):65–72. doi: 10.1007/BF00295684. [DOI] [PubMed] [Google Scholar]
  45. Sinet P. M., Couturier J., Dutrillaux B., Poissonnier M., Raoul O., Rethore M. O., Allard D., Lejeune J., Jerome H. Trisomie 21 et superoxyde dismutase-1 (IPO-A). Tentative de localisation sur la sous bande 21Q22.1. Exp Cell Res. 1976 Jan;97:47–55. doi: 10.1016/0014-4827(76)90653-4. [DOI] [PubMed] [Google Scholar]
  46. Skovby F., Krassikoff N., Francke U. Assignment of the gene for cystathionine beta-synthase to human chromosome 21 in somatic cell hybrids. Hum Genet. 1984;65(3):291–294. doi: 10.1007/BF00286520. [DOI] [PubMed] [Google Scholar]
  47. 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]
  48. Stetten G., Sroka B., Corson V. L., Boehm C. D. Prenatal detection of an unstable ring 21 chromosome. Hum Genet. 1984;68(4):310–313. doi: 10.1007/BF00292590. [DOI] [PubMed] [Google Scholar]
  49. Tan Y. H., Tischfield J., Ruddle F. H. The linkage of genes for the human interferon-induced antiviral protein and indophenol oxidase-B traits to chromosome G-21. J Exp Med. 1973 Feb 1;137(2):317–330. doi: 10.1084/jem.137.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Tandon R., Edwards J. E. Cardiac malformations associated with Down's syndrome. Circulation. 1973 Jun;47(6):1349–1355. doi: 10.1161/01.cir.47.6.1349. [DOI] [PubMed] [Google Scholar]
  51. Taysi K., Sparkes R. S., O'Brien T. J., Dengler D. R. Down's syndrome phenotype and autosomal gene inactivation in a child with presumed (X;21) de novo translocation. J Med Genet. 1982 Apr;19(2):144–148. doi: 10.1136/jmg.19.2.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Vora S., Francke U. Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3738–3742. doi: 10.1073/pnas.78.6.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Vora S., Francke U. Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3738–3742. doi: 10.1073/pnas.78.6.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Watkins P. C., Tanzi R. E., Gibbons K. T., Tricoli J. V., Landes G., Eddy R., Shows T. B., Gusella J. F. Isolation of polymorphic DNA segments from human chromosome 21. Nucleic Acids Res. 1985 Sep 11;13(17):6075–6088. doi: 10.1093/nar/13.17.6075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Williams J. D., Summitt R. L., Martens P. R., Kimbrell R. A. Familial Down syndrome due to t(10;21) translocation: evidence that the Down phenotype is related to trisomy of a specific segment of chromosome 21. Am J Hum Genet. 1975 Jul;27(4):478–485. [PMC free article] [PubMed] [Google Scholar]

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